Afreen Shariff

PURPOSE OF REVIEW: The purpose of this review is to summarize our current knowledge of factors that influence clinical decision making and management of type 2 diabetes mellitus (T2DM) and atherosclerotic cardiovascular disease (ASCVD) among South Asians (SA). RECENT FINDINGS: ASCVD and T2DM in SAs have been examined in recent times. Pathophysiologic and genetic factors including the role of adiponectin, visceral adiposity, lower beta cell function, and psycho-social factors like sedentary lifestyle, poor adherence to medications, and carbohydrate dense meals play a role in early development and the high-risk presentation of both ASCVD and T2DM in SA. Recently, large population-based cohort studies have attempted to compare outcomes and interventions that can be translated to timely detection and targeted interventions in this high-risk group. SAs in the USA are more likely to be diagnosed with T2DM and ASCVD when compared to non-Hispanic whites, non-Hispanic Blacks, and Hispanic populations. The development of personalized ethnic risk assessment tools and better representation of SAs in prospective studies are essential to increasing our understanding and management of cardio-metabolic disease in SA living in the USA.

Immune checkpoint inhibitors (ICI), such as PD-1/PDL-1 and CTLA-4, have become widely used in the treatment of solid and hematological malignancies; their use and side effects are increasingly seen in the palliative care (PC) population. These drugs can result in immune-mediated endocrinopathies; the thyroid is the most common endocrine gland affected, but the pituitary, adrenals, and pancreas may be affected as well. Symptoms may be insidious and nonspecific. A high index of suspicion and routine laboratory monitoring allows for prompt diagnosis and treatment, which can significantly improve symptoms and increase quality of life. In this study, we present an approach to monitoring and initial management of ICI-induced endocrinopathies in the PC patient population.

INTRODUCTION: Most patients with advanced NSCLC will experience disease progression and death within 2 years. Novel approaches are needed to improve outcomes. METHODS: We conducted an open-label, nonrandomized, phase 2 trial in patients with treatment-naive, advanced NSCLC to assess the safety and efficacy of nivolumab 360 mg every 3 weeks, ipilimumab 1 mg/kg every 6 weeks, and four to six cycles of paclitaxel 80 mg/m2 on days 1 and 8 of every 21-day treatment. The primary end point of the study was median progression-free survival (PFS), with secondary end points of safety, objective response rate, and median overall survival (OS). RESULTS: A total of 46 patients underwent consent and received treatment. The median age was 66 (range: 48-82) years, most had adenocarcinoma (63%), and 50% (23) had programmed death-ligand 1 greater than or equal to 1%. The median follow-up on the study as of October 2021 was 19 months. The primary end point of median PFS was 9.4 months (95% confidence interval [CI]: 5.9-16.6) in all patients regardless of programmed death-ligand 1 expression. The objective response rate for patients in the study was 47.8% (95% CI: 33.4-62.3). The 12-month OS rate was 69.5% (95% CI: 53%-81%), and median OS was not yet reached. Treatment-related grade greater than or equal to 3 adverse events was found in 54.3% of the patients. CONCLUSIONS: The toxicity observed was consistent with other reported chemo-immunotherapeutic combinations and was manageable. The primary end point of exceeding median PFS of 9 months was achieved with nivolumab, ipilimumab, and weekly paclitaxel and should be evaluated further in a randomized trial.

Newly approved systemic treatment options for metastatic urothelial cancer (mUC) have diversified treatments and improved responses and survival for chemotherapy refractory disease. These systemic treatments have associated toxicities which need appropriate management for patients to stay on treatment and potentially have longer benefit from treatment. We review the expected toxicities of immune checkpoint inhibitors, FGFR inhibitors such as erdafitinib, and antibody drug conjugates such as enfortumab vedotin and sacituzumab govitecan.

OBJECTIVE: To describe a rare case of Wernicke encephalopathy (WE) as a result of hyperemesis gravidarum due to primary hyperparathyroidism (PHPT) in pregnancy. METHODS: We present the clinical presentation, supportive laboratory values, diagnostic dilemmas, treatment, clinical outcome, and supportive literature review of a patient with WE as a result of hyperemesis gravidarum due to PHPT in pregnancy. RESULTS: A 27-year-old previously healthy G1P0 female presented with initial symptoms of right upper-quadrant pain, nausea, vomiting, and paresthesias at 17.3 weeks of gestation. The patient later developed neurologic symptoms including acute encephalopathy, ataxia, and intranuclear ophthalmoplegia. The suspicion for WE was confirmed with characteristic findings on brain magnetic resonance imaging. WE was attributed to severe malnutrition from hyperemesis gravidarum and poor prenatal care. Hypercalcemia with an elevated parathyroid hormone level was identified following an unfortunate intrauterine fetal demise, raising suspicion for PHPT. PHPT was confirmed, and after undergoing successful parathyroidectomy, the patient regained normal neurologic function, with the exception of mild lower-extremity paresthesias. CONCLUSION: This case is an example where early recognition and treatment of hyperparathyroidism can be masked by severe malnutrition and present in an unusual way with neurologic symptoms of WE. Early recognition and suspicion are critical in preventing poor fetal outcomes and long-term consequences.