Citations

The classification and management of central nervous system (CNS) tumours have undergone substantial transformation over the past two decades, with the recognition of an expanding set of molecularly defined disease entities. Genome-wide DNA methylation profiling has emerged as an important complement to histopathology and targeted molecular testing, providing an epigenetic framework that captures tumour lineage, biological state and large-scale genomic alterations within a single assay. Accumulating evidence demonstrates that methylation-based approaches improve diagnostic precision, resolve biologically heterogeneous entities and support clinically meaningful risk stratification across a broad spectrum of CNS tumours. Methylation profiling has also increasingly been applied to outcome prediction, liquid biopsy-based analyses and the resolution of diagnostically challenging or misclassified cases. In addition, advances in multi-omic integration, computational inference from routinely acquired clinical data and evolving implementation frameworks are extending the clinical applicability of epigenetic profiling. This review synthesises the current state of DNA methylation profiling within the diagnostic and clinical framework of CNS tumours and considers how emerging technologies and practice models are shaping its ongoing integration into neuro-oncological care.

Abstract Context Patients with mild autonomous cortisol secretion (MACS) have higher rates of vertebral fractures compared to patients with non-functioning adrenal nodules, yet bone density is not always reduced. Objective To characterize the effect of MACS on bone density, metabolism, and microstructure as measured by high-resolution peripheral quantitative computed tomography (HR-pQCT). Design Cross-sectional study, 2019-2022 Setting Tertiary referral center Participants Seventy-five patients with MACS and 75 age-, sex-, and gonadal status–matched referent subjects. Measurements Bone turnover markers, dual-energy x-ray absorptiometry (DXA) scan, and HR-pQCT. Outcomes Areal and volumetric bone mineral density (aBMD, vBMD), trabecular bone score (TBS), microstructural parameters including trabecular bone volume to total volume (BV/TV) ratio. Results While no differences in aBMD were observed at any skeletal site, patients with MACS had decreased TBS (1.389 vs 1.475, P < .001) and lower osteocalcin concentration (17.1 vs 19.5 ng/mL, P = .030) than referent subjects. On HR-pQCT at the tibia, patients with MACS had reduced trabecular BV/TV (0.220 vs 0.233, P = .015) compared to referent subjects. On multivariable analysis, MACS was associated with lower TBS (odds ratio [OR] per SD decrease 2.87 [1.65-5.00]), lower trabecular BV/TV at the radius (OR per SD decrease 2.58 [1.33-5.00]), and lower trabecular BV/TV at the tibia (OR per SD decrease 4.06 [2.10-7.86]). Conclusion Patients with MACS have microstructural deterioration that may not be evident on routine DXA aBMD testing.

Abstract Objectives Understanding trends in end-of-life care for bladder cancer patients is essential in improving palliative care planning. This study analyzes trends in preferred place of death among bladder cancer patients in the United States from year 2000 to 2020. Methods Data from the CDC WONDER database were used to identify 293,906 deaths caused by bladder cancer. Further data on patient place of death, age, demographics, census geographic region, and year of death were recorded. Place of death was used as a proxy for preferred place of death. A multivariable binary logistic regression analysis was performed to determine associations between preferred place of death and other variables. Results At-home deaths were most common among individuals aged 75–84 years of age (42,644 deaths) and 85+ years of age (32,806 deaths). Hospice use was highest among the 75–84 age group (8,754 deaths) and 85+ age group (7,358 deaths). Nursing home deaths were highest in the 85+ age group (26,216 deaths), with significant age-related differences ( p < 0.001). In terms of racial variations, White individuals accounted for 93.6% of all deaths. Black individuals were less likely to utilize hospice care ( p < 0.001). Overall, race differences were significantly associated with place of death ( p < 0.001). The number of home deaths rose from 4,281 in 2000 to 8,554 in 2020, and hospice deaths also rose significantly during this time period. Interestingly, younger individuals were more likely to die in hospice compared to those aged 85 years or older, though the odds decreased with age. Black individuals had significantly lower odds of hospice use than White patients (OR = 0.699, p < 0.001) and hospice use increased annually by an average of 13.4% ( p < 0.001). Significance of results The results indicate that utilization of hospice care and home-based end-of-life care have risen in prominence though disparities are present across racial and regional groups. Further studies are needed to better understand potential barriers to end-of-life care among bladder cancer patients.

Abstract Purpose The purpose of this systematic review was to compare the inter‐ and intra‐observer reliability of Kellgren–Lawrence (KL) grading versus minimum joint space width (mJSW) measurement on knee radiographs, and to examine the influence of rater type, radiographic view and atlas‐based training. Methods A systematic search of PubMed/MEDLINE, Embase, Scopus and Web of Science was conducted through July 2025 following Preferred Reporting Items for Systematic reviews and Meta‐Analyses (PRISMA) guidelines. Studies reporting inter‐ and/or intra‐observer reliability for KL or mJSW on standard knee radiographs were included. Extracted data included kappa ( κ ) and intraclass correlation coefficient (ICC) values, rater expertise, radiographic view and atlas usage. Raters were categorized as expert, trainee/non‐expert or artificial intelligence (AI)‐assisted/automated. Results Twenty‐four studies (10,394 radiographs) met the inclusion criteria. Inter‐observer reliability was generally higher for mJSW (mean ICC = 0.82 ± 0.17) compared with KL (mean k = 0.72 ± 0.17), with similar trends observed for intra‐observer reliability. Experts and AI‐assisted systems outperformed trainees/non‐experts for both metrics. Reliability improved with semiflexed posteroanterior/Rosenberg views and atlas‐guided training. Conclusion This systematic review demonstrates that mJSW measurement generally shows higher reproducibility than KL grading. Reliability improved with expertise, standardized imaging and structured training, and AI‐assisted approaches performed comparably to expert raters. Quantitative mJSW should complement KL grading, particularly when combined with alignment measures, to enhance consistency and clinical relevance of radiographic assessment. Level of Evidence Level III.

Background: Surgical trauma disrupts hormone networks, but the duration required for these systems to recover remains unclear. We hypothesize that significant perioperative stress would trigger protracted abnormalities of the thyroid axis extending past 28 days. Methods: This retrospective exploratory study analyzed opportunistically obtained thyroid-related laboratory values (free T3 [FT3], free T4 [FT4], and thyroid-stimulating hormone [TSH]) and serum albumin from electronic medical records of patients undergoing CABG, AVR, or PCI between 2017 and 2022. Preprocedural baseline values were compared with post-procedural serum levels measured during the acute peri-procedural period (0–30 days), early recovery (31–90 days), intermediate recovery (91–180 days), late recovery (181–365 days), medium-term follow-up (1–2 years), and long-term follow-up (>2 years). Results: Free T3 demonstrated early suppression across all procedures, most pronounced in CABG during the acute peri-procedural period, with partial recovery at later timepoints. AVR showed moderate suppression at early and long-term follow-up, while PCI demