Tag: pubmed

Cancer Res Commun. 2026 Jul 23. doi: 10.1158/2767-9764.CRC-26-0373. Online ahead of print.

ABSTRACT

As Helicobacter pylori prevalence declines, understanding the contribution of modifiable systemic factors to gastric cancer (GC) risk becomes increasingly important. We evaluated the association of metabolic syndrome (MetS), its individual components, and anatomical subsites with incident GC in 471,540 UK Biobank participants. Multivariable Cox proportional hazards models were used to estimate the risk of overall, cardia, and non-cardia GC, and restricted cubic splines were used for exploratory non-linear analyses. Over a mean follow-up of 6.5 years, 332 incident GC cases were identified. In the fully adjusted model, baseline MetS was associated with increased GC risk (HR = 1.36, 95% CI: 1.08-1.71). A positive trend was observed with the accumulation of metabolic components (P trend = 0.033). Subsite analyses showed a directionally positive association for cardia GC (HR = 1.48, 95% CI: 1.03-2.11) and a non-significant positive association for non-cardia GC (HR = 1.28, 95% CI: 0.95-1.73); however, formal testing found no statistical evidence of subsite heterogeneity (P heterogeneity = 0.547). Exploratory spline analysis suggested a possible non-linear association for systolic blood pressure. Overall, MetS and the accumulation of its components were associated with a moderately increased risk of GC. Waist circumference showed the most consistent component-level signal, and further studies are needed to clarify the role of metabolic health in GC risk assessment.

PMID:42490138 | DOI:10.1158/2767-9764.CRC-26-0373

J Pediatr Orthop. 2026 Jul 24. doi: 10.1097/BPO.0000000000003424. Online ahead of print.

ABSTRACT

INTRODUCTION: STAC3 Disorder (STAC3D) is a rare genetic condition characterized by musculoskeletal abnormalities, myopathic facies, palatal anomalies, micrognathia, short stature, and an increased susceptibility to malignant hyperthermia. It was initially described in the Lumbee Native Americans of North Carolina, though it is now found globally. This study aims to characterize the musculoskeletal phenotype of STAC3D to aid in its diagnosis and clinical management.

METHODS: A retrospective cohort study of STAC3D patients from 2014 to 2025 at a single institution was conducted. Patients diagnosed with STAC3D were included. Data collected included demographics, genetic testing, musculoskeletal conditions, and their management. Descriptive and comparative statistics were utilized, with rates reported as percentages and variables expressed as median and means with standard deviation.

RESULTS: A total of 26 patients met the selection criteria and were included; 23 patients had musculoskeletal data available for analysis. The median age at diagnosis and time of data collection was 22 days and 4 years (25 d to 55 y), respectively (n=26). The median height and weight percentiles are 1%. In all, 83% (n=19/23) of patients had scoliosis, 48% (n=11/23) had hyperkyphosis, 61% (n=14/23) had joint contractures (8 upper extremity, 3 lower extremity, 3 unspecified), and 61% (n=14/23) had a congenital foot deformity (13 clubfoot deformities, 1 bilateral vertical talus). In all, 57% (n=13/23) of all STAC3D patients required at least one orthopaedic procedure, 78% (n=18/23) underwent at least one non-orthopaedic surgery, and 87% (n=20/23) had at least one general anesthesia event.

CONCLUSION: STAC3D is associated with many musculoskeletal problems, including spinal and congenital foot deformities, joint contractures, and other less frequent pathologies. This study is the first to assess the rates of all musculoskeletal conditions in STAC3D patients. Our cohort represents the largest North American cohort and the second largest global cohort of STAC3D patients in the current literature. The results of our study aim to facilitate early diagnosis and expectation management of STAC3D.

LEVEL OF EVIDENCE IV: This is a retrospective cohort study aimed at describing the musculoskeletal conditions associated with STAC3D.

