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Vol. 16 • Num. 62 • January-March 2014 Vol. 16 • Num. 62 • January-March 2014 • ISSN 1665-5796 SCIENCE AND RESEARCH JOURNAL OF THE SCHOOL OF MEDICINE AND "DR. JOSÉ ELEUTERIO GONZÁLEZ" UNIVERSITY HOSPITAL UNIVERSIDAD AUTÓNOMA DE NUEVO LEÓN ONE BIG evolutionary step INFILTRATION VS. INSTILLATION of ropivacaine 7.5% in radical mastectomies for postoperative analgesia MEDICINA UNIVERSITARIA MATERNAL MORTALITY and severe obstetric morbidity in a tertiary care hospital www.elsevier.es medicina universitaria SCIENCE AND RESEARCH JOURNAL OF THE SCHOOL OF MEDICINE AND "DR. JOSÉ ELEUTERIO GONZÁLEZ" UNIVERSITY HOSPITAL UNIVERSIDAD AUTÓNOMA DE NUEVO LEÓN EDITORIAL COMMITTEE General Director Chief editor Editor Editor Santos Guzmán López Ariel Ernesto Arias Ramírez Félix Ramón Cedillo Salazar Alejandro Arroliga David Gómez Almaguer Norbert W. Brattig Francisco Javier Bosques Padilla María de los Ángeles Castro Corona Ottawa, Canadá Temple, EEUU Hamburgo, Alemania Monterrey, México Technical Editor Carlos Alberto Acosta Olivo Ricardo Cerda Flores Monterrey, NL Technical Editor Beatriz Elizabeth De la Fuente Cortez Salvador Cruz Flores St. Louis, EEUU Technical Editor Alfredo Arias Cruz Assistant Editor José Carlos Jaime Pérez José A. González González Monterrey, México Oscar González Llano Monterrey, México Patricia de Gortari EDITORIAL BOARD Hugo Alberto Barrera Saldaña Monterrey, México DF, México Francisco Forriol Campos Madrid, España Alejandra García Quintanilla Mérida, México Elvira Garza González Monterrey, México René Raúl Drucker Colín DF, México Rubén Lisker Y. DF, México Pali Hungin Ruy Pérez Tamayo DF, México José Luis Iglesias Benavides Monterrey, México Puebla, México Patricia Ileana Joseph Bravo Cuernavaca, México Guillermo J. Ruiz Argüelles Ralph Weissleder Oliverio Welsh Lozano Boston, EEUU Monterrey, México Susana Kofman Alfaro DF, México David Kershenobich Stalnikowitz DF, México Francisco López Jiménez Rochester, EEUU Xavier López Karpovitch DF, México Laura E. Martínez de Villarreal Nahum Méndez Sánchez Monterrey, México Nueva York, EEUU Mario Henry Rodríguez Cuernavaca, México Puebla, México Guillermo J. Ruiz Delgado Puebla, México José Javier Sánchez Madrid, España Josep María Segur Vilalta Gregorio A. Sicard Antonio Costilla Esquivel Monterrey, México Rolando Tijerina Menchaca Lyuba Varticovski Juan Pablo Figueroa Delgado Monterrey, México Alejandro Ruiz Argüelles Monterrey, México Emma Bertha García Quintanilla DF, México Guillermo I. Pérez Pérez Eloy Cárdenas Estrada English translation and style: Monterrey, México Claudia Elizalde Molina Isaías Rodríguez Balderrama Biostatistics advisor: Stockton-on-Tees, Reino Unido Joseph Varon Carlos E. Baena-Cagnani Jordi Sierra Gil Barcelona, España St. Louis, EEUU Monterrey, México Maryland, EEUU Houston, EEUU Córdoba, Argentina Barcelona, España Medicina Universitaria, Volumen 16, número 62, enero-marzo de 2014, es una publicación trimestral de la Revista de Investigación y Ciencia de la Facultad de Medicina y Hospital Universitario Dr. José E. González de la U.A.N.L. ISSN 1665-5796. Editada por: Masson Doyma México, S.A. Av. Insurgentes Sur 1388, Piso 8, Col. Actipan Del. Benito Juárez, CP 03230, México, D.F. Tels.: 5524-1069, 5524-4920, Fax: 5524-0468. Reservados todos los derechos. El contenido de la presente publicación no puede ser reproducido, ni transmitido por ningún procedimiento electrónico o mecánico, incluyendo fotocopia, grabación magnética, ni registrado por ningún sistema de recuperación de información, en ninguna forma, ni por ningún medio, sin la previa autorización por escrito del titular de los derechos de explotación de la misma. Cualquier forma de reproducción, distribución, comunicación pública o transformación de esta obra sólo puede ser realizada con la autorización de sus titulares, salvo excepción prevista por la ley. Impresa por Editorial de Impresos y Revistas S. A. de C. V. Emilio Carranza No. 100 Col. Zacahuizco C.P. 03550. Delegación Benito Juárez, México D.F. Este número se terminó de imprimir en marzo de 2014 con un tiraje de 1,200 ejemplares. Índices en los que aparece esta revista: ARTEMISA (Artículos Editados en México sobre información en Salud). En Internet, compilada en el Índice Mexicano de Revistas Biomédicas (IMBIOMED) y LATINDEX. medicina universitaria SCIENCE AND RESEARCH JOURNAL OF THE SCHOOL OF MEDICINE AND “DR. JOSÉ ELEUTERIO GONZÁLEZ” UNIVERSITY HOSPITAL UNIVERSIDAD AUTÓNOMA DE NUEVO LEÓN Contents EDITORIAL Volume 16 Issue 62 January-March 2014 1 One big evolutionary step S. Guzmán-López, F. R. Cedillo-Salazar, D. Gómez-Almaguer and F.J. Bosques-Padilla ORIGINAL ARTICLES 2 Discrimination in clinical settings and its relationship to depression and anger in women living with HIV J. Moral-de la Rubia and M. P. Segovia-Chávez 9 Frequency of metabolic syndrome in women treated at the Menopause Clinic of the “Dr. José Eleuterio González” University Hospital of the UANL in Northeastern Mexico M. Cervantes-Flores, J. Vázquez-Méndez, D. Saldívar-Rodríguez, O. VidalGutiérrez, I. Y. González-Carrillo and G. Guerrero-González 12 Correlation between BMI and climateric symptoms in menopausal women I. Y. González-Carrillo, J. Vázquez-Méndez, G. Guerrero-González, O. Vidal-Gutiérrez and M. Cervantes-Flores 15 Infiltration vs. instillation of ropivacaine 7.5% in radical mastectomies for postoperative analgesia B. I. Yolanda-Prieto, A. L. Millán-Corrales, D. Palacios-Ríos, B. I. GarduñoChávez, N. G. López-Cabrera, G. A. Millán-Cornejo and B. T. González-Rocha 19 Maternal mortality and severe obstetric morbidity in a tertiary care hospital J. L. Iglesias-Benavides, M. S. Vidales-Hernández, W. E. Treviño-Ledezma, S. N. Delgado-Muñiz and A. Guzmán-López scientific LETTER 25 Sweet syndrome presenting late after non Hodgkin’s lymphoma and dermatomyositis L. A. Olguín-Ramírez, J. C. Jaime-Pérez, C. Mendoza-Rodríguez and D. GómezAlmaguer REVIEW ARTICLES 28 Mild cognitive impairment J. Isordia-Martínez, F. Gongora-Rivera, H. Leal-Bailey and X. Ortiz-Jiménez 37 Trichosporon spp.: an emerging fungal pathogen A. M. Montoya and G. M. González Medicina Universitaria 2014;16(62):1 medicina universitaria www.elsevier.com.mx Editorial One big evolutionary step It’s been a long and exciting journey since it was decided that a medical journal should be a fundamental part of the strategy to fulfill our Institution’s Subdivision of Continuing Medical Education’s main goal, which is to strengthen the bond between graduated biomedical professionals and our medical school, keeping them on the leading edge of medical knowledge. And so, the Medicina Universitaria journal was born. As the years went by, an evident evolution occurred in this journal. Since the first issue was published in January 1970, a constant transformation has taken place. We now have a larger group of people involved in its process, a new and renovated image, improved economic support, and a well-established trimestral periodical production. Furthermore, a greater number of papers are considered for publication, and last but not least, we are now published by Elsevier, a very well-known and prestigious editorial company. Today, we are very proud to announce that another important evolutionary change in our journal has occurred. From now on, the entire Medicina Universitaria journal will be published in the English language, starting with this year’s first issue. Although it could be seen as a small transformation, in reality it is a very big one. This will allow our journal to be read by almost all health professionals worldwide, as English is the world’s official scientific language. Thus, the possibility of our articles being read and cited is far greater; the scientific medical community from larger countries such as India, China, Brazil, Russia etc., will have the possibility to read and discuss our papers. Hopefully, this will keep us in the right direction to become an indexed medical journal, as we have been so far. In spite of these transformations, we are completely certain that something very important in our journal has not changed; it’s still being made by a selfless group of professors who follow the original vision of it is founder Dr. Álvaro Gómez-Leal. That is, to be an effective journal that assists health professionals in their continuous pursuit of excellence and in giving their patients the best medical treatment available in a humanist way. This is the engine that moves every physician’s mind; to reach their main practice’s objective by offering the best medical treatment possible, in accordance with international guidelines, in a human, caring, and passionate way. Throughout the last four decades, our journal has played an important role as a communication tool. Its pages have witnessed some of the most relevant, dramatic and visionary advances in the health sciences over the last 44 years. That being said, we are sure that one of Dr. Gómez-Leal’s greatest legacies was his original idea to create a useful journal within our medical school, to serve all generations of health professionals. We wish to congratulate everyone who has participated in any way to make our Medicina Universitaria journal a reality. We are proud to present it in its new format which will help everybody in his or her constant pursuit of excellence and truth. Let’s enjoy it. S. Guzmán-López, MD General Director F. R. Cedillo-Salazar, MD* Chief Editor D. Gómez-Almaguer, MD Editor F. J. Bosques-Padilla, MD Editor * Corresponding author: Eduardo Aguirre Pequeño Avenue and Gonzalitos Avenue, Mitras Centro, Z.P. 64460, Monterrey, N. L., Mexico. Telephone: +52 (81) 8329 4193, 8346 1370, 8347 5867. Fax: 8333 6687. E-mail address: [email protected] (F. R. Cedillo-Salazar). 1665-5796 © 2014 Revista Medicina Universitaria. Facultad de Medicina UANL. Publicado por Elsevier México. Todos los derechos reservados. Medicina Universitaria 2014;16(62):2-8 medicina universitaria www.elsevier.com.mx Original article Discrimination in clinical settings and its relationship to depression and anger in women living with HIV J. Moral-de la Rubia*, M. P. Segovia-Chávez Faculty of Psychology, Universidad Autónoma de Nuevo León, Monterrey, N. L., Mexico Received: November 2012; Accepted: November 2013 KEYWORDS Depression; Anger; Discrimination; Women; AIDS; Mexico. Abstract Objectives: To describe the frequency of feared discrimination in various social situations and of perceived discrimination in clinical settings, as well as to study the relationship between discrimination and depression and anger in women living with human immunodeficiency virus (HIV). Material and methods: The scale of Feared and Perceived Discrimination for Women with HIV (DTP-40-MV), the Beck Depression Inventory (BDI-2), and the Anger Expression scale of StateTrait-Anger Expression Inventory (STAXI-2-AX/EX) were applied to a random sample of 200 women living with HIV. Results: These women feared being discriminated against, perceived discrimination upon the review of medical records, but perceived little discrimination in clinical care. A model with good adjustment to the data showed that the fear of being discriminated against creates a disposition toward perception of discrimination in the clinical settings (latent variable with 2 indicators: review of the medical records and clinical care) and increases cognitive/affective depressive symptoms; higher anger control decreases the anger manifestation; greater discrimination perceived in the clinical settings decreases anger control, which facilitates the expression of anger and slows cognitive/affective depressive symptoms; and these latter symptoms sensitize the perception of discrimination before the clinical records. Conclusion: Feared discrimination is a clinically relevant aspect due to its frequency and effect on depressive symptoms and perception of discrimination before the review of medical records. 1665-5796 © 2014 Revista Medicina Universitaria. Facultad de Medicina UANL. Publicado por Elsevier México. Todos los derechos reservados. Introduction Human immunodeficiency virus (HIV) infection is a chronic degenerative disease which has a life expectancy of over 40 years if detected early, and with an uninterrupted adherence to an antiretroviral treatment under medical supervision. Nowadays, HIV infection eventually evolves into a very advanced immunodeficiency stage, in which the organism * Corresponding author: Dr. Carlos Canseco 110, Mitras Centro, Z.P. 64460, Monterrey, N. L., México. Telephono: (81) 8333 8233, ext. 423. Fax: ext. 103. E-mail address: [email protected] (J. Moral-de la Rubia). Discrimination in clinical settings and its relationship to depression and anger in women living with HIV undergoes other diseases as a result of the body’s low immunological competence such as Pneumocystis jiroveci pneumonia or Kaposi’s sarcoma.1 When first diagnosed as HIV-seropositive, the patient is faced with a death prognosis, as well as a lifetime of expensive treatments with side effects. Additionally, there is the social stigma involved with the diagnosis. HIV infection diagnosis is associated with morally-condemned behaviours such as men having sex with men, having multiple and concurrent sex partners, commercial sex, and intravenous drug use.2 In recent years, HIV infection risk factors have shifted, gaining ground amongst heterosexual transmission.3 In 2013, females represented half of the cases worldwide (17.7 million out of the 35.3 million infected people are women); as known, in the past the epidemic was found predominantly in males.4 In Mexico, the ratio of female cases has increased since 1983; however, cases are still mostly found in males.3 From 1983 to 2012, 18% of the cases corresponded to women and 82% to men.5 In 2013, in Nuevo Leon, Mexico the number of HIV-seropositive people was 4,938 with a male:female ratio of 7 to 1.5 Discrimination and stigmatization against people living with HIV and those around them is one of this infectious diseases’ negative consequences, and a major obstacle in prevention and assistance.6 Oftentimes people with HIV are ostracized by their families as well as their communities;7 they are subjected to social and institutional discrimination, and on occasion even denied access to healthcare, insurance coverage, entry to some countries, and access to job opportunities.8 Fear of discrimination makes people avoid detection tests, which impedes early treatment.9 Depression is twice as common in people with HIV compared to the general population.10 Discrimination contributes to depression, especially in women.11 We must point out that most people experience anger when discriminated against as they feel their rights are being infringed upon. If discrimination persists and intensifies, it usually leads to helplessness and depression; however, there are people who do not react with anger but go straight to depression due to a personal history of helplessness.12 Anger, especially uncontrolled anger, can have a negative effect in medical attention as well as in the provider-patient relationship, possibly acting as a cause of discrimination. On the other hand, its assertive expression can increase awareness and a possible rectification of the injustice suffered.13 It is exactly this complaint of discrimination from HIV seropositive patients which is the most frequent in the clinical field, in which there is a great sensitivity to the patients’ rigths.14 Even though there are studies that consider depression and anger as a response to discrimination against HIVseropositive patients,15,16 these studies do not distinguish between discrimination feared (expectations) and discrimination perceived (experienced); besides, all of these studies have been conducted outside of Mexico. Therefore, the objective of the present investigation is to describe the frequency of feared discrimination in different social situations, and perceived discrimination in clinical settings against HIV-seropositive women, as well as to study the relationship between discrimination, depression, and anger in women living with HIV, in which anger and depression are consequences of discrimination.11,12,15,16 Anger management 3 increases depressive symptoms, and the manifestation of anger decreases them.13,17 Methods and materials The population of our study consisted of women diagnosed as HIV-positive getting medical attention in Nuevo Leon. The inclusion criteria were: being 18 years or older, knowing how to read and write, and signing a consent form before 2 witnesses.18 Exclusion criteria were the presence of symptoms impeding a proper comprehension and focus on the questionnaire. We took into consideration the recommendations made by the American Psychological Association for conducting research with human participants,19 thus we provided each participant with information on the purpose of the study, guaranteed confidentiality of their information, and requested a signed consent form. Considering that 60% of a population of 576 cases of women with HIV reported in Nuevo Leon during 20095 suffered discrimination,20 with a 95% confidence interval and a 5% exact standard error, we required a sample of 200 individuals. The 200 women who participated in the study were outpatients in Monterrey. They were interviewed by a psychologist while waiting for their appointments. The sampling process was performed between June 2010 and May 2011. In a face-to-face interview we questioned patients in order to obtain sociodemographic and clinical information. After the interview, the patients were given 3 scales so they could answer them in the presence of the interviewer. The scale of feared and perceived discrimination for women with HIV (DTP-40-MV)21 was developed for this study at a qualitative phase.19 This scale measures discrimination in expectation and perception aspects as a consequence of being HIV positive or having acquired immunodeficiency syndrome (AIDS). It consists of 40 Likert scale questions with a range from 1 “nothing” to 5 “completely”. Patients are presented with a series of situations of discrimination against HIV-seropositive people and/or people with AIDS, and asked how much these situations describe their own expectations or experiences. All items are direct and their total discrimination score is obtained simply by adding them. Their internal consistency is high (α = 0.92). It incorporates 6 correlated factors: feared discrimination with 11 indicators (α = 0.94), perceived discrimination at work and in the neighborhood with 8 indicators (α = 0.93), perceived discrimination at home with 8 indicators (α = 0.88), perceived discrimination in clinical care with 5 indicators (α = 0.91), perceived discrimination upon review of medical records with 2 indicators (α = 0.91), and moments of discrimination with 6 indicators (α = 0.85), with an accepted scalefree least squares: χ2/gl = 1.75, GFI = 0.94, AGFI = 0.93, NFI = 0.92, RFI = 0.91, and RMS SR = 0.01.21 These psychometric properties were estimated in the same sample as the study. The BDI-222,23 consists of 21 questions with 4 options each scored 0 to 3. A higher score reflects a greater presence and intensity of depressive symptoms. The adjustment of the model of 2 correlated factors by least squares was acceptable: χ2/gl = 2.14, FD =2.02, PNCP = 1.08, GFI = 0.81, AGFI = 0.76, and RMSEA = 0.08. 4 The Anger Expression Scale of State-Trait-Anger Expression Inventory (STAXI-2-AX/EX)24,25 includes 21 Likert scale questions ranging from 1 “almost never” to 4 “almost always”. It uses a 4-point frequency scale, 3 with 6 items each (anger control-out, anger control-in, anger expressionout), and 1 with 3 items (anger expression-in). The total score is obtained by adding the items. Total score of anger expression is obtained by adding the 9 items of anger expression-out and anger expression-in, constant 39 and deducting 12 items in anger control-in and anger control-out. In the present sample, in order to accomplish an acceptable solution in the confirmatory factor analysis, following the exploratory factor result, we added anger expression-in and anger expression-out (α = 0.89), anger control-in remained with 6 items (α = 0.88), just as anger control-out (α = 0.79). This correlated-factors model displayed good adjustment to generalized least squares: χ2/gl = 2.04, FD = 1.54, PNCP = 0.79, GFI = 0.84, AGFI = 0.80, and RMSEA = 0.07. The internal consistency of the 21 items was high (α = 0.89). Using statistics we analyzed the relationship between sociodemographic and affective variables with 3 subscales of studied discrimination through Pearson’s product-moment correlation coefficient (with numerical variables), biserial-punctual (with dichotomous variables), and ETA (with polytomous variables). We compared the statistical averages of each of the 3 studied discrimination subscales; analysis of variance and Student t test were used for paired samples. Using linear structural equation modelling, we contrasted a relationship model between discrimination, depression, and anger. We performed this utilizing the maximum likelihood method. For linear structural equation modeling, a model was contrasted between discrimination, depression, and anger using the maximum verisimilitude method.This method was chosen because it is the most accurate for parameter estimation and the multivariate normality assumption, required for this method, was fulfilled as it was indicated by a normalized value of the multivariate kurtosis of Mardia (critical reason) lower than 2.26 Nine adjustment indexes were considered: the statistical chi-squared (x2), the quotient between the statistical chi-squared and its degrees of freedom (x2/gl), the function of discrepancy (FD), the parameter of non-central populations (PNCP), Jöreskog and Sörbom’s goodness-of-fit index (GFI) and its corrected form (AGFI), Bentler-Bonett’s normed fit index (NFI) and comparative fit index (CFI), and Steiger-Lind’s root mean square error of approximation (RMSEA). The following were stipulated as good adjustment values: p of χ2 > 0.05, χ2/gl ≤ 2, FD and PNCP ≤ 1/5 of the corresponding values to the independent model, GFI and CFI ≥ 0.95, AGFI, NFI and RFI ≥ 0.90, RMSEA and RMS SR ≤ 0.05. And as aceptable adjustment values: p of χ2 > 0.01 χ2/gl ≤ 3, FD and PNCP ≤ 1/4 of the values corresponding to the independent model, GFI, CFI and RFI ≥ 0.85, AGFI and NFI ≥ 0.80, RMSEA and RMS SR < 0.08. 