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A 56 year old man with a history of roux-en-y gastric bypass presented with abdominal pain,
nausea, and bilious emesis. What is the diagnosis?
Anastomotic stricture
Incisional hernia
Intussusception
Dumping syndrome
Internal hernia
The correct answer is internal hernia. This patient presented with symptoms and radiologic findings
consistent with a small bowel obstruction. CT scan revealed swirling of the bowel and mesenteric
vessels as they herniated through the jejunojejunostomy mesenteric defect; exploratory
laparoscopy showed an internal hernia of the small bowel. Small-bowel obstructions associated
with internal hernias after gastric bypass can progress to bowel necrosis and death, and require
early surgical intervention.
Der Roux-en-Y-Magenbypass (RYGB) ist die
international am häufigsten durchgeführte
chirurgische Operationstechnik im Rahmen der
Adipositaschirurgie. Bei extrem adipösen
Personen kann mit ihrer Hilfe eine
Gewichtsreduktion erzielt werden, weil sie den
natürlichen Weg der Nahrung durch den MagenDarm-Trakt verändert und so zu einer gewollten
Malabsorption führt und gleichzeitig bewirkt,
dass die Patienten geringere Mengen an fester
und flüssiger Nahrung aufnehmen. Der Eingriff
gilt als das letzte Mittel der Wahl, wenn
konservative Methoden zur Gewichtsreduktion
versagt haben. Die operierten Patienten können
bereits nach wenigen Tagen beginnen, wieder
feste Nahrung zu sich zu nehmen. Relativ
gefürchtet beim R/Y-Magenbypass ist das
sogenannte Dumping-Syndrom, die sogenannte
Sturzentleerung flüssiger und fester Nahrung
vom Magen in den Dünndarm mit ihren Folgen.
Anastomosenstriktor könnte an zwei Stellen
stattfinden.
An incisional hernia is a type of hernia caused
by an incompletely-healed surgical wound. Since
median incisions in the abdomen are frequent
for abdominal exploratory surgery, ventral
incisional hernias are often also classified as
ventral hernias due to their location. Not all
Ventral Hernias are from incisions, as some may
be caused by other trauma or congenital
problems. Clinically, incisional hernias present
as a bulge or protrusion at or near the area of a
surgical incision. Virtually any prior abdominal
operation can develop an incisional hernia at the
scar area (provided adequate healing does not
occur due to infection), including large
abdominal procedures such as intestinal or
vascular surgery, and small incisions, such as
(appendix removal or abdominal exploratory
surgery).
Als Intussuszeption (Synonym: Invagination) des
Darmes wird die in Längsachse erfolgende Einstülpung
eines Darmabschnittes in einen anderen bezeichnet.
Hierbei kommt es durch Störungen in der
Blutversorgung der Darmwand infolge von Blutstauung
und Ödemen zur Ausbildung der Symptomatik eines
Darmverschlusses.
Der eingestülpte Darmteil wird als Invaginat (oder
Intussusceptum) bezeichnet. Die Darmeinstülpung
verläuft meist in die aborale Richtung in das Invaginans
(oder auch Intussuscipiens), der Darm stülpt sich also
in der Richtung seiner Peristaltikwellen ein. Relativ
selten liegt eine Invagination nach oral vor (retrograde
Invagination), was hauptsächlich als Komplikation nach
einer Magenresektion beschrieben wird. Hauptsächlich
werden Säuglinge und Kleinkinder (Verhältnis
Jungen:Mädchen 3:1) bis zum zweiten Lebensjahr von
der Erkrankung betroffen; hier liegt als Ursache meist
eine (vorübergehende) Störung der Darmmotorik vor.
Der invaginierte Wurmfortsatz ist die zweithäufigste
Ursache des akuten Abdomens im Säuglings- und
Kleinkindesalter.
Tritt die Invagination in einem höheren Lebensalter auf,
kann häufig eine morphologische Ursache (MeckelDivertikel, Polyp, Tumor, Darmduplikatur) für ihre
Entstehung gefunden werden.
Eine Hernie (von griech. ἔρνος érnos „Knospe, Spross“) ist der Austritt von Eingeweiden aus der
Bauchhöhle durch eine angeborene oder erworbene Lücke in den tragenden Bauchwandschichten.
Ihr deutscher Name Bruch oder Eingeweidebruch verwendet die Nebenbedeutung von Bruch als
Riss.
Es werden nach dem Ort ihres Auftretens innere und äußere Hernien unterschieden. Ist die Hernie
von außen zu erkennen oder führt die Bruchpforte vom Körperinneren in Richtung Haut, spricht
man von einer äußeren Hernie. Liegt die Hernie innerhalb des Rumpfes (z. B. vom Bauch in den
Brustkorb gerichtet) und kann deshalb nicht ohne Hilfsmittel erkannt werden, dann ist es eine
innere Hernie. Bei der Treitz-Hernie sind Darmanteile im Recessus duodenalis superior, einer sehr
engen Bauchfelltasche hinter dem sogenannten Treitz'schen Band (Ligamentum suspensorium
duodeni), welches den Zwölffingerdarm fixiert und Darmgefäße enthält, eingeklemmt.