PMID:42490135 | DOI:10.1097/BPO.0000000000003424

JAMA Netw Open. 2026 Jul 1;9(7):e2624772. doi: 10.1001/jamanetworkopen.2026.24772.

ABSTRACT

IMPORTANCE: Despite the goal of utilization management (UM) to facilitate high-value cancer care, concerns about care denials persist. Evaluating justifications for denied claims can clarify the quality of UM decisions.

OBJECTIVE: To examine second-level appeals for denied anticancer medications in Medicare Part D to assess the quality of UM decisions.

DESIGN, SETTING, AND PARTICIPANTS: This cross-sectional study used a large language model (ChatGPT 5 Mini, OpenAI) to analyze texts of second-level appeals decisions on denied Part D medications, rendered by a Medicare-contracted reviewer. Data were analyzed from March 13, 2025, to May 12, 2026.

MAIN OUTCOMES AND MEASURES: From decision summaries, the reasons for first-level denials (as cited by Part D plans) and the outcomes of second-level appeals (favorable vs unfavorable) were examined. The reasons for unfavorable reviews (clerical vs nonclerical) were also examined.

RESULTS: We included 4952 second-level appeals from 2020 to 2024 by beneficiaries with hematological (n = 1155 [23.3%]), prostate (n = 876 [17.7%]), digestive (n = 650 [13.1%]), breast (n = 613 [12.%]), and lung, bronchus, and respiratory (n = 430 [8.7%]) cancers. Most appeals were for targeted therapy (n = 2889 [58.9%]) or hormonal therapy (n = 959 [19.4%]). The most common reasons for initial denial or appeals were “non-medically acceptable” indications (ie, off-label use; 3410 [68.9%]), formulary exceptions (545 [11.0%]), and failure to meet preapproval coverage criteria (mostly on-label prescribing; 463 [9.3%]). Overall, 19.5% (95% CI, 18.4%-20.6%) received favorable reviews, and 55.2% (95% CI, 53.8%-56.6%) and 25.3% (95% CI, 24.1%-26.5%) received unfavorable reviews due to clerical and nonclerical issues, respectively. Favorable reviews were more prevalent among appeals for drugs initially failing to meet preapproval coverage criteria (61.1% [95% CI, 56.7%-65.6%]), but less so among appeals for off-label therapies (16.5% [95% CI, 15.2%-17.8%]). More than 87.9% (95% CI, 86.1%-89.6%) of successfully appealed off-label therapies were for medically acceptable indications supported by Medicare-approved clinical compendia and/or peer-reviewed literature.

CONCLUSIONS AND RELEVANCE: In this cross-sectional study of second-level appeals for denied anticancer medications in Medicare Part D, a considerable number of successfully appealed claims (especially for therapies prescribed on label) were found, which suggests potentially inappropriate UM decisions by Part D plans. However, the appeal outcomes varied substantially by the nature of the denials. Streamlining the preapproval process for on-label therapies and establishing accessible, transparent criteria for off-label prescribing may optimize UM processes for anticancer medications.

PMID:42490111 | DOI:10.1001/jamanetworkopen.2026.24772

JAMA Netw Open. 2026 Jul 1;9(7):e2624972. doi: 10.1001/jamanetworkopen.2026.24972.

ABSTRACT

IMPORTANCE: The transition from child restraint systems (CRSs) to seat belts (SBs) is often based on fixed age or height thresholds. However, the association between height and injury patterns among injured children remains insufficiently characterized within clinical trauma settings.

OBJECTIVES: To examine the association between height and regional injury patterns among children involved in motor vehicle crashes evaluated at trauma centers and to assess how these patterns vary between CRS and SB users.

DESIGN, SETTING, AND PARTICIPANTS: This retrospective cohort study of children 6 to 11 years old who were involved in motor vehicle crashes evaluated at trauma centers used inverse probability of treatment weighting with gradient boosting machine-derived propensity scores and restricted cubic spline modeling to evaluate height-dependent associations between protective device and injury pattern. Data from the American College of Surgeons-Trauma Quality Improvement Program (2017-2020) were used. Statistical analyses were conducted between June 1, and August 31, 2025.

