Hypopituitarism Presenting as Recurrent Episodes of Hypoglycemia: Houssay Phenomenon.

Hypopituitarism, a rare disorder, is defined as decreased production and secretion of one or more of the hormones that are normally secreted by the pituitary gland, resulting from the diseases of the pituitary gland itself or the hypothalamus. The clinical manifestations of this disorder are usually nonspecific and can lead to life-threatening complications and mortality. Here, we present a case of a 66-year-old female patient who was brought to the ER by her family with concerns of altered mentation. The altered mentation was found to be secondary to a severe hypoglycemic episode, which was later discovered to be due to underlying panhypopituitarism with secondary adrenal insufficiency. Endocrinology was consulted and recommended assessment of the hypothalamic-pituitary axis. The tests revealed low levels of serum insulin and C-peptide along with decreased levels of luteinizing hormone (LH), follicle-stimulating hormone (FSH), prolactin, cortisol, free thyroxine (T4), and adrenocorticotropic hormone (ACTH). She was started on intravenous hydrocortisone and levothyroxine, which were later switched to oral hydrocortisone and levothyroxine after the stabilization of her blood glucose levels. She was later advised to follow up with endocrinology upon discharge. While evaluating a patient with hypoglycemia, it is important to keep hypopituitarism causing secondary adrenal insufficiency in mind as a differential diagnosis because it can be life-threatening if not recognized early and treated in a timely manner.

The association of antibiotic exposure with new-onset inflammatory bowel disease: A systematic review and meta-analysis.

INTRODUCTION: The role of antibiotics in the development of inflammatory bowel disease (IBD) remains controversial, primarily due to conflicting data from individual studies. We conduct a systematic review and meta-analysis to study the effect of antibiotic exposure on IBD development. METHODOLOGY: The MEDLINE and Cochrane CENTRAL databases were queried from their inception to April 2021 for published articles studying the association between antibiotic exposure and new-onset IBD. Our analysis was stratified by timing of antibiotic exposure - exposure in childhood and any lifetime exposure. Adjusted odds ratios (ORs) and corresponding 95% confidence intervals (CIs) from each study were pooled using a random-effects model. RESULTS: 10 case-control studies and 2 cohort studies (N = 29,880 IBD patients and N = 715,548 controls) were included. Patients with Crohn's Disease (CD), compared with controls, were associated significantly with antibiotic exposure in childhood and any lifetime exposure to antibiotics (OR 1.52 [1.23-1.87]; p<0.00001). Patients with Ulcerative Colitis (UC), compared with controls, reported non-significant association with antibiotic exposure in childhood and any lifetime exposure. (OR 1.11 [0.93-1.33]; p = 0.25) CONCLUSION: This meta-analysis suggests that exposure to antibiotics significantly increases the odds of developing CD and IBD. These findings re-emphasize the importance of cautious and judicious use of antibiotics.

Postmortem findings in COVID-19 fatalities: A systematic review of current evidence.

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is responsible for the ongoing pandemic of coronavirus disease 2019 (COVID-19). Almost 17 months after the first COVID-19 case was reported, the exact pathogenesis of the virus is still open to interpretation. Postmortem studies have been relatively scarce due to the high infectivity rate of the virus. We systematically reviewed the literature available for studies that reported gross, histological, microscopic, and immunohistochemical findings in COVID-19 fatalities with the aim of reporting any recurrent findings among different demographics. PubMed and Scopus were searched up till the second of May 2021 and 46 studies with a total of 793 patients were shortlisted after the application of inclusion and exclusion criteria. The selected studies reported gross, histological, microscopic, and immunohistochemical autopsy findings in the lungs, heart, liver, gallbladder, bowels, kidney, spleen, bone marrow, lymph nodes, CNS, pancreas, endocrine/exocrine glands, and a few other miscellaneous locations. The SARS-CoV-2 virus was detected in multiple organs and so was the presence of widespread microthrombi. This finding suggests that the pathogenesis of this highly infectious virus might be linked to some form of coagulopathy. Further studies should focus on analyzing postmortem findings in a larger number of patients from different demographics in order to obtain more generalizable results.

Efficacy and Safety of Oral P2Y12 Inhibitors in Older Patients with Acute Coronary Syndrome: A Frequentist Network Meta-Analysis.