It’s a complicated neurological
disease, with head pain and other
symptoms, like nausea, vomiting,
dizziness, sensitivity to touch,
sound, light, and odors. Abdominal
pain and mood changes can occur,
too. While kids generally have fewer
and shorter migraine attacks than
adult sufferers, childhood migraine
can be just as disabling, and it can
seriously affect the child’s quality of
life. Unfortunately, migraine is very
common in children. It’s been
reported in kids as young as 18
months old. About 10% of schoolage children suffer from migraine.
Half of all migraine sufferers have
their first attack before the age of
12. Before puberty, boys suffer from
migraine more often than girls. As
adolescence approaches, the
incidence increases more rapidly in
girls than in boys. By the time they
turn 17, as many as 8% of boys and
23% of girls have experienced a
migraine.
Trial of Amitriptyline, Topiramate, and Placebo for Pediatric Migraine
Which, medication, if any, to use to prevent the headache of pediatric migraine has not been
established. We conducted a randomized, double-blind, placebo-controlled trial of amitriptyline (1
mg per kilogram of body weight per day), topiramate (2 mg per kilogram per day), and placebo in
children and adolescents 8 to 17 years of age with migraine. Patients were randomly assigned in a
2:2:1 ratio to receive one of the medications or placebo. The primary outcome was a relative
reduction of 50% or more in the number of headache days in the comparison of the 28-day
baseline period with the last 28 days of a 24-week trial. Secondary outcomes were headacherelated disability, headache days, number of trial completers, and serious adverse events that
emerged during treatment.
The first three PedMIDAS questions relate
to the impact of headache on school
performance. Caution needs to be taken to
minimize duplication of days (i.e., don’t
count a half day missed both as a full day
missed and a half day missed)
Patients with a Relative Reduction of 50% or More in the Number of Headache Days.
Shown is the percentage of patients with a relative reduction of 50% or more in the number of headache days in the
comparison of the 4-week baseline period with the last 4 weeks of a 24-week trial (primary end point). Results are shown for
the primary analysis and two a priori sensitivity analyses to assess the effect of missing data. Sample sizes for the trial
groups represent the primary analysis population. For observed data, the population is the subgroup with observed data at
week 24.
At this point, reaching for the prescription pad may not be the best answer for pediatricians caring for
patients with migraine headache. Whatever clinicians use, they can expect improvement on the basis of
the powerful placebo effect and by selecting the most benign option that is acceptable to children and their
parents.
Neuroendokrine Tumoren (NET) sind gut- oder
bösartige Tumoren, die ihren Ursprung aus dem
Neuroektoderm (Neuralleiste) nehmen und deren
Zellen in der immunhistochemischen Charakterisierung
den endokrinen Drüsenzellen gleichen. Epitheliale
neuroendokrine Tumoren kommen vor allem im MagenDarm-Trakt und in der Bauchspeicheldrüse vor. Für
neuroendokrine Tumoren im Magen und Darm ist auch
die alte Bezeichnung Karzinoid (karzinomähnlicher
Tumor) noch sehr verbreitet. Dieser sollte wie auch der
Begriff APUDom (amine precursor uptake and
decarboxylation) nicht mehr verwendet werden. Das
kleinzellige Bronchialkarzinom wie auch das MerkelzellKarzinom der Haut zählen ebenfalls zu den
neuroendokrinen Tumoren. Eng verwandt sind die
nervenähnlichen Neuroblastome, Phäochromozytome,
und Paragangliome. 75 % aller neuroendokrinen
Tumoren sind im gastroenteropankreatischen System
lokalisiert (Gastroenteropankreatischer
Neuroendokriner Tumor – Abk. GEP-NET). Die GEPTumoren entwickeln sich aus endokrinen
(hormonproduzierenden) Zellen, die überall im
Verdauungssystem oder damit zusammenhängenden
Stellen des Körpers vorkommen und die Aufgabe
haben, bestimmte Stoffe zu produzieren, die den
Verdauungsprozess steuern. Von ihren Eigenschaften
her besitzen diese Zellen Ähnlichkeiten mit
Nervenzellen und von ihrer Funktion her zählen sie zu
den inneren Drüsen. Daher werden sie neuroendokrine
Zellen genannt.
DOTA-TATE, DOTATATE or DOTA-octreotate is
a substance which, when bound to various
radionuclides, has been tested for the treatment
and diagnosis of certain types of cancer, mainly
neuroendocrine tumours. DOTA-TATE is an
amide of the acid DOTA (top left in the image),
which acts as a chelator for a radionuclide, and
(Tyr3)-octreotate, a derivative of octreotide. The
latter binds to somatostatin receptors, which are
found on the cell surfaces of a number of
neuroendocrine tumours, and thus directs the
radioactivity into the tumour. Lutetium (177Lu)
DOTA-TATE has been tested for the treatment of
tumors such as carcinoid and endocrine
pancreatic tumor.