26,27 The correlation values less than 0.30 were considered low, from 0.30 to 0.69 were considered moderate, and greater than 0.69 were considered high. 28 In contrasts of parameters, the equivalence to 0 null hypothesis was rejected with p ≤ 0.05.28 J. Moral-de la Rubia and M. P. Segovia-Chávez Results Sample description Seventy-nine percent of patients reported having been infected by their spouse or live-in partner, 15.5% by a casual partner, 2% by a customer, 1.5% by a partner outside of marriage, 1% by a boyfriend, 0.5% as a result of rape, and 0.5% by vertical transmission (mother-child). The average time elapsed from the moment they had been diagnosed was 3.7 years (SD= 3.17), varying from 1 month to 18 years. Patients’ average age was 34.8 years (SD = 8.63; 18 to 50 years). Median and average level of education was incomplete junior high school. Forty-three percent of participants reported being married, 22.5% single, 14% living with a partner, 9.5% widows, 6% separated, and 5% divorced. Sixty-two percent of these women reported having children. Concerning religious beliefs; 88.5% were catholic and 11.5% christian. Discrimination feared in diverse social situations By dividing the average discrimination feared subscale (M = 35.2) by its number of items (11), and rounding up the result, we obtained 3 which corresponded to “a lot”, in a range from 1 (“nothing”) to 5 (“completely”). Feared discrimination correlated with a younger age in the participants, a lower average of their children’s ages, a lower frequency in attendance to religious services, their marital status, religion, and occupation; moreover, and among the affective variables with a higher total score of anger, higher anger expression-out, and lower anger control-out. Single women who were living from commercial sex and catholics had a greater fear of being discriminated against (Table 1). Discrimination perceived in clinical care, and upon review of medical records After dividing the average of the discrimination perceived subscale in the clinical care (M = 11.0) by the number of items (5) and rounding up the result, we obtained 2, which corresponds to “a little”. Discrimination perceived in clinical care was independent of sociodemographic variables. It correlated with a lower total score of depression and its 2 factors of cognitive-affective and somatic-motivational symptoms, as well as a higher total score of anger, higher anger expression-out, and a lower anger control-out (Table 1). After dividing the average of the discrimination perceived upon review of medical records (M = 6.4) by the number of items (2) and rounding up the result, we obtained 3, which corresponds to “a lot”. Discrimination perceived upon review of medical records correlated with religion (catholics perceived more discrimination), a higher total score of anger, lower anger control-out, and a lower frequency of attendance to religious services (Table 1). Correlation and differences of averages between 3 discrimination subscales Correlation of feared discrimination with perceived discrimination in clinical care was moderate (r = 0.40, p < 0.01), Discrimination in clinical settings and its relationship to depression and anger in women living with HIV 5 Table 1 Discrimination correlations with emotional and sociodemographic variables. Discrimination Emotional and sociodemographic Variables Feared PAC PEC Total score 0.06 ns -0.25** 0.04 ns Cognitive-affective(1) 0.08 ns -0.27** 0.03 ns 0.01 ns -0.15* 0.05 ns Total score 0.22** 0.30** 0.20** Expression-out(1) 0.20** 0.28** 0.13 ns Control-in(1) -0.05 ns -0.12 ns -0.14* Control-out(1) -0.25** -0.25** -0.20** Age(1) -0.18** -0.09 ns -0.07 ns Number of children(1) -0.12 ns -0.11 ns -0.01 ns (1) Depression (BDI-21) Somatic-motivational (1) (1) Anger (AX-21) -0.20** -0.04 ns -0.09 ns Level of education(1) -0.04 ns -0.01 ns 0.03 ns Religious practices -0.31** -0.12 ns -0.17* -0.20** -0.13 ns -0.22** Marital status(3) 0.45** 0.22 ns 0.21 ns Occupation 0.30** 0.19 ns 0.09 ns Children’s average age Sociodemographic variables (1) (1) Religion(2) (3) (1) r = Pearson’s product-moment, (2) rbp: biserial-punctual and (3) η = eta. * p ≤ 0.05 ns p > 0.05. ** p ≤ 0.01. PAC: discrimination perceived in clinical care; PEC: discrimination perceived upon review of medical records. Religion: (1) = catholic, (2) = christian. whereas correlation with perceived discrimination upon review of medical records was low (r = 0.29, p < 0.01). Correlation between both perception subscales was moderate as well (r = 0.40, p < 0.01). In order to accomplish a homogeneous range from 1 to 5, thus to be able to make intra-group average comparisons, we divided each scale’s score by its number of items. There was a difference between averages in the 3 subscales (F[2, 398] = 68.76, p < 0.01, assuming sphericity in the Mauchsly test: W = 0.99, χ2[2, N = 200] = 1.11, p = 0.57). The average of perceived discrimination in clinical care was lower than the average of perceived discrimination upon review of medical records (t[199] = -10.67, p < 0.01), and feared discrimination average (t[199] = -9.92, p < 0.01), being the averages statistically equivalent in these last 2 subscales (t[199] = -0.20, p = 0.83) (Fig. 1). Structural model of discrimination, anger, and depression The model was calculated only with the subscales. We specified a latent perception of discrimination in clinical settings factored with 2 indicators (clinical care and upon review of medical records). Given its highest correlation with the 3 discrimination subscales, we considered cognitive-motivational depression symptoms as well as anger expression-out and control-out. Cognitive-affective symptoms correlated with anger expression-out (r = -0.19, p < 0.01) and were independent from anger control (r = 0.13, p = 0.06). Taking into account these last 2 correlations, we specified a first model where the loss of anger control-out predicted anger expression-out. Anger expression-out predicted a reduction of the cognitive-affective symptoms of depression. Feared discrimination (manifest exogenous variable) predicted awareness of perceived discrimination in clinical settings (latent endogenous variable), loss of anger control-out, anger expression-out, and cognitive-affective symptoms of depression. Perceived discrimination in clinical settings predicted loss of anger control-out, anger expression-out, and a decrease in cognitive-affective symptoms of depression. Three out of the 9 adjustment indexes were bad (χ2[4, N = 200] = 20.49, p < 0.01, χ2/gl = 5.12 and RMSEA = 0.14), 2 were acceptable (AGFI = 0.84 and CFI = 0.91), and 4 good (GFI = 0.97, NFI = 0.90, FD = 0.10 and PNCP = 0.08). Three parameters of the directional relations of the structural model were not significant: the determination of anger control-out and anger manifestation due to feared discrimination, and the determination of the cognitive-affective symptoms due to expression-out. We explained 28% of perceived discrimination in clinical settings, 14% of anger control-out, 30% of anger expression-out, and 14% of cognitive-affective symptoms of depression (Fig. 2). According to the BDI in samples from the United States22 and Spain23, the internal consistency of its 21 items of BDI-2 was high, varying from 0.87 to 0.92; BDI-2’s factorial analysis provided a 2 correlated factors solution (cognitive-affective and somatic-motivational symptoms) with an acceptable adjustment to data. In the present Mexican sample, BDI-2’s 6 J. Moral-de la Rubia and M. P. Segovia-Chávez Medidas en un rango de 1 a 5 χ2 (4, N = 200) = 20.49, p < 0.01, χ2/gl = 5.12, GFI = 0.97, AGFI = 0.84, CFI = 0.91, NFI = 0.90, FD = 0.10, PNCP = 0.08 y RMSEA = 0.14 3.25 3.22 3.20 3.00 14% 2.75 -0.08 Anger control-out e1 2.50 Discrimination feared -0.33 2.20 2.25 DT PAC -0.46 PEC DT: discrimination feared; PAC: discrimination perceived in clinical care; PEC: discrimination perceived upon review of medical records. 30% e2 0.53 -0.01 Anger expression-out 0.29 -0.16 e3 Cognitive-affective depression factor Discrimination perceived in clinical settings e6 0.68 0.58 14% -0.34 Figure 1 Averages diagram. 28% 0.18 Review of medical records Clinical care 34% 21 items had high internal consistency (α = 0.94), as well as the 14 items of factors of cognitive-affective symptoms (α = 0.93) and the 7 factors of somatic-motivational symptoms (α = 0.83). After reviewing the adjustment improvement indexes of this first model, we suggested the introduction of determination of perceived discrimination upon review of medical records by cognitive-affective symptoms of depression. We must take into account that when we partialized the effect of discrimination perceived upon review of medical records (latent factor), the correlation between anger expressionout and cognitive-affective symptoms of depression ceased to be significant (rp = -0.12, p = 0.08). When we partialized the effect of discrimination perceived in clinical care and upon review of medical records (latent factor), the correlation between discrimination feared and anger expressionout ceased to be significant (r p = 0.13, p = 0.07). The correlation between perceived discrimination and anger control-out only ceased to be significant when we partialized anger expression-out apart from the latent factor (rp = -0.12, p = 0.09). On the contrary, the correlation of feared discrimination and cognitive-affective symptoms of depression was significant, when we partialized anger expression-out effect and anger control-out (rp = 0.15, p < 0.05), and when partializing the effect of perceived discrimination in clinical care (rp = 0.17, p = 0.01), yet it had not been before (r = 0.08, p = 0.27). Furthermore, when we patialized the effect of perceived discrimination in clinical care, the correlation between cognitive-affective symptoms of depression and perceived discrimination upon review of medical records was significant (rp = 0.16, p < 0.05), yet it had not been before (r = 0.03, p = 0.68). We specified a second model, eliminating non-significant parameters from the first one and considering partial correlations data, as well as suggested correction from the adjustment improvement indexes. Loss of anger control-out predicted anger expression-out. Feared discrimination (exogenous manifest variable) predicted perceived discrimination in the clinical setting (endogenous manifest variable) and cognitive-affective symptoms of depression. Perceived discrimination in the clinical setting predicted anger control-out and anger expression-out, as well as cognitiveaffective symptoms of depression. Cognitive-affective symptoms predicted perception of discrimination upon review of medical records. e4 46% e5 Figure 2 Standardized model of anger and depression as a consequence of discrimination, estimated by maximum verisimilitude. The value of the 9 adjustment indexes was good. The parameters of the 6 directional relationships in the structural model, and both of the parameters in the measurement model were significant. We explained 25% of perceived discrimination in the clinical setting, 17% anger control-out, 31% anger expression-out, and 33% cognitive-affective symptoms of depression (Fig. 3). Discussion These HIV-seropositive women, mostly young women, reported fearing being discriminated against in several social situations and perceive discrimination upon review of medical records; however, the perception of discrimination in clinical care, without considering review of medical records, was low. We must point out that perception of discrimination upon review of medical records, within the group of the 6 subscales of DTP-40-MV, defined a factor of second order with feared discrimination, thus reflecting a greater connotation of expectations rather than facts. Therefore, this perception seems to be generated by administrative and auxiliary staff, and not at the moment of going in to see the doctors, nurses, psychologists, and social workers. If any of the previous studies in Mexico have directed discrimination perception in the clinical setting,29 these also seem to focus upon review of medical records amongst administration staff and auxiliaries. Moreover, we must point out the fact that the low frequency of discrimination in clinical consultations observed is coherent with other reports.30 This tendency is also reflected by the second National Survey on Discrimination in Mexico,31 in which as compared with the first one,32 the percentage of people who would not agree to live with an HIVseropositive person went from 44% to 35.9%. Besides the fact that the expected discrimination level in different social situations was higher than the discrimination perception in clinical care, requiring intervention, such Discrimination in clinical settings and its relationship to depression and anger in women living with HIV χ2 (6, N = 200) = 6.21, p = 0.40, χ2/gl = 1.03, GFI = 0.99, AGFI = 0.96, CFI = 1, NFI = 0.97, FD = 0.03, PNCP < 0.01 y RMSEA = 0.01 17% e1 Anger control-out Discrimination feared -0.41 -0.44 0.50 31% e2 25% Anger expression-out 0.20 0.40 Discrimination perceived in clinical settings e6 0.64 0.74 33% -0.65 e3 Cognitive-affective factor of depression Review of medical records 0.36 Clinical care 44% e4 41% e5 Figure 3 Reviewed standardized model of anger and depression as a consequence of discrimination, estimated by maximum verisimilitude. expectations influence perception, creating awareness. This is an aspect that is not addressed in any program directed toward HIV-seropositive patients.33,34 Frequency of attendance to religious services is an indicator of a degree of religiousness, in addition to a strong social support. This study’s correlated data show that women who practice their religion more often suffer less expectations of being rejected, and perceive less discrimination upon review of medical records, as observed in other researches.35 We shall not attribute this to the context of religious community communication and support, since their effect is often the opposite, 36 this due to the fact that amongst women who practice their religion more often are the widows and married who were infected by their husbands, which frees them from the social stigma of the main risk factors of HIV infection, and brings compassion from the people closer to them; on the contrary, amongst women who practice religion the least there are single women and sex-workers who attract greater social stigma.12,20 In favor of this argument we have the correlations between religious practice and discrimination increased when calculated without married women, but it ceases to be significant when single women are disregarded, making the association between marital status and religious practice significant (η = 0.38, p < 0.01). Within depression, the cognitive-affective symptoms factor was the most related to discrimination, which can be explained by a higher affinity to evaluated contents in comparison to the somatic-motivational symptoms factor. Contrary to what was expected, cognitive-affective symptoms of depression seem to be independent of feared discrimination, but when we partialized the effect of anger controlout and anger expression-out, the relation was significant; that is, anger would disguise the relationship with the adjustment improvement of data that fear of being discriminated against increases cognitive-affective symptoms of depression. 7 Furthermore, perception of discrimination in the clinical setting which generated an activating reaction (more anger and less depression) was hiding the fact that the cognitiveaffective symptoms of depression aroused by feared discrimination increased the perception of discrimination upon review of medical records. These data seem to reflect the fact that these women consider it a right to be attended to and an obligation of clinical and administrative staff to provide respectful and quality care,31 hence the infringement of this right creating a reaction of anger which even reduces depressive feelings or thoughts. This relation is so well defined that it annuls anger expression-out over depression, when there is a negative correlation between these 2 variables. We must point out as one of the limitations of the study the fact that we utilized a sample composed solely of women. Given the size of the sample, with a sample fraction of a third of the women attended to in Nuevo León, Mexico, this sample is representative, with an absolute error of 5% and a confidence interval of 95%; however, the extrapolation to similar populations must be made in the form of a hypothesis. In conclusion, these HIV-seropositive women fear being discriminated against; however, the perception of discrimination in clinical care, aside from review of medical records, is low. As is the perception of a clinical chart with a different color from other patients’, or subtle markings, certain gestures or distances from administrative and auxiliary staff seem to generate expectation of discrimination which is not confirmed by the doctors. The expectation of discrimination increases depressive thoughts and feelings, as expected; however, this relation is only observed when we statistically control the effect of perception of discrimination in clinical care by a strong anger outburst (activator) which it generates; besides, the expectation of discrimination sensitizes perception of discrimination, in accordance with expectations. On the other hand, cognitive-affective symptoms of depression aroused by the expectation of discrimination sensitize perception of discrimination upon review of medical records, which seems to define a closed self-reinforcing circle. This is broken by an anger outburst when discrimination in the clinical settings by doctors is perceived, when patients feel deprived of care which they are entitled to, and which has to be performed then and there without complaining. Based on these data, we suggest contemplating the expectation of discrimination in interventions within this population of women with HIV, especially because of its depressive effect and sensitizing to the perception of discrimination upon review of medical records by administrative and auxiliary staff, which constitutes as the most frequent act of perceived discrimination in the clinical setting, even when in the consult with doctors, nurses, psychologists, and social workers they do not confirm the expectation generated by this first impression. Conflicts of interest The authors have no conflicts of interest to declare. 8 Funding No financial support was provided. References 1. Nakagawa F, Lodwick RK, Smith CJ, et al. Projected life expectancy of people with HIV according to timing of diagnosis. AIDS 2012;26:335–343. 2. Flores PF, Leyva FR. Representación social del SIDA en estudiantes de la Ciudad de México. Salud Publica Mex 2003;45(suppl 5):624-631. 3. Magis C, Barrientos H. VIH/SIDA y salud pública. Manual para personal de salud (2ª. edición). Cuernavaca, Morelos, México: Instituto Nacional de Salud Pública (INSP); 2009. 4. Joint United Nations Programme on HIV/AIDS (UNAIDS). Global report. UNAIDS report on the global AIDS epidemic 2013. Ginebra: WHO Library Cataloguing-in-Publication Data; 2013. 5. Centro Nacional para la Prevención y el Control del VIH/SIDA (CENSIDA). Vigilancia epidemiológica de casos de VIH/SIDA en México. Registro nacional de casos de SIDA. Actualización al 30 de junio de 2013. México, DF: CENSIDA; 2011. 6. Lee RS, Kochman A, Sikkema KJ. Internalized stigma among people living with HIV/AIDS. AIDS Behav 2002;6:309-319. 7. Dray-Spira R, Legeai C, Le Den M, et al. Burden of HIV disease and comorbidities on the chances of maintaining employment in the era of sustained combined antiretoviral therapies use. AIDS 2012;26:207-215. 8. Maman S, Abler L, Parker L, et al. A comparison of HIV stigma and discrimination in 5 international sites: The influence of care and treatment resources in high prevalence settings. Soc Sci Med 2009;68:2271-2278. 9. Hosseinzadeh H, Hossain SZ. Functional analysis of HIV/AIDS stigma: consensus or divergence? Health Educ Behav 2011;38:584-595. 10. Ciesla JA, Roberts JE. Meta-analysis of the relationship between HIV infection and risk for depressive disorders. Am J Psychiatry 2001;158:725-730. 11. Li L, Lee SJ, Thammawijaya P, et al. Stigma, social support, and depression among people living with HIV in Thailand. AIDS Care 2009;21:1007-1013. 12. Zukoski AP, Thorburn S. Experiences of stigma and discrimination among adults living with HIV in a low HIV-prevalence context: A qualitative analysis. AIDS Patient Care STDS 2009;23:267-276. 13. Hansen N, Sassenberg K. Exploring the self-directed anger of the stigmatized: The interplay between perceived legitimacy and social identification. Group Processes Intergroup Relations 2011;14:807-818. 14. Health Policy Initiative (HPI). Measuring the degree of HIV-related stigma and discrimination in health facilities and providers: Working report. Washington, DC: HPI; 2010. 15. Vanable PA, Carey MP, Blair DC, et al. Impact of HIV-related stigma on health behaviors and psychological adjustment among HIV-positive men and women. AIDS Behav 2006;10:473482. 16. Bogart LM, Cowgill BO, Kennedy D, et al. HIV-related stigma among people with HIV and their families: A qualitative analysis. AIDS Behav 2008;12:244-254. 17. Borders A, Liang CT. Rumination partially mediates the associations between perceived ethnic discrimination, emotional distress, and aggression. Cultur Divers Ethnic Minor Psychol 2011;17:125-133. J. Moral-de la Rubia and M. P. Segovia-Chávez 18. Secretaría de Salud. Norma Oficial Mexicana NOM-039SSA2-2002. Para la prevención y control de las infecciones de transmisión sexual. México: Diario Oficial de la Federación, 2003, 19 de septiembre: 100-117. Disponible en: http://www. hsph.harvard.edu/population/aids/mexico.aids.02.htm 19. American Psychological Association. Ethical principles of psychologists and code of conduct. American Psychologist 2002;57:1060-1073. 20. Moral J, Segovia MP. Discriminación en mujeres que viven con VIH/SIDA. Revista Iberoamericana de Psicología y Salud 2011;2:139-159. 21. Moral J, Segovia MP. Propiedades psicométricas de la escala de discriminación temida y percibida para mujeres con VIH (DTP-40-MV). Revista Iberoamericana de Psicología y Salud 2013;4:37-62. 22. Beck AT, Steer RA, Brown GK. Manual for the Beck Depression Inventory-II.San Antonio, TX: Psychological Corporation; 1996. 23. Sanz J, Perdigón LA, Vázquez C. Adaptación española del Inventario para la Depresión de Beck-II (BDI-II): 2. Propiedades psicométricas en población general. Clínica y Salud 2003;14:249280. 24. Spielberger CD. State-Trait Anger Expression Inventory-2 (STAXI-2). Professional manual. Florida: Psychological Assessment Resources; 1999. 25. Moral de la Rubia J, González Ramírez MT, Landero Hernández R. Factor structure of the STAXI-2-AX and its relationship to the burnout in housewives. Span J Psychol 2010;13:418-430. 26. Kline RB. Principles and practice of structural equation modeling (3rd ed.). New York: The Guilford Press; 2010. 27. Moral J. Análisis factorial confirmatorio. En: Landero R, González MT (eds.), Estadística con SPSS y metodología de la investigación. México, DF: Trillas; 2006. p. 445-528. 28. Cohen J, Cohen P, West SG, et al. Applied multiple regression/ correlation analysis for the behavioral sciences (3rd ed.). Mahwah, NJ: Psychology Press; 2003. 29. Infante C, Zarco A, Magali S, et al. El estigma asociado al VIH/ SIDA: el caso de los prestadores de servicios de salud en México. Salud Pública Méx 2006;48:141-150. 30. Córdova JA, Ponce-de-León S, Valdespino JL. 25 años de SIDA en México. Retos, logros y desaciertos. México: CENSIDA; 2009. 31. Consejo Nacional para Prevenir la Discriminación (CONAPRED). Encuesta Nacional sobre Discriminación en México 2010. Resultados generales. México, DF: CONAPRED; 2011. 32. Consejo Nacional para Prevenir la Discriminación (CONAPRED). Primera encuesta nacional sobre discriminación en México. México, DF: CONAPRED; 2005. 33. Apinundecha C, Laohasiriwong W, Cameron MP, et al. A community participation intervention to reduce HIV/AIDS stigma, Nakhon Ratchasima province, Northeast Thailand. AIDS Care 2007;19:1157-1165. 34. Wu S, Li L, Wu Z, et al. A brief HIV stigma reduction intervention for service providers in China. AIDS Patient Care STDs 2008;22:513-520. 35. Kudel I, Cotton S, Szaflarski M, et al. Spirituality and religiosity in patients with HIV: A test and expansion of a model. Ann Behav Med 2011;41:92-103. 36. Muturi N, An S. HIV/AIDS stigma and religiosity among African American women. J Health Commun 2010;15:388-401. Medicina Universitaria 2014;16(62):9-11 medicina universitaria www.elsevier.com.mx Original article Frequency of metabolic syndrome in women treated at the Menopause Clinic of the “Dr. José Eleuterio González” University Hospital of the UANL in Northeastern Mexico M. Cervantes-Flores*, J. Vázquez-Méndez, D. Saldívar-Rodríguez, O. Vidal-Gutiérrez, I. Y. González-Carrillo, G. Guerrero-González Department of Gynecology and Obstetrics, “Dr. José Eleuterio González” University Hospital, Universidad Autónoma de Nuevo León, Monterrey, N. L., Mexico Received: February 2013; Accepted: October 2013 KEYWORDS Metabolic syndrome; Menopause; Estrogen; Diabetes mellitus; Obesity; Mexico. Abstract Objectives: To determine the frequency of metabolic syndrome (MS) in patients with menopause, and to compare the incidence of MS between surgical and natural menopause. Methods: This was an observational, longitudinal, descriptive, retrospective, unblinded study of cases seen at the Menopause Clinic of the University Hospital “Dr. José Eleuterio González” of the Universidad Autónoma de Nuevo León from March 2009 to December 2011. The frequency of MS was determined based on Adult Treatment Panel III (ATPIII) classification. Results: At the end of the study, 391 patients were evaluated. The mean age was 50.1 years. We found a frequency of MS of 38.1%, the risk factor most often found was low HDL-cholesterol (62.5%), followed by obesity (46.5%), hypercholesterolemia (42.3%), hyperglycemia (11.5%), and hypertension (7.7%). The incidence of natural and surgical menopause was 37.6% vs. 39.2% respectively; however, the result was not statistically significant (p = 0.093). Conclusions: Patients with menopause are at increased risk of developing MS. It is important to detect MS early in this of patients, when they have one risk factor to avoid complications which may trigger the syndrome. We recommend screening for MS during perimenopause, in order to detect and try to delay it in a timely manner and recommend primary prevention (diet and exercise), or secondary prevention in cases with one or more risk factors. 1665-5796 © 2014 Revista Medicina Universitaria. Facultad de Medicina UANL. Publicado por Elsevier México. Todos los derechos reservados. * Corresponding author: Domingo Gayoso 240, Centro, Z.P. 64000, Monterrey, N. L., México. Telephone: (81) 1066 1243, (81) 1516 4865. E-mail address: [email protected] (M. Cervantes-Flores). 