It takes a big heart to shape atrophic hepatocytes: Hypoxic hepatitis secondary to congestive heart failure

Introduction: Hypoxic hepatitis (HH) also known as ischemic hepatitis is the result of a hypoperfusion state during diffuse hepatic injury1. The incidence of HH is 2:1000 of patients within any hospital care level. 94% of HH are related to chronic heart failure (HF). In this setting, hepatic dysfunction occurs as a result of passive venous congestion2. The most common predisposing factors are acute heart failure and shock states, however, more than half of the cases are not related to any hemodynamic change, thus, underrecognized. Case description: A 77-year-old woman is admitted to the hospital for acute decompensated HF. She has a medical history of HF with reduced EF of 30%, paroxysmal atrial fibrillation, coronary artery disease with bypass grafting. Medication lists include sacubitril-valsartan, furosemide, metoprolol, and amiodarone. Upon admission, vital signs are within normal limits, she is in mild respiratory distress, with JVD at 3 cm, upper lobe crackles and wheezing on lung fields, and lower extremity non-pitting edema. Laboratory studies showed BUN/Cr 29/1.4 mg/dl, AST 377 IU/L, ALT 295 IU/L, BNP \u3e4500, troponin 0.3, with unremarkable ECG. The patient was started on furosemide, and amiodarone and sacubitril-valsartan are suspended due to suspected hepatic toxicity and acute kidney injury, respectively. Echocardiogram reported EF 20-25% with severe diffuse hypokinesis, RVSP of 54 mmHg, tricuspid valve with moderate-severe regurgitation. The abdominal US with a prominence of the hepatic veins and inferior vena cava. Patient LFTs continued to trend up during hospitalization, with a peak in AST 2080 IU/L, ALT 1371IU/L, ALP 75IU/L, total bilirubin 1.1 mg/dL. Viral serologic markers were negative as well as a workup for autoimmune hepatitis, and primary biliary cholangitis. Gastroenterology is consulted, the patient is initiated on N-Acetylcysteine, and transaminases trended down. Admission Day 3 Day 8 AST 377 2080 69 ALT 295 1371 319 Discussion: The prevalence of hepatic dysfunction in acute HF is 20% to 30%. The mechanism of injury was previously thought to be solely related to HF, however, new studies suggest that patients with underlying liver conditions and even mild hemodynamic changes are predisposed to develop HH. The mechanism involves the liver’s high metabolic demands and oxygen requirements. The hepatocytes compensate for impaired blood flow by increasing oxygen extraction, which may lead to hepatocellular hypoxia and necrosis. HH is diagnosed clinically by three main criteria, 1. Presence of cardiac, circulatory, or pulmonary failure; 2. Severe and transient increase in aminotransferase levels \u3e20 times the upper limit of normal and 3. Exclusion of other possible causes of liver damage. HH is usually self-limited, and aminotransferases trend down within 3-5 days, however fulminant hepatic failure can develop. Management involves treating underlying HF, as there is no specific treatment for HH. In our case, the progression of the HF was the cause that explained the acute increase in transaminases. It is important to keep in mind the gastrointestinal manifestation of HF, furthermore, that even with mild circulatory changes patients can develop HH

Interrupting the Axis: A Case of IgG-4 Related Hypophysitis in a Young Hispanic Male

