Citations

Abstract Background Precise delineation of non-contrast-enhancing tumor (nCET) in glioblastoma (GB) is critical for maximal safe resection, yet routine imaging cannot reliably separate infiltrative tumor from vasogenic edema. The aim of this study was to develop and validate an automated method to identify peritumoral subregions compatible with nCET and assess its prognostic value. Methods Pre-operative T2-weighted and FLAIR MRI from 940 patients with newly diagnosed GB in four multicenter cohorts were analyzed. A deep-learning model segmented enhancing tumor, edema and necrosis; a non-local, spatially varying finite mixture model was applied to identify edema subregions characterized by relatively lower FLAIR hyperintensity, hypothesized to reflect nCET-related tissue. The ratio of these subregions to total edema volume defined the T2/FLAIR Heterogeneity Index (TFHI). Associations between TFHI and overall survival (OS) were examined with Kaplan–Meier curves and multivariable Cox regression. Results Higher TFHI values stratified patients with shorter OS. In the NCT03439332, TFHI above the optimal threshold was associated with a twofold increased hazard of death (hazard ratio [HR] 2.07, 95 % confidence interval 1.33-3.21; P = .0013) and a reduction in median survival of 98 days. Significant, though smaller, prognostic effects were confirmed in GLIOCAT & BraTS (HR= 1.37; P = .047), OUS (HR = 1.37; P = .0032) and pooled analysis (HR= 1.26; P = .0008). TFHI remained an independent predictor after adjustment for age, extent of resection and MGMT methylation. Conclusions We present a reproducible, server-hosted tool for automated identification of imaging-defined, putative nCET-related peritumoral subregions and TFHI biomarker extraction that enables independent prognostic stratification. This approach provides a quantitative framework for studying peritumoral heterogeneity in GB.

Abstract Objective: Suppressive antibiotic therapy (SAT) is used to prevent recurrent prosthetic joint infections (PJI) among patients who undergo debridement, antibiotics, and implant retention (DAIR). We aimed to assess SAT outcomes among younger, immunocompetent patients. Design: Retrospective cohort study. Patients: Immunocompetent patients <65 years of age who received DAIR for PJI of the hip, knee, or shoulder. Setting: Veterans Affairs hospitals. Methods: SAT was divided into short-term (oral antibiotics given for <3 months after guideline concordant therapy) and long-term SAT (>3 months to 5 years of oral antibiotics). The primary outcome was treatment failure (TF) and mortality combined. SAT was a time-dependent covariate in Cox proportional hazards models. Results: Of the 938 patients, 15% received short-term SAT, 20% received long-term SAT, and 65% did not receive SAT. Short- and long-term SAT were significantly associated with decreased hazards of TF or mortality (short-term SAT adjusted hazard ratio (aHR) = 0.27; 95% confidence interval (CI): 0.11, 0.67; Long-term SAT aHR = 0.52; 95% CI: 0.30, 0.89). Short-term SAT was significantly associated with C. difficile infection (aHR: 3.47; 95% CI: 1.38, 8.74). Short-term SAT (aHR: 7.83; 95% CI: 4.80, 12.77) and long-term SAT (aHR: 1.68; 95% CI: 1.19, 2.38) were significantly associated with antibiotic-associated diarrhea. Long-term SAT was not significantly associated with TF alone (aHR = 0.61; 95% CI: 0.32, 1.16). Conclusions: SAT was significantly associated with decreased death or TF and increased side effects. Benefits and risks must be weighed before prescribing SAT to younger, immunocompetent patients.

Obesity is a global health concern affecting all income levels, with body mass index (BMI) traditionally used for diagnosis. However, BMI does not accurately reflect body composition. Normal weight obesity (NWO) describes individuals with a normal BMI but elevated body fat percentage and has been associated with metabolic abnormalities and reduced physical fitness. This cross-sectional study included 384 adults aged 18–40 years with a BMI between 18.5 and 24.9 kg/m2. Anthropometric measurements and body composition were assessed using an InBody H20 bioelectrical impedance device, and handgrip strength was measured with a Camry electronic dynamometer. NWO was defined as body fat percentage ≥20% in men and ≥30% in women. The overall prevalence of NWO was 77.3%. Although prevalence appeared higher in men than in women, this difference was not statistically significant after adjustment for multiple comparisons. Participants with NWO showed significantly higher body fat percentage, visceral fat index, hip circumference, and blood pressure compared with normal weight non-obese individuals after Holm–Bonferroni correction. Skeletal muscle mass was lower in the NWO group, although this difference did not remain statistically significant after adjustment. Multivariate logistic regression identified right-hand grip strength as an independent protective factor against NWO.

