North Shore University Hospital (formerly known as Manhasset Hospital) is a part of Northwell Health, New York State's largest healthcare provider and private employer. It is a primary teaching hospital for the Donald & Barbara Zucker School of Medicine at Hofstra/Northwell (along with Long Island Jewish Medical Center), offering residency programs, postgraduate training programs and clinical fellowships. It is located in Manhasset, New York.A level I trauma center, North Shore University Hospital has 738 beds and a staff of approximately 4,000 specialty and subspecialty physicians. It offers care in all medical and surgical specialties, including cardiovascular services, cancer care, orthopedics, maternal-fetal medicine and women's health services. The hospital offers neuroscience capabilities, including the Harvey Cushing Institutes of Neuroscience. These include the Chiari Institute, Movement Disorders Institute, Brain Tumor Institute, Brain Aneurysm Center, Headache Center and Spine Center as well as a state-designated stroke center. The campus also contains the Sandra Bass Heart Hospital and Sandra Atlas Bass center for Liver Diseases which both collaborate to perform transplant services including Heart, Liver and Kidney.The campus is home to the Feinstein Institute for Medical Research.
Mitochondria are essential organelles responsible for cellular energy production and diverse metabolic processes. Mitochondrial dysfunction is implicated in a wide range of diseases. Specifically, genetic mitochondrial diseases, arising from mutations in mitochondrial or nuclear DNA, lead to significant mitochondrial deficits, which result in debilitating and often life-threatening symptoms. Conventional treatments frequently fail to address these underlying mitochondrial defects, leaving few therapeutic options. Mitochondrial transplantation (MTx), an emerging therapeutic approach involving the delivery of healthy exogenous mitochondria to target cells, has demonstrated beneficial effects in various mitochondria-mediated diseases in both preclinical and early clinical studies. However, its application to inherited mitochondrial disorders remains largely unexplored and raises important questions about the need for repeated or continuous administration to sustain therapeutic effects. This review systematically examines the potential of MTx for inherited mitochondrial disorders by classifying these diseases by mitochondrial and nuclear DNA origin, critically assessing MTx evidence and mechanisms, and identifying unique translational requirements for chronic inherited disorders. While significant challenges remain, MTx represents a promising approach to directly address mitochondrial dysfunction in these life-threatening conditions with limited therapeutic alternatives.
PURPOSE:Sotorasib represents an early example in which the US Food and Drug Administration (FDA) requested formal dose optimization under Project Optimus. Although 960 mg remains the labeled dose, tolerability is often challenging. After the FDA Oncologic Drugs Advisory Committee discussion of CodeBreak100 part B, Ratain and Popat argued there was no clear basis for doses above 240 mg. We conducted a systematic review and meta-analysis comparing the efficacy and tolerability of standard versus reduced starting doses of sotorasib in KRAS G12C-mutated non-small cell lung cancer. METHODS:We conducted a systematic search of PubMed, EMBASE, SCOPUS, CINAHL, and Web of Science through October 28, 2025. Eligible studies included randomized trials, prospective studies, and retrospective studies reporting objective response rate (ORR), progression-free survival (PFS), and treatment-related adverse events (TRAEs). Pooled estimates were calculated using a random-effects model. RESULTS:Among 5,133 studies screened, 145 studies were reviewed, with 10 studies meeting inclusion criteria. The pooled ORR was 33% (95% CI, 29% to 36%) for patients starting at 960 mg (n = 1,347) versus 26% (95% CI, 19% to 34%) for those starting at reduced dose (n = 130), similar to the dose-optimization study (32.7% v 24.8%). There was no statistically significant improvement in ORR with the higher dose (risk ratio, 1.26 [95% CI, 0.87 to 1.83]). Similarly, pooled PFS did not favor 960 mg dosing (hazard ratio, 0.77 [95% CI, 0.56 to 1.05]). At 960 mg dose, TRAEs were common, with any-grade and grade ≥3 TRAE in 83% and 22%, respectively, with dose reductions in 17% and discontinuation in 10% of patients. CONCLUSION:The labeled 960 mg dose did not demonstrate meaningful improvement in efficacy, while toxicity remained substantial. These findings support efforts under Project Optimus to identify the lowest effective dose. Lower doses, including 240 mg, may provide comparable outcomes while reducing toxicity, pill burden, and treatment costs.
Cerebral venography remains an important tool in neurovascular practice despite the increasing reliance on non-invasive imaging modalities such as CT and MR venography. While catheter venography is no longer the primary diagnostic method for cerebrovenous disorders, its role has evolved alongside the expanding indications for intracranial venous interventions. This work explores the indications, technical considerations, and clinical utility of catheter venography and venous manometry in the evaluation and management of cerebrovenous diseases. It highlights the evolving role of venous interventions in neurointerventional practice and provides insights into optimizing procedural outcomes.
Clostridioides difficile is a common cause of hospital-acquired diarrheal infections and immunocompromised patients, including heart transplant patients, are vulnerable to severe Clostridioides difficile infections (CDI). Primary prophylaxis of CDI with oral vancomycin can be utilized in these patients but data regarding efficacy is limited. This was an IRB-approved retrospective observational chart review conducted at North Shore University Hospital evaluating the efficacy of oral vancomycin for primary prophylaxis of CDI in heart transplant recipients admitted between January 2018 and December 2023. The study compared patients who received oral vancomycin prophylaxis (OVP) for CDI with those who did not, based on a protocol change in January 2022. Patients with a history of CDI were excluded. The primary objective was to compare the development of CDI within one-year post-transplant between patients who received OVP and those who did not. The secondary objective was the incidence of vancomycin-resistant Enterococcus infections within one-year post-transplant. Statistical analysis involved Fisher’s exact test for categorical data and Wilcoxon rank-sum test for continuous data. The study included 122 patients. Of these, 44 (36%) did not receive OVP, while 78 (64%) did. For the primary outcome, 2 patients developed CDI within one-year post-transplant, both of whom had not received prophylaxis, but this difference was not statistically significant. These patients developed CDI within 24 days and 39 days respectively. For the secondary outcome, 8 patients developed VRE within one-year post-transplant of which 63% (n=5) received prophylaxis. There was no significant difference in VRE development between those who did and did not receive OVP (6.4% vs. 6.8%, respectively). This study did not show a benefit for OVP in the prevention of CDI in heart transplant recipients without a history of CDI. However, these results have limitations, primarily due to the low incidence of CDI and the small sample size. Further research is needed to assess the efficacy of oral vancomycin primary prophylaxis in heart and other solid organ transplant recipients. All Authors: No reported disclosures
