Days Of Fatigue Research Articles

Patient and Physician Perspectives of Systemic Lupus Erythematosus Flare: A Qualitative Study.

Systemic lupus erythematosus (SLE) flares are associated with increased damage and decreased health-related quality of life. We hypothesized that there is discordance between physicians' and patients' views of SLE flare. In this study, we aimed to explore patient and physician descriptions of SLE flares. We conducted a qualitative descriptive study using in-depth interviews with a purposeful sample of patients with SLE (who met 1997 American College of Rheumatology or Systemic Lupus International Collaborating Clinics criteria) and practicing rheumatologists. Interviews were audio-recorded, transcribed, and analyzed using applied thematic analysis. Forty-two patient participants with SLE, representing a range of SLE activity, completed interviews. The majority described flare symptoms as joint pain, fatigue, and skin issues lasting several days. Few included objective signs or laboratory measures, when available, as features of flare. We interviewed 13 rheumatologists from 10 academic and 3 community settings. The majority defined flare as increased or worsening SLE disease activity, with slightly more than half requiring objective findings. Around half of the rheumatologists included fatigue, pain, or other patient-reported symptoms. Patients and physicians described flare differently. Participants with SLE perceived flares as several days of fatigue, pain, and skin issues. Providers defined flares as periods of increased clinical SLE activity. Our findings suggest the current definition of flare may be insufficient to integrate both perceptions. Further study is needed to understand the pathophysiology of patient flares and the best way to incorporate patients' perspectives into clinical assessments.

335: RARE CO-OCCURRENCE OF FAVISM-INDUCED HEMOLYSIS AND METHEMOGLOBINEMIA SECONDARY TO G6PD DEFICIENCY

Introduction: G6PD deficiency testing is performed in all American newborns but this diagnosis is largely unknown in the immigrant population. Consequently, it is under-recognized as many are asymptomatic until an exposure; fava beans are known oxidative stressors causing hemolytic anemia. They can also induce methemoglobinemia in G6PD deficiency due to low levels of NADPH; a co-factor involved in regulation of methemoglobin (MetHb). The diagnosis of favism-induced hemolysis & methemoglobinemia in G6PD deficient individuals is rarely reported. The first line treatment for methemoglobinemia is methylene blue, however in patients with G6PD deficiency methylene blue can potentiate the hemolytic anemia. Therefore, the recognition of these two processes’ occurring simultaneously has clinical and therapeutic significance. Description: 37-year-old male born in Yemen presented to the emergency department with 2 days of fatigue, presyncope and dark urine. He consumed 2 large cans of fava beans in the days preceding presentation. On admission, vitals were notable for SpO2 of 67% on room air with no significant change despite oxygen support. Physical exam showed mild scleral icterus and jaundice. ABG revealed PaO2 452 mmHg, O2 saturation 83% and MetHb 14%. Labs also notable for Hgb 11.8 g/dL, haptoglobin < 30 mg/dL, T.Billi 4.8 mg/dL, LDH 310 U/L and peripheral blood smear with blister cells. EKG, CXR and urinalysis were unremarkable. Favism-induced hemolytic anemia and methemoglobinemia due to G6PD deficiency was suspected therefore ascorbic acid 1000 mg every 6 hours was initiated. Despite treatment, the Hgb down trended to a nadir of 5.7 g/dL requiring 4 U PRBC. T.Billi and LDH peaked at 6.2 mg/dL and > 1800 U/L, respectively. MetHb levels dropped immediately after initiation of ascorbic acid to a nadir < 2%. On day 3 the G6PD screen was positive for deficiency and by day 4 the SpO2 returned to 100% on room air. On day 5, labs had stabilized, ascorbic acid was discontinued, and patient was discharged home with hematology follow up. Discussion: The co-occurrence of favism induced hemolysis and methemoglobinemia in G6PD deficient individuals is scarcely reported in the literature. When correctly diagnosed with subsequent initiation of appropriate treatment patients can have complete recovery.

RF30 | PSAT135 Rare Case of Hypercalcemia Mediated by an Ectopic Parathyroid Hormone (PTH), and Parathyroid Hormone-Related Peptide (PTHrP) Co-Secretion Secondary to Metastatic Cervical Carcinoma

