The hospital was established in 1912 under the name Maimonides Hospital, with a mission of serving poor immigrants from Europe while providing training to Jewish physicians, primarily of Eastern European descent. After a period of financial difficulty, it closed in 1918, and was reopened as "Mount Sinai Hospital" in 1919, with 60 beds and continuing its original mission.
Severe obesity (body mass index ≥ 40 kg/m2 or ≥ 35 kg/m2 with obesity-related comorbidities) is increasingly prevalent and independently associated with elevated perioperative morbidity and inferior oncologic outcomes in patients with colorectal cancer (CRC). Despite these risks, intentional preoperative weight optimization is not routinely incorporated into CRC management, owing to concerns regarding treatment delay, absence of guideline endorsement, and limited supporting evidence. A literature review was conducted using PubMed and Embase to evaluate the impact of severe obesity on morbidity, mortality, and oncologic outcomes in CRC. Peer-reviewed English-language studies involving adult human subjects were included, while conference abstracts, non-English publications, and studies unrelated to obesity and CRC were excluded. In the absence of published reports describing synchronized weight loss and CRC management in patients with severe obesity, three novel retrospective case examples were included to demonstrate feasibility during neoadjuvant treatment, with institutional review board approval obtained for all cases. Severe obesity complicates CRC staging due to limitations in cross-sectional imaging and anatomic delineation. Furthermore, severe and particularly visceral obesity is associated with increased rates of anastomotic leak, surgical site infection, and conversion to open surgery. Current CRC guidelines do not incorporate structured weight-loss strategies into standard treatment algorithms. Metabolic bariatric procedures, such as sleeve gastrectomy, achieve rapid and clinically meaningful weight reduction, often resulting in improved operative exposure and technical conditions for subsequent resection. Pharmacologic therapies, while more broadly accessible and less invasive, typically yield more modest reductions in visceral adiposity. Task force members report early experience across three distinct cases of locally advanced CRC in patients with severe obesity, demonstrating successful preoperative visceral fat reduction through multidisciplinary coordination incorporating metabolic bariatric surgery or pharmacologic therapy during neoadjuvant windows, followed by definitive oncologic resection. Severe obesity adversely influences CRC staging, operative complexity, and perioperative outcomes. Intentional metabolic optimization—through bariatric surgery or pharmacologic therapy—may represent a viable adjunct within multidisciplinary, patient-centered CRC care pathways. However, the absence of prospective short- and long-term outcome data underscores the need for systematic investigation to define optimal timing, safety parameters, and oncologic efficacy of weight-loss interventions in this high-risk population.
The peptide hepcidin is produced by the liver and serves as the central negative regulator of iron trafficking. Recently, drugs that affect the hepcidin pathway have been evaluated as potential treatment options for both controlling the degree of erythrocytosis in polycythemia vera (PV) patients as well as correcting anemia associated with myelofibrosis (MF). Under normal conditions, increased hepcidin levels limit iron absorption from the gastrointestinal tract and iron recycling from liver and splenic macrophages, thus decreasing plasma iron levels and restricting iron availability for erythropoiesis. In PV, however, unrestricted erythropoiesis occurs despite low systemic iron levels. Since hepcidin levels are relatively low in PV patients, hepcidin agonists (rusfertide, divesiran, sapablursen) are undergoing clinical development to control PV associated erythrocytosis, thereby reducing the need for therapeutic phlebotomies and myelosuppressive therapeutic options. By contrast, hepcidin levels are increased in MF patients leading to the trapping of iron in tissue macrophages which creates a picture which resembles the anemia of chronic inflammation. A number of strategies to lower hepcidin levels (the JAK2 inhibitors pacritinib and momelotinib, anti-hemojuvelin monoclonal antibody DISC-0974C) are currently undergoing clinical development to make systemic iron available for erythropoiesis and alleviate the degree of MF associated anemia. These new therapeutic options that modulate iron trafficking in PV and MF patients represent the application of greater knowledge of iron trafficking to create novel therapeutic options to treat patients with hematological malignancies.
We re-evaluated GPT-5 using our published pipelines: 500 emergency vignettes across 32 sociodemographic labels for bias, and adversarial prompts with fabricated details. GPT-5 showed no measurable improvement over GPT-4o in sociodemographic-linked decision variation, with several LGBTQIA+ groups flagged for mental-health screening in 100% of cases. Adversarial hallucination rates were higher (65% vs 53% for GPT-4o); a mitigation prompt reduced this to 7.67%.
Endometrial cancer incidence and mortality are rising globally, largely driven by the obesity epidemic. Treatment options remain limited for obesity-associated, hormone-resistant, or fertility-preserving endometrial cancer, highlighting the need for novel therapies that address both tumor biology and metabolic dysfunction. In this study, we synthesize the molecular rationale, preclinical, population-based, and emerging clinical trial evidence on glucagon-like peptide-1 receptor (GLP-1R) agonists (GLP-1 RA) in endometrial cancer. GLP-1R is expressed in benign and malignant endometrial tissues, where activation of cAMP–PKA and AMPK–mTOR signaling has been shown to mediate antiproliferative, proapoptotic, and autophagy-inducing effects. Preclinical models demonstrate that class-wide GLP-1 RAs may restore progesterone receptor expression, overcome hormone resistance, and synergize with progestin therapy; however, the effects may vary by agent. Retrospective studies suggest that combining GLP-1 RAs with local progestin therapy, commonly a levonorgestrel-releasing intrauterine device (preferred in obesity because oral progestin bioavailability is reduced), is associated with a reduced risk of endometrial cancer in high-risk women. Ongoing clinical trials are assessing their role in fertility-sparing settings—evaluating complete response to progestin-based therapy, relapse rates, and time to conception outcomes—as well as in adjuvant settings, in which disease-free survival is a key endpoint; however, gastrointestinal tolerability and the absence of long-term safety data in endometrial cancer populations remain important considerations. As a class, GLP-1 RAs represent a promising therapeutic approach to targeting both the obesogenic milieu and tumor-intrinsic pathways in endometrial cancer; however, agent-specific differences warrant attention. Prospective, subtype-stratified trials are essential to establish their role in comprehensive endometrial cancer care.
We tested state-of-the-art LLMs under clinical-scale workloads using two designs: a single agent handling all tasks and a multi-agent orchestrator assigning each task to a dedicated worker. Across retrieval, extraction, and dosing tasks, batch sizes ranged from 5-80. Multi-agent accuracy remained high (90.6% at 5 tasks; 65.3% at 80), while single-agent accuracy collapsed (73.1% to 16.6%; p < 0.01). Multi-agent runs used up to 65-fold fewer tokens and limited latency growth. These findings show that lightweight orchestration preserves accuracy and efficiency under mixed-task clinical loads.
