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Abstract Case Description Initially neurologyResults was consulted (Research for concern over acute Only) paralysis and vascular surgery was consulted concurrently. Neurology workup was deferred after vascular surgery did doppler exam showing no obvious This case describes a young patient diagnosed previously with a rare This case is a 56 year old female with a PMH significant for plamacytoid pulses. The pt was taken for emergent vascular surgery and thrombectomy metastatic plasmacytoid urothelial cancer who presented with acute paralysis carcinoma who presented to the Huntsman Cancer center with 24 hours of bilaterally and was also found to have compartment syndrome requiring over the preceding 24 hours. The pt was found to have bilateral femoral progressive bilateral lower extremity weakness. This had been evaluated bilateral fasciotomies. The pt regained pulses and was starting to regain thrombosis and taken to emergent vascular surgery for thrombectomy. The pt the day prior in the ER at South Jordan were a MRI of the L spine was done some strength in her lower extremities. She continued to have some also was found to have compartment syndrome requiring fasciotomy. She did and did not show any spinal cord compression or other etiologies of her sxs. numbness and tingling in her legs but this did improve over the next several not have any trauma or other symptoms that would have caused compartment The pt had some improvement at that time and was sent home. The next syndrome. A CTA done in the ER also showed splenic and renal infarcts and a days. The pt developed abdominal bloating and pain which required NG day she noted worsening of her sxs to the point that she could no loner get CT head revealed infarcts in the brain as well. Testing for anticardiolipin tube for a SBO. The pt had increasing leukocytosis up to 30 but this was up and walk. She was taken to the ACC by her husband for further antibody was positive. The pt did have a complication of SBO after her surgery thought to be due to the administration of neulasta in the week prior to requiring bowel resection as well and a long hospitalization. This case evaluation. The pt also noted paresthesia that progressed and started in her presentation. The pts sxs did not improve and repeat CT abdomen was highlights a rare complication of hypercoagulability as a result of underlying toes and was now at her knees. By the time she had arrived at the done showing bowel perforation. She was taken to the OR a second time malignancy. There is very little data available about this patients particular Hunstman she had total numbness in both of her legs up to her knees. She and required bowel resection. The pt improved and was eventually cancer and according to some reviews there are only 75 case reports also noted some constipation, but did not have any problems voiding urine. discharged after a long hospital stay. She will be on indefinite available.1 It may be that these types of cancer are particularly thrombogenic anticoagulation. There is some thought the pt had catastrophic but it is likely that the pts underlying malignancy led to acute arterial occlusion. antiphospholipid syndrome, however follow up labs are needed to diagnose She did recover some ability Objectivesto remove her lower extremities although was still Physical Exam: significant for numbness bilaterally from the knees down to as it is difficult to determine this during acute illness. experiencing some paresthesia at discharge and will be on life long the toes, decreased hip flexor strength bilaterally 2-3/5, unable to dorsiflex anticoagulation going forward. or plantarflex the ankles, absent lower extremity reflexes, Babinski with down going toes, Rectal exam with decreased tone, Ext were cool to the touch and it was difficult to palpate distal pulses Discussion

The pt is a rare presentation of hypercoagulability due to malignancy. Very Laboratory studies were positive for thrombocytopenia with platelets in the high mortality rates of pts with malignancy presenting with acute limb 80s. Alkaline phosphatase was elevated in the 500s. The pt was also ischemia up to 83% have been reported in previous studies.3 Fortunately for hyponatremia with sodium of 132. LFTs were otherwise normal. Other this patient, she was able to have limb salvage as a result of this laboratory evaluation was unrevealing. Further laboratory eval showed complication. The initial decision was made to consult vascular surgery Introduction elevated cardiolipin IgM antibodies elevated at over 150. instead of starting immediate anticoagulation as has been recommended in CTA Abd/Pelvis showing splenic infarcts: treatment of acute limb ischemia. This decision was made because of the pts confusing presentation including rectal tone absence which made a Plasmacytoid urothelial cancer is a rare type of urothelial carcinoma. neurological disorder high on the differential. The migration of sxs from the The prognosis for these patients is almost universally poor as they are toes upwards also led us to believe that the possibility of a neurologic usually diagnosed at a high stage and treatment options are limited.2 syndrome was high. Luckily this potential delay in treatment did not result in Previous studies have noted no survival at one year follow up in a worsening outcomes for the pt. In addition the pt suffered a bowel case series of 17 patients.1 Generally pts are treated with radical perforation as a result of complications from the initial surgery. This was cystectomy and adjuvant chemotherapy, although there has been initially managed as a SBO but we did not consider the rising WBC to be a evidence that neoadjuvant therapy may provide some benefit.2 This pt complication as this was instead difficult to interpret with recent neulasta had been treated with TURBT initially upon noting a bladder mass. administration. Overall this case illustrates that striking presentation that She had then received 1 cycle of ddMVAC prior to her initial acute limb ischemia and compartment syndrome can cause. In addition, presentation. because of the rarity of this particular type of cancer it may indicate a particularly thrombogenic nature to this disease. References

1.Histological variants of urothelial carcinoma: diagnostic, therapeutic and prognostic implications, Journal of Modern Pathology 2009 2.Plasmacytoid variant urothelial bladder cancer: is it time to update the treatment paradigm?, Urologic Oncology 3.Outcome of acute limb ischemia in cancer patients, Vascular Medicine

Acknowledgements: Dr. Ben Solomen Fellow in Hematology-Oncology for his contributions on this case Granulomas Galore Anees Daud, MD PGY3 University of Utah Internal Medicine

Abstract Case Description Discussion

Hypercalcemia is a common finding, but can be associated with many uncommon diseases, such as This is a case of a 57-year-old woman who was ™ Pathogenesis of sarcoidosis: sarcoidosis. Sarcoidosis can be an elusive diagnosis because of the seemingly disconnected brought by her husband to an outside hospital • Accumulation of granulomas (Figure 6) organs that are often involved. While “bilateral hilar lymphadenopathy” is the classic chest because of acute onset of encephalopathy. Based • Inciting event is unknown – generally granulomas form to radiographic finding described in exam questions, the presentation of sarcoidosis can be variable. on history provided by her husband, she was sequester infection, inflammation, and collateral damage Up to 30% of patients present with extra-thoracic manifestations of sarcoidosis, and since no single working in the garden in high heat, and felt • Granulomas are compact, centrally organized collections of diagnostic modality is sufficient, the diagnosis is often missed or delayed. unusually tired. The following day, she slept for macrophages and epithelioid cells encircled by lymphocytes most of the morning, and was confused upon • Presence of CD4+ T cells that interact with antigen-presenting Discussed here is the case of a 57-year-old woman who presented with encephalopathy, and was awaking. She was wandering through the house cells to initiate the formation and maintenance of granulomas Figure 6 found to have hypercalcemia, along with widespread lymphadenopathy and other internal organ without purpose, throwing food on the floor, and ™ Clinical features: involvement. While the initial imaging modalities were concerning for lymphoma, it was not until was not able to prepare for bed or dress herself. • Diagnosis of sarcoidosis is considered based on abnormalities detected on chest x-ray additional laboratory and pathologic evaluation was done that the diagnosis of sarcoidosis was When this behavior continued the following • Constitutional symptoms are common, solidified. Although the initial treatment of hypercalcemia in this patient was relatively morning, her husband became concerned and often mimics lymphoma straightforward, confirming the diagnosis of sarcoidosis was important in directing future care. brought her to their local hospital. Figure 3 • Organ system involvement greatly varies (Figure 7) Management of sarcoidosis can be varied, and treatment is dependent on the level of symptoms At presentation, the patient had normal vital signs. ™ Diagnosis: and organ involvement. Since this patient’s primary presenting finding was symptomatic Initial examination did not comment on any • Remains a diagnosis of exclusion hypercalcemia, treatment was indicated. She responded well to steroids, eventually was abnormal physical exam findings other than her • Compatible clinical and radiographic findings, transitioned to mycophenolate, and continues to do well. altered mental status. A complete blood count along with histologic finding of non-caseating showed normal cell counts and differential. granulomas Chemistry was significant for BUN 35 mg/dL, Cr • Exclusion of other etiologies of non-caseating Introduction 3.4 mg/dL and Ca 14.3 mg/dL. The rest of the granulomas, which includes neoplasms, chemistry, including LFTs, TSH/FT4, and Vitamin infections, particles from occupational exposure, etc. B12 were within normal limits. A 12-lead EKG was • If diagnosis remains elusive, FDG-PET can be used within normal limits, and urinalysis was also to identify organs involved ™ Hypercalcemia is present in anywhere from unremarkable. She was started on intravenous • Angiotensin-converting enzyme elevated in 60% of 0.5% to 4% of patients, depending on the fluids for her hypercalcemia. Imaging initially patients, use is controversial clinical setting (outpatient vs inpatient). It is included a normal chest x-ray. CT Figure 4 • Certain phenotypes of sarcoidosis may not require much more common among patients with chest/abdomen/pelvis (Figure 3 & 4) was biopsy for diagnosis (i.e., Lofgren’s syndrome, which cancer, occurring in 20-30% of these cases. subsequently done, which showed “countless tiny is characterized by erythema nodosum, periarticular Figure 7 ™ Etiology of hypercalcemia can best be largely peripheral pulmonary nodules,” along with inflammation (especially at ankles), and hilar lymphadenopathy) determined by dividing it into PTH-mediated mediastinal and retroperitoneal lymphadenopathy ™ Treatment vs non-PTH mediated causes (Figure 1). and splenomegaly. Additional labs included a low • Most organ involvement responds to steroids ™ Primary hyperparathyroidism and PTH, low 25-OH Vit D, high 1,25-OH Vit D, and a • Decision to treat pulmonary sarcoidosis is based on pulmonary symptoms, deteriorating lung malignancy account for about 90% of cases 2 negative PTHrP. At this point, lymphoma was function, and progressive radiographic changes of hypercalcemia. strongly considered, and she was transferred to the • Decision to treat extra-pulmonary sarcoidosis is based on involvement of eyes, CNS, heart, ™ Mechanisms of malignancy-associated University of Utah for additional care. kidneys, and associated hypercalcemia hypercalcemia • Primary treatment: glucocorticoids • Tumor secretion of PTHrP Bone marrow FNA was performed, but was not • Other treatment regimens • Osteolytic metastases consistent with a hematologic malignancy. PET-CT • Anti-metabolites, which include methotrexate, azathioprine, mycophenolate, leflunomide • Production of 1,25-OH Vit D 2 scan was done, which again confirmed the diffuse • Anti-TNF biologic agents have been used in refractory disease ™ Clinical manifestations (Figure 2): adenopathy and splenomegaly, but also showed ™ My Patient • Usually absent in mild elevations (<12 renal and liver parenchymal involvement (Figure 5). • In retrospect, did have a few months of fatigue and cough mg/dL). She underwent mediastinoscopy for lymph node • Responded well to steroids, but hypercalcemia returned with tapering • Moderate elevations (between 12-14 excisional biopsy. Pathology showed “non- • Started on mycophenolate mg/dL), if acute, may result in relatively necrotizing granulomatous inflammation.” • Continues to do well severe symptoms. Figure 1 Pathology and flow cytometry were again not ™ Treatment consistent with hematologic malignancy. Stains and • Saline hydration: most important therapy cultures were negative for viral, bacterial, fungal, or as patients are often hypovolemic References mycobacterial involvement. Diagnosis of • Calcitonin: helps kidneys excrete sarcoidosis was considered most likely. She was 1. Al-Kofahi, Khalid, Peter Korsten, Christian Ascoli, Shanti Virupannavar, Mehdi Mirsaeidi, Ian Chang, Naim Qaqish, Lesley calcium and prevents calcium resorption Saketkoo, Robert P. Baughman, and Nadera Sweiss. 2016. “Management of Extrapulmonary Sarcoidosis: Challenges and followed up by Rheumatology and was started on Solutions.” Therapeutics and Clinical Risk Management Volume 12 (November): 1623–34. doi:10.2147/TCRM.S74476. from bones prednisone, which did keep her serum calcium low. 2. Horwitz MJ. Hypercalcemia of malignancy: Mechanisms. In: UpToDate, Rosen C.J., et al. (Ed), UpToDate, Waltham, MA. • Bisphosphonates: decreases calcium 3. Iannuzzi, Michael C., Benjamin A. Rybicki, and Alvin S. Teirstein. “Sarcoidosis.” The New England Journal of Medicine 357, no. 21 However, her calcium began to rise when (November 22, 2007): 2153–65. doi:10.1056/NEJMra071714. resorption from bones, which is the most prednisone was tapered. She was subsequently 4. Shane E, Berensen, JR. Treatment of hypercalcemia. In: UpToDate, Rosen C.J., et al. (Ed), UpToDate, Waltham, MA. common reason for hypercalcemia 5. Shane E. Clinical manifestations of hypercalcemia. In: UpToDate, Rosen CJ, et al. (Ed), UpToDate, Waltham, MA. started on mycophenolate. Her calcium has Figure 5 • Glucocorticoids: if the mechanism of 6. Shane E. Diagnostic approach to hypercalcemia. In: UpToDate, Rosen CJ, et al. (Ed), UpToDate, Waltham, MA. remained normal, and her renal function has 7. Tebben, Peter J., Ravinder J. Singh, and Rajiv Kumar. “Vitamin D-Mediated Hypercalcemia: Mechanisms, Diagnosis, and hypercalcemia is increased 1,25-OH Vit Treatment.” Endocrine Reviews 37, no. 5 (October 2016): 521–47. doi:10.1210/er.2016-1070. 2 returned almost to baseline. She is currently doing D production Figure 2 8. Yee, Arthur M. F. “Sarcoidosis: Rheumatology Perspective.” Best Practice & Research. Clinical Rheumatology 30, no. 2 (April well, and continues to follow with Rheumatology. 2016): 334–56. doi:10.1016/j.berh.2016.07.001.

Radiographic Images Courtesy of University of Utah Health Care Seeing Double: A Rare Presentation of Non-Hodgkin Lymphoma Lindsey Fitzgerald, MD University of Utah

Abstract Hospital Course Discussion

Neurolymphomatosis (NL) is a rare clinical entity that can be a manifestation of non-Hodgkin • This case demonstrates the timely identification of malignant nervous system involvement. lymphoma and leukemia. This poster illustrates the case of a 65 year-old female presenting with 9/30 • Pt. admitted to Neurology • Why this patient most likely had NL: symptoms suggestive of stroke. However, upon further evaluation, she is diagnosed with non- • CT and MRI negative for stroke • However, CT-A Head & Neck Hodgkin lymphoma (NHL) and neurologic morbidities become attributable to NL. • Given finding of mass, there is reveals large subcarinal mass concern for leptomeningeal 10/1 • This is later confirmed by CT Learning Objectives: metastasis causing neurologic Chest • Consider neurolymphomatosis in the differential diagnosis of patients with or without NHL signs presenting with neurologic complaints. • Lumbar Puncture is performed • Prompt recognition can prevent neurologic deterioration and prolong survival. – CSF studies, including cytology, are unremarkable Introduction • Transbronchial FNA of 10/4 • Secondary involvement of the nervous system by NHL subcarinal mass is performed can manifest in multiple ways, including: Diagnosis of NL • Pathology shows high-grade • leptomeningeal metastasis B-cell non-Hodgkin’s • parenchymal brain metastasis lymphoma (NHL) • Unfortunately, specimen was • intramedullary spinal metastasis • Pt. transferred to Medicine High Clinical placed in improper fixative and 10/5 • neurolymphomatosis • Neurologic status worsens as Suspicion deteriorated prior to NHL • paraneoplastic disease. she develops additional CN classification • Neurolymphomatosis (NL) is a rare manifestation of palsies and worsening nausea NHL and is defined as the invasion of peripheral nerve • The significance of prompt recognition lies in the potential for rapid treatment to prevent further roots by malignant lymphoma cells, typically involving neurologic morbidity and preserve quality of life. Despite absence of definitive NHL classification, Multi-Modal the cranial or spinal nerve roots. Histopathology • Serum testing for which would determine overall treatment, R-CHOP was initiated as the oncologist recognized that Imaging •Nerve biopsy 10/8 delaying treatment may worsen neurologic morbidity. • The most common presentations include: peripheral Studies paraneoplastic process: •Post-mortem • Voltage-gated Ca2+ neuropathy or radiculopathy, cranial neuropathy, or • high-resolution • Bone painless polyneuropathy.2 MRI Marrow 10/11 channel Ab: Negative •FDG-PET • AchR Antibodies: • In a large retrospective study on NL, the majority of biopsy performed Negative cases were due to B-cell NHL. NL was the initial •ACE: Negative 2 and returns presenting feature in 26% of those cases. Figure 1 – Diagnosis of NL is difficult and • Neurolymphomatosis (NL) requires a combination of clinical negative • The prompt recognition of NL is imperative to providing • PET-CT becomes leading diagnosis for suspicion, multimodal imaging, and a nerve neurologic symptoms rapid treatment to prevent further neurologic biopsy. Typically, conventional MRI and CT shows deterioration and possibly prolong survival. imaging are normal in NL. wide- • Unfortunately, without definitive spread NHL classification, unable to disease in commence treatment lymph system, Case Description bones/skull • Thoracen- HPI Social History tesis • Pelvic lymph node biopsy • A 65 year-old female presents with weakness, • Lives locally with family and works part-time as showed 10/13 performed and again shows double vision, and slurred speech. a Costco sales associate malignant high-grade B-cell NHL. • Symptoms occurred acutely and have • Former smoker with >40 pack-year history effusion progressively worsened • Quit drinking alcohol 10 years ago. • In the ED, the patient also endorsed headache, abdominal pain, nausea, and dry Medications on Admission KEY POINTS heaves. Propranolol, Sertraline, Levothyroxine, Ambien • Given worsening neurologic 10/15 • Keep secondary involvement of the CNS by NHL on the differential diagnosis in patients • She was noted to have multiple cranial nerve status, the patient undergoes presenting with neurologic complaints palsies on exam; thus, the stroke team was PHYSICAL EXAM initial cycle of R-CHOP • Rapid control of the disease can prevent neurologic morbidity and potentially prolong survival activated. Vital Signs: 157/90 | HR 58 | RR 17 | Temp 36°C despite unknown NHL | O2 Saturation: 96% on room air classification Past Medical History References 1. Cirrhosis of the Liver, secondary to chronic Physical examination was notable for: • Pt undergoes XRT to skull base Hepatitis C infection. Complicated by ascites, • inward gaze of the right eye (CN IV palsy) 1. Yu Y, Ren M, Qi X. Pathologically proven peripheral neurolymphomatosis. Neurol India 2016;64:805-7 esophageal varices, chronic thrombocytopenia. • right-sided facial droop (CN VII palsy) 10/17 2. Grisariu S, Avni B, Batchelor TT, van den Bent MJ, Bokstein F, Schiff D, et al. Neurolymphomatosis: An International 2. Hepatitis C, cured s/p Harvoni treatment 2015 • mild slurring of speech (CN IX/X) Primary CNS Lymphoma Collaborative Group report. Blood 2010;115:5005-11 3. Depression with Anxiety, Insomnia • Strength was full and sensation was intact. 3. Baehring JM, Damek D, Martin EC, Betensky RA, Hochberg FH: Neurolymphomatosis. Neuro-oncol 5: 104–115, 2003 4. Hypothyroidism • NIH Stroke Scale of 5 4. Norden A, Hochberg E, Hochberg F. Clinical presentation and diagnosis of secondary central nervous system • Pelvic LN biopsy positive for • Discharged to Home lymphoma. UpToDate. Last updated: April 04, 2016 Family History Myc rearrangement - consistent 10/27 • Neurologic signs noted to have 5. Shree R, Goyal MK, Modi M, et al. The diagnostic dilemma of neurolymphomatosis. J Clin Neurol. 2016 Jul; 12(3): 274-81 Noncontributory with Burkitt Lymphoma 11/9 “improved slightly” 6. Mead GM, Kennedy P, Smith JL, et al. Involvement of the central nervous system by non-Hodgkin's lymphoma in adults. A review of 36 cases. Q J Med. 1986;60(231):699

