tbuckley/cabot-search huggingface dataset:
Meconium-Related Obstruction and Clinical Outcomes in Term and Preterm Infants
Authors: Jordan M. Rook, Nikhil Chervu, Kara L. Calkins, Peyman Benharash, Daniel A. DeUgarte
Journal: JAMA Network Open (2025)

Importance Textbooks attribute 80% of meconium-related small bowel obstructions to cystic fibrosis and 15% of colonic obstructions to Hirschsprung disease. It is unknown whether these estimates are accurate, particularly among preterm infants, whose immature bowel predisposes them to meconium-related obstruction (MRO). Objective To estimate the incidence of MRO by type and to assess its association with clinical outcomes. Design, Setting, and Participants This retrospective cohort study of live-born infants included in the National Inpatient Sample from January 1, 2016, to December 31, 2020, used survey weighting methods to estimate the national incidence of MRO by etiology. Data were analyzed from November 27, 2023, to November 12, 2024. Exposure MRO. Main Outcomes and Measures The primary outcome was diagnosis with MRO. Secondary outcomes included mortality, need for abdominal surgery, hospitalization duration, and cost. Multivariable regression models were developed to evaluate characteristics associated with MRO and to assess the association of MRO of prematurity with clinical outcomes after adjusting for demographic and clinical covariates. Results Of 3 550 796 infants, 51.2% were male and 46.7% were privately insured. Overall, 9.1% (n = 322 499) were born preterm. Of 1844 (0.1%) infants treated for MRO, 41 (2.2%) had cystic fibrosis, 60 (3.3%) had Hirschsprung disease, and 1743 (94.5%) had neither predisposing condition. Preterm infants were at highest risk for MRO, with 4.7 MRO cases per 100 000 births associated with cystic fibrosis, 4.7 MRO cases per 100 000 births associated with Hirschsprung disease, and 187.3 MRO cases per 100 000 births associated with neither predisposing condition. Among infants with neither cystic fibrosis nor Hirschsprung disease, those with gestational ages from 28 weeks to 31 weeks 6 days were most likely to develop MRO compared with term infants (adjusted odds ratio, 6.08 [95% CI, 4.27-8.67]). Among preterm infants, having an MRO was associated with a 4.2 percentage point increase in the probability of abdominal surgery (95% CI, 3.1-5.4 percentage points), a 7.3-day increase in length of stay (95% CI, 5.8-8.8 days), and a $23 215 increase in hospitalization costs (95% CI, $17 739-$28 690) compared with infants who did not have an obstruction, with no change in mortality rate (0.1 percentage point change [95% CI, −0.6 to 0.8 percentage points]). Conclusions and Relevance In this cohort study of over 3.5 million infants, MRO was most likely to occur among preterm infants without cystic fibrosis or Hirschsprung disease. These infants more frequently required surgery and had longer and more costly hospitalizations, indicating a need for dedicated prevention and treatment pathways for this understudied disease.
Tracking US Health Care Spending by Health Condition and County
Authors: Joseph L. Dieleman, Meera Beauchamp, Sawyer W. Crosby, Drew DeJarnatt, Emily K. Johnson, Haley Lescinsky, Theresa McHugh, Ian Pollock, Maitreyi Sahu, Vivianne Swart, Kayla V. Taylor, Azalea Thomson, Golsum Tsakalos, Maxwell Weil, Lauren B. Wilner, Anthony L. Bui, Herbert C. Duber, Annie Haakenstad, Bulat Idrisov, Ali Mokdad, Mohsen Naghavi, Gregory Roth, John W. Scott, Tara Templin, Christopher J. L. Murray
Journal: JAMA (2025)

Importance Understanding health conditions with the most spending and variation across locations and over time is important for identifying trends, highlighting inequalities, and developing strategies for lowering health spending. Objective To estimate US health care spending for each of 3110 US counties, across 4 payers (Medicare, Medicaid, private insurance, and out-of-pocket payments), and according to 148 health conditions, 38 age/sex groups, and 7 types of care from 2010 to 2019. Design, Setting, and Participants Observational analysis using more than 40 billion insurance claims and nearly 1 billion facility records. Exposures Ambulatory care, dental care, emergency department care, home health care, hospital inpatient care, nursing facility care, and purchase of prescribed retail pharmaceuticals. Main Outcomes and Measures Health care spending and utilization (eg, number of visits, admissions, or prescriptions) estimates from 2010 through 2019. Results Between 2010 and 2019, 76.6% of personal health care spending was captured by this study. More spending was on type 2 diabetes ($143.9 billion [95% CI, $140 billion-$147.2 billion]) than on any other health condition, followed by other musculoskeletal disorders, which includes joint pain and osteoporosis ($108.6 billion [95% CI, $106.4 billion-$110.3 billion]), oral disorders ($93 billion [95% CI, $92.7 billion-$93.3 billion]), and ischemic heart disease ($80.7 billion [95% CI, $79 billion-$82.4 billion]). Of total spending, 42.2% (95% CI, 42.2%-42.2%) was on ambulatory care, while 23.8% (95% CI, 23.8%-23.8%) was on hospital inpatient care and 13.7% (95% CI, 13.7%-13.7%) was on prescribed retail pharmaceuticals. At the county level, age-standardized spending per capita ranged from $3410 (95% CI, $3281-$3529) in Clark County, Idaho, to $13 332 (95% CI, $13 177-$13 489) in Nassau County, New York. Across counties, the greatest variation was in age-standardized out-of-pocket spending, followed by private insurance spending. Cross-county variation was driven more by variation in utilization rates than variation in price and intensity of care, although both types of variation were substantial for all payers but Medicare. Conclusions and Relevance Broad variation in health care spending was observed across US counties. Understanding this variation by health condition, sex, age, type of care, and payer is valuable for identifying outliers, highlighting inequalities, and assessing health care gaps.
Development of a policy model for pediatric acute lymphoblastic leukemia to facilitate economic evaluation
Authors: Petros Pechlivanoglou, Linda Luu, Qing Li, J David Rios, Alexandra Moskalewicz, Sumit Gupta
Journal: JNCI Journal of the National Cancer Institute (2025)

Abstract: Background New highly effective, but expensive, immunotherapies have revolutionized the treatment of relapsed pediatric acute lymphoblastic leukemia (ALL) but their long-term clinical and economic impact is unclear. We developed the ALL Policy microsimulation model to estimate long-term clinical and economic outcomes for patients with pediatric ALL aged 0-17 in Ontario, Canada. We also illustrate the model’s clinical utility through a cost-effectiveness analysis of blinatumomab in relapsed B-cell ALL. Methods The ALL Policy model is informed using health administrative data and chart abstracted data from Ontario, Canada, and published literature. The model estimates lifetime risk of relapse, bone marrow transplant (BMT), conditional life expectancy, quality-adjusted life years (QALY), and total healthcare costs for individuals with pediatric ALL, and can be stratified by relevant clinical characteristics (eg, B-cell or T-cell lineage). Additionally, we subset the model to patients with relapsed B-cell ALL to illustrate use of the model in estimating the cost-effectiveness of blinatumomab vs standard chemotherapy. Results Simulated pediatric ALL patients diagnosed from 2002-2012 had a projected conditional life expectancy of 64.90 years. The lifetime risk of BMT was estimated at 12.5%. Lifetime healthcare costs were $244,433 CAD (95% CI $213,314, $303,430). Treatment with blinatumomab compared to standard chemotherapy post-relapse was estimated to result in 1.08 additional QALYs and an additional cost of $59,410 CAD (incremental cost-effectiveness ratio of $54,885/QALY). Conclusion The ALL policy model can serve as a modeling foundation for timely economic evaluation. Introduction of blinatumomab in relapsed B-cell ALL may be a cost-effective strategy.