10 Introduction Metabolic syndrome is the coexistence of several pathologies or risk factors in a person. This cluster of conditions increases the risk of heart disease, stroke, and diabetes mellitus. MS has several genetically determined phenotypic variances, as well as being conditioned by environmental factors, cardiovascular disease risk factors and abdominal fat accumulation.1,2 Menopause refers to the last menstruation cycle as a consequence of the loss of activity in the ovaries. It is identified after 12 months of amenorrhea and it only occurs in humans. The follicle-stimulating hormone, which stimulates growth and storage of the ovarian follicles in the ovary, confirms menopause when found in blood greater or equal to 40 mU/dl. As a result of the complete cessation of ovarian activity, 3,4 menopause can also be produced artificially following bilateral oophorectomy, after abruptly and completely suppressing the action of the ovaries, causing a sharp estrogen drop and losing the ovarian androgenic capacity.5 Menopause brings both hormonal and metabolic changes that condition an increase in body weight, producing peripheral insulin resistance, rise in blood pressure, and disorders of lipid metabolism; these are the main components of MS. Women between the ages of 17 and 24 and from 25 to 44 have a prevalence of MS of 3.8% and 16.6% respectively, compared to women between the ages of 45 and 64 with menopause, who show a prevalence of 35.8%.6,7 In order to diagnose MS the current consensus is based on criteria by the National Cholesterol Education Program, which indicates that 3 or more of the following risk factors are required in order to make a diagnosis in women: abdominal circumference of 88 cm or body mass index (BMI) of 30 or higher; triglyceride levels higher than 150 mg/dl; blood pressure of 130/85 mmHg; blood sugar levels greater than 110 mg/dl, and HDL-cholesterol < 50 mg/dl.8,9 The objective of our study was to determine the frequency of MS in women with menopause. Methods We carried out an observational, longitudinal, descriptive, retrospective, unblinded study of cases seen at the Menopause Clinic of the University Hospital “Dr. José Eleuterio González” of the Universidad Autónoma de Nuevo León from March 2009 to December 2011. We included patients consulting for the first time, patients who had had amenorrhea for over a year, patients having undergone bilateral oophorectomy, and patients who had not received hormone replacement therapy for at least 3 months prior to the study. We performed lab tests as well as a complete somatometry. We excluded patients who did not wish to participate and those who did not have the required tests. We eliminated patients who abandoned the study or who did not hand in complete lab results. We determined the existence of MS based on the presence of 3 or more criteria of the ATPIII classification.8,9 We created a database with collected information and analyzed it using SPSS ® v. 20.0; we applied descriptive M. Cervantes-Flores et al Table 1 Metabolic syndrome risk factors and frequency. Risk factor Patients (n) Percentage Hypertension 30 7.70% Hyperglycemia 45 11.50% Hypertriglyceridemia 144 36.80% Hypercholesterolemia 166 42.30% Obesity 182 46.50% Low HDL-cholesterol 245 62.50% statistics to the different variables analyzed with average, median, mode, and ranges. In addition, we analyzed age, occupation, parity, and surgical or artificial menopause. During physical examinations, we assessed blood pressure, weight, height, and BMI, as well as lab tests, specifically lipid profile and fasting serum glucose results. We performed a statistical analysis using Pearson’s chi square in order to analyze the frequency of MS in patients with natural vs. surgical menopause. We used convenience sampling. This study was approved by the Ethics Committee of “Dr. José Eleuterio González” University Hospital. Results Data from 391 patients were evaluated. The mean age was 50.1 years with a minimum of 21 and a maximum of 84. Most patients were multiparous (73.5%, n = 28), housewives (82.4%, n = 322), and had attended the menopause clinic as a result of climacteric symptoms (79.3%, n = 310). We found a frequency of MS of 38.1% (n = 149). Only 10% (n = 43) were healthy and 50.8% (n = 199) displayed 1 or 2 criteria for MS, i.e., 1 in every 2 patients with menopause present at the University Hospital has at least 1 MS factor. Regarding the patients with MS, we found that 92 (23%) displayed 3 criteria, 44 (11.27%) 4, and 17 (4.34%) 5 or more criteria for the syndrome. The risk factor most often found was low HDL-cholesterol (62.5%, n = 245), followed by obesity (182 [46.5%] and patients who had a BMI greater than 30 kg/m2]. The third most frequent factor found was hypercholesterolemia (42.3%, n = 166), followed by hypertriglyceridemia (38.3%, n = 144). The least frequent factors were hyperglycemia and high blood pressure (11.5% [n = 45] and 7.7% [n = 30], respectively) (Table 1). Regarding the comparison of the incidence of MS between women with natural and surgical menopause, we found a frequency of 37.6% (n = 49) vs. 39.2% (n = 100), respectively; this result was not statistically significant (p = 0.093). Metabolic syndrome was more frequent in patients in the fifth decade of their lives; comparing the onset of natural versus surgical menopause we observed in the latter group an onset at a younger age (mean age of 49.2), beginning even in the third decade of their lives (21 years). Frequency of metabolic syndrome in women treated at the Menopause Clinic of the “Dr. José Eleuterio González” University Hospital of the UANL in Northeastern Mexico Discussion Conflicts of interest In recent years, MS has become more and more common throughout the world, occuring in 25% of the population, especially in the US and Latin America where up to one third of the population suffers from obesity.10 We found the syndrome in over a third of our patients (38.1%), which concurs with the literature, where an incidence of 30% to 70% is reported.10,11 Results from studies carried out in Latin America are similar to ours. In 2011, Tabares et al. analyzed the cases of MS in 189 postmenopausal women, finding an incidence of 31%.12 In Brazil, Albuquerque evaluated the presence of MS in pre- and postmenopausal women, finding a similar percentage to ours (34.7%),13 being greater in menopausal women than those premenopausal, which concurs with the hypothesis in this study. When comparing in our study the frequency of MS in natural and surgical menopause, no significant differences were found; however, the percentage was lower in the first group. In 2008, Dorum A et al. carried out a study in Norway finding a higher prevalence of MS in patients who had undergone bilateral oophorectomy before 50, hence a greater risk of heart diseases.14 The authors have no conflicts of interest to declare. Conclusion MS is frequent among postmenopausal women attending the Menopause Clinic of the “Dr. José Eleuterio González” University Hospital. The most frequent criteria for this diagnosis were -in order of importance-: low concentrations of HDL-cholesterol, obesity, and hypercholesterolemia. Only a few patients with menopause did not show any risk factor; on the contrary, 50% showed 1 or 2 factors for this syndrome. It can be infered that these women are prone to suffer some chronic disease; therefore, early detection and action to reverse this condition are essential. We did not find a difference between MS frequencies in patients with natural vs. surgical menopause; however, analysis of age groups showed that patients who had undergone bilateral oophorectomy were younger than those with natural menopause. We recommend screening for MS during perimenopause, to detect and try to delay it in a timely manner, having as an advantage the fact that this prevention is low-cost and easy to perform. 11 Funding No financial support was provided. References 1. Balas M, Perichart O, Pantoja L, et al. Evaluación nutricional en mujeres mexicanas posmenopáusicas con síndrome metabólico. Ginecol Obstet Mex 2007;75:515-526. 2. Carranza S, Guerrero L, Castro A. Frecuencia del síndrome metabólico en mujeres postmenopáusicas mexicanas y su relación con la terapia hormonal. Ginecol Obstet Mex 2009;77:367-371. 3. Janssen I, Powell LH, Crawford S, et al. Menopause and the metabolic syndrome: the Study of Women’s Health Across the Nation. Arch Intern Med 2008;168:1568-1575. 4. Brantes S. Current concepts in the diagnosis of permimenopause. Medwave 2009;9(11):e464. 5. García M, Rodríguez E. Caracterización del síndrome climatérico en mujeres castradas por vía quirúrgica. Rev Cubana Obstet Ginecol 2001;27:106-113. 6. Rocabado Urquieta EJ, Rocha Soria MI, Rivera Rojas CM, et al. Síndrome metabólico en la menopausia. Rev Méd (Cochabamba) 2007;18:85-90. 7. Reaven GM. Banting Lecture 1988. Role of insulin resistance in human disease. diabetes 1988:37;1595-1607. 8. Puche C, Cabero A, Meseguer A. 17 b hydroxylase activity in human adipose tissue. European Journal of Endocrinol 2002;146:223-229. 9. González A. Consenso mexicano sobre el tratamiento integral del síndrome metabólico. Rev Mex Cardiol 2002;13:4-31. 10. Cameron AJ, Shaw JE, Zimmet PZ. The metabolic syndrome: Prevalence in worldwide populations. Endocrinol Metab Clin North Am 2004;33:351-375. 11. Fenochio-González F. Prevalencia de síndrome metabólico en mujeres posmenopausicas con y sin tratamiento hormonal sustitutivo. Rev Invest Med Sur Mex 2012;19:60-66. 12. Tabares-Trujillo M. Síndrome metabólico en menopausia: implicaciones de la terapia hormonal. Perinatol Reprod Hum 2012;26:25-29. 13. Albuquerque J. Síndrome metabólico y menopausia. Arq Bras Cardiol 2010;95:339-345. 14. Dorum A, Tonstad S, Liavaag A, et al. Bilateral oophorectomy before 50 years of age is significantly associated with the metabolic syndrome and Framingham risk score: A controlled, population-based study (HUNT-2). Gynecol Oncol 2008;109:377-383. Medicina Universitaria 2014;16(62):12-14 medicina universitaria www.elsevier.com.mx Original article Correlation between BMI and climateric symptoms in menopausal women I. Y. González-Carrillo*, J. Vázquez-Méndez, G. Guerrero-González, O. Vidal-Gutiérrez, M. Cervantes-Flores Department of Gynecology and Obstetrics, “Dr. José Eleuterio González” University Hospital, Universidad Autónoma de Nuevo León, Monterrey, N. L., Mexico Received: February 2013; Accepted: November 2013 KEYWORDS Climateric symptoms; Body mass index; Blatt-Kupperman index; Obesity; Mexico. Abstract Objectives: To determine the association between climateric symptoms and body mass index (BMI). In addition, to define the age of onset of climateric symptoms and to associate a patient’s occupation and marital status with climateric symptom severity. Materials and methods: Observational, retrospective and cross-cohort study including 403 patients attending the Menopause Clinic of the University Hospital of the Universidad Autónoma de Nuevo León from November 2008 to December 2011. Clinical history, physical examination, weight and height, and BMI were evaluated. Climateric symptoms were assessed through the Blatt-Kupperman modified index. Marital status and occupation were also analyzed. Results: No relation was found between BMI and climateric severity, nor was there any relation between climateric symptoms and marital status or occupation. Conclusions: Additional research is needed to assess the influence of climateric risk factors. 1665-5796 © 2014 Revista Medicina Universitaria. Facultad de Medicina UANL. Publicado por Elsevier México. Todos los derechos reservados. Introduction Menopause is the natural biological process in which a woman’s menstrual period stops permanently. During climaterium, the progressive disappearance of the ovarian function occurs leading to a gradual decline in estrogen secretions and several associated hormonal alterations giving rise to a series of organic and psychological changes. In healthy women, menopause occurs between the fifth and the sixth decades of life (from ages 47 to 52).1 Climateric symptoms worsen in relation to social determinants linked to race, social and cultural entitlements which fall upon their gender.2 The manifestations produced as a consequence of the ovarian function ceasing and the subsequent hormonal deficit, * Corresponding author: Laguna de Catemaco 1359, Las Quintas, Z.P. 80060, Culiacán, Sin., Mexico. Telephone: (667) 715 8045. E-mail address: [email protected] (I. Y. González-Carrillo). Correlation between BMI and climateric symptoms in menopausal women are expressed with very unique symptoms known as climateric.1-3 In order to evaluate climateric symptoms, different scales have been developed, for instance the Kupperman index,4 the Utian Quality of Life (UQOL) Scale,5 the Greene scale,6 and the SUMEVA scale.7 Some assess the impact of climateric symptoms in the quality of life, especially the influence on perimenopausal patients, this information being useful in the follow-up of patients who receive hormone replacement treatment (HRT).8 Hypoestrogenism has been related to physiological changes which are, in part, responsible for the weight gain during that period.9 In Mexico, an overweight prevalence of 72% in adult women has been reported.10 Obesity in connection with vasomotor symptoms is controversial. Previous studies suggest that body fat protects women from vasomotor symptoms due to the aromatization of androgens to estrogens in the adipose tissue; however, other evidence suggests that a greater body mass index (BMI), and increased body fat in particular, are associated with reports of greater climateric manifestations.11,12 In this study we assess the hypothesis that there is a correlation between BMI and the severity of climateric symptoms, studying overweight (according to BMI) connection with climaterium, through the Blatt-Kupperman index,4 with the purpose of determining whether or not obese or overweight patients suffer from more severe climateric symptoms. Materials and methods An observational, retrospective, descriptive, cross-cohort study was described. We included 431 patients who attended the Menopause Clinic of the “Dr. José Eleuterio González” University Hospital of the Universidad Autónoma de Nuevo León, in Monterrey, N. L., Mexico, from November 2008 to December 2011. Patients who had received HRT during the previous 3 months and those who did not comply with the required data were excluded. We performed a full clinical history check in order to obtain personal data and background information, a physical examination including measurement of height and weight to obtain BMI and a questionnaire on climateric symptoms through the Blatt-Kupperman modified index.5 The BlattKupperman index is a scale used to determine the severity of climateric symptoms; it assesses 15 symptoms, which are rated by the patients as follows: 0 = none, 1 = mild, 2 = moderate, 3 = severe. Subsequently, a score was obtained which was categorized as mild (0-20), moderate (21-35), or severe (> 35).13 The variables included were: Age, marital status, occupation, BMI, number of years of menopause, and modified BlattKupperman index. With the data obtained we created a database in Microsoft Excel®, for subsequent analysis using SPSS® v. 14. All the variables were analyzed with traditional descriptive statistics such as statistical average and dispersion measures (standard deviation). Pearson’s correlation test was used to assess the correlation between BMI and Blatt-Kupperman, as well as a dispersion graph. Using Pearson’s correlation, a value of -1 to 1 was obtained (a value closer to 1 indicates a positive correlation while a value closer to -1 indicates a negative correlation; if the value is close to 0, it implies 13 that there is no lineal relation). We assessed the correlation between marital status and occupation with the Blatt-Kupperman index through Pearson’s R test. Results A total of 403 patients with an average age of 50.01 (± 7.70) years, with an average of 5.69 (± 5.97) years of menopause were included in the study. The average BMI was 28.98 (± 5.71) kg/m2. The average value of the Blatt-Kupperman index was 25.78 ± 13.48. Regarding marital status, 334 (83%) of the patients were married, 52 (13%) were single, and 17 (4%) were widows. Three hundred forty-nine patients (87%) were housewives, 42 (10%) were employed outside their homes and 12 patients (3%) were retired. We found that the symptoms in 113 patients (28%) were rated as severe, in 140 (35%) as moderate, and in 150 (37%) as mild, according to the Blatt-Kupperman index. Concerning BMI and degree of obesity, 0.3% of the patients were thin, only 20.1% had what is considered to be a normal BMI, 41.0% were overweight, and 37.7% were obese. We evaluated the correlation between BMI and the BlattKupperman index through Pearson’s R test, obtaining a value of 0.053; consequently, we did not find a relationship between these 2 variables. In order to show a correlation between BMI and the BlattKupperman index, a dispersion graph was created; no correlation was found since we were not able to see an increasing or decreasing tendency of the Blatt-Kupperman index regarding BMI (Fig. 1). We evaluated the relationship between marital status and occupation with the Blatt-Kupperman index, through Pearson’s R test, with a value of -0.074 and 0.017 respectively; therefore, no relationship was found between these variables. Discussion The information regarding the association between BMI and climateric symptoms is controversial. In this study we assessed the correlation between the degree of obesity and the Blatt-Kupperman index, since some authors concur that estrogen production in adipose tissue in overweight and obese patients protects them from suffering climateric symptoms,9 in contrast with other authors who conclude that a greater BMI and weight gain are associated with reports of greater climateric manifestations, mainly hot flashes, during transition to menopause. These findings concur with a thermoregulatory model of vasomotor symptoms in which body fat acts as an insulator, preventing heat dissipation.14 Riley et al. found that 30% of 468 perimenopausal and 287 postmenopausal females reported hot flashes. Perimenopausal patients with a BMI > 25 kg/m2 reported more hot flashes with a relative risk (RR) of 2.00 (RI 95% = 1.28 3.12). We did not find an association with hot flashes in postmenopausal patients.15 Martínez Pérez et al. carried out a study with 10,514 women with an average age of 57.9 (± 7.1) years, finding that smoking, use of alcohol, BMI > 25 kg/m2, marital status, educational level, and social level were associated with more severe menopausal symptoms for BMI (RR = 3.64; RI 95% = 2.96 - 4.32).16 14 I. Y. González-Carrillo et al presenting symptoms and to develop appropriate preventative strategies, including lifestyle modifications and the establishment of better treatment. 70 60 50 Conflicts of interest 40 The authors have no conflicts of interest to declare. 30 Funding 20 No financial support was provided. 10 0 0 100 200 Blatt Kupperman 300 400 500 BMI Figure 1 Dispersion chart between BMI and the Blatt-Kupperman index. Thurston et al. assessed the connection of the adiposity with vasomotor symptoms in the study of Women’s Health Across the Nation, which included 1,776 women aged 47 to 59 years with an intact uterus and at least 1 ovary, in whom vasomotor symptoms and hormonal serum levels were evaluated. They concluded that a greater percentage of body fat was associated with vasomotor symptoms (RR = 1.27; RI 95% = 1.14 - 1.42).17 In this study, no connection between BMI and Blatt-Kupperman index was found; a probable reason for this is the fact that estrogens of peripheral origin do not have the biological action that ovarian estrogen has. The reason for the inconsistent findings regarding a connection between BMI and climateric symptoms is unknown. Some studies suggest that the inconsistencies may be related to the different endogenous estrogen and other hormones levels in women with different body sizes. Hormonal changes are customary during the transition into menopause. Furthermore, for the formation of estrogens from circulating androgen precursors, the adipose tissue produces hormones such as leptin and tumor necrosis factor, which suppress ovarian production of steroids and have an influence on thermoregulation.18 Pérez-Pérez found that women who work in public spaces adapt more easily to hormonal changes in climaterium and menopause, in contrast to those who are housewives who feel misunderstood, rejected, and have a low self-esteem.19 However, no connection was established between the BlattKupperman index and occupation or marital status in our study. Further studies assessing all risk factors, like health problems, use of alcohol, smoking, role at work, family dynamics, presence of depression, as well as their connection with weight gain or loss in the female in transition to menopause are required. While the results of this study report that the degree of obesity does not have an impact on climateric symptoms severity, most patients showed some degree of overweight or obesity; hence obese patients should undergo more complete tests, including sociological, physical, and personal history, in order to identify those with a higher risk of References 1. Accessed in January 2014. http://www.consultorsalud.com/biblioteca/Guias/Menopausia.pdf 2. Accessed in January 2014. http://www.scog.sld.cu/Articulos/ consenso2006seccclimymenop.pdf 3. Accessed in January 2014. http://www.docstoc.com/ docs/74212096/The-Menopause-Handbook 4. Kupperman HS, Wetchler BB, Blatt M. Contemporary therapy of the menopausal syndrome. JAMA 1959;171:103-113. 5. Utian WH, Janata JW, Kingsberg SA, et al. The Utian Quality of Life (UQOL) scale: development and validation of an instrument to quantify quality of life through and beyond menopause. Menopause 2002;9:402-410. 6. Greene JG. Construcción de una escala climatérica estándar. Rev Climaterio 1998;1:292-301. 7. Carranza LS, Reyes RP, Chan VR. SUMEVA, a new system of climateric symptom evaluation, and its correlation with FSH and estradiol levels. Int J Fertil Womens Med 2006;51:140-144. 8. Carranza LS, Cruz Sánchez K. Relación entre síntomas del climaterio y la calidad de vida. Ginecol Obstet Méx 2008;76:703705. 9. Pavón de Paz I. Obesidad y menopausia. Nutrición Hospitalaria España 2006;21:633-637. 10. Díaz Villaseñor A. La obesidad en México. Salud Pública. México: Fundación Este País; 2011. p. 61-64. 11. Lambrinoudaki I, Brincat M, Erel CT, et al. EMAS position statement: Managing obese postmenopausal women. Maturitas Grecia 2010;66:323-326. 12. Thuston RC, Sowers MR, Sternfeld B, et al. Gains in body fat and vasomotor symptom reporting over the menopausal transition. Am J Epidemiol 2009;170:766-774. 13. Casado Méndez PR, Arró Martínez Y, Arias Hernández D. Repercusión del tabaquismo pasivo en el síndrome climatérico. Rev Cubana Hig Epidemiol 2012;50:1-10. 14. Schwingl PJ, Hulka BS, Harlow SD. Risk factors of menopausal hot flashes. Obstet Gynecol 1994;84:29-34. 15. Hyde Riley E, Inui TS, Kleinman K, et al. Differential association of modifiable health behaviors with hot flashes in perimenopausal and postmenopausal women. J Gen Intern Med 2004;19:740746. 16. Martínez JA, García FC, Palacios S, et al. Epidemiology of risk factors and symptoms associated with menopause in Spanish women. Maturitas 2009;62:30-36. 17. Thurston RC, Sowers MR, Chang Y, et al. Adiposity and reporting of vasomotor symptoms among midlife women. Am J Epidemiol 2008;167:78-85. 18. Whiteman MK, Staropoli CA, Benedict JC, et al. Risk factors for hot flashes in midlife women. J Womens Health 2003;12:459472. 19. Pérez-Pérez R, Medina Barragán RA, Espiricueta-Medina M. Respuestas adaptativas de mujeres en climaterio y menopausia. Rev Enferm Inst Mex Seguro Soc 2011;19:123-126. Medicina Universitaria 2014;16(62):15-18 medicina universitaria www.elsevier.com.mx Original article Infiltration vs. instillation of ropivacaine 7.5% in radical mastectomies for postoperative analgesia B. I. Yolanda-Prieto*, A. L. Millán-Corrales, D. Palacios-Ríos, B. I. Garduño-Chávez, N. G. López-Cabrera, G. A. Millán-Cornejo, B. T. González-Rocha Department of Anesthesiology, “Dr. José Eleuterio González” University Hospital, Universidad Autónoma de Nuevo León, Monterrey, N. L., Mexico Received: June 2013; Accepted: October 2013 KEYWORDS Radical mastectomy; Ropivacaine; Infiltration; Instillation; Mexico. Abstract Objective: Determining the effectiveness of infiltration versus instillation with 7.5% ropivacaine in reducing the intensity of postoperative pain in patients undergoing a radical mastectomy. Material and methods: Clinical, prospective, and comparative analytical study in a sample of 20 female patients between 20 and 60 years of age, ASA I and II, weight 50-90 kg, who were divided into 2 groups (10 patients each). In Group 1 infiltration with ropivacaine 7.5% (20 ml) was applied prior to closure of the surgical wound, meanwhile in Group 2 ropivacaine 7.5% (20 ml), was instilled into the surgical wound. Pain intensity was assessed by a visual analog scale (VAS) upon extubation. The need for rescue medication and the incidence of nausea and vomiting were measured from 0 to 30 minutes postoperatively and at 2, 4, 8 and 12 hours. Results: There was no statistical difference between the groups (only the group managed through infiltration required rescue medications), but the infiltration group had a lower perception of pain. Conclusions: This study reported the same efficacy of preventive treatment of postoperative pain in patients who underwent radical mastectomy for instillation and infiltration with 7.5% ropivacaine and little need for rescue medication postoperatively. 1665-5796 © 2014 Revista Medicina Universitaria. Facultad de Medicina UANL. Publicado por Elsevier México. Todos los derechos reservados. Introduction Preventive analgesia was described by Crile in 1913 as an option to prevent alterations in the autonomic nervous system resulting from postoperative pain, based in regional blocks with local and general anesthetics. 