Background: Hypophysitis refers to inflammation of the pituitary gland that can lead to the disruption of the hypothalamic-pituitary-adrenal axis. Primary hypophysitis has five variants differentiated by histologic findings: lymphocytic, granulomatous, xanthomatous, IgG4-related, and necrotizing. IgG4-related hypophysitis is very rare and is commonly a manifestation of a multi-organ systemic disorder. We present a case of a 43-year-old man presenting with severe headache and symptomatic hyponatremia in the setting of isolated IgG-4 related hypophysitis. Case Presentation: A 43-year-old male presented with a two-day history of severe posterior headache associated with several episodes of vomiting, photophobia, generalized weakness and fatigue. Patient had no history of headaches and denied any recent trauma, focal weakness, altered mentation, changes in vision or seizure activity. Vitals on admission were remarkable for BP 179/99 mmHg. Neurological examination was non-focal, cranial nerves were grossly intact. Labs showed unremarkable CBC, sodium 117 mmol/L, potassium 3.3 mmol/L, chloride 84 mmol/L, glucose 244 mg/d, TSH 0.6 uIU/mL, cortisol 4.6 ug/dL, urine osmolality 540, serum osmolality 259 and prolactin level 7.8. CT head without contrast showed a mass-like enlargement of the Sella measuring 1.6 cm x 1.4 cm suspicious for macroadenoma. Patient was started on hypertonic saline, fludrocortisone, hydrocortisone, and salt tablets in the setting of suspected macroadenoma. Once the patient was stabilized, he underwent transsphenoidal resection of pituitary lesion. Pathology of the lesion showed a small area rich in plasma cells with positive IgG4 immunostaining in most of the plasma cells, consistent with IgG4-related pituitary hypophysitis. Conclusion: IgG4 hypophysitis usually presents in a context of multiple organ IgG4 involvement, however isolated hypophysitis has been reported. The patients present with mass effect symptoms and/or anterior hypopituitarism. When histologic diagnosis is obtained via biopsy, IgG4 hypophysitis can be managed exclusively with corticosteroids

A Case of Recently Diagnosed Uncontrolled Hyperthyroidism Associated with Bilateral Pulmonary Embolism

Background: Pulmonary embolism (PE) is a relatively common acute cardiovascular disorder with considerable mortality, despite advances in diagnosis and treatment. In 25 to 50% of first-time cases, no readily identifiable risk factor can be found. Several studies have suggested hyperthyroidism to be a potential hypercoagulable and hypofibrinolytic state. In this case, we present a patient with uncontrolled hyperthyroidism with incidental bilateral PE. Case Presentation: A 47-year-old Hispanic lady with past medical history of recently diagnosed hyperthyroidism who was not compliant with medical therapy, presented to the emergency department with 4-hour history of chest pain. She described it as sudden onset, pressure-like pain that occurred during exertion and radiated to the back. She had associated palpitations, diarrhea, arthralgias and dyspnea that did not improved with rest. She also states having poor appetite and some weight loss for at least 1 year. The patient does mention having been diagnosed with hyperthyroidism one month ago by an endocrinologist in Mexico, who prescribed her propranolol and methimazole, which she was not taking as prescribed. Her vital signs were temperature of 98.1, heart rate of 124, respiratory rate of 18 and blood pressure of 112/84 mm Hg with a SpO2 of 99% on room air. Upon physical examination, she was alert, anxious and in mild distress. She was tachycardic, with no murmur or gallop and lungs were clear to auscultation. She did not have any skin lesions. Laboratory findings were remarkable for elevated D-dimer of 643, alkaline phosphatase of 228 with liver function tests within normal range and troponin I of 0.27. Thyroid function test revealed TSH of 0 uLU/mL, total T3 493 ng/dl, free T3 22.5 pg/ml, T3 uptake of 62.5 %, total T4 24.9 ug/dl and free T4 of 5.06 ng/dl. CT of the chest with contrast revealed subsegmental bilateral lower lobe pulmonary emboli. It also revealed a soft tissue prominence within the anterior mediastinum. Thyroid US revealed an enlarged thyroid gland with heterogeneous echotexture and hyperemic Doppler flow, compatible with active thyroiditis. Burch-Wartofsky score was 35 points. Patient was admitted for uncontrolled hyperthyroidism with impending thyroid storm as well as bilateral PE with possible right heart strain. She was started on Propranolol, Methimazole, potassium iodide and heparin drip. Patient status overall improved and Echocardiogram revealed EF 60-65% without signs of right heart strain. Thyroid workup then revealed TSI of 297, positive ANA with nuclear pattern and TPO of 151 IU/mL. She was later discharged with Eliquis, methimazole and propranolol for close follow up. Conclusions: Hyperthyroidism has well known effects on the cardiovascular system, however, further data suggests that it modifies physiologic processes of hemostasis, leading to bleeding or thrombosis. This is due by upregulating adhesion molecules and endothelial marker proteins. Most studies have shown that hyperthyroidism is related to venous thromboembolism risk, however just a few have focused on specifically its association with PE. There are currently no recommendations in regard to prophylactic anticoagulation in hyperthyroid state, however physicians should be alert for possible thrombotic events with these patients

