tbuckley/cabot-search huggingface dataset:
Pediatric Traumatic Brain Injury and Microvascular Blood-Brain Barrier Pathology
Authors: Josie L. Fullerton, Jennifer Hay, Charlotte Bryant-Craig, Josephine Atkinson, Douglas H. Smith, William Stewart
Journal: JAMA Network Open (2024)

Importance Pediatric traumatic brain injury (TBI) is a major cause of morbidity and mortality, with an increased risk of catastrophic outcome compared with adult TBI, including diffuse brain swelling and so-called second impact syndrome. Nevertheless, the biological substrates driving adverse outcomes in pediatric TBI remain poorly described. Objective To compare neuropathological evidence of brain swelling and blood-brain barrier (BBB) disruption after moderate or severe acute TBI in adult vs pediatric case material. Design, Setting, and Participants In this retrospective case series, cases of pediatric (aged 3-18 years) and adult (aged ≥19 years) TBI were accrued from January 1, 1979, to December 31, 2005, and underwent laboratory-based assessment of autopsy material from the Glasgow TBI Archive. Data analysis was performed from January 2019 to January 2024. Exposures Single moderate or severe TBI. Main Outcomes and Measures Evaluation of representative brain tissue sections stained for markers of endothelia (CD34) and BBB integrity (fibrinogen and immunoglobin G). Results Eighty-one pediatric patients (mean [SD] age, 12.1 [4.6] years; 50 [62%] male) and 62 adult patients (mean [SD] age, 38.7 [12.9] years; 35 [56%] male) were studied. At autopsy, when present, brain swelling was more often diffuse and bilateral among pediatric patients (64 of 81 cases [83%]) when compared with adult patients (21 of 62 [34%]) ( P &amp;amp;lt; .001). Histologic evidence of BBB disruption was common in material from both adult (57 of 62 [91%]) and pediatric (65 of 81 [80%]) ( P = .06) patients. In pediatric patients, however, this was a predominantly microvascular, capillary-level pathology, which was a less common finding in adult case material (mean [SD], 84.7% [8.6%] vs 31.2% [7.7%]; P &amp;amp;lt; .001). Conclusions and Relevance This autopsy case series of patients dying in the acute phase after single moderate or severe TBI provides neuropathological evidence of age-dependent differences in vascular pathology. Specifically, although BBB disruption in pediatric material was typically confined to microvascular, capillary-level vessels, in adult case material, BBB disruption more typically involved larger-diameter vessels. This observation of distinct microvascular pathology in pediatric acute TBI requires further investigation. In the meantime, this study presents an intriguing potential candidate pathology contributing to diffuse brain swelling in this age group.
Attributing Racial Differences in Care to Health Plan Performance or Selection
Authors: Jacob Wallace, Chima D. Ndumele, Anthony Lollo, Danil Agafiev Macambira, Matthew Lavallee, Beniamino Green, Kate A. Duchowny, J. Michael McWilliams
Journal: JAMA Internal Medicine (2024)

There is increased interest in public reporting of, and linking financial incentives to, the performance of organizations on health equity metrics, but variation across organizations could reflect differences in performance or selection bias.
Psychiatric Comorbidities in Persons With Epilepsy Compared With Persons Without Epilepsy
Authors: Churl-Su Kwon, Ali Rafati, Ruth Ottman, Jakob Christensen, Andres M. Kanner, Nathalie Jetté, Charles R. Newton
Journal: JAMA Neurology (2024)

