Download Hypothermia: Incidental finding or critical illness?

Hypothermia: Incidental finding or critical illness?
Jennifer Beckman, MD
University of Utah Department of Internal Medicine
Case Presentation
This is a case of incidentally found hypothermia in a
26 year old male who was transferred from the prison
infirmary for hematemesis during the month of May.
He reports having chills for he at least the last week
with nausea and vomiting and development of
hematemesis starting within the last 24 hours.
Further questioning revealed that he had headaches,
worsening lower extremity weakness, and urinary
incontinence in the last several days. His initial
temperature was 36°C but repeat readings were
consistently around 30. His blood pressure was
124/91 with a heart rate of 60, respiratory rate of 15,
and oxygen saturation of 98% on room air. His WBC
was 6 with a normal differential. The prison infirmary
stated that the patient’s only past medical history was
possible sarcoidosis.
Hospital Course
A lumbar puncture was performed with a protein level
of 552, glucose of 8, total WBC count of 138 with 13%
PMN, 51% lymphocytes. Gram stain and culture
remained negative. MRI imaging showed findings
consistent with basilar meningitis. Reports obtained
from a previous hospitalization had imaging with hilar
lymphadenopathy and a pulmonary nodule biopsy
with positive AFB organisms suggesting that his
symptoms were from TB meningitis.
Discussion
Hypothermia due to environmental exposure is often
thought about, however, other causes include
metabolic, neurologic, and sepsis.
TB meningitis can cause hypothermia by direct
involvement of the CNS or sepsis. TB can infiltrate
the hypothalamus or causes hydrocephalus which
places pressure on the hypothalamus, which is
responsible for thermoregulation. Hypothermia due
to sepsis is caused by a failure of vasoconstriction
or by inducing an abnormality in the hypothalamic
response via a cytokine response.
Conclusion
In the case of this patient, TB infiltration of his basal
ganglia and hydrocephalous were the causes of his
hypothermia. With treatment of his meningitis his
hypothermia and presenting symptoms did improve.
Many of his presenting symptoms can be linked to
manifestations of his hypothermia. His hematemesis
was likely the punctate hemorrhages found with
hypothermia. His new on-set urinary incontinence can
be attributed to the cold-induced diuresis.
Signs and symptoms of hypothermia can manifest in
almost every organ system:
Bradycardia
and
repolarization
abnormalities are found in the
cardiovascular system.
Manifestations of the nervous system
include ataxia, hyporeflexia, and
decreased nerve conduction.
Cold-induced diuresis is caused by
the loss of the ability to reabsorb
water and resistance for ADH.
Ileus or punctate hemorrhages develop
in the GI system.
References
1. Dick DJ, et al. Chronic hypothermia following tuberculosis meningitis. Journal of
Neurology, Neurosurgery, and Psychiatry, 1981,44,255-57.
2. Joshi VV, et al. Hypothermia due to transient hypothalamic dysfunction in tuberculosis
meningitis with hydrocephalus. British Journal of Neurosurgery. 1992;6(4):385-7
3. McCullough L, et al. Diagnosis and Treatment of Hypothermia. American Family
physician. Volume 70, number 12, 2325-32. Dec 14,2004
4. Mallet ML. Pathophysiology of accidental hypothermia. QJ Med 2002: 95: 775-85
Chronic Kidney Disease in an Elderly Patient
Lucille Brunker1 C. P. Brunker1,2
History
Evaluation
General: Cheerful, energetic thin elderly woman, enjoying
visiting with family
Vital Signs: 127/62, P 60, R 20, T 96.1, Ht 66” weight 125,
BMI 20
Eyes: wears glasses, mono-ocular vision, 20/200
Pulm: normal respiratory mechanics, clear
CV: RRR Ext: 2+ bilateral pedal edema
Back: kyphosis, no vertebral tenderness to palpation
Geriatric Assessment: mini-cog unable to draw clock due
to low vision, 3/3 recall, Oriented x 3
Differential Diagnosis
-Chronic glomerulonephritis
-Vasculitis
-Multiple myeloma
-Rheumatoid Arthritis
-Wegener Granulomatosis
-Infection
-Malignancy
-Acute Injury
Conclusions
The prevalence of chronic kidney disease (CKD) is
growing most rapidly in people ages 60 and older .
22
1.3
Following practice guidelines can result in significant cost
19
1.1
Vit D 27 Ca 9.8,
savings, even in (or perhaps especially in) older adults. In
iPTH 56
accordance with recommendations, our patient was
23
1.4 37
Ca 9.8, T Chol 153
referred to nephrology where she received biopsy for
TG 105 HDL 43 LDL
96
diagnosis and was treated for Wegener’s Granulomatosis
27
1.5
Vit D 40, Hct 34.3
Prot 200 mg/dl, 19
with prednisone and cyclophosphamide. Her therapy was
leuk, 90 RBC
adjusted to monotherapy with prednisone because of an
35
1.8 28
Phos 4.3
adverse reaction to the cyclophosphamide. She had
(bisphosphonate
dramatic improvement in renal function, almost returning
discontinued)
to baseline.
3/2011
22
2.1 23
Nephrology
Progression of chronic kidney disease to end stage renal
4/2011
28
4.4 <10 Alb 2.6
disease (ESRD) changes health care costs dramatically.
6/2011
32
1.8 28
Alb 3.7
In 2009, the cost for hemodialysis treatment at a clinic per
Shared Decision
7/2012
49
1.9Making with patient → Nephrology Referral
patient was roughly $82,000, much greater expense than
Patient’s Goals:
maintain
high quality of life and function, avoid dialysis
3/13
42
1.8
the cost to evaluate and treat our patient. In accordance
2/2011 Serum Immunofixation: IgG monoclonal protein, lambda
with practice guidelines, early referral to nephrology
light chain Immunologic studies: neg except c-ANCA +
resulted in improvement of her renal function to almost
Radiology: Renal U/S kidneys normal in size and echotexture,
baseline and approximately $110,000 savings over 2
no hydronephrosis, lesions, calculus & cortex well-preserved
years and she reports excellent quality of life and
Aasarød K et al. Wegener's granulomatosis: : clinical course in 108 patients with renal
4/2011 Biopsy: CKD, “onion skinning”
maintenance
of independence in ADLs.
involvement. Nephrology Dialysis Transplantation. 2000;15(5):611-618.
Necrotizing glomerulonephritis 25/37, with crescents
Fink et al. Screening for, Monitoring, and Treatment of Chronic Kidney Disease Stages 1 to
H & E example from Stone, John H. - Rheumatology, 1547
3: A Systematic Review for the U.S. Preventive Services Task Force and for an American
DATE
90 year old woman with osteoporosis, chronic kidney disease,
hypertension with lower extremity edema, mild dyspnea &
2/2007
feeling weak for past few weeks presents to her PCP
3/2008
PCP
ROS: no weight loss, falls, depression, other resp, CV, GI all neg
PMHx: chronic back pain, hx of vertebral fxs, macular degeneration 1/2010
polymyalgia rheumatica
ADLS: independent in all IADLS: help with transportation,
1/2011
shopping, finances (decreased vision)
Referral
Meds: Calcium/Vit D 600 mg/1000 IU bid, Alendronate 70 mg/wk 2/2011
Physical
1 University of Utah School of Medicine, 2 Intermountain Healthcare, Salt Lake City, UT
BUN
Cr
GF
R
Other
UA, micro
References
College of Physicians Clinical Practice Guideline. Annals of Internal Medicine.
2012;156(8):570-81.
Improving Global Outcomes 2012 CPG. Ann Intern Med. 2013;158(11)
Hoffman et al. Wegener Granulomatosis: An Analysis of 158 Patients. Ann of Intern Med.
1992
Evaluation and Management of Chronic Kidney Disease: Synopsis of the Kidney Disease:
Improving Global Outcomes 2012 CPG. Ann Intern Med. 2013;158(11):825-830.
Kidney Disease Statistics for the United States. National Kidney and Urologic Diseases
Information Clearinghouse. U.S. Department of Health and Human Services. NIH
Publication No. 12-3895. 2012.
Matsushita K et al. Chronic Kidney Disease Prognosis Consortium. Comparison of risk
prediction using the CKD-EPI equation and the MDRD study equation for estimated
glomerular filtration rate. JAMA. 2012;307:1941-51.
Palmer SC, Craig JC, Navaneethan SD, et al. Benefits and harms of statin therapy for
A Therapeutic Vaccine for Prevention of Metastatic Outgrowth of Breast Cancer
Kimberley Davenport, Atakan Ekiz, Alana Welm, PhD
Department of Oncological Sciences, Huntsman Cancer Institute, University of Utah, Salt Lake City, Utah
A Therapeutic Vaccine for Prevention of Metastatic Outgrowth of Breast Cancer
Background Breast cancer is the second biggest cause of mortality in women with cancer – mostly as a result of metastasis. An estimated 40% of
human breast tumors over-express a tyrosine kinase called Ron. The Ron-MSP pathway functions as a critical immunosuppressive signal between a
tumor and the immune system, thereby promoting tumor growth and especially metastasis. Ron is a receptor tyrosine kinase that is expressed on
certain cell types, including some macrophages. When Macrophage Stimulating Protein (MSP) is in the tumor environment, it binds to Ron and
initiates a signal that serves to suppress the immune system as reflected by the number of CD8+ cells activated, the cytotoxicity of these effector
CD8+ cells and other immune cytokines. The exact mechanism by which the Ron-MSP pathway signals is presently unknown. A previous study from
Cancer Discovery established that in female mice with transplanted PyMT-MSP tumors, similar tumor growth was seen in wild type mice (WT)
compared with mice genetically engineered to not express Ron (Ron knock outs). However, the WT mice saw significantly greater incidence of
metastasis compared with the Ron knock out mice. This is due to the fact that if the Ron receptor is not expressed, then there is no signaling when
MSP is present in the environment. Therefore, inhibition of Ron translates to significantly lower metastasis. Our hypothesis is that inhibition of Ron
(and thereby the Ron-MSP pathway) in conjunction with a therapeutic whole cell tumor vaccine, will produce even lower rates of both primary tumor
growth and metastasis than inhibition of Ron alone.