Patients are typically treated with an intravenous
infusion of 7.5 GBq of lutetium-177 octreotate.
After about four to six hours, the exposure rate
of the patient has fallen to less than 25
microsieverts per hour at one metre and the
patients can be discharged from hospital.
A course of therapy consists of four infusions at
three monthly intervals. Lutetium-176, decays
via beta decay with a half-life of 3.78×1010
years.
A total of 852 adverse events were reported (301 with amitriptyline, 419 with topiramate, and 132 with placebo),
in 272 patients
During the trial, the FDA approved topiramate for the treatment of episodic migraine in
adolescents 12 to 17 years of age. Although our trial included patients outside this age range
and included those with either episodic or chronic migraine, the trial results suggest that
prevention medication for pediatric migraine might be reexamined.
Phase 3 Trial of 177Lu-Dotatate for Midgut Neuroendocrine Tumors
Patients with advanced midgut neuroendocrine
tumors who have had disease progression during
first-line somatostatin analogue therapy have
limited therapeutic options. This randomized,
controlled trial evaluated the efficacy and safety of
lutetium-177 (177Lu)–Dotatate in patients with
advanced, progressive, somatostatin-receptor–
positive midgut neuroendocrine tumors. We
randomly assigned 229 patients who had welldifferentiated, metastatic midgut neuroendocrine
tumors to receive either 177Lu-Dotatate (116
patients) at a dose of 7.4 GBq every 8 weeks (four
intravenous infusions, plus best supportive care
including octreotide long-acting repeatable [LAR]
administered intramuscularly at a dose of 30 mg)
(177Lu-Dotatate group) or octreotide LAR alone
(113 patients) administered intramuscularly at a
dose of 60 mg every 4 weeks (control group). The
primary end point was progression-free survival.
Secondary end points included the objective
response rate, overall survival, safety, and the
side-effect profile. The final analysis of overall
survival will be conducted in the future as
specified in the protocol; a prespecified interim
analysis of overall survival was conducted and is
reported here.
In this randomized, phase 3 trial involving patients with progressive midgut neuroendocrine
tumors, treatment with 177Lu-Dotatate resulted in a risk of progression or death that was 79%
lower than the risk associated with high-dose octreotide LAR. The estimated rate of progressionfree survival at month 20 was 65.2% (95% CI, 50.0 to 76.8) in the 177Lu-Dotatate group and
10.8% (95% CI, 3.5 to 23.0) in the control group. The median progression-free survival was 8.4
months in the control group and had not yet been reached in the 177Lu-Dotatate group. A
subgroup analysis showed consistent benefit across major subgroups.
Tranexamsäure ist eine Substanz, die in der
Medizin zur Hemmung des Fibrinolysesystems
verwendet wird. Der Wirkungsmechanismus
beruht dabei auf einer Komplexbildung mit
Plasminogen, wodurch dessen Bindung an die
Fibrinoberfläche gehemmt wird. Damit resultiert
letztendlich eine Hemmung der
Gerinnselauflösung (Fibrinolyse). Es wird daher
als Antifibrinolytikum (Fibrinolysehemmer)
bezeichnet. Tranexamsäure ist ein synthetischer
Stoff, der dem Lysin ähnelt. Er zählt wie εAminocapronsäure und pAminomethylbenzoesäure zur Gruppe der
sogenannten ε-Aminocarbonsäuren.
Tranexamsäure blockiert die Bildung von
Plasmin durch Hemmung der proteolytischen
Aktivität der Plasminogenaktivatoren. Dadurch
wird Plasmin in seiner Fähigkeit Fibrin zu
lysieren behindert. Bei niedriger Dosis wirkt
Tranexamsäure als kompetitiver Hemmer des
Plasmins, bei hoher Dosierung als nichtkompetitiver Hemmer. Alle ε-Aminocarbonsäuren
wirken analog. Tranexamsäure ist nach
peroraler Gabe zu 30–50 % bioverfügbar. Das
Verteilungsvolumen beträgt 9–12 L. Die
Halbwertszeit ist 2 Stunden.
Tranexamic Acid in Patients Undergoing Coronary-Artery Surgery
Tranexamic acid reduces the risk of
bleeding among patients undergoing
cardiac surgery, but it is unclear
whether this leads to improved
outcomes. Furthermore, there are
concerns that tranexamic acid may
have prothrombotic and
proconvulsant effects. In a trial with a
2-by-2 factorial design, we randomly
assigned patients who were
scheduled to undergo coronaryartery surgery and were at risk for
perioperative complications to
receive aspirin or placebo and
tranexamic acid or placebo. The
results of the tranexamic acid
comparison are reported here. The
primary outcome was a composite of
death and thrombotic complications
(nonfatal myocardial infarction,
stroke, pulmonary embolism, renal
failure, or bowel infarction) within 30
days after surgery.