Several psychiatric disorders have been found to occur more frequently in persons with epilepsy (PWE) than in persons without epilepsy. To summarize the prevalence of 20 psychiatric disorders in PWE compared with persons without epilepsy. The search included records from inception to February 2024 in Ovid, MEDLINE, Embase, and PsycINFO. Published epidemiological studies examining the prevalence of psychiatric disorders among PWE compared with persons without epilepsy were systematically reviewed. There were no restrictions on language or publication date. Abstracts were reviewed in duplicate, and data were extracted using a standardized electronic form. Descriptive statistics and meta-analyses are presented. Data were recorded on the prevalence of 20 psychiatric disorders among PWE compared with persons without epilepsy. Meta-analyses were performed along with descriptive analyses. The systematic search identified 10 392 studies, 27 of which met eligibility criteria. The meta-analyses included 565 443 PWE and 13 434 208 persons without epilepsy. The odds of most psychiatric disorders studied were significantly increased in PWE compared with those without epilepsy, including anxiety (odds ratio [OR], 2.11; 95% CI, 1.73-2.58); depression (OR, 2.45; 95% CI, 1.94-3.09); bipolar disorder (OR, 3.12; 95% CI, 2.23-4.36); suicidal ideation (OR, 2.25; 95% CI, 1.75-2.88) but not suicide attempt (OR, 3.17; 95% CI, 0.49-20.46); psychotic disorder (OR, 3.98; 95% CI, 2.57-6.15); schizophrenia (OR, 3.72; 95% CI, 2.44-5.67); obsessive-compulsive disorder (OR, 2.71; 95% CI, 1.76-4.15); posttraumatic stress disorder (OR, 1.76; 95% CI, 1.14-2.73); eating disorders (OR, 1.87; 95% CI, 1.73-2.01); alcohol misuse (OR, 3.64; 95% CI, 2.27-5.83) and alcohol dependence (OR, 4.94; 95% CI, 3.50-6.96) but not alcohol abuse (OR, 2.10; 95% CI, 0.60-7.37); substance use disorder (OR, 2.75; 95% CI, 1.61-4.72); autism spectrum disorder (OR, 10.67; 95% CI, 6.35-17.91); and attention-deficit/hyperactivity disorder (OR, 3.93; 95% CI, 3.80-4.08). In this comprehensive study, most psychiatric comorbidities examined were significantly more prevalent in PWE than in those without epilepsy. These findings show the high burden of psychiatric comorbidities in PWE. This, in turn, underscores the need for appropriately identifying and treating psychiatric comorbidity in epilepsy to manage patients effectively and improve quality of life.
Current and Future Roles of Chimeric Antigen Receptor T-Cell Therapy in Neurology
Authors: Fatme Seval Ismail, Marco Gallus, Sven G. Meuth, Hideho Okada, Hans-Peter Hartung, Nico Melzer
Journal: JAMA Neurology (2024)

Importance Advancements in molecular engineering have facilitated the creation of engineered T cells that express synthetic receptors, termed chimeric antigen receptors (CARs). This is promising not only in cancer treatment but also in addressing a spectrum of other conditions. This review provides a comprehensive overview of the current approaches and future potential of CAR T-cell therapy in the field of neurology, particularly for primary brain tumors and autoimmune neurological disorders. Observations CAR T-cell therapy for glioblastoma is promising; however, first-in-human trials did not yield significant success or showed only limited success in a subset of patients. To date, the efficacy of CAR T-cell therapies has been demonstrated in animal models of multiple sclerosis, but larger human studies to corroborate the efficacy remain pending. CAR T cells showed efficacy in treatment of patients with relapsed or refractory aquaporin 4–immunoglobulin G–seropositive neuromyelitis optica spectrum disorders. Further studies with larger patient populations are needed to confirm these results. Success was reported also for treatment of cases with generalized myasthenia gravis using CAR T cells. Chimeric autoantibody receptor T cells, representing a modified form of CAR T cells directed against autoreactive B cells secreting autoantibodies, were used to selectively target autoreactive anti– N -methyl- d -aspartate B cells under in vitro and in vivo conditions, providing the basis for human studies and application to other types of autoimmune encephalitis associated with neuronal or glial antibodies. Conclusions and Relevance CAR T cells herald a new era in the therapeutic landscape of neurological disorders. While their application in solid tumors, such as glioblastoma, has not universally yielded robust success, emerging innovative strategies show promise, and there is optimism for their effectiveness in certain autoimmune neurological disorders.
Modeling Health and Economic Outcomes of Eliminating Sex Disparities in Youth Physical Activity
Authors: Kosuke Tamura, Marie F. Martinez, Yangyang Deng, Jessie Heneghan, Colleen Weatherwax, Kavya Velmurugan, Kevin L. Chin, Breanna Rogers, Mohammad Moniruzzaman, Meredith Whitley, Sarah M. Bartsch, Kelly J. O’Shea, Alexis Dibbs, Sheryl Scannell, Bruce Y. Lee
Journal: JAMA Network Open (2024)