Methods A total of 20 FVB mice were used for two cohorts. Because a target antigen for breast cancer has not yet been identified, a whole cell tumor
vaccine was used consisting of 1 million irradiated cells per injection. PyMT-MSP breast tumor cells were irradiated with 10,000 rads. Initial
vaccination was administered subcutaneously to six female FVB Wild Type (WT) mice and six female FVB Ron knock out mice. Follow up booster
shots were subsequently given at day 8 and day 15 to half these mice. For the control cohort: four female FVB WT mice and four female FVB Ron
knock out mice were injected with HBSS saline on the day of initial vaccination. One cohort was sacrificed at day 5 and the other on day 18.
Peripheral blood cells and splenocytes were harvested, blood cells were stained with antibodies to detect levels of lymphocytes and cytokines then
analyzed using FACS. Investigators in this study did not use an adjuvant, to remove any confounding effect that an adjuvant could have on inducing
the immune response. Once proof of concept is confirmed using the vaccine, then an endogenous adjuvant, GM-CSF, will be added to the vaccine to
measure any amplification of the anti-tumor effect.
Results Vaccinated mice (both WT and Ron knock out) demonstrated a roughly three-fold increase in activated CD8+ cells in the spleen vs. the
control mice vaccinated with HBSS. The largest increase in vaccinated spleen CD8+ cell markers was in INF gamma. However, peripheral blood did
not yield nearly as great an increase in CD8+ cell activation. When comparing WT to Ron knock outs, both the day 5 cohort and day 18 cohort
showed no significant difference in higher immune markers.
Conclusions Whole cell irradiated tumor vaccination when used in conjunction with inhibition of the Ron-MSP pathway appears to slightly augment the
anti-tumor effect at certain time points as measured by CD8+ and CD4+ activation and elevations of anti-tumor cytokines including INF gamma,
Granzyme B, IL-2, TNF alpha, CD69, CD62, LAMPI, and CD25. Along with increasing the number of lymphocytes activated, it also slightly increased
effector cell toxicity. However, neither elevations represented a significant difference.
Fever, Dyspnea, and a Previously Septic Knee
Eric B. Fox, MD and John C. Christensen, MD
Intermountain Medical Center
HIstory
A 72 year-old man presented to the Emergency Department with a 3 day
history of progressive dyspnea on exertion and hypoxia. He has a history
of COPD and wears 2LPM of O2 at baseline, but was now using 4-6LPM to
maintain his oxygen saturations. He also noted a cough productive of
black-red sputum and wonders if it may be bloody.
He had recently undergone a left total knee replacement 1.5 months prior,
which was complicated by a joint infection that grew out methicillin
sensitive Staphylococcus aureus. For unclear reasons, the patient was
started on vancomycin for this infection. This was changed to daptomycin
9 days prior to admission after he exhibited symptoms consistent with redman syndrome.
Physical Exam/Diagnostic Studies
On exam, temp. 38.3 deg. C, BP 119/61, HR 109, and 92% on 4LPM of O2.
He was a morbidly obese, pleasant gentleman who appeared in mild
distress secondary to dyspnea, speaking in 3-5 word phrases. His lungs
demonstrated mild end-expiratory wheezes and distant breath sounds with
mildly increased work of breathing. His left knee demonstrated a healing
surgical incision with no fluctuance, erythema, or drainage. He had 2+
pitting edema to the knee in bilateral lower extremities, with the remainder
of the exam unremarkable.
Differential Diagnosis and Hospital
Course
Discussion
Initial diagnoses thought most likely included: pneumonia (healthcare
associated), pulmonary embolism, COPD exacerbation, or heart failure.
Although eosinophilic pneumonia (EP) can be idiopathic, often an
inciting drug can be identified, with antibiotics (ampicillin, sulfonamides,
minocycline, nitrofurantoin, daptomycin) and NSAIDs being the most
commonly implicated.1
The patient was treated for presumed HCAP, with the CTA ruling out
significant PE. COPD exacerbation and CHF were felt less likely based
on his clinical picture. Despite 2 days of appropriate antibiotics, his
clinical status worsened, and the diagnosis of eosinophilic pneumonia
was entertained based on his peripheral eosinophilia and exposure to
daptomycin.
The disease is characterized by fevers, diffuse pulmonary infiltrates,
hypoxemia, and >25% eosinophils on BAL. Drug induced EP is
suspected when there is: temporally related exposure to a possible
drug, no other cause that can be identified, resolution after cessation of
drug, and recurrence on re-challenge with the suspected drug (though
this is not recommended in clinical practice!).2
Bronchoscopy and bronchoalveolar lavage (BAL) demonstrated no
growth on cultures, and 34% eosinophils, cementing the diagnosis of
eosinophilic pneumonia, likely secondary to daptomycin use. The
patient was taken off HCAP therapy and started on systemic
corticosteroids, with notable respiratory improvement over the ensuing
5 days.
EP associated with daptomycin appears to be relatively rare, with 20
confirmed/probable case reports and 38 possible case reports.2 In
2010, the FDA issued a safety announcement highlighting the
association of daptomycin with EP and added this to the Adverse
Reactions section of the drug label.3
Treatment involves discontinuation of daptomycin often in conjunction
with systemic glucocorticoids, though there is no consensus on the
appropriate dose or duration of therapy. Most individuals will make a
full recovery, though ongoing need for corticosteroid therapy has also
been described.4
The mechanism of daptomycin toxicity is unclear. It is known to bind
pulmonary surfactant, and it has been postulated to incite an
eosinophilic response via accumulation in the alveolar spaces and
antigen presentation by macrophages.2
Initial labs demonstrated a white count of 13.2 (69% PMNs, 10%
lymphocytes, 13% monocytes, 6.5% eosinophils). Serum chemistries were
notable for a sodium of 129, a creatinine of 1.39, and elevated ESR/CRP at
45 and 10.7 respectively.
References
A CXR demonstrated bilateral lung opacities (R>L) consistent with
pneumonia (Figure 1). A CT pulmonary angiogram demonstrated no PE,
and probable multifocal pneumonia (Figure 2).
Figure 1.
Figure 2.
Images courtesy of Intermountain Medical Center
1. Solomon, Joshua, and Marvin Schwarz. "Drug-, toxin-, and radiation therapy-induced eosinophilic
pneumonia." Seminars in Respiratory and Critical Care Medicine. Vol. 27. No. 02
2. Kim, Peter W., et al. "Eosinophilic Pneumonia in Patients Treated with Daptomycin." Drug safety 35.6
(2012): 447-457.
3. US Food and Drug Administration. FDA drug safety communication: eosinophilic pneumonia associated
with the use of Cubicin (daptomycin) [online]. Available from
URL:http://www.fda.gov/Drugs/DrugSafety/PostmarketDrugSafetyInformationforPatientsandProviders/uc
m220273.htm. [accessed Sept. 16, 2013]
4. Lal, Yasir, and Aristides P. Assimacopoulos. "Two cases of daptomycin-induced eosinophilic pneumonia
and chronic pneumonitis." Clinical infectious diseases 50.5 (2010): 737-740.
Little Ulcer, Big Problem
Hannah Gaedtke, MD
University of Utah-Department of Internal Medicine
History of Present Illness
Mr. L is a 76 yo M with a history of atrial fibrillation and chronic
systolic heart failure admitted to the internal medicine service
from the dermatology clinic for evaluation and management of
worsening lower extremity ulcers.
The ulcers were located on both lower extremities (right
greater than left) at the posterior calf and had been present for
approximately 2 months.
Mr. L had previously been treated with antibiotic therapy for
possible cellulitis without improvement. He had no prior history
of skin breakdown or recurrent infections.
One week prior to this admission, Mr. L had undergone repeat
biopsy of the ulcer which showed microvascular thrombi. The
patient was started on warfarin, but noted worsening of his
ulcers shortly after. This prompted the patient’s current
admission to internal medicine for further evaluation and
management.
Medications at the time of admission included amiodarone,
warfarin, allopurinol. Dapsone was discontinued prior to
admission.
Labs, Pathology, Imaging
Labs:
ANA, Protein S/C, Anti-thrombin: WNL
Lupus Anticoagulant not detected
Beta 2 glycoprotein IgM, IgG, IgA: WNL
Anti-Cardiolipin IgG: 25 (0-14)
Anti-Cardiolipin IgM: 80 (0-12)
Biopsy Results:
Many of the blood vessels show intraluminal fibrin
thrombi. Other vessels show vasculitis with neutrophils
and dust in vessel walls.
Lower Extremity Duplex:
No thrombus of the right lower extremity.
Mr. L presented with persistent lower extremity ulcers despite
appropriate management of community acquired cellulitis.
Biopsy results were concerning for microthrombi which
prompted evaluation for coagulopathy. Initial results showed
elevated anti-cardiolipin IgG and IgM.