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7KDQN\RXWRWKH0LGYDOH&OLQLFIRUDOORZLQJXVWROHDUQKRZWRLPSOHPHQWOLIHVW\OHPHGLFLQHLQWKHFOLQLFDOVHWWLQJ NAILING THE DIAGNOSIS: A CASE OF PLANTAR PAIN, PLANTAR KERATODERMA, & TOENAIL DYSTROPHY www.pachyonychia.org

Laura J. Gardner, University of Utah School of Medicine | C. David Hansen MD, Department of Dermatology, University of Utah

a) COMMON SYMPTOMS b) SYMPTOMS NOT OF PC: PART OF PC: II. Case Description III. Diagnosis & Management Alopecia Oral leukokeratosis . Hoarseness Deafness The physician suspects genetic etiology and orders .. Natal teeth HISTORY OF PRESENT ILLNESS . Diabetes PAST MEDICAL HISTORY genetic testing for inherited skin diseases. The results Follicular Hyperkeratosis Mental retardation - Broken wrist at age 6 after jumping off of a swing, no show a mutation in the KRT16 gene, and the patient is . Cysts JL is a 31yo woman presenting to internal medicine complications correctly diagnosed with the PC-K16 subtype of PC. . Bone deformities clinic for evaluation of “foot pain” and to establish - Persistent plantar pain and calluses since age 4 Palmar keratoderma Fingernail dystrophy Cataracts primary care. Around the age of 4 JL first developed - No other medical history The patient is referred to the Pachyonychia Congenita Menstrual the formation of thick plantar calluses, along with Project, a non-profit that provides genetic testing and irregularities plantar pain, which she recalls prevented her from PAST SURGICAL HISTORY Plantar pain supports medical research for PC. It also serves as a hub Plantar keratoderma Tooth loss playing tag and jump-rope at recess as a child. At - Has never had surgery for the PC community worldwide. Follow-up care began Toenail dystrophy the age of 6 JL first noticed thickening of her to address appropriate pain management. Currently, no toenails, which was refractive to anti-fungal Figure 1. a) Symptoms of PC. b) Symptoms previously believed to be associated with PC. cure exists for PC. therapy prescribed by her pediatrician. As the MEDICATIONS & ALLERGIES plantar pain persisted into her teenage years, she - 800mg Ibuprofen daily for the past 2 weeks for foot pain I. Introduction was referred to a podiatrist who told her the foot - 200mg Acetaminophen for foot pain PRN, says ibuprofen pain was due to “growing”, and fitted her for works better IV. Discussion orthotic inserts for her shoes. - 180mg Fexofenadine for hay fever as needed in the spring Pachyonychia congenita (PC) is a rare inherited skin diseasecausedbyamutationinoneoffivekeratin SOCIAL HISTORY In patients presenting with the The plantar pain is so intense that JL often crawls triad of plantar pain, plantar genes. The phenotypic presentation varies around her home to avoid standing on her feet. She - Works at a call center, enjoys her work when she doesn’t depending on the specific keratin gene affected, keratoderma, and toenail describesthispainasaching.However,shealso have to be on her feet, considers coworkers to be friends 82.9% of all - Never tried illicit drugs, drinks 1-2 glasses of wine per week dystrophy, genetic testing for PC patients thus, the nomenclature of the disease has recently occasionally feels a burning sensation in her feet been re-classified based on the gene involved. - Denies depression, feels socially isolated due to foot pain PC is recommended as these are while she is seated with her feet flat on the ground. the three most common symptoms Historical Classification Plantar Pain JL works at a call center and was promoted to team FAMILY HISTORY in PC across all mutation types. Type I “Jadassohn–Lewandowsky syndrome” leader 3 weeks ago, which requires her to be on Type II "Jackson–Lawler syndrome " - Mother 62yo, alive. Hay fever in spring, otherwise healthy Figure 3. The presence of these 3 her feet more often than she is used to. Since then - Father 63yo, alive. Diagnosed with Type 2 DM at age 61yo symptoms indicates a high likelihood Fingernail dystrophy is not that PC is present. New Classification the pain has been almost unbearable and she is - Brother 34yo, alive, healthy PC-K6a always present in PC, but most PC-K6b considering asking to be moved back to her - Family members lack plantar callus/pain, toenail dystrophy medical texts erroneously list twenty-nail dystrophy as PC-K6c previous job, where she could sit in a cubicle during a diagnostic feature of PC. PC-K16 the day and did not have to walk around as much. PC-K17 REVIEW OF SYSTEMS She has been taking 800mg ibuprofen almost every Table 1. A new classification scheme was accepted in 2012 - Negative for dyspnea, palpitations Plantar pain is a complex symptom of PC that can based on analysis of genomic data in 254 patients with PC day for the past 2 weeks, which only provides mild severely impact quality of life. The pain reported by PC atientimages. . pain relief. She denies thick fingernails, oral patients tends to be out of proportion to the Patients.. with PC are often misdiagnosed or fail to leukokeratosis, hoarseness, hyperhidrosis, follicular PHYSICAL EXAM appearance and extent of the plantar keratoderma and receive a diagnosis for many years, with most hyperkeratosis, cysts, and the presence of natal patients being diagnosed in adulthood. Because the Skin: must be managed appropriately. Many patients require teeth. - Yellow plantar calluses in a pressure distribution. Toenails of plantar. . pain associated with this disease can chronic pain medication and/or the use of durable . . digits 1-5 show increased curvature with subungual thickening & medical equipment such as a wheelchair. severely. impair functionality in daily activities, dystrophy of nail plate. No plantar or web space scale. making the correct diagnosis is important. - No palmar keratoderma or callus. Fingernails normal. Musculoskeletal: MisdiagnosisofPCcanleadtounnecessary - Both feet are tender to palpation across the plantar surfaces IV. References treatments, lack of access to durable medical - Range of motion, strength, reflexes, & sensation normal equipment, and inappropriate pain management. DIFFERENTIAL DIAGNOSIS Eliason, M. J., MD, Leachman, S. A., MD, PhD, Feng, B., PhD, Schwartz, M. E., AA, & Hansen, DIFFERENTIAL DIAGNOSIS C. D., MD. (2012). A review of the clinical phenotype of 254 patients with genetically confirmed pachyonychia congenita. Journal of the American Academy of Dermatology. Pachyonychia congenita, palmoplantar keratoderma, Clouston a) b) syndrome, Olmsted syndrome, Carvajal syndrome, 20-nail Fu, T., Leachman, S. A., Wilson, N. J., Smith, F. J., Schwartz, M. E., & Tang, J. Y. (2011). Laura J. Gardner Genotype–Phenotype Correlations among Pachyonychia Congenita Patients with K16 dystrophy, psoriasis, lichen planus, onychomycosis Mutations. Journal of Investigative Dermatology, 131(5), 1025-1028. UniversityUnive of Utah School of Medicine Figure 2. a) Plantar keratoderma in a pressure distribution bilaterally. b) Toenail [email protected] dystrophy. Pachyonychia Congenita Project. (n.d.). Retrieved January 13, 2017, from http://www.pachyonychia.org/ Thank you to Pachyonychia Congenita Project for p for the providing Project Congenita Pachyonychia to you Thank Disseminated Mucormycosis (Lichtheimia corymbifera) in a Patient with Relapsed, Refractory Acute Myeloid Leukemia David Gaston, M.D. Ph.D.1, Jessica Donigan, M.D.2, and Robert Odrobina M.D.3 Departments of 1Internal Medicine, 2Dermatology, and 3Infectious Diseases; The University of Utah, Salt Lake City, UT

Abstract The opportunistic fungus Lichtheimia corymbifera is a zygomycete in the family Mucoraceae. Infection of patients with a hematologic A B malignancy carries significant mortality and disseminated infection is nearly universally fatal. Herein we present the case of a woman in her 60’s with relapsed, refractory acute myeloid leukemia who was found to have disseminated Lichtheimia corymbifera after presenting with multifocal cerebral infarctions. Her cerebral infarctions were deemed secondary to vessel invasion and thrombosis after skin biopsy demonstrated angio-invasive fungi, and other workup was non-diagnostic. Combination antifungal therapy was attempted but the patient chose hospice care and died at home. Her case exemplifies terminal infectious complications in patients with hematologic malignancies as well as the importance of maintaining a broad differential diagnosis. Additionally, her case highlights the need for continuing research into Mucoraceae pathogenesis and therapy given the poor prognosis of this condition and limited efficacious antifungal therapies. Patient History Clinical Course Figure 3: Dermatopathology indicating Angio-Invasive Fungi Consistent with a Disseminated Fungal Infection. Medical, Family, and Social History: ABC Punch biopsies obtained from mid-back as demonstrated in Figure 2. A: Periodic acid-Schiff stain, 100x, demonstrating fungi in subcutaneous tissue. Broad, acutely branching organisms seen in the vessels, dermis, and subcutis. Fungi - 60+ year old woman; acute myeloid leukemia (AML) and hypothyroidism appear bright purple. B: Hematoxylin and eosin stain, 200x, demonstrating small and medium vessel fungal angio- invasion and thrombosis. Panel highlights two thrombosed vessels in cross-section; one medium-sized vessel in - Mother with lymphoma; married with children, no occupational exposures longitudinal section and a small vessel in transverse section. Fungi appear purple. • Disseminated fungal infection suspected, antifungal regimen changed to AML History and Complications 2016: 3% MB; Tetraploid, 8q22 Voriconazole and liposomal Amphotericin B 2006: 23% MB 2011: 35% MB (RUNX1T1) • Fungal identification: Lichtheimia corymbifera, zygomycete in the family Mucoraceae. Identification by culture, DNA sequencing, and phenotype.

D Figure 1: Admission Radiography. A-C: T2 FLAIR MRI. • Presentation deemed secondary to Lichtheimia corymbifera Slices ascend. Multifocal infarct involving left parietal lobe, dissemination (pulmonary, cutaneous, and cerebral) 2007: 7+3, 22% MB D14 2013: GvHD, GI high posterior right parietal/frontal, right subcortical 2016: HiDAC x4 cycles posterior parietal lobe, and anterior left high frontal lobe. • Patient chose hospice care, denied autopsy, and died at home. 2011: Vidaza x14 cycles DAH x3 Neuroradiology image review without consistent arterial distribution. D: Contrasted chest CT. Right middle lobe focal consolidation and diffuse bilateral ‘gray’ lung Abbreviations: 7+3- cytarabine and idarubicin; D14- day 14; attenuation; findings deemed consistent with infectious Discussion DAH- diffuse alveolar hemorrhage; GvHD-graftversushost 2012: 9/10 MUD allo HSCT process or diffuse intrapulmonary hemorrhage. disease; GI- gastointestinal; HiDAC- high dose cytarabine; • Significant baseline immunosuppression, repeat DAH requiring etanercept LFTs-liverfunctiontests;MB-myeloblast;MUD allo HSCT- mixed unrelated donor allo-hematopoietic stem cell transplant • Initially admitted to Neurologic Intensive Care Unit for stroke, with high dose prednisone tapers, and subtherapeutic posaconazole (due to MRI concerning for central embolic source (Figure 1 A-C) missed doses per family) likely lead to disseminated Lichtheimia corymbifera. 2016: DAH admission one month prior to presented admission with: • Neuroradiology review of MRI without clear arterial distribution • Multifocal infarction suspected secondary to fungal dissemination and - Etanercept x4 doses • Transthoracic echocardiogram negative, transesophageal with invasion/thrombosis of cerebral vasculature (Figure 1 A-C). Consolidation on chest CT may be pulmonary hemorrhage with infarction (Figure 1D). Lesion - Prednisone 100mg BID at discharge; tapered to 60mg BID on readmission possible small vegitation on aortic valve vs papillary fibroelastoma on back is due to vessel invasion and cutaneous infarction (Figures 2, 3). - Voriconazole transitioned to Posaconazole due to elevated LFTs • Mild hypoxia persisted; chest CT with focal consolidation and diffuse infiltrates concerning for infection vs repeat DAH (Figure 1 D) •Inalargeretrospective study of zygomycosis, Lichthemia sp. infected 5% • Vancomycin and Cefepime (changed to Meropenem with ESBL of patients, and intracerebral zygomycosis carried a 98% mortality rate 1 Presentation Klebsiella pneumoniae positive blood culture) for neutropenic fever • Lichthemia corymbifera is a more virulent member of the Lichtheimiaceae 2 Notable admission medications: Acyclovir 800mg BID • Posaconazole continued for antifungal coverage • Vessel invasion and thrombosis are commonly seen with infection; vessel Bactrim DS M/W/F Penicillin V 500 QD • Transferred to Huntsman Cancer Center for continuing care invasion is required for dissemination. 3 Posaconazole 300mg QD Prednisone 60 BID • Lesion noted on back (Figure 2), subsequently biopsied (Figure 3) • Combination antifungal therapy is indicated for disseminated infection. 4 Initial Evaluation • Lichtheimia corymbifera is moderately susceptible to multiple antifungals, A B - One day of confusion (on “space ship”) and right arm/leg weakness but resistant strains have been reported. 5 - Vital signs: T 38.7, HR 91, BP 128/66, RR 18, SpO2 88% (room air) • Additional research is needed into pathogenesis and effective therapies for - ROS obscured by encephalopathy mucormycoses given the dismal prognosis of infection with these organisms. - Posaconazole level: 0.9 ug/mL (2.9 ug/mL two weeks prior) - WBC 2.17 k/uL (ANC 700), Hgb 8.6 mg/dL, Platelet 18 k/uL References

1. Roden, M. M., Zaoutis, T. E., Buchanan, W. L., Knudsen, T. A., Sarkisova, T. A., Schaufele, R. L., et al. (2005). Epidemiology and outcome of zygomycosis: a review of 929 - ALT 103, all other labs grossly within normal limits reported cases. Clinical infectious diseases : an official publication of the Infectious Diseases Society of America, 41(5), 634–653. 2. Schwartze, V. U., Hoffmann, K., Nyilasi, I., Papp, T., Vágvölgyi, C., de Hoog, S., et al. (2012). Lichtheimia species exhibit differences in virulence potential. PLoS One, 7(7), -Exam: e40908. doi:10.1371/journal.pone.0040908 - Moon facies; No murmur; Diffuse bilateral crackles 3. Spellberg, B., Edwards, J., & Ibrahim, A. (2005). Novel perspectives on mucormycosis: pathophysiology, presentation, and management. Clinical microbiology reviews, 18(3), 556–569. doi:10.1128/CMR.18.3.556-569.2005 - RUE and RLE weakness, positive R pronator drift, Figure 2: Dermatologic Findings. A: A lesion measuring roughly 5 x 3 cm was found on the back of 4. Cornely, O. A., Arikan-Akdagli, S., Dannaoui, E., Groll, A. H., Lagrou, K., Chakrabarti, A., et al. (2014, April). ESCMID and ECMM joint clinical guidelines for the diagnosis and management of mucormycosis 2013. Clinical microbiology and infection : the official publication of the European Society of Clinical Microbiology and Infectious Diseases. decreased sensation to light touch and vibration on R the patient. The lesion was not raised nor painful to palpation. B: Enlargement of lesion demarcated in doi:10.1111/1469-0691.12371 panel A. Dusky purple center with blanched rim surrounded by erythema. Dotted circles demarcate 5. Espinel-Ingroff, A., Chakrabarti, A., Chowdhary, A., Cordoba, S., Dannaoui, E., Dufresne, P., et al. (2015). Multicenter evaluation of MIC distributions for epidemiologic cutoff - Oriented x2, somnolent, perseverating about “space ships” value definition to detect amphotericin B, posaconazole, and itraconazole resistance among the most clinically relevant species of Mucorales. Antimicrobial agents and areas sampled by punch biopsy for tissue culture and dermatopathology (Figure 3). chemotherapy, 59(3), 1745–1750. doi:10.1128/AAC.04435-14 Open Sesame! Uncovering a rare cause of acute eosinophilic pneumonia Casey Gradick, MD, MPH; Aidin Iravani, MD Department of Internal Medicine, University of Utah, Salt Lake City, UT

Abstract Case Description HOSPITAL COURSE: INITIAL PRESENTATION: • Started on empiric Ceftriaxone and Azithromycin for CAP • Objective: To report an unusual case of acute eosinophilic pneumonia in a female patient receiving IM Progesterone-in-oil (P-in-oil) •33 year-old woman presented with two weeks of dry cough, fevers, chills. • Oxygen need increased to 6-8L, dyspnea worsened supplementation after IVF and embryo transfer Then 3 days of worsening dyspnea, fevers up to 104.5, pleuritic chest pain and intermittent hemoptysis. Recently returned from trip to Wisconsin, and • Bronchoscopy for cell count and to exclude infectious causes • Interventions: Corticosteroid therapy, replacement of IM Progesterone was complaining of left calf cramping. • Respiratory virus panel, PJP, mycoplasma pneumoniae, chlamydia with intravaginal preparation •PMH: Exercise-induced asthma and infertility pneumoniae, HSV, CMV, malignancy, ANCA, Legionella, Hantavirus, • Main outcome measures: Clinical symptom improvement, resolution of fungal and bacterial cultures: all negative imaging findings •MEDS: Asthma well controlled with PRN Albuterol, started treatment a few weeks prior with Progesterone 100 mg IM qday as part of infertility • Differential on cell count on BAL: 50% macrophages, >25% • Results: Treatment with corticosteroids led to improvement in dyspnea, treatment eosinophils, 15% neutrophils eosinophil count, and radiographic findings. Symptoms did not recur •SH: Distant history of smoking, 1 PPD for 6 months, quit nine years ago • CBC repeated and eosinophils 12.7% (normal 0.4-6.7%) with an after switching to intravaginal preparation, thus sesame oil was likely absolute count of 2.11 (nl 0-0.5) cause. Physical exam: • Started on Prednisone 60 mg daily for AEP and within 48 hours was • Conclusion: Despite the rarity of severe allergic reactions to IM •Vitals: 38.8㼻C (101.8㼻F), pulse 105, respiratory rate 22, BP 119/75. O2 able to wean off oxygen, discharged on two month taper progesterone, clinicians treatingObjectives patients undergoing IVF need to be saturation >90% on 2L NC. aware of this potentially lethal adverse effect and consider using • Pulmonary follow-up clinic two months later: dyspnea completely alternative routes or preparations of progesterone administration. •Exam: In mild respiratory distress. Diffuse rales, with no wheezing. resolved, off Prednisone Tachycardia, cyanosis, no clubbing, and dry cough throughout exam. No swelling or tenderness in lower extremities • Switched to vaginal preparation of Progesterone and scheduled to have allergy testing for sesame oil. Labs: Introduction WBC 21.8 with 87% neutrophils, 7.3% lymphocytes, and 0.1% eosinophils, Discussion negative B-hCG, normal CMP, lactate of 1.1, and D-dimer of 2.43 (elevated)

