Mass General Brigham

Mechanisms driving aggressive meningiomas remain poorly understood. Given the pivotal role of the immune microenvironment in tumor progression, we developed a comprehensive atlas of the meningioma microenvironment, with a view toward identifying modifiable opportunities. The immune microenvironment of 2,727 meningiomas was profiled using orthogonal methodologies, including 24 with mass cytometry, 24 single-cell RNAseq, 1,437 bulk RNAseq, 1,125 DNA methylation, 117 multiplex immunofluorescence, as well as that of 5 paired peripheral blood samples and 10 human meninges. Patient-derived organotypic tumor spheroids (PDOTS) were established to assess the effect of STING stimulation combined with anti-PD-1 treatment. We revealed a rich immune infiltration in meningioma, among the highest across 34 human cancer types (n = 12,188). Macrophages predominated in meningioma microenvironment, in contrast to the lymphoid dominance of peripheral blood, with meninges exhibiting an intermediate immune profile between meningiomas and peripheral blood. Cellular states and phenotypes of both immune and tumor cells shifted during tumor progression, with aggressive meningiomas possessing earlier-stage, immunosuppressive immune cells and proliferative tumor cells. Using ex vivo meningioma PDOTS, we demonstrated inducible responses to STING activation, marked by elevated cytokine release, which were synergistic when combined with PD-1 blockade. These findings offer an extensive resource on the cellular heterogeneity of the meningioma microenvironment and provide a framework for rational therapeutic modeling and strategy development.

Avoidant/restrictive food intake disorder (ARFID) involves restrictive eating driven by sensory sensitivity, low interest in food, or fear of negative consequences of eating. ARFID affects males and females equally and presents across the weight spectrum. Leptin, an anorexigenic hormone linked to adiposity, may contribute to low hunger and early satiety in ARFID. Prior findings indicate low leptin levels in low-weight females with ARFID; however, the role of leptin in ARFID across weight status and sex remains unknown. We hypothesized that youth with full/subthreshold ARFID, including a subgroup of low-weight males, would exhibit lower fasting leptin levels than healthy controls (HCs). We explored cross-sectional and longitudinal associations between leptin and clinical characteristics. Participants were youth aged 10-23 years (BMI percentile M [SD] = 41.4 (33.6)) with full/subthreshold ARFID (n = 95; 49.5% female) and HCs (n = 28; 50.0% female). At baseline, participants completed questionnaires, a fasted blood draw, and a diagnostic interview for ARFID, readministered at 1- and 2year follow-ups. Leptin levels did not differ between ARFID and HC groups. Low-weight ARFID males had significantly lower leptin than HC males (η 2 = 0.258); however, this difference was nonsignificant after adjusting for BMI percentile. Leptin showed medium-to-large positive associations with age, BMI, and anxiety but not appetite or ARFID severity. Baseline leptin did not predict symptom or weight changes longitudinally. Hypoleptinemia was only evident in low-weight ARIFD and strongly correlated with BMI percentile. However, relationships with anxiety may suggest additional roles of leptin in underlying ARFID psychopathology. Findings should be replicated in larger, more representative samples.

The current study aimed to estimate the percentage of US adults who disagree or do not know that addiction is a health condition and explore associations between disagreement that addiction is a health condition with indicators of beliefs about addiction treatment and intentions to support loved ones with addiction. A nationally representative sample of US adults was recruited from Gallup's probability-based panel. A total of n=5250 (out of n=12,500 invited) responded to a web-based survey including questions about beliefs about drug or alcohol addiction and treatment. Survey sample weights were applied to correct for unequal selection probability and nonresponse rates, and data were analyzed using descriptive statistics and regression. Close to one-quarter of US adults (23.0%) are estimated to either disagree or not know that addiction is a health condition. Respondents who disagreed or did not know that addiction is a health condition were less likely to believe that addiction is treatable by health care professionals (disagreed: OR=0.33, 95% CI=0.28-0.39; did not know: OR=0.28, 95% CI=0.21-0.36), early intervention for addiction is helpful (disagreed: OR=0.57, 95% CI=0.48-0.66; did not know: OR=0.40, 95% CI=0.31-0.53), or medications are effective treatments for addiction (disagreed: OR=0.47, 95% CI=0.40-0.55; did not know: OR=0.28, 95% CI=0.21-0.37). They were also less likely to indicate that they would help a loved one with addiction (disagreed: OR=0.50, 95% CI=0.40-0.63; did not know: OR=0.65, 95% CI=0.44-0.97). US adults likely have heterogenous views on addiction, and more research is needed to further understand how US adults conceptualize addiction.

INTRODUCTION: This is the case of a 31-year-old G0 with dysmenorrhea, catamenial shoulder pain, infertility, and recently aborted laparoscopic excision of endometriosis secondary to extent of disease. She presented to a MIGS provider at an academic medical center for surgical resection of endometriosis. OBJECTIVE: To review preoperative planning and intraoperative technique for resection of diaphragmatic endometriosis in a patient with dysmenorrhea and hemorrhagic pleural effusion. METHODS: Robotic-assisted laparoscopic excision of pelvic and diaphragmatic endometriosis. RESULTS: This is a case of a patient with a recently aborted laparoscopy at an outside facility who presented for consultation. On imaging, she was found to have a large right-sided hemorrhagic pleural effusion requiring preoperative drainage. She was subsequently taken to the operating room for robotic-assisted laparoscopic excision of pelvic and diaphragmatic endometriosis, which included resection of a full-thickness diaphragmatic lesion and placement of a chest tube. CONCLUSIONS: While rare, diaphragmatic endometriosis can be associated with significant morbidity. Interdisciplinary surgical and anesthetic planning, as well as sound operative technique, allow for successful robotic excision of diaphragmatic lesions.

The integration of generative AI (GenAI) and large language models (LLMs) in healthcare presents both unprecedented opportunities and challenges, necessitating innovative regulatory approaches. In this perspective, we discuss the risks of GenAI and LLM-based medical devices, the limitations of current medical device regulation frameworks when applied to GenAI or LLMs, and advocate for global collaboration in regulatory science research through engaging multidisciplinary expertise and focusing on the needs of diverse populations.

Painful trigeminal neuropathy (PTN) is a very disabling but often unrecognized facial pain from various etiologies. Patients with PTN suffer from persistent, intense facial pain with significantly impaired sensory function in the trigeminal territories. This article reviews the anatomy and pathophysiology of PTN, as well as its clinical presentation and management. The peripheral inflammatory cascades, including immune cell activation, inflammatory mediator-induced nociceptor activation, and sensory hyperexcitability in the trigeminal nerve, are discussed, as are the central sensitization processes, including postsynaptic NMDA receptor activation, glial cell-mediated inflammation, and reduced inhibitory pathways in the central nervous system. A comprehensive literature review that covers multiple specialties and discusses various treatment options based on the available evidence is presented. Collectively, a practical algorithm is proposed to improve current PTN management. It provides novel guidance for managing PTN in an evidence-based, integrative, and mechanism-specific approach. In conclusion, a multidisciplinary team approach targeting both peripheral and central sensitization would be an ideal strategy for delivering optimal, mechanism-specific management in painful trigeminal neuropathy.