Longitudinal Determination of Diabetes Complications and Other Clinical Variables as Risk Factors for Diabetic Ketoacidosis in Type 1 Diabetes
Authors: Priya Bapat, Dalton R. Budhram, Abdulmohsen Bakhsh, Mohammad I. Abuabat, Natasha J. Verhoeff, Doug Mumford, Wajeeha Cheema, Cesar Falappa, Andrej Orszag, Akshay Jain, David Z.I. Cherney, Michael Fralick, Alanna Weisman, George Tomlinson, Leif Erik Lovblom, Bruce A. Perkins
Journal: Diabetes Care (2025)

OBJECTIVE We aimed to determine whether diabetes complications, such as kidney disease that may impair acid-base buffering capacity, independently predict the risk of subsequent diabetic ketoacidosis (DKA). RESEARCH DESIGN AND METHODS We accessed previously collected 34-year data from the Diabetes Control and Complications Trial and Epidemiology of Diabetes Interventions and Complications study through public data access. Multivariable Cox proportional hazards models with time-varying exposures and covariates were used to examine the associations of macrovascular disease and early and late stages of neuropathy, nephropathy, and retinopathy, with subsequent DKA occurrence as the outcome. RESULTS Of 1,441 participants, 297 experienced 488 DKA events over follow-up. Major adverse cardiovascular events [hazard ratio (HR) 3.16, 95% CI 1.57–6.35, P = 0.001] and late-stage neuropathy, which comprised serious foot ulcer or amputation (HR 1.59, 95% CI 1.04–2.45, P = 0.03) were independently associated with higher DKA risk. Higher risk was also associated with shorter diabetes duration (HR 0.76, 95% CI 0.64–0.91, P = 0.002), female sex (HR 2.04, 95% CI 1.56–2.67, P &amp;lt; 0.001), current insulin pump use (HR 3.04, 95% CI 2.29–4.02, P &amp;lt; 0.001), higher time-updated HbA1c (per additional 1%: HR 1.39, 95% CI 1.29–1.50, P &amp;lt; 0.001), and higher current insulin dose (per 1 additional unit/kg/day: HR 2.32, 95% CI 1.62–3.33, P &amp;lt; 0.001). CONCLUSIONS A major cardiovascular event, foot ulcer, or amputation confers the greatest risk of future DKA independent of previously recognized risk factors, implying a need to target patients with these events for DKA prevention interventions, such as self-management skills for metabolic control, management of depression, and DKA education.
Arterial Stiffness Is Related to Diabetes-Associated Microvascular Complications: The SEARCH for Diabetes in Youth Study
Authors: Ryan P. Brady, Elaine M. Urbina, Zhiqian Gao, Dana Dabelea, Eva Lustigova, Santica Marcovina, Amy K. Mottl, Catherine Pihoker, Kristi Reynolds, LeAnne Sancrainte, Lawrence M. Dolan, Amy S. Shah
Journal: Diabetes Care (2025)

To assess the relationship between arterial stiffness, an early marker of macrovascular cardiovascular disease, and microvascular complications in adolescents and young adults with youth-onset diabetes. This study included 1,226 individuals (median age at initial visit 18 years; 58% female; 53% non-Hispanic White, 22% non-Hispanic Black, and 20% Hispanic) with youth-onset type 1 or type 2 diabetes from the SEARCH for Diabetes in Youth Study. Arterial stiffness measures included pulse wave velocity for carotid femoral, carotid radial, femoral foot, and augmentation index (AIx). Microvascular complications included microalbuminuria, peripheral neuropathy, and retinopathy. Participants were followed up once at ∼5 years. Cross-sectionally, in type 1 diabetes, AIx was associated with higher odds of having any one microvascular complication (odds ratio [OR] 1.35; 95% CI 1.04-1.76), microalbuminuria (OR 2.76; 95% CI 1.78-4.39), neuropathy (OR 1.63; 95% CI 1.07-2.50), and retinopathy (OR 1.37; 95% CI 1.06-1.79). In type 2 diabetes, AIx was associated with higher odds of microalbuminuria (OR 2.05; 95% CI 1.04-4.33; all P < 0.05). In longitudinal analysis, in type 1 diabetes, a change in AIx was associated with the development of any one microvascular complication (OR 1.45; 95% CI 1.15-1.82), microalbuminuria (OR 5.42; 95% CI 1.98-14.80), neuropathy (OR 2.03; 95% CI 1.22-3.40), and retinopathy (OR 1.48; 95% CI 1.15-1.90). In type 2 diabetes, a change in AIx was associated with the development of microalbuminuria (OR 21.98; 95% CI 1.30-372.88; all P < 0.05). Arterial stiffness is related to and predicts microvascular complications in youth-onset type 1 and type 2 diabetes.