• Acute eosinophilic pneumonia (AEP) is a rare syndrome characterized Imaging: • A rare, but potentially life-threatening complication of IM progesterone is drug-induced AEP by acute onset of fever, cough, and dyspnea •CXR: diffuse bilateral parenchymal opacities with interstitial edema • Diagnosis: • Systemic hypersensitivity reactions in case reports attributed to sesame •CTA to exclude PE: Diffuse peripheral ground glass and alveolar opacities oil as an excipient in IM progesterone, as symptoms did not recur after • Peripheral/pulmonary eosinophilia, >25% in bronchoalveolar bilaterally, with interstitial edema. switching to peanut oil lavage (BAL) • Symptom onset typically 3-5 weeks after initiating daily IM progesterone • Peripheral alveolar and ground glass opacities on CT scan, or exposure to a drug known to cause AEP • Drug-induced AEP typically has lower eosinophil % in BAL (14-42%) compared to idiopathic AEP or chronic eosinophilic pneumonia • Differential diagnosis: Vasculitis (Churg-Strauss syndrome), atypical pneumonia (fungal, viral or parasitic infections), drug induced • Common to present initially with neutrophil predominance on CBC, with pneumonitis peripheral eosinophils rising later in the course • More couples utilizing assisted reproductive technology (ART) • Since steroids are mainstay of treatment, testing for atypical pulmonary infection is important • Infertility affects 15% of couples worldwide and 2.1 million in the United States. In vitro fertilization (IVF) is the most common type of ART, accounting for >95% of all procedures References • Progesterone to support luteal improves outcomes of IVF, now 1.Bouckaert Y, Robert F, Englert Y, De Backer D, De Vuyst P, Delbaere A. Acute eosinophilic pneumonia standard of care associated with intramuscular administration of progesterone as luteal phase support after IVF: case report. Hum Reprod 2004;19:1806–1810. • Most common side effect erythema and induration at injection site 2. Richards CJ, Hsu D, Weinstock TG, Clardy P. Eosinophils. An Unexpected Delivery. Ann Am Thorac Soci. 2013;19(4): 390-2 • Case reports have described acute onset of hypoxemic respiratory 3.Khan AM, Jariwala S, Lieman HJ, Klapper P. Acute eosinophilic pneumonia with intramuscular progesterone failure from drug-induced AEP after P-in-oil injection after in vitro fertilization. Fertil Steril 2008;90:1200.e3–6. 4.Phy JL, Weiss WT, Weiler CR, Damario MA. Hypersensitivity to progesterone-in-oil after in vitro fertilization • All presented with tachycardia, hypoxia, bilateral rales, bilateral diffuse and embryo transfer. Fertil Steril 2003;80:1272–1275. 5. Veysman B, Vlahos I, Oshva L. Pneumonitis and eosinophilia after in vitro fertilization treatment. Ann alveolar infiltrates, and prominent leukocytosis with eosinophilia Emerg Med 2006;47:472–475. 6. Aboulghar M. Luteal support in reproduction: when, what and how? Curr Opin Obstet Gynecol 2009;21:279–284. Acute esophageal necrosis (AEN) is a rare form of esophageal History: The patient is a 51-year-old male presenting with a five- Hospital Course: The patient was found to have an initial injury characterized by circumferential black mucosa. day history of nausea associated with non-bloody vomiting and lactate of 13.9, anion gap of 33, and no osmolar gap. He was Individuals with AEN predominantly present with symptoms absent oral intake, a one-day history of non-bloody diarrhea, and appropriately resuscitated in the Emergency Department and consistent with upper GI bleeding. profound generalized weakness. He denied caustic ingestion. was transferred to the ICU for further care. There, he had coffee-ground emesis and hematemesis and underwent urgent In the following case, a 51-year-old gentleman who initially Physical Examination: Initial blood pressure was unable to be EGD. Findings were consistent with AEN (Figure 1). presented with evidence of shock, was noted to have coffee- obtained by forearm cuff; arterial line was placed with systolic ground emesis and hematemesis while in the hospital. He blood pressure in the 60s. Normal heart rate with thready radial Chest CT was obtained to evaluate for esophageal perforation; underwent urgent on esophagogastroduodenoscopy (EGD) for pulses. Hypothermic to 33.8oC. Mottled in appearance. Alert and as no evidence of perforation was seen, there was no role for evaluation and was discovered to have the pathognomonic oriented. Dry mucous membranes. Mild RUQ abdominal pain. surgical intervention at that time. He was stabilized with fluids findings of circumferential mucosal injury seen in AEN. Moved all extremities, but was unable to lift legs against gravity. and IV proton-pump inhibitors, with improvement of his lactate Objectives to 1.7. After transfer to the general medicine floor, he left Through the following case, the presentation, work-up, A B treatment, and complications of AEN are discussed. Against Medical Advice and was subsequently lost to follow-up.

• Pathogenesis: Thought to be due to a combination of 1 • First described in 1990 by Goldenberg et al . ischemia, gastric outlet obstruction, and decreased mucosal • Approximately 100 cases reported in the literature2. repair mechanisms. Coinfection with viral agents has been seen in immunocompromised patients3. • Incidence between 0.01% and 0.28%3, however this likely under represents true incidence of AEN due to the transient • Treatment: Generally supportive with fluid resuscitation, IV nature of the disease. C D proton-pump inhibitors and the correction of any underlying pathology3. Surgical intervention is required in cases of • 4:1 male-to-female ratio; mean age of presentation 67 years2. esophageal perforation, and includes esophagectomy/VATS4. • Associated with multiple systemic disease states, including • Complications: Mortality is as high as 32%, with death hemodynamic compromise, gastric outlet obstruction, acute predominantly secondary to the underlying systemic disease. alcohol abuse, diabetes, malnourishment, and malignancy3. AEN specific mortality is approximately 6%. Perforation is • Commonly presents with signs of upper GI bleeding, relatively rare (6% of cases), but increases mortality particularly with melena or hematemesis3. secondary to AEN to approximately 20%2. • Diagnosis is made by EGD, with circumferential necrotic • Conclusions: The EGD findings of circumferential necrosis mucosa extending proximally from a sharp demarcation at the E F involving the distal portion of the esophagus and a sharp gastroesophageal junction (GEJ). This almost always delineation at the GEJ is pathognomonic for AEN. Careful encompasses the the bottom 1/3rd of the esophagus. The consideration should be made to evaluate for esophageal distal 2/3rds of the esophagus is involved 36% of the time. perforation, a life-threatening complication of this disease. The entire esophagus is involved 52% of the time3. • Biopsy is not necessary, but can confirm diagnosis. Biopsy shows necrotic mucosa without viable epithelium, often with 1. Goldenberg S. P., Wain S. L., Marignani P. Acute necrotizing esophagitis. Gastroenterology. 1990;98(2):493–496. submucosal involvement. Necrosis can occasionally extend 2. Inayat F, Hurairah A, Virk HUH. Acute Esophageal Necrosis: An Update. North American Journal into muscularis propria3. of Medical Sciences. 2016;8(7):320-322. 3. Gurvits G. E., Shapsis A., Lau N., Gualtieri N., Robilotti J. G. Acute esophageal necrosis: a rare • Differential diagnosis includes caustic ingestion, malignant Figure 1. Necrotic tissue seen coating the esophagus, sharply demarcated at the syndrome. Journal of Gastroenterology. 2007;42(1):29–38. gastroesophageal junction (arrows A, B) and extending proximally to 20cm distal 3 4. Groenveld RL, Bijlsma A, Steenvoorde P, Ozdemir A. A black perforated esophagus treated with melanoma, melanosis, and pseudomelanosis . to incisors (C-E), proximal to which the esophagus is pale and patulous (F). surgery: Report of a case. World Journal of Gastrointestinal Surgery. 2013;5(6):199-201. Wells’ Syndrome ProceededCity,CitCity ybby, yUtah UtU Leukocytoclasticaah h Vasculitis: A Discussion with NeNeww IInsightsnsights iintonto AAnalogousnalogous PathopPathophysiologyhysiology

a S.S BBrandonrar nddono Nickle, DODDO,O, b RoRoxanneoxanne RaRajaii,jajaiii, MSMMS,S DO, c ZaZZacharychcharry HoHHopkins,opkpkinins,s, BBS,S,S, d NNelsonele ssoon ChCCharlie,haarlil e,e, MMDD City,CiCityty, UtahUtUtahah a BrBBrowardowwaard HealthHeealthh MedicalMede icicall CCenter,enenteter,r, FFt.tt. Lauderdale,Laua ded rdr ala e,e FLFL (PGY-IV)(P(PGGYY-IVV) b BeBBeaumonteaumom ntt HHospital,ospitaal, FFarmingtonarmiminggtoon HiHHills,lls,s MMII (P(PGY-II)PGYY-II) c SScSchoolchoool ooff MMeMedicine,dicine, UnUniversityivvere sisityy ooff UtUtah,tahh, SaSSaltltt LLakeakke CiCity,tyy, UTUT ((MSIII)MSSIIIIII)) d LauderdaleLaL udu erdad le AcademicAcaadeemiic Dermatology,Dermmattoology, DermatologistDeermatoloogistt andandd AttendingAttene dingn ProfessorProofesss oror aatt BrowardBrB owowarrd MedicalMMediicaal Center,Center, Ft.Ftt. Lauderdale,LaLaudere daalel , FLFL Abstract Case Presentation/Figures • 55 year-old African American female presented with a two-month history of Wells’ syndrome is an uncommon inflammatory purpuric vesicular eruption of the lower extremities that was clinically and dermatosis, with very few cases reported pathologically consistent with LCV, thought to be secondary to worldwide. Its etiology is unknown but it is hydrochlorothiazide therapy (figure 1). thought to be an abnormal eosinophilic response • Switching the Hydrochlorothiazide to Lisinopril led to partial resolution of to a number of causative agents. Its cutaneous symptoms. manifestations vary in morphology and severity, • At her three month follow-up she returned with more widespread eruption Figure 2: but the disease often follows a relapsing remitting consisting of scattered urticarial papules, nodules, and plaques involving the Multiple Erythematous course. This case report presents a patient with trunk, upper and lower extremities as well as an occasional vesicle and urticarial plaques on the Wells’ syndrome proceeding leukocytoclastic bullae present in a similar distribution (figure 2). chest, back, and upper vasculitis (LCV). • Clinical differential included bullous pemphigoid, arthropod assault, bullous extremities. sweet’s syndrome and Wells syndrome with or without coexisting LCV. • Two 4.0mm punch biopsies were performed. One was a perilesional biopsy Introduction directly adjacent to the bullae which was sent for direct immunofluorescence (DIF). The biopsy revealed an overwhelming number of eosinophils in the superficial and deep dermis (figure 3). Biopsy suggested bullous pemphigoid Wells’ syndrome, also referred to as eosinophilic vs Wells’ syndrome, but negative DIF together with clinical findings suggested cellulitis, is an uncommon inflammatory Wells’ syndrome. dermatosis. Fewer than 200 cases have been Figure 1: Left and Top Right: Patient with 2-3 cm non- reported worldwide. blanchable purpuric vesicular plaques on left lower Figure 3: extremity with background petechial macules and Superficial and deep It often presents with a prodromal burning or post-inflammatory hypopigmentation on bilateral lower extremities. Clinically and histologically infiltrate with pruritic sensation followed by a widespread consistent with LCV. Bottom Right: The biopsy on prominently eruption consisting of urticarial erythematous the left lateral leg revealed epidermal necrosis with lymphocytes and an papules, plaques, and bullae of the trunk, upper neutrophils and neutrophilic debris in the epidermis. In the underlying dermis, neutrophils abundant amount of and lower extremities. Recurrences are common. and eosinophils were present along with significant eosinophils. leukocytoclastic debris, vessel fibrin, and thrombi. Although the exact pathophysiology of the DIF was negative and there was no evidence of the presence of spirochetes, fungi, intravascular disease is unknown, many associations have bacteria, or acid-fast organisms. This pattern was been reported. consistent with LCV. Here we present a patient with a one-year history Discussion of LCV who subsequently developed Wells’ syndrome, an association not yet reported in the • Peripheral eosinophilia during the acute phase and dermal eosinophilic infiltration differentiate Wells’ syndrome from infectious cellulitis. Dermal edema literature. Whether this case depicts a causal and diffuse dermal infiltration of eosinophils is seen. A characteristic infiltrate of phagocytic histiocytes and flame figures are also seen on histopathology. association or reflects a shared pathophysiology In older phases of disease, fewer eosinophils, histiocytes, giant cells, and flame figures are present. is unknown. However, it can potentially lead to • This case may offer potential insight into the pathophysiology of Wells’ Syndrome. Like other diseases associated with Well’s syndrome, LCV is a form of further research and awareness of Wells’ vasculitis characterized by inappropriate infiltration of vessels by inflammatory cells such as neutrophils. This process is thought to be due to a syndrome in an effort to better understand the dysregulation in the complex process of inflammatory cell recruitment and homing to specific tissues. In the case of LCV, one of the most common findings pathophysiology, diagnosis, and treatment options is that of immune complex deposition leading to the inappropriate recruitment of neutrophils to a tissue. Two studies have suggested immune signal for this uncommon condition. dysregulation, IL-5 specifically, to be the underlying mechanism in Wells’ syndrome. • Thus, while the exact underlying mechanisms of both LCV and Well’s syndrome are not well understood, it is plausible that the processes underlying the dysregulation involved in neutrophil recruitment in LCV could also trigger in some patient’s alterations in IL-5 or other homing signals, leading to inappropriate recruitment of eosinophils to the skin. It is our hope that this presented case may offer direction and insight into future studies aimed at better understanding the pathophysiology involved in Wells’ syndrome. • The mainstay of treatment for Wells’ syndrome is steroids with a reported 92% success rate. The Differential Diagnosis of a Neck Mass: Infectious, Inflammatory, or Both? John H. Murray, MD Dept. of Internal Medicine, University of Utah, Salt Lake City, UT

Introduction Imaging/Pathology DiagnosisResults Autoimmune disease is commonly mistaken for infection, and both Necrotizing histiocytic lymphadenitis (Kikuchi-Fujimoto processes can co-exist. The following case is an example of an disease, NHL) vs lupus lymphadenitis of the retropharyngeal uncommon autoimmune phenomenon that presented in the setting of concurrent infection. space. History of Present Illness Conclusions A 21-year old Native-American female with a PMH of lupus NHL, although rare, should be considered in the presented to the hospital in Idaho with sudden onset of neck pain and differential diagnosis of fever and lymphadenopathy. It is swelling, fever, and hypotension. She had an MRI of her neck associated with systemic lupus erythematosis, occurring prior to, demonstrating soft tissue swelling vs. a fluid collection in the concurrent with, or after the diagnosis of SLE1. It is also superior mediastinum, and was noted to have Strep. pneumoniae associated with various infections2, and affects predominantly bacteremia that cleared on day 2. She spent a week in the ICU with females in their 20s and 30s1. The disease follows a benign unrelenting fevers despite antibiotic escalation, developing course, resulting in constitutional symptoms such as fever, pancytopenia prior to transfer to the University of Utah for surgical arthralgias, myalgias and lymphadenopathy. It is treated with management. Physical Exam NSAIDs or steroids depending on its severity. The patient in this case presented in septic shock from VS 68/32 HR 131 99% 4L Tm 103 CV Tachycardia, no m/g/r Figure 1. Strep. pneumoniae bacteremia, which most likely originated from GEN No apparent distress PULM Crackles in the upper lobes A. Sagittal view MRI of the head and neck demonstrating an enhancing retropharyngeal mass. B. Cross sectional CT chest with contrast demonstrating bilateral pulmonary infiltrates. C and D: H&E stain of the retropharyngeal mass demonstrating her pharyngeal NHL or from her pulmonary lesions. At the same HENT Swollen neck, normal voice. ABDO Benign, + Bowel sounds necrosis and histiocytic infiltration with lack of neutrophils. Malar rash SKIN No lesions time, she presented with signs of uncontrolled SLE heralded by Differential Diagnosis myocarditis, pneumonitis, malar rash, and elevated DS-DNA. Initial Work-up After the initial control of her infection with narrow spectrum Retropharyngeal abscess, lymphoma, Lupus lymphadenitis, antibiotics and fluid resuscitation, she remained febrile to 103o F 9.1 141 111 35 8.9 84 103 Lemierre’s syndrome, granuloma, tuberculosis, sarcoidosis as a result of her autoimmune disease. NHL is a spectrum of 3.5 103 4.8 15 4.8 7.3 41 disease that can happen outside of lupus flares, but is 3.1 56 Hospital Course pathologically very similar to lupus lymphadenitis when occurring INFECTIOUS WORKUP in the context of active lupus, making it difficult to distinguish the The patient was continued on IV caspofungin, meropenem and Legionella PCR BAL: (-) Chlamydophila PCR: (-) 0.4 two diseases3. vancomycin for two days after transfer until her infectious Quant GOLD: (-) Nocardia Culture: (-) UA – Benign workup was negative. Interventional radiology was unable to Respiratory Viral PCR: (-) HSV/CMV BAL Culture: (-) Lactate: 3.5 References ESR/CRP: 53/3.3 aspirate any fluid from the retropharyngeal space, so biopsies P. Jiroveci PCR BAL: (-) Aspergillus PCR BAL: (-) 1. Guillaume D., et al. “Kikuchi-Fujimoto Disease: Retrospective Study of 91 Cases and Review of the Literature.” C3/4: 27/6 (L) were taken demonstrating histiocytic necrotizing lymphadenitis Medicine, 2014;93:372-382. Lippincott Williams & Wilkins. DS-DNA: 1:5120 2. Chiu CF, Chow KC, Lin TY, et al. “Virus infection in patients with histiocytic necrotizing lymphadenitis in Taiwan. Histoplasma Antibodies: (-) Mycoplasma PCR BAL: (-) with a paucity of neutrophils. Her fevers, hypoxic respiratory Detection of Epstein-Barr virus, type I human T-cell lymphotropic virus, and parvovirus B19. Am. J. Clin. Pathol. LDH 561 2000;113:774-781 Respiratory BAL Culture: Polymicrobial respiratory 3.Hu, S. et al. “Lupus Lymphadenitis Simulating Kikuchi’s Lymphadenitis in Patients with Systemic Lupus Erythematosus: Ferritin: 925 failure and neck pain resolved with the initiation of solu-medrol. a Clinicopathologic Review of 6 Cases and Review of the Literature.” Pathology International 2003. 53:221-226 flora. Yeast in ½ cultures A Game of Cat and Mouse; Respiratory Distress in the Setting of Multiple Zoonotic Exposures Stacy Johnson MD, Devin Horton MD, Matthew G Petersen BS University of Utah Department of Internal Medicine