Abstract Introduction Hypercalcemia of malignancy occurs in ∼20-30% of cancer patients. This mostly occurs by three mechanisms: humoral mediated from excess production of PTHrP, osteoclast mediated bone resorption from osteolytic metastasis and calcitriol mediated in granulomatous diseases such as lymphoma. Very rarely, PTH mediated hypercalcemia can occur in the setting of ectopic PTH production from tumor cells. Case presentation A 57 year- old woman with a medical history of hypertension and hyperthyroidism presented to the emergency department with several days of fatigue, nausea, vomiting, constipation and abdominal pain. Exam was remarkable for a heart rate (HR) of 140, lethargy, dry mucous membranes and chronic bilateral proptosis. Labs were remarkable for corrected calcium level of 18.38 mg/dl, Phosphorous of 3.2 mg/dL, Mg level of 1.2 mEq/L, blood urea nitrogen (BUN) of 20 mg/dL, creatinine of 1.6 mg/dL alkaline phosphatase of 170 units/L, and Lactic acid was 3.0 mmol/L. TSH 0.291 (0.40-4.7), FT4 1.51 ng/dl (0.70-1.80), FT3 3.2 pg/ml (2.8-5.3). Patient was treated with IV fluids, calcitonin 4u/kg bid, zoledronic acid 4 mg and started on cinacalcet. Further workup revealed elevated PTH of 1351 pg/ml (16-80), PTH-rP of 28 (&amp;lt;2), 25-hydroxyvitamin D of 25.5 ng/ml (30-100), 1,25-dihydroxy vitamin D level of 59.8 pg/ml (19.9-79.3). Patient couldn't tolerate sestamibi scan. 4DCT couldn't be performed due to creatinine elevation Bedside US performed did not show any evidence of parathyroid adenoma. CT, abdomen and pelvis a large mass in the cervix and cecum. Cervical biopsy revealed necrotic tumor with vary rare nests of viable atypical cells. Given persistent hypercalcemia, despite additional treatment, CRRT was initiated on hospital day 15 with rapid normalization of calcium level. However, patient continued to rapidly deteriorate with multi-organ failure and was transitioned to comfort care before expiring. Autopsy revealed poorly differentiated necrotic cervical carcinoma measuring 12×6×8 cm with metastasis to the left ovary as well as multiple tumor lesions in the liver. Parathyroid glands were normal on gross exam. PTH staining could not be performed given degree of tumor necrosis Discussion Hypercalcemia with elevated PTH and negative localization studies, should raise suspicion for ectopic PTH production from underlying malignancy. In PTHrP mediated hypercalcemia, PTH as well as 1,25 (OH) D are expected to be suppressed. This patient had an elevated PTHrP but not enough to suppress PTH or 1,25 (OH) D level. Given that parathyroid glands were normal on gross exam; this is consistent with ectopic PTH mediated hypercalcemia with component of PTHrP co-secretion. Hypercalcemia of malignancy presents late and portends a poor prognosis and therefore appropriate diagnosis and management is critical. Presentation: Saturday, June 11, 2022 1:00 p.m. - 3:00 p.m., Monday, June 13, 2022 12:42 p.m. - 12:47 p.m.

TREATMENT OF HYPEREOSINOPHILIA WITH MEPOLIZUMAB IN A 6-YEAR-OLD BOY

<h3>Introduction</h3> Hypereosinophilic syndrome (HES) is a rare cause of hypereosinophilia among pediatric patients. Mepolizumab, an IL-5 antagonist, is an effective treatment for hypereosinophilia approved for patients ≥12 years of age, but for younger children treatment remains limited to corticosteroids or other cytoreductive agents. This case illustrates successful treatment of hypereosinophilia with mepolizumab in a child. <h3>Case Description</h3> A previously heathy 6-year-old male presented with three days of fatigue, fever, and right cervical lymphadenopathy with an elevated absolute eosinophil count (AEC) that peaked at 83,350 cells/microliter. Work up for infectious disease, end-organ damage, and malignancy with flow cytometry and cytogenetics from blood, bone marrow and lymph node biopsy were negative. Mepolizumab 100 mg injected subcutaneously was given, leading to progressive decline in AEC to 3,370 cells/microliter after 14 days. Fevers, fatigue, and lymphadenopathy resolved. Monthly mepolizumab and close monitoring is planned. <h3>Discussion</h3> HES is a heterogenous group of disorders; of paramount concern is development of malignancy and end-organ damage due to eosinophilic infiltration of tissues. Although effective for hypereosinophilia, long-term treatment with corticosteroids is associated with significant adverse events and may cause diagnostic uncertainty when monitoring pre-malignant conditions. While mepolizumab is approved for children ≥6 years of age for the treatment of asthma, it is not approved for HES in this age group. This case highlights that mepolizumab is an effective steroid-sparing therapy in young children with hypereosinophilia that allows continued monitoring for malignancy without masking or delaying diagnosis from corticosteroid use.

