Aysha Aslam

Background: Neuroendocrine tumors (NET) are a rare group of epithelial neoplasm present in gastrointestinal tract (GI) (67.5%), bronchopulmonary tree (25.3-30%), and in 15% of cases, the primary sites cannot be identified. Although endoscopic screening, improvement in pathological techniques, and early detection have shown improvement in NET survival rates, the prognosis of advanced, metastatic, and poorly differentiated NET is very poor. In this study, we aimed to evaluate the effect of Gastrointestinal and pancreatic (GEPs) NETs grade on overall survival. Method: We searched observational studies describing the overall survival or prognostic factors of primary GEP NETs from May 2011 -May 2021 following PRISMA guidelines. Studies describing the effect of primary grade 3 GEP NETs on overall survival were included. Meta-analysis was performed, and pooled hazard ratio and their 95% confidence interval (95% CI) were obtained. The forest plots were created using random-effects models and sensitivity analysis was performed to account for the heterogeneity. Results: Seven studies with 7692 confirmed patients were included. In our meta-analysis grade 3 GEP NET were associated with higher odds of poor survival (pooled HR: 2.73; 95% CI: 1.36–5.47; p = 0.005), with 92% heterogeneity between studies (p < 0.0001). To account for heterogeneity, sensitivity analysis was performed by removing two outlying studies (Fathi et al. and Foubert et al.) on funnel plots. The results after sensitivity analysis did not change and still showed significant association of grade 3 with poor survival (pooled HR: 4.53; 95% CI: 3.54–5.78; p < 0.00001), with no heterogeneity between studies (p = 0.72; I2 = 0%). Conclusion: Our meta-analysis found that grade 3 GEP NETs are associated with poor survival and additional future studies are needed to identify other risk factors associated with poor survival in GEP NETs to improve mortality.

Strongyloidiasis is a parasitic infection caused by nematode helminth Strongyloides stercoralis. Severe infection with S. stercoralis is rare and often missed by clinicians which may cause worsen the outcomes. A 57-year-old Hispanic female with past medical history of HIV and breast cancer was transferred from an outside hospital to a tertiary care facility with complaint of persistent abdominal pain and melena. She underwent Esophagogastroduodenoscopy (EGD) twice before her presentation for the same complaints which showed severe duodenitis with multiple erosions; however, at both occasions, biopsies were deferred. A third EGD done at tertiary care hospital also revealed severe duodenitis. Another notable finding was pseudo-membranous dusky appearing mucosa with duodenal narrowing causing gastric outlet obstruction (GOO). The duodenal mucosa involved was biopsied during EGD. Pathology was consistent with Strongyloidiasis. At that time, a diagnosis of severe Strongyloidiasis causing duodenal ulceration, bleeding, and GOO was made. She was started on Ivermectin. Her hospital course was further complicated by strongyloidiasis hyperinfection syndrome (SHS) leading to her demise. Severe infection with S. stercoralis causing SHS is associated with significant morbidity and mortality. High index of suspicion, timely diagnosis and management is prudent for preventing serious complications.

This study aims to develop, characterize and validate analytical method and perform stability studies of Racecadotril capsules to treat acute diarrhea. Six formulations of Racecadotril 100mg Capsules were prepared with different excipients by varying their concentrations. The HPLC method was validated on analytical parameters recommended by ICH Q2R guidelines, including specificity, accuracy and recovery, precision, quantitation limit, detection limit, range, linearity, and robustness. Forced degradation studies were performed as per the Stability Indicating Method under various stress conditions. Accelerated stability studies were performed on three stability batches of best fit formulation of Racecadotril 100mg Capsules as per ICH guidelines. Among the six formulations of Racecadotril 100mg Capsule, F6 was the best fit with a comparatively good dissolution profile with 76.9% release in 60 minutes. The HPLC system was suitable as % R.S.D. was 0.619147%, within the acceptance criteria. Furthermore, parameters including specificity, accuracy and recovery, precision, quantitation limit, detection limit, range, linearity, and robustness lie within the acceptance criteria. The percent degradation of Racecadotril after photolytic (sunlight for 6 hr.), oxidative (3% H2O2), acidic (0.1N HCl) and necessary (0.1N NaOH) stress was found to be 6.5%, 5.8%, 11.4%, and 28.4%, respectively. The product remains unchanged after thermal stress. HPLC method was successfully validated for Racecadotril 100mg Capsule as per ICH Q2R guidelines.

Hepatitis B virus (HBV) infection remains a global public problem despite the availability of an effective vaccine. In the past decades, nonalcoholic fatty liver disease (NAFLD) has surpassed HBV as the most common cause of chronic liver disease worldwide. The prevalence of concomitant chronic hepatitis B (CHB) and NAFLD thus reaches endemic proportions in geographic regions where both conditions are common. Patients with CHB and NAFLD are at increased risk of liver disease progression to cirrhosis and hepatocellular carcinoma. Due to the complexity of the pathogenesis, accurate diagnosis of NAFLD in CHB patients can be challenging. Liver biopsy is considered the gold standard for diagnosing and determining disease severity, but it is an invasive procedure with potential complications. There is a growing body of literature on the application of novel noninvasive serum biomarkers and advanced radiological modalities to diagnose and evaluate NAFLD, but most have not been adequately validated, especially for patients with CHB. Currently, there is no approved therapy for NAFLD, although many new agents are in different phases of development. This review provides a summary of the epidemiology, clinical features, diagnosis, and management of the NAFLD and highlights the unmet needs in the areas of CHB and NAFLD coexistence.

Hyponatremia is a common clinical condition encountered in the hospital setting. Syndrome of inappropriate antidiuretic hormone (SIADH) is an important and one of the most common causes of hyponatremia. SIADH accounts for approximately one-third of all cases of hyponatremia. Tolvaptan is a vasopressin receptor antagonist used to treat SIADH. Hepatoxicity is a rare yet dangerous side effect from Tolvaptan use. We present a case of cholestatic liver injury in an elderly female who presented with hyponatremia. She received two doses of tolvaptan 15mg and developed worsening in her total bilirubin (T Bili) and alkaline phosphatase (Alk Phos) levels. Tolvaptan is known to cause elevated transaminase levels and the mechanism of action is thought to be idiosyncratic. Fortunately, the patient responded with an improvement in T Bili and Alk Phos levels after stopping tolvaptan. This case highlights the cautious use of tolvaptan in elderly patients with SIADH as even small doses can potentiate hepatotoxicity.

Although the clinical presentation of hypertriglyceridemic pancreatitis is usually similar to other forms of acute pancreatitis, it is frequently associated with increased clinical severity and rate of complications. Therefore, appropriate and timely management is of paramount importance in these patients. We performed a structured literature search of the medical databases PubMed and Google Scholar, using the terms “hypertriglyceridemia,” “acute pancreatitis,” “insulin,” and “treatment.” In this search, we identified 34 cases of hypertriglyceridemia-related pancreatitis available in the full-text form in English. The data on patients’ characteristics, epidemiology, clinical features, comorbid conditions, and diagnostic modalities were collected and summarized. This review illustrates that the use of insulin therapy with close monitoring of blood glucose levels is safe. It can be considered as an important component of management in patients with hypertriglyceridemia-related pancreatitis, especially in a clinical setting without the availability of plasmapheresis. Randomized clinical trials are warranted to outline a generalized and efficient treatment regimen for hypertriglyceridemic pancreatitis.