1 Initially, preventive analgesia for postoperative pain treatment was not well accepted, due to controversial results in experimental and * Corresponding author: Department of Anesthesiology, University Hospital “Dr. José Eleuterio González”. Francisco I. Madero, Mitras Centro, Z.P. 64460, Monterrey, N. L., Mexico. Telephone: (+01) 8389 1136. E-mail address: [email protected], [email protected] (B. I. Yolanda-Prieto). 16 B. I. Yolanda-Prieto et al clinical research work; however, nowadays its use is being reconsidered.2-5 Underestimated postoperative pain by medical personnel as well as lack of knowledge and adherence to a multimodal analgesic management, are factors accounting for an inadequate therapeutic management of postoperative patients. This has a direct impact on the patient’s optimal recovery, in addition to allowing the development of chronic complications following the surgical procedure. Studies published in recent years show a prevalence of moderate to unbearable pain of 11% (in a hospital with an acute postoperative pain unit), and in 70% of the patients who have undergone surgery during the first 24 to 48 hours; nevertheless, prevalence has always exceeded 30%.6 There are surgical procedures such as mastectomies in women, which besides producing pain may cause diverse emotional reactions.7 Breast cancer is one of the 2 most common malignancies in women worldwide and the main treatment for this pathology is surgery.7-10 Despite different therapeutic approaches with several analgesics and routes of administration to avoid pain, the desired analgesic effect is not accomplished in some patients; a reason for this could be the route of administration used or the fact that the strength of the medication may be insufficient. Radical mastectomy is an extensive and disfiguring procedure, which causes acute postoperative pain due to soft tissue injury of the anterior wall of the thorax. During dissection, tissue traction takes place producing damage to the axons of the intercostal nerves and brachial plexus emergence. There are several anesthetic strategies; some of the most commonly utilized are intercostal nerve blocks, preoperative thoracic epidural block, thoracic paravertebral block, local infiltration blocks, and direct instillation.11-13 Instillation is the introduction of a liquid (by pouring or injection), drop by drop over mucous membranes or the skin. It is a very commonly used method. Postoperative infiltration (direct administration of the analgesic into the surgical area), as a strategy for pain management in this pathology has not been studied extensively and is underconsidered regarding patient management, hence this study. We carried out a comparison between these 2 local analgesic administration techniques by means of a pain scale and the use of rescue medication; by doing so, we attempted to decrease the endocrine response caused by pain and the side effects in the cardiopulmonary and immunology functions that patients with postoperative pain suffer.14 Material and methods We included female patients scheduled for radical mastectomy at “Dr. José Eleuterio González” University Hospital of the Universidad Autónoma de Nuevo León (UANL), Mexico. The patients agreed to participate in the study by signing an informed consent form. We obtained demographic variables such as age, weight and relevant background. Patients were divided into 2 groups; in Group 1 infiltration with ropivacaine 7.5% (20 ml) was applied prior to closure of the surgical wound, while in Group 2 ropivacaine 7.5% (20 ml) was instilled into the surgical wound. Inclusion criteria required patients to be between 20 and 60 years of age, to have a weight between 110 and 198 lb (50-90 kg), ASA I or II, to be scheduled for radical mastectomy, and have preoperative test results within normal limits. Patients with a history of coagulopathy, radiotherapy, neurological alterations, and previous analgesic or antiinflammatory treatment were excluded. Subsequently, we assessed blood pressure, heart rate, respiratory rate, and pain using a visual analogue scale (VAS) in both groups; in addition the presence of nausea and/or vomiting was measured from 0 to 30 minutes postoperatively and 2, 4, 8, and 12 hours afterwards. Data was inputted into a database created in Excel® 2010 and analyzed using IBM® Statistic 21; for the quantitative variables, traditional descriptive statistics, measures of central tendency, dispersion and position, as well as the observed frequencies in the qualitative variables were calculated. The values were verified by group through hypothesis tests for median and proportion, according to each variable type (quantitative and qualitative respectively) with a reliability of 95%. Results Average age was 49.7 ± 7.8 years for Group 1 (infiltration) and 43.8 + 12.5 years in Group 2 (instillation); there was no significant difference in both groups (p = 0.2234). Average weight was 71.4 kg ± 9.7 for Group 1, and 65.4 ± 14.3 for Group 2; we did not find significant differences between the groups (p = 0.2863). Regarding ASA classification, 50% of the patients in Group 1 and 60% in Group 2 presented with ASA I; the rest of the patients in both groups were ASA II. We did not observe a statistically significant difference regarding vital signs in either group (Tables 1 and 2). No presence of nausea in either group was observed. Table 1 Systolic blood pressure comparison in both groups. Baseline Mean (SD) 30 min Mean (SD) 2 hours Mean (SD) 4 hours Mean (SD) 8 hours Mean (SD) 12 hours Mean (SD) Group 1 n = 10 128.70 (24.10) 124.80 (15.50) 125.80 (12.49) 124.10 (13.99) 120.70 (13.28) 120.50 (13.44) Group 2 n = 10 126.40 (16.41) 120.00 (20.63) 121.50 (19.26) 123.10 (16.46) 117.80 (12.95) 119.20 (13.09) NS NS NS NS NS NS N = 20 p Infiltration vs. instillation of ropivacaine 7.5% in radical mastectomies for postoperative analgesia 17 Table 2 Diastolic blood pressure comparison in both groups. Baseline Mean (SD) 30 min Mean (SD) 2 hours Mean (SD) 4 hours Mean (SD) 8 hours Mean (SD) 12 hours Mean (SD) Group 1 n = 10 73.10 (14.12) 69.20 (9.94) 73.20 (7.21) 77.60 (9.51) 71.60 (9.87) 71.70 (9.61) Group 2 n = 10 72.10 (8.02) 70.50 (15.41) 72.80 (11.89) 71.80 (7.90) 72.20 (10.70) 70.90 (7.99) NS NS NS NS NS NS N = 20 p 10.00 9.00 8.00 7.00 VAS 6.00 5.00 4.00 3.00 2.00 1.00 0.00 VAS 0 VAS 30 min min VAS 2 hrs VAS 4 hrs VAS 8 hrs VAS 12 hrs Installation Figure 1 Visual analog scale. Regarding the VAS results, Group 2 showed better results in all of the evaluation periods, except at 12 hours when results were better in Group 1; however, such differences did not prove to be statistically significant (Fig. 1). A higher number of rescue medication (dexketoprofen 50 mg intravenously [IV]) for Group 1 at 30 minutes and 4 hours was required. In addition, 1 patient from Group 1 required buprenorphine as rescue medication, as she failed to show a decrease in pain. Neither group showed side effects. Discussion When cross-referencing both groups, no differences were seen; in both cases the behavior of the variables was the same statistically, mainly concerning pain, except for the group managed with infiltration requiring rescue medication. Despite advances in the knowledge of pain and the constitution of Algology as a new specialty, postoperative pain is frequent in patients after a surgical procedure; if avoided; side effects may be prevented.15-18 Most clinical research studies on preventive analgesia in patients who undergo radical mastectomy refer to spinal blocks. Epidural anesthesia has also been evaluated as anesthesia and management of acute pain during the performance of the mastectomy; yet in the present study we decided not to use it for anesthetic purposes, given the fact that it must be placed in the metamers between C VII y D IV. The puncture of the intervertebral spaces in this region is technically difficult and the position the patient must assume in order to place it may increase the anxiety that involves a morbidity risk due to ventilation problems; this increases if there is a need to sedate the patient.19 Infiltration of the wound and instillation of local anesthetics is another simple and effective technique providing pain relief during the early postoperative period following surgical procedures. There are studies indicating that ropivacaine infiltration on the surgical wound after surgery reduces pain intensity, reducing the requirement of postoperative analgesics and inpatient days. In addition, the amount of applied anesthetics and its absorption through the peritoneal surface provide an additional mechanism of analgesia. Multiple studies have been performed in order to demonstrate the clinical safety of ropivacaine in animals as well as in humans (5 mg/ml IV infusions).19 The literature reports few studies on instillation and infiltration of ropivacaine 7.5%; thus, having found similar results with this route of administration in the present study, it is recommended as an alternative for optimal postoperative analgesia in patients who undergo radical mastectomy. Incidence of nausea and vomiting, if any, is low. We found that ropivacaine infiltration or instillation in the surgical wound prior to skin closure showed no significant difference on postoperative pain (except for the necessity of using rescue medication in the infiltrated analgesic group); this was proven when cross-referencing VAS recordings at 2, 4, 8 and 12 postoperative hours between each group (p > 0.05 in every crossing); however, when looking at the numerical behavior, lower values of pain in the “infiltration” group were found. Nevertheless, this could also be caused by the use of rescue medications; in addition, the patient’s resistance to the analgesic can also be a variable presented at random. Consequently, the use of a larger sample for future related studies should be the next step, with the purpose of increasing the statistical value in search of establishing whether or not there is a significant difference. 18 Conclusions No statistical difference was found between the use of ropivacaine 7.5% infiltrated or instilled in patients undergoing radical mastectomy. Conflicts of interest The authors have no conflicts of interest to declare. Funding No financial support was provided. References 1. González ML, Martínez MA, Ramírez ML. Opciones analgésicas para el control del dolor posterior a mastectomía radical. Cir Ciruj 2004;72:363-368. 2. Katz J. Preemptive analgesia. Anesthesiology 2002;77:439-446. 3. Kissin I. Preemptive analgesia: why its effect is not always obvious. Anesthesiology 1996;84:1015-1019. 4. McCartney CJ, Sinha A, Katz J. A qualitative systematic review of the role of N-methyl-D-aspartate receptor antagonists in preventive analgesia. Anesth Analg 2004;98:1385-1400. 5. Leach A. Old ideas, new applications. Br J Anesth Anaesthesiol 1998;89:500-506. 6. Soler E, Faus MT, Montaner MC. Servicio de farmacia. El dolor postoperatorio en la actualidad: un problema de calidad asistencial. Hospital francesc de Borja de Gandía y Departamento de Farmacología de la Universidad de Valencia. 2000;24:123135. 7. Bard M, Sutherland AM. Psychological impact of cancer and its treatment. Adaptation to radical mastectomy. Cancer 1995;8:652-672. B. I. Yolanda-Prieto et al 8. Perkins GH, Middleton L. Breast cancer in men. Br Med J 2003;327(7409):238-240. 9. Secretaría de Salud. Dirección General de Estadística e Informática. Incidencia y prevalencia de cáncer en México. Salud Publica Mexico 2006;38:75-81. 10. Borgen PI, Wong GY, Vlamis V. Current management of male breast cancer: a review of 104 cases. Ann Surg 2002;215:451459. 11. Belfer I, Wu T, Kingman A, et al. Candidate gene studies of human pain mechanisms. Anesthesiology 2004;100:1562-1572. 12. Prithvi R. Tratamiento práctico del dolor. Estados Unidos de América. Mosby/Doyma;1995. p. 7. 13. Arner S, Meyerson BA. Lack of analgesic effect of opioids on neuropathicand idiopathic forms of pain. Pain 1998;33:11-23. 14. Rodríguez OL. Anestesia local en cirugía oral y maxilofacial. Parte I, Hospital General Docente “Aleida Fernández Chardiet”. Revista de Ciencias Médicas La Habana 1999;5(2). 15. Suresh S, Barcelona SL, Young NM, et al. Does a preemptive block of the great auricular nerve improve postoperative analgesia in children undergoing tympanomastoid surgery? Anesth Analg 2004;98:330-333. 16. Wurm WH, Concepción M, Sternlicht A, et al. Preoperative interscalene block for elective shoulder surgery: loss of benefit over early postoperative block after patient discharge to home. Anesth Analg 2003;97:1620-1626. 17. Marret E, Flahault A, Samama C, et al. Effects of postoperative, nonsteroidal, antiinflammatory drugs on bleeding risk after tonsillectomy. Meta-analysis of randomized, controlled trials. Anesthesiology 2003;98:1497-1502. 18. Beilin B, Shavit Y, Trabekin E, et al. The effects of postoperative pain management on immuneresponse to surgery. Anesth Analg 2003;97:822-827. 19. Bromage P. Analgesia peridural. España: Editorial Salvat; 1984. p. 335-387. 20. Lewis CD. Control of postoperative pain. Nonnarcotic and narcoticalternatives and their effect on pulmonary function. Chest 1987;92:520-527. Medicina Universitaria 2014;16(62):19-24 medicina universitaria www.elsevier.com.mx Original article Maternal mortality and severe obstetric morbidity in a tertiary care hospital J. L. Iglesias-Benavides*, M. S. Vidales-Hernández, W. E. Treviño-Ledezma, S. N. Delgado-Muñiz, A. Guzmán-López Department of Gynecology and Obstetrics, “Dr. José Eleuterio González” University Hospital, Universidad Autónoma de Nuevo León, Monterrey, N. L., Mexico Received: October 2013; Accepted: October 2013 KEYWORDS Maternal death; Severe obstetric morbidity; Incidence; Mexico. Abstract Introduction: Maternal mortality (MM) is a reflection of the quality of care given to pregnant women. However, it does not reflect many illnesses and medical complications of women at risk of death, who do not die. Severe obstetric morbidity (SOM) refers to women who are “pregnant or recently postpartum, very ill, who would have died if not for the good health care received”. Objective: To review the incidence of MM and SOM at the Obstetric Service of the University Hospital, Universidad Autónoma de Nuevo León (UANL) in the years 2007-2011. Material and methods: Observational, cross-sectional, retrospective study, at the Obstetric Service of the University Hospital, UANL. Results: We attended 19,985 births; there were 37 maternal deaths: 14 due to hypertensive disorders (37.8%), 3 due to hemorrhage (8.1%), 13 (35.1%) due to medical complications, 1 (2.7%) due to an anesthetic problem, and 6 due to sepsis (16.2%). Twenty-three (62.1%) maternal deaths were catalogued as direct and 14 (37.8%) as indirect. Of 407 cases of SOM, 310 (76.1%) were due to hypertensive disorders, 58 (14.2%) to obstetric hemorrhage, 26 (6.3%) to medical complications, 1 (0.2%) to anesthetic complication, and 12 (2.9%) to sepsis. The MM rate was 1.85 per 1,000 live births; the incidence of MOS was 81.4 per year, with 1 death per every 11 cases. Conclusions: The MM and the SOM provide more reliable data on the prevalence of serious complications in obstetrics. This allows us to take preventive measures, offer better medical care, and improve the allocation of resources. 1665-5796 © 2014 Revista Medicina Universitaria. Facultad de Medicina UANL. Publicado por Elsevier México. Todos los derechos reservados. * Corresponding author: Department of Gynecology and Obstetrics, “Dr. José Eleuterio González” University Hospital. Madero y Gonzalitos Avenue, Mitras Centro, Monterrey, N. L., México. E-mail address: [email protected] (J. L. Iglesias-Benavides). 20 Introduction Maternal mortality (MM) is an occurrence which reflects the quality of the healthcare system. The World Health Organization defines maternal death as “the death of a woman while pregnant or within 42 days of termination of pregnancy, from any cause related to or aggravated by the pregnancy or its management but not from accidental or incidental causes”. Direct maternal death is the result of a complication of the pregnancy, delivery or management of the 2 while an indirect maternal death (IMD) is a pregnancyrelated death in a patient with a preexisting or newly developed health problem unrelated to pregnancy. The standard indicator is the MM rate which is defined as the relationship between the numbers of maternal deaths for every 1,000 births.1 Severe obstetric morbidity (SOM) refers to “a pregnant or postpartum patient, very ill, who if not treated appropriately, would result in death”.2 It is safe to assume that the same disease processes which cause SOM are closely related to the ones which cause MM. It is possible to study the circumstances surrounding women with SOM, therefore we are able to implement a better surveillance on maternal care.3 In medical literature, different inclusion criteria are used in the selection of SOM cases such as acute organ system dysfunction,4 severe obstetric complications between the 28th week of gestation and 42 days of puerperium,5 admissions to the intensive care unit,6,7 patients receiving a blood transfusion,8 and anesthetic accidents.9 The MM rate and other indexes have been created as a result of the study of such data. These indexes provide a better understanding of the medical problems surrounding pregnant women. Mortality rate represents the number of deaths in accordance to the number of SOM cases, morbidity rate expresses the relationship between SOM cases for every maternal death, and SOM incidence indicates the number of very ill women who are attended per year.10-13 The objective of this study was to review the main causes and incidence of maternal death, as well as SOM at the “Dr. José Eleuterio González” University Hospital of the Universidad Autónoma de Nuevo León (UANL), between 2007 and 2011. Another objective was the analysis of medical and social factors related to the care and attention of obstetric complications and maternal deaths. Material and methods In this retrospective, transversal, analytic study, files of patients classified as maternal death, and those who met the criteria for SOM between January 2007 and December 2011 were reviewed. According to the literature, we considered as SOM pregnant women with severe preeclampsia, eclampsia and HELLP syndrome (a life-threatening pregnancy complication usually considered to be a variant of preeclampsia, named after its characteristics: hemolysis, elevated liver enzymes, and low platelet count); women who had hemorrhage before, during or after delivery higher than 500 ml and who required a blood transfusion; severe medical diseases complicating pregnancy (cardiomyopathy, nephropathy, AIDS, thrombocytopenic purpura, etc.); women admitted to the J. L. Iglesias-Benavides et al intensive care unit who underwent an obstetric hysterectomy, laparotomy or pelvic packing, as well as anesthetic accidents and puerperal sepsis cases.4-9 In order to obtain a better data analysis of MM and SOM, we divided the patients into 5 groups: hypertensive disorders, obstetric hemorrhage, medical conditions, anesthetic accidents, and sepsis. The studied variables were: discharge diagnosis, number of surgeries practiced, blood transfusions, age, schooling, marital status, prenatal care (5 visits or more), gestational age, days of overnight stay, admittance to the Neonatal Intensive Care Unit (NICU -UCIN in its Spanish acronym) and newborn conditions (NB). We calculated the MM rate (number of maternal deaths over the number of live births and stillbirths per 1,000),10 the mortality rate (maternal deaths over the number of SOM cases times 100)11,12 morbidity rate (number of SOM cases divided by the number of maternal deaths) and SOM incidence (number of SOM cases over the sum of periods of time).13,14 We performed descriptive statistics of frequency. Results During the 5-year reviewed, 19,985 births took place and 37 maternal deaths were registered (0.18%). The causes of death were as follows: 14 corresponded to hypertensive disorders (37.8%), 3 to hemorrhage (8.1%), 13 to medical complications (35.1%), 1 to an anesthetic problem (2.7%), and 6 to sepsis (16.2%) (Table 1). In 23 of the cases (62.1%), maternal death was classified as direct and in 14 (37.8%) as indirect. Maternal death rate was 1.85 per 1,000 born alive and dead. We gathered 407 SOM cases: 310 (76.1%) hypertensive disorders, 58 (14.2%) with an obstetric hemorrhage, medical complications in 26 (6.3%), 1 case (0.2%) with anesthetic complications, and 12 (2.9%) with sepsis (Table 2). Mortality rate was 9.09% and morbidity rate resulted in 1 death for every 11 SOM cases (Table 3). SOM incidence was 81.4 cases per year. After measuring mortality and morbidity rates within each of the SOM pathology groups, we found that for hypertensive disorders, morbidity rate resulted in 1 death for every 22.1 cases and mortality was 4.5%; in the hemorrhage cases, morbidity rate resulted in 1 death for every 19.3 and mortality was 5.1%; regarding medical complications and sepsis, morbidity rate resulted in 1 death for every 2 and mortality was 50%; for anesthetic complications, morbidity rate was a single case which resulted in death with a mortality rate of 100% (Table 4). Sixty patients underwent hysterectomy (14.7%) and 56 files were reviewed. Background of a previous C-section occurred in 34 cases (60.7%). The diagnosis corresponded to placenta accrete in 30 cases (53.5%), uterine atony in 12 (21.4%), cornual and cervical ectopic pregnancy in 3 (5.35%), uterine myomatosis in 3 (5.35%), uterine perforation in 3 (5.35%), and 3 (5.35%) cases with sepsis. In 2 patients a carcinoma in situ diagnosis was established. In 52 patients (92.8%) blood transfusion was required, ranging from 1 to 25 blood packs with an average of 4.3; fresh frozen plasma was applied in a range between 1 and 40 with an average of 3.8; platelets concentrates were applied in a range between 1 and 33 with an average of 4.4. Maternal mortality and severe obstetric morbidity in a tertiary care hospital 21 Table 1 Causes of maternal deaths from 2007 to 2011. Maternal death causes 2007 2008 2009 2010 2011 Total % Hypertensive disorders 2 2 4 0 6 14 37.8 Obstetric hemorrhage 2 0 1 0 0 3 8.1 Medical condition 3 1 5 3 1 13 35.1 Anesthetic complication 0 1 0 0 0 1 2.7 Sepsis 2 1 3 0 0 6 16.2 Total 9 5 13 3 7 37 99.9 Table 2 Number of cases of severe obstetric morbidity from 2007 to 2011. Severe obstetric morbidity 2007 2008 2009 2010 2011 Total % Hypertensive disorders 61 57 39 64 89 310 76.1 Obstetric hemorrhage 18 6 13 10 11 58 14.2 Medical condition 4 2 10 5 5 26 6.3 Anesthetic complication 0 1 0 0 0 1 0.2 Sepsis 4 1 3 2 2 12 2.9 Total 87 67 65 81 107 407 99.7 Table 3 Relation between number of births, morbidity, severe obstetric morbidity (SOM), maternal deaths and associated data of the period 2007-2011. Year Births SOM Maternal deaths Mortality rate (1,000 newborns) Morbidity rate Mortality index (%) 2007 3,890 87 9 2.31 9.6 10.3 2008 3,915 67 5 1.27 13.4 7.4 2009 3,718 65 13 3.49 5 20 2010 4,074 81 3 0.73 27 3.7 2011 4,388 107 7 1.59 14.5 6.8 Total 19,985 407 37 1.85 11 9.09 Admittance to the NICU occurred in 132 cases (32%) as follows: 80 due to hypertensive disorders (19.6%), 20 due to hemorrhage (4.9%), 24 due to a medical condition (5.8%) and 8 due to sepsis (1.96). Hospital stay ranged from 5 to 90 days, with an average of 10 days. Maternal age was analyzed in 368 cases and ranged from 14 to 42 years, with an average of 25.3. The most frequent age group was under 20 years with 128 cases (34.7%), followed by 21 to 25 years with 81 (22%). As for marital status, the distribution of the 327 cases was as follows: 195 single or in common-law marriage (59.6%) and 132 married (40.3%). Schooling for the 327 cases was: 56 with elementary school completed (17.1%), 193 with junior high school completed (59.02%), and 78 with high school or higher education completed (23.8%) (Table 5). Distribution by gestational age in weeks at the moment of admission was, out of the 327 SOM patients: of 43 cases with 25-30 weeks of age; 93 cases between 31-35 weeks (28.44%); 181 between 36-40 weeks (55.35%), and 10 cases with 41 weeks or more (3.05%). Prenatal care in 327 files was considered positive in 233 cases (71.2%) and negative in 94 (28.7%). Obstetric care in 354 reviewed cases was of 3 uterine curettage (0.84%), 38 deliveries (10.73%) and 313 C-sections (88.41%). 