Abstract Case Description Discussion

Respiratory compromise may progress very rapidly in the History of Present Illness The key to diagnosis and successful management in this case was hospitalized patient, causing significant morbidity and mortality. our clinical suspicion for Hantavirus which was based on the A 56-year-old previously healthy woman is transferred from an Acutely ill patients are at particularly high risk for acute respiratory patient’s self-reported exposure to rodent droppings. Although outside hospital with worsening respiratory status. She has a one- distress syndrome (ARDS), a process presenting initially with Hantavirus is rare, the patient history directly informed our workup week history of fevers, chills, headaches and two observed syncopal dyspnea and tachypnea. Diagnostic criteria for ARDS include and management. While there is no definitive treatment for episodes. The patient reports no significant medical or surgical profound hypoxemia and bilateral pulmonary infiltrates in the Hantavirus, early supportive intervention with intubation and history, takes no medications and has no known drug allergies. She absence of cardiac causes. The overall mortality rate for ARDS is ECMO contributed to the patient being discharged after one week has no recent travel outside the US, does not endorse substance 41%. The differential diagnosis is broad, including many infectious without the need for supplemental oxygen. To date, the patient has abuse and reports no sick contacts. She lives alone in a trailer in agents, environmental exposures, and inflammatory processes. had no complications from her hospitalization. rural Montana and has contact with many animals including rodents, A thorough workup is important in identifying the etiology of ARDS cattle, horses and deceased rabbits killed by her cat. On admission, Chasing the etiology of a diagnosis like ARDS can feel a little like a and thus informing management. However, the workup is most patient endorsed nausea, shortness of breath, arthralgia and game of cat and mouse, but when workup is guided by a carefully effective when it is informed by a comprehensive history with close myalgia. elicited history it can drastically change patient management as we attention payed to social Objectiveshistory including sick contacts, living have seen in this case. Physical Exam conditions, travel and environmental exposures. Here we present a patient with ARDS in which zoonotic exposures elicited in the On admission, exam was pertinent for a temperature of 98.1, pulse history led to a diagnosis of Hantavirus. 105, respiratory rate 14 and blood pressures ranging from 70/40 to 130/70. She was alert, oriented and cooperative initially, but severe respiratory distress required sedation and intubation. Cardiovascular exam was grossly normal, demonstrating regular rate and rhythm Introduction without appreciable murmurs. Lung fields were diffusely course with References inspiratory rales. A patient is transferred from an outside hospital after a 3-day Investigative Studies 1.Yadav H, Thompson BT, Gajic O. Fifty Years of Research in ARDS. Is Acute Respiratory Distress course of nausea, weakness, poor intake and worsening Syndrome a Preventable Disease? Am J Rspir Crit Care Med. 2016 Dec 31. [Epub ahead of print] respiratory status requiring intubation. Rapid progression to Chest x-ray showed 5-lobe alveolar and interstitial infiltrates. CBC 2.Anand S, Jayakumar D, Aronow WS, Chandy D. Role of Extracorporeal Membrane Oxygenation in Adult Respiratory Failure: An Overvoew. Hosp Pract (1995). 2016;44(2):76-85. ARDS necessitated extracorporeal membrane oxygenation and BMP were within normal limits. Bronchoalveolar lavage showed 3.Warner GS. Hantavirus illness in humans: review and update. South Med J. 1996 Mar;89(3):264- (ECMO) and precipitated severe sequelae including hemorrhagic bronchus. Respiratory cultures showed no growth. 71. hypokalemia, hypernatremia, encephalopathy, acute tubular Patient’s infectious workup was negative for hepatitis C, adenovirus, 4.Marx G, Stinson K Deatrich M, Albanese B. Notes from the Field: Hantavirus Pulmonary Syndrome in a Migrant Farm Worker – Colorado, 2016. MMWR Morb Mortal Wkly Rep. 2017 Jan 20;66(2):62- necrosis, acute blood loss anemia, and sepsis. Thorough HSV 1 and 2, influenza A and B, parainfluienza, and RSV. Urinalysis, 6. investigation of social history allowed for the timely workup blood, viral respiratory panel and fungal cultures showed no growth. and diagnosis of Hantavirus a rare but serious infectious After discharge, Hantavirus antibodies were found to be positive disease. while Francisella Tularensis antibodies were negative. Progress and Outcome Given the patient’s symptoms and imaging, causes of ARDS were considered including sepsis, inhalation injury, aspiration and severe pneumonia. Ultimately the patient’s history of infectious prodrome, pulmonary symptoms and zoonotic exposures led to a thorough infectious disease workup. Exposure to rodents and their droppings was strongly suggestive of Hantavirus. The patient received supportive respiratory care in the ICU including intubation and ECMO. Approximately one week after admission, the patient was discharged to home without supplemental oxygen.

Photos courtesy of The Center for Disease Control and Prevention THE IMPORTANCE OF BEING EARNEST S Tyler Williams, MD1, John C Christensen, MD, FACP2 1 PGY3 Internal Medicine Department University of Utah 2 Assistant Professor Internal Medicine University of Utah, Hospitalist Intermountain Medical Center

Abstract Case Description Discussion

Untreated hypothyroidism is often an insidious disease process with A 67 year-old man with past medical history notable for alcohol abuse, This case represents a rare form of hypothyroid myopathy also known numerous clinical manifestations. Hypothyroid myopathy, also known hepatitis c, cirrhosis, and coronary artery disease presented to the as Hoffman’s syndrome in the medical literature. as Hoffman’s syndrome, is a rare clinical entity which can lead to emergency department with two days of dark tarry stools, generalized muscle weakness and rhabdomyolysis in severe cases. weakness, confusion, and years of lower extremity pain. On further review of the patient’s medical history he had presented to the emergency department multiple times over the preceding two In this case, a 67 year-old man presented with symptoms of The patient was hypotensive on presentation with a blood pressure of years, often with concern for confusion, generalized weakness, and generalized weakness, confusion, melena, and years of bilateral lower 94/52 and heart rate of 83. On physical exam he was noted to have bilateral lower extremity pain. His history of alcohol abuse often extremity pain. He was found to have acute upper GI bleed. altered mental status with report of dysarthria as well as increased clouded the picture and took precedence over documented physical Incidentally, he was noted to have a two year history of an elevated muscular rigidity of bilateral lower extremities. exam findings and laboratory abnormalities. creatinine kinase. After acute stabilization in the ICU he was transferred to the medical floor where a complete physical exam and Initial laboratory studies were notable for a hemoglobin of 3.8 g/dL, He was noted to have elevated CK levels dating back at least two thorough review of the patient’s medical history revealed an untreated platelet count of 80 k/uL, sodium 131 mmol/L, AST 216 U/L, and years prior to this encounter and was found to have mild and undiagnosed history of hypothyroidism which lead to the diagnosis lactate of 4.6 mmol/L. He also had an elevated creatinine kinase (CK) hypothyroidism though this was apparently never addressed. of hypothyroid myopathy. level of 6,875 U/L. The clinic course of hypothyroidism is often insidious but due to early This case demonstrates the importance of a thorough history and The patient was given 1 liter of normal saline and 4 units of packed red screening and treatment it rarely progresses to the level of neurological physical exam as well as a complete work-up of abnormal laboratory blood cells and admitted to the intensive care unit (ICU).Upper and muscle involvement which were seen in this patient. values. endoscopy revealed grade III esophageal varices which were then banded. After intervention, the remainder of the patient’s ICU course This case demonstrates the importance of physicians earnestly taking was uneventful and he was transferred to the medicine ward for further a complete history, performing a thorough physical exam, and following Introduction inpatient monitoring. up all abnormal laboratory values no matter how common and insignificant they may seem. On the medicine floor the patient was noted to have persistent Patients often present with extraneous history and confounding encephalopathy and continued lower extremity pain. The physical symptoms that mask the true diagnosis. Such is the case with the exam at that time was notable for mental slowing, thinning of the lateral patient presented here. His symptoms were misdiagnosed for years eyebrows (madarosis), increased muscular rigidity, gastrocnemius leading to the rare disease presentation of hypothyroid myopathy. It muscle hypertrophy, and delayed relaxation of the deep tendon was through history and physical exam with confirmatory lab testing reflexes. that the patient was finally diagnosed with hypothyroidism and treated. The patient’s CK was again checked and found to be persistently elevated at 4,588 U/L. A chart review revealed that this value was similar to CK levels which had been checked on multiple occasions over the prior two years. Thyroid stimulating hormone (TSH) was found Figure 2. Madarosis (lateral eyebrow loss)1 to be elevated at 97.6 ulU/mL with free T4 level less than 0.40 ng/dL. Notably, he had a TSH check two years prior to presentation that was also elevated but never acted upon. References

Treatment was initiated with levothyroxine 50 mcg orally per day and 1. Khong, J. J., Casson, R. J., Huilgol, S. C., & Selva, D. (2006). Madarosis. Surv Ophthalmol, 51(6), the patient’s mental status subsequently improved over the next 550-560. doi:10.1016/j.survophthal.2006.08.004 several days with decreased evidence of muscular rigidity. 2. Lee, K. W., Kim, S. H., Kim, K. J., Kim, S. H., Kim, H. Y., Kim, B. J., . . . Choi, D. S. (2015). A Rare Manifestation of Hypothyroid Myopathy: Hoffmann's Syndrome. Endocrinol Metab (Seoul), 30(4), 626-630. doi:10.3803/EnM.2015.30.4.626 3. Mangaraj, S., & Sethy, G. (2014). Hoffman's syndrome - A rare facet of hypothyroid myopathy. J Neurosci Rural Pract, 5(4), 447-448. doi:10.4103/0976-3147.140025 4. Sindoni, A., Rodolico, C., Pappalardo, M. A., Portaro, S., & Benvenga, S. (2016). Hypothyroid Figure 1. Hypertrophy of calf muscles2 myopathy: A peculiar clinical presentation of thyroid failure. Review of the literature. Rev Endocr Metab Disord. doi:10.1007/s11154-016-9357-0 An Unexpected Etiology of Encephalopathy Alex J. Wright, MS3 University of Utah School of Medicine

Salient points of the patient’s case are as follows: Case conclusion: Over the next several days, the patient’s Abstract • Reported nearly 3 weeks of daily nausea and vomiting improvement plateaued. She then developed waxing and waning • Paracentesis performed in Idaho pulling off 2.2L of fluid, with a somnolence. A family meeting was held and the decision was This clinical vignette presents a patient with a history of decompensated peripheral WBC of 21 and lactic acidosis. She was then admitted to cirrhosis secondary to Primary Sclerosing Cholangitis and Crohn’s disease made to move toward comfort care. Early the next morning, the who transferred from an outside hospital with sepsis and concerns for the outlying hospital. patient was extubated and she passed away from Wernicke䇻s spontaneous bacterial peritonitis. • Despite treatment with appropriate antibiotics, lasix, spironolactone Encephalopathy with failure to protect her airway and subsequent and anti-hypertensives, her condition continued to worsen, thus, respiratory failure. Although nystagmus was noted on the initial exam, the etiology was not she was transferred to the University of Utah hospital. further investigated due to confounding information from her husband. On • Upon arrival, she was noted to be 䇾very lucid䇿 and had 䇾prominent Clinical Manifestations of WE hospital day five, the patient developed worsening encephalopathy and new vertical nystagmus䇿 as well as asterixis. Labs showed an anion gap Classic Triad: Other signs: 1. Confusion onset seizures. An MRI and a neurology consult were obtained, which metabolic acidosis and acute kidney injury. Malnutrition Hypothermia revealed the diagnosis. Key historical information that was suggestive of 2. Gait ataxia Vestibular dysfunction Tachycardia • Over the next several days, the nystagmus was continually noted in 3. Oculomotor dysfunction Peripheral neuropathy Exertional dyspnea the etiology of the nystagmus was missed until that time. Treatment was All features are only present in about 1/3 of begun promptly and mild improvement was seen over the next week. charting, but the husband reported improvement since being patients. Usually only 1 or 2 are apparent. However, lack of significant improvement and the inability to protect her transferred from the outside hospital. airway, in the setting of decompensated liver failure, led to a family decision • On hospital day 2, an abdominal CT showed partial obstruction and Discussion to pursue comfort care only. Shortly after being extubated the patient an NG tube was placed. Her respiratory drive declined due to passed away. presumed aspiration. There are several interesting take away points from this case. First • It was then decided to sedate her and place an endotracheal tube. and foremost being the clinical decision making and potential for This case underlines the importance of obtaining a thorough history and • On hospital day 4, she had three seizures in the morning. A diagnostic errors. Complications from this severe form of maintaining a broad differential diagnosis. If a more thorough history was neurology consult was placed and a brain MRI without contrast Wernicke’s encephalopathy were deemed to be the principle cause performed, it is possible this information would have been available sooner, (figure 1) was ordered due to worsening encephalopathy with of the patient’s death. Although symptoms of this disease were which could have prompted an investigation into the cause of the evident at presentation, a further work up was not pursued. It was nystagmus. Whether that would have made a substantial difference in the cessation of both extremity movement and ability to follow end is unknown, but the principles highlighted here are important, commands. not until an MRI was obtained for worsening encephalopathy, and especially for those early in their training. • Further interview from the family yielded history of a fall attributed to seizures provoked a neurology consult, that this diagnosis was leg weakness. She denied change in position or lightheadedness. reached. Fortunately, prompt treatment was begun, but it was The family also reported episodes of confusion. already five days after presentation. Introduction Figure 1 It is true that hindsight is always 20/20, and that she presented This is a clinical vignette of a complicated patient with multiple with several problems that were life threatening. The husbands comorbidities who transferred from an outside hospital to the MICU claim of improving nystagmus was also a confounding factor. at the University of Utah Hospital. It was eventually discovered that However, as a more thorough history was performed later, the the patient had severe Wernicke䇻s Encephalopathy with an atypical symptomatic clues of the etiology of the nystagmus were revealed. presentation. The symptoms of this were charted on arrival, but the Perhaps if a more thorough history was taken at admission, or diagnosis and treatment were delayed until 5 days after admission. MRI results from hospital day 4. Six serial images taken from axial FLAIR, caudal to cranial from left to right. infarction in basal ganglia, medial thalami, superior frontal soon thereafter, with the help of her family, these clues could have The patient eventually died from complications of Wernicke䇻s lobe, perirolandic area, and pontomedullary junction in region of 6th cranial nerve prompted the necessary workup to reach the diagnosis sooner. Encephalopathy with failure to protect her airway and subsequent nuclei. FLAIR showed hyperintense signal through the periaqueductal gray, tectum respiratory failure. and mammillary bodies consistent with thiamine deficiency. This case underlined the importance of maintaining a broad • Following MRI, propofol was held to allow for neurologic exam. working differential diagnosis and avoiding cognitive errors like Over the next several days her neurologic exam improved slightly anchoring. Both of which are difficult and exhausting, but as Case Description with small volitional movements in all four extremities, return of evidenced in this case, can be crucial in the care of patients. HJ was a 28-year-old female with a history of decompensated horizontal eye movements for the first time on hospital day 9, and References cirrhosis secondary to Primary Sclerosing Cholangitis and Crohn䇻s improving responsiveness. disease who presented with sepsis and concern for spontaneous • Repeat MRI was obtained 3 days later that showed “decreased 1.Differential Diagnosis for Bilateral Abnormalities of the Basal Ganglia and Thalamus, RadioGraphics 2011. FLAIR hyperintensity and diffusion restriction of the effected 2.Nonalocoholic Thiamine-Related Encephalopathy (Wenicke-Korsakoff Syndrome) Among Inpatient with bacterial peritonitis. She was transferred from an outside hospital Cancer: A Series of 18 Cases, Psychosomatics 2016. in Idaho for further treatment and evaluation for possible liver regions.” It also showed “new small foci of gradient susceptibility 3.Wernicke Encephalopathy: A Future Problem Even After Sleeve Gastrectomy? A Systematic Literature within the putamen bilaterally consistent with microhemorrhages,” Review, Obes Surg. 2016. transplant. 4.The Wernicke-Korsakoff syndrome and related disorders due to alcoholism and malnutrition. FA Davis, without vasculitis. Philadelphia 1989. A Case of Recurrent Pneumothorax, the cause will leave you Breathless. Eric Johnson MD & H. Evin Gulbahce MD

CASE PRESENTATION LEFT PNEUMOTHORAX (FIG 1) PULMONARY LESION (FIG 2) BACKGROUND

The patient was a previously healthy 25-year- Primary pleuropulmonary synovial old male who began having sharp, left sided sarcomas (PPSS) are rare, representing 0.1- chest pain and shortness of breath shortly after 0.5% of pulmonary malignancies1,2. These he returned to his home town at altitude of 7,000 tumors may present initially with chest pain, feet from sea level. cough, or hemothorax4. Entirely cystic/bullous PPSS presenting with recurrent Chest x-ray revealed a left sided pneumothorax have been rarely reported1. pneumothorax and a chest tube was placed. Following resolution of his pneumothorax, the Most primary pulmonary and mediastinal chest tube was removed and the patient was synovial sarcomas are located in the lung discharged only to return the following day with parenchyma1, and rarely extend into the similar symptoms. Chest x-ray showed recurrent bronchial tree or occur in the heart or left sided pneumothorax without evidence of pericardium3. Current treatment consists of pulmonary lesions (Figure 1). surgical resection followed by chemotherapy, radiation therapy, or both3. Subsequent imaging showing left sided lesion (Figure 2). Video-assisted thoracic resection of a This patient’s tumor was both cytokeratin left lower lobe wedge was performed. Gross and EMA negative, a very unusual Figure 1: There is a pneumothorax on the left Figure 2: A small opacity is present in relation examination revealed a unilocular bleb measuring immunohistochemical staining pattern seen in with approximately 3.8 cm of the distance to the inferior-lateral pleural surface and 1.1 cm in size with clear resection margins. only 1 of 100 cases of PPSS highlighting between the pleural space apically. adjacent left hemidiaphragm Microscopically, the collapsed bleb had a spindle importance of ancillary FISH testing for the cell proliferation in the cystic (bleb) wall which SS18 (18q11.2) rearrangement in this was covered with single layer of reactive diagnosis3. mesothelium (Figure 3A). The spindle cells PATHOLOGIC FINDINGS (FIG 3) FISH SS18 GENE (FIG 4) focally extended into the immediate underlying This case report serves to increase lung parenchyma (Figure 3A). The lesional cells awareness of neoplasms clinically presenting were hyperchromatic with high nuclear to as a pneumothorax without evidence on cytoplasmic ratios and were arranged in orderly A B imaging of lesion or mass and to emphasize fascicles (Figure 3B). There were 2 mitoses per the role of FISH testing in such cases as this 10 high power fields and no tumor necrosis was of non-typical synovial sarcoma. observed. REFERENCES Immunohistochemical stains were performed which showed the spindle cells to be negative for 1. Cummings, N.M., Desai, S., Thway, K., Stewart, S., Hill, cytokeratins (cytokeratin AE1/3, cytokeratin 7, D.A., Priest, J.R., Nicholson, A.G., Rintoul, R.C., Cystic primary pulmonary synovial sarcoma presenting as cytokeratin 5/6) epithelial membrane antigen recurrent pneumothorax: report of 4 cases. Am J Surg (EMA), and Wilms tumor protein 1 (WT1). The Pathol, 2010. 34(8): p. 1176-9. neoplastic cells showed weak staining with CD99 2. van der Heijden, E.H., Kaal, S.E., Hassing, H.H., and BCL2. FISH for a SS18 (18q11.2) Verhagen, A.F., Looijen-Salamon, M., Mesenchymal cystic rearrangement showed a break apart consistent hamartoma? A revised diagnosis after 23 years. Thorax, with a translocation involving the SS18 gene 2014. 69(1): p. 84-5. characteristic of synovial sarcoma (Figure 4). Figure 3: Collapsed bleb (cyst wall) containing Figure 4: Dual color, break apart interphase 3. Essary, L, Vargas, S, Fletcher, C, Primary pleuro Metastatic work up was negative. monotonous spindle shaped cells with FISH for SS18 (18q11.2) gene rearrangement. pulmonary synovial sarcoma: reappraisal of recently mesothelial cells on one side (A and B, H&E, 4x Within a single nucleus, split red and green described anatomic subset. Cancer, 2002. 94(2): p. 459-69 The patient was treated with Doxorubicin / and 20x). Spindle cells focally extended into the signal indicate the presence of SS18 (18q11.2). 4. Frazier AA, Franks TJ, Pugatch RD, Galvin JR.From the Ifosfamide chemotherapy and had a complete adjacent alveolar spaces without forming a Rearrangement involving one chromosome Archives of the AFIP: Pleuropulmonary Synovial Sarcoma. response to therapy. nodular mass. while a fused red-green signal within the same Radiographics 2006; 26: 923-940. nucleus indicates an intact 18q11.2. Rheumatological Disease from Cardiac Point of View: A Systematic Review Mossab A. Aljuaid, MD, Gurusher Panjrath, MD Heart and Vascular Institute, George Washington University School of Medicine, Washington, DC, USA.