Importance Sex disparities in physical activity (PA) and sports participation among US children and adolescents have been persistent. Quantifying the impact of reducing or eliminating these disparities may help determine how much to prioritize this problem and invest in interventions and policies to reduce them. Objective To quantify what might happen if existing PA and sports participation disparities were reduced or eliminated between male and female children and adolescents. Design, Setting, and Participants This simulation study used an agent-based model representing all children (aged 6 to 17 years) in the US, their PA and sports participation levels, and relevant physical and physiologic characteristics (eg, body mass index) as of 2023. Experiments conducted from April 5, 2024, to September 10, 2024, simulated what would happen during the lifetime of each cohort member if PA and sports participation levels for female participants were increased (to varying degrees) to match male participants in the same age group. Main Outcomes and Measures Health outcomes, such as body mass index, incidence of weight-related conditions (eg, stroke, coronary heart disease, type 2 diabetes, and cancer), and economic outcomes (eg, direct medical costs and productivity losses). Results This simulation study modeled 8 299 353 US children and adolescents (4 240 119 [51.1%] male and 4 059 234 [48.9%] female) aged 6 to 17 years. Eliminating PA sex disparities averted 28 061 (95% CI, 25 358-30 763) overweight and obesity cases per cohort by age 18 years, which in turn averted 4869 (95% CI, 4007-5732) weight-related disease cases during their lifetimes and resulted in recurring savings of $333.45 million (95% CI, $290.22 million to $376.68 million) in direct medical costs and $446.42 million (95% CI, $327.39 million to $565.44 million) in productivity losses (in 2024 US dollars) for every new cohort of 6- to 17-year-olds. Reducing PA disparities by 50% averted 9027 (95% CI, 6942-11 112) overweight and obesity cases. Eliminating sex disparities in sports participation averted 41 499 (95% CI, 37 874-45 125) cases of overweight and obesity and 8939 (95% CI, 8088-9790) weight-related disease cases during their lifetimes, generating recurring savings of $713.48 million (95% CI, $668.80 million to $758.16 million) in direct medical costs and $839.68 million (95% CI, $721.18 million to $958.18 million) in productivity losses. Conclusions and Relevance In this simulation study of youth PA and sports participation, eliminating sex disparities could save millions of dollars for each new cohort of 6- to 17-year-olds, which could exceed the cost of programs and investments that could enable greater equity.
Moving Deprescribing Beyond Potentially Harmful Medications
Authors: Julie C. Lauffenburger
Journal: JAMA Network Open (2024)

Michelle C. Odden, PhD; Laura A. Graham, PhD; Xiaojuan Liu, PhD, MS; Chintan V. Dave, PharmD, PhD; Sei J. Lee, MD, MAS; Yongmei Li, PhD; Bocheng Jing, MS; Kathy Fung, MS; Carmen A. Peralta, MD, MAS; Michael A. Steinman, MD
Severe Maternal Morbidity and Subsequent Birth—Understanding and Informing a Woman’s Choice
Authors: Anders Husby, Heather A. Boyd
Journal: JAMA (2024)

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A novel AAV Vector for gene therapy of RPE-related retinal degenerative diseases via intravitreal delivery
Authors: Yajun Gong, Xianyu Huang, Tianxiang Tu, Cenfeng Chu, Chunrui Xian, Yushun Yuan, Xin Fu, Ruobi Li, Guisheng Zhong, Xiaolai Zhou
Journal: Molecular Neurodegeneration (2024)
Neisseria gonorrhoeae induces local secretion of IL-10 at the human cervix to promote colonization
Authors: Yiwei Dai, Vonetta L. Edwards, Qian Yu, Hervé Tettelin, Daniel C. Stein, Wenxia Song
Journal: Journal of Clinical Investigation (2024)