ODP552 Hypercalcemic Crisis Due to PTH Secretion From a Poorly Differentiated Esophageal Neuroendocrine Tumor

Abstract Background Paraneoplastic secretion of PTH is described in a number of solid organ tumors. Hypercalcemia occurs in up to 30% of patients with malignancy. The most common cause of this phenomenon is PTHrP production. We present a rare case of PTH mediated hypercalcemic crisis from a tumor of presumed esophageal lineage. Clinical Case A 54-year-old man presented with several days of fatigue, lethargy and polyuria. Initial calcium was markedly elevated at 18.4 (8.3-10.1mg/dL). Past medical history included Barrett's esophagus, history of gastric bypass, and prior alcohol abuse. He also had progressive dysphagia and 30lb weight loss over the prior month. On examination, he had tachycardia, cachexia, and encephalopathy. Laboratory testing revealed an elevated PTH of 281 (nl 18.4-80.1pg/mL), creatinine 1.34mg/dL, and low phosphorus at 2.8 (nl 2.7-4.5mg/mL). Hypercalcemia was treated with IV fluids, calcitonin, and pamidronate. The calcium normalized but PTH remained 210pg/mL. Subsequent PTHrP and 1,25 di-hydroxy vitamin D levels were normal. Esophagogastroduodenoscopy (EGD) revealed a friable esophageal mass and biopsy identified a poorly differentiated carcinoma with neuroendocrine features, immunoreactive to synaptophysin and high Ki-67 index of 90%. Immunostains for chromogranin and PTH were negative. A CT of the chest, abdomen, and pelvis revealed diffuse metastases in the liver, lungs, and enlarged mediastinal lymph nodes. The source of primary tumor could not be fully identified from pathology but suspected to be esophageal. Parathyroid scan showed a subtle persistent uptake posterior to right side of trachea suspicious for a parathyroid adenoma, but that could not account for the severity of PTH elevation. He was readmitted in 1 month with recurrent symptomatic severe hypercalcemia to 18mg/dL and PTH to 619.4pg/mL. Again, he received IV fluids, calcitonin, and zoledronic acid. He received 3 cycles of platinum and etoposide based chemotherapy. After chemotherapy, PTH decreased to 123pg/mL and calcium to 9.7mg/dL but he continued to have rapid disease progression including jaundice, pathological bone fractures and orbital metastases. He elected hospice care and passed away in about 4 months from initial diagnosis. Final PTH was 916.8pg/mL. Conclusion PTH is a normally secreted by parathyroid gland chief cells, which are part of the embryonic neural crest cells found in various neuroendocrine tissues. It is plausible that malignancies with neuroendocrine features may secrete neuropeptides including PTHrP and PTH. Few case reports exist describing PTH secretion by neuroendocrine tumors, though most common are tumors of gastroenteropancreatic origin. PTH stain and focal chromogranin tends to be negative with poorly differentiated neuroendocrine tumors. PTH gene is usually intact and upregulation of the regulator sequence of PTH gene promotor is suspected to be the mechanism of elevated PTH levels and hypercalcemia. This case demonstrates the potential for poorly differentiated neuroendocrine malignancies to cause hypercalcemic crises from paraneoplastic secretion of PTH. Presentation: No date and time listed

USE OF PLASMA EXCHANGE TO TREAT REFRACTORY DIFFUSE ALVEOLAR HEMORRHAGE FROM ANTINEUTROPHIL CYTOPLASMIC ANTIBODY-ASSOCIATED VASCULITIS

USE OF PLASMA EXCHANGE TO TREAT REFRACTORY DIFFUSE ALVEOLAR HEMORRHAGE FROM ANTINEUTROPHIL CYTOPLASMIC ANTIBODY-ASSOCIATED VASCULITIS

S3201 Zieve's Syndrome: A Case of Hemolytic Anemia in the Setting of Alcoholic Liver Disease

Introduction: Zieve’s syndrome is a rare condition which typically manifests with hemolytic anemia, hyperlipidemia, jaundice in the setting of alcohol-induced liver injury. This is distinct from alcoholic hepatitis which may present simultaneously or develop later. Case Description/Methods: 42-year-old man with a history of alcohol abuse and compensated cirrhosis presented to the emergency department for evaluation of 7 days of fatigue and jaundice in the setting of heavy alcohol use. He was noted to have a normocytic anemia with hemoglobin of 5.6 g/dl, INR of 3.0, total bilirubin of 26.2 mg/dl, AST of 65, and ALT of 23 IU/L. Lipid profile was normal. US liver and Doppler US revealed heterogenous liver with biphasic flow through majority of the veins consistent with portal hypertension. Patient denied recent use of new medications or herbal supplements. Prophylactic antibiotics for suspected gastrointestinal bleeding were started. He underwent EGD which revealed trace esophageal varices and portal hypertensive gastropathy without active bleeding. A peripheral blood smear showed spur cells, but no spherocytes or schistocytes consistent with Zieve's syndrome. Direct and indirect Coombs tests were negative, low haptoglobin levels, and elevated serum LDH. Blood cultures were all negative. In view of evidence of hemolysis and lack of infectious source a diagnosis of Zieve’s syndrome was made and patient treated with supportive care and blood transfusions as needed. Unfortunately, the patient was placed in comfort measures after developing refractory grade IV hepatic encephalopathy and hepato-renal syndrome despite supportive measures. Discussion: Hyperlipidemia in Zieve’s syndrome results from cholestasis and hemolysis induced by alcohol liver injury, but was not present in our case. It is postulated that vitamin E deficiency secondary to alcohol use can result in pyruvate kinase instability which affects RBC metabolism resulting in hemolytic anemia. It is important to recognize that Zieve’s can mimic or present concurrently with alcoholic hepatitis as both conditions present with anemia, jaundice, and alcohol use. An important distinction is the presence of hemolytic anemia in the former. Management is supportive as well as abstinence from alcohol.

Sleep and Exercise among Young Doctors in a Tertiary Care Hospital in India: A Pilot Cross-Sectional Study.

Limited information is available on the sleep and propensity for daytime sleepiness in young medical doctors of India. The 2-week self-reported data surrounding sleep and exercise habits, and the Epworth sleepiness scale (ESS) score obtained from volunteering doctors of a tertiary care hospital in India, were summarized as median (Q1-Q3). Comparisons with Mann-Whitney U test and correlations with Spearman's rank correlation were done. Forty-seven doctors (28 [26-33] years, 16 males) reported a total sleep duration (TSD) of 6.3 (6-6.7) hours, sleep latency of 9 (5.1-15.8) minutes, and ESS score of 8 (5-10). The number of days (out of 14) when the subjective feeling of 'refreshed', 'somewhat refreshed', and 'fatigued' was experienced was respectively 6 (2-9), 5 (3-8), and 1 (0-4). Junior-level doctors experienced more days of 'fatigue' than senior-level doctors (3 [0-4.3], 0 [0-0]; p = 0.002). Doctors who did not exercise reported greater days of fatigue than those who exercised (2 [0-4.8], 0 [0-2]; p = 0.047). The young doctors of our study slept less than the recommended amount of 7 hours by the American Academy of Sleep Medicine. Their short sleep latency and normal propensity for daytime sleepiness, though encouraging, may be an effect of insufficient sleep and mentally alerting daytime schedule respectively. Notably, we found a positive association between exercise habits and subjective restoration following sleep in our study population. The sleep requirements and sleep structure among Indians are yet to be established. Our findings add to the data on sleep in the Indian context.

P430 TUMORAL THROMBOTIC MICROANGIOPATHY: A RARE CAUSE OF ACUTE PULMONARY HYPERTENSION

Abstract Introduction Among the causes of acute pulmonary hypertension, the occlusion of the little pulmonary vessels caused by tumoral microemboli, even from an unknown neoplasm, is an infrequent condition with a very poor prognosis. Clinical Case A 55–years old woman with no relevant past medical history presented to the Emergency Department with dyspnea at rest, desaturation, palpitations and a brief episode of chest pain, after several days of fatigue and exertional dyspnea. ECG showed sinus tachycardia and signs of right ventricle pressure overload with inverted T waves in V3–V4 and in the inferior leads (Fig. 1). On laboratory tests there were high D–dimer values and a slightly elevated TnI. Blood gas analysis showed hypoxemic hypocapnic respirstory alkalosis. An Echocardiogram revealed severe dilatation and dysfunction of the right ventricle and signs of high probability of pulmonary hypertension (Fig. 2). Pulmonary CT scan ruled out embolism and showed irregular thickening of the interstitium and mediastinal lymphoadenopathy. Then, a rapid clinical deterioration happened, refractory to inotropes infusion and larger volumes of oxygen. The programmed diagnostic pathway cannot be pursued. On day 4, there was respiratory distress and pulseless electrical activity cardiac arrest during endotracheal intubation. ECMO mechanical support was positioned but on day 7 the patient died. Autopsy, made to discover the cause of pulmonary hypertension, revealed the presence of a colonic invasive adenocarcinoma with micropapillary pattern and thoracic and pelvic lymph–nodal metastases. Microscopic evaluation of the lungs showed a widespread neoplastic vascular invasion with microthromboemboli (Fig. 3). Discussion Tumoral thrombotic microangiopathy is a cause of pulmonary hypertension of multifactorial origin and should be suspected in cases of pulmonary hypertension without pulmonary embolism or interstitial lung disease. The rarity of this condition and the absence of an oncological medical history make difficult the diagnostic hypothesis. Besides, the lacking of an effective therapy makes the prognosis poor.

A Child With Jaundice

Question: An 11-year-old Haitian boy with a history of hemoglobin S/β thalassemia heterozygous hemoglobinopathy (HbS/β-Thal) presented with 3 days of fatigue, pruritis, jaundice, and hematochezia. He had no abdominal pain, fever, nausea, or vomiting and no appreciable tenderness or organomegaly on physical examination. He had no prior clinical manifestations or complications related to his HbS/β-Thal disease. Peripheral blood indices revealed a red blood cell count of 5.73 M/μL, a mean corpuscular volume of 62.7 fL, and a hematocrit of 35.9%.