22 J. L. Iglesias-Benavides et al Table 4 Relation between severe obstetric morbidity, maternal deaths, mortality rate and morbidity rate for each group. Severe obstetric morbidity Hypertensive disorders N Maternal deaths (n) Morbidity rate Mortality rate (%) 310 14 22.1 4.5 Obstetric hemorrhage 58 3 19.3 5.1 Medical condition 26 13 2 50 Anesthetic complications 1 1 1 100 Sepsis 12 6 2 50 Total 407 37 11 9.09 Table 5 Maternal age, marital status and level of education frequencies in severe obstetric morbidity patients between 2007 and 2011. Maternal age 2007 2008 2009 2010 2011 Total (%) < 15 4 0 2 4 6 16 4.3 16-20 16 27 14 33 38 128 34.7 21-25 22 11 11 14 23 81 22 26-30 12 5 9 8 11 45 12.2 31-35 17 14 10 10 13 64 17.3 36-40 7 4 4 6 7 28 7.6 > 40 2 1 1 1 1 6 1.6 Total 68 62 51 76 99 368 99.7 Married 29 28 16 28 31 132 40.3 Single/ common-law marriage 43 28 30 34 60 195 59.6 Total 72 56 46 62 91 327 99.9 Elementary 12 10 10 10 14 56 17.1 Junior high school 45 34 20 40 54 193 59.02 High school or higher 15 12 16 12 23 78 23.8 Total 72 56 46 62 91 327 99.9 Marital status Level of education Discussion Maternal mortality is the result of a series of events which reveal a lack of action to improve the conditions and the exclusion conditions which many women in Mexico live in. Behind every maternal death there is a series of severe socioeconomic problems such as a high child morbidity/mortality rate, malnutrition, orphanage, schooling drop-outs, and a premature start for children in the workforce.15 MM is a reflection of the quality of care given to pregnant women. However, this parameter does not show the frequency of many of the pathologies of women who were close to dying but survived. The undeniable benefits of this knowledge allow us to know what is really happening in the obstetric units, while MM provides us with limited information. Around 1% of pregnant women suffer some sort of event which puts their lives at risk and there is an estimate of 120 events for every direct MM, most of which are related to Maternal mortality and severe obstetric morbidity in a tertiary care hospital hypertension and hemorrhage. Severe maternal morbidity is quantifiable and can be the best way of measuring the improvements in health care.15,16 In Mexico, 90% of maternal deaths occur in hospitals or medical units. This is why the hospital MM rate is so high, compared to the general population.17 In Nuevo Leon for this period of time, the average MM rate was 9.9 per 100,000 born alive. When we compare our MM rate of 1.85 per 1,000 births with that from other hospitals, it is below the 2.46 and 2.48% reported by the Hospital Materno Perinatal del Estado de México during 2007 and 200818 and by Peru (11.25 per 1,000 births).19 A common problem in concentration hospitals is the admittance of severe maternal complications, which are referred very tardily. In our MM group we found that 25 patients (67.5%), were referred in a bad condition. The relation is as follows: of the hypertensive disorders, 12 out of the 14 fatal cases (85.7%) were referred to our hospital with brain hemorrhage; the 3 fatal cases resulting from hemorrhage were treated in other hospitals and then sent here; of the 6 fatal cases due to sepsis, 5 (83.3%) were treated in other hospitals and then sent here; of the 13 fatal cases from medical complications, 5 (19.2%) were admitted to our department being very ill. The pattern of the main obstetric causes of morbidity and mortality has remained unchanged in the last decades; however, the frequency of all the causes have risen. The 5 main causes worldwide are complications of abortion, postpartum hemorrhage, high blood pressure, antepartum hemorrhage and pre-existing medical conditions.20,21 The 407 SOM cases represent 2.03% of total births, i.e., 1 SOM case for every 49 births. Obstetric morbidity and MM have a direct or close relationship. In our review, there were 37 maternal deaths and the 3 main reasons were: Hypertensive disorders (37.8%), medical conditions (35.1%), and sepsis (16.2%). In the same period of time, SOM incidence was as follows: hypertensive disorders (76.1%, hemorrhage 14.2%, and medical conditions 6.3%). There was only one difference in the hemorrhage cases: they occupied the second place in obstetric morbidity, while they appear in 4th place as a cause of maternal death with only 3 cases (Table 1). When we applied the rates to all of the 5 groups of SOM cases, a greater relationship with the severity of the illness comparative with the number of cases (Table 4) was seen. Therefore, among hypertensive diseases there was 1 death for every 22 cases (4.5%) with hemorrhage, 1 for every 19.3 cases (5.1%) with medical complications and 1 death for every 2 cases of sepsis (50%); there was also only 1 anesthetic complication which resulted in death (100%). These results were positively correlated with the admittances to NICU: 19.6% from hypertensive disorders, 4.9% hemorrhage, 92.3% medical conditions, and 66.6% sepsis. The age group with the highest number of SOM were teenagers with almost 35%; 60% were single or in common-law marriage. Eighty-two percent had finished junior high school or higher (Table 5). Becoming pregnant at an early age marks the beginning of long-term economic and social responsibilities, as most of these mothers have low income and limited work options, favoring a vicious cycle of poverty. This situation worsens with the inter-generational repetition of teenage pregnancy, increasing the risk of complications.22,23 Being single or living in common-law marriage favors social exclusion and reduces economic expectations 23 as well as medical care for women.24 In our study all of the patients were low income and did not have medical care services. Obstetric care in 354 reviewed cases was of 3 uterine curettages (0.84%), 38 deliveries (10.73%) and 313 C-sections (88.41%). Historically, performing C-sections is related with obstetric complications or associated with medical conditions.25 Conclusion Assessment of MM in addition to SOM provides reliable data about the prevalence of severe obstetric complications; thus, this relevant information allows taking specific preventive measures as well as improving medical care and the allocation of resources addressed at caring for women of childbearing-age.26 Conflicts of interest The authors have no conflicts of interest to declare. Funding No financial support was provided. References 1. Clasificación estadística internacional de enfermedades y problemas relacionados con la salud. Décima revisión. Publicación científica 554. Organización Mundial de la Salud 1992;2:29-64. 2. Say L, Pattinson RC, Gulmezoglu AM. WHO systematic review of maternal morbidity and mortality: the prevalence of severe acute maternal morbidity (near miss). Reprod Health 2004;1:3– 7. 3. Pattinson RC, Buchmann E, Mantel G, et al. Can enquiries into severe maternal morbidity act as a surrogate for maternal death enquiries? Br J Obstet Gynaecol 2003;110:889–893. 4. Mantel GD, Buchmann E, Rees H, et al. Severe acute maternal morbidity: A pilot study for a near miss. Br J Obstet Gynaecol 1998;105:985-990. 5. Prual A, Bouvier-Colle MH, de Bernis L, et al. Severe maternal morbidity from direct obstetric causes in West Africa: Incidence and case fatality rates. Bull World Health Organ 2000;78:593602. 6. Fitzpatrick C, Halligan A, McKenna P, et al. Near-miss maternal mortality (Letter). Irish Med J 1992;85:37. 7. Baskett TF, Sternadel J. Maternal intensive care and near miss mortality in obstetrics. Br J Obstet Gynaecol 1998;105:981-984. 8. de Bernis L, Dumont A, Bouillin D, et al. Maternal morbidity and mortality in two different populations of Senegal: A prospective study (MOMA Survey). BJOG 2000;107:68-74. 9. Mantel GD, Buchmann E, Rees H, et al. Severe acute maternal morbidity: A pilot study for a near miss. Br J Obstet Gynaecol 1998;105:985-990. 10. Cabero Ll, Cerqueira Ma J. Protocolos de medicina materno-fetal (perinatología). 2da Ed. Barcelona: Ed. Ergon; 2000. p. 372. 11. Pattinson RC, Hall MH. Near misses: a useful adjunct to maternal death enquiries. Br Med Bul 2003;67:231-243. 12. Vandecruys HI, Pattinson RC, Macdonald AP, et al. Severe acute maternal morbidity and mortality in the Pretoria Academic Complex: changing patterns over 4 years. Eur J Obstet Gynecol Reprod Biol 2002;102:6-10. 24 13. Fabre E, Carrera José M, Monleón J, et al. Cómo diseñar, realizar y comunicar la investigación clínica en perinatología. Depto. Obstetricia y Ginecología Instituto Universitario Dexeus. Barcelona: Ed. Masson; 1998. p. 199-200. 14. Castañeda M. La mortalidad materna en México. Cuatro visiones críticas. Xochimilco, México: Fundar-UAM; 2004. p. 18. 15. Waterstone M, Bewley S, Wolfe Ch. Incidence and predictors of severe morbidity: case control study. BMJ 2001;322:1089-1093. 16. Danel I, Berg C, Johnson Ch, et al. Magnitude of maternal morbidity during labor and delivery: United States, 1993-1997. Am J Public Health 2003;93:631-634. 17. Instituto Nacional de Estadística y Geografía. Estadísticas de defunciones, 2010. Base de datos. México: INEGI; 2011. 18. Briones JC, Díaz de León M, Meneses J. Estrategias para reducir la mortalidad materna hospitalaria en el Estado de México. Rev Asoc Mex Med Crit y Ter Int 2009;23:16-24. 19. Díaz J, Salvador JL, Hidalgo F. Mortalidad materna. Experiencia de 4 años en el Hospital Nacional Cayetano Heredia. Ginecol Obstet 2004;50:97-100. 20. Pattinson RC, MacDonald AP, Backer F, et al. Effect of audit on critically ill pregnant women. Clin Govern Int J 2006;11:278288. J. L. Iglesias-Benavides et al 21. Brace V, Penney G, Hall M. Quantifying severe maternal morbidity: a Scottish Population Study. BJOG 2004;111:481-484. 22. Karam CM, Bustamante MP, Camarena GA. Aspectos sociales de la mortalidad materna. Estudio de caso en el Estado de México. Medicina Social 2007;2:205-211. 23. Alatorre RJ, Atkin CL. “El embarazo adolescente y la pobreza”, en Paloma Bonfil y Vania Salles (eds.) Mujeres pobres: salud y trabajo. México: Gimtrap; 1998. p. 13-30. 24. Lipman EL, Boyle MH. Social support and education groups for single mothers: a randomized controlled trial of a communitybased program. CMAJ 2005;173:1451-1456. 25. Liu S, Liston RM, Joseph KS, et al. Maternal mortality and severe morbidity associated with low risk planned cesarean delivery versus planned vaginal delivery at term. CMAJ 2007;176:455460. 26. Brace V, Penney G. Learning from adverse outcomes: A system for identification and assessment of severe maternal morbidity. Fetal Matern Med Rev 2007;18:121–144. Medicina Universitaria 2014;16(62):25-27 medicina universitaria www.elsevier.com.mx Scientific letter Sweet syndrome presenting late after non Hodgkin’s lymphoma and dermatomyositis L. A. Olguín-Ramíreza, J. C. Jaime-Péreza,*, C. Mendoza-Rodríguezb, D. GómezAlmaguera Hematology Department, Internal Medicine Division, “Dr. José Eleuterio González” University Hospital, School of Medicine of the Universidad Autónoma de Nuevo León, Monterrey, N. L., Mexico a b Dermatology Department, Internal Medicine Division, “Dr. José Eleuterio González” University Hospital, School of Medicine of the Universidad Autónoma de Nuevo León, Monterrey, N. L., Mexico Received: November 2013; Accepted: November 2013 KEYWORDS Sweet syndrome; Dermatomyositis; Non-Hodgkin’s lymphoma; Pulmonary fibrosis; Mexico. Abstract Sweet syndrome is a rare neutrophilic dermatosis consisting in the onset of high fever, neutrophilia, and typical painful skin lesions including erythematous papules, nodules, and plaques on the face, trunk, and extremities, with a bilateral and asymmetrical pattern. Sweet syndrome is classified as idiopathic, predominating in women; malignancy-associated, mainly with hematological cancer, and drug-induced. The diagnosis is based on clinical history and skin manifestations, being confirmed by a complete blood count showing neutrophilic leukocytosis, and specific findings in the skin biopsy. We report the case of a 68 year-old man with a 10-year evolution of dermatomyositis complicated by lung fibrosis, followed 8 years later by non-Hodgkin lymphoma (NHL) accompanied by worsening of his fibrosis. Two years after the successful treatment of NHL the patient developed an acute episode of severe dyspnea, multiple skin lesions, and 95% neutrophilia. At that time the patient had a severe lung function impairment complicated by nosocomial pneumonia that led to his death, a few days after the diagnosis of Sweet syndrome was established by histopathology examination. Sweet syndrome is a rare dermatologic entity that can appear several years after diseases characterized by immune dysfunction such as dermatomyositis and NHL. 1665-5796 © 2014 Revista Medicina Universitaria. Facultad de Medicina UANL. Publicado por Elsevier México. Todos los derechos reservados. * Corresponding author: Hematology Departments, Internal Medicine Division, “Dr. José Eleuterio González” University Hospital. Dr. Rodrigo Barragán Building, 2nd Floor. Madero y Gonzalitos Avenue, Mitras Centro, Z.P. 64460, Monterrey, N. L., Mexico. Telephone: +52 (81) 1257 2905. Fax: +52 (81) 1257 2906. E-mail address: [email protected] (J. C. Jaime-Pérez). 26 Introduction Sweet syndrome was first described in 1964 by Robert Douglas Sweet.1 In 1986 Su and Liu postulated the criteria for its diagnosis.2 There is no racial predilection, and it is more frequent in women (4:1).3-5 The disease consists of high fever, neutrophilia, and typical painful skin lesions including erythematous papules, nodules, and plaques on the face, trunk, and extremities, with a bilateral and asymmetrical pattern.6,7 Sweet syndrome is classified as: a) idiopathic, which predominantly affects women between 30 and 50 years of age;6,8 b) malignancy-associated, which appears to affect men and women equally; in about 20% of the cases the syndrome is associated with a malignancy, most often acute leukemia;9,10 c) drug-induced, which may occur as a reaction to a medication, most frequently to granulocyte colony-stimulating factor (G-SCF).11-14 The diagnosis is confirmed by a complete blood count (CBC) showing leukocytosis with a predominance of neutrophils, and a skin biopsy demonstrating edema of the papillary dermis and a dense inflammatory leukocyte infiltrate in the lower dermis.5,6,15 The treatment includes prednisolone, or potassium iodide, colchicine, and Lugol’s solution.5,6,16 Usually recovery is complete with no recurrence. L. A. Olguín-Ramírez et al coupled with the presence of disseminated macular dermatosis, which prompted a consultation to a dermatologist; at that time the patient had painful erythematous papules both over the dorsum of his forearm and face. The lesions rapidly progressed to become nodules and a few of them coalesced forming plaques (Fig. 1, panel C). A skin punch biopsy performed on a left cheek lesion, demonstrated prominent infiltration of leucocytes into the dermis, consistent with the diagnosis of sweet syndrome. (Fig. 1, panels D and E). A CBC reported 10.9 x 109/l WBC, and neutrophilia of 10.3 x 109/l, representing 94.7% of total leukocytes. During his stay at the hospital, the patient developed nosocomial pneumonia that progressed to respiratory failure, and broad spectrum antibiotics were started; a CT scan of the chest showed diffuse bilateral infiltrates, as well as A B Case report The patient, a 68-year-old man, first showed symptoms in April 2000 with minimum effort dyspnea, accompanied by constitutional symptoms and generalized myalgias with weakness and muscular fatigue. At the time the CBC was normal, but blood chemistry results showed diverse abnormalities including albumin 1.7 g/dl, globulin 4.1 g/dl, lactic dehydrogenase 688 U/l, creatine kinase 7,402 U/l, alanine aminotransferase 283 U/l and aspartate aminotransferase 521 U/l. Chest X-rays showed a bibasal reticular infiltrate (Fig. 1, panel A). Computed tomography (CT) imaging documented interstitial fibrosis in the descamative phase. Spirometry reported a mild to moderate restrictive process. Electromyography of the 4 extremities reported myopathic inflammatory pattern. A muscle biopsy of the quadriceps was normal. Diagnosis of dermatomyositis with secondary lung fibrosis was established and treatment with prednisone and methotrexate was started. In 2008, physical examination revealed a 12 x 6 cm mass of coalescent adenopathies, firm, nontender, fixed to deep planes in the parotid gland, as well as cervical, retroauricular, bilateral axillary and inguinal lymphadenopathies; in addition, the patient presented B symptoms; there was no visceral enlargement. An excisional biopsy of the axillary and left groin lymph nodes was carried out, leading to the diagnosis of high-grade diffuse large cell non-Hodgkin lymphoma (NHL) with a B immunophenotype. Bone marrow aspirate showed a moderate granulocytic hyperplasia (Fig. 1, panel B). Treatment included rituximab, cyclophosphamide, doxorubicin, and vincristine. The patient had no major complications until November 2010, when he was admitted to the emergency room after 3 weeks of experiencing malaise, fatigue, and weakness, C D E Figure 1 A) The chest X-rays from 2008 (left) show a bibasal reticular infiltrate; 2 years later on the last X-rays (right) diffuse bilateral infiltrates as well as significant progression of pulmonary fibrosis were documented. B) Bone marrow aspirate; moderate granulocytic hyperplasia. C) Sweet syndrome. Sixtyeight male patient with disseminated dermatosis to the face, predominating on the right supraorbital area and near the nasogenian ipsilateral furrow, characterized by ulcerated plaques filled with necrotic central tissue and partly covered with crust, surrounded by eritema, giving a targetoid appearance. D) Microscopic low-power magnification view of a hematoxylin and eosin-stained skin punch biopsy performed on a left cheek lesion, demonstrating slight spongiosis and superficial erosions scattered in the epidermis, with prominent dense infiltration of leucocytes into the dermis. E) Microscopic high-power view demonstrating dense neutrophilic infiltration in the upper and mid-dermis and neutrophil karyorrhexis. Sweet syndrome presenting late after non Hodgkin’s lymphoma and dermatomyositis significant progression of pulmonary fibrosis. The ventilatory function worsened, leading to a cardiorespiratory arrest and death of the patient a week after his admission to the hospital. Discussion Several theories to explain the pathogenesis of Sweet syndrome exist. 17 3 are widely supported a type III hypersensitivity reaction, an activation of T cells by antigens or superantigens, and a disturbance in the function of the neutrophiles. An additional theory notes that inappropriate secretion of interleukin 1 (IL-1) can stimulate macrophages and then cause a rise in the production of G-CSF, responsible for increasing IL-8, a chemotactic factor for neutrophils.5,6 Confirming the knowledge about dermatomyositis in that 10% to 25% of the cases progress to a malignancy,18,19 eight years after its diagnosis and successful therapy, the patient developed NHL that was also successfully treated and remained in remission. Our patient presented three conditions associated with the diagnosis of Sweet syndrome: an hematologic disorder, a severe infectious process, and an autoimmune disease.20 In this case it is difficult to establish definitively whether the syndrome was associated to NHL or its therapy, as his dermatomyositis was not completely controlled, as shown by progressive lung fibrosis and subsequent fatal pneumonia; another possibility is that both conditions acted as a trigger for the development of Sweet syndrome. Conflicts of interest The authors have no conflicts of interest to declare. Funding No financial support was provided. References 1. Anzalone CL, Cohen PR. Acute febrile neutrophilic dermatosis (Sweet’s syndrome). Curr Opin Hematol 2013;20:26-35. 2. Su WP, Liu HN. Diagnostic criteria for Sweet’s syndrome. Cutis, cutaneous medicine for the practitioner 1986;37:167-174. 27 3. Morita Y, Ogura T, Yamamura M, et al. Sweet’s syndrome associated with undifferentiated connective tissue syndrome. Ann Rheum Dis 1995;54:937-938. 4. Mizoguchi M, Matsuki K, Mochizuki M, et al. Human leukocyte antigen in Sweet’s syndrome and its relationship to Behcet’s disease. Arch Dermatol 1988;124:1069-1073. 5. Gonzalez GE, Haro RR, Fariña MC, et al. Sindrome de Sweet en la infancia. Piel 2008;23:118-124. 6. Cohen PR. Sweet’s syndrome--a comprehensive review of an acute febrile neutrophilic dermatosis. Orphanet J Rare Dis 2007;2:34. 7. Boudysova M, Ettler K, Podhola M, et al. Acute febrile neutrophilic dermatosis - Sweet syndrome. Casopis lekaru ceskych 2012;151:359-361. 8. Knipstein JA, Ambruso DR. Sweet syndrome in an infant with chronic granulomatous disease. J Pediatr Hematol Oncol 2012;34:372-374. 9. Hünermund A, Wendel AM, Geissinger E, et al. Typically atypical: histiocytoid Sweet syndrome associated with malignancy. J Dtsch Dermatol Ges 2011;9:666-669. 10. Reina D, Cerdà D, Roig D, et al. Sweet syndrome associated with myelodysplastic syndrome: Report of a case. Review of the literature. Reumatol Clin 2013:9;246-247. 11. Kawakami T, Ohashi S, Kawa Y, et al. Elevated serum granulocyte colony-stimulating factor levels in patients with active phase of Sweet syndrome and patients with active Behcet disease: Implication in neutrophil apoptosis dysfunction. Arch Dermatol 2004;140:570-574. 12. Ginarte M, Toribio J. Sweet’s syndrome. Med Clin (Barc) 2009;133:31-35. 13. Akpinar F, Dervis E. Drug eruptions: An 8-year study including 106 inpatients at a dermatology clinic in turkey. Indian J Dermatol 2012;57:194-198. 14. Trickett HB, Cumpston A, Craig M. Azacitidine-associated Sweet’s syndrome. Am J Health Syst Pharm 2012;69:869-871. 15. Lear JT, Atherton MT, Byrne JP. Neutrophilic dermatoses: Pyoderma gangrenosum and Sweet’s syndrome. Postgrad Med J 1997;73:65-68. 16. Schadt CR, Callen JP. Management of neutrophilic dermatoses. Dermatologic Therapy 2012;25:158-172. 17. Martinez Martinez ML, Cordoba Soriano JG, Rodriguez Vazquez M, et al. Sweet syndrome. Med Clin (Barc) 2012;139:e7. 18. Owen CE, Malone JC, Callen JP. Sweet-like dermatosis in 2 patients with clinical features of dermatomyositis and underlying autoimmune disease. Arch Dermatol 2008;144:1486-1490. 19. Pelosof LC, Gerber DE. Paraneoplastic syndromes: An approach to diagnosis and treatment. Mayo Clin Proc 2010;85:838-854. 20. Saffie M, Sun D, Hsia C. Sweet’s syndrome in chronic myelomonocytic leukemia. American Journal of Hematology 2013;88:630. Medicina Universitaria 2014;16(62):28-36 medicina universitaria www.elsevier.com.mx REVIEW ARTICLE Mild cognitive impairment J. Isordia-Martíneza,*, F. Gongora-Riverab, H. Leal-Baileyb, X. Ortiz-Jiménezc Department of Internal Medicine, “Dr. José Eleuterio González” University Hospital, Universidad Autónoma de Nuevo León, Monterrey, N. L., Mexico a Service of Neurology, “Dr. José Eleuterio González” University Hospital, Universidad Autónoma de Nuevo León, Monterrey, N. L., Mexico b c Laboratory of Psychophysiology, Faculty of Psychology, Universidad Autónoma de Nuevo León, Monterrey, N.L. Mexico Received: May 2013; Accepted: December 2013 KEYWORDS Mild cognitive impairment; Dementia; Cognitive function; Mexico. Abstract Mild Cognitive Impairment (MCI) is a disease between normal cognitive ageing and dementia. In recent years the term MCI has been recognized as a pre-dementia state, raising an important subject for investigation in the prevention of dementia. There are various terms related to pre-dementia MCI, such as isolated memory complaint and pre-Alzheimer’s disease; most of them do not comprise all the areas related to MCI. A central cholinergic deficit is present in amnestic MCI with neuronal loss in the Meynert basal nucleus. It is estimated that the rate of progression to dementia is about 10% every year. The prevalence of MCI is 10%-11% and the risk of progression to dementia is about 5%-16%. The continual development of pharmacologic approaches to modify and delay the natural history of progression of the disease motivates a great interest in an earlier diagnosis. 1665-5796 © 2014 Revista Medicina Universitaria. Facultad de Medicina UANL. Publicado por Elsevier México. Todos los derechos reservados. Introduction Mild cognitive impairment (MCI) is an intermediate mental state between a normal cognitive state and dementia. In recent years, MCI has been recognized as a pre-dementia state, becoming an important subject for investigation in the prevention of dementia. There are several terms related to pre-dementia MCI, such as isolated memory complaint and pre-Alzheimer disease (AD); most of them do not comprise all the area related to MCI.1 MCI is a heterogeneous pathology in terms of clinical presentation, etiology, prognosis and prevalence; however, there is still controversy in its definition. Some studies have demonstrated that MCI can be reversed to a normal cognitive state. Prevalence is 3-19% in the elderly population, with an incidence between 8 to 58 per 1,000 people a year and a risk of developing into dementia of 11-33% within 2 years. 