In this trial, we found no evidence that
the use of tranexamic acid resulted in a
higher risk of death or thrombotic
complications than that with placebo
among patients undergoing coronaryartery surgery. We also found that the
tranexamic acid group had a lower risk of
blood loss, blood transfusion, and
reoperation but a higher risk of
postoperative seizures than did the
placebo group. Subgroup analyses of the
primary outcome showed no significant
interactions. The results were consistent
among patients who were being treated
with aspirin and those who were not.
Patients in the tranexamic acid group
received 46% fewer units of blood
products than did those in the placebo
group. In a cardiac surgical practice
similar to the practices in which our trial
population was treated, the use of
tranexamic acid would save
approximately 57 units of blood products
for every 100 patients treated. The
observed blood-sparing effects are
consistent with those reported in metaanalyses.
Screening for Colorectal Neoplasia
A 79-year-old woman visits your office for routine health maintenance. She has normal daily bowel
movements without rectal bleeding. Her medical history is notable for osteoarthritis but no other
medical conditions. She takes nonsteroidal antiinflammatory medication and multivitamins. Her
maternal uncle received a diagnosis of colorectal cancer at 65 years of age, but she has never
undergone screening for colorectal cancer. Would you advise this patient to undergo screening for
colorectal cancer, and if so, which screening strategy would you recommend?
The percentage of U.S. residents with up-to-date screening for colorectal cancer has not increased
appreciably since 2010 and remains at approximately 60%. Costs remain a barrier despite the
mandate in the Affordable Care Act that health plans cover colorectal cancer screening with no
patient cost-sharing, because Medicare and other insurers impose a cost-sharing requirement
when a colonoscopy is performed to evaluate a positive screening test or when a screening
colonoscopy becomes a therapeutic procedure with the inclusion of polypectomy. Those with
increased risk (below).
Because it is not feasible to summarize the entire menu of options during the span of a routine
health maintenance visit, I would initially focus the discussion on colonoscopy or on annual FIT,
followed by colonoscopy if the test was positive, and engage the patient in shared decision
making. If she declined colonoscopy and FIT, I would discuss additional screening options, with
the understanding that insurance coverage, cost-sharing, and other barriers may affect the
feasibility of some options.
A 37-year-old man presented to the emergency department with a 7-day history of genital
lesions. He also had weight loss (approximately 4 kg), fatigue, and back pain but no
gastrointestinal symptoms. Two months before presentation, he had had dysuria and urethral
discharge, both of which resolved spontaneously. He took no medications on a regular basis,
and his medical history was unremarkable. Physical examination revealed erythematous, welldemarcated annular plaques on the glans penis and meatal inflammation (Panels A and B). He
also had conjunctival injection in both eyes. The patient had a positive test result for infection
with the human immunodeficiency virus (HIV), with a viral load of 15,000 copies per milliliter. His
CD4 T-cell count was 172 per microliter. A test for rheumatoid factor was negative, and a test for
HLA-B27 was positive. A serum sample was obtained to evaluate the patient for infection with
hepatitis B virus, hepatitis C virus, and syphilis; the test results were negative. Infection with
Chlamydia trachomatis was detected on nucleic acid amplification testing with a sample from a
urethral swab. A single oral dose of 1 g of azithromycin was administered, and antiretroviral
therapy was started. During the next month, the circinate balanitis persisted. Topical tacrolimus
0.1% was administered, and the patient had complete remission within the next 10 days.
A 70-Year-Old Woman with Gradually Progressive Loss of Language
The patient had reportedly been well until
approximately 8 years before this evaluation,
when gradually progressive difficulties with word
finding developed, along with associated
confusion about the meaning of some words.
For example, during a conversation about a
recent family event, she did not understand what
the phrase “punch bowl” meant. She also had
increased egocentric behavior, during which she
spoke most frequently about herself. She had a
good memory for recent events of her life and
could recount multiple stories (at times to an
excessive extent during history taking, such that
she required refocusing). She had an excellent
sense of direction. She had an
uncharacteristically matter-of-fact reaction to the
death of a sibling and of her dog (being less
upset than her family expected). She
occasionally had mildly inappropriate behavior,
such as saying “I love you” to people to whom
she was not particularly close. She had a score
on the Mini–Mental State Examination of 28
(with scores ranging from 0 to 30 and higher
scores indicating better cognitive function),
because she was unable to recall the name of
the hospital or the county.
MRI of the Head.
A high-resolution coronal T1-weighted image obtained at the
level of the temporal lobes shows generalized loss of
parenchymal tissue (arrow) and superimposed severe,
asymmetric atrophy (arrowhead) of left temporal lobes, including
cortical thinning of the temporal gyri and severe shrinkage of the
left hippocampal formation, with resultant expansion of the left
temporal horn and sulci.