Web Exclusive. Annals for Hospitalists Inpatient Notes - Myocarditis After Vaccination for SARS-CoV-2.

Web Exclusive. Annals for Hospitalists Inpatient Notes - Myocarditis After Vaccination for SARS-CoV-2.

Acknowledging the Blind Spot of Bitemporal Hemianopsia: Keeping a High Index of Suspicion for Pituitary Macroadenomas in Uncommon Presentations

Background: Hyperglycemia in patients with type 2 diabetes mellitus commonly manifests as symptoms of polyuria, polydipsia, fatigue, and weight loss as a result of insulin resistance. In cases of severe hyperglycemia, patients may also experience visual disturbances and dizziness as a result of swelling of the lens and dehydration respectively. These symptoms are not generally accompanied by gait disturbance or fixed, focal deficits on neurological examination. As such, symptoms such as double vision, peripheral field vision loss, cranial nerve deficits, or significant unsteadiness may warrant a more extensive neurologic workup rather than simply attributing all symptoms to hyperglycemia. Clinical Case: A 57-year-old woman presented to the emergency department with five days of fatigue, polyuria, polydipsia and pre-syncope associated with dizziness. She also described double vision in her peripheral visual fields and episodes of gait disturbances causing her to have to lower herself to the ground on multiple occasions, without loss of consciousness. Her neurologic examination demonstrated mildly ataxic finger-to-nose testing and concern for peripheral field vision loss. Intake lab work revealed a blood glucose of 725 mg/dL and a hemoglobin A1C of 13.4%. Initial neuroimaging with computed tomography was unremarkable. Though her symptoms were thought to be due to severe hyperglycemia, an MRI brain was obtained due to abnormal neurologic examination. MRI demonstrated a 1.9 cm pituitary macroadenoma abutting the optic chiasm with concern for hemorrhage. Subsequent lab evaluation determined the pituitary macroadenoma non-functional with TSH, free T4, free T3, AM cortisol, AM ACTH, and prolactin all within normal limits. Her hyperglycemia was treated with insulin with clinical improvement in all regards except visual symptoms. She was deemed safe for discharge with neurosurgical follow-up regarding surgical removal of her macroadenoma. Conclusion: Although hyperglycemia may present with broad symptoms including vague neurologic symptoms, it is critical to keep a broad differential diagnosis when atypical symptoms such as persistent vision changes and gait disturbances are present, especially after improvement in glycemic control has been obtained. A low threshold should be held for obtaining neuroimaging, as it is prudent to rule-out life-threatening causes of neurologic dysfunction.

S2400 Typhoid Fever: An Unusual Cause of Acute Hepatitis

INTRODUCTION: Typhoid fever, a disease highest in incidence in South Asia, is due to Salmonellae ingestion via feces-contaminated food or water. While hepatic involvement is not rare given colonization of reticuloendothelial tissues, an acute hepatitis picture, as seen here, is unusual. CASE DESCRIPTION/METHODS: A 25 year old female without past medical history presented febrile, tachycardic, and hypotensive after 8 days of fatigue, fevers, chills, myalgias, headaches, nausea, and emesis following a trip to Miami. She had taken daily Acetaminophen since onset and denied other medication, herbal, and alcohol consumption. Of note, the patient emigrated to the United States 9 months prior and made a 3 month trip home to the Indian subcontinent 3 weeks before presentation. While there, she took Acetaminophen and a course of Amoxicillin. She and multiple family members also experienced fever, nausea, emesis, and diarrhea after consuming raw vegetables. Notable labs include leukopenia at 4.1, AST 593, ALT 560, and ALP 148. Urgent care labs 2 days prior were significant for AST 68, ALT 59, ALP 106, and negative hepatitis serologies. She received Ceftriaxone, IV fluids, and NAC, though plasma Acetaminophen level resulted as < 5 mcg. After blood cultures yielded gram negative rod bacteremia, antibiotics were changed to Piperacillin/Tazobactam. Abdominal ultrasound was unremarkable and triple phase CT showed mild hepatic heterogeneity. Repeat hepatitis serologies, CMV, EBV, autoimmune markers, malarial smears, and HIV were among tests ordered to determine acute transaminitis etiology. Blood cultures eventually revealed Salmonella enterica susceptible to Amoxicillin. Transaminases continued to downtrend after 5 days of hospitalization and she was successfully discharged home. DISCUSSION: Acute febrile illness in a patient recently abroad prompts investigation into diseases endemic to the region from which a patient has travelled. For the Indian subcontinent, typhoid fever may be a culprit, but its nonspecific presentation renders suspicion difficult especially when complicated by acute transaminitis and DILI concerns. As with our patient, diseases such as malaria, hepatitis, and HIV should also be considered. Depending on individual inoculum as well as host immunocompetence, incubation may be 5-21 days with prolonged fever for up to 1 month if the disease goes untreated. Interestingly, leukopenia is noted in 15-25% of cases. Blood cultures, integral to the work-up of recurrent fever, ultimately led to our diagnosis.