Identification of Urinary Metabolic Biomarkers for H3K27M Mutation Diagnosis in Brainstem Gliomas
Authors: Xiaoou Li, Wei Sun, Zhengguang Guo, Feng Qi, Tian Li, Yujin Wang, Mingxin Zhang, Aiwei Wang, Zhuang Jiang, Luyang Xie, Yiying Mai, Yi Wang, Zhen Wu, Nan Ji, Yang Zhang, Liwei Zhang
Journal: Neuro-Oncology (2025)

Brainstem gliomas (BSGs) harboring a histone 3 lysine27-to-methionine (H3K27M) mutation represent one of the deadliest brain tumors with a dismal prognosis, as they exhibit a much worse response to therapy compared to the wildtype BSGs. Early non-invasive recognition of the H3K27M mutation is paramount for clinical decision-making in treating BSGs. Plasma and urine samples were prospectively collected from BSG patients before biopsy or surgical resection and were chronologically divided into discovery, test, and validation cohorts. Utilizing the discovery and test cohort samples, an untargeted metabolomic strategy was exploited to identify candidate metabolite biomarkers, related to the H3K27M mutation. The candidate biomarkers were validated in the validation cohort with a targeted metabolomic method. Differential metabolomic profiles were detected between the H3K27M-mutant and wild-type BSGs in both the plasma and urine, the metabolomic changes were more dramatic in urine than in plasma. After rigorous screening for candidate biomarkers and validation with a targeted metabolomic approach, three metabolites, nomilin, Lys-Leu, and hawkinsin, emerged as significantly elevated biomarkers in H3K27M-mutant BSG urine samples. The biomarker panel combining the three metabolites had a diagnostic area under the curve (AUC) of approximately 75%. Furthermore, the biomarker panel improved the prediction accuracy of radiomics/clinical models to an AUC value high as 93.38%. A urinary metabolite biomarker panel that exhibited high accuracy for non-invasive prediction of the H3K27M mutation status in BSG patients was identified. This panel has the potential to improve the predictive performance of current radiomics models or clinical features.
Local tumor control and neurological outcomes after surgery for spinal hemangioblastomas in sporadic and Von-Hippel-Lindau Disease: A multicenter study
Authors: Johannes Wach, Alim Emre Basaran, Martin Vychopen, Tarik Tihan, Maria Wostrack, Vicki M Butenschoen, Bernhard Meyer, Sebastian Siller, Nils Ole Schmidt, Julia Onken, Peter Vajkoczy, Alejandro N Santos, Laurèl Rauschenbach, Philipp Dammann, Ulrich Sure, Jan-Helge Klingler, Roberto Doria-Medina, Jürgen Beck, Bianca-Ioana Blaß, Christine Juliane Gizaw, Romina Hohenhaus, Sandro Krieg, Obada T Alhalabi, Lukas Klein, Claudius Thomé, Nikolaus Kögl, Przemyslaw Kunert, Tomasz Czernicki, Tobias Pantel, Maximilian Middelkamp, Sven Oliver Eicker, Ahed H Kattaa, David J Park, Steven D Chang, Fatma Kilinc, Marcus Czabanka, Erdem Güresir
Journal: Neuro-Oncology (2025)

Abstract Background Spinal hemangioblastomas (sHBs) are rare vascular tumors with significant neurological implications. Their management, particularly in von Hippel-Lindau (VHL) disease, remains challenging due to recurrence and functional decline. Timely identification and intervention are critical for optimal outcomes. Methods This international, multicenter retrospective cohort study included 357 patients (199 VHL-associated, 158 sporadic) from 13 neuro-oncological centers. Clinical and imaging data were analyzed to assess progression-free survival (PFS) and functional outcomes using the Modified McCormick Scale (mMCS) at 12 months. Secondary analyses identified factors associated with VHL disease in sHBs. Results Complete resection (CR) was achieved in 87.7% of cases, leading to significantly improved PFS at 72 months (sporadic: 