Gonorrhea, caused by the human-restricted pathogen Neisseria gonorrhoeae, is a commonly reported sexually transmitted infection. Since most infections in women are asymptomatic, the true number of infections is likely much higher than reported. How gonococci (GC) colonize women's cervixes without triggering symptoms remains elusive. Using a human cervical tissue explant model, we found that GC inoculation increased the local secretion of both pro- (IL-1β and TNF-α) and anti-inflammatory (IL-10) cytokines during the first 24-h. Cytokine induction required GC expression of Opa isoforms that bind the host receptors carcinoembryonic antigen-related cell adhesion molecules (CEACAMs). GC inoculation induced NF-κB activation in both cervical epithelial and subepithelial cells. However, inhibition of NF-κB activation, which reduced GC-induced IL-1β and TNF-α, did not affect GC colonization. Neutralizing IL-10 or blocking IL-10 receptors by antibodies reduced GC colonization by increasing epithelial shedding and epithelial cell-cell junction disassembly. Inhibition of the CEACAM downstream signaling molecule SHP1/2, which reduced GC colonization and increased epithelial shedding, decreased GC-induced IL-10 secretion. These results show that GC induce local secretion of IL-10, a potent anti-inflammatory cytokine, at the cervix by engaging the host CEACAMs to prevent GC-colonizing epithelial cells from shedding, providing a potential mechanism for GC asymptomatic colonization in women.
Elevated microRNA-187 causes cardiac endothelial dysplasia to promote congenital heart disease through inhibition of NIPBL
Authors: Chao Li, Zizheng Tan, Hongdou Li, Xiaoying Yao, Chuyue Peng, Yue Qi, Bo Wu, Tong-Jin Zhao, Chengtao Li, Jianfeng Shen, Hongyan Wang
Journal: Journal of Clinical Investigation (2024)

Cardiac endothelial cells are essential for heart development, and disruption of this process can lead to congenital heart disease (CHD). However, how miRNAs influence cardiac endothelial cells in CHD remains unclear. This study identified elevated miR-187 expression in embryonic heart endothelial cells from CHD fetuses. Using a conditional knock-in model, we showed that increased miR-187 levels in embryonic endothelial cells induce CHD in homozygous fetal mice, closely mirroring human CHD. Mechanistically, miR-187 targets NIPBL, which is responsible for recruiting the cohesin complex and facilitating chromatin accessibility. Consequently, the endothelial cell-specific upregulation of miR-187 inhibited NIPBL, leading to reduced chromatin accessibility and impaired gene expression, which hindered endothelial cell development and ultimately caused heart septal defects and reduced heart size both in vitro and in vivo. Importantly, exogenous miR-187 expression in human cardiac organoids mimicked developmental defects in the cardiac endothelial cells, reversible by NIPBL replenishment. Our findings establish the miR-187/NIPBL axis as a potent regulator that inhibits cardiac endothelial cell development by attenuating the transcription of numerous endothelial genes, with our mouse and human cardiac organoid models effectively replicating severe defects from minor perturbations. This discovery suggests that targeting the miR-187/NIPBL pathway could offer a promising therapeutic approach for CHD.
Association of PCSK9 inhibitors with risk of nonmelanoma skin cancer: a retrospective cohort study
Authors: Cheng-Yuan Li, Wei-Ting Wang, Sheng-Hsiang Ma, Li-Wei Lo, Chen-Yi Wu, Wei-Chuan Chang, Yi-Ju Chen, Tai-Li Chen
Journal: British Journal of Dermatology (2024)

Growing evidence has shown that cholesterol metabolism abnormalities involve carcinogenesis. Proprotein convertase subtilisin/kexin type-9 (PCSK9) inhibitors have been reported to inhibit tumor progression and prevent ultraviolet-related skin damage.
SNMMI PIC case competition finalist: Subcutaneous Panniculitis-Like T-Cell Lymphoma on 18F-FDG PET/CT
Authors: Murat Alp Oztek, Wala Elhussein, Marguerite T. Parisi
Journal: Clinical Nuclear Medicine (2024)