MAIN OUTCOMES AND MEASURES: Prevalence of severe regional injuries (Abbreviated Injury Scale score ≥3).

RESULTS: A total of 6503 children aged 6 to 11 years (mean [SD] age, 8.48 [1.69] years; 3251 male [50.0%], 3252 female [50.0%]) were identified from the database; 1066 (16.4%) had used a CRS. After weighting, CRS use was associated with a higher prevalence of severe head and neck injury (13.9% vs 10.5%; odds ratio, 1.41; 95% CI, 1.06-1.88, P = .02) and severe spinal cord injury (2.9% vs 1.8%; odds ratio, 1.70; 95% CI, 1.02-2.84, P = .04) compared with SB use. Height-dependent analysis revealed a nonlinear association between restraint type and injury patterns. Among children measuring 110 to 140 cm, CRS use was associated with a higher prevalence of severe spinal and thoracic injuries, whereas the prevalence of abdominal injury was lower within the same height range.

CONCLUSIONS AND RELEVANCE: In this cohort study, the association between protective devices and injury patterns was height dependent and nonlinear. A shift in regional injury anatomy was observed across the 110- to 140-cm spectrum, suggesting that a uniform threshold may not adequately characterize growth-specific vulnerabilities.

PMID:42490109 | DOI:10.1001/jamanetworkopen.2026.24972

Invest Ophthalmol Vis Sci. 2026 Jul 1;67(8):49. doi: 10.1167/iovs.67.8.49.

ABSTRACT

PURPOSE: The purpose of this study was to compare the effects of intravitreal injection and laser treatment for retinopathy of prematurity (ROP) on the optic nerve in infants.

METHODS: This was a retrospective cohort study. The participants were 551 eyes of preterm infants from January 2022 to March 2025. The preterm infants enrolled in this study were divided into the ROP treatment group, the ROP group, and the healthy control group. The treatment group was further subdivided into the intravitreal injection group and the laser group.

RESULTS: The vertical cup-to-disc ratio of the optic nerve in retinal images was measured at 4-week intervals from 36 to 60 weeks postmenstrual age (PMA). From PMA 36 to 60 weeks, the cup-to-disc ratio demonstrated significantly greater growth in the ROP treatment group in comparison to the other two groups. Starting from 40 weeks PMA, a statistically significant elevation in the cup-to-disc ratio was observed in the intravitreal injection group compared with the laser group and the control group. Additionally, except for the 56- to 60-week PMA, the intravitreal injection group showed higher cup-to-disc ratio increases than the laser group.

CONCLUSIONS: The present study found that treated ROP leads to a higher cup-to-disc ratio. Furthermore, intravitreal injections result in a greater increase in cup-to-disc ratio compared to laser treatment, with this effect persisting up to 60 weeks PMA.

PMID:42490100 | DOI:10.1167/iovs.67.8.49

Invest Ophthalmol Vis Sci. 2026 Jul 1;67(8):51. doi: 10.1167/iovs.67.8.51.

ABSTRACT

PURPOSE: The purpose of this study was to characterize the intraocular cytokine context of growth differentiation factor 15 (GDF15), a stress-response cytokine implicated in tissue injury and immune regulation, in eyes with idiopathic epiretinal membrane (iERM) by evaluating paired aqueous humor (AH) and vitreous humor (VH) samples and their compartment-specific associations with other soluble cytokines.

METHODS: This cross-sectional study included 38 eyes of 38 patients with iERM and no history of intraocular surgery. Undiluted paired AH and VH samples were collected at the beginning of pars plana vitrectomy (PPV). Twenty-seven cytokines were quantified using a multiplex bead-based immunoassay, and GDF15 concentrations were measured by enzyme-linked immunosorbent assay. Paired AH-VH comparisons and compartmental correlations were analyzed.