Based on Sapporo Criteria, Mr. L met criteria for diagnosis of
antiphospholipid syndrome.
1.Clinical Feature: Biopsy showing microthrombi, Livedo
Reticularis
2.Presence of autoantibody: Anti-Cardiolipin Antibodies
Autoantibodies were repeated at 12 weeks and again showed
elevated anti-cardiolipin Ab, confirming the diagnosis of
antiphospholipid syndrome. ANA was negative and no other
Conclusions
clinical or laboratory criteria
was found to suggest SLE.
Mr. L was found to have subtherapeutic INR. It was thought
that initiating warfarin without heparin bridging may have
exacerbated his hypercoagulable state and led to worsening of
the ulcers. He was placed on heparin therapy and bridged
until warfarin was therapeutic. Ulcers improved following
therapeutic anticoagulation.
Exam
Description of Ulcer per dermatology consult:
Right lower posterio-medial leg, large tender malodorous ulcer
down to subcutaneous fat with surrounding reticulated/livedo
change. Base of ulcer with yellow fibrinous exudate. Anterior of
leg with atrophic hypopigmented patches. Mild erythema
surrounding wound, no undermined border.
Discussion
Differential Diagnosis
1. Vasculopathy secondary to hypercoagulable
state
2. Vasculitis
3. Calciphylaxis
References
Miyakis s, et al. International consensus statement on an update of the
classification criteria for definite antiphospholipid syndrome (APS). Journal
of Thrombosis and haemostasis, 4: 295-306.
Pierangeli SS, Erkan D. Antiphospholipid syndrome treatment beyond
anticoagulation: are we there yet? Lupus 2010 19: 475.
Printed by
Pruritic Purpura and Acute Respiratory Failure
Verena C. Haringer, M.D.
University of Utah, Department of Internal Medicine
Case Description
Differential Diagnoses
A 61 year old white male presented to the Emergency Department with a
6-month history of pruritic purpura in his bilateral lower extremities as well
as polyarticular arthralgias and weight loss.
His only past medical history are multiple musculoskeletal injuries and a
s/p septic arthritis in both knees. The patient endorses iv drug abuse in the
past and cocaine abuse with the last use about 1 year prior to admission.
His family history is positive for lymphomas in multiple relatives.
Fig. 3
On admission he was found to have palpable, macular purpura on the
dorsal hands and prominent on his bilateral legs, including the soles of his
feet (Fig. 1), a 3 cm mobile, non-tender, soft mass on the right neck,
periodontal disease with gingivitis, diffuse small oral ulcers , punctate oral
hemorrhages, and an exudate on his right tonsil. Labs showed a WBC of
11.8 with 11% eosinophils, CRP of 10, a CK of 1300 and 5 RBC on UA. CT
chest on admission showed scattered ground glass opacities (Fig. 3).
-
Lymphoma
-
Endocarditis with septic emboli
-
Chronic hepatitis with cryglobulinemia
-
Henoch-Schönlein purpura preceded by oral infection
-
Microscopic polyangiitis
-
Churg-Strauss syndrome
-
Levimasole-induced vasculitis in a patient with a history of cocaine
abuse
-
Granulomatosis with polyangiitis (Wegener’s)
Fig. 4
Discussion
Hospital Course
Extensive work-up revealed anemia, positive Hepatitis B core antigen IgM
antibody, elevated rheumatoid factor and positive ANCA-PR3. Urine was
initially negative for red cell casts. TTE/TEE showed no evidence of
endocarditis, urine was negative for cocaine, SPEP was within normal
range, cryoglobulins were negative.
The overall clinical picture in this middle-aged white male points
towards a small vessel vasculitis, most likely granulomatosis with
polyangiitis (Wegener’s).
Fig. 1
Although it is best to have a confirmation of diagnosis by tissue
biopsy at a site of active disease, patients should be treated
empirically if the clinical suspicion is high and initiation of therapy is
life saving and organ sparing.
Fig. 5
A skin biopsy of the patient’s lower back showed leukocytoclastic vasculitis
with IgM and C3 deposition (Fig 2). A biopsy of a lower lip ulcer showed
eosinophil-predominant vasculitis.
On Day 11 after admission, the patient had to be transferred to the MICU
for acute hypoxic respiratory failure requiring BiPAP treatment. He was
found to have ARDS secondary to diffuse pulmonary hemorrhage (Fig. 4).
At this time his urine was found to be positive for red cell casts as well as
dysmorphic red cells, and the patient underwent renal biopsy which was
inconclusive. Due to the acute worsening of the patient’s clinical picture, he
was treated with a 3-day course of plasmapheresis and high-dose iv
steroids, followed by po steroids and cyclophosphamide which led to an
improvement of his respiratory function (Fig. 4).
References
1.
2.
3.
Fig. 2
Falk et al. Granulomatosis with polyangiitis (Wegener’s): an alternative name for Wegener’s
granulomatosis. Arthritis Rheum. 2011 Apr; 63(4):863-4
Lee et al. Complications associated with levimasole-contaminated cocaine: an emerging public health
challenge. Mayo Clin Proc. 2012 Jun;87(6):581-6
Peng et al. Culture-negative subacute bacterial endocarditis masquerades as granulomatosis with
polyangiitis (Wegener’s granulomatosis) involving both the kidney and lung. BMC Nephrol. 2012 Dec
26;13:174
Fig. 1 courtesy of Brian J. Horner, M.D.; Fig. 2 courtesy of Scott R. Florell, M.D.; Fig. 3-5 courtesy of the University of Utah Hospital
Behcet’s disease with Crohn’s disease
Abdul Haseeb, MD MPH
University of Utah Department of Internal Medicine
Conclusions
Purpose/Methods
A distinct diagnosis of Behcet’s disease or inflammatory
bowel disease can be perplexing with a significant overlap in
the systemic and gastrointestinal features of both disorders.
Behcet’s disease classified as an auto-inflammatory disease,
usually runs an abating course with time compared to lifelong
course of Crohn’s. Although intestinal Behcet’s disease
accounts only for a minimal 1-2%, the histological features
closely resemble Crohn’s on endoscopy. The diagnosis of
Behcet’s is based mainly on clinical findings due to lack of
pathognomonic laboratory test. A few case reports are
published describing the co-existence of Crohn’s disease
with Behcet’s; these are mostly from Turkey and along the
“silk route.” Familial studies reviewed also suggested a close
relation between the two diseases indicating them to be part
of spectrum rather than two distinct disease entities. Coexistent Crohn and Behcets’ disease should be considered a
diagnostic possibility in patients who present with
overlapping symptoms.
To describe the coexistence of “auto-inflammatory” Behcet’s
disease with Crohn’s disease and to demonstrate clinical and
diagnostic presentations that make it difficult to identify them
as separate entities.
Retrospective chart review and bibliographic database
search for relevant studies pertaining to the patient’s clinical
presentation.
Case Discussion
37-year-old Hispanic male with a known history of Crohn’s
disease presents with recurrent oro-genital ulcers, anterior
uveitis, and papulopustular lesions. He had frequent Crohn’s
flares since his initial diagnosis three years ago, despite being
on maintenance mesalamine therapy and corticosteroid use
during acute flares. He had failed 6-mercaptopurine treatment
in the past due to liver toxicity and Infliximab treatment due to
anaphylaxis. In addition to recurrent colitis, the patient
presented with a plethora of extraintestinal findings including
neutrophilic vasculitis, skin abscesses, sinusitis, nasal polyps,
oral ulcers, pulmonary granulomas, granulomas on bone
marrow biopsy, splenic granulomas, uveitis, and non-specific
arthritis. He underwent an extensive rheumatological work-up
and the top two differential diagnoses were Crohn’s disease
with extra-intestinal manifestations and Behcet’s disease.
Labs were significant for an elevated proteinase-3-antibody,
but negative for ANA, and ANCA. Colonoscopy revealed
inflammation in the terminal ileum and colitis in the ascending
and transverse colon.
References
Although these findings were consistent with a Crohn’s flare,
the patient was concurrently diagnosed with Behcet’s based on
his recurrent episodes of oral aphthae, genital aphthae, uveitis,
and papulopustular skin lesions. Diagnosis was based on most
widely accepted International Study Group (ISG) criteria for
Behcet’s disease. He was initially started on Azathioprine, but
treatment was complicated with the development of
neutrophilic dermatoses leading to a diagnosis of drug induced
Sweet’s syndrome. Treatment was finally switched to
cyclosporine and low dose prednisone. The patient has shown
significant clinical response to this regimen and has had no
readmissions with Crohn or Behcets’ flares.
Insert Footer or Copyright Information Here
1. Akay N, Boyvat A, Heper AO, Soykan I, Arica IE, Bektas M, et al.
Behcet's disease-like presentation of bullous pyoderma gangrenosum
associated with Crohn's disease. Clin Exp Dermatol. 2006;31(3):384-6.
2. Cheifetz AS. MAnagement of active crohn disease. JAMA.
2013;309(20):2150-8.
3. Kim ES, Chung WC, Lee KM, Lee BI, Choi H, Han SW, et al. A case
of intestinal Behcet's disease similar to Crohn's colitis. J Korean Med
Sci. 2007;22(5):918-22.
4. Koksal AS, Ertugrul I, Disibeyaz S, Tola M, Kacar S, Arhan M, et al.
Crohn's and Behcet's disease association presenting with superior
vena cava thrombosis. Dig Dis Sci. 2005;50(9):1698-701.
5. Yazici H, Fresko I. Behcet's disease and other autoinflammatory
conditions: what's in a name? Clin Exp Rheumatol. 2005;23(4 Suppl
38):S1-2.