Speech pathological evaluation revealed that the patient had fluent, articulate speech with
pauses for word finding, vague word substitutions, and circumlocutions. She was somewhat
tangential in her speech and was fixated on telling stories from her life, such that she required
frequent refocusing on the topic at hand. She had substantial impairment on a test of naming,
with superordinate responses, and she had impairment on word–picture matching. Rare
phonemic paraphasias were present. Auditory comprehension was impaired for words she no
longer recognized and for sentences with complex syntax. Sentence repetition was intact. A
written language assessment revealed that she could read normally and had mild agrammatism
in written language samples. A semantic picture–picture matching test revealed no evidence of
visual agnosia.
18F-Fluorodeoxyglucose–Positron-Emission Tomographic (FDG-PET) Scans.
Four months after the initial evaluation, FDG-PET scans show hypometabolism of the bilateral frontal lobes asymmetrically and of
the bilateral temporal lobes that is greater on the left side than on the right side. Panel A shows cortical surface projections of the
FDG distribution. Panel B shows cortical surface projections of a statistical analysis derived from comparison of the patient’s scans
with a sample of normal scans; the distribution of the patient’s abnormal metabolism in the frontal and temporal lobes is shown in
dark blue, and normal variation in visual activation is shown in red and white. The color scale represents standard deviations from
the normal scans. The letters surrounding each projection indicate the orientation of the image: A denotes anterior, I inferior, L left,
P posterior, R right, and S superior.
In patients with primary progressive aphasia, the underlying pathologic process is usually caused
by frontotemporal lobar degeneration or Alzheimer’s disease. Approximately 60% of cases of
primary progressive aphasia are associated with frontotemporal lobar degeneration, and 40% are
associated with Alzheimer’s disease. PET with amyloid-binding compounds (amyloid PET) would
be useful in this patient to determine whether her primary progressive aphasia is likely to be
caused by Alzheimer’s disease. A positive result on amyloid PET increases the likelihood of
Alzheimer’s disease, whereas a negative result definitively rules out Alzheimer’s disease and
makes frontotemporal lobar degeneration the most likely cause. Therefore, the next step in this
patient’s evaluation should be to perform amyloid PET.
PET Scans for Amyloid.
Amyloid PET scans, obtained with the administration of 11C-labeled Pittsburgh compound B, in accordance with a research protocol,
show uptake in the medial and lateral prefrontal and temporoparietal cortexes. The color scale represents the distribution volume
ratio of 11C-labeled Pittsburgh compound B. All images are displayed in radiographic orientation (i.e., the right side of the image is
the patient’s left side).
There is a strong correlation between the
semantic variant of primary progressive aphasia
and a type of frontotemporal lobar degeneration
that is linked to the presence of abnormal
deposits of TAR DNA-binding protein 43
(TDP-43), an RNA-binding protein with a wide
range of targets. TDP-associated frontotemporal
lobar degeneration has several subtypes,
defined according to the pattern of inclusions,
and the semantic variant of primary progressive
aphasia is associated with type C in 80% of
cases. Therefore, despite the positive result on
amyloid PET, I think that this patient’s primary
progressive aphasia is caused by TDPassociated frontotemporal lobar degeneration,
type C, rather than Alzheimer’s disease.
Ultimately, she “forgot” how to walk. When the
patient was 77 years of age, she had decreased
interest in food and increased difficulty with
swallowing, and hospice services were engaged.
She was enrolled in a Namaste Care program
(i.e., a program for persons with advanced-stage
dementia), which provided her with calming,
supportive end-of-life care, and she passed
away peacefully 1 day before her 78th birthday.
A photograph of the ventral surface of the brain shows
atrophy of the temporal lobes that is greater on the left side
than on the right side (Panel A). Photographs of coronal
slabs obtained at the levels of the anterior and body of the
hippocampus (Panels B and C, respectively) show severe
atrophy of the inferior and medial temporal lobe and lesser
degrees of atrophy of the insula, cingulate, and anterior
frontal lobes. Immunohistochemical staining for TAR DNAbinding protein 43 (TDP-43) shows multiple long, dystrophic
neurites (Panel D, arrow); a single long, dystrophic
TDP-43–positive neurite (Panel E); and neuronal loss from
area CA1 of the hippocampal formation (hippocampal
sclerosis) (Panel F).
. Two Types of Transfer to Reduce the Risk of Mitochondrial DNA Disease. Pronuclear transfer involves the removal of the male
and female pronuclei, which form after fertilization and contain the haploid paternal and maternal genomes, respectively. The
pronuclei from the carrier zygote (fertilized egg) are fused with the enucleated donor zygote. In the case of spindle transfer, the
nuclear envelope is absent, but the chromosomes are typically aligned on the meiosis II spindle. Spindles are removed from both
oocytes, and the carrier's spindle is fused with the enucleated donor oocyte, which is then fertilized. The end product for both
procedures is a reconstructed zygote consisting of nuclear DNA from the carrier and her partner and cytoplasm — and hence
mitochondrial DNA (mtDNA) — from the donor oocyte. However, in both cases, nuclear DNA is removed in a karyoplast consisting
of a small amount of cytoplasm, which will contain some mtDNA carryover from the carrier's oocyte or zygote. For research
purposes, embryos can be cultured, and embryonic stem cells can be derived from the embryos that develop to the blastocyst
stage.