Fatal COVID-19 in a Patient with End-Stage Liver Disease Wait-Listed for Liver Transplantation: An Evidence-Based Review of COVID-19 Screening Modalities Prior to Transplant.

Fatal COVID-19 in a Patient with End-Stage Liver Disease Wait-Listed for Liver Transplantation: An Evidence-Based Review of COVID-19 Screening Modalities Prior to Transplant.

SUN-573 Use of PCSK9 Inhibitors Post-Transplant

Background:Dyslipidemia is common in patients after transplant. While statins are the mainstay of therapy, interactions with immunosuppressants such as calcineurin inhibitors (CNIs) can limit dose titration or lead to intolerance of this important drug class. Withdrawal of statin therapy can precipitate hyperlipidemia and potentially accelerate cardiovascular disease in transplant recipients, including coronary allograft vasculopathy (CAV) in heart transplant (HT) patients. Proprotein convertase subtilisin-kexin type 9 inhibitors (PCSK9i) may provide a safe, effective option for such patients. PCSK9i profoundly reduce low-density lipoprotein (LDL) and subsequently the risk of cardiovascular events in nontransplant patients. Further, these novel agents have no known interactions with CNIs. There is a paucity of data describing PSCK9i use post-transplant, with only a few small case series reported in HT recipients. Here, we summarize our experience along with available literature on this topic.Methods:In this retrospective case series we investigated adult recipients of heart transplant who were treated with PCSK9 inhibitors from July 2015 to 2019 because of statin intolerance or refractory hyperlipidemia. We compared the data of patients at baseline and after various durations of therapy with the PSCK9i evolocumab and alirocumab using the median and interquartile range (IQR). Specifically, we evaluated PCSK9i efficacy, effect on immunosuppressant levels, cardiac function and adverse events.Results:Five patients (4 men; median age 54, IQR 52-60) underwent heart transplant an average of 7.4 years ago. Median treatment duration of evolocumab or alirocumab was 12 months (IQR 7-17). This led to a reduction of total cholesterol by 94 mg/dl (p=0.04) (47% decrease) and LDL cholesterol by 83 mg/dl (p=0.04) (69% decrease). No statistically significant difference in HDL cholesterol, triglycerides or liver function tests (LFTs) were observed. There were no episodes of rejection. Immunosuppressant levels remained at goal. One patient noted a few days of fatigue after alirocumab injections but otherwise no side effects were reported.Conclusion:The PCSK9 inhibitors evolocumab and alirocumab are promising alternatives to statin therapy in transplant recipients with statin intolerance or refractory hyperlipidemia. Our study showed their potential to significantly reduce LDL cholesterol in heart transplant patients without altering IST levels. No episodes of transplant rejection were noted. Further long-term studies to establish the safety and efficacy of PSCK9 inhibitors post-transplant are needed.

PROSTATE LACTATE: A CASE OF SEVERE LACTIC ACIDOSIS WITH AN INTERESTING MECHANISM OF ACTION

SESSION TITLE: Wednesday Medical Student/Resident Case Report Posters SESSION TYPE: Med Student/Res Case Rep Postr PRESENTED ON: 10/23/2019 09:45 AM - 10:45 AM INTRODUCTION: In the era of the surviving sepsis campaign, there is mounting pressure for early detection and escalation of care for patients with sepsis and septic shock; obtaining serum lactate is recommended in the Hour-1 Bundle as an early indicator of inadequate tissue perfusion from shock. However, there are many other causes of lactic acidosis that are often overlooked during the initial evaluation. We present a rare case of severe lactic acidosis due to metastatic prostate cancer and the Warburg Effect. CASE PRESENTATION: An 85-year-old man with prostate cancer, coronary artery disease, and atrial fibrillation was admitted with two days of fatigue and generalized weakness. He was hemodynamically stable but initial labs revealed a serum lactate of 9.2 mmol/L, triggering the hospital’s “Sepsis Bundle” and leading to transfer to the Intensive Care Unit. Fluid resuscitation and empiric antibiotics were started with blood cultures later positive for sensitive enterococcus faecalis. After resolution of his bacteremia, the lactate level remained elevated at 6-9 mmol/L, and transiently increased to 20 mmol/L following a ureteral stent exchange, despite normal blood pressures and urine output and warm, dry skin. There was no reported history of metformin use or other toxic etiology. Cross-sectional imaging obtained to evaluate for localized tissue ischemia only showed progression of his metastatic prostate cancer with diffuse lymphadenopathy and osseous metastases. No liver metastases were identified. The persistent, severe lactic acidosis was thought to be due to metastatic prostate cancer and the patient elected to focus on comfort care. DISCUSSION: With increased emphasis on early detection of sepsis, serum lactate has become a common marker of inadequate tissue perfusion. However, clinicians must also consider other causes to include mitochondrial dysfunction, severe liver disease, and medications. More rarely, it can be caused by cancer, most commonly leukemia and lymphoma, but also some solid malignancies. Multiple mechanisms have been proposed to include impaired lactate metabolism and clearance due to liver metastases as well as the Warburg Effect, which is the likely etiology in this case. First described in 1920, it describes how cancer cells have increased glucose uptake with preferential use of glycolysis, leading to increased lactate production, even in the presence of adequate oxygen and functioning mitochondria. Unfortunately, the only therapeutic option is treatment of the underlying malignancy and both patients died in the only two other case reports of prostate cancer related lactic acidosis. CONCLUSIONS: With increased utilization of serum lactate levels, being mindful of the broad differential is critical in addressing the underlying cause. Providers should exercise pause when treating patients with elevated lactate who are hemodynamically stable without evidence of poor perfusion. Reference #1: Munoz J, Mohd K, Amr H, Stoltenberg M. Severe lactic acidosis in a patient with metastatic prostate cancer. J Can Res Ther. 2011;7:201-2. Reference #2: Van der mijn JC, Kuiper MJ, Siegert CEH, Wassenaar AE, Van noesel CJM, Ogilvie AC. Lactic Acidosis in Prostate Cancer: Consider the Warburg Effect. Case Rep Oncol. 2017;10(3):1085-1091. Reference #3: Vander heiden MG, Cantley LC, Thompson CB. Understanding the Warburg effect: the metabolic requirements of cell proliferation. Science. 2009;324(5930):1029-33. DISCLOSURES: No relevant relationships by Kimberly Fabyan, source=Web Response No relevant relationships by Arthur Holtzclaw, source=Web Response No relevant relationships by John Sherner, source=Web Response