95.1%, VHL-associated: 91.1%; HR: 0.18, 95%CI: 0.08–0.4). Multivariable analysis identified predictors of unfavorable outcomes at 12 months: Preoperative mMCS ≥2 (OR: 5.17, p=0.008), intramedullary tumor location (OR: 9.48, p=0.01), and preoperative bleeding (OR: 31.12, p=0.02). Factors independently associated with VHL disease in sHBs included non-cervical tumor location (OR: 2.08, p=0.004), intramedullary growth (OR: 2.39, p&amp;lt;0.001), and age &amp;lt;43 years (OR: 3.24, p&amp;lt;0.001). Functional improvements were observed in most patients, particularly those with sporadic sHBs. Conclusions Complete surgical resection is essential for long-term tumor control and favorable functional outcomes in both sporadic and VHL-associated sHBs. Early intervention, particularly in mild symptomatic and progressive cases, before neurological deterioration or hemorrhage, optimizes recovery. This study, the largest of its kind in a multicentric international setting, provides robust evidence to guide the management of both sporadic and VHL-associated sHBs.
The Assessment of SpondyloArthritis International Society (ASAS) Consensus-Based Expert Definition of Difficult-to-Manage, including Treatment-Refractory, Axial Spondyloarthritis
Authors: Denis Poddubnyy, Victoria Navarro-Compán, Murat Torgutalp, Suzanne Arends, Sibel Zehra Aydin, Simone Battista, Filip van den Bosch, Christine Bundy, Alberto Cauli, Jo Davies, Maxime Dougados, Tuncay Duruöz, Bassel El-Zorkany, Warren Fong, Floris van Gaalen, Rodrigo Garcia-Salinas, Marco Garrido Cumbrera, Pál Géher, Lianne Gensler, Simeon Grazio, Feng Huang, Mitsumasa Kishimoto, Robert Landewé, Ying Ying Leung, Pedro M Machado, Helena Marzo-Ortega, Bhowmik Meghnathi, Anna Molto, Elena Nikiphorou, Sofia Ramiro, Martin Rudwaleit, Carla G S Saad, Alexandre Sepriano, James Wei, Xenofon Baraliakos, Désirée van der Heijde
Journal: Annals of the Rheumatic Diseases (2025)

To develop a consensus-based expert definition of difficult-to-manage (D2M) axial spondyloarthritis (axSpA), incorporating treatment-refractory (TR) disease. A literature review was conducted in 2022 to identify potential definitions for D2M/TR axSpA from prior studies, followed by a 2-round Delphi consensus process conducted in 2022 and 2023 to identify components of D2M axSpA. Based on the results of the Delphi process, a draft of the D2M axSpA definition was developed and presented to the expert task force, including patient representation, and, subsequently, to the Assessment of SpondyloArthritis International Society (ASAS) membership for endorsement in January 2024. Consensus was reached on a D2M definition encapsulating treatment failure (treatment according to the ASAS-European Alliance of Associations for Rheumatology recommendations and failure of ≥2 biological or targeted synthetic disease-modifying antirheumatic drugs with different mechanisms of action unless contraindicated), suboptimal disease control, and physician or patient acknowledgement of problematic signs/symptoms in patients diagnosed with axSpA by the rheumatologist. This definition represents a broad concept that includes various reasons that lead to an unsatisfactory treatment outcome. TR axSpA is covered by the D2M definition but requires a history of treatment failure, the presence of objective signs of inflammatory activity, and the exclusion of noninflammatory reasons for nonresponse. The proposed D2M definition incorporating TR disease was endorsed by ASAS at the annual meeting in January 2024, with 89% votes (109/123) in favour of it. The ASAS D2M axSpA definition, including TR disease, allows for identifying patients with unmet needs, paving the way for further research in this condition and its clinical care improvement.