Das Sturge-Weber-Syndrom, auch unter den
Synonymen Sturge-Weber-Krabbe-Syndrom,
meningofaciale Angiomatose, encephalotrigeminale
Angiomatose oder Angiomatosis encephalofacialis
bekannt, ist eine angeborene fortschreitende
Erkrankung aus der Gruppe der neurokutanen
Phakomatosen. Es ist gekennzeichnet durch
hohlräumige gutartige Gefäßtumoren (Angiome) im
Gesichtsbereich, im Bereich der Meningen, im Bereich
der ipsilateralen weichen Hirnhaut (Leptomeninx) und
der Aderhaut des Auges (Choroidea); häufig mit
nachfolgender Augensymptomatik. Äußerlich erkennbar
sind die Gefäßfehlbildungen in der Regel an einer
kapillären vaskulären Malformation in Form eines meist
einseitigen rötlich bis portweinfarbenen Naevus
flammeus (Feuermal) im Gesicht betroffener Kinder,
dieses umfasst immer das Augenlid. Lange Zeit wurde
eine somatische Mutation als Ursache vermutet, was
schließlich in einer DNA-Sequenzierungs-Studie
bestätigt werden konnte. Bei 23 von 26 amerikanischen
Patienten (88 %) zeigte sich in den untersuchten
Biopsien eine somatische Mosaik-Mutation mit
Austausch eines Basenpaares (EinzelnukleotidPolymorphismus: c.548G→A, p.Arg183Gln auf
Chromosom 9q21) im Gen GNAQ, das das Protein Gαq
codiert, ein Protein der q-Klasse der G-Protein-αUntereinheiten, das zur intrazellulären
Signalweiterleitung von G-Protein-gekoppelten
Rezeptoren auf weitere Effektorproteine dient.
Should recommendations about starting inhaled corticosteroid treatment for
mild asthma be based on symptom frequency: a post-hoc efficacy analysis of
the START study
Low-dose inhaled corticosteroids (ICS) are highly effective for reducing asthma exacerbations and
mortality. Conventionally, ICS treatment is recommended for patients with symptoms on more than
2 days per week, but this criterion has scant evidence. We aimed to assess the validity of the
previous symptom-based cutoff for starting ICS by establishing whether there was a differential
response to budesonide versus placebo for severe asthma exacerbations, lung function, and
asthma symptom control across subgroups identified by baseline asthma symptom frequency. We
did a post-hoc analysis of the 3 year inhaled Steroid Treatment As Regular Therapy (START) study.
Interaction with baseline symptom frequency was investigated, with patients grouped by more than
two symptom days per week and two or fewer symptom days per week (divided into no days to 1
day, and more than 1 day to 2 days). Analysis was done by intention to treat.
This post-hoc analysis of the START study showed that, in patients with mild, recently diagnosed
asthma, low-dose budesonide halved the long-term risk of serious asthma-related events,
reduced the decline in lung function, and improved day-to-day symptom control compared with
placebo, even in participants with infrequent baseline symptoms. These findings challenge longstanding recommendations that asthma should be treated with SABA alone if the patient has
symptoms on 2 or fewer days per week at presentation. The extent of benefit with low-dose ICS
suggests that guidelines about treatment of mild asthma should take into account the potential to
reduce the population-level risk of serious asthma-related events, even if day to day symptoms
are not burdensome.
A cleaner burning biomass-fuelled cookstove intervention to prevent pneumonia
in children under 5 years old in rural Malawi (the Cooking and Pneumonia
Study)
WHO estimates exposure to air
pollution from cooking with solid
fuels is associated with over 4
million premature deaths
worldwide every year including half
a million children under the age of
5 years from pneumonia. We
hypothesised that replacing open
fires with cleaner burning biomassfuelled cookstoves would reduce
pneumonia incidence in young
children. We did a community-level
open cluster randomised controlled
trial to compare the effects of a
cleaner burning biomass-fuelled
cookstove intervention to
continuation of open fire cooking
on pneumonia in children.
We did a cluster randomised controlled trial with two groups of equal size comparing the
effects of a cleaner burning biomass-fuelled cookstove intervention with continued use of
open fire cooking on pneumonia incidence in children under 5 years of age living in rural
Malawi over a 2 year period (the Cooking and Pneumonia Study, CAPS).
Advanced-combustion cook stoves
Incidence rate and incidence rate ratio of severe pneumonia defined according to IMCI criteria, oxygen saturation less than 90%, or
death. IMCI=WHO Integrated Management of Childhood Illness.