A Very Rare Complication of Hepatitis a Infection: Acute Myocarditis

Hepatitis A is a common viral infection with a benign course but in rare cases can progress to acute liver failure. A rare manifestation of hepatitis A is acute myocarditis. We report a case of a 30-year-old female, without significant past medical history who presented with four days of fatigue, myalgias, nausea, non-bloody, non-bilious emesis and non-bloody diarrhea along with anorexia. Physical exam was significant for mild scleral icterus and right upper quadrant abdominal tenderness, without peritoneal signs or fluid wave. She had intact mentation, no asterixis or stigmata of liver disease. Lab work revealed severe elevations in liver transaminases, AST = 6,769U/L, ALT = 8.479U/L., INR = 2.0 and acute viral hepatitis panel was positive for hepatitis A IgM only. EBV IgG and IgM were positive but heterophile assay and EBV PCR was negative (Figure 1 and 2). Abdominal US revealed homogenous hepatic echotexture without evidence of focal hepatic lesions. There was mild intrahepatic biliary ductal dilatation with common bile duct measuring 2mm. On her 3rd day of admission the patient developed chest pain and nonspecific ECG changes. Her troponin rose to 16.4 ng/mL, and an echocardiogram revealed global hypokinesis and a depressed ejection fraction (EF) at 30%. A coronary CT angiography showed no evidence of significant coronary artery disease. The patient was managed supportively and symptoms and laboratory findings slowly improved over the next 7 days. Her chest pain resolved and follow up echocardiogram showed improved EF to 45%. To our knowledge, there are 3 case reports of myocarditis associated with hepatitis A (Figure 3). Like previous case reports, a presumptive diagnosis of myocarditis secondary to hepatitis A was made, despite endomyocardial biopsy (EMB) being the gold standard for definitive diagnosis. However, EMB is not always indicated especially if it would not change management. Despite improving liver indices, the patient developed myocarditis. Therefore, it may be worthwhile to monitor patients for cardiac abnormalities despite signs of improving transaminases. Comparison of these case reports also highlights that higher elevations in transaminases may be associated with more severe cardiomyopathy. However, given the rarity of this manifestation, true associations are yet to be elucidated. The purpose of this case report is to increase awareness of this disease entity, so it can be recognized and considered in clinical practice.2305_A Figure 1. Key laboratory values on admission.2305_B Figure 2. Trend of liver function tests and troponin obtained during hospital course. Day 1 is day of admission. Day 17 is outpatient follow up.2305_C Figure 3. Other reported cases of myocarditis in hepatitis A.