Printed by
Valve Replacement in Infective Endocarditis
Mark Kaeppler, MD
University of Utah, Department of Internal Medicine
HPI
A 76-year-old male with CAD, hypertension and prostate cancer s/p
prostatectomy presented with a 6-week history of progressively
worsening back pain. This pain was initially associated with fevers
and chills. He presented both to an InstaCare and an outside ED,
where he was found to have a persistent leukocytosis prior to his
current presentation in the IMC ED.
Treatment of the prostate cancer (diagnosed in 1998) included
surgery and androgen deprivation therapy.
He denied IV drug abuse. Further questioning also revealed a new
complaint of chest pain exacerbated by deep breathing.
Studies
Potassium
3
Albumin
2.8
Hgb
11.1
WBC
16,000
ESR
40
CRP
20
Figure 1: EKG demonstrating ST segment
depression in precordial leads V3-V6.
Discussion
Despite substantial improvement in morbidity and mortality since the
advent of modern antibiotics, infective endocarditis (IE) continues to
carry a high in-hopsital death rate (18-23%) and at 6-months after
presentation (22-27%). Furthermore, as many as 50% of patients with
IE suffer at least one complication as a direct result of this blood borne
infection1.
Figure 2: Blood cultures revealed the presence
of Gram-positive cocci in chains.
Imaging
Initial Workup
The patient was found to be hypothermic to 34.9 degrees Celsius and
tachycardic to 109 bpm. Physical examination demonstrated a 3/6
holosystolic ejection murmur best heard at the apex that radiated to
the axilla. Lower extremity strength was rated as 5/5 throughout
with normal sensation and 2+ patellar reflexes.
A chest X-ray was normal. MRI of the lumbar spine demonstrated
osteomyelitis/discitis. EKG demonstrated significant ST segment
depression consistent with coronary ischemia (Figure 1).
Blood cultures were obtained before the initiation of Vancomycin
and Ceftriaxone. TTE was performed on the day of admission and
TEE a day later (Figures 3 & 4). Microbiology results yielded
identification of Streptococcus sanguinis (Figure 2).
Diagnosis
#1. Infective endocarditis of the mitral valve, #2. L4-L5
osteomyelitis/discitis, #3. Acute coronary syndrome
Figure 3: TEE image demonstrating a large
mobile vegetation present on the anterior
leaflet of the mitral valve.
Figure 4: TEE Doppler image demonstrating
severe mitral regurgitation associated
with the vegetation.
Clinical Course
The patient acutely developed aphasia, R facial numbness and R
hand clumsiness. MRI brain demonstrated ischemia within regions
of the L frontal lobe and punctate foci within the bilateral parietal
lobes consistent with subacute stroke. In the following days, two
further ASSERT calls were performed for similar symptoms. He
was otherwise hemodynamically stable. Left heart catheterization
was performed, demonstrating obstructive disease within the LAD.
By hospital day #9, the patient underwent mitral valve replacement
and CABG (LIMA to LAD). Five days s/p CT surgery, he was
discharged without further complication.
This patient presented with sepsis in the setting of a new systolic
murmur, prompting further evaluation by echocardiogram due to
suspicion of IE. Neurologic complications—principally
stroke/embolism among the ICA distribution—are common, occurring
in 20-40% of cases of IE2. Treatment with prolonged courses of IV
antibiotics remains the cornerstone of management of this disease.
Additionally, valve replacement is an important consideration in
severe cases of IE, which requires coordination between Medicine and
Surgery. It should be emphasized that the decision to undergo valve
replacement should be individualized, but a few generally agreed upon
indications for valve replacement include3:
•CHF
•≥2 major embolic events
•Vegetations >10 mm
•Fungal IE
References
1. The complications of infective endocarditis. A reappraisal in the 1980s. Mansur AJ, Grinberg
M, da Luz PL, Bellotti G. Arch Intern Med. 1992;152(12):2428.
2. Neurological manifestations of infective endocarditis. Review of clinical and therapeutic
challenges. Jones HR Jr, Siekert RG. Brain. 1989;112 (Pt 5):1295.
3. AHA Scientific Statement: Infective Endocarditis. Baddour, LM, et al. Circulation. 2005; 111:
e394-e434 doi: 10.1161/CIRCULATIONAHA.105.165564
Figure 2 image obtained from: www.vcu.edu
Thank you to Drs. Scott Woller and Corwin Edwards for obtaining the included Echo images
Dental Appliances in the Treatment of OSA
Surabhi Kasera*, Scott Hollingshaus MD #, Krishna M. Sundar MD #, Gary Lowder DDS+, Julia Whitaker MD#
*Washington University in St. Louis, Departments of #Medicine & +Dentistry, University of Utah
Introduction
Results
Dental appliances are recommended for patients with mild to
moderate obstructive sleep Apnea (OSA) that are intolerant
to continuous positive airway pressure (CPAP) therapy. The
Sleep Wake Center (SWC) has a dental appliance program
that custom-fits appliances for referred patients. This study
measured the efficacy and follow-up of the TAP III dental
appliance given to patients for OSA or upper airway
resistance syndrome (UARS) in the last 2 years.
Objectives
Figure 1 Baseline data for patients given TAP III appliance
Figure 3 Compliance in patients with OSA and UARS
1. Assess follow-up visit frequency, compliance with
provider visits, and long-term care for patients on a dental
appliance received through the SWC.
40
35
30
2. Assess efficacy of TAP III appliance based on patientreported efficacy and objective follow-up measures.
BMI
25
15
Methods
Data on patients that received the TAP III device at the SWC
within the last 2 years (since inception of EPIC electronic
medical records) were reviewed. Demographic data and
reason for dental referral were obtained from the medical
records. Duration and frequency of follow-up after dental
appliance application was obtained from EPIC. TAP III
appliance efficacy in patients was assessed using the
following:
-Patient and provider-reported subjective
assessments of TAP III appliance efficacy.
-Oximetry and PSG findings while using the dental
appliance.
Statistical analysis using a student’s t-test was done to find
significant differences in TAP III efficacy with age, sex, BMI,
etc. The results of this analysis was used to develop
protocols for future follow-up of patients following dental
appliance application.
20
10
5
0
Figure 2 Follow-up durations of dental visits and visits with
referring provider at SWC
Effective
Ineffective
Figure 4 Obesity and dental appliance efficacy, p < .05, student’s t-test
Conclusions
References
1. Efficacy of dental appliances is increased in obese subjects. This has been noted in
prior studies as well 1-2.
1.Use of Flow-Volume Curves to Predict Oral
Appliance Treatment Outcome in Obstructive
Sleep Apnea, American Journal of Respiratory
and Critical Care Medicine 2007; 175: 726-730
2. For patients receiving dental appliances at the SWC, significant deficiencies in followup care were noted in the following ways:
a. Lack of follow-up with referring provider and with dentist fitting the appliance
b. Lack of pre-defined objective testing and validated questionnaires to assess
efficacy of dental appliance
c. Lack of comprehensive program aimed at improving BMI along with dental
appliance therapy for OSA or UARS patients
1.Efficacy of an Adjustable Oral Appliance and
Comparison with Continuous Positive Airway
Pressure for the Treatment of Obstructive
Sleep Apnea Syndrome, Chest 2011; 140:
1511-1516
Primary Sclerosing Cholangitis in the Setting of Normal Liver Chemistries
Can Be Associated with Severe Ductal Disease and Dominate Strictures
Thomas Queen, MD, Kristen Cox MS, RN, Douglas G. Adler, MD
Division of Gastroenterology, University of Utah Health Sciences Center, Salt Lake City, UT
INTRODUCTION
Primary sclerosing cholangitis (PSC) is a chronic progressive disease
characterized by inflammation, fibrosis and stricturing within the intra and
extrahepatic biliary ducts.
It is commonly associated with abnormal liver function tests such as alkaline
phosphatase, AST, ALT and total bilirubin.
A subset of PSC patients will present with normal laboratory studies.
RESULTS
There were 102 PSC patients in our PSC database from 2000 to 2013.





OBJECTIVE
The aim of this study is to evaluate patients with PSC with normal liver
function tests.
All 11 patients underwent ERCP which confirmed the diagnosis of PSC.

METHODS

We conducted a retrospective study of PSC patients with normal liver
chemistries to evaluate their clinical course, endoscopic, and pathologic
findings.

This study was approved by the institutional review board at the University
of Utah School of Medicine, Salt Lake City, Utah.
We reviewed electronic medical records, procedure reports, imaging
studies, and pathology reports on patients with known or suspected PSC
between the period of February 2000 to April 2013.

All 11 patients had intrahepatic ductal disease manifesting as innumerable
strictures and pruning.
4 patients were felt to have dominant strictures: 3 of these dominant strictures
were in the common hepatic duct and 1 was in the common bile duct.
3 patients were felt to have mild PSC, 6 were felt to have moderate PSC, and 2
were felt to have severe PSC.
There were no complications following ERCP.
PSC patients with normal serum liver chemistries has not been previously
well described.
PSC patients can have cirrhosis and significant ductal disease, including
dominant strictures and abnormal tissue samples, in the setting of normal
liver chemistries.
Patients with PSC and normal liver chemistries were less likely to have IBD
and colitis than were patients with PSC and abnormal labs.
All patients tolerated ERCP exams without difficulty and had no
complications: this may be explained, at least in part, by undergoing ERCP by
experienced operators.