Abstract Methods Results

Rheumatologic disorders have been associated with Online databases (PubMed and Medline) were searched Online databases (PubMed and Medline) were searched premature atherosclerosis leading to ischemic heart from inception to January 2016. Search terms included: from inception to January 2016. Search terms included: disease at a young age. The increased risk for coronary “systemic lupus erythematosus”, “rheumatoid arthritis”, “systemic lupus erythematosus”, “rheumatoid arthritis”, events may be a result of chronic systemic inflammation “cardiovascular diseases”, “cardiovascular mortality”, “cardiovascular diseases”, “cardiovascular mortality”, from the rheumatic disease. A close collaboration is “sudden cardiac death”, and “atherosclerosis”. Studies “sudden cardiac death”, and “atherosclerosis”. Studies needed between cardiologists and rheumatologists in meeting the following criteria were included: (a) Articles meeting the following criteria were included: (a) Articles managing this group of patients for overlapping are written in English language, (b) Reference to the are written in English language, (b) Reference to the conditions. Further researchObjectives is needed to understand the cardiac involvement in rheumatic diseases, and (c) cardiac involvement in rheumatic diseases, and (c) impact of cardiovascular diseases on morbidity and Articles where full text available. Articles where full text available. mortality in rheumatic diseases. .

Introduction Discussion

Cardiac involvement in rheumatic diseases is associated Cardiovascular diseases are commonly encountered in with increased risk of mortality compared to general rheumatic disease. The current systematic review was population and require prompt diagnosis and treatment. It useful in describing the prevalence of cardiovascular can be the first presentation in patients with no previous involvement in each of the rheumatic diseases. diagnosis or manifest in patients with a known References rheumatologic disorder. The aim of our study was to conduct a systematic review of the literature regarding the 1. Cardiac manifestations of rheumatological conditions: a narrative review. ISRN Rheumatol. cardiovascular involvement in various rheumatic 2. Prevalence and correlates of accelerated atherosclerosis in systemic lupus erythematosus. N Engl J Med. diseases. Commonly used treatments for rheumatic Figure 1. Cardiovascular involvement in different rheumatological diseases. 3. Connective-tissue disease, antibodies to ribonucleoprotein, disease and their cardiovascular side effects were studied and congenital heart block. N Engl J Med. 4. Epidemiology of the rheumatic diseases. Oxford as well. Safety Analysis of Bariatric Patients Undergoing Outpatient Upper Endoscopy with Non-Anesthesia Administered Propofol Sedation 7\OHU 0F9D\-RKQ & )DQJ/LQGD7D\ORU$OH[DQGHU$X:HVOH\:LOOLDPV$QJHOD33UHVVRQ 5DJKHHG $O'XODLPL(ULF9ROFNPDQQ$QQD,EHOH 8QLYHULVW\ RI8WDK&ROOHJHRI0HGLFLQH'HSDUWPHQWRI*DVWURHQWHURORJ\

Background Control Severely Obese P-value Results (N=265) (N=130) :H LQFOXGHG  FRQVHFXWLYH 1RQDQHVWKHVLD DGPLQLVWHUHG SURSRIRO Desaturations 19 (7%) 29 (22%) <0.001 1$$3 KDV EHHQ VKRZQ WR EH D VDIH DQG Hypotension (SBP <90mmHg) 50 (19%) 16 (12%) 0.1 SUHRSHUDWLYH EDULDWULF VXUJLFDO SDWLHQWV HIIHFWLYH PHWKRG RI VHGDWLRQ IRU SDWLHQWV Lowest Systolic BP (mmHg) 100.6 106.8 <0.001 ZLWK DYHUDJH %0,  NJP UDQJH  experienced by each patient - Mean XQGHUJRLQJ JDVWURLQWHVWLQDO HQGRVFRS\  DQG  FRQWURO SDWLHQWV ZLWK DYHUDJH  %DULDWULF VXUJHU\ SDWLHQWV DUH SRWHQWLDOO\ DW Bradycardia (Heart Rate <60bpm) 75 (28%) 17 (13%) <0.001 %0, NJP UDQJH   7KH VHYHUHO\ REHVH JURXS KDG D KLJKHU KLJKHU ULVN IRU VHGDWLRQ UHODWHG Lowest Heart Rate (bmp) experienced 65.9 72.3 <0.001 FRPSOLFDWLRQV GXH WR FRPRUELGLWLHV by each patient - Mean SUHYDOHQFH RI VOHHS DSQHD  YV  LQFOXGLQJ REVWUXFWLYH VOHHS DSQHD 7KH S   H[SHULHQFHG PRUH R[\JHQ Tachycardia (Heart Rate >100bpm) 23 (9%) 18 (14%) 0.11 RXWFRPHV RI 1$$3 LQ EDULDWULF SDWLHQWV GHVDWXUDWLRQV  YV  S  DQG KDYH QRW EHHQ SUHYLRXVO\ UHSRUWHG  Highest Heart Rate (bpm) experienced 80.3 85.9 <0.001 UHFHLYHG PRUH FKLQ OLIW PDQHXYHUV  by each patient - Mean YV  S  7DEOH   $GYDQFHG

Admission to Hospital 1 (0.4%) 0 1 DLUZD\ LQWHUYHQWLRQV ZHUH UDUHO\ UHTXLUHG Methods Table 1. Adverse Events during Procedure and Recovery LQ HLWKHU JURXS DQG ZHUH QRW PRUH ,Q WKLV UHWURVSHFWLYH FRKRUW VWXG\ VHYHUHO\ BMI 34 – BMI 41 –50 BMI 51 – 80 P-value IUHTXHQW LQ WKH EDULDWULF JURXS 7DEOH    REHVH SDWLHQWV XQGHUJRLQJ SUHVXUJLFDO 40 (N=32) (N=71) (N=27) RXWSDWLHQW (*' ZHUH FRPSDUHG WR QRQ Desaturations 5 (16%) 15 (21%) 9 (33%) 0.25 Chin Lift/Jaw Thrust 4 (12%) 15 (21%) 7 (26%) 0.41 Conclusion REHVH FRQWURO SDWLHQWV %0,”NJP 3DWLHQWV ZLWK VHYHUH REHVLW\ FDQ VDIHO\ XQGHUJRLQJ GLDJQRVWLF (*' DW RXU LQVWLWXWLRQ Oral/Nasal Airway 0 0 1 (4%) 0.21 XQGHUJR RXWSDWLHQW XSSHU HQGRVFRS\ ZLWK IURP 0DUFK   6HSWHPEHU  XVLQJ 1$$3 SURYLGHG E\ HQGRVFRSLVWV DQG RXU HQGRVFRS\ GDWDEDVH 3DWLHQWV¶ Bag-valve Mask 0 0 1 (4%) 0.21 HQGRVFRS\ VWDII ZKR DUH SURSHUO\ WUDLQHG GHPRJUDSKLFV SURFHGXUDO DQG UHFRYHU\ Ventilation LQ SURSRIRO VHGDWLRQ DQG DLUZD\ GDWD LQFOXGLQJ DQ\ DLUZD\ LQWHUYHQWLRQV CPAP/BiPAP 0 0 1 (4%) 0.21 PDQDJHPHQW LQFOXGLQJ DFWLYH ZHUH VWDWLVWLFDOO\ DQDO\]HG 7DEOH   Table 2. Severely Obese BMI Subgroups - Desaturations FHUWLILFDWLRQV LQ $&/6 DQG %/6 :H KDYH and Airway Interventions VKRZQ WKDW WKH\ UHTXLUH KLJKHU GRVHV RI Control Severely Obese P-value SURSRIRO DQG PRUH PLQRU DLUZD\ (N=265) (N=130) LQWHUYHQWLRQV :H VXVSHFW WKDW WKHVH Chin Lift/Jaw Thrust 17 (6%) 26 (20%) <0.001 Oral/Nasal Airway 0 1 (0.8%) 0.33 ILQGLQJV DUH JHQHUDOL]DEOH WR RWKHU Bag-valve Mask 1 (0.4%) 1 (0.8%) 0.55 SURYLGHUV RI SURSRIRO VHGDWLRQ LQFOXGLQJ Ventilation &51$V DQG DQHVWKHVLRORJLVWV KRZHYHU CPAP/BiPAP 1 (0.4%) 1 (0.8%) 0.55 ODUJHU DQG SURVSHFWLYH VWXGLHV DUH Intubation 00 - Table 3. Airway Interventions UHTXLUHG HYDOXDWH WKLV The Descriptive Epidemiology of Multimorbidity and Health Service Utilization in Primary Care in England Anna Cassell, Duncan Edwards, and Amelia Harshfield University of Cambridge Department of Public Health and Primary Care

Abstract Methods Results

Background: Studies suggest that increasing numbers of people have multimorbidity, which is the Descriptive Epidemiology of Multimorbidity: simultaneous presence of two or more long-term illnesses, such as diabetes or depression. Data for this study was obtained from the Clinical Practice Research Datalink (CPRD) • 27.4% of patients were multimorbid Multimorbidity places a substantial burden on patients as well as on primary care medicine •Females had significantly higher prevalence than males, 30.1% versus 24.6%. providers, especially General Practitioners (GPs), who must treat and manage patients with • Anonymized patient information from electronic medical recrods in UK • Prevalence was higher with greater levels of socioeconomic deprivation; 25.8% in the multiple illnesses and diseases. This study used routinely collected primary care medical record • Information from 6.9% of UK population, and representative of the whole UK least deprived quintile compared to 30.0% in the most deprived quintile. data to describe the prevalence of multimorbidity in adults in England and to investigate the population • The most prevalent morbidities were: Hypertension (18.2%), Depression and Anxiety association of multimorbidity with usage of health services. • 403,985 random adult patients participated in the study (10.3%), Painful Condition (10%), and Hearing Loss (9.5%)

Methods: Medical records from the UK’s Clinical Practice Research Datalink (CPRD) were used to Data linkages: Health Service Utilization: conduct a cross-sectional study of the prevalence of multimorbidity and a cohort study of health • CPRD only provides information from general practice electronic medical record • A majority of GP consultations, prescriptions, and hospital admissions were devoted to service utilisation. In the cross-sectional component of this study, data was extracted from patient • Linked data to Index of Multiple Deprivation (IMD) for socioeconomic status multimorbid patients. records for a random sample of 403,985 adult patients in England who were registered with a • Linked to Integrated Hospital Episode Statistics for information on • 53.35% of GP consultations during the study’s 4-year follow-up period were in general practice as of January 1, 2012. Multimorbidity was defined as the presence of two or more hospitalizaitons multimorbid patients, despite only 27.4% of patients having multimorbidity. of 36 comorbidities and comorbidities were identified based on diagnostic and prescription codes in • Data linkage was only available for English practices (not Scotland, Wales, or N. • The incident rate for GP consultations in multimorbid patients was 2.45 the patients’ medical records. Health service utilization was determined by following the cohort of Ireland) • The median number of GP consultations for a non-multimorbid patient was 2 per year patients from the initial sample for four years to investigate the association between multimorbidity compared to 9 consultations per year for multimorbid patients. and the yearly incident rates of GP consultations, prescription medications, and hospital Definition of multimorbidity: • 77.46% of all prescriptions were given to patients with multimorbidity. admissions, as well as the all-cause mortality rate. • Multimorbidity was defined by creating a list of comorbidities that consisted of • 63.9% of “unique prescriptions” (only counting each type of prescription medication chronic diseases and long-term illnesses that had face value validity as once) were for multimorbid patients. Results: 27.4% of patients had multimorbidityObjectives and increased multimorbidity was strongly conditions contributing to multimorbidity in primary care. • The incident rate of unique prescriptions in multimorbid patients being 3.49 times the associated with higher levels of socioeconomic deprivation. Multimorbidity was strongly associated • The list of comorbidities was created by a group of researchers and GP rate in the non-multimorbid group. with health service utilisation. While 27% of the population were multimorbid, those patients physicians in the University of Cambridge’s Primary Care Unit, and drew largely • 55.82% of hospitalizations were multimorbid patients. accounted for 53% of GP consultations, 64% of issued prescriptions, and 56% percent of hospital on the previous work of Barnett et al. (published in 2012) that had examined the • The incident rate of hospital admissions in multimorbid patients was 2.47 times the rate admissions. epidemiology of multimorbidity in primary care in Scotland. in non-multimorbid patients. • The morbidities that were selected for our study followed the same criterion as Conclusion: Multimorbidity is common condition and is highly associated with increased health Barnett et al., which was to identify “those morbidities which were likely to be service utilisation. This study highlights the need for practice and national-level policies to improve chronic (defined as having significant impact over at least the most recent year) the quality and efficiency of general practice care provided to multimorbid patients. and with significant impact on patients in terms of need for chronic treatment, reduced function, reduced quality of life, and risk of future morbidity and Discussion Introduction mortality.”42 • The population prevalence of multimorbidity was slightly higher in this study 36 conditions that defined multimorbidity: hypertension; depression compared with previous studies on similar populations in Scotland and England Multimorbidity is generally defined as the coexistence of two or more chronic medical and anxiety; painful condition; asthma; coronary heart disease; diabetes; thyroid (23.2% and 16% respectively). conditions or diseases. Patients with numerous chronic conditions often have more disorders; rheumatoid arthritis and inflammatory polyarthropathies; hearing loss; • Higher frequency of multimorbidity in socioeconomically deprived individuals is likely complicated medical needs, which include understanding and self-managing multiple illnesses COPD; IBS; recent cancer diagnosis; alcohol problems; psychoactive substance partially attributable to disproportionately higher levels of mental-health morbidities and managing complex medication regimens. Multimorbidity can be challenging to manage misuses; treated constipation; stroke; chronic kidney disease; diverticulitis; atrial in those patients from a healthcare perspective because these patients often require more intensive treatment fibrillation; peripheral vascular disease; heart failure; prostate disorders; treated • Higher rates of GP consultations in multimorbid patients might be reduced by 2 and monitoring by physicians, nurses, and other healthcare team members. As the population epilepsy; dementia; schizophrenia and non-organic psychosis; psoriasis or eczema; increasing the length of consultations for patients with multimorbidity so that all of of elderly individuals in England continues to grow, multimorbidity will become an increasingly inflammatory bowel disease; migraine; blindness; chronic sinusitis; learning their health problems can be addressed in one visit. Expanding routine, outpatient common and burdensome medical problem in primary care. disability; anorexia or bulimia; bronchiectasis; Parkinson’s disease; multiple care that is conducted by non-physician medical professionals might also reduce the Patients with multiple chronic conditions place great strains on individual GPs, which is sclerosis; chronic liver disease and viral hepatitis. number of GP consultations, while not compromising quality of care. compounded by the fact that in England consultation rates and overall GP clinical workload • High rates of hospitalizations in multimorbid patients could be reduced by providing have been increasing substantially, and it has been suggested that this rate of increase in the Extracting data from medical records: multimorbid patients with secondary care that intermediates between their primary 15 primary care workload is unsustainable. Thus, describing the relationship and quantifying the • Information identifying morbidities was extracted from CPRD by applying care physician and the hospital. This could help reduce the number of associations between multimorbidity and health service utilisation is essential to optimising the algorithms to the medical and prescription codes in the patient’s record. hospitalizations, which would benefit patients while also reducing healthcare costs. planning, organisation, and delivery of health services to multimorbid patients in order to • Medical codes (med codes) provided medical diagnoses and prescription codes provide sustainable, high quality medical care. Investigating these associations can provide provided information on prescriptions that could be used to diagnose a morbidity. information about the aspects of primary care that are overburdened, identifying areas for For example, for a patient to have asthma, they had to have a medical code for References increased resource allocation or systems-level restructuring to target. asthma in their record and 4 prescriptions for asthma medication in the last year. This study sought to replicate and expand upon previous work that had been conducted 4 by Karen Barnett studying the prevalence of multimorbidity in Scotland. Our study achieved Study Design: 1.van den Akker, M., Buntinx, F., Metsemakers, J. F. M., Roos, S. & Knottnerus, J. A. Multimorbidity in General this by consulting with GP physicians to improve the list of diseases and conditions that were 1. A cross-sectional study design to describe the prevalence of multimorbidity in Practice: Prevalence, Incidence, and Determinants of Co-Occurring Chronic and Recurrent Diseases. J. considered multimorbidity and the diagnostic and prescription codes that we used to identify English general practice, and to describe the prevalence of multimorbidity in Clin. Epidemiol. 51, 367–375 (1998). patients with these conditions. Additionally, we sought to take our study a step further by not relation to sex, age, and socioeconomic status. 2.Salisbury, C., Johnson, L., Purdy, S., Valderas, J. M. & Montgomery, A. A. Epidemiology and impact of multimorbidity in primary care: a retrospective cohort study. Br. J. Gen. Pract. 61, e12–21 (2011). only describing the epidemiology of multimorbidity, but also evaluating the way that multimorbid 2. A cohort study design to describe health service utilization based on GP patients utilize health services. consultations, number of prescriptions, and number of hospitalizations between 3.van Oostrom, S. H. et al. Multimorbidity of chronic diseases and health care utilization in general practice. BMC Fam. Pract. 15, 61 (2014). 2012 and 2015. 4.Barnett, K. et al. Epidemiology of multimorbidity and implications for health care, research, and medical education: a cross-sectional study. Lancet 380, 37–43 (2012). 5.Clinical Practice Research Datalink - CPRD. at 6.Herrett, E. et al. Data Resource Profile: Clinical Practice Research Datalink (CPRD). Int. J. Epidemiol. dyv098– (2015). doi:10.1093/ije/dyv09