BACKGROUND AND OBJECTIVE: Previous studies and meta-analyses have assessed optimal P2Y12 inhibitors following acute coronary syndrome in overall trial cohorts. However, there are insufficient data for the elderly cohort who are prone to high bleeding and ischemic events. We aimed to assess the optimal P2Y12 inhibitor therapy for older patients. METHODS: PubMed, CENTRAL, and ClinicalTrials.gov databases were searched from inception through July 2020 to identify randomized controlled trials and propensity-matched observational studies including older patients (aged ≥ 65 years) that reported study-defined major adverse cardiovascular events (MACE) or major bleeding events. Outcomes at the mid-term follow-up were pooled to conduct a frequentist network meta-analysis. RESULTS: Fourteen studies involving 12,953 older patients were included in our analysis. No significant difference was observed with MACE when all three P2Y12 inhibitors were compared with each other. Compared with clopidogrel, ticagrelor significantly increased the risk of major bleeding (risk ratio 1.35, 95% confidence interval 1.10-1.67) while prasugrel did not (risk ratio 1.02, 95% confidence interval 0.67-1.57). A sensitivity analysis of only randomized controlled trials yielded similar results for both MACE and major bleeding. The P score displayed prasugrel (0.5871) as the best treatment for MACE, while clopidogrel (0.7701) was the best P2Y12 inhibitor to decrease the risk of major bleeding. Ticagrelor (0.0634) was ranked the lowest because of an increased bleeding risk. CONCLUSIONS: No significant difference is observed between the three P2Y12 inhibitors in study-defined MACE. Ranking by p-score suggests prasugrel as the best P2Y12 inhibitor to reduce the risk of MACE while clopidogrel is a better alternative than ticagrelor in older patients with acute coronary syndrome to decrease the risk of major bleeding. Because of a lack of individual-patient data analysis and heterogeneity amongst studies, future studies representing older patients with acute coronary syndrome are required to strengthen evidence regarding optimal antithrombotic therapy in this cohort.

Visual Hallucinations After a Russell's Viper Bite.

Visual hallucinations (VHs) are extremely rare in snakebites. We report a case of Russell's viper bite in an otherwise healthy 55-y-old woman who presented to a hospital in south India with established clinical features of systemic and local envenomation, including coagulation failure, without any neurologic manifestations on admission. She reported simple VH on the third day, which abruptly stopped on the fifth day without any specific medications. Clinical, laboratory, imaging, and electrophysiological studies did not reveal any neuropsychiatric disorders. Including this case, only 5 cases of VH are documented in the literature, 2 following cobra and viper bites and 1 after a sea snake bite. Two cases were reported from Australia and 1 each from the United States, Iran, and India.

Antidiabetic drugs and non-alcoholic fatty liver disease: A systematic review, meta-analysis and evidence map.

BACKGROUND: The efficacy of antidiabetic agents for the treatment of non-alcoholic fatty liver disease (NAFLD) remains unclear. AIM: To conduct a meta-analysis to study the efficacy of pioglitazone and three novel anti-diabetic agents: glucagon-like peptide-1 (GLP-1) agonists, sodium-glucose co-transporter-2 (SGLT2) inhibitors, and dipeptidyl-peptidase-4 (DPP4) inhibitors in treating NAFLD. METHODS: Online databases were searched in May 2020 for randomized clinical trials. Results from random-effects meta-analysis are presented as weighted mean differences (WMDs) or standard mean differences (SMDs) and corresponding 95% confidence intervals (CIs). RESULTS: Twenty-six studies (n=946 NAFLD patients) were included. Reductions in ALT were seen with all four drugs: pioglitazone (MD -38.41, p<0.001), SGLT2 inhibitors (MD -16.17, p<0.001), GLP-1 agonists (MD -27.98, p=0.04) and DPP-4 inhibitors (MD -7.41, p<0.001). Pioglitazone (SMD -1.01; p<0.001) and GLP-1 agonists (SMD -2.53, p=0.03) also demonstrated significant improvements in liver steatosis. SGLT2 inhibitors (SMD -4.64, p=0.06) and DPP-4 (SMD -2.49, p=0.06) inhibitors trended towards reduced steatosis; however, these results were non-significant. CONCLUSION: Pioglitazone demonstrates significant improvements in transaminases and liver histology in both diabetic and non-diabetic NAFLD patients. Early evidence from diabetic NAFLD patients suggests that novel antidiabetics may lead to improvements in liver enzymes and hepatic steatosis, and this should encourage further research into possible utility of these drugs in treating NAFLD.

Giant Leiomyosarcoma Arising in Posterior Thigh: Management of a Rare Case.

Leiomyosarcoma, primarily a tumor of smooth muscle origin, frequently originates from the uterus, retroperitoneum, and intra-abdominal region. Rarely, the tumor may arise from the conjunctiva, inferior vena cava, or oral cavity. Here we report a case of a 65-year-old male patient who presented with a swelling in the posterior thigh for six months. The swelling was progressively increasing in size for the last two months. Examination of thigh showed a swelling of 20×30 cm in size, which was firm, non-compressible, immobile, and not transilluminating. CT scan showed no metastasis in the liver, lung, or bone. The histopathology report showed poorly differentiated leiomyosarcoma involving the muscles of the posterior compartment of the left thigh. The tumor was resected, and the patient was referred to rehabilitation clinic. Early diagnosis of such cases is essential to improve the outcome in patients as these tumors can metastasize early.