No patient has had significant progression of disease over a mean follow up
period of 50 months. This is in contrast to most PSC patients who can be
expected to have progression when followed over the same timeframe.
8 patients underwent tissue sampling by brushings and/or biopsy during ERCP.



We also evaluated a prospectively evaluated database of PSC patients.
Patients in this study were diagnosed with PSC by laboratory studies, liver
biopsy, MRCP, ERCP, or a combination thereof.
11 patients had normal liver chemistries at time of presentation (8M, 3F, mean
age 47.1Y)
5 patients had IBD: 3 out of 5 had Crohn’s disease ( 1 had colitis), 2 out of 5
had ulcerative colitis.
On CT scan, 8 out of the 11 patients had evidence of cirrhosis.
8 out of the 11 patients underwent MRI/MRCP and 5 of these patients had
ductal findings suggestive of PSC.
1 patient had an MRI/MRCP that was suggestive of PSC and
cholangiocarcinoma.
CONCLUSIONS

3 patients were not felt to warrant tissue sampling.
1 patient had a mass lesion at the common hepatic duct that to date has
yielded only benign brushing, histology, and FISH results .
The 1 patient with the dominant CBD stricture had brushing that showed
atypical cells suspicious for malignancy and positive FISH study. This patient
underwent a pancreaticoduodenectomy for presumed cholangiocarcinoma.
Final pathology showed evidence of high grade dysplasia but no cancer.
None of the remaining patients who underwent tissue sampling had positive
FISH testing or positive brushings for malignancy.
Severe ductal disease seen in a
patient t with PSC with normal
labs
Budd-Chiari Syndrome Secondary to
Hepatic Zygomycosis in a Neutropenic Patient
Craig D. Robison,1 Bert K. Lopansri1,2
of Internal Medicine, University of Utah School of Medicine, Salt Lake City, Utah;
2Department of Infectious Disease, Intermountain Healthcare, Salt Lake City, Utah
1Department
Introduction
• Zygomycosis is a devastating fungal infection, mostly
seen in immunocompromised persons and diabetics
• Mostly associated with rhino-orbital-cerebral and
pulmonary infections but occasionally can be found in
other organ systems
• Mortality remains extremely high despite treatment
Case Presentation
A
A 46 year old previously healthy female underwent idarubicin and
cytarabine induction chemotherapy for newly diagnosed AML M2.
Prophylactic treatment with levofloxacin, penicillin, acyclovir, and
micafungin was initiated.
On day #7 She developed neutropenic fever and vancomycin and
cefepime were empirically started with evidence for central venous
catheter (CVC) exit site infection. Blood cultures were negative.
Fungal biomarkers were obtained on day #11 and yielded a negative 1,3
Beta D-glucan and a weakly positive Galactomannan initially thought
to be a false positive from total parenteral nutrition.
B
*
A
B
On day #16 the patient developed worsening abdominal pain.
Micafungin dosing was increased and metronidazole was added. On
day #17 the patient developed elevated LFTs (normal on day #14) and
liver failure. Micafungin was replaced with liposomal amphotericin B.
Autopsy limited to the liver demonstrated massive hepatonecrosis
secondary to portal vein thrombosis and extensive venous thrombosis
with broad, irregularly shaped, largely aseptate hyphae, some with right
angle branching, consistent with mucormycosis. Leukemic infiltrates
into the liver were not identified. Mechanism of hepatic involvement
of remains unexplained but may be related to extension from colitis
and/or dissemination from CVC exit site infection.
Figure 1. Patient’s axial (a) and coronal (b) CT
imaging demonstrating multiple large hepatic masses
including invasion into the inferior vena cava (*)
consistent with hepatic mucormycosis.
Day #
1
4.5
14
0.2
17
0.1
9.9/29
9.527.3
8.6/24.9
94
43
9
Na+ (mmol/L)
K+ (mmol/L)
Cl- (mmol/L)
CO2- (mmol/L)
BUN/Cr (mg/dL)
Glu (mg/dL)
139
4.1
102
27
12/0.52
88
140
3.6
101
31
10/0.30
132
134
5.2
101
7
29/1.48
84
Alk Phos (U/L)
AST (U/L)
107
53
493
23
33
22,614
ALT (U/L)
T Bili (mg/dL)
INR
25
0.6
1.1
55
0.5
1.1
8,904
5.7
4.0
WBC (K/μL)
Hgb/Hct (g/dL; %)
CT imaging demonstrated mild colitis of the descending and sigmoid
colon along with multiple new large hepatic and intra-abdominal
hypodense masses extending into the suprahepatic IVC thought to be
leukemic tumors vs. infectious etiology, most likely mucormycosis.
She rapidly developed septic shock, ascites, encephalopathy, respiratory
failure, and renal failure requiring transfer to the intensive care unit,
intubation, and hemodialysis. Surgery was not possible due to
progressive decline. Her LFTs continued to increase consistent with
fulminant hepatic necrosis. Care was withdrawn at the family’s request
and the patient expired on day #21.
Discussion
Plts (K/μL)
C
D
Figure 2. Extensive hepatic portal vein and inferior vena cava zygomycosis with broad, irregularly
branched, aseptate hyphae demonstrated via Grocott-Gömöri’s methenamine silver (A,B) and
Hematoxylin and eosin (C,D) staining at 400x and 1000x respectively.
Hepatitis Panel
Neg
Neg
Table 1. Patient’s lab results on days #1, #14 and #17.
Zygomycosis
• Zygomycetes is a class of fungi include the following
species: Mucor, Rhizomucor, Rhizopus, Absidia
• Angioinvasion leading to tissue necrosis is a hallmark
of zygomycosis.
• Healthcare-associated infections have been reported
• Gastrointestinal mucormycosis thought to be
secondary to translocation of ingested spores
• Diagnosis relies upon identification of organisms by
histopathology
• Fungal cultures often negative
• Treatment involves aggressive surgical debridement
and antifungal therapy
• Duration of therapy is variable and cure requires
recovery of neutrophil function
• Prognosis is very poor despite early appropriate
treatment
Budd-Chiari syndrome from
Zygomycosis/Mucormycosis
• Fewer than 15 cases reported in the literature
• Mostly in patients with hematological malignancies
(AML, ALL), solid organ transplant recipients, and
diabetics
• Pooled mortality > 50% despite treatment with
amphotericin
We present a case of fatal hepatic necrosis from Budd-Chiari
syndrome attributed to angioinvasive mucormycosis in a patient
undergoing chemotherapy for AML. Diagnosis was confirmed only
at time of autopsy, but imaging helped narrow the differential when
vascular invasion was seen.
Despite timely diagnosis and initiation of systemic antifungal
therapy this patient expired. Surgery was not an option given
hemodynamic instability, extensive liver involvement and
chemotherapy-induced pancytopenia.
ACE-I/ARB Administration following Cardiac Catheterization
Is Associated with Reduced Contrast-Induced Nephropathy
Craig D. Robison2, MD; Heidi T. May1, MSPH; Benjamin D. Horne1, PhD, MPH;
Donald L. Lappe1, MD; Joseph B. Muhlestein1,2, MD; Jeffrey L. Anderson1,2, MD
1Intermountain Heart Institute, Intermountain Medical Center, Murray, Utah; 2Department of Internal Medicine, University of Utah School of Medicine, Salt Lake City, Utah
Results
Background
• Contrast-induced nephropathy (CIN) is a
complication of cardiac catheterization
• Angiotensin converting enzyme inhibitors (ACE-I)
and angiotensin receptor blockers (ARB) are
frequently prescribed in those undergoing cardiac
catheterization
• Studies evaluating ACEI/ARB use and cardiac
catheterization thus far have produced mixed
results on the effect of these medications on
contrast-induced nephropathy.
Objective
• To evaluate the association between ACE-I and ARB
administration and development of contrast induced
nephropathy following cardiac catheterization
A
B
Characteristics
Age (years)
Sex (male)
Hypertension
Dyslipidemia
Diabetes
Family History CAD
Tobacco Abuse
Renal Failure
Prior MI
Prior CVA
Prior CAD
A-Fib History
No ACE-I/ARB
(n=2463)
65.1±13.3
63.8%
57.1%
54.9%
24.4%
33.6%
12.3%
1.5%
14.0%
6.7%
57.1%
19.8%
C
ACE-I/ARB (n=2628)
p-Value
66.0±12.7
67.3%
68.5%
62.4%
30.3%
37.4%
12.9%
1.1%
17.2%
5.8%
61.9%
18.9%
0.02
0.008
<0.0001
<0.0001
<0.0001
0.005
0.52
0.17
0.002
0.18
<0.0001
0.42
Presentation
Methods
• 5,091 patients in the Intermountain Heart Collaborative Study
Registry (Salt Lake City, UT) undergoing cardiac
catheterization
• Evaluate for administration of ACE-I/ARB prior to discharge
following admission for cardiac catheterization
• Require baseline creatinine < 2.5 mg/dL
• Follow-up for one year
• Evaluate for development of CIN within 10 days:
• Increase in baseline creatinine of ≥ 25% mg/dL OR
• Absolute increase of ≥ 0.5 mg/dL
• Evaluate for persistent CIN between 6-12 months:
• Persistent Δ in Creatinine ≥ 0.5 mg/dL from baseline
• Perform multivariable logistic regression analysis, adjusting
for cardiovascular risk factors, baseline creatinine, contrast
amount, medications, and CAD status
• Include secondary outcomes at 1 year of creatinine increase
and all-cause mortality
<0.0001
Stable Angina/Other
Unstable Angina
NSTEMI/STEMI
64.2%
24.7%
11.1%
49.7%
30.0%
20.3%
IABP
Pulmonary Edema
2.4%
4.4%
2.9%
3.7%
0.23
0.17
PCI
Drug Eluting Stent,
n=2155
Bare Metal Stent,
n=2155
30.7%
64.2%
(485/756)
43.1%
(326/756)
131.2±102.7 (median
107)
53.2%
64.0%
(896/1399)
43.9%
(614/1399)
168.1±114.0 (median
150)
<0.0001
1.12±0.38
(median 1.00)
1.22±0.50
(median 1.10)
0.10±0.34
(median 0.06)
1.09±0.32
(median 1.01)
1.18±0.43
(median 1.10)
0.09±0.33
(median 0.05)
Total Contrast (mL)
Baseline Creatinine (mg/dL)
Follow-up Creatinine (mg/dL)
Creatinine Change (mg/dL)
0.96
0.73
<0.0001
0.02
0.02
0.54
Conclusions
D
Figure 1. Kaplan-Meier 1 year event free survival for (A) Death, (B) Myocardial
Infarction, (C) Revascularization, and (D) New Onset Atrial Fibrillation for patients
receiving ACE-I/ARB and controls.