In conclusion, we found no evidence of a
reduction in pneumonia in young Malawian
children in a rigorously conducted clinical trial of
a cleaner burning biomass-fuelled cookstove
intervention. The lack of effect on pneumonia
might be explained by exposure to other sources
of air pollution, including rubbish burning and
tobacco smoke, that could have overwhelmed
any potential effects of the cookstoves. It is also
possible that the cookstoves used simply did not
reduce emissions sufficiently to have an effect.
The Healthy Activity Program (HAP), a lay counsellor-delivered brief psychological treatment for
severe depression, in primary care in India:
Although structured psychological treatments
are recommended as first-line interventions for
depression, only a small fraction of people
globally receive these treatments because of
poor access in routine primary care. We
assessed the effectiveness and costeffectiveness of a brief psychological treatment
(Healthy Activity Program [HAP]) for delivery by
lay counsellors to patients with moderately
severe to severe depression in primary healthcare settings. In this randomised controlled trial,
we recruited participants aged 18–65 years
scoring more than 14 on the Patient Health
Questionnaire 9 (PHQ-9) indicating moderately
severe to severe depression from ten primary
health centres in Goa, India. Primary outcomes
were depression symptom severity on the Beck
Depression Inventory version II and remission
from depression (PHQ-9 score of <10) at 3
months in the intention-to-treat population,
assessed by masked field researchers.
Data are mean (SD), n (%), or median (IQR). EUC=Enhanced
usual care. PHQ-9=Patient Health Questionnaire 9.
*Includes students and people not working outside of the home.
An international expert in behavioural activation
(SD) trained and provided ongoing supervision
for five local specialists, who in turn provided
onsite training and supervision for lay
counsellors. Training of lay counsellors involved
a 3 week participatory workshop covering both
HAP and CAP treatments, followed by an
internship phase of 6 months, in which trainee
counsellors delivered the treatment to eligible
patients in primary health-care clinics, combined
with peer-led group supervision as the trainees
gained experience in delivery of the treatment.
11 counsellors who met competency standards
as assessed by standardised roleplays and
therapy quality measures participated in the trial.
They received weekly peer-led supervision in
groups of four to six that involved rating of a
randomly selected (using a random selection
strategy stratified by counsellor and phase of
session) 10% of recorded sessions on the HAP
Therapy Quality Scale (TQS)26 and individual
supervision twice monthly. HAP delivery costs
included patient contact and counsellor training,
supervision, and salary.
Cost-effectiveness acceptability curve:
willingness to pay per quality-adjusted lifeyear gained from the Healthy Activity
Program from a health system perspective
Effect of baseline PHQ-9 score on depression severity according to BDI-II score at 3 months
BDI=Beck Depression Inventory. EUC=enhanced usual care. HAP=Healthy Activity Program. PHQ=Patient Health
Questionnaire.
HAP as delivered by non-specialist health workers in routine primary care settings is effective
in treatment of moderately severe and severe depression. HAP produced a moderate effect
on depressive symptoms, an almost two-thirds increase in remission, and small effects on
secondary outcomes related to functional impairment after only six to eight sessions of
treatment.
Counselling for Alcohol Problems (CAP), a lay counsellor-delivered brief
psychological treatment for harmful drinking in men, in primary care in India: a
randomised controlled trial
Although structured psychological treatments
are recommended as first-line interventions for
harmful drinking, only a small fraction of people
globally receive these treatments because of
poor access in routine primary care. We
assessed the effectiveness and costeffectiveness of Counselling for Alcohol
Problems (CAP), a brief psychological treatment
delivered by lay counsellors to patients with
harmful drinking attending routine primary
health-care settings. In this randomised
controlled trial, we recruited male harmful
drinkers defined by an Alcohol Use Disorders
Identification Test (AUDIT) score of 12–19 who
were aged 18–65 years from ten primary health
centres in Goa, India. Primary outcomes were
remission (AUDIT score of <8) and mean daily
alcohol consumed in the past 14 days, at 3
months. Secondary outcomes were the effect of
drinking, disability score, days unable to work,
suicide attempts, intimate partner violence, and
resource use and costs of illness.
Ethanol consumption at 3 months by baseline AUDIT score
AUDIT=Alcohol Use Disorders Identification Test.
CAP was associated with strong effects on abstinence and
remission 3 months after enrolment, but had no effect on other
alcohol-related outcomes. The economic analysis indicates that
CAP is likely to be cost-effective with regard to remission and nondrinking outcomes.
Acute myocardial infarction
Acute myocardial infarction has traditionally been divided into ST elevation or non-ST elevation
myocardial infarction; however, therapies are similar between the two, and the overall
management of acute myocardial infarction can be reviewed for simplicity. Acute myocardial
infarction remains a leading cause of morbidity and mortality worldwide, despite substantial
improvements in prognosis over the past decade. The progress is a result of several major trends,
including improvements in risk stratification, more widespread use of an invasive strategy,
implementation of care delivery systems prioritising immediate revascularisation through
percutaneous coronary intervention (or fibrinolysis), advances in antiplatelet agents and
anticoagulants, and greater use of secondary prevention strategies such as statins. This seminar
discusses the important topics of the pathophysiology, epidemiological trends, and modern
management of acute myocardial infarction, focusing on the recent advances in reperfusion
strategies and pharmacological treatment approaches.
