Faculty Bibliography

Capiversatib is a pan-Ak strain transforming inhibitor used in combination with fulvestrant for the treatment of hormone receptor-positive advanced breast cancer and has a known adverse effect of hyperglycemia. We present 3 cases of severe hyperglycemia, 2 of which presented as diabetic ketoacidosis, in patients being treated with capivasertib. These cases demonstrate the severity of hyperglycemia that can result from capivasertib use, as well as highlight treatment regimens and patient outcomes.

The psychosocial evaluation plays an essential role in the multidisciplinary assessment of pediatric patients for thoracic organ transplantation or ventricular assist device (VAD) placement. However, there is considerable practice variation with regard to the content and process of the evaluation, with no known recent published guidelines. Furthermore, the pediatric evaluation necessarily differs from the adult evaluation in a number of substantive ways, including caregiver roles and decision-making. A writing committee of 25 multidisciplinary experts in pediatric cardiothoracic transplantation/VAD was established, who conducted a comprehensive literature review which resulted in the development of this consensus-based framework. This framework, which is a collaborative effort of the International Society for Heart and Lung Transplantation (ISHLT), the International Pediatric Transplant Association (IPTA), the Pediatric Heart Transplant Society (PHTS), the Advancing Cardiac Therapies Improving Outcomes Network (ACTION), and Transplant Families, represents the first known framework specific to both the content and process of the psychosocial evaluation for pediatric cardiothoracic transplantation/VAD. Attention was paid to relevant ethical, cultural and health equity considerations inherent in the pediatric evaluation process. Rather than provide a proscriptive evaluation process, the goal was to create a flexible framework to encourage consistency across centers, while also acknowledging the complexities inherent in evaluating children and their families for cardiothoracic transplant and VAD.

Introduction: COVID-19, in combination with steroid treatment, is known to propagate hyperglycemia in diabetic patients. The purpose of this study was to establish a new insulin protocol for diabetic patients with COVID-19 on the dexamethasone protocol for better glycemic control. Research Design and Methods: This was a retrospective cohort study conducted at NYU Langone Long Island Hospital from 1 July 2020 to 1 July 2021. Eligible cases had to meet the following inclusion criteria: age of 18 years or greater, history of or new-onset diabetes, diagnosis of COVID-19 and receiving the 10 day dexamethasone treatment, length of stay of at least 3 days with a minimum of 48 h of glucose monitoring, and requiring basal and prandial insulin with correction during hospital stay. Data were collected using the hospital"™s electronic record system. The total basal, prandial, and daily doses of insulin on the day at which glycemic control was achieved, or if glycemic control was not achieved by the discharge date, then on the completion date of the dexamethasone treatment, were collected and assessed. Results: A total of 145 patient cases were analyzed. About 46% of patients achieved glycemic control. The average insulin dose required was 0.67 (0.61"“0.74) unit/kg. The mean total dose of insulin was 59 units. The mean total basal dose was 21 units. The mean total prandial dose was 38 units. The average prandial doses were higher than the basal doses for all participants. Conclusions: Diabetic patients with COVID-19 on dexamethasone should be initiated on at least 0.6"“0.7 u/kg of insulin to achieve glycemic control.

Transcription factor MEF2C regulates multiple genes linked to autism spectrum disorder (ASD), and human MEF2C haploinsufficiency results in ASD, intellectual disability, and epilepsy. However, molecular mechanisms underlying MEF2C haploinsufficiency syndrome remain poorly understood. Here we report that Mef2c ^+/-(Mef2c-het) mice exhibit behavioral deficits resembling those of human patients. Gene expression analyses on brains from these mice show changes in genes associated with neurogenesis, synapse formation, and neuronal cell death. Accordingly, Mef2c-het mice exhibit decreased neurogenesis, enhanced neuronal apoptosis, and an increased ratio of excitatory to inhibitory (E/I) neurotransmission. Importantly, neurobehavioral deficits, E/I imbalance, and histological damage are all ameliorated by treatment with NitroSynapsin, a new dual-action compound related to the FDA-approved drug memantine, representing an uncompetitive/fast off-rate antagonist of NMDA-type glutamate receptors. These results suggest that MEF2C haploinsufficiency leads to abnormal brain development, E/I imbalance, and neurobehavioral dysfunction, which may be mitigated by pharmacological intervention.