Unusual case of disseminated Langerhans cell histiocytosis in a young male, a case report

Background: Langerhans cell histiocytosis (LCH), is an uncommon hematological disorder characterized by uncontrolled stimulation and proliferation of normal antigen presenting cells, Langerhans cells. It’s estimated incidence in adults is approximately one to two cases per million. The purpose of this report is to describe the case of LCH in a 21-year-old male with multiple organ involvement including the brain, liver, bone; also, to discuss clinical, radiological, and histopathological features of LCH, and the role of internist in diagnosing and managing such disease. Case presentation: We describe the case of a 21-year-old Hispanic man with Langerhans cell histiocytosis involving his liver, skull, brain, and lungs. Initially patient presented to the hospital with upper GI bleeding. Upon review of his chart, it was found that the patient had previously a skull mass resection with immunohistochemistry confirming Langerhans cells which stain strongly positive for S100, CD 1a and langerin 3 year previous, and also a diagnosis of panhypopituitarism with a brain MRI with a 1 1.4 x 1.5 x 1.4 cm mass within the hypothalamus. Liver biopsy during current admission demonstrated a CD68 positive for histiocytes. Conclusions: This case report might contribute to a better understanding of the pathogenesis of LCH and will help to expand the knowledge of health professionals about this condition

Improving inpatient hyperglycaemia in non-critically ill adults in resident wards through audit and feedback

Inpatient hyperglycaemia is associated with an increase in morbidity and mortality, number of rehospitalisations and length of hospitalisation. Although the advantages of proper glycaemic control in hospitalised patients with diabetes are well established, a variety of barriers limit accomplishment of blood glucose targets. Our primary aim was to decrease the number of glucose values above 180 mg/dL in non-critical care hospitalised patients using an audit and feedback intervention with pharmacy and internal medicine residents. A resident-led multidisciplinary team implemented the quality improvement (QI) project including conception, literature review, educating residents, iterative development of audit and feedback tools and data analysis. The multidisciplinary team met every 5 weeks and undertook three ‘plan–do–study–act’ cycles over an 8-month intervention period (August 2022 to March 2023) to educate residents on inpatient hyperglycaemia management, develop and implement an audit and feedback process and assess areas for improvement. We performed 1045 audits analysing 16 095 accu-checks on 395 non-duplicated patients. Most audits showed compliance with guidelines. The monthly run-on chart shows per cent of glucose values above 180 mg/dL in our non-ICU hospitalised patients and an overall pre-to-post comparison of 25.1%–23.0% (p value\u3c0.05). The intervention was well accepted by residents evidenced by survey results. We did not meet our primary aim to reduce hyperglycaemia by 30% and this combined with the audits showing mostly compliance with guidelines suggests that prescribing behaviour was not a key driver of inpatient hyperglycaemia in our population. This internal medicine resident and pharmacy interprofessional collaboration with audit and feedback for inpatient hyperglycaemia was feasible, well accepted and had a statistically significant yet small improvement in inpatient hyperglycaemia. The project may be helpful to others wishing to explore inpatient hyperglycaemia, interprofessional QI with pharmacists, resident-led QI and audit and feedback

Learners Engaging with Hispanic Communities to address COVID19 Inequities by Developing a Cultural Competence Guide for Public Health Messaging

Introduction: The Rio Grande Valley (RGV) has the highest rates of obesity and diabetes nationwide which have compounded the impact of COVID-19. We propose addressing underlying mistrust and systemic racism through a resident-and-student-learner-led, community-engaged, educational public health campaign targeting the Hispanic community in the RGV. Methods: Twelve students were provided interdisciplinary leadership skills in a community-engaged public messaging campaign covering issues of COVID-19 inequities. Learners used these skills to engage with clinic community partners in qualitative interviews regarding the patient population to guide the creation of a culturally competent public health messaging rubric for the Hispanic community. Results: Pre-intervention survey results showed that the patient population was 97% Hispanic/Latino with a 73% language preference for Spanish and a 98% uninsured status. Clinic leaders described 67% of their patient population as being high risk for COVID-19 with multiple underlying risk factors, including obesity, hypertension, and diabetes. Surveyed clinic leaders selected that PSAs need to have clarity of the message and availability in the patient’s preferred language. Our team created two focused, culturally competent rubrics for the Hispanic community. Discussion: This research has shown that it is imperative to be able to evaluate which PSAs are effective in delivering their intended message as well as being able to monitor the effects on their target audience. The Hispanic and Spanish-speaking communities needs more effective public health messaging to decrease testing fears, improve contact tracing, motivate individuals to seek medical care, and to ultimately address the rampant COVID-19 inequities that exist