2 Memory disorders represent a public health issue, with an average of 4.5 years until a patient is diagnosed with dementia, with major disabilities and economic loss for the family and the health sector.3,4 In Mexico there is no information about patients’ survival. * Corresponding author: Madero y Gonzalitos Avenue, Z.P. 64700, Monterrey, N. L., Mexico. Telephone/Fax: (81) 8333 7798. E-mail address: [email protected] (J. Isordia-Martínez). Mild cognitive impairment Mild cognitive impairment subgroups Amnestic MCI It is considered to be AD’s main predecessor; it is the most common subgroup with a 2:1 ratio compared with non-amnestic MCI. There are 2 classifications within this subgroup: single non-memory domain MCI and multi-domain MCI. The former refers to individuals who have a significant memory deficit (classified by the result of a battery of neuropsychological tests) but do not meet the criteria for a dementia diagnosis; criteria for this classification are: presence of a cognitive complaint (confirmed by an informant), impaired memory determined objectively (correlated with age and educational level, and represented by an impairment greater than 1.5 standard deviations [SD] from the normal parameter), preserved general cognitive functions, the fact that everyday activities remain normal, and not meeting criteria for a dementia diagnosis. Amnestic multi-domain MCI includes those people who do not manifest a cognitive decline greater than 0.5-1 SD for their age and educational level. We have followed up on these patients and they generally do not display an evolution towards vascular dementia or AD.5 Within this MCI subgroup, the cognitive profile reflects normal aging; prognostic usefulness of this MCI is not clear. There is controversy among the different studies regarding this subgroup’s conversion to dementia or the return to a normal cognitive state.6 Non-amnestic MCI This type of MCI is characterized by an isolated impairment in a single non-memory domain, for instance an impairment of the executive function, language, or visuospatial skills. The non-amnestic MCI-single domain subgroup will progress, depending on the affected domain, to fronto-temporal dementia, primary progressive aphasia, Lewy body dementia, progressive supranuclear palsy, or corticobasal degeneration. Individuals in this group are considered to have a lower risk of conversion to dementia; however, evidence supporting this theory is limited. In regard to the non-amnestic multiple domains MCI subtype, it is considered that one of the main disorders is the development of neurofibrillary plaques caused by the proteins tau and alfa-synuclein.7 Epidemiology There is a great variation between the reported prevalence rates, fluctuating between 2% and 20% in different series. Studies which have used different measurements such as age-related cognitive decline, cognitive impairment, no dementia, and minimal dementia estimate prevalence between 16% and 22% in adults older than 60. In several cohort-type studies, incidences between 14 and 77 for every 1,000 patients older than 60 years have been reported. Males have an odds ratio of 1:5 in community studies of patients between 70 and 89 years.2 The National Health and Aging Study in Mexico (ENASEM by its Spanish acronym) assessed the prevalence of cognitive impairment and its relationship with sociodemographic factors in the population, 29 finding that just 7% had cognitive impairment and 3.3% had cognitive impairment and functional dependency.3 Pathology Regarding histopathological findings, and MCI being a clinical expression of early symptoms of dementia, researchers detected intermediate findings between normality and advanced dementia. A central cholinergic deficit is present in amnestic MCI, related to neuronal loss in the basal nucleus of Meynert.8 In postmortem studies, evidence of a positive regulation in the acetyl transferase activity in the frontal cortex and hippocampus has been found.9 There is evidence that cerebrovascular and neurodegenerative conditions contribute to MCI, especially white matter lesions and small lacunar infarcts.10 One of the main problems in the diagnosis of MCI is determining how much the memory processes are affected. Some criteria establish that in order to reach a diagnosis of MCI, the patient’s performance carrying out memory tasks must be inferior to the average obtained by normal adults; however, other criteria establish that for a diagnosis of MCI, patients must be compared with subjects of the same age and educational level. A very important point in the subgroup of patients with diabetes mellitus is to recognize that there is an exacerbated neurotoxicity caused by the beta amyloid plaques secondary to the advanced glycation end-products in their matrix; moreover, in animal models the existence of a diminished cholinergic transporter in patients with cognitive impairment and diabetes has been found4 (Fig. 1). Hypertension has been studied as a risk factor for cognitive impairment because it affects cerebral vasculature through different mechanisms, including strokes, leukoaraiosis, atherosclerosis, etc. In transversal studies, it has not been possible to find an evident association with arterial hypertension as a risk factor while in longitudinal studies such association has been demonstrated. Dyslipidemia has also been studied in different population samples finding a correlation between MCI and hyperlipidemia (especially hypercholesterolemia) in middle-aged patients. Furthermore, we are able to see in different studies that there is a protective association between the use of statins and MCI. Other risk factors which have been analyzed include chronic renal failure, vitamin B12 deficiency, vitamin D deficiency, hyperhomocysteinemia, testosterone deficiency, subclinical hypothyroidism, smoking, and excessive alcohol consumption. Population studies Many authors and institutions (The World Health Organization and The American Academy of Neurology, among others) have supported the term MCI. In recent years they have been trying to establish a greater delimitation of the term, mainly because different types of mild cognitive impairments have arisen (amnestic, non-amnestic, aphasia, apraxia or agnostic). Most of the studies are directed at evaluating MCI, and are focused, mainly, in observing the performance in the memory processes in older people, considering there is well-founded evidence showing that cognitive complaints 30 J. Isordia-Martínez et al OVERPRODUCTION AND DECREASE OF AMYLOID-BETA PURIFICATION PRECLINICAL STAGE BETA-AMYLOID ACCUMULATION MCI ACTIVATION OF NEUROTOXIC CASCADES BETA-AMYLOID OLIGOMERS HYPERPHOSPHORY LATION OF THE TAU PROTEIN GLIAL INFLAMMATION, OXIDATIVE STRESS, MITOCHONDRIAL DYSFUNCTION AMYLOID PLAQUES SYMPATHETIC AND AXONAL DYSFUNCTION NEURITIC PLAQUES NEUROFIBRILLARY PLAQUES DEMENTIA DEMENTIA Figure 1 Histopathologic changes in the brain and its clinical correlation. have a high prevalence in this population, suggesting a preclinical phase of a process of dementia; even though there are many longitudinal cohort studies of non-demented subjects, who have been developing cognitive impairment. One of the most representative investigations about MCI, and one which has been taken as a reference, was carried out by the researchers at Mayo Clinic in the United States. The objective of the researchers was to clinically classify subjects with MCI through a transversal and longitudinal study. A sample of 76 subjects with MCI was compared to 234 control subjects and with 106 patients with mild AD from the clinic or from the community register of patients with AD in Rochester. All 3 groups were evaluated longitudinally using instruments which evaluate cognitive performance (MMSE, WAIS-R, WMS-R, Dementia Rating Scale, Free and Cued Selective Reminding Test and Rey’s Auditory Verbal Learning Test, among others). Mild AD diagnosis was established by the DSM-III-R and the NINCDS-ADRDA. The results showed that in general intelligence measurements, subjects with MCI performance were more similar to that from control subjects than from patients with mild AD. In particular, in the complete WAIS-R scale, control subjects obtained an average IQ = 101.8 and subjects with MCI obtained an average IQ = 98, while patients with mild AD obtained an average IQ = 83.9. The results with the MMSE were very similar; control and MCI subjects obtained an average score of 28.3 and 26 respectively, while patients with mild AD obtained an average score of 22.6. On the other hand, subjects with MCI obtained a lower result than control subjects in the Controlled Oral Word Association Test, even though these results were within the normal expected range for their age, based on the community studies used for this research. However, performance carrying out memory tasks was very similar in subjects with MCI and patients with mild AD, yet the declining range of subjects with MCI performing these kinds of tasks was lower to the one showed by patients with mild AD but higher than that in control subjects. Researchers came to the conclusion that subjects considered under MCI criteria may be differentiated both from control subjects and patients with mild AD, thus considering MCI as a clinical entity characterized by a group of symptoms and amenable to of pharmacologically interactive treatment.5 Another study with great significance in MCI research was one carried out in St. Luis Missouri, US, where the local elderly population volunteered. The sample was of 454 subjects, who were classified according to the CDR as “cognitively healthy” (n = 177 y CDR = 0) and Lewy body dementia (LBD) (n = 277 and CDR = 0.5). Based on the clinical suspicion that MCI represents an early stage of Alzheimer’s, the MCI group with a score on the CDR = 0.5 was subdivided into three subgroups. The study had a follow-up of 9-and-a-half years, evaluating subjects with a neuropsychological battery and a neuropathological test for the subjects who passed away during research. The objective was to observe the progression of subjects towards a score in the CDR = 1, which characterizes Mild cognitive impairment “definite” mild Alzheimer’s. The evaluation protocol included items from brief standardized cognitive assessment batteries, such as MMSE and the Short Blessed Test (Katzman et al. 1983), among others. In general, the results showed that all the subjects with CDR = 0-5 displayed memory impairment and a higher frequency of alelo e4 of the gene apoe compared to normal subjects CDR = 0. The second cognitive domain frequently more impaired was the judgment and problem solving skill. On the other hand, the results showed that 100% of the subjects of the group CDR=5Alzheimer’s progress to a severe dementia in a period of 9.5 years, of the rate of conversion of this group to Alzheimer’s in 5 years 60.5% with an equal or superior score to 1 in the CDR. In the CDR = 0.5- incipient Alzheimer’s, the range of conversion to Alzheimer’s in 5 years was 35.7% and, for the CDR = 0.5- uncertain dementia, its range of conversion in the same period of time was 19.9%; However, in the control subjects (CDR = 0), the conversion range was only 6.8%. The conclusion was that MCI generally represents an early stage of Alzheimer’s, due to the fact that progression to a severe dementia correlates with the base line of the degree of impairment, in other words, 96% of the subjects with CDR = 0.5 progressed to a neuropathological state of dementia, and out of these, 84% were an Alzheimer-type dementia1 In a different study, Ritchie et al, with the objective of evaluating the predictive validity and temporal stability of the diagnosis criteria of MCI, analyzed a sample of 833 subjects with subclinical cognitive impairments, taken from a previous longitudinal study called the Eugeria Project, carried out in Montpellier, in the south of France. The sample was representative of the population and covered urban as well as rural populations. The study followed the cohort of subjects during a period of 3 years. During the first year, subjects were evaluated with an instrument used to screen cognitive functioning denominated Détérioration Cognitive Observée (DECO), which has demonstrated in diverse studies its high sensitivity to detect early changes in cognitive functioning due to different causes, observing the degree of change during the last year. Its estimation is similar to the one of a close person who has had continuous monthly contact with the patient during a period of three years. Using a neuropsychological computerized exam which covers most of the cognitive functions, six cognitive domains were selected; attention, primary memory, secondary memory, visuospacial skills, language and reasoning. In a second phase, MCI subjects were classified. The results showed that MCI prevalence in the general population was approximately 3.2%, and of cognitive impairment adjusted to their age of 19.3%. Thus, MCI turned out to be a poor background to a preclinical dementia phase in a period of three years, with a risk of conversion of 11.1% constituting, in general, an unstable group, because most of the subjects who belonged to this group, experimented category switches every year. On the contrary, the cognitive impairment adjusted group proved to be more homogenous and stable, with a conversion rate to dementia of 28.6% in a period of 3 years. The researchers came to the conclusion that criteria for MCI provide a poor performance when applied to a representative sample, given the fact that in most of the investigations which proposes MCI as a clinical diagnostic entity, samples have been obtained out of small selected clinical groups. Because cognitive complaints in older adults are the main 31 symptom to establish MCI criteria, several clinical studies have been carried out. These studies have tried to establish the predictive power of cognitive complaints in the memory processes.6 Furthermore, it is important to emphasize “The Canadian Study of Health and Aging” for its importance in which they carried out a 5-year follow-up of 10,263 elderlies (over 65 years and up), representing the general population of older adults (residents of the community, as well as institutionalized). In this epidemiologic study about health care, dementia and functional state the term “nodementia cognitive impairment” surfaces, which represents a cognitive disorder accompanied by a mild neuro-cognitive disorder, also, it is attributable to a subjacent functional disorder. In this study they obtained results which indicate that non-dementia cognitive impairment prevalence is 16.8% in people older than 64 years. From this study on, several parallel studies utilized samples from this study7 (Fig. 2). Clinical assessment The corner stone of diagnosis consists of a detailed clinical interview, ideally with the presence of an informant. There are several scale systems, since 1982 there have been 2 main ones which are used to this day: Clinical Dementia Rating (CDR) which gives a point system of 0 for normal people, 1 for mild dementia, and 0.5 for mild cognitive deterioration, and The Global Deterioration Scale (GDS) which scores mild cognitive deterioration with a score of 3 where patients display cognitive deficits and suffer alterations in the executive function which affects social and occupational activities. It is important to keep in mind that the scales do not mean 100% MCI diagnosis, because it is necessary to check it with the clinical findings, and medical history. In order to evaluate the subjects’ cognitive profile using the Folstein Mini-Mental State Examination Tool (MMSE), or via Montreal Cognitive Assessment (MOCA) taking into account their respective sensitivity and specificity. A medical and neurological examination must be carried out in order to identify non-degenerative cognitive alterations causes8,9 (Fig. 3). Emphasizing MMSE is one of the most utilized tests to evaluate these cognoscitive symptoms, it is very important to remember that this test assesses memory, orientation, language, spatial skills, attention, and calculus. It takes about 10 minutes to apply. Its score ranges from 0 to 30. A cut-off PERFORMANCE COGNITIVE NORMAL AGING FUNCTIONAL MILD COGNITIVE IMPAIRMENT Figure 2 Dementia spectrum. DEMENTIA 32 J. Isordia-Martínez et al point of 23 is generally recommended as an indicator of cognitive impairment. The test has a reliability of 0.89. One of its limitations is the fact that it is influenced by several factors; for example, the level of education. Some authors even consider the test to be affected by the patient’s ability to read. Other authors believe the test is affected by demographic factors such as gender and age. Therefore, differential cut-off points between subgroups have been suggested and alternative items have been generated (Galasko: the months of the year backwards). There are certain considerations which must be taken into account for MCI diagnosis: 1. An international working group has formulated specific recommendations in MCI criteria: The individual is not demented nor fits in the normal category. There should be evidence of impairment in cognition, demonstrated by a decline in time, or subjective reports made by an informant. Everyday activities are preserved and complex functions are intact or minimally affected.10 2. It has been noted that neuropsychiatric symptoms including dysphoria, irritability, hallucinations, apathy, depression, agitation, and delusions are more frequent in MCI and Alzheimer dementia patients. The presence of neuropsychiatric symptoms involves a greater risk for MCI patients of progressing into AD. The Neuropsychiatric Inventory (Cummings et al., 1994) is the most used scale to assess neuropsychiatric alterations including 12 areas (agitation, delusion, hallucinations, depression, euphoria, abnormal motor activity, apathy, irritability, disinhibition, anxiety, drowsiness and hunger); a patient’s relative who may have the information is questioned about these symptoms.11 CLINICAL DEGENERATIVE CLASSIFICATION AMNESTIC MCI NONAMNESTIC MCI 3. Psychiatric conditions (depression), medication adverse events (anticholinergics, antihistamines), sleep disorders, infections, metabolic diseases (vitamin B12 deficiency, hypothyroidism, hyperglycemia, hypoglycemia, uremia, hepatopathy, sodium disorders), structural brain diseases.11 Due to a great diversity of pathologies, researchers have tried to find ideal biomarkers for a more accurate diagnosis; we must remember that markers may be positive in non-demented subjects. Some of these markers reflect key cognitive impairment processes in the cerebrospinal fluid, such as the levels of isoform of beta 42 amyloid and Tau protein. Other studied markers include amyloid deposits or neurofibrillary plaques like Pittsburgh B compound or the 18-FDDNP.12 There are other markers which reflect secondary processes like neuron dysfunction or neuronal loss either by electroencephalogram (EEG), nuclear magnetic resonance or positron emission tomography scan. As far as EEG goes, researchers have found that the rate between theta and alpha 1 waves is a reliable individual rate of cerebrovascular damage.13 4. Cerebral biopsy plays a very limited role in the diagnosis of dementia; its diagnostic capabilities are minimal, the procedure is invasive and involves risk for major complications. The biopsy is reserved for younger patients and for those with atypical clinical presentations with potentially treatable causes. It is very important to promote the recognition and acknowledgement of this pathology as several studies have shown that between 29% and 76% of the cases may be identified in first contact care.14 Studies show that patients with SINGLE DOMAIN ALZHEIMER DISEASE MULTIPLE DOMAINS ALZHEIMER DISEASE SINGLE DOMAIN FRONTOTEMPORAL DEMENTIA MULTIPLE DOMAINS LEWY BODY DEMENTIA Figure 3 Clinical classification and cause of MCI. VASCULAR PSYCHIATRIC DEPRESSION VASCULAR DEMENTIA VASCULAR DEMENTIA DEPRESSION Mild cognitive impairment 33 MCI display a wide range of malnutrition. A study by The European Society for Clinical Nutrition and Metabolism found that from a sample of 623 patients, 18% had a normal nutrition status, 58% were at risk of malnutrition, and 24% showed clear malnutrition; thus, we must keep in mind that these types of patients display more alterations within the corporal economy in addition to neurological deficiencies.15 Within a pragmatic approach in the study of MCI, it is of great importance to cite several key questions for a proper assessment16 (Fig. 4): 1. What is the patient’s basal functional status? 2. How is the symptomatology’s evolution? (regarding time of onset) 3. What is the main characteristic of this deficit? (short-term or long term memory) SUBJECTIVE MEMORY COMPLAINT NORMAL COGNITIVE FUNCTION NORMAL AGING SIGNIFICANT FUNCTIONAL DISABILITY DEMENTIA INCOMPLETE COGNITIVE IMPAIRMENT NORMAL DEPRESSION AGING ALZHEIMER DISEASE Figure 4 Clinical approach to MCI. Neuroimaging Neuroimaging use is controversial; most guides do not recommend routine imaging studies, but they include rules to help identify patients who may have reversible causes of dementia, with factors that include being under 60 years old, showing focal neurological signs, and having been affected less than 2 years from the onset of the disease. However, their sensitivity and specificity are low. Magnetic resonance imaging (MRI) findings include focal and generalized atrophy, as well as white matter lesions; in general, these are unspecified findings. A tomography is important in those patients with acute unsaturation of the cognoscitive impairment and rapid neurological deterioration.17 A longitudinal cohort study was carried out in Rotterdam, The Netherlands. The main objective of this study was to determine whether or not the hippocampus and amygdala volume measured by MRI were useful for predicting the development of dementia in older people without cognitive impairment. The investigators monitored 511 patients between 60 and 90 years of age, for an average period of 6 years. Over this period of time, the atrophy of the hippocampus and the amygdala measured by MRI predicted a time of development of dementia of 6 years, with a risk rate adjusted to age, gender, and educational level of 3 (95% confidence interval [CI] 2.0-4.6) for every unit of standard deviation for the hippocampus and of 2.1 (95% CI 1.5-2.9) for the amygdalin level. In patients with cerebral atrophy and leukoaraisis, the exact correlation degree and influence between imaging findings and the results of the neuropsychological tests are unknown. Therefore, it is hard to classify this type of patient, because there are cases with major pathological findings and imaging representing a preserved cognition.18 Transcranial Doppler ultrasound PROMINENT MEMORY DISABILITY AMNESTIC MILD COGNITIVE IMPAIRMENT 4. Are there any changes in behavior? 5. Is there a co-existence of depression in this patient? 