Acknowledgements: Special thanks to Dr. Lucy Gerza and James Brimicombe The Reasons for Discontinuation of Combination Therapy with Methotrexate and Tumor Necrosis Factor #652 Inhibitors Versus Triple Therapy Differ Significantly Because of Higher Adverse Events with Triple Therapy 'DQLHO(UKDUGW%ULDQ&6DXHU&KLD&KHQ7HQJ7HG50LNXOV-HIIUH\5&XUWLV DQG *UDQW:&DQQRQ 6DOW/DNH&LW\9$0HGLFDO&HQWHUDQG8QLYHUVLW\RI8WDK6DOW/DNH&LW\872PDKD9$0HGLFDO &HQWHUDQG8QLYHUVLW\RI1HEUDVND0HGLFDO&HQWHU2PDKD1('LYLVLRQRI&OLQLFDO,PPXQRORJ\ DQG5KHXPDWRORJ\8QLYHUVLW\RI$ODEDPDDW%LUPLQJKDP%LUPLQJKDP$/ Background ‡ :HKDYHSUHYLRXVO\UHSRUWHGSHUVLVWHQFHDIWHURQH\HDURIFRPELQDWLRQ'0$5' Results Summary WKHUDS\LQ869HWHUDQVZLWKUKHXPDWRLGDUWKULWLV 5$ XVLQJ9HWHUDQV$IIDLUV 9$  ‡ 66=ZDVWKHDJHQWPRVWIUHTXHQWO\GLVFRQWLQXHGLQWULSOHWKHUDS\JURXS SKDUPDF\GDWDEDVHVWKHVHRQH\HDUSHUVLVWHQFHIRU Definition of Combination Therapy ‡ 71)LZDVWKHDJHQWPRVWIUHTXHQWO\GLVFRQWLQXHGLQWKH07;71)L ‡ 7ULSOHWKHUDS\>PHWKRWUH[DWH 07; 6XOIDVDOD]LQH 66= DQG JURXS K\GUR[\FKORURTXLQH +&4 @DW Q  ‡ 66=+&4ZDVWKHGUXJFRPELQDWLRQPRVWIUHTXHQWO\GLVFRQWLQXHGLQ ‡ 07;7XPRUQHFURVLVIDFWRULQKLELWRU 71)L FRPELQDWLRQWKHUDS\DW WKHWULSOHWKHUDS\JURXS Q  ‡ 7KHPRVWFRPPRQDGYHUVHHYHQWLQWKHWULSOHWKHUDS\JURXSZDV*, ‡ 7KLVGLIIHUHQFHLQSHUVLVWHQFHZDVVWDWLVWLFDOO\VLJQLILFDQWDQGUREXVWWRYDULDWLRQVLQ WR[LFLW\ PHDVXUHPHQWRISHUVLVWHQFH S   VHHUHIHUHQFH  ‡ 7KHPRVWFRPPRQDGYHUVHHYHQWLQWKH07;71)LZDVLQIHFWLRQ ‡ $ODUJHQXPEHURIVXEMHFWVZHUHORVWWRIROORZXSDQGRUKDGQRFOHDU 2QH\HDUSHUVLVWHQFHRQFRPELQDWLRQWKHUDS\  UHDVRQIRUGLVFRQWLQXDWLRQVWDWHG  07;71)L   Strengths  ‡ 5HDOZRUOGFRKRUWGHVFULELQJDFWXDOFOLQLFDOSUDFWLFH   ‡ 0RVW869HWHUDQVZLWK5$UHFHLYH5$PHGLFDWLRQVLQ9$V\VWHP  ‡ 1DWLRQDOGDWDEDVHVDOORZFDSWXUHRIFRPSUHKHQVLYHSKDUPDF\GDWD  Results: Individual Drug Discontinuation ‡ 1DWLRQDOHOHFWURQLFPHGLFDOUHFRUGDWPXOWLSOHVLWHVDFURVV86  3URSRUWLRQ3HUVLVWHQW               Triple Rx MTX+ TNFi 'D\V3HUVLVWHQWRQ&RPELQDWLRQ7KHUDS\ Limitations Single drug Discontinued ‡ 6WXG\RIWKLVSUHGRPLQDQWO\ROGHUPDOH9$SRSXODWLRQPD\QRWEH Objective 71)L 1$ 62 (53.9%) DSSOLFDEOHWRRWKHU5$SRSXODWLRQV ‡ 5HSRUWWKHGUXJVWHUPLQDWHGDQGUHDVRQVIRUGLVFRQWLQXDWLRQRIWKHVHWZR ‡ 2EVHUYDWLRQDOFRKRUWVWXG\QRWDUDQGRPL]HGFRQWUROOHGWULDO 07; 10 (8.7%) 22 (19.1%) FRPELQDWLRQUHJLPHQV ‡ 9DULDEOHDFFXUDF\RIPHGLFDOUHFRUGGRFXPHQWDWLRQIRUWKHUHDVRQRI Methods 66= 24 (20.9%) 1$ WHUPLQDWLRQ ‡ 3RSXODWLRQ +&4 9 (7.8%) 1$ ‡ &XUUHQWGHILQLWLRQIRUFRPELQDWLRQPD\KDYHFODVVLILHGVRPHSDWLHQW ‡ +LVWRULFDOFRKRUWVWXG\-DQXDU\WR'HFHPEHU One or more drugs ZLWKSODQHGLQWHUUXSWLRQDVSHUPDQHQWGLVFRQWLQXDWLRQ ‡ 869HWHUDQV!\HDUVRIDJHZLWK,&'&0FRGHVIRU5$ discontinued simultaneously ‡ 6LJQLILFDQWQXPEHURIVXEMHFWVZHUH³ORVWWRIROORZXSXQNQRZQ´ ‡ %DVHOLQHDQG&RPELQDWLRQ7UHDWPHQW 66=+&4 43 (37.4%) 1$ ‡ %DVHOLQH07;•GD\EHIRUHFRPELQDWLRQWKHUDS\LQLWLDWHG Conclusion 07;+&4 2 (1.7%) 1$ ‡ 1RRWKHU'0$5'V HLWKHUELRORJLFRUQRQELRORJLF •GD\VSULRUWR ‡ 7KHGLIIHUHQFHVLQSHUVLVWHQFHEHWZHHQWKH07;71)LDQG7ULSOH5[ $OOGUXJVRIWKHFRPELQDWLRQ 27 (23.5%) 31 (27.0%) FRPELQDWLRQWKHUDS\ JURXSVLQWKLVUHDOZRUOGREVHUYDWLRQFRKRUWVWXG\DSSHDUWREHSULPDULO\ Total discontinuation 115 (100%) 115 (100%) UHODWHGWRDGYHUVHGUXJHYHQWV ‡ &RPELQDWLRQVWDUWHGZLWKLQLWLDWLRQRI71)LRU66=DQG+&4VLPXOWDQHRXVO\ ‡ 7KHPRVWFRPPRQGUXJDVVRFLDWHGZLWKDGYHUVHGUXJHYHQWVZDV66= VHHILJXUH Results: Reasons for Drug Discontinuation ZKLFKZDVDOVRWKHGUXJPRVWIUHTXHQWO\GLVFRQWLQXHG ‡ $WOHDVWRQHGLVSHQVLQJRI07;DIWHULQLWLDWLRQRIFRPELQDWLRQWKHUDS\ Triple Rx MTX+ TNFi ‡ 7KHVHILQGLQJVPD\KDYHLPSOLFDWLRQVRQIXWXUHSUHVFULELQJSDWWHUQVDQG ‡ 'HILQLWLRQRI7HUPLQDWLRQRI&RPELQDWLRQWKHUDS\ Lack of Efficacy 18 (15.7%) 25 (21.7%) FRXQVHOLQJRISK\VLFLDQVWRZDUGWKHLUSDWLHQWV ‡ 'LVFRQWLQXDWLRQRIDQ\RIDJHQWLQWKHFRPELQDWLRQZLWK!GD\JDSRU Adverse Drug Event 50 (43.5%) 41 (35.7%) ‡ ,QLWLDWLRQRIQHZGUXJWUHDWPHQWVIRU5$ Support ‡ 5HSRUWRIUHDVRQVIRUGUXJGLVFRQWLQXDWLRQQRWHGRQFKDUWUHYLHZ GI toxicity     ‡ 7KLVPDWHULDOLVEDVHGXSRQZRUNVXSSRUWHGE\WKH'HSDUWPHQWRI ‡ 3DWLHQWVGLVFRQWLQXLQJWULSOH5[RU07;71)LZHUHPDWFKHGE\DJH “\HDUV  Rash     9HWHUDQV$IIDLUV2IILFHRI$FDGHPLF$IILOLDWLRQVDQG2IILFHRI JHQGHUDQGVLWHRIFDUH Infection     6SHFLDOW\&DUH6HUYLFHV ‡ 2IRULJLQDOFRKRUWVXEMHFWVIURPWKHWULSOHWKHUDS\JURXSZHUHDEOHWREH Other adverse drug event     PDWFKHGE\DERYHDJHJHQGHUDQGVLWHRIFDUH Other 47 (40.9%) 49 (42.6%) ‡ 7KHVSHFLILFGUXJVGLVFRQWLQXHGDUHGHVFULEHG Reference Step-down of therapy     ‡ 5HDVRQVIRUGLVFRQWLQXLQJWKHFRPELQDWLRQWKHUDS\ZHUHQRWHGDV ‡ (UKDUGW 'HWDO&OLQLFDO3UDFWLFH([SHULHQFHLQ5KHXPDWRLG$UWKULWLV ‡ /DFNRIHIILFDF\ Discontinued prior to surgery     3DWLHQWV7UHDWHGZLWK7ULSOH7KHUDS\DQG0HWKRWUH[DWH7XPRU ‡ $GYHUVHGUXJHYHQWDQGVSHFLILFHYHQWUHFRUGHG Lost to follow-up/unknown     1HFURVLV)DFWRU,QKLELWLRQ'LIIHUVIURP7KDWRI5DQGRPL]HG ‡ 2WKHU VWHSGRZQWKHUDS\SUHRSHUDWLYHGLVFRQWLQXDWLRQQRQFRPSOLDQFH Total discontinuation 115 (100%) 115 (100%) &RQWUROOHG7ULDOV$PHULFDQ&ROOHJHRI5KHXPDWRORJ\6DQ ORVWWRIROORZXS )UDQFLVFR Neutrophil-to-Lymphocyte Ratio as Prognostic Indicator in Gastrointestinal Cancers: A Systematic Review and Meta-analysis J. H. Harmer1, N. A. B. Little1, R. C. Bowen1, J. Ma1, L. G. Mirabelli1, K. D. Roller1, A. M. Breivik1, E. Signor1, A. Miller1, H. T. Khong1 1. University of Utah-Huntsman Cancer Institute, Salt Lake City, UT

Abstract Results Methods

• An accurate, time efficient, and inexpensive • “GI cancer” was defined as prognostic indicator is needed to reduce cost and cancers originating from assist with clinical decision making for cancer esophagus to rectum including management. hepatobiliary. • The neutrophil-to-lymphocyte ratio (NLR), • Randomized Control Trials, which is derived from common serum testing, has Cohort, and Case Control been explored in a variety of cancers. studies were included. • We sought to determine its prognostic value in • Overall survival was the gastrointestinal cancers by performing a meta- primary enpoint, analyzed in relation to NLR > cutoff value. analysis of pertinent published literature. • 6 reviewers independently • We analyzed 144 studies comprising 45,905 assessed articles in 3 pairs. patients; 2/3 were published after 2014. • All data was collected by 2 • The mean, median, and mode cutoffs for NLR independent reviewers and a reporting OS from multivariate models were 3.4, 3rd reviewer resolved 3.0, and 5.0, respectively. disagreements. • Overall, NLR greater than the cutoff was • Hazard ratios were combined associated with a HR for OS of 1.63. using the random effect • This association was observed in all subgroups method. based on tumor site, stage, and geographic • Heterogeneity of NLR cutoff region. values was assessed by the Q and I squared statistics. Figure 2: Systematic Flow Diagram Introduction Discussion • The neutrophil-to-lymphocyte ratio (NLR), calculated by dividing the absolute neutrophil count • Available evidence suggests that NLR greater than the cutoff reduces (ANC) by the absolute lymphocyte count (ALC), can OS, independent of geographic location, gastrointestinal cancer type, serve as an index of systemic inflammatory or stage of cancer. response in critically ill patients and may predict • The individual cancer types analyzed and disease stages had varying overall survival. median NLR cutoff values that appear to predict survival prognosis and • The purpose of this meta-analysis was to could be used for appropriate treatment planning. demostrate the usefulness of the NLR as a Figure 1: Overall Survival Analysis • NLR should be included in correlative studies in future clinical trials to prognostic marker and provide insight into the Figure legend: Overall survival analysis of NLR cut off, geographic location, and disease stage. (A) Overall survival in patients with GI cancers and further assess and validate these findings. optimal cutoff value for NLR for different GI per individual GI cancer types. (B) Overall survival analysis within geographic regions. (C) Overall survival within each disease stage. cancers. Contact : [email protected] Role of MFN2 in Platelets Kelly B. Hoerger1, Matt T. Rondina1, , Jane E. Freedman2 , Jesse W. Rowley1 1. Program in Molecular Medicine, University of Utah School of Medicine, Salt Lake City, UT 2. Boston University School of Medicine

BACKGROUND A. D. A. Compounding the obesity epidemic are the associated risks and diseases that contribute to the morbidity and mortality of the affected individuals. Of note, obesity increases the risk of a thrombotic event, in which clots are formed from platelets that can lead to life-threatening emergencies.1 While clotting is normal and necessary to maintain hemostasis, hyper-reactive platelet activity can be detrimental. It is known that mitochondrial function regulates platelet reactivity. Furthermore, 20000 QPCR Gel Electrophores mitochondrial metabolism is altered in metabolic syndrome. To maintain normal mitochondrial Real time PCR 2-Ct(avg)*1E6 function, mitochondria undergo processes of fusion, in which two separate mitochondria come B. C. 18000 together to share DNA, proteins, and metabolites.2 Mitofusin 2 (MFN2), a GTPase, assists in fusing two 14 16000 mitochondria together, and its absence is associated with metabolic and neurodegenerative 12 diseases.3,4,5 Platelets express a novel isoform of MFN2 that is associated with platelet counts9. 14000

Whether MFN2 regulates mitochondrial function in megakaryocytes and platelets, and whether 10 12000 MFN2 expression is related to platelet reactivity in metabolic syndrome is not known. 10000 WT 8 8000 KO 6 6000

4 ImageJ by as measured Pixels #*1E6 2^-Ctavg Average A. 4000 B. E. 2 Variable 2000

0 0 Sample Size 1819 WT KO

Female Sex, n(%) 993 (51) Figure 5. Analysis of mitochondrial DNA levels and mitochondrial DNA damage in Mfn2 KO and WT platelets. To assess changes in mitochondrial DNA load and mitochondrial damage, we Age, y 66.9±8.6 used quantitative PCR (QPCR) in MFN2 KO versus WT murine platelets and used ImageJ to quantify the pixels from the image of the gel electrophoresis (seen in Fig 1). We normalized 2 BMI, kg/m 28.3±5.3 mitochondrial copy number by using real time PCR (qPCR) to amplify short fragments (less than 300 bp) of the mitochondrial gene. In Furda, et al, it was suggested that the probability of B. amplifying such short bps will produce only undamaged DNA.8 We then monitored copy C. F. number of the mitochondrial genome by comparing large fragments obtained from QPCR on the principle that DNA lesions can slow down or block the construction of product and DNA with fewer lesions will amplify in QPCR more than damaged DNA.8 A. QPCR on electrophoresis gel. Pixels quantified by ImageJ as shown in C. Real time PCR threshold counts of WT and KO murine platelets. C. Quantitative PCR of WT and KO murine platelets

SUMMARY Both Mfn2 known and platelet specific isoforms are potentially increased in platelets from obese subjects. G. 10 9 Mfn2 plays a role in megakaryocyte morphology, but this was not observed in platelets. Figure 1. Relative MFN2 platelet expression stratified by obesity status on offspring 8 participants in 8 the Framingham Heart Study (N=1819) 7 In this experiment, there were no significant changes in mitochondrial DNA load (for WT n=6, A. Demographics of individuals used from Mfn2 RNA expression analysis. B. Mfn2 RNA expression in 6 KO n=4), however, future tests need to be done. There was also no significant observed platelets. Individuals with BMI<25 are the referent category. The fold-change (and 95% confidence 5 change in mitochondrial damage between WT and KO murine platelets. interval) associated with being overweight or obese estimated from multivariable adjusted models 4 are presented. MFN2 expression in obese individuals was 1.16-fold (1.02-1.34, p=0.02) higher than 3 normal weight individuals and 1.15-fold (1.02-1.28, p=0.02) higher than overweight individuals. There 2 was no difference in MFN2 expression in overweight relative to normal-weight individuals (1.02 (0.90- 1 1.15), p=0.8). 0 WT KO

Min Outlier Max Outlier

Figure 3. Mitochondrial morphology in Mfn2 WT and KO megakaryocytes. Using the Evos Cell References RESULTS Imaging System, we captured in real time fused and non-fused mitochondria in MFN2 WT and KO Santilli, F, Vazzana, N, Liani, R, Guagnano, M, Davì, G. "Platelet Activation In Obesity And A. 12 B. 12 mouse megakaryocytes and platelets. A through C: Wild type MFN2 megakaryocyte displaying Metabolic Syndrome." Obesity Reviews 13.1 (2012): 27-42. Academic Search Premier. Web. fused mitochondria. D through F: Knockout MFN2 megakaryocyte displaying punctate 25 Jan. 2016. 10 10 mitochondria. G. Images from Evo Cell Imaging System were validated with lab members who Hall, A. R., et al. "Mitochondrial fusion and fission proteins: novel therapeutic targets for

8 combating cardiovascular disease." British journal of pharmacology 171.8 (2014): 1890-1906. 8 were blinded and asked to rate 14 images at three different times to determine whether mitochondria were punctate or fused (1=fused; 10=punctate). Chen H, Detmer SA, Ewald AJ, Griffin EE, Fraser SE, Chan DC. (2003). Mitofusins MFN1 and 6 6 Mfn2 coordinately regulate mitochondrial fusion and are essential for embryonic development. J Cell Biol 160: 189–200. 4 4 Zuchner S, Mersiyanova IV, Muglia M, Bissar-Tadmouri N, Rochelle. J, Dadali EL et al. (2004). B. 2 A. Mutations in the mitochondrial GTPase mitofusin 2 cause Charcot-Marie-Tooth neuropathy 2 type 2A. Nat Genet 36: 449–451. Ct (Avg Ct - Avg Btubb Ct)

ǻ 0 Ct -Ct (Avg Btubb Ct) Avg Baloh, Robert H., et al. "Altered axonal mitochondrial transport in the pathogenesis of

HL HO ǻ 0 HL HO Charcot-Marie-Tooth disease from mitofusin 2 mutations."The Journal of neuroscience 27.2 -2 -2 (2007): 422-430.