Characteristics
CIN
Persistent CIN
CIN or
Persistent CIN
Death at 1 year
MI at 1 year
CVA at 1 year
HF admit at 1 year
Revasc at 1 year
New onset
A-Fib at 1 year
No ACE-I/ARB
(n=2463)
16.7% (412/2463)
8.0%
ACE-I/ARB
(n=2628)
11.0% (290/2628)
7.4%
<0.0001
0.44
p-Value
21.3%
16.3%
<0.0001
3.8% (89/2369)
8.4% (199/2369)
3.2% (75/2369)
12.4% (293/2369)
23.7% (531/2239)
3.2% (82/2544)
13.5% (344/2544)
2.8% (71/2544)
13.1% (334/2544)
20.0% (487/2438)
0.31
<0.0001
0.44
0.43
0.002
<0.0001
20.5% (389/1902)
13.0% (268/2063)
Multivariable Regression
OR
95% CI
P-Value
CIN
Persistent CIN
CIN or
Persistent CIN
0.70
0.99
(0.59-0.84)
(0.80-1.24)
<0.0001
0.97
0.81
(0.70-0.94)
0.006
Table 2. Primary and secondary outcomes at 1 year. CIN = Contrast Induced
Nephropathy; MI = Myocardial Infarction; CVA = Cerebrovascular Accident; HF =
Heart Failure, Revasc = Revascularization; A-Fib = Atrial Fibrillation.
Multivariable regression analysis for primary outcomes adjusted by baseline
characteristics.
Characteristics
Baseline Creatinine
(mg/dL)
Follow-up Creatinine
(mg/dL)
Creatinine Change
(mg/dL)
No ACE-I/ARB
1.14±0.41
(median 1.09)
1.37±0.58
(median 1.20)
0.23±0.40
(median 0.20)
ACE-I/ARB
1.05±0.36
(median 1.00)
1.31±0.53
(median 1.20)
0.26±0.39
(median 0.20)
• ACE-I/ARBs following cardiac catheterization
associated with reduced contrast-induced
nephropathy
• Consistent even after adjustment for cardiovascular
risk factors and differences in creatinine
• No difference in creatinine changes and mortality at
1 year in all patients
• No difference in creatinine at 1 year in patients with
contrast-induced nephropathy
Discussion
• ACE-I/ARB administration was associated with a
decreased incidence of CIN despite more comorbidities
and more contrast used.
• Literature reports evidence both for and against a
renoprotective effect of ACE-I/ARBs in the
development of contrast-induced nephropathy.
• Possible renoprotective mechanisms include opposing
arteriolar vasoconstrictive effects of contrast media and
attenuating contrast-induced renal tubular cell
apoptosis.
• Most other studies are limited by small sample sizes
and short follow-up.
• Randomized controlled trials are needed to clarify
conflicting results in the literature.
References
p-Value
0.006
0.16
1.
2.
0.55
3.
Table 1. Cohort characteristics. CAD = Coronary Artery Disease; MI = Myocardial
Infarction; CVA = Cerebrovascular Accident; A-Fib = Atrial Fibrillation; NSTEMI = NonST Elevation Myocardial Infarction; STEMI = ST-elevation Myocardial Infarction; IABP =
Intra-Aortic Balloon Pump; PCI = Percutaneous Coronary Intervention
Table 3. Sub-group analysis for patients who developed contrast-induced
nephropathy (No ACE-I/ARB: n=412, ACE-I/ARB: n=290).
p-Value for comparison of log-transformed variables.
4.
Patel K, King CA, Jovin IS. Angiotensin-converting enzyme inhibitors and their effects on
contrast-induced nephropathy after cardiac catheterization or percutaneous coronary
intervention. Cardiovascular Revascularization Medicine. 2011;12:90-93.
Rim MY, Ro H, K WC, et al. The Effect of Renin-Angiotensin-Aldosterone System
Blockade on Contrast-Induced Acute Kidney Injury: A Propensity-Matched Study. Am J
Kidney Dis. 2012;60(4):576-582.
Rosenstock JL, Bruno R, Kim JK, et al. The effect of withdrawal of ACE inhibitors or
angiotensin receptor blockers prior to coronary angiography on the incidence of contrastinduced nephropathy. Int Urol Nephrol. 2008;40(3):749-755.
Cirit M, Toprak O, Yesil M, et al. Angiotensin-converting enzyme inhibitors as a risk
factor for contrast-induced nephropathy. Nephron Clin Pract 2006;104:20-7.
Drug Rash
Jennifer A Springer, MD
University of Utah Department of Internal Medicine/Intermountain Medical Center
HPI
Images
61 yo F presented to clinic with a full body rash and fevers.
Toxic Epidermal Necrosis (TENS)
 Patient was diagnosed with a DVT, treated with Coumadin and
Lovenox.
Discussion
 One week later she developed skin lesions concerning for skin
necrosis; anticoagulation was changed to Xarelto.
 Most likely causative agents are Xarelto and Diltiazem. The
onset of the rash was later than would be expected for Xarelto but
sooner than would be expected for Diltiazem.
 Two weeks after starting Xarelto, she was started on Diltiazem
for HTN.
 The next day she developed a full body rash that started in the
extremities and spread to her trunk. The rash was pruritic and
associated with fevers. Patient stopped Diltiazem but rash
continued to worsen.
 There are reports of SJS/TENS from Diltiazem and rare reports of
SJS/TENS from Xarelto.
Past medical history significant for CAD, DM, COPD, HTN,
hepatitis C, chronic kidney disease and multiple drug allergies mostly to antibiotics.
Exam and Labs
Exam: T 37.7, HR 94, BP 146/75, RR 16, O2 sat 95% on 4L NC
Morbidly obese female, skin had a maculopapular rash that
coalesced into erythematous plaques on the trunk with skin
desquamation. Lower extremities had bullae and pustules. 0.5 cm
ulceration under tongue.
Hospital course
Labs:
Na 134, K 4.7, Cl 94, Bicarb 31, BUN 42, Cr 1.69, Glu 232
Ca 9.1, Prot 7.6, Alb 3.7, AST 55, ALT 33, Alk Phos 128, Bili 0.8
WBC 18, Hgb 11.2, Plt 378
CRP 10.8, ESR 66
Biopsy:
Spongiform eosinophilic dermatitis with dermal perivascular
neutrophils consistent with drug rash
Diagnosis
Hospital Course
 All non-essential medications held. Dermatology consulted.
 Treated with PO and topical steroids.
 Xarelto discontinued, treated DVT with heparin drip and restarted
Coumadin.
 Swab of leg pustule grew MRSA. MRSA cellulitis treated with
Cefotaxime.
 Patient remained hemodynamically stable. WBC trended up to a
max of 30,000/uL before trending down, no eosinophilia.
 Rash quickly resolved, patient had near complete desquamation
of epidermis.
 If there was no involvement of oral mucosa, the diagnosis would
be Acute Generalized Exanthematous Pustulosis (AGEP).
Patient did not have elevation of liver enzymes or other evidence
of systemic involvement to raise concern for DRESS (Drug
Reaction with Eosinophilia and Systemic Symptoms).
Vasculitities are common with hepatitis C, the status of her
hepatitis is unknown, but there was no evidence of vasculitis on
exam or biopsy.
 There is mixed data for the use of oral steroids to treat drug
rashes.
References
1. “Severe Adverse Cutaneous Reactions to Drugs” NEJM Nov 1994
2. “Cutaneous Adverse Reactions Associated with Calcium Channel Blockers” Arch
Intern Med 1989
3. “Xarelto (Rivaroxaban) Prescribing information” Janssen Pharmaceuticals Aug
2013
4. Emedicine.medscape.com
5. Uptodate.com
Small Vessel Vasculitis—No Small Thing
Miguel G. Teixeira, BS, MSIV. Internal Medicine. University of Utah, Salt Lake City, UT.
HISTORY OF PRESENT ILLNESS
Patient is a 63 year old previously healthy woman from
Wyoming with a recent exposure to pesticides and
fertilizers who presents to the ED with complaints of a
painful and swollen bilateral purpuric rash in her lower
extremities. She reports she noticed small "red spots" that
were non-blanchable on the dorsum of her feet
approximately one week ago. These spread to her legs and
thighs with progressively worsening edema. She took
Benadryl and ibuprofen without relief of her pain or
swelling. Patient was seen by a family medicine physician
and ED in Wyoming and was given Lortab for pain and Lasix
for diuresis. She reports these gave her symptomatic relief,
but noticed her entire legs became red and then purple
with weeping serous fluid bullae and vesicles throughout.