6. Could the patient in question have a serious subclinical pathology? Imaging techniques to analyze cerebral circulation are very diverse, there is no such thing as the ideal study. Transcranial Doppler ultrasound is a test performed with a portable device which allows measuring several blood flow parameters as well as the Circle of Willis, providing information about the velocity of blood flow (cm/s) through the brain’s blood vessels, resistance rates, and pulsatility, as well as the brain’s vasoreactivity following stimuli such as hyperventilation, induced hypercapnia, and even medications like acetazolamide. This study is performed with the patient in a decubitus position, after resting for 10 minutes, at room temperature, and comfortable, with the head at a 30 degree angle in a semi-Fowler position; a basal register is recorded and blood pressure registered every 5 minutes during the inhalation of 5%-7% carbon dioxide (CO2) for 5 minutes with an aesthetic mask covering both mouth and nose. The most utilized protocol is to register the velocity of systolic and diastolic flow, as well as the average resting 34 J. Isordia-Martínez et al flow of the middle cerebral artery and then again 5 minutes after inhaling CO2, assessing the responsive ability of cerebral arteries on entrance of carbon dioxide, numbers that adjust to age, gender, and changes in blood pressure. In patients with hypertension, after the vasodilator stimulus there is a decrease in the cerebral microvascular reactivity (explained by the decrease in the dilation ability to the vasodilator stimulus), which can be improved through the administration of antihypertensive medications.19 It has been shown that cerebral blood flow and cerebral vasoreactivity gradually decrease with age, and that this decrease is directly related to the presence of cerebral micro-strokes and impairment of cognitive function; in addition, vasoreactivity of the occipital is diminished even more in vascular dementia which is statistically significant compared to AD.20 is a scale with 6 categories, and is based in orientation, judgment, memory, personal care, performance within the house and hobbies, with a score of over 1, a specificity of 94% was demonstrated and a sensitivity of 92%. Diabetic patients have an odds ratio of 1.2-1.5 to obtain lower scores than those who are non-diabetics, regarding cognitive function; measured by Mini-Mental and the digital symbol test.22 An adequate conversion to dementia prediction must be made on those patients with mild cognitive impairment already established, there are several models; one of the most important is the “Five-Predictor Combination” with a sensitivity of 85.2% and 90% specificity based on age, MiniMental result, “Selective Reminding Test”, Functional activities questionnaire and University of Pennsylvania smell identification test23 (Fig. 5). Progression to dementia Importance of the subject The risk of dementia progression is estimated to be 10% per year; as for MCI patients, yearly progression rates fluctuate between 5% and 16%. Several long-term studies (over 5 years) have found that the risk of conversion decreases with time. Some of the factors associated with an increased risk of progression to dementia are socioeconomic variables and age while gender and level of education are not considered as factors. Age constitutes the main predictor of progression, risk increasing exponentially for every year people get older. The apolipoprotein E-epsilon4 (APOe4) genotype has been associated with an increased risk, as well as raised levels of the protein Thr phosphorylated tau 181, low levels of amyloid beta 42, rise in the activity of the beta-secretase, and of neprilysin (a degrading enzyme beta-amyloid peptide) activity diminution. An important rate of reversion of MCI to a normal cognitive state is observed (20%-25%).21 The American Academy of Neurology’s evidence–based guidelines for early detection states that MCI patients should be detected early and followed long-term, because of their high risk of subsequent development of dementia.2 For dementia detection in individuals suspected of cognoscitive impairment, screening instruments used to assess progression are: Mini-Mental State Examination (score of 224 or less, specificity 57%-99%, sensitivity 82%-99%, positive predictive value 68%-91%, negative predictive value 96%99%, evidence class I and II, the percentages vary because of the risk of dementia in each population, age classification, etc.), Kokmen short test of mental state (specificity 88%, sensitivity 86%), 7-minute screen, memory impairment screen (specificity 96%, sensitivity 87%, positive predictive value 54%-85%), Clock drawing test (specificity 96%, sensibility 92%), and Blessed dementia rating scale (specificity 46%, sensitivity 94%). Moreover, different instruments should be applied for different aspects of the cognoscitive function, being more useful the ones which emphasize memory, for example the Mattis dementia rating scale (mainly focused on attention, initiative, perseverance, building, memory, and conceptualization, between 129/144, sensitivity 98%, specificity 97%). It is necessary to apply neuropsychological batteries on the risk population, like the IQCODE (Informant Questionnaire on Cognitive Decline in the Elderly) or the CDR which The constant emergence of pharmacological and non-pharmacological preventive treatments to slow down or modify the course in AD and the other types of dementia, boost a great interest of reaching an early diagnosis in order to start acting as soon as possible with these patients. MCI is an adequate state for new therapies, thus its differential diagnosis is crucial, and a thing that nowadays is controversial, with great debates regarding its delimitation and acceptance as a new diagnostic entity. The development of specific instruments for MCI diagnosis is one of the most urgent tasks, given the fact that the current instruments have a significant tendency to only detect risk factors. Different studies agree that an adherence to the Mediterranean-style diet (hazard ratio [HR] = 0.60, CI 0.42-0.87) and high physical activity (HR = 0.67, CI 0.47-0.95) are independently associated with a reduced risk of cognitive impairment.24 Knowledge of an adequate control of systemic hypertension reduces the risk of developing vascular dementia, dementia with Lewy bodies, and frontotemporal dementia; nevertheless, it does not significantly decrease the development of MCI (RR = 0.97, CI 0.92-1.03) or AD.25 Currently, there is little evidence of the effectiveness and specificity of interventions that ALZHERIMER´S DISEASE AMNESIC MCI AMNESIC VASCULAR DEMENTIA MULTIPLE DOMAIN MCI NOT AMNESIC LEWY BODY DEMENTIA FRONTAL TEMPORAL DEMENTIA NON-AMNESIC MCI PSYCHIATRIC DISORDERS Figure 5 Progression of mild cognitive impairment. Mild cognitive impairment improve memory in the healthy elderly and those with MCI; studies show that after a systemic training the results improved in immediate and delayed verbal memory. Information to recommend MCI screening in asymptomatic individuals is lacking. Therefore, there is ongoing research and population analysis in order to determine which subjects will benefit the most from the search of this pathology.26 Treatment Adherence to a Mediterranean-style diet has been marginally associated with the reduction of progression of MCI to AD (HR = 0.55, 95% CI 0.34-0.9).27 According to the Cochrane Collaboration, there are no studies assessing the role that carbohydrates play in improving the performance of the evaluation in older people with MCI.28 High-intensity aerobic exercise may be beneficial for patients with MCI; results of studies carried out with small randomized samples to exercise 40 to 60 minutes 4 days a week for a period of 6 months, have shown that exercise improved the levels of the factor similar to the growth hormone, plasma insulin reduction when fasting, cortisol, and executive function.29 Cholinesterase inhibitors slow down the conversion to full dementia for up to 3 years, but it has been associated with adverse effects in adults with MCI (diarrhea, nausea, vomiting, cramps, insomnia, headaches, syncope or vertigo); the most studied are donepezil, galantamine, and rivastigmine, the relative risks of progression to dementia are 0.69 (95% CI 0.47-1) within 1 year, 0.67 (95% CI 0.55-0.83) within 2 years, and 0.84 (95% CI 0.7-1.02) within 3 years.30which is frequently updated from the major healthcare databases (MEDLINE, EMBASE, CINAHL, PsycINFO and Lilacs Galantamine is not recommended because of the mortality risk increase, with a number needed to harm (NNH) of 100;31 in addition, it has not really been associated with a diminution in the progression to dementia.32 In regards to donepezil, it may slow down the progression of AD; this is based on randomized studies of patients who received this medication at 5 mg a day for 6 weeks, which was titrated to 10 mg a day for 3 years. In general, the progression to dementia was seen in 16% of the 769 patients, with a significant improvement at 6, 12 and 24 months; among patients who were carriers of APOe4, the improvement in executive function was notable up to 3 years of follow-up.33 The most common adverse effects were diarrhea (NNH 10), cramps (NNH 7), insomnia (NNH 11), nausea (8.4%), vomiting (6%), and arthritis (2.5%).34 There are other diverse therapies for which the net clinical benefit provided is unknown; these include nicotine patch,35 gingko biloba,36 vitamin E,11 vitamins B637 and B12,38 folic acid,39 procaine,40 piracetam,41 and huperzine A.42 Conflicts of interest The authors have no conflicts of interest to declare. Funding No financial support was provided. 35 Acknowledgement Our acknowledgement and appreciation to the Neurology Services of “Dr. José Eleuterio González” University Hospital, particularly to Dr. Hector Jorge Villarreal, for all the facilities provided. References 1. Petersen RC, Doody R, Kurz A, et al. Current concepts in mild cognitive impairment. Arch Neurol 2001;58:1985–1992. 2. Panza F, D’Introno A, Colacicco AM, et al. Current epidemiology of mild cognitive impairment and other predementia syndromes. Am J Geriatr Psychiatry 2005;13:633–644. 3. Mejía AS, Miguel JA, Villa A, et al. Deterioro cognoscitivo y factores asociados en adultos mayores en México. Salud Publica Mex 2007;49:s475–s481. 4. Pasquier F, Boulogne A, Leys D, et al. Diabetes mellitus and dementia. Diabetes Metab 2006;32:403–414. 5. Petersen RC, Smith GE, Waring SC, et al. Aging, memory, and mild cognitive impairment. International Psychogeriatrics 1997;9:65-69. 6. Artero S, Touchon J, Ritchie K. Disability and mild cognitive impairment: a longitudinal population-based study. Int J Geriatr Psychiatry 2001;16:1092–1097. 7. The Canadian Study of Health and Aging: risk factors for Alzheimer’s disease in Canada. Neurology 1994;44:2073–2080. 8. Rosenberg PB, Johnston D, Lyketsos CG. A clinical approach to mild cognitive impairment. Am J Psychiatry 2006;163:1884– 1890. 9. Kelley RE, Minagar A. Memory complaints and dementia. Med Clin North Am 2009;93:389–406. 10. Winblad B, Palmer K, Kivipelto M, et al. Mild cognitive impairment--beyond controversies, towards a consensus: report of the International Working Group on Mild Cognitive Impairment. J Intern Med 2004;256:240–246. 11. Burns A, Iliffe S. Dementia. BMJ 2009;338:b75–b75. 12. Visser PJ. Use of biomarkers to select the target population for clinical trials in subjects with mild cognitive impairment. Journal of Nutrition, Health & Aging 2009;13:344-345. 13. Moretti DV, Miniussi C, Frisoni G, et al. Vascular damage and EEG markers in subjects with mild cognitive impairment. Clin Neurophysiol 2007;118:1866–1876. 14. Holsinger T, Deveau J, Boustani M, et al. Does this patient have dementia? JAMA 2007;297:2391–2404. 15. Orsitto G, Fulvio F, Tria D, et al. Nutritional status in hospitalized elderly patients with mild cognitive impairment. Clin Nutr 2009;28:100–102. 16. Young J, Meagher D, Maclullich A. Cognitive assessment of older people. BMJ 2011;343:5042–5042. 17. Oppenheim C, Naggara O, Frédy D, et al. Démences : place de l’imagerie. Journel Radiologie 2003;84:1819–1828. 18. Podemski R, Pokryszko-Dragan A, Zagrajek M, et al. Mild cognitive impairment and event-related potentials in patients with cerebral atrophy and leukoaraiosis. Neurol Sci 2008;29:411– 416. 19. Settakis G, Páll D, Molnár C, et al. Cerebrovascular reactivity in hypertensive and healthy adolescents: TCD with vasodilatory challenge. J Neuroimaging 2003;13:106–112. 20. Asil T, Uzuner N. Differentiation of vascular dementia and Alzheimer disease: a functional transcranial Doppler ultrasonographic study. J Ultrasound Med 2005;24:1065–1070. 21. Cukierman T, Gerstein HC, Williamson JD. Cognitive decline and dementia in diabetes--systematic overview of prospective observational studies. Diabetologia 2005;48:2460– 2469. 36 22. Devanand DP, Liu X, Tabert MH, et al. Combining early markers strongly predicts conversion from mild cognitive impairment to Alzheimer’s disease. Biol Psychiatry 2008;64:871–879. 23. Scarmeas N, Luchsinger JA, Schupf N, et al. Physical activity, diet, and risk of Alzheimer disease. JAMA 2009;302:627–637. 24. Chang-Quan H, Hui W, Chao-Min W, et al. The association of antihypertensive medication use with risk of cognitive decline and dementia: a meta-analysis of longitudinal studies. Int J Clin Pract 2011;65:1295–1305. 25. Martin M, Clare L, Altgassen AM, et al. Cognition-based interventions for healthy older people and people with mild cognitive impairment. Cochrane Database Syst Rev 2011;(1):CD006220. 26. Petersen RC, Stevens JC, Ganguli M, et al. Practice parameter: early detection of dementia: mild cognitive impairment (an evidence-based review). Report of the Quality Standards Subcommittee of the American Academy of Neurology. Neurology 2001;56:1133–1142. 27. Scarmeas N, Stern Y, Mayeux R, et al. Mediterranean diet and mild cognitive impairment. Arch Neurol 2009;66:216–225. 28. Ooi CP, Loke SC, Yassin Z, et al. Carbohydrates for improving the cognitive performance of independent-living older adults with normal cognition or mild cognitive impairment. The Cochrane Database of Syst Rev 2011;13:1-39. 29. Baker LD, Frank LL, Foster-Schubert K, et al. Effects of aerobic exercise on mild cognitive impairment: a controlled trial. Arch Neurol 2010;67:71–79. 30. Russ TC, Morling JR. Cholinesterase inhibitors for mild cognitive impairment. Cochrane Database Syst Rev 2012;9:Cd009132. 31. Accesed in January 2014: http://www.fda.gov/Drugs/DrugSafety/PostmarketDrugSafetyInformationforPatientsandProviders/DrugSafetyInformationforHeathcareProfessionals/ ucm085186.htm J. Isordia-Martínez et al 32. Winblad B, Gauthier S, Scinto L, et al. Safety and efficacy of galantamine in subjects with mild cognitive impairment. Neurology 2008;70:2024–2035. 33. Barnes DE, Yaffe K. Vitamin E and donepezil for the treatment of mild cognitive impairment. N Engl J Med 2005;353:951-952. 34. Stiles MM, Martin S, Persons RK. Clinical inquiries. Does treatment with donepezil improve memory for patients with mild cognitive impairment? J Fam Pract 2006;55:435–436. 35. Newhouse P, Kellar K, Aisen P, et al. Nicotine treatment of mild cognitive impairment: a 6-month double-blind pilot clinical trial. Neurology 2012;78:91–101. 36. Birks J, Grimley Evans J. Ginkgo biloba for cognitive impairment and dementia. Cochrane Database Syst Rev 2007;18:CD003120. 37. Farina N, Isaac M, Clark AR, et al. Vitamin E for Alzheimer’s dementia and mild cognitive impairment. Cochrane Database Syst Rev 2012;11:CD002854. 38. Smith AD. Homocysteine-lowering by B vitamins slows the rate of accelerated brain atrophy in mild cognitive impairment: a randomized controlled trial. PloS one 2010;5:e12244. 39. Ford AH. Vitamins B(12), B(6), and folic acid for cognition in older men. Neurology 2010;75:1540–1547. 40. Malouf M, Grimley EJ, Areosa SA. Folic acid with or without vitamin B12 for cognition and dementia. Cochrane Database Syst Rev 2003;CD004514. 41. Szatmári S, Bereczki D. Procaine treatments for cognition and dementia. Cochrane Database Syst Rev 2008;CD005993. 42. Flicker L, Grimley Evans G. Piracetam for dementia or cognitive impairment. Cochrane Database Syst Rev 2011;CD001011. Medicina Universitaria 2014;16(62):37-43 medicina universitaria www.elsevier.com.mx REVIEW ARTICLE Trichosporon spp.: an emerging fungal pathogen A. M. Montoya*, G. M. González Department of Microbiology, Faculty of Medicine, Universidad Autónoma de Nuevo León, Monterrey, N. L., Mexico Received: September 2013; Accepted: December 2013 KEYWORDS Trichosporon; White piedra; Onychomycosis; Trichosporonosis; Mycoses; Opportunistic infection; Mexico. Abstract Trichosporon spp. has gained importance as the cases of immunosuppressed patients increase. The genus Trichosporon includes 6 species of clinical relevance that may cause superficial infections, such as white piedra and onychomycosis, or deep and invasive infections with high mortality rates. These microorganisms have a broad geographical distribution and some species are resistant to antifungal drugs in vitro. The present paper is a review on the virulence factors, associated infections, and in vitro susceptibility of the species with the highest incidence as pathogenic agents in humans. 1665-5796 © 2014 Revista Medicina Universitaria. Facultad de Medicina UANL. Publicado por Elsevier México. Todos los derechos reservados. Introduction Trichosporon spp. Trichosporon spp. was first described by Beigel in 1865 as the agent responsible for a benign hair infection called white piedra (meaning “stone” in Spanish). Beigel classified the microorganism as algae and placed it in the genus Pleurococcus. It wasn’t until 1890 when Behrend identified the microorganism causing white piedra as a fungus which he called Trichosporon ovoides.1 Although generally associated with this superficial infection, Trichosporon spp. has gained importance as one of the most opportunistic systemic infections since the first case of invasive trichosporonosis involving the brain, reported in 1970.2 Trichosporon spp. belongs to the phylum Basidiomycota. It is a yeast-like fungus macroscopically characterized by forming radially symmetrical colonies; these colonies may be white or yellowish, with a smooth texture, creamy, cerebriform, powdery or moist. Microscopically, Trichosporon spp. forms hyaline septate hyphae, with abundant arthroconidia and blastoconidia, and in some cases presents appressoria. Regarding physiological tests, they assimilate several carbohydrates and other carbon sources, yet they do not possess fermentation capabilities. A major characteristic of the Trichosporon spp. genus is their ability to hydrolize urea.1,3-5 * Corresponding author: Department of Microbiology, Faculty of Medicine, Universidad Autónoma de Nuevo León, Monterrey, N. L., Mexico. E-mail address: [email protected] (A. M. Montoya). 38 In 1902 Vuillemin grouped the species described for this genus under the Trichosporon beigelii denomination, a practice that remained until the late 90’s.5,6 Nevertheless, posterior classifications at morphological, biochemical, and molecular levels provided evidence of the existence of more than one species in the genus. Approximately 50 species of the genus Trichosporon have been characterized, 16 of which are associated with diseases in humans. Guého et al. (1994) typified species that had displayed a major adaptation to the human body: T. asahii, T. asteroides, T. cutaneum, T. inkin, T. mucoides and T. ovoides. These 6 species, reclassified from the Trichosporon beigelii taxon, remain the most relevant clinical species to date.7 Virulence factors There is little information regarding virulence factors produced by this microorganism. Hemolysins, proteases, and lipases allow protein degradation and destabilization of the membranes of the host cell, increasing fungus pathogenicity. Dağ and Cerikçioğlu analyzed the production of proteases, phospholipases, and esterases of 48 T. asahii clinical isolates, and did not detect protease nor phospholipase activity in any of the isolates analyzed; however, all the evaluated strains displayed esterase activity.8 Similarly, Sun et al. evaluated protease, phospholipase, and hemolysine production in 23 T. asahii clinical isolates, and observed no protease nor phospholipase activity, yet 100% of isolates showed hemolysin activity. This activity, however, varied for the different T. asahii genotypes identified.9 It is important to underline that there are no reports about the production of lytic enzymes for Trichosporon non-asahii species. Phenotypic switching is a fast and reversible change of colonial morphology and/or microscopic features. These changes may occur as a response to different environmental stimuli such as oxidative stress or lack of nutrients, or intrinsic factors such as a mutation in the deoxyribonucleic acid (DNA) repair systems.10 When phenotypic switching occur in vivo, they involve modifications in the expression of virulence factors, or alterations in the microorganism-host cell interactions, thus provoking an increment in the pathogenicity and evasion of the immune response, as observed in Candida albicans and Cryptococcus neoformans.11-13 Lee et al., reported phenotypic switching in vitro for the first time for T. beigelii. The isolated microorganism, recovered from a patient with a systemic infection, was capable of producing two different morphologies when cultivated at 30°C. Such morphotypes were accompanied by their respective structural microscopic changes. Thus, a rough, cerebriform, moist colony with irregular edges was accompanied microscopically by hyphae while a second powder morphotype, with a more regular topography and borders, showed microscopically a greater proportion of arthroconidia or blastoconidia. 4 The phenotypic switching was also reported in vivo by Karashima et al., who performed experiments involving repetitive inoculation of T. asahii in mice. They observed macro- and microscopic morphological differences when comparing the fungi before being inoculated and the same fungi recovered after 3 repetitive passages in 8-week-old A. M. Montoya and G. M. González ICR mice. Similar to the results obtained by Lee et al., Karashima observed that the rugged colony was accompanied microscopically by a greater proportion of hyphae, while a powdery colony was accompanied by a greater amount of conidia.14 In the same paper, Karashima et al. reported the production of a cell wall component similar to the glucuronoxylomannan (GXM) of C. neoformans. They observed that a larger amount of GXM was present in the recovered microorganism after repeated inoculations in mice. GXM has been proposed to offer C. neoformans protection against phagocytosis by neutrophils and monocytes.14 Another factor providing protection to the fungus is the formation of biofilms. Some microorganisms have the ability to produce an extracellular matrix, formed by polysaccharides, proteins, and DNA, which allow conglomeration of cells and their adherence to both organic and inorganic surfaces.15 Due to the association of invasive infections to the use of catheters and similar devices, the microorganism’s ability to adhere itself and form a biofilm could play a very important role in the pathogenesis during trichosporonosis. In 2006, Di Bonaventura et al. assessed the biofilm growth kinetics in vitro for some clinical isolates of T. asahii. They found that T. asahii cells were capable of quickly adhering to polystyrene after incubation for 30 minutes, displaying a low metabolic activity during the first 4 hours. The biofilm’s complexity increased after 6 to 8 hours of incubation, period during which it was possible to observe a monolayer formed by filamentous structures. At 72 hours, the cells showed both yeast-like and filamentous structures embedded in an extracellular matrix, forming a mature biofilm ranging from 20 to 40 µm in thickness. Biofilm formation was accompanied by a consequent increase in the resistance to voriconazole (up to 16,000 times more compared to planktonic cells).16 That same year, Dağ and Cerikçioğlu reported a moderate to weak production of biofilms in 58% of the clinically isolated T. asahii species that were analyzed.8 Associated infections Table 1 summarizes the main clinical manifestations and risk factors in infections caused by Trichosporon spp. White piedra White piedra is an infection in which white nodules are formed due to the aggregation of conidia around the hair shaft. These nodules are soft, whitish, have a defined border, and measure approximately between 1 and 3 mm of diameter. White piedra mainly affects capital hair; however, the infection may present itself in the hair of armpits, pubis, and in a lesser degree moustaches and beards. It is a chronic and asymptomatic disease. It is a superficial infection in which fungi remain in contact with the cuticle, without invading neither the hair medulla, scalp, nor skin.3 White piedra is a cosmopolitan and exogenous mycosis occurring more frequently in tropical and temperate climates. Humidity and poor hygiene are among the risk factors for the attainment of this pathology. Women and children are the groups mainly affected by capital white piedra.17,18 Most cases of genital white piedra, second in incidence, Trichosporon spp.: an emerging fungal pathogen 39 Table 1 Infections caused by Trichosporon spp., main clinical manifestations and risk factors. Principal agents Transmission Clinical manifestations Main risk factors and associated conditions T. ovoides, T. inkin, T. cutaneum Exogenous White nodules around parasitized hair Humidity and poor hygiene Shaving the affected area and topical imidazoles T. asahii, T. cutaneum, T. mucoides, T. inkin Exogenous Thickening and discoloration of nails Humidity and poor hygiene Topical imidazoles Neutropenia and catheter use No optimal treatment exists. Triazoles have shown the best inhibitory effectiveness in vitro Infection White piedra Onychomycosis Trichosporonosis T. asahii, T. mucoides, T. asteroides Endogenous Fever, fungemia, invasion of soft tissues involve males between 15 and 44 years of age.19,20 T. asahii, T. inkin, T. cutaneum, T. mucoides, and T. ovoides have all been associated with white piedra, T. ovoides being the one with the highest incidence.1,21 Trichosporonosis When Trichosporon spp. develops as an invasive infection, the disease is known as trichosporonosis. This infection has a mortality rate between 50% and 80%,22 and it is the second or third cause of fungemia in immunocompromised patients just after Candida spp.23-25 Trichosporonosis is considered an endogenous disease because the microorganism is commonly found as a part of the flora in the gastrointestinal tract, lungs, and skin.1,3 These opportunistic systemic infections have gained clinical importance due to their growing prevalence in certain groups of patients. Neutropenia is the main risk factor. A relationship between trichosporonosis and having undergone an invasive clinical procedure (e.g., probes and catheters) has been established as well. Kontoyannis et al. (2004) evaluated risk factors associated with the infection caused by Trichosporon spp. in 17 cancer patients. They observed that out of the 10 patients who displayed fungemia, 41% developed trichosporonosis subsequent to the use of catheters. The underlying disease in most patients was acute leukemia, and in 65% of the cases neutropenia was observed. Some patients had received chemotherapy (76%) or high doses of corticosteroids (89%) 1 month prior to the trichosporonosis diagnosis.26 Girmenia et al. (2005) performed a retrospective study including 287 cases of trichosporonosis worldwide. They found that 62.8% of the patients had suffered from a hematologic disease previous to the trichosporonosis diagnosis. Acute leukemia had the highest incidence (68%). Other conditions of risk associated with the development of trichosporonosis were solid tumors, transplants, peritoneal