Supplement: "Localization and broadband follow-up of the gravitational-wave transient GW150914" (2016, ApJL, 826, L13)

This Supplement provides supporting material for Abbott et al. (2016a). We briefly summarize past electromagnetic (EM) follow-up efforts as well as the organization and policy of the current EM follow-up program. We compare the four probability sky maps produced for the gravitational-wave transient GW150914, and provide additional details of the EM follow-up observations that were performed in the different bands

Optimasi Portofolio Resiko Menggunakan Model Markowitz MVO Dikaitkan dengan Keterbatasan Manusia dalam Memprediksi Masa Depan dalam Perspektif Al-Qur`an

Risk portfolio on modern finance has become increasingly technical, requiring the use of sophisticated mathematical tools in both research and practice. Since companies cannot insure themselves completely against risk, as human incompetence in predicting the future precisely that written in Al-Quran surah Luqman verse 34, they have to manage it to yield an optimal portfolio. The objective here is to minimize the variance among all portfolios, or alternatively, to maximize expected return among all portfolios that has at least a certain expected return. Furthermore, this study focuses on optimizing risk portfolio so called Markowitz MVO (Mean-Variance Optimization). Some theoretical frameworks for analysis are arithmetic mean, geometric mean, variance, covariance, linear programming, and quadratic programming. Moreover, finding a minimum variance portfolio produces a convex quadratic programming, that is minimizing the objective function ðð¥with constraintsð ð 𥠥 ðandð´ð¥ = ð. The outcome of this research is the solution of optimal risk portofolio in some investments that could be finished smoothly using MATLAB R2007b software together with its graphic analysis

Rare predicted loss-of-function variants of type I IFN immunity genes are associated with life-threatening COVID-19

Background: We previously reported that impaired type I IFN activity, due to inborn errors of TLR3- and TLR7-dependent type I interferon (IFN) immunity or to autoantibodies against type I IFN, account for 15–20% of cases of life-threatening COVID-19 in unvaccinated patients. Therefore, the determinants of life-threatening COVID-19 remain to be identified in ~ 80% of cases. Methods: We report here a genome-wide rare variant burden association analysis in 3269 unvaccinated patients with life-threatening COVID-19, and 1373 unvaccinated SARS-CoV-2-infected individuals without pneumonia. Among the 928 patients tested for autoantibodies against type I IFN, a quarter (234) were positive and were excluded. Results: No gene reached genome-wide significance. Under a recessive model, the most significant gene with at-risk variants was TLR7, with an OR of 27.68 (95%CI 1.5–528.7, P = 1.1 × 10−4) for biochemically loss-of-function (bLOF) variants. We replicated the enrichment in rare predicted LOF (pLOF) variants at 13 influenza susceptibility loci involved in TLR3-dependent type I IFN immunity (OR = 3.70[95%CI 1.3–8.2], P = 2.1 × 10−4). This enrichment was further strengthened by (1) adding the recently reported TYK2 and TLR7 COVID-19 loci, particularly under a recessive model (OR = 19.65[95%CI 2.1–2635.4], P = 3.4 × 10−3), and (2) considering as pLOF branchpoint variants with potentially strong impacts on splicing among the 15 loci (OR = 4.40[9%CI 2.3–8.4], P = 7.7 × 10−8). Finally, the patients with pLOF/bLOF variants at these 15 loci were significantly younger (mean age [SD] = 43.3 [20.3] years) than the other patients (56.0 [17.3] years; P = 1.68 × 10−5). Conclusions: Rare variants of TLR3- and TLR7-dependent type I IFN immunity genes can underlie life-threatening COVID-19, particularly with recessive inheritance, in patients under 60 years old

Measurement of t(t)over-bar normalised multi-differential cross sections in pp collisions at root s=13 TeV, and simultaneous determination of the strong coupling strength, top quark pole mass, and parton distribution functions

Peer reviewe