Comparison of anticoagulants used to treat acute coronary syndrome
Patients taking the novel anticoagulants (direct thrombin inhibitor dabigatran, FXa inhibitors rivaroxaban and apixaban) are often
encountered; there are no guidelines to direct anticoagulation for acute coronary syndrome or during PCI in these patients.
AT=antithrombin III. FXa=factor Xa. aPTT=activated partial thromboplastin time. PCI=percutaneous coronary intervention.
STEMI=ST elevation myocardial infarction. NSTEMI=non-STEMI. CrCl=creatinine clearance. CKD=chronic kidney disease.
*Given increased risk of catheter thrombosis, if fondaparinux is used, a second anticoagulant is recommended during PCI.
Complications of acute myocardial infarction
Common complications following acute myocardial infarction and their approximate timing.
Approximately 50% of bradyarrhythmias are Mobitz I, 50% are Mobitz II or third degree atrioventricular
block. Posterior papillary muscle rupture is the most common mechanical complication of acute
myocardial infarction, most often because of infarction of the right communicating artery (which is
dominant in 85% of patients). Not listed above, atrial fibrillation could be seen any time after acute
myocardial infarction, most often in patients with left atrial enlargement. LSB=left sternal border. LV=left
ventricle. MR=mitral regurgitation. PCI=percutaneous coronary intervention. STEMI=ST segment
elevation myocardial infarction.
Viral bronchiolitis
Viral bronchiolitis is a common clinical syndrome
affecting infants and young children. Concern
about its associated morbidity and cost has led
to a large body of research that has been
summarised in systematic reviews and
integrated into clinical practice guidelines in
several countries. The evidence and guideline
recommendations consistently support a clinical
diagnosis with the limited role for diagnostic
testing for children presenting with the typical
clinical syndrome of viral upper respiratory
infection progressing to the lower respiratory
tract. Management is largely supportive,
focusing on maintaining oxygenation and
hydration of the patient. Evidence suggests no
benefit from bronchodilator or corticosteroid use
in infants with a first episode of bronchiolitis.
Evidence for other treatments such as
hypertonic saline is evolving but not clearly
defined yet. For infants with severe disease, the
insufficient available data suggest a role for
high-flow nasal cannula and continuous positive
airway pressure use in a monitored setting to
prevent respiratory failure.
Meta-analysis of studies assessing average clinical score after treatment in patients with bronchiolitis receiving bronchodilators
versus placebo
Test for heterogeneity in the inpatient studies demonstrated low inconsistency between the nine studies (I2=36%; p=0·13) and the
summary effect was not significant (Z=1·06; p=0·29), the outpatient studies demonstrated very high inconsistency between the 12
studies (I2=81%; p<0·00001) and the summary effect was significant (Z=2·26; p=0·024), and the overall heterogeneity of the metaanalysis demonstrated high inconsistency between the 21 studies (I2=73%; p<0·00001) and the overall summary effect was
significant (Z=2·4; p=0·016). IPR=ipratropium. SAL=salbutamol. neb=nebulised.
Intravenous urogram showing laterally displaced distal ureters (green arrows), backflow of
contrast from the renal calyces (white arrows), displacement and compression of the left
kidney inferiorly (blue arrow), coarsening of bone trabeculations throughout the pelvic girdle
and spine, and gallstones (red arrow).
A 28-year-old woman of Jewish descent with a history of sickle β-thalassaemia disorder and
uterine fibroids presented to the emergency department with a 2-week history of frank haematuria.
She had been taking paracetamol daily for persistent headaches. On examination she was pale
and tachycardic and had a palpable spleen. Full blood count showed haemoglobin 60 g/L.
Creatinine was 97 µmol/L. Intravenous urogram showed pyelotubular reflux, splenomegaly,
gallstones, uterine fibroids, and coarsening of the pelvic bones and spine. We believe that the
analgesic acted synergistically with the existing hypoxia of the renal medulla caused by her
chronic anaemia state leading to medullary ischaemia and renal papillary necrosis, causing gross
haematuria and the pyelotubular reflux evident on radiography. The coarse appearance of bone
seen on the plain film is due to bone marrow expansion, and the mass effect on the left kidney
caused by her splenomegaly; the lateral displacement of the ureters is likely due to uterine
fibroids. Paracetamol was stopped and she was admitted by the nephrologists for intravenous
hydration. She received two units of packed red cells and was discharged 3 days later after
resolution of her haematuria, with haemoglobin 82 g/L.
Sickle cell-beta thalassemia is caused by inheritance of a sickle cell allele from one parent and a
beta thalassemia allele from the other.