Background/Objectives: Diagnostic evaluation and management of nontraumatic osteonecrosis of the femoral head (ONFH) vary substantially. This systematic review was conducted to inform development of the Association Research Circulation Osseous (ARCO) clinical practice guideline for diagnosis and treatment of ARCO stages I to III ONFH. Methods: We searched MEDLINE, EMBASE, Web of Science, SCOPUS, Global Index Medicus, and the Cochrane Library for studies evaluating imaging modalities and treatments for adult ONFH. We assessed risk of bias using the QUADAS-2, the ROB-2, and the ROBINS-I tools; conducted meta-analyses using random-effects regression; and evaluated certainty of evidence using GRADE methodology. Results: Among 36 included studies, 18 addressed diagnostic test accuracy and 18 addressed comparative effectiveness of treatments. Magnetic resonance imaging (MRI) demonstrated the highest pooled sensitivity (0.91; 95% confidence interval (CI), 0.87 to 0.94) and specificity (0.96; 95% CI, 0.87 to 0.99) for ONFH diagnosis. Bone marrow edema and grade 2+ joint effusion on MRI differentiated symptomatic versus asymptomatic disease. Computed tomography and MRI better detected subchondral fractures than plain radiography. Very low-grade evidence suggested lower rates of femoral head collapse with core decompression plus bone marrow concentrate compared with core decompression alone (pooled relative risk [RR], 0.55; 95% CI, 0.36 to 0.83), and with vascularized versus non-vascularized bone grafting (RR, 0.35; 95% CI, 0.14 to 0.84) over a ≤5-year follow-up. Based on three non-comparative case series, osteotomies might have a lower risk of collapse over a 10- to 20-year follow-up, but this needs to be evaluated in future comparative research. Inconsistent outcome reporting hindered treatment outcome pooling. There were no comparative studies that evaluated observation only versus intervention in asymptomatic disease or strategies for monitoring treatment response. Conclusions: Evidence supporting optimal imaging modalities and early joint-preserving interventions remains limited and predominantly observational, underscoring the need for high-quality comparative studies with consistently defined core outcomes to guide clinical decision-making.

Caudal type homeobox 2 (CDX2) is an intestine-specific transcription factor that serves as a diagnostic marker of enteric differentiation and may also reflect tumor behavior and therapeutic susceptibility. Emerging evidence suggests that CDX2 expression may predict sensitivity to fluoropyrimidine-based therapy independent of tissue of origin. We report a retrospective case series of three patients with metastatic adenocarcinoma (aggressive variant prostate, minor salivary gland, and intestinal-type sinonasal tract) exhibiting strong CDX2 nuclear expression. In all cases, tumors were refractory to or lacked established standard systemic therapy. Treatment decisions were informed by the CDX2-positive enteric phenotype, leading to the initiation of fluoropyrimidine-based regimens. Response was assessed using PET-CT and MRI. All three patients achieved marked metabolic and clinical responses, including a sustained complete metabolic response in the prostate cancer case and durable disease control in the salivary gland and sinonasal tumors. These findings highlight CDX2 as a potential biomarker requiring validation, which may identify tumors intrinsically susceptible to fluoropyrimidines regardless of anatomical origin. CDX2 immunohistochemistry is widely available and inexpensive, and may complement genomic profiling in rare malignancies or in settings where standard treatment algorithms are limited. This report is hypothesis-generating and not intended to estimate response rates or treatment efficacy.

ABSTRACT HLA‐DQB1*06:549 differs from HLA‐DQB1*06:02:01:01 by one nucleotide substitution in exon 2.