RESULTS: GDF15 was significantly higher in VH than in AH. Ten other cytokines also differed significantly between compartments: eotaxin, IFN-γ, IL-8, IP-10, MCP-1, and RANTES were higher in VH, whereas IL-1β, IL-6, IL-17A, and TNF-α were higher in AH (all P < 0.01). Significant AH-VH correlations were observed for eotaxin, IL-6, IP-10, MCP-1, MIP-1β, RANTES, and GDF15 (all P < 0.01). When VH GDF15 was used as the reference, significant positive correlations were identified with IL-6, IL-8, IP-10, MCP-1, and MIP-1α (all P < 0.01). No significant negative correlations with GDF15 were observed.

CONCLUSIONS: In eyes with iERM, intraocular GDF15 showed compartment-weighted associations that were concentrated predominantly on vitreous chemokines, with limited coupling to classical upstream inflammatory cytokines. These findings provide a compartment-specific view of the cytokine context in which intraocular GDF15 is observed.

PMID:42490098 | DOI:10.1167/iovs.67.8.51

J Chem Inf Model. 2026 Jul 23. doi: 10.1021/acs.jcim.6c01004. Online ahead of print.

ABSTRACT

Equilibrist is a free, open-source platform for the quantitative analysis of chemical equilibria and kinetics. It runs in a local web browser, requires no installation, and uses a plain-text scripting language to specify reversible and irreversible reactions, polyprotic acid-base networks, and thermodynamic-cycle constraints. Five fitting modes cover species concentration, NMR shifts (fast exchange), NMR integrations (slow exchange), a mixed mode, and UV-vis/emission spectrophotometry, optimized by the L-BFGS-B and Nelder-Mead methods. A comprehensive statistical layer adds information criteria (AIC, AICc, BIC) with Akaike weights and a Fisher F-test for model selection, residual diagnostics (Durbin-Watson and Shapiro-Wilk statistics, Q-Q plot), and three uncertainty quantification families (bootstrap, jackknife, and Monte Carlo input propagation). Parameter identifiability is mapped by 1D and 2D RMSE profiles, sloppy-spectrum eigen decomposition, correlation heatmaps, t-tests, and a novel local sensitivity coefficient ξ. The combined diagnostics let the user move past R² coefficients and Hessian standard errors to assess parameter estimates and the chemical model itself.

PMID:42490057 | DOI:10.1021/acs.jcim.6c01004

Gastric Cancer. 2026 Jul 23. doi: 10.1007/s10120-026-01776-1. Online ahead of print.

ABSTRACT

BACKGROUND: Mismatch-repair deficient (dMMR)/microsatellite instability-high (MSI-H) gastroesophageal adenocarcinoma (GEA) is associated with favorable prognosis but limited benefit from perioperative chemotherapy. Although immune checkpoint inhibition (ICI)-based approaches have shown promising activity in early-phase studies, the optimal therapeutic combinations and the feasibility of non-operative management (NOM) in resectable disease remain unclear.

METHODS: This exploratory, retrospective, multicenter, real-world study included 55 patients with resectable dMMR/MSI-H GEA, who were divided into subgroups, characterized and compared according to treatment strategy (chemotherapy, chemoimmunotherapy, immunotherapy and initial resection). Pathological and clinical complete response (pCR, cCR), progression-free (PFS) and overall survival (OS) were evaluated.

RESULTS: Patients received chemotherapy (n=10), chemoimmunotherapy (n=16), immunotherapy (n=13), or initial resection without subsequent systemic treatment (n=16). Forty five (82%) patients had surgical resection. The pCR rate was 22% (n=2/9) in the chemotherapy, 27% (n=4/15) in the chemoimmunotherapy, and 100% (n=5/5) in the immunotherapy (i.e., doublet ICI) subgroup, respectively. The overall cCR rate in NOM patients was 33% (n=3/9), with rates of 37.5% (n=3/8) in the immunotherapy subgroup and 0% (n=0/1) in the chemoimmunotherapy subgroup. Complete response rates (pCR/cCR) were significantly associated with PD-L1 CPS ≥10 (p=0.027).