<scp>CSF3R</scp> Mutations in Hematological Disorders Undergoing Allogeneic Hematopoietic Stem Cell Transplantation
Authors: Jiaxin Cao, Yawei Zheng, Ruixin Li, Dan Feng, Xiaofei Ni, Hongye Gao, Mingyang Wang, Yigen Cao, Weihua Zhai, Rongli Zhang, Donglin Yang, Yi He, Sizhou Feng, Mingzhe Han, Haixiao Zhang, Aiming Pang, Erlie Jiang
Journal: American Journal of Hematology (2025)
Probiotic supplementation mitigates sex-dependent nociceptive changes and gut dysbiosis induced by prenatal opioid exposure
Authors: Salma Singh, Yaa Abu, Danielle Antoine, Daniel Gomez, Junyi Tao, Bridget Truitt, Sabita Roy
Journal: Gut Microbes (2025)

The gut microbiome has emerged as a promising target for modulating adverse effects of opioid exposure due to its significant role in health and disease. Opioid use disorder (OUD) has become increasingly prevalent, specifically in women of reproductive age, contributing to an increased incidence of offspring exposed to opioids in utero. Recent studies have shown that prenatal opioid exposure (POE) is associated with notable changes to the maternal gut microbiome, with subsequent implications for the offspring's microbiome and other adverse outcomes. However, the role of the gut microbiome in mediating sex-based differences in pain sensitivity has not yet been investigated. In this study, both male and female C57BL/6 offspring were used to determine sex-based differences in nociception and gut microbial composition as a result of POE. Our data reveals significant sex-based differences in offspring prenatally exposed to opioids. The gut microbiome of opioid-exposed females showed an enrichment of commensal bacteria including Lactobacillus compared to opioid-exposed males. Additionally, POE females demonstrated decreased nociceptive sensitivity, while males demonstrated increased nociceptive sensitivity. RNA sequencing of the prefrontal cortex showed sex-based differences in several canonical pathways, including an increase in the opioid signaling pathway of opioid-exposed females, which was not observed in males. Microbiome modification via maternal probiotic supplementation attenuated sex-based differences throughout the early stages of life. Together, our study provides further insight on sex-based differences arising from POE and highlights the pivotal role of the gut microbiome as a modifiable target for mitigating its negative effects.
Longer Acting Injectable: Continuous, Linear Release of a Progestin Contraceptive From an Oxidized Porous Silicon Host
Authors: Geoffrey Hollett, Ruhan Fan, Tushar Kumeria, Heidi Leonard, Byungji Kim, Taylor R. Martin, Irmak Ipekci, Joanna Wang, Jiuk Byun, Nicole A. Chan, Amber Pierron, Curtis E. Moore, Jennifer Ayres, Michael J. Sailor
Journal: Advanced Healthcare Materials (2025)

Abstract Maintaining stable drug concentrations in the bloodstream is a challenge for injectable hydrophobic progestin contraceptives. This work investigates porous silicon dioxide (pSiO 2 ) microparticles as a delivery vehicle for progestins via melt‐infiltration of drugs into the mesopores. The pSiO 2 is prepared through electrochemical anodization of single‐crystalline silicon followed by thermal oxidation, yielding vertically oriented pores (≈50 nm diameter) with porosity varied (between 35–75%) to optimize drug loading and release. Among the progestins tested, etonogestrel and levonorgestrel (LNG) decompose near their melting points, preventing melt infiltration. However, addition of 20% cholesterol by mass suppresses the melting point of LNG sufficiently to enable loading without degradation. Mass loadings exceeding 50% (drug: drug + carrier) are achieved for segesterone acetate (SEG) and LNG, retaining drug crystallinity as confirmed by X‐ray diffraction. In vitro, both SEG and LNG‐loaded pSiO 2 display sustained drug release for up to 3 months, with reduced burst release, more constant steady‐state concentrations, and a substantially reduced tail compared to pure LNG or SEG, or SEG loaded into pSiO 2 from a chloroform solution. In a pilot in vivo study, SEG‐loaded pSiO 2 microparticles are well tolerated in 20‐week‐old female rats over a 25‐week period, with no signs of toxicity.