-4 Nicholaos Kakouros, Jeffrey J. Rade, Antonios Kourliouros, Jon R. Resar. “Platelet Function in -4 Patients with Diabetes Mellitus: From a Theoretical to a Practical Perspective.” International -6 -6 Journal of Endocrinology. Vol. 2011. Web 25 Jan. 2016. http://www.hindawi.com/journals/ije/2011/742719.

Min Outlier Max Outlier Min Outlier Max Outlier Guthikonda, Sasidhar, et al. "Role of reticulated platelets and platelet size heterogeneity on platelet activity after dual antiplatelet therapy with aspirin and clopidogrel in patients with Figure 2. Assessment of both known and novel isoforms of platelet MFN2 mRNA in platelets from stable coronary artery disease." Journal of the American College of Cardiology 52.9 (2008): obese human subjects (HO) matched with lean control human subjects (HL) using real-time PCR 743-749. (qPCR). A. Normal isoform of MFN2 exon found in most cells. B. Novel isoform of MFN2 found Figure 4. Mitochondrial morphology in platelets. A. Wild type MFN2 platelets. B. Knockout Furda, Amy, et al. “Quantiative PCR-Based Measurement of Nuclear and Mitochondrial DNA specifically in platelets. MFN2 platelets. Damage and Repair in Mammalian Cells.” Methods Mol Biol. 2014; 1105: 419-437. Simon et al. “Integrative Multi-omic Analysis of Human Platelet eQTLs Reveals Alternative Start Site in Mitofusin 2.” The American Journal of Human Genetics. 2016. http://dx.doi.org/10.1016/j.ajhg.2016.03.007.

THE PREVALENCE AND CORRELATES OF HYPERTENSION AMONG RURAL GHANAIAN ADULTS

M. Jaziri1, M. E. Lyman1, G. R. Sunada,1 L. S. Benson1, D. Ansong2,3, E. A. Williams4, J. M. Boaheng2, E. X. Amuzu2, O. A. Owusu3, E. Kwarteng3, M. G. Quansah3, S. D. Walker1, T. T. Dickerson1 1University of Utah, Salt Lake City, UT, USA, 2Komfo Anokye Teaching Hospital, Kumasi, Ghana, 3Kwame Nkrumah University of Science & Technology, Kumasi, Ghana, 4University Hospital of Southampton, Southampton, Hampshire, UK

50 50 44.3% 60 54.95 45 45 Background 39.19% 50 40 40 34.09% •Low and middle income countries carry 35 35 40 30.17% nearly 80% of the burden of death from 30 30 30 26.7

25 Percent cardiovascular-related diseases (CVD)1.In 25 20 Percent 20 Percent 20 16.51% 14.13% 8.22 7.75 2012, Ghana’s age-adjusted mortality rate for 13.42% 15 10 15 1.91 0.48 CVD was 2.5 times higher than in the US2 (see 10 8.19% 10 0 Table 1). 5 5 0 0 Normal Pre-HTN Stage I HTN Stage II HTN •Previously studies in rural Ghana found a Normal Pre-HTN Stage I HTN Stage II HTN Diastolic Blood Pressure Systolic Blood Pressure surprisingly high prevalence of hypertension Figure 1 – Prevalence of isolated diastolic hypertension Figure 2 – Prevalence of isolated systolic hypertension defined Figure 3 –Body mass index (BMI) of all participants. Categories: (50.9%) in adults aged >35 years3, 4. defined as prehypertension (80>DBP>89), hypertension Stage as prehypertension (120DBP>99)), and hypertension Stage II (DBP>100). SBP<159), and hypertension Stage II (SBP>160). (ϮϱчD/фϯϬŬŐͬŵϮͿ͕KďĞƐŝƚLJ/(30чD/фϯϱŬŐͬŵϮͿ͕KďĞƐŝƚLJ//;ϯϱч •Despite Ghana’s high prevalence of BMI <40 kg/m2) Extreme Obesity (D/шϰ0 kg/m2) hypertension, the typical risk factors Table 2: Multiple regression analysis according to sex (p-value< 0.05) for risk factors of hypertension. associated with hypertension, such as BMI, Risk factors according to sex High Blood Pressure Conclusion Women Systolic Diastolic smoking, alcohol, and lack of physical activity, • There was a high burden of hypertension are relatively low when compared to the US5. Coef. Std. Err. p-value Coef. Std. Err. p-value Age 0.30 0.02 <0.01* 0.15 0.02 <0.01* in the sample of rural Ghanaian adults. •To better understand the disease burden of Educational status 0.00 0.02 0.88 0.03 0.02 0.16 Family history of hypertension 0.21 0.09 0.01* 0.30 0.09 <0.01* • The high prevalence of prehypertension is hypertension in rural Ghana, this study sought Family history of diabetes 0.22 0.11 0.04* 0.17 0.11 0.12 concerning, but it indicates a potential for to estimate the point prevalence of Ever smoked 0.54 0.20 0.01* 0.39 0.21 0.06 early medical intervention in Ghana in order hypertension in all adults aged >18 years as Ever drunk alcohol 0.27 0.11 0.02* 0.31 0.12 0.01* to prevent future morbidity and premature wellastheroleofpotentialriskfactors. Physical activity -0.19 0.07 0.01* -0.05 0.07 0.46 BMI 0.16 0.04 <0.01* 0.18 0.04 <0.01* mortality within this population. Table 1- NCD mortality – Comparable estimates of NCD mortality (total • In order to better manage this silent NCD deaths in 000s; % of NCD deaths occurring under the age of 70; and Men age-standardized death rate for NCDs per 100 000), 2012, Source: WHO5. Age 0.19 0.04 <0.01* 0.10 0.04 0.01* epidemic, it is crucial to regularly screen all Educational status 0.06 0.04 0.18 0.06 0.04 0.16 All NCDs Cancers Chronic Cardiovascul Diabetes adults in order to identify those in need of respiratory ar disease Family history of hypertension 0.41 0.15 0.01* 0.42 0.15 0.01* medical intervention in a timely manner. diseases Family history of diabetes -0.13 0.19 0.49 -0.37 0.19 0.05 US males 488.9 143.6 43.1 169.5 16.3 Ever smoked 0.28 0.18 0.12 0.16 0.17 0.34 • Further, by collaborating with local BCCDP US females 350.1 104.2 32.8 107.8 10.9 Ever drunk alcohol 0.15 0.14 0.27 0.12 0.14 0.37 partners, the following public health Physical activity -0.19 0.12 0.13 -0.02 0.12 0.88 Ghanaian 688.5 93.3 36.4 320.0 41.9 strategy is recommended to improve health males BMI 0.44 0.10 <0.01* 0.47 0.10 <0.01* Ghanaian 652.8 72.6 29.6 350.0 37.3 access, behaviors, and lower the high females * p<0.05 * p<0.05 prevalence of uncontrolled hypertension: o Conduct a comprehensive nutrition Methods Discussion analysis and/or genetic testing The Barekuma Collaborative Community o Design and implement community- Development Project (BCCDP) is a partnership This study included 196 male and 649 224 participants (26.7%) were overweight based interventions 2 between 20 rural, Ghanaian communities and female community members aged ш18 (25чD/ф30 kg/m )(seeFigure 3). The o Improve health policy researchers from the Komfo Anokye Teaching years. The point prevalence of isolated majority of adults were found to have a Hospital (Kumasi, Ghana), the Kwame Nkrumah systolic hypertension (30.64%) and diastolic normal BMI (18.5чD/ф25 kg/m2)or References University of Science and Technology (Kumasi, hypertension (21.61%) was relatively high underweight BMI (BMI<18.5), with 1. A global brief on hypertension: silent killer, global public health Ghana), and the University of Utah (Salt Lake considering this study, in contrast to frequencies of 55% and 8%, respectively. The crisis. World Health Day, World Health Organization (WHO) 2013 City, USA). This cross-sectional study used a previous studies3,4, included all adults (see low prevalence of obese and overweight BMIs 2. Causes of Death 2008 [online database]. Geneva, World Health Organization questionnaire based on the World Health Figure 1 and 2). This younger population among participating adults is similar to ;ŚƚƚƉര͗ͬͬǁǁǁ͘ǁŚŽ͘ŝŶƚͬŚĞĂůƚŚŝŶĨŽͬŐůŽďĂůͺďƵƌĚĞŶͺĚŝƐĞĂƐĞͬĐŽĚͺϮϬ Organization Study on Global Aging and Adult (median age = 42, IQR = 29-58) had a very estimates for Ghana reported by the WHO7. ϬϴͺƐŽƵƌĐĞƐͺŵĞƚŚŽĚƐ͘ƉĚĨ͘Ϳ 3. Williams EA, Keenan KE, Ansong D, Simpson LM, Boakye I, et al. 6 Health administered to 845 adults aged ш18 high prevalence of systolic prehypertension These findings seem to conflict with the high (2013) years. Modifiable and non-modifiable risk factors (39.2%) and diastolic prehypertension prevalence of hypertension within this The burden and correlates of hypertension in rural Ghana: Acro ss-sectional study. Diabetes Metab Syndr 7: 123--128. of hypertension were assessed in participants (34.1%). Interestingly, only 18.1% of all population. In addition to low BMIs, 4. Williams EA, Ansong D, Alder S, Benson LS, Campbell SJ, et al., participants reported a prior diagnosis of participants self-reported a high level of Silent Crisis: Epidemic Hypertension in Rural West Africa. J including: Hypertens (2014) • Socioeconomic status, hypertension. regular, physical activity, and few participants 5. Global status report on non-communicable diseases. World used tobacco or consumed alcohol. Health Organization (WHO) 2014. • Educational level, 6. World Health Organization. WHO Study on global AGEing and • Family health history, A multiple regression analysis showed that adult health (SAGE). World Health Organization, Geneva risk factors such as increased age, family The study findings suggest that genetic factors 7. World Health Organization. Ghana – WHO Statistical Profile. • Physical activity level, Retrieved on March 18, 2016 from • Social habits (e.g., smoking, alcohol), history of hypertension, and increased BMI may play a significant role in the high http://www.who.int/gho/countries/gha.pdf • Psychosocial factors, were significantly correlated with increased prevalence of hypertension in rural Ghana • Anti-hypertension medication use, and blood pressure among both sexes (see whereas BMI, physical activity level, stress, Acknowledgements • Hypertension knowledge. Table 2). Women also had a statistically and behavior habits (tobacco and alcohol use) significant correlation for family history of play minor roles. • Barekuma Collaborative Community Development Project Systolic and diastolic blood pressures (mmHg) • Kwame Nkrumah University of Science and Technology diabetes, tobacco and alcohol use, and • Komfo Anokye Teaching Hospital were recorded in duplicate for each participant, decreased physical activity. One limitation of this study is that it did not and averages were used for analysis. Height (cm), assess nutrition and other environmental weight (kg), and waist circumference (cm) were However, only 85 participants (10.1%) were influences, which are associated risk factors Contact Information 2 collected, and BMI (kg/m )andwaist-to-hip found to be obese (BMI ш30 kg/m2 for hypertension. Miriam Jaziri; [email protected] ), and Matthew Lyman, MPH; [email protected] ratios were calculated. Grant Sunada, MPH; [email protected] Latino Health Report Card, City of Long Beach, CA

Nahel Kapadia, University of Utah School of Medicine| Dr. Gail C Farmer, Dr.PH, Chair, Department of Health Science, California State University Long Beach

I. Introduction IV. Future Plans

Latinos represent approximately 40% of the total population in the city of Long Beach One of the many programs implemented by the City of (N=465,000). It is critical to assess their health Long Beach to address the economic and social needs in terms of mortality, morbidity and disparities faced by Latinos and other disadvantaged environmental risk factors. The Latino Health populations is the Long Beach Community Health Report Card will provide the information Improvement Plan 2014-2020. This plan consists of 3 needed by Government agencies, community goals: based organizations and non-profit foundations to develop, implement and evaluate health Goal 1: Ensure healthy living by addressing preventable programs within the city. (Community Health Assessment, 2013) and treatable health conditions such as obesity, chronic (Crampon & Norman, 2014) diseases, mental health, and increasing access to care. Long Beach is within the county of Los Angeles thus, much of the published data pertain to the county and not easily identified for long beach Goal 2: Create safe physical and social environments residents. To obtain valid and reliable health that promote good health. indicators we must review and extract data from county and state databases. Goal 3: Achieve health equity, eliminate disparities, and improve the health of Long Beach community residents.

(Community Health Assessment, 2013) II. Socioeconomic and Figure 1 V. Conclusions Ethnic Disparities III. Health Care The diversity and socioeconomic and ethnic distribution As shown in Figure 1, the percentage of Consequences within the city of Long Beach have many far-reaching Latinos is higher in west Long Beach, a consequences. From access to education and health region of the city that also scores the lowest care to employment opportunities , where one lives on the socioeconomic index. East Long More than 30 percent, greater than any other plays a major role in determining life expectancy, Beach, where the majority of the population racial group, of Latinos in Long Beach do not propensity for chronic diseases, and overall quality of is white, scores highest on the have health insurance (Figure 2). Compared life. As the Latino population in Long Beach continues socioeconomic index. The impact of this to the rest of the population, Latinos have to grow, it will become even more crucial to address the disparity in education level, household relatively higher incidences of death as a barriers facing disadvantaged groups. income, and other factors within the same result of accidents, intentional self-harm, city can be visualized in the chart in Figure 1 chronic liver disease and cirrhosis, and assault detailing life expectancy. Moving from east (Community Health Assessment, 2013). References Long Beach to west Long Beach, there is a 7.2 year decrease in the median life Figure 2 also shows that hospitalization rates 1. Crampon, W. J., & Norman, A. J. (2014, July). Ethnic Disparities in Long Beach. Retrieved from expectancy of the population. for heart disease and diabetes, leading causes http://www.rethinklongbeach.org/resources/Ethnic Disparities in Long Beach.pdf 2. Community Health Assessment. City of Long Beach Department of Health and Human Services. (2013, July). Retrieved of morbidity and mortality in Long Beach, are from http://www.longbeach.gov/health/medialibrary/ documents/planning-and-research/reports/community-health- assessment/community-health-assessment/

higher in the more heavily Latino-populated 3. Community Health Improvement Plan 2014-2020. City of Long Beach Department of Health and Human Services. (2014, March). Retrieved from http://www.longbeach.gov/health/media-library/documents/planning-and- western part of city. research/plans/community-health-improvement-plan/chip-final-approved-3-17_14/ Figure 2(Community Health Assessment, 2013) Adam Kilian, MD1,2 & Lauran Hardin, MSN, RN-BC, CNL1 1Trinity Health-Michigan d/b/a Mercy Health Saint Mary’s, Grand Rapids, Michigan 2Department of Medicine, University of Utah, Salt Lake City, Utah

Abstract Complex Care Maps© Results We developed a cross-continuum intervention process and a succinct tool called a Complex Care Map© (CCM) that addresses fragmentation in the system and links providers to a ($+
comprehensive indiviualized analysis of the patient story and causes for frequent access to * * health services. This intervention is associated with decreased healthcare system '$+
overutilization and cost of care. &$+
Introduction 
%$+
* The overuse of our nation’s healthcare system by “super utilizer patients” is well 

documented. Health care spending in the United States spent on the sickest five percent $+
causes more than 60% of health care cost. 







The complexity of high-need, high-cost (HNHC) patients often extends beyond %$+
* medical diagnoses to include community, behavioral, cultural, addiction, and socioeconomic challenges. Studies suggest that the complexity of these patients’ medical and/or &$+
* socioeconomic maladies hinders their ability to navigate the healthcare system, contributing * * * * * * * * * * to the cycle of overutilization, often through multiple institutions that are often '$+
disconnected from one another, leading to an expensive, inefficient healthcare environment that fails these patients. $+

Whereas most interventions focus on changing the patient, our approach to %$+
* improve the effectiveness, efficiency, and value in care was to focus on innovating a 


replicable intervention that changes the system of care around these &$+
* 
 !
patients to effectively identify and target the underlying root causes * driving the high-utilization behavior. '$+
* * The Complex Care Map© is a cross-continuum tool that addresses fragmentation in ($+
the system by linking providers to a comprehensive individualized analysis of a patient’s root causes contributing to return visits with supporting data. The CCM© is a guide that demystifies the complexity of a frequent user‘s clinical presentation *designates p-value <0.001 and utilization patterns by capturing the longitudinal story and bringing forward considerations to improve delivery of care. Discussion

Our intervention provides a successful approach to stabilize HNHC patients. Methods The intervention, which was associated with a 72.5% increase in operating margin, may prove particularly valuable as health systems shift further into Study Design: Using a pre-/post-test design in which each subject served as his/her own risk-based contracts. Rather than creating another care management and cost historical control, this QI project focused on determining if the interdisciplinary intervention infrastructure, the intervention is primarily managed by existing resources in the called CCM© had an impact on healthcare utilization and costs for HNHC patients. healthcaresystem and system operates and operates by improving coordination efficiency Setting: Analysis conducted Nov 2012 to Dec 2015 at Mercy Health Saint Mary’s in Grand through coordination of existing providers. Rapids, MI, an inner city tertiary care hospital with >80k annual ED visits. Subject Population: All referred patients with 3 or more hospital visits (ED or inpatient Individualized CCMs© for a select [IP]) in the 12 months prior to initiation of a CCM© (n=339) were included in the study. group of patients are associated with Outcome Variables: We compared utilization, cost, social, and healthcare access decreased healthcare system variables from the EMR and cost-accounting system for 12 months before and after overutilization and cost of care. CCMs© implementation. Statistical Procedures: We used Wilcoxon signed rank tests and McNemar’s chi-squared test to examine whether the difference in pre- and post-outcome measures were statistically significant. Tests were two-sided and a p value < 0.05 was considered statistically References significant. In an effort to examine distributional differences in utilization changes from the pre- to post-period, we conducted an analysis using patients in the 25th and 75th percentiles 1. Hardin L, Kilian A, et al. Cross-Continuum Tool is associated with Reduced Utilization and Cost of the distribution for each utilization outcome. for Frequent High-Need Users. Western Journal of Emergency Medicine. Dec 2016. http:// escholarship.org/uc/item/6hf0g27g. Accessed January 16, 2017.