CONCLUSION: This real-world study is, to our knowledge, the first to evaluate a broad spectrum of therapeutic combinations in patients with resectable MSI-H/dMMR GEA, showing meaningful antitumor activity, particularly with doublet ICI. Given the challenges of conducting randomized prospective trials in this setting, such real world data may support clinicians in guiding therapeutic decision-making.

PMID:42490032 | DOI:10.1007/s10120-026-01776-1

Int Microbiol. 2026 Jul 23. doi: 10.1007/s10123-026-00867-4. Online ahead of print.

ABSTRACT

Gastric cancer (GC) remains highly lethal, and although gastric microbiome dysbiosis has been linked to carcinogenesis, the viral component is still poorly explored. Here, we used metatranscriptomics to characterize the gastric virome and evaluate its association with GC and clinicopathological features. We analyzed 238 gastric tissues (214 GC and 24 non-tumors, NT) with clinicopathological data. Viral classification was performed using Kraken2 with the RVDB database. Virome diversity, composition, and clustering were assessed using phyloseq-based analyses, Jensen-Shannon divergence with PAM clustering, and ordination methods. Differential abundance and diversity were evaluated using LEfSe and statistical tests, and viral gene expression was investigated for clinical relevant viruses. We identified 106 viral genera, predominantly bacteriophages and dsDNA viruses, with distinct GC- and NT-associated viral signatures. Clustering revealed three viral community types (GT-1, GT-2, GT-3) that significantly separated GC and NT samples and showed reduced alpha diversity in GC-associated clusters. GT-1 was dominated by Lymphocryptovirus, GT-2 by Gorganvirus, and GT-3 (NT) exhibited the highest diversity. GC tissues were enriched in oncologically relevant viruses, including Lymphocryptovirus (EBV), Cytomegalovirus, and Alphapapillomavirus, whereas several bacteriophages predominated in NT. Virome composition was significantly associated with Lauren histological subtype, but not with clinical stage, tumor location, or neoadjuvant therapy. EBV-high tumors displayed a predominantly latent transcriptional program, with strong expression of ncRNAs (RPMS1, EBERs) and low lytic activity. These findings highlight major virome restructuring in GC and support a potential role of the gastric virome in tumor-associated microbial ecology, warranting further mechanistic and clinical investigation.

PMID:42490025 | DOI:10.1007/s10123-026-00867-4

Primates. 2026 Jul 23. doi: 10.1007/s10329-026-01276-x. Online ahead of print.

ABSTRACT

Cercocebus lunulatus, an endangered primate species, is endemic to three countries in West Africa, including Côte d’Ivoire. In this country, remnant populations of this species have survived in four protected areas including Comoé National Park, which is considered to harbor the largest wild population. However, the park faces significant anthropogenic pressures, including poaching, mining, and agricultural activities in peripheral areas, which hinder sustainable management and conservation efforts. For two decades, updated information on this species’ population size, group structure and food availability has been almost non-existent due to non-focused studies. From November 2021 to November 2022, we collected data using camera traps and phenological data in the park’s forest habitats. A total of 25 groups of white-naped mangabeys, estimated at about 1396 individuals, were recorded with seasonal variations in group size comprising 10 to 249 and 10 to 192 individuals in dry and rainy seasons, respectively. The mean density is 25.38 individuals /km². Groups comprise 44% juveniles, 27% adult females, 18% infants, and 10% adult males. Food item productivity (TotPI) averaged 2912 items/month in gallery forests and 1756 items/month in forest patches, but the choice of specific habitats is not statistically significant. Relying on phenological features, the group structure, marked by a high rate of juveniles and infants and a sex ratio largely in favor of females, we can assume that despite their endangered status, the viability of this species is not engaged.

PMID:42490020 | DOI:10.1007/s10329-026-01276-x