dialysis, and human immunodeficiency virus.27 Ruan et al. (2009), based on a Treatment study of 19 cases of invasive trichosporonosis, reported the use of central catheters as the main risk factor (90%).22 Suzuki et al. (2010) analyzed 33 patients with hematological diseases; the results were similar to the ones previously reported: acute leukemia (82%) and neutropenia (85%) were the main risk factors for trichosporonosis. Moreover, it was observed that most patients were undergoing chemotherapy when diagnosed with this mycosis.28 The main trichosporonosis manifestations are fever and fungemia. However, tissue invasion may develop. Cases of inflammation and abscesses in different organs and tissues (heart, brain, liver, spleen, esophagus, urinary tract, joints, peritoneum) have been reported. T. asahii, T. asteroides, T. cutaneum, T. inkin and T. mucoides are the 5 most common species associated with trichosporonosis cases.9,22,29-32 Tissue invasion and damage There are reports using murine models for evaluating tissue damage in invassive infections by Trichosporon spp.. Mice require cyclophosphamide-induced immunosuppression prior to high doses of fungi inoculation, which emulates the neutropenia in patients who develop trichosporonosis. Studies in animal survival have proven that the establishment of the infection is dose dependent. However, both the inoculum size causing mortality and time elapsed until tissue invasion is detected vary in different reports. Gokaslan and Anaissie determined that an inoculum of ≥ 2 x 107 colony forming units (CFU) causes 100% mortality and invasion of organs in immunosupressed mice 6 days after infection.34 On the other hand, Hospenthal et al. reported that an inoculum of ≥ 7 x 106 CFU caused 100% mortality with tissue invasion 6 hours after infection.35 These models were developed with infection by T. beigelii, therefore the observed differences in infectivity and progress of the disease could be a result of an induced infection by an unidentified species of the genus Trichosporon. Yamagata et al. utilized an inoculum of 3 x 106 CFU of T. asahii in a model in which mice were 40 immunosuppressed at week 1, showing a significant difference compared to the animals which were not immunosuppressed or those receiving a second cyclophosphamide dose at week 3 (20% of mortality). They concluded that the first 3 weeks are critical for the development of systemic trichosporonosis by T. asahii.29 Fungi presence in the affected organs is generalized. Persistence of the microorganism in kidneys of immunosuppressed mice as well as of immunocompetent ones has been reported. In animal groups where mortality is induced via inoculation of lethal doses, the initial inoculum has been recovered as much as 36-fold from brain, heart and kidney. A resolution of the infection in re-immunosuppressed animals has not been observed. The presence of Trichosporon spp. has been confirmed by molecular methods, even when the cell count is under the detection limits.29,34,35 Hyphae and conidia have been observed in different proportions depending on the organ and the stage of infection. Yeast-like structures are often found in earlier stages, while hyphae and arthroconidia are present in later stages of the infection. Predominance of yeast-like structures in the lungs of the infected animals has been reported.35 One of the most prevalent signs of invasive trichosporonosis is the granulomatous inflammation reported in lungs, liver, lymph nodes, and spleen in immunosuppressed and immunecompetent mice, as well as a fungal invasion of the blood vessels’ lumen or periphery.34-36 Other findings include kidney, spleen, lung, and heart hyperemia. Tubular edema, focal parenchymal destruction, cortical tubular necrosis, and chronic inflammation with fibrosis have been observed in the kidneys of mice surviving infection. In the liver, hepatic sinus dilation and congestion have been reported, as well as degeneration and necrosis of some hepatocytes and proliferation of Kupffer cells. Splenic sinuses dilation and splenomegaly have also been observed. In lungs, edema, hemorrhage, and alveolar ectasia have been described. In the heart, evidence of hemorrhage and cardiomyocytes necrosis have been reported. 34-37 Onychomycosis In the last few years, cases of onychomycosis associated with infections caused by Trichosporon spp. have increased. Around the world, this genus is the agent responsible for 1.3% to 10% of onychomycosis cases, being T. asahii, T. mucoides, and T. inkin the most frequently involved microorganisms.38-40 There have been discrepancies between cases reported in Mexico and other countries. In a study performed in pediatric patients from a rural area, Archer-Dubon et al. isolated T. cutaneum in 42% of the patients with onychomycosis and athlete’s foot, a percentage higher than the estimated for infections by dermatophytes and Candida spp., microorganisms typically responsible for foot infections.41 Laboratory diagnosis Clinical laboratory diagnosis varies in cases of superficial and systemic infections. In the case of white piedra, the hair sample is submerged in a potassium hydroxide solution for observation under the microscope of the nodules formed A. M. Montoya and G. M. González by the aggregated spores around the hair shaft, which allows differential diagnosis of other parasitizations such as pediculosis or trichomycosis. Similarly, onychomycosis diagnosis requires the nail scrape to be submerged in potassium hydroxide for microscopic observation of conidia and hyphae. In both cases, precise etiologic diagnosis requires a culture. Trichosporonosis diagnosis is made routinely by the recovery of fungi from blood and/or biopsies.3 Cultures obtained from diverse clinical samples are used for identifying the etiologic agent through its microscopic morphology by confirming the presence of the 3 characteristic structures of the genus Trichosporon: hyphae, arthrocondia, and blastocondia. The biochemical profile may be obtained by auxanography, which evaluates the ability to assimilate different sources of carbon. However, the complete biochemical characterization of species of the genus Trichosporon is based on the assimilation of approximately 50 carbon compounds and requires anywhere between 5 and 15 days for the readings; consequently, it is not practical to carry out this battery of tests for the precise identification of pathogenic species. There are commercial methods which systematize the application of assimilation tests and reduce the required identification time. The API 20C AUX system by bioMérieux is a commercial micromethod, which has turned into the most used in clinical laboratories. This system evaluates the assimilation ability of 19 carbohydrates and allows identification within a timeframe of 24 to 72 hours of incubation. However, a limitation of this test is that it only allows the identification of 3 species of the genus: T. asahii, T. inkin, and T. mucoides. This last characteristic prevents its generalized use. Different molecular methods have been developed as fast and effective alternatives for the precise identification of many pathogens at the species level. Ribosomal DNA is widely used in the systematic identification of microorganisms. Molecular identification of fungi is typically performed by sequencing of the internal transcribed spacer (ITS) region. One of the inconveniences of this region is the fact that it is highly homologous between the different species in the genus Trichosporon; therefore, the analysis of other genes or regions with higher heterology is needed in order to obtain a more accurate identification. Sugita et al. analyzed 84 strains corresponding to 25 species of the genus Trichosporon to evaluate the efficacy of sequencing the ITS region and the intergenic spacer 1 (IGS1) region for the precise identification at a species level. They found a higher heterology between IGS1 regions in comparison to ITS. This makes the IGS1 sequencing analysis superior compared to ITS for the differentiation between species of the genus. In addition, this method allows genotypification.42 A growing number of reports reveal the effectiveness of molecular methods in the identification of this microorganism. These publications show the lack of specificity of the conventional identification methods based in morphologic and biochemical criteria.43-46 Treatment Superficial infections caused by Trichosporon spp. may be treated with galenic solutions such as 1% mercuric chloride, 1% iodine solution, and 30% salicylic acid. They may be Trichosporon spp.: an emerging fungal pathogen 41 treated with topical antifungals, mainly imidazoles like econazole, isoconazole, miconazole, and ketoconazole. In patients with white piedra, the trimming or shaving of parasitized hairs or affected areas prior to topical treatment is recommended.1,3,17 Management of deep infections has been a bigger challenge. Trichosporon spp. has displayed variable resistance to the most common antifungal treatments; consequently, there is no optimal treatment for trichosporonosis cases. 5-Flucytosine (5-FC) is an inhibitor of the synthesis of nucleic acids; it interacts with the fungal RNA disrupting the synthesis of proteins. 5-FC has shown poor antifungal activity against the most clinically relevant species, with MICs ≥ 2 µg/ml and reaching concentrations of up to 128 µg/ml for T. mucoides.9,22,44,49 Caspofungin (CAS) is an echinocandin that inhibits the synthesis of the fungal cell wall. CAS MICs are high for T. asahii (≥ 4 µg/ml) and T. asteroides (16 µg/ml).49,50 In vitro susceptibility Immunotherapy Trichosporon spp. was first reported as an amphotericin Bresistant pathogen by Walsh et al. in 1990, after evaluating 2 T. beigelii isolates obtained from patients with systemic infections.47 Since its taxonomic revision, several studies have assessed the efficacy of different antifungals against the species of the genus, mainly T. asahii. It is important to mention that to this day there is not an established method to determine in vitro susceptibility of species belonging to the genus Trichosporon. The most widely used protocol is an adaptation of the method used for Candida spp. and C. neoformans described in documents M27 and M44 of the Clinical and Laboratory Standards Institute. One of the most evaluated antifungals has been amphotericin B (AMB). This is a polyenic derivate that destabilizes the fungal cytoplasmic membrane; it is the treatment of choice for systemic infections. The resistance of Trichosporon spp. to AMB has been reported. T. asahii consistently exhibits a MIC of ≥ 2 µg/mL (Minimal Inhibitory Concentration, which prevents visible growth of 90% of isolates).22,44,48,49 There are similar MICs for other clinical isolates including T. asteroides, T. cutaneum, and T. ovoides.22 Rodríguez-Tudela et al. (2005), contrary to the previous study, reported low MICs for T. cutaneum (0.25-0.5 µg/ml) and T. ovoides (0.37 µg/ml). T. mucoides showed great variability regarding susceptibility to AMB, with MICs ranging between 0.015 and 16.0 µg/ml.44 T. inkin is the species which has displayed greater in vitro susceptibility to the inhibitory activity of AMB, with MICs from 0.14 to 1.0 µg/ml.44,48 Triazolic compounds are inhibitors of the ergosterol synthesis, the main component of the fungal cytoplasmic membrane. In addition, they interact with enzymes at a mitochondrial level causing the accumulation of free radicals inside the cell and provoking the inhibition of fungal growth. Triazolics include fluconazole (FLC), voriconazole (VRC), itraconazole (ITR), and posaconazole (POS). These agents have displayed better in vitro activity against Trichosporon spp., with relatively low MICs for T. asahii (FLC 1.27 to ≤ 10.3 µg/ml, ITR ≤ 1.4 µg/ml, POS 0.25 µg/ml), T. asteroides (FLC 0.8 µg/ml, ITR 0.06 µg/ml), T. inkin (FLC ≤ 4 µg/ml, ITR ≤ 1 µg/ml), T. cutaneum (FLC ≤ 32 µg/ml, ITR ≤ 1 µg/ ml), and T. ovoides (FLC 1.74 µg/ml, ITR 0.1 µg/ml).22,44,48,49 Voriconazole is particularly effective for fungal inhibition in vitro, with MICs of ≤ 0.28 µg/ml for the 6 more frequently isolated Trichosporon species causing human pathology.44,49 Terbinafine (TER) is a synthetic antifungal derived from allylamines that inhibits ergosterol synthesis. TER requires high concentrations in order to inhibit T. asahii (12.6 µg/ ml), as opposed to the inhibition of T. cutaneum o T. inkin (1 µg/ml).48 Since neutropenia is the main condition associated with the development of trichosporonosis, the use of cytokines has been considered for the treatment of these infections. Some of the factors used are the granulocytes colony stimulating factors (G-CSF), which increase polymorphonuclear cell count, and the granulocytes-macrophages colony stimulating factors (GM-CSF), which activate monocytes and macrophages functions. Muranka et al. (1997) used a murine model with disseminated T. asahii trichosporonosis for the evaluation of G-CSF and GM-CSF as therapy against systemic infection. They observed that the use of G-CSF prior to fungal infection increased the survival in mice from 25% to 100%, decreasing the fungal load and tissue damage in affected organs, with the most notable improvement in the lungs. The increase in neutrophils by GM-CSF was lower than the one caused by G-CSF, so the use of GM-CSF therapy did not generate any major improvements in animals. In the same study, they observed an increase of tumor necrosis factor alpha (TNF-α) in bronchoalveolar lavage fluid in mice infected with lethal doses of T. asahii and treated with GMCSF compared to non-immunosuppressed animals or animals treated with G-CSF. In addition, a negative correlation between TNF-α production and the presence of leukocytes in peripheral blood was observed, decreasing as mice recuperated from the neutropenia. Anti-TNF-α therapy did not favor infection resolution. The investigators concluded that neutrophil count was the most critical factor in the development of trichosporonosis; however, other factors, such as TNF-α in lung, played an important role in the resolution of the infection.51 Similarly, the use of macrophages colony stimulating factor (M-CSF) has been evaluated as an activator of phagocytosis in a trichosporonosis murine model with T. asahii. M-CSF increased fungicidal activity in mononuclear cells, with a notable increase in survival and a decrease in fungal load. In addition, an increase in TNF-α in lungs and plasma in animals treated with M-CSF was noticeable. Different from the results reported by Muranaka et al., anti-TNF-α treatment did increase survival in mice. Results showed how M-CSF exponentially increased fungal activity by mononuclear phagocytes, helped partly by the production of TNF-α.52 Similar results regarding the effect of G-CSF, GM-CSG, and M-CSF on leukocytes and their role in trichosporonosis resolution were reported by Roilides et al. (2002).53 Conclusion Vast distribution, antifungal resistance, and an increase in the number of patients presenting risk factors have made 42 relevant the study of species belonging to the genus Trichosporon as opportunistic fungal agents relevant. High mortality rates in patients with systemic infections as well as a lack of an optimal treatment generate the need to increase the knowledge of this particular pathogen, in a way that allows us to understand its virulence mechanisms, and consequently, to obtain the necessary tools for the development of effective therapies against these microorganisms. Conflicts of interest The authors have no conflicts of interest to declare. Funding No financial support was provided. References 1. Colombo AL, Padovan ACB, Chaves GM. Current knowledge of Trichosporon spp. and trichosporonosis. Clin Microbiol Rev 2011;24:682–700. 2. Watson KC, Kallichurum S. Brain abscess due to Trichosporon cutaneum. J Med Microbiol 1970;3:191–193. 3. Bonifaz A. Micología médica básica. México: McGraw Hill/Interamericana; 2012. p. 161-168. 4. Lee JW, Melcher GA, Rinaldi MG, et al. Patterns of morphologic variation among isolates of Trichosporon beigelii. J Clin Microbiol 1990;28:2823–2827. 5. Guého E, de Hoog GS, Smith MT. Neotypification of the genus Trichosporon. Antonie van Leeuwenhoek 1992;61:285–288. 6. Guého E, Smith MT, de Hoog GS, et al. Contributions to a revision of the genus Trichosporon. Antonie van Leeuwenhoek 1992;61:289–316. 7. Guého E, Improvisi L, de Hoog GS, et al. Trichosporon on humans: a practical account. Mycoses 1994;37:3–10. 8. Dağ A, Cerikçioğlu N. Investigation of some virulence factors of Trichosporon asahii strains isolates from the clinical samples of hospitalized patients. Mikrobiyoloji Bülteni 2006;40:225–235. 9. Sun W, Su J, Xu S, et al. Trichosporon asahii causing nosocomial urinary tract infections in intensive care unit patients: genotypes, virulence factors and antifungal susceptibility testing. J Med Microbiol 2012;61:1750–1757. 10. Alby K, Bennett RJ. Stress-induced phenotypic switching in Candida albicans. Mol Biol Cell 2009;20:3178–3191. 11. D’Souza CA, Heitman J. It infects me, it infects me not: phenotypic switching in the fungal pathogen Cryptococcus neoformans. J Clin Invest 2001;108:1577–1578. 12. Geiger J, Wessels D, Lockhart SR, et al. Release of a potent polymorphonuclear leukocyte chemoattractant is regulated by white-opaque switching in Candida albicans. Infect Immun 2004;72:667–677. 13. Kumamoto CA, Vinces MD. Contributions of hyphae and hyphaco-regulated genes to Candida albicans virulence. Cell Microbiol 2005;7:1546–1554. 14. Karashima R, Yamakami Y, Yamagata E, et al. Increased release of glucuronoxylomannan antigen and induced phenotypic changes in Trichosporon asahii by repeated passage in mice. J Med Microbiol 2002;51:423–432. 15. Hall-Stoodley L, Costerton JW, Stoodley P. Bacterial biofilms: from the natural environment to infectious diseases. Nat Rev Microbiol 2004;2:95–108. 16. Di Bonaventura G, Pompilio A, Picciani C, et al. Biofilm formation by the emerging fungal pathogen Trichosporon asahii: A. M. Montoya and G. M. González development, architecture, and antifungal resistance. Antimicrob Agents Chemother 2006;50:3269–3276. 17. Kiken DA, Sekaran A, Antaya RJ, et al. White piedra in children. J Am Acad Dermatol 2006;55:956–961. 18. Vieira da Silva Pontes ZB, Lira Ramos A, de Oliveira Lima E, et al. Clinical and mycological study of scalp white piedra in the state of Paraíba, Brazil. Mem Inst Oswaldo Cruz 2002;97:747–750. 19. Kalter DC, Tschen JA, Cernoch PL, et al. Genital white piedra: Epidemiology, microbiology, and therapy. J Am Acad Dermatol 1986;14:982–993. 20. Schwinn A, Ebert J, Hamm H, Bröcker EB. Genitale weisse Piedra. Der Hautarzt 1996;47:638–641. 21. Shivaprakash MR, Singh G, Gupta P, et al. Extensive white piedra of the scalp caused by Trichosporon inkin: A case report and review of literature. Mycopathologia 2011;172:481–486. 22. Ruan SY, Chien JY, Hsueh PR. Invasive trichosporonosis caused by Trichosporon asahii and other unusual Trichosporon species at a medical center in Taiwan. Clin Infect Dis 2009;49:e11–e17. 23. Córdoba S, Vivot W, Bosco-Borgeat ME, et al. Species distribution and susceptibility profile of yeasts isolated from blood cultures: results of a multicenter active laboratory-based surveillance study in Argentina. Rev Argent Microbiol 2011;43:176– 185. 24. Dotis J, Pana ZD, Roilides E. Non-aspergillus fungal infections in chronic granulomatous disease. Mycoses 2013;56:449-462. 25. Oberoi JK, Wattal C, Goel N, et al. Non-albicans Candida species in blood stream infections in a tertiary care hospital at New Delhi, India. Indian J Med Res 2012;136:997–1003. 26. Kontoyiannis DP, Torres HA, Chagua M, et al. Trichosporonosis in a tertiary care cancer center: risk factors, changing spectrum and determinants of outcome. Scand J Infect Dis 2004;36:564– 569. 27. Girmenia C, Pagano L, Martino B, et al. Invasive infections caused by Trichosporon species and Geotrichum capitatum in patients with hematological malignancies: a retrospective multicenter study from Italy and review of the literature. J Clin Microbiol 2005;43:1818–1828. 28. Suzuki K, Nakase K, Kyo T, et al. Fatal Trichosporon fungemia in patients with hematologic malignancies. Eur J Haematol 2010;84:441–447. 29. Yamagata E, Kamberi P, Yamakami Y, et al. Experimental model of progressive disseminated trichosporonosis in mice with latent trichosporonemia. J Clin Microbiol 2000;38:3260–3266. 30. Heslop OD, Nyi Nyi MP, Abbott SP, et al. Disseminated trichosporonosis in a burn patient: meningitis and cerebral abscess due to Trichosporon asahii. J Clin Microbiol 2011;49:4405–4408. 31. Matsue K, Uryu H, Koseki M, et al. Breakthrough trichosporonosis in patients with hematologic malignancies receiving micafungin. Clin Infect Dis 2006;42:753–757. 32. Rastogi VL, Nirwan PS. Invasive trichosporonosis due to Trichosporon asahii in a non-immunocompromised host: a rare case report. Indian J Med Microbiol 2007;25:59–61. 33. Kalawat U, Sharma KK. Trichosporon peritonitis following duodenal perforation. Saudi J Gastroenterol 2010;16:43–45. 34. Gokaslan A, Anaissie E. A novel murine model of disseminated trichosporonosis. Infect Immun 1992;60:3339–44. 35. Hospenthal D, Belay T, Lappin P, et al. Disseminated trichosporonosis in a neutropenic murine model. Mycopathologia 1993;122:115–122. 36. Lacy SH, Gardner DJ, Olson LC, et al. Disseminated trichosporonosis in a murine model of chronic granulomatous disease. Comp Med 2003;53:303–308. 37. Lin YP, Yang YP, Huang WM, et al. Experimental pathogenicity of a clinical isolate of Trichosporon dermatis in a murine model. Mycopathologia 2011;172:381–387. 38. Dhib I, Fathallah A, Yaacoub A, et al. Clinical and mycological features of onychomycosis in central Tunisia: a 22 years retrospective study (1986-2007). Mycoses 2012;56:273–280. Trichosporon spp.: an emerging fungal pathogen 39. Pontes ZB, Lima Ede O, Oliveira NM, et al. Onychomycosis in João Pessoa City, Brazil. Rev Argent Microbiol 2002;34:95–99. 40. Kim ES, Kim DH, Chang SE, et al. Trichosporon species in onychomycosis and tinea pedis. Korean J Dermatol 2003;41:702–707. 41. Archer-Dubon C, Orozco-Topete R, Leyva-Santiago J, et al. Superficial mycotic infections of the foot in a native pediatric population: a pathogenic role for Trichosporon cutaneum? Pediatr Dermatol 2003;20:299–302. 42. Sugita T, Nakajima M, Ikeda R, et al. Sequence analysis of the ribosomal DNA intergenic spacer 1 regions of Trichosporon species. J Clin Microbiol 2002;40:1826–1830. 43. Middelhoven WJ, Scorzetti G, Fell JW. Systematics of the anamorphic basidiomycetous yeast genus Trichosporon Behrend with the description of five novel species: Trichosporon vadense, T. smithiae, T. dehoogii, T. scarabaeorum and T. gamsii. Int J Syst Evol Microbiol 2004;54:975–986. 44. Rodriguez-Tudela JL, Diaz-Guerra TM, Mellado E, et al. Susceptibility patterns and molecular identification of Trichosporon species. Antimicrob Agents Chemother 2005;49:4026–4034. 45. Ahmad S, Al-Mahmeed M, Khan ZU. Characterization of Trichosporon species isolated from clinical specimens in Kuwait. J Med Microbiol 2005;54:639–646. 46. Taj-Aldeen SJ, Al-Ansari N, El Shafei S, et al. Molecular identification and susceptibility of Trichosporon species isolated from clinical specimens in Qatar: isolation of Trichosporon dohaense Taj-Aldeen, Meis & Boekhout sp. nov. J Clin Microbiol 2009;47:1791–1799. 43 47. Walsh TJ, Melcher GP, Rinaldi MG, et al. Trichosporon beigelii, an emerging pathogen resistant to amphotericin B. J Clin Microbiol 1990;28:1616–1622. 48. Li HM, Du HT, Liu W, et al. Microbiological characteristics of medically important Trichosporon species. Mycopathologia 2005;160:217–225. 49. Chagas-Neto TC, Chaves GM, Melo ASA, Colombo AL. Bloodstream infections due to Trichosporon spp.: species distribution, Trichosporon asahii genotypes determined on the basis of ribosomal DNA Intergenic Spacer 1 Sequencing, and antifungal susceptibility testing. J Clin Microbiol 2009;47:1074–1081. 50. Guo LN, Xiao M, Kong F, et al. Three-locus identification, genotyping, and antifungal susceptibilities of medically important Trichosporon species from China. J Clin Microbiol 2011;49:3805– 3811. 51. Muranaka H, Suga M, Nakagawa K, et al. Effects of granulocyte and granulocyte-macrophage colony-stimulating factors in a neutropenic murine model of trichosporonosis. Infect Immun 1997;65:3422–3429. 52. Sasaki E, Tashiro T, Kuroki M, et al. Effects of macrophage colony-stimulating factor (M-CSF) on anti-fungal activity of mononuclear phagocytes against Trichosporon asahii. Clin Exp Immunol 2000;119:293–298. 53. Roilides E, Gil Lamaignere C, Farmaki E. Cytokines in immunodeficient patients with invasive fungal infections: an emerging therapy. Int Journal Infect Dis 2002;6:154–163. medicina universitaria www.elsevier.com.mx Standards for authors Manuscripts should be written in line with the recommendations of the International Committee of Medical Magazines Publishers (N Engl J Med 1997;336:309-15) and articles should adhere to the following rules: 1. The text should be delivered in printed letter size sheets (21 × 27 cm [8.5 × 11 inches]). 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