Role of TRPC Channels in Cardiac Myocytes Bradley P. Meyer2,3, Azmi A. Ahmad1,2, Frank B. Sachse1,2 1 Department of Bioengineering, University of Utah, Salt Lake City, UT 84112, USA 2Nora Eccles Harrison Cardiovascular Research and Training Institute, University of Utah, Salt Lake City, UT 84112, USA 3University of Utah School of Medicine, Salt Lake City, UT 84112, USA

Introduction RESULTS

Heart disease is the epidemic of the 21st century. Most current therapies delay, A B C DA B but do not prevent mortality and have limited efficacy in preventing progression of heart disease. The precise course and molecular mechanisms of many types of heart disease are unknown. However, understanding the molecular mechanisms underlying heart disease is important for developing therapies to reduce morbidity and mortality. 10 μm In this project we studied transient receptor potential cation (TRPC) channels, TRPC 1 and TRPC 6, in cardiac muscle cells (myocytes) that are thought to be Figure 2: Cross-sectional images of NRVMs infected with A) wild-type, B) eGFP, C) eGFP- TRPC1, and D) eGFP-TRPC6. GFP is shown in green, SERCA in blue, TRPC1/6 in red. Scale bar involved in calcium signaling in the heart and development of heart disease and Figure 5: Measurement of calcium signals in neonatal rat ventricular myocytes. (A) The in A applies to B, C and D. failure (Seth et al., 2009). While several types of TRPC channels have been experimental protocol include pacing, rest in calcium and sodium free solution, and identified in the human body, the exact location and physiologic role of TRPC 1 application of caffeine to measure SR calcium load. and TRPC 6 within cardiomyocytes remains ill-defined (Nilius et al., 2007). Figure 3: Colocalization of TRPC-1, SERCA, and eGFP 2+ Currently, TRPC channels are thought to underlie store-operated and receptor- We measured the SR Ca load using the peak signal after caffeine application measured in images of NRVMs. + 2+ operated calcium entry into myocytes. Also, it is thought that the channels are following bathing in 0Na /0Ca solution in TRPC1-eGFP infected and eGFP The Manders’ overlap infected cells (Figure 4). We found an average SR load in TRPC1-eGFP infected located in the sarcolemma of cardiomyocytes (Parekh & Putney, 2005). However, coefficient was generally high cells of 1.89 ± 0.7, and an average SR load in eGFP infected cells of 2.79 ± 0.6 recent findings suggest that up-regulation of TRPC channels leads to increased (>0.6) among all studied calcium leak from the sarcoplasmic reticulum (SR) (Ohba et al., 2007), which protein labels. Cell numbers: (Figure 5). Similar studies with cells infected with TRPC6-eGFP were not possible would indicate that TRPC channels are located in the SR and not in the WT: n= 3, eGFP: n= 3, and due to low viability of cells. sarcolemma as previously thought. TRPC1: n = 2. CONCLUSIONS Hypothesis ‡ Immunolabeling, three-dimensional scanning confocal microscopy, and quantitative colocalization analysis indicated an intracellular location of We hypothesize that the TRPC channels are found in the SR and specifically We imaged non-infected wild-type, eGFP, eGFP-TRPC1 and eGFP-TRPC6 TRPC 1 with the SR of NRVMs. 2+ involved in intracellular calcium signaling as calcium leak channels (Figure 1). infected cells (Figure 2). After eGFP-TRPC6 infection, we rarely found viable cells ‡ Two-dimensional scanning confocal microscopy with a Ca sensitive dye for analysis. (RHOD-3) revealed a smaller SR content load in TRPC1-eGFP infected In TRPC1-eGFP infected NRVMs we measured colocalization between eGFP and cells. We explain this finding by upregulation of TRPC1 channels leading to SERCA, eGFP and TRPC1, and SERCA and TRPC1. Average Manders overlap increased SR leak and thus a lower SR content load. coefficients were 0.735, 0.796, and 0.691, respectively (Figure 3). In eGFP infected ‡ Infection of NRVMs with TRPC6 was associated with low viability, NRVMs we measured colocalization between eGFP and SERCA, eGFP and indicating that infection with TRPC6 has cytotoxic effects. Mechanisms endogenous TRPC1, and SERCA and endogenous TRPC1. Average Manders might include excessive Ca2+ leak from the SR and, thus, high cytosolic overlap coefficients were 0.878, 0.906, and 0.847, respectively. In wild-type, non- Ca2+ concentration triggering apoptosis. infected NRVMs we measured colocalization between eGFP and SERCA, eGFP Figure 1: EC couplings in cardiac myocytes with TRPC channels and endogenous TRPC1, and SERCA and endogenous TRPC1. Average Manders overlap coefficients were 0, 0, and 0.761, respectively. We attempted to measure METHODS the same parameters on cells infected with TRPC6-eGFP, but did not find viable REFERENCES cells. All functional and structural studies were performed on isolated neonatal rat [1] Nilius B, Owsianik G, Voets T, Peters JA. Transient receptor potential cation ventricular myocytes (NRVMs). Immunolabeling of the cells was performed after channels in disease. Physiol Rev. 2007; 87:165-217. isolation and fixation of the NRVMs. The NRVMs were infected with adenovirus [2] Ohba, T., Watanabe, H., Murakami, M., Takahashi, Y., Iino, K., Kuromitsu, S., at 200 MOI with either eGFP alone, TRPC1 conjugated eGFP (TRPC1-eGFP), or . . . Ito, H. (2007). Upregulation of TRPC1 in the development of cardiac TRPC6 conjugated eGFP (TRPC6-eGFP) to upregulate and identify TRPC hypertrophy. J Mol Cell Cardiol, 42(3), 498-507. channels within the cells. We applied three-dimensional confocal microscopy on Doi:10.1016/j.yjmcc.2006.10.020 cells infected with eGFP as well as labeled with antibodies specific for TRPC1/6, [3] Parekh, A. B., & Putney, J. W., Jr. (2005). Store-operated calcium channels. antibodies specific for sarco/endoplasmic reticulum Ca2+-ATPase (SERCA), and Physiol Rev, 85(2), 757-810. Doi: 10.1152/physrev.00057.2003 DAPI to validate and assess infection, visualize and reconstruct the distribution [4] Seth M, Zhang ZS, Mao L, Graham V, Burch J, Stiber J, et al. TRPC1 channels of the TRPC channels, visualize the distribution of SERCA channels in the SR, are critical for hypertrophic signaling in the heart. Circ Res. 2009; 105:1023-30. and identify the nucleus, respectively. We performed quantitative colocalization analyses to investigate the spatial relationship of TRPC channels with the sarcolemma and SERCA. Using two-dimensional scanning confocal microscopy and a Ca2+ sensitive dye ACKNOWLEDGEMENTS 2+ + 2+ (RHOD-3), we evaluated the rest decay of [Ca ] of cells bathed in Na and Ca Figure 4: Imaging of calcium transients in NRVMs using a pacing protocol. A) eGFP signal. Red free solution. SR Ca2+ content load was assessed through the amplitude of This work has been supported by the Nora Eccles Treadwell Foundation. Mr. box shows imaging window in B. B) Imaging window for measurement of of calcium signals. Meyer acknowledges funding from the Short-Term Training: Students in Health caffeine-induced peak of self-ratioed Ca2+ signals. White box shows ROI for calcium signal analysis during C) diastole, D) systole, E) 0Na+/0Ca2+, and F) after application of caffeine. Professionals Schools, a NIH/NHLBI grant to the University of Utah. (*0(.
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ABSTRACTAbstract METHODSMethods RESULTSResults From 2009-2014 data were collected at St. Diabetes is becoming a growing problem Table 1. Demographic Characteristics of worldwide. It is greatly influencing the health of Jude Hospital’s weekly outpatient diabetes Patients seen in the St. Jude Hospital Diabetes the small Caribbean nation of St. Lucia1. The clinic. Each of the 708 patients were entered Clinic from 2009-2014 (N=708). purpose of this study was to collect and analyze into a daily log and the following information baseline data from a weekly diabetes clinic at St. was recorded from each visit: gender, age, Variable Number Percentage Males 258 36% Jude Hospital on the rural southern tip of St. blood pressure, HbA1c value, lipid panel, Females 395 56% creatinine value, and ACE inhibitor or statin Lucia. The data was trended from 2009-2014. Unknown 55 8% There does not appear to be a significant change use. The data were analyzed by calculating Average age 60 in HbA1c or systolic blood pressure (SBP) over the mean, median, quartiles, standard Patients on ACE inhibitors 64 9% this time. The data were compared to U.S. deviation, and standard error. The data were Patients on Statins 240 34% Picture 1. Map depicting the location of St. Jude national data from the Centers for Disease organized into graphs, several of which are Patients with Complications 100 14% Hospital in St. Lucia. St. Lucia is located in the West Hospitalizations 78 Indies of the Caribbean. The island is approximately 27 Control and Prevention (CDC). The HbA1c and pictured below. They illustrate trends over miles long and 14 miles wide1. St. Jude Hospital is located time and a comparison to U.S. national data Foot ulcers 11 SBP values appear to be slightly higher in the Other 11 on the southern end of St. Lucia. St. Lucian diabetic population compared to the collected by the CDC. U.S. diabetic population. Conclusion Results Continued Goal 1: Provide baseline data for the diabetes INTRODUCTIONIntroduction clinic at St. Jude Hospital. From 2013 to 2015 the reported prevalence of • As change is implemented in the diabetes clinic, diabetes in St Lucia increased from 8.35% to progress can be tracked by comparing new data 10.9%, close behind the U.S. increase from Figure 1. HbA1c Among Adults with to the existing data. 10.9% to 12.8% 2,3. Over the next 20 years the Diagnosed Diabetes, United States 1988- • There does not appear to be any significant number of people with diabetes is estimated to 2006 and St. Lucia 2009-2014. Overall the St. change in HbA1c or SBP values from 2009- Lucian diabetic population has a higher median, 1st 2,3 2014 at St. Jude Hospital. increase by 40% . Increased funding for cost- rd quartile, and 3 quartile distribution of HbA1c Goal 2: Compare diabetic patient data in St. effective diabetes prevention and treatment is values compared to the U.S. population4. needed2,3. The purpose of this study is to Lucia to U.S. data collected by the CDC. provide baseline data. Future interventions can • The HbA1c and SBP values appear to be slightly be tracked using outcome measures to ensure higher in the St. Lucian diabetic population compared to the U.S. population that quality of care is improving.

References LIMITATIONSLimitations Figure 2. Systolic Blood Pressure (SBP) Distribution Among Adults with Diagnosed 1. The World Factbook. Central Intelligence Agency (CIA). https://www.cia.gov/library/publications/the-world- Ideally the data collected at St. Jude hospital factbook/geos/st.html . Accessed 17 November 2016. Diabetes, United States 1988-2006 and St. 2. International Diabetes Federation North America and Caribbean (IDF) St. Lucia. 2014. from 2009-2014 would be directly compared to http://www.idf.org/membership/nac/st-lucia. . Accessed on 17 November 2016. Lucia 2009-2014. Compared to the U.S., the St. 3. International Diabetes Federation North America and Caribbean (IDF) United States. 2013. U.S. data from the same time period. http://www.idf.org/sites/default/files/attachments/USA_Scorecard.pdf.. Accessed 21 November 2016. Lucian population has a higher percentage of 4. Diabetes Public Health Resource. Center for Disease Control and Prevention (CDC). Unfortunately, the most relevant and relatable diabetic patients in the elevated SBP ranges4. http://www.cdc.gov/diabetes/statistics/a1c/index.htm. Accessed 28 November 2016. data was collected by the CDC from 1988-2006. Additionally, data from St. Jude Hospital in 2009 ACKNOKLEDGMENTSAcknowledgments and 2014 is a less accurate representation of the I would like to thank the staff at the diabetes clinic and medical records department at St. Jude Hospital for collaborating to design this project and for collecting data. I would also like to population because data was not collected for the thank Melissa Duncanson for helping collect and organize data and Dr. Robison and Dr. entire 12 months during those years. Dickerson for helping create project goals and manage the logistics. Colon Pathology Characteristics in Li-Fraumeni Syndrome: Age and Size Don’t Matter

Hailey M. Shepherd1, William Rengifo-Cam MD2, Wendy Kohlmann MS, CGC3, Joshua D. Schiffman MD3, Kory Jasperson MS, CGC3, Jewel Samadder MD4, Wade Samowitz MD5, S. Tripp5 MD, Randall Burt MD3,4 University of Utah Medical School1, Jupiter Medical Center2, University of Utah Huntsman Cancer Institute3, University of Utah Division of Gastroenterology4, University of Utah Department of Pathology5

ABSTRACT RESULTS The purpose of this study was to examine the ¾ Among 66 confirmed TP53 mutation carriers, 31 ¾ The most aggressive colon pathology frequency and characteristics of colon polyps and (47%) individuals underwent a total of 73 phenotypes were observed in Del Exon 1, colorectal cancer (CRC) in individuals with Li- procedures, 36 (49%) included abnormal findings R258W, I125L, and P177R TP53 mutations Fraumeni Syndrome (LFS). LFS is an inherited (Fig 2). (Fig. 4). cancer predisposition syndrome caused by TP53 mutations. LFS is associated with a dramatically Figure 2: LFS patients receiving colonoscopy Figure 4: Distribution of TP53 Germline increased risk for a spectrum of cancers. Bone and Mutations in Colorectal lesions soft tissue sarcomas, breast cancer, brain tumors, adrenal cortical carcinoma and leukemia have been classically associated with this syndrome. Approximately 50% of the individuals carrying mutations in TP53 will develop cancer by the age of 30 years, with a lifetime risk of up to 70% in men and almost 100% in women. ¾ A total of 58 lesions were detected and biopsied INTRODUCTION including 23 (40%) TA, 5 (9%) SSP, 8 (13%) HP, 12 (21%) BCM, and 8 (13%) CRC/HGD. Early onset colon cancer has been described ¾ Small TA (2-6 mm) in the descending colon was the as a component of LFS, and current most frequent lesion found, while the sigmoid colon guidelines recommend colonoscopy Figure 5: SSA with HGD from LFS participant was the most common site for all lesion types. screening begin at age 25 and repeat every 2 to 5 years in patients with LFS. Early Figure 3: Colonoscopy lesion size in LFS patients detection is key for preventative treatment in these patients, yet guidelines for colorectal screening have not yet been evaluated in this population. To our knowledge, no prior study High grade dysplasia (200X) has yet to extensively detail the characteristics of the lesions found during screening colonoscopy in LFS patients DISCUSSION regarding number, size, location, histology, ¾ Although one patient presented with a significantly and genotype/phenotype associations. larger CRC lesion (7 cm), all other CRC/HGD lesions (average 6.7 mm) were considerably smaller than Table 1: Features of CRC/HGD in LFS patients the 4.5 cm average colon tumor size reported in the METHODS general population. ¾ Participants were identified from the ¾ Current guidelines are likely to be insufficient to IRB approved Cancer Genetics Study identify colon cancers at an early stage because the protocol at Huntsman Cancer Institute. majority may occur before age 25. ¾ All participants had a confirmed ¾ Colonoscopy is an important part of screening for all pathogenic TP53 variant. patients with LFS, but earlier and more frequent ¾ Medical records were reviewed to screening may be necessary for families with a determine the number of polyps, age history of colon cancer. at colonoscopy, histologic features of polyps [tubular adenoma (TA), sessile ACKNOWLEDGMENTS serrated polyps (SSP), hyperplastic ¾ A special thanks to Wendy Kohlmann and Joshua polyps (HP), normal or benign colonic Schiffman for input and collaboration with this mucosa (BCM), and colorectal project, as well as the study participants and the cancer/high grade dysplasia ¾ 8 CRC/HGD lesions found in 5 patients with a Genetic Counseling core facilities supported by P30 (CRC/HGD)]. medium size of 13.4 mm (2-70 mm) predominately CA042014 awarded to Huntsman Cancer Institute. arising from TA (63%)

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BACKGROUND PATIENT-LEVEL FACTORS PATIENT FLOW DIAGRAM ‡ Critically-ill patients are at high risk for developing venous ASSOCIATED WITH aFXa LEVELS thromboembolism (VTE), which includes deep vein thrombosis and pulmonary embolism. ‡ Enoxaparin, a low molecular weight heparin (LMWH), is commonly used as VTE prophylaxis for surgical patients. Current enoxaparin dosing paradigms support a “one size fits all”, or fixed dose prophylaxis strategy. ‡ Previous studies have shown that standard enoxaparin dosing is inadequate for the majority of trauma patients. ‡ We plan to determine whether a fixed dose enoxaparin prophylaxis provided effective anticoagulation and VTE prevention, assess the usefulness of real time enoxaparin dose adjustment in optimizing anticoagulation, and examine patient- RESULTS level factors as potential predictors of enoxaparin metabolism in Figure 1: Patients’ peak aFXa levels corresponding with weight. acute care and trauma surgical patients. Grey box represents appropriate levels (0.2-0.4 IU/ml). METHODS ‡ Population: Acute care and trauma surgical patients, ≥ 18 years old, enoxaparin 30 BID began within 36 hours after surgery. ‡ Blood draws: aFXa levels were drawn 4 hours and 12 hours, respectively, after patient’s 3rd dose of enoxaparin. ‡ aFXa monitoring: Goal aFXa range was 0.2-0.4 IU/ml and a real time dose adjustment algorithm was implemented for patients with out of range aFXa levels. ‡ Follow-up: Chart review, patient phone calls, and/or certified letters were utilized 3 months post-operatively to screen for Patients with sub-therapeutic aFXa levels were more likely to symptomatic VTE events. have post-operative VTE (16.1% vs 8.3%, p = .38). Figure 2: Patients’ peak anti-Xa levels corresponding with APACHE II. DOSE ADJUSTMENT ALGORITHM Grey box represents appropriate levels (0.2-0.4 IU/ml). CONCLUSIONS PATIENT DEMOGRAPHICS ‡ At a standard enoxaparin dose of 30 BID, 56.4% of patients had below-range aFXa peaks, and 80.4% had below-range troughs. Out-of-range aFXa In-range aFXa P value (n=32) (n=23) ‡ Patient-level factors including APACHE II score and gross weight Age in years, mean ±SD 49 ±15 46 ±21 .53 correlate with aFXa levels. Gender, % .007 Female 25 61 ‡ A greater proportion of patients achieved in range aFXa levels Male 75 39 with dose adjustment (74.5% vs 43.6%, p < .001). Body mass index in kg/m2, mean ± SD 28.0 ±5.8 25.5 ±5.3 .10 Gross weight in pounds, mean ±SD 189 ±35 157 ±30 .001 ‡ Real time aFXa level monitoring and dose adjustment can Creatinine in mg/dL, mean ±SD 0.82 ±0.24 0.76 ±0.19 .32 increase the proportion of patients who receive adequate Current smoker, % 34 26 .43 Caprini score, mean ±SD 10 ±4 10 ±5 .94 prophylaxis and may result in reduced VTE outcomes. APACHE II score, median (IQR) 7.5 (3, 11.5) 6.0 (5, 8) .43 Patient Type, % .22 Acute care 47 30 REFERENCES Trauma 53 70 Length of operation prior to enrollment in 99 (71, 190) 138 (91, 189) .48 ‡ Berndtson AE, Costantini TW, Lane J, et al. If some is good, more minutes, median (IQR) Length of hospital stay in days, median (IQR) 11 (7, 18) 8 (5, 12) .09 is better: an enoxaparin dosing strategy to improve pharmacologic venous thromboembolism prophylaxis. J Trauma Length of enoxaparin prophylaxis in days, 13.5 (5, 32) 9 (5, 31) .89 median (IQR) Acute Care Surg. 2016;81(6):1095-1100. ,
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