The impact of cognitive fatigue on aerobic output in a 6‐minute walk test among older adults

PurposeThe purpose of this study was to determine the impact of cognitive fatigue on aerobic output during a 6‐minute walk test (6MWT) in older adults.MethodsHealthy older adults (N=9, age= 67.39±4.58 yrs, height=168.01±55.82 cm, weight=60.80±12.41 kg) were involved in 2 days of testing. One day was a 2‐hour protocol of cognitively fatiguing tasks (S3 and S7, continuous performance task (CPT), rapid visual input processing (RVIP),) after which they were tasked to complete a 6MWT at their normal speed and VO2 was measured using the Cosmed Fitmate Pro. The other day, a baseline 6MWT was performed and VO2 were measured. A One‐Sample Kolmogorov‐Smirnov Test to determine distribution of peak VO2 scores prior to performing an independent sample T‐test to determine differences between cognitive fatigue and non‐cognitive fatigue days.ResultsResults yielded a normal distribution (Mean=871,33, SD=265.89) and T‐test analysis yielded no significant differences (p=.734) between cognitive fatigue and non‐cognitive fatigue days.ConclusionAlthough analysis yielded no difference in peak VO2 scores between days, it should be noted that 6 out of the 9 subjects had lower peak VO2 on cognitive fatigue days than on non‐cognitive fatigue days. Further research needs to be conducted to determine whether cognitive fatigue does decrease aerobic performance in older adults.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

Acute liver failure complication of brucellosis infection: a case report and review of the literature

BackgroundBrucellosis is one of the most widespread zoonoses worldwide. It can affect any organ system, particularly the gastrointestinal system, but there is no report of acute liver failure as a brucellosis complication.Case presentationWe present a case of acute liver failure secondary to brucellosis infection. A 75-year-old Hispanic man presented to a University Hospital in Chía, Colombia, with a complaint of 15 days of fatigue, weakness, decreased appetite, epigastric abdominal pain, jaundice, and 10 kg weight loss. On examination in an emergency room, abdomen palpation was normal with hepatosplenomegaly and the results of a liver function test were elevated. The diagnosis of brucellosis was confirmed by epidemiological contact and positive Rose Bengal agglutination with negative enzyme-linked immunosorbent assay immunoglobulin M for Brucella. He was then treated with doxycycline plus trimethoprim/sulfamethoxazole, with a favorable clinical outcome.ConclusionsThe clinical presentation of brucellosis can be very imprecise because it can affect any organ system; however, there is no report of acute liver failure as a brucellosis complication. This is the first reported case in the Colombian literature of acute liver failure due to brucellosis. We found this case to be of interest because it could be taken into account for diagnosis in future appearances and we described adequate treatment and actions to be taken at presentation.

Efficacy of heat-killed Lactococcus lactis JCM 5805 on immunity and fatigue during consecutive high intensity exercise in male athletes: a randomized, placebo-controlled, double-blinded trial

BackgroundLactococcus lactis JCM 5805 (LC-Plasma) is a unique lactic acid bacteria (LAB) which activates plasmacytoid dendritic cells (pDC). We aimed to evaluate the effect of LC-Plasma on dendritic cell (DC) activity and subjective indices of upper respiratory tract infections (URTI) and fatigue in athletes under high intensity exercise.MethodsWe conducted a randomized, placebo-controlled, double-blinded trial. Fifty-one male subjects belonging to a university sports club were randomized into placebo (n = 25) and LC-Plasma (n = 26) groups. Individuals ingested placebo capsules containing cornstarch or LC-Plasma capsules containing 100 billion cells of heat-killed LC-Plasma per day for 13 days. During the intervention period, subjects performed high intensity exercise according to their sports club training regime. Blood and saliva sampling were obtained at days 1 and 14, and physical conditions were recorded in a diary. We investigated expression of maturation markers on DCs, muscle damage and stress markers and used student’s t test adjusted by Bonferoni’s method for multiple comparison between groups. These data were presented as mean ± SD. We also investigated cumulative days of symptoms regarding infections and fatigue and used Chi-square test for comparison between groups. These data were presented as cumulative number.ResultsCD86 as maturation marker on pDC was significantly increased in the LC-Plasma group at day 14 (Placebo: 296 ± 70 vs. LC-Plasma: 365 ± 115; Mean Fluorescent Intensity; p = 0.013). Cumulative days of URTI were significantly lower in the LC-Plasma group (Placebo: URTI positive 56, URTI negative 256 vs. LC-Plasma: URTI positive 39, URTI negative 299; days; p = 0.028) and symptoms like sneeze or running nose were significantly lower in the LC-Plasma group (Placebo: Symptom positive 52, Symptom negative 258, vs. LC-Plasma: Symptom positive 36, Symptom negative 301; days; p = 0.032). Moreover, the cumulative days of fatigue were significantly fewer in the LC-Plasma group (Placebo: Symptom positive 128, Symptom negative 182, vs. LC-Plasma: Symptom positive 110, Symptom negative 225; days; p = 0.032). Markers of muscle damage and stress markers were not significantly different between groups.ConclusionWe consider that heat-killed LC-Plasma supplementation relieves morbidity and symptoms of URTI via activation of pDC and decreases fatigue accumulation during consecutive high intensity exercise in athletes. However, LC-Plasma ingestion did not affect markers of muscle damage and stress.Trial registrationUMIN-CTR, UMIN000020372. Registered 28 December 2015.