COVID-19 and Liver Injury: A Systematic Review and Meta-Analysis.

Background and Aims The prevalence and extent of liver damage in coronavirus disease 2019 (COVID-19) patients remain poorly understood, primarily due to small-sized epidemiological studies with varying definitions of "liver injury". We conducted a meta-analysis to derive generalizable, well-powered estimates of liver injury prevalence in COVID-19 patients. We also aimed to assess whether liver injury prevalence is significantly greater than the baseline prevalence of chronic liver disease (CLD). Our secondary aim was to study whether the degree of liver injury was associated with the severity of COVID-19. Materials and Methods Electronic databases (PubMed and Scopus) were systematically searched in June 2020 for studies reporting the prevalence of baseline CLD and current liver injury in hospitalized COVID-19 patients. Liver injury was defined as an elevation in transaminases >3 times above the upper limit of normal. For the secondary analysis, all studies reporting mean liver enzyme levels in severe versus non-severe COVID-19 patients were included. A random-effects model was used for meta-analysis. Proportions were subjected to arcsine transformation and pooled to derive pooled proportions and corresponding 95% confidence intervals (CIs). Subgroup differences were tested for using the chi-square test and associated p-value. Means and their standard errors were pooled to derive weighted mean differences (WMDs) and corresponding 95% CIs. Results Electronic search yielded a total of 521 articles. After removal of duplicates and reviewing the full-texts of potential studies, a total of 27 studies met the inclusion criteria. Among a cohort of 8,817 patients, the prevalence of current liver injury was 15.7% (9.5%-23.0%), and this was significantly higher than the proportion of patients with a history of CLD (4.9% [2.2%-8.6%]; p < 0.001). A total of 2,900 patients in our population had severe COVID-19, and 7,184 patients had non-severe COVID-19. Serum ALT (WMD: 7.19 [4.90, 9.48]; p < 0.001; I2 = 69%), AST (WMD: 9.02 [6.89, 11.15]; p < 0.001; I2 = 73%) and bilirubin levels (WMD: 1.78 [0.86, 2.70]; p < 0.001; I2 = 82%) were significantly higher in patients with severe COVID-19 when compared to patients with non-severe disease. Albumin levels were significantly lower in patients with severe COVID-19 (WMD: -4.16 [-5.97, -2.35]; p < 0.001; I2 = 95%). Conclusions Patients with COVID-19 have a higher than expected prevalence of liver injury, and the extent of the injury is associated with the severity of the disease. Further studies are required to assess whether hepatic damage is caused by the virus, medications, or both.

Effect of ertugliflozin on glycemic levels, blood pressure and body weight of patients with type 2 diabetes mellitus: a systematic review and meta-analysis.

PURPOSE: To conduct a meta-analysis to evaluate the effect of ertugliflozin on long-term hemoglobin A1c (HbA1c), body weight and blood pressure (BP). METHODS: Online databases available were searched from their inception to February 2020. Randomized controlled trials (RCTs) comparing ertugliflozin to either placebo or an active control drug were included. Data on four efficacy outcomes were extracted, namely: HbA1c, systolic blood pressure (SBP), diastolic blood pressure (DBP) and body weight. Continuous outcomes were pooled using a random-effects model and presented as weighted mean differences (WMDs) and corresponding 95% CIs. Additionally, a subgroup analysis was done to compare two doses of ertugliflozin (5 mg and 15 mg). A sensitivity analysis was also performed by eliminating studies using active drugs as controls. RESULTS: From a total of 123 search results, eight studies were included. Compared to the control group, ertugliflozin was associated with a significant decrease in SBP (WMD: -3.64 mmHg, 95% CI [-4.39,-2.90]; p < 0.001; I2 = 0%) and DBP (WMD: -1.13 mmHg, 95% CI [-1.67,-0.60], p < 0.001; I2 = 0%). Similarly, significant reductions in body weight (WMD: -2.35 kg, 95% CI [-2.94,-1.77]; p < 0.001; I2 = 0%) as well as HbA1c (WMD: -0.41%, 95% CI [-0.62,-0.20]; p < 0.001; I2 = 0%) were seen with ertugliflozin. Subgroup analysis demonstrated no significant difference in efficacy between the two doses in any of the four outcomes. CONCLUSION: Ertugliflozin results in significant reductions in HbA1c, body weight, SBP and DBP, when compared to control. Subgroup analyses suggest that these effects are not dose-dependent.