Abstract A 9-month-old girl was evaluated for recurrent fevers, rash, and indurated plaques, with laboratories demonstrating hyperferritinemia, hypertriglyceridemia, and pancytopenia, concerning for hemophagocytic lymphohistiocytosis. Biopsy of thigh lesion ultimately demonstrated subcutaneous panniculitis-like T-cell lymphoma. In a rare neoplasm of cytotoxic T-cells, subcutaneous panniculitis-like T-cell lymphoma presents with subcutaneous nodules in all age groups including children. Prognosis is generally good with immunosuppressive drugs being first line of treatment. 18 F-FDG PET/CT demonstrates hypermetabolic lesions and is used to determine the extent of disease burden, identify sites of occult disease, and assess response to treatment.
Cardiovascular Complications and Their Association With Short- and Long-Term Outcomes in Patients With Multiple Myeloma and Lymphoma Undergoing Chimeric Antigen Receptor T-Cell Therapy
Authors: Osnat Itzhaki Ben Zadok, Panagiotis Simitsis, Caron Jacobson, Omar Nadeem, Matthew J. Frigault, Noopur Raje, Caitlyn Duffy, Patrick Costello, Jamie Dela Cruz, Andrew Looka, Anju Nohria
Journal: Circulation (2024)
Timing of Extubation in Adult Patients with Acute Brain Injury
Authors: Federico Angriman, Andre C. K. B. Amaral, Eddy Fan, Shaurya Taran, Victoria A McCredie, Andrew Baker, Karen J. Bosma, Laurent Brochard, Neill K. J. Adhikari, Brian H Cuthbertson, Damon C. Scales, Niall D Ferguson
Journal: American Journal of Respiratory and Critical Care Medicine (2024)

Whether extubation immediately after a successful spontaneous breathing trial is associated with clinical benefits in adult patients with acute brain injury is unknown.
Labor and Delivery Outcomes in Australian Mothers after Kidney Transplantation
Authors: Nishanta Tangirala, Erandi Hewawasam, Christopher E. Davies, Amanda Poprzeczny, Elizabeth Sullivan, Stephen P. McDonald, Shilpanjali Jesudason
Journal: Journal of the American Society of Nephrology (2024)

Key Points Women with kidney transplantation had higher rates of cesarean sections, deliveries without labor, and vaginal delivery complications. Women with a kidney transplant had more cesarean sections, even after accounting for maternal factors, preterm delivery, and past cesarean sections. Hypertensive disorders of pregnancy and breech presentation were the main drivers of planned cesarean section delivery among transplant recipients. Background Factors influencing high cesarean section rates among mothers with a kidney transplant remain unclear. Methods Using linked Australia and New Zealand Dialysis and Transplant Registry (1970–2016) and perinatal datasets (1991–2013), we compared deliveries of women with a functioning kidney transplant with those without KRT (non-KRT). Results Of 2,946,851 babies (1,627,408 mothers), 211 were born to 137 mothers with a kidney transplant. Overall cesarean section rates were twice more frequent in the transplant cohort (63% versus 26% non-KRT; P &lt; 0.001) across all gestational periods compared with the non-KRT cohort and highest in preterm births (≥37 weeks, 48% versus 25%; P &lt; 0.001, 33–36 weeks, 77% versus 40%; P &lt; 0.001, and &lt;33 weeks, 75% versus 41%; P &lt; 0.001). Cesarean section rates remained higher after adjusting for maternal factors (incidence rate ratio, 1.5; 95% confidence interval, 1.3 to 1.7). In women with a kidney transplant with past pregnancy, 53% with no previous cesarean sections had a cesarean section in the current pregnancy (versus 19% non-KRT; P &lt; 0.001). Mothers with a kidney transplant had less spontaneous labor (30% versus 63%; P &lt; 0.001) and more planned deliveries (induced or elective cesarean sections; 70% versus 36%; P &lt; 0.001) than non-KRT mothers. Nearly half of the women with transplantation (45%) delivered by nonlabor cesarean sections, mostly occurring preterm (&lt;37 weeks, 70% versus ≥37 weeks, 30%; P = 0.002). In the transplant cohort, the main indications for nonlabor cesarean sections were hypertensive disorders of pregnancy and breech presentation (&gt;50% versus 18% non-KRT cohort; P &lt; 0.001) and were linked to gestational age. Nonlabor cesarean sections for fetal distress were higher in women with transplantation (10% versus 4% non-KRT; P = 0.03). In the non-KRT cohort, previous cesarean sections were the main indication for nonlabor cesarean sections (40% versus 24% transplant; P = 0.06). Postpartum hemorrhage (13% versus 7% non-KRT; P = 0.003) and fetal distress (18% versus 10% non-KRT; P = 0.001) were higher among the transplant cohort. Conclusions Women with a kidney transplant have higher rates of cesarean section delivery even after accounting for maternal factors, preterm delivery, and past cesarean sections compared with non-KRT cohorts.