She admits to experiencing new joint pains including her
ankles, knees and hands. These pains are worse in the
morning. Patient denies a history of chronic sinusitis, cough,
hemoptysis, dyspnea and gross hematuria. She also denies
a history of asthma or GI complaints including any
abdominal pain or melena. She denies any fevers, chills or
night sweats, and has no risk factors for sexually
transmitted diseases. She has not taken any new
medications before onset of symptoms and denies any
.
family history ofREVIEW
rheumatologic
OFdiseases
SYSTEMS
DIAGNOSTIC WORK UP
PHYSICAL EXAM
A
Vital Signs: T 37.3 HR 93 RR 20 BP 113/53 SpO2 92% RA
General: Alert and Oriented x4. NAD. Patient is tearful.
HEENT: No scleral icterus. No conjunctivitis. No rhinorrhea. Small 25mm erosions (A) on the soft palate, upper gingiva and lower lip
mucosa.
Neck: Supple without lymphadenopathy.
Heart: Regular rate and rhythm, no murmurs or gallops.
Lungs: CTAB, no wheezes or crackles.
Abdomen: Soft, non-distended, non-tender. Normoactive bowel sounds.
BACK: No CVA tenderness. No point tenderness along the spine.
Skin: Discrete, small purpuric macules in palmer aspect of digits. (B)
Many non-blanchable palpable purpuric maculopapular lesions on
both feet extending to the thighs with several weeping bullae and
vesicles with serous fluid. (C, D) Minimal tenderness to palpation.
Bilateral peripheral edema up to knees. Right medial thigh incision with
stiches in place from biopsy.
LABS
B
ESR 34
CRP 14.5
INR 1.2
Lactate 1.5
14.5
9.9
42.6
259
142
4.0
PAST MEDICAL HISTORY
25
1.06
136
Normal Differential
Tox Screen: Negative other than for opiates
UA: Hgb +, Protein 1+, WBC 8/hpf, RBC 3/hpf
Tonsillectomy, right ankle surgery with post-op allergy to
hardware and subsequent removal.
No DM, CAD, Hep B/C, autoimmune disorders including lupus,
rheumatoid arthritis or renal disease
SKIN BIOPSY by punch technique
C
15 pack year smoker. Currently smokes 3 cigarettes/daily. No
EtOH or IV drug use. She lives in WY. Monogamous relationship
with male partner.
FAMILY HISTORY
E
No history of DVTs, cancer, lupus or other
autoimmune/dermatologic disease.
MEDICATIONS AND ALLERGIES
Calcium, vitamin D. Lortab prn and Lasix started one week prior to
presentation. Allergies: Titanium.
99
28
ANA negative, RF 15H, c-ANCA negative
Hep C negative
Cyrofibrinogen negative
A full review of systems was conducted and was positive for
painful mouth sores, otherwise negative.
SOCIAL HISTORY
DISCUSSION
D
F
G
Photomicrograph of
skin biopsy of patient
(F, G) shows
neutrophilic
infiltration into the
dermis and fibrinoid
vasculitis. Immunofluorescence
microscopy (E)
showing deposition
of IgA.
IF slide (E) is similar to patient’s
actual slide and is courtesy of the
Univ. of Utah dept. of Dermatology
teaching slides.
The patient was a previously healthy 63 year-old woman who
presented with clinical stigmata of Henoch-Schönlein Purpura (HSP)
including non-blanchable palpable purpura of her lower extremities,
hematuria and proteinuria, GI involvement (mouth ulcers) and
arthralgias with joint swelling. In addition to physical exam findings
and abnormal UA, patient had elevated inflammatory markers with
skin biopsy showing small vessel vasculitis with IgA and C3 deposition
confirming leukocytoclastic vasculitis (LcV)-HSP.
HSP is a systemic, immune complex–mediated, leukocytoclastic
vasculitis that presents acutely with an incidence in the adult
population of 2-5/100,000 yearly. It is usually associated with a history
of an upper respiratory illness (which this patient did not have) and is
by far predominately a pediatric disease. Patients with HenochSchönlein purpura always present with a purpuric rash, 75% develop
arthritis, 65% have GI involvement (usually abdominal pain) and 50%
develop renal disease. It is usually a self limited disease (90%) treated
with supportive care and oral steroids for joint pain alone. End-stage
renal disease is a fairly uncommon occurrence (5%) although it is more
likely to occur in the adult population.
Other forms of LcV were considered in our differential. Our patient did
not have an elevated ANA or Hep C titer, making lupus or
cryoglobulinemia unlikely. She also did not have signs of systemic
infection or a history of new medications as etiologies for small vessel
vasculitis. Of note however, patient’s recent exposure to pesticides
and fertilizer prompted the question whether this could be a
chemical/environmental hypersensitivity vasculitis. There have been
several studies including a systematic review and two case-control
studies that show an association between organic solvents, silica, and
allergens found in the farming industry with primary vasculitis.
Although this evidence does not show causation of farming chemicals
and IgA vasculitis, such chemicals should be considered when working
patients up for vasculitis.
References
Blanco R, Martinez-Taboada VM, Rodriguez-Valverde V, Garcia-Fuentes M, Gonzalez-Gay MA. Henoch-Schonlein
purpura in adulthood and childhood: two different expressions of the same syndrome. Arthritis Rheum. May
1997;40(5):859-64. .
Chartapisak W, Opastirakul S, Hodson EM, Willis NS, Craig JC. Interventions for preventing and treating kidney
disease in Henoch-Schonlein Purpura (HSP). Cochrane Database Syst Rev. Jul 8 2009;CD005128.
Gedalia A. Henoch-Schonlein purpura. Curr Rheumatol Rep. Jun 2004;6(3):195-202.
Hogan, SL et al. Association of silica exposure with anti-neutrophil cytoplasmic autoantibody small-vessel vasculitis:
a population-based, case-control study. Clin J Am Soc Nephrol. 2007 Mar;2(2):290-9. Epub 2007 Feb 7.
Lane SE, et al. Are environmental factors important in primary systemic vasculitis? A case-control study. Arthritis
Rheum. 2003 Mar;48(3):814-23.
Pillebout E, Thervet E, Hill G, Alberti C, Vanhille P, Nochy D. Henoch-Schonlein Purpura in adults: outcome and
prognostic factors. J Am Soc Nephrol. May 2002;13(5):1271-8.
Reamy BV, et al. Henoch-Schönlein purpura. Am Fam Physician. 2009 Oct 1;80(7):697-704.
Saulsbury FT. Clinical update: Henoch-Schonlein purpura. Lancet. Mar 24 2007;369(9566):976-8.
Szer IS. Henoch-Schonlein purpura. Curr Opin Rheumatol. Jan 1994;6(1):25-31.
William, JR.
Environmentally
Triggered
Small Vessel
AnnalsDr.
of Allergy,
38: 245-251,
Apr.Christian
1977.
Special
thanks
to Dr. Corwin
Edwards,
Dr.Vasculitis.
Myung Lee,
Alalia Berry
and Dr.
Perez for really letting me be a part of Medicine as a student.
When Macrophages Attack!
Madeline Torres BS, Matthew Feurer, MD, Shiven Patel, MD
University of Utah Health Sciences Center, Dept. of Internal Medicine, Division of Hematology, Salt Lake City, Utah
Laboratory Data
Case Presentation
A 45-year-old Mexican female with past medical history of hyperlipidemia,
hypertension, psoriatic arthritis, and drug-induced lupus presented to the
ED with worsening joint pain, fever, chills, night sweats, and blurry vision
over a 5 month period. She also complained of hair loss, fatigue, shortness
of breath, nausea/vomiting, and a recent 15 pound weight loss on review of
systems. Physical exam was notable for tenderness to palpation in both
knees and bilateral DIP joints. She had a tender nodule on her left fourth
DIP and psoriatic type rash on the extensor surfaces of her fingers
bilaterally and elbows. She also had a diffuse erythematous rash covering
arms and legs.
Ferritin
Fibrinogen
D-dimer
Triglycerides
PT
INR
PTT
IgA
IgG
IgM
53612 ng/mL
123 mg/dL
7.8 u/mL
397 mg/dL
28.3 sec
2.7 ratio
35 sec
125 mg/dL
1710 mg/dL
367 mg/dL
Serum IL-2 R
14.8
135
16
3.0
16
0.7
Diagnosis
Hemophagocytic Lymphohistiocytosis
48
9.1 130
5.6
23
2.6
181
0.8
Hep A Ab, IgM Negative
2390 pg/mL
M.TB amp CSF negative
33
25
104
Histoplasma
Y/M CSF
CSF %PMN
CSF
appearance
CSF glucose
CSF RBC
CSF WBC
CSF total
protein
<1:2,
negative
4%
Clear,
colorless
41 mg/dL
2
2
22 mg/dL
Imaging
Diagnostic Workup
After extensive medical evaluation, three diagnostic possibilities were
raised: CNS tuberculosis (TB), Adult-onset Still’s disease, and
Hemophagocytic Lymphohistiocytosis (HLH). Given the concern for TB she
was started on pyrazinamide, rifampin ethambutol and isoniazid.
Immunosupressants that would have been appropriate for treatment of the
other possible diagnosis were held given concern that these medicines
would worsen a tuberculosis infection. Our patient represented two weeks
later with a deteriorating clinical status. It was felt at that time that she most
likely did not have TB and her care was focused on HLH that was likely
triggered from a rheumatologic disorder. She was started on daily
dexamethasone 10mg/m2. Clinical parameters such has joint pain, rash,
fever curve, and splenomegaly were monitored for improvement. Abnormal
laboratory parameters such as platelet count, elevated PT and aPTT, liver
function tests, ferritin, and soluble IL-2 receptor levels were closely
monitored for normalization.
8.3
Discussion
Fig 1 and 2: Hemophagocytic macrophages identified on bone marrow aspiration
Fig 3: Bilateral hand x-ray
demonstrating erosions involving DIPs.
Fig 4: Axial abdominal CT scan with splenomegaly
measuring up to 14.3 cm in diameter
References
1. Henter J-I, Elinder G, O ¨ st Å, and the FHL Study Group of the Histiocyte Society. Diagnostic guidelines
for Hemophagocytic lymphohistiocytosis. Semin Oncol 18:29–33, 1991.
2. Michael B. Jordan, Carl E. Allen, Sheila Weitzman, Alexandra H. Filipovich, Kenneth L. McClain. How I
treat Hemophagocytic lymphohistiocytosis Blood. 2011 October 13; 118(15): 4041–4052. Prepublished
online 2011 August 9. doi: 10.1182/blood-2011-03-278127
3. Henter J-I, Arico M, Egeler M, et al. HLH-94: A treatment protocol for Hemophagocytic
Lymphohistiocytosis. Med Pediatric Oncol 1197;28:342-347
HLH is a syndrome characterized by a constellation of 8 clinical criteria that
include: fever >38.5, splenomegaly, cytopenias, hypertriglyceridemia and/or
hypofibrinogenemia, hemophagocytosis in bone marrow, spleen, lymph
nodes or liver, low or absent NK-cell activity, elevated ferritin and sCD24
levels1. The genetic form of this disease is inherited in an autosomal
recessive manner which most often presents in the pediatric population, but
has been initially diagnosed in adulthood2.
Specific molecular mutations include PRF1, UNC13D, Munc18-2, Rab27a,
STX11, SH2D1A, and BIRC4. Although multiple mutations have been
identified, they share a common phenotype of impaired cytotoxic function of
NK and T cells. The genes may affect granule-dependent lymphocyte
cytotoxicity by impairing trafficking, docking, exocytosis priming or membrane
fusion of cytolytic granules. The genetic defect may also impair the pathway
by loss of functional perforin2. This leads to the impaired elimination of
activated macrophages by NK and T cells. These persistent macrophages not
only phagocytize normal hematopoietic cells but also produce excess
cytokines that lead to tissue damage throughout the body.
More commonly, adult HLH is secondarily acquired after a strong
immunological activation. The most common triggers are infectious (viral,
more so than bacterial or fungal), hematologic malignancy such as leukemia
or lymphoma, and autoimmune disease. In our patient’s case we felt that she
most likely had a macrophage activating syndrome triggered by her known
psoriatic arthritis. Therefore she was treated with steroids in hopes of
controlling both her rheumatologic condition and HLH. Inadequate response
would require standard induction per the HLH-94 protocol with
dexamethasone and etoposide3. Antagonists to IL-1 and IL-6 have been
reported to be helpful in patients with HLH secondary to rheumatologic
disease as well2. Untreated, the average survival of patients with HLH is 2
months. With treatment however, a survival rate of 55% after a mean followup of 3.1 years is reported2.
Patients with HLH can present in many forms: fevers of unknown origin,
hepatitis with acute liver failure, bone marrow failure, multiple skin
manifestations, pulmonary dysfunction, sepsis-like physiology, cardiac and
neurological abnormalities. Our patient obtained an initial diagnosis of CNS
tuberculosis, leading to exacerbation and delay in treatment of her HLH. We
present this case to increase the recognition of HLH. Prompt recognition and
treatment are critical for this otherwise uniformly fatal disease.
T em p la te & pr i nt i ng b y Me d ic a l Gr ap hi c s & P h ot og r a p hy •
U n iv er s it y of Ut a h S c h oo l of M ed i c in e
• 80 1 . 58 7 . 343 5 / b ar b ar a .s te p ha n@ hs c .u ta h. ed u 8 / 20 12
Gluteal Diffuse Large B-cell Lymphoma presenting with Hypercalcemia
Khine Win, MD
University of Utah, Department of Internal Medicine
History of Present Illness
Diagnostic Lab and Imaging
• A 59 year-old man with no significant past medical
history presented with four weeks history of:
 Bilateral leg weakness
 Left buttock pain and swelling
 Constipation
 Mild confusion
 Weight loss
Discussion
•
The large gluteal mass biopsy showed the diffuse large B-cell lymphoma (DLBCL), confirmed with
positive CD20 and CD45 antigens. Fortunately, he has the localized disease on PET CT scan with no
bone marrow involvement, based on the normal bone marrow biopsy and flow cytometry.
•
Severe hypercalcemia at presentation with very low parathyroid hormone level indicated the malignancyassociated hypercalcemia. He was treated with IV fluid hydration, zolendronic acid and calcitonin. His
calcium level was normalized at discharge.
•
Hypercalcemia is not a common presentation for non-Hodgkin lymphoma such as DLBCL. Only up to
13% of incidence was reported previously in the literature. Elevated parathyroid hormone related protein
(PTHrP) and bone metastases are the two most common etiologies responsible for malignancyassociated hypercalcemia. Interestingly, our patient has no bone metastases and low PTHrP level at
presentation.
•
Even though PTHrP is the most common humoral mediator in all malignancies, the ectopic calcitriol was
reported to be a key mediator responsible for the malignancy-associated hypercalcemia in 30-40% of
non-Hodgkin lymphoma. Calcitriol may be secreted by the lymphoma-associated macrophages and
increased the intestinal absorption of calcium, leading to hypercalcemia. Unfortunately, the calcitriol level
was not measured during the admission.
•
The receptor activator of nuclear factor κB (RANK) and its ligand, RANKL, are known to be involved in
the osteoclastic bone resorption, releasing calcium from the bone. RANKL is secreted by the activated
lymphocytes and its expression was upregulated by the PTH, PTHrP, calcitriol and prostaglandins. Other
cytokines such as IL-1, IL-6, tumor necrosis factor-1α (TNF-1α), macrophage inflammatory protein-1
alpha (MIP-1α), MIP-1β were also reported to increase the local osteolysis in diffuse large B-cell
lymphoma cells.
•
Malignancy-associated hypercalcemia can be life-threatening without the urgent intervention.
•
As we are learning more about the molecular pathophysiology of the bone resorption, many new
targeted therapies for the malignancy-associated hypercalcemia, such as monoclonal anti-RANKL
antibody (denosumab) and the decoy receptor (osteoprotegerin), have been identified.
•
Trials to compare the new targeted therapies with the traditional bisphosphonate therapy such as
zolendronate, are underway.
CT pelvis showed the marked asymmetry of the pelvis with soft tissue
attenuation mass on the left buttock, extending medially.
>X< = Patient Result (Ca 14.4, PTH 7)
• Previously treated with prednisone and narcotics
as outpatient without any improvement
Physical Exam
p = Primary Hyperparathyroidism
s = Secondary Hyperparathyroidism
h = Hypoparathyroidism
m = Hypercalcemia of Malignancy
PET CT showed a large hypermetabolic mass in the left pelvis,
along with the hypermetabolic lymph nodes in the peri-aortic
region of the retroperitoneum.
H & E
• A large, firm, fixed mass on the left buttock
 protruding laterally and posteriorly
 mildly tender to palpation
Conclusion
CD20+
• Pertinent findings during the neurological exam
 Alert and oriented
 Decreased sensation to the light touch in both
legs up to the knees
 Normal reflexes
 Normal rectal tone
No distant metastasis.
References
CD45+
1.
2.
3.
4.
5.
6.
7.
Seymour, J.F., Grill, V., Martin, T.J., et al. Hypercalcemia in the blastic phase of chronic myeloid leukemia associated with elevated parathyroid
hormone-related protein. Leukemia, 7, 1672-1675 (1993).
Clines, G.A., Guise, T.A. Hypercalcemia of malignancy and basic research on mechanisms responsible for osteolytic and osteoblatic metastasis
to bone. Endocrine-Related Cancer, 12, 549-583 (2005).
Hewison, M., Kantorovich, V., Liker, H.R., et al. Vitamin D-mediated hypercalcemia in lymphoma: evidence for hormone production by tumoradjacent macrophages. Journal of Bone and Mineral Research, 18, 579-582 (2003).
Matsuhashi, T., Tasaka, T., Uehara, E., et al. Diffuse large B-cell lymphoma presenting with hypercalcemia and multiple osteolysis. Leukemia and
Lymphoma, 45, 397-400 (2004).
Roodman, G.R. Pathogenesis of myeloma bone disease. Leukemia, 23,435-441 (2009).
Kearns, A.E., Khosla, S., Kostenui, P.J. Receptor activator of nuclear factor kappaB ligand and osteoprotegerin regulation of bone remodeling in
health and disease. Endocrine Reviews, 29, 155-192 (2008).
Sargent, J.T., Smith, P.O. Haematological emergencies managing hypercalcemia in adults and children with haematological disorders. British
Journal of Haematology, 149, 465-477 (2010).
All biopsy and radiographic images
Insertwere
Footer
obtained
or Copyright
through
Information
the courtesy of Dr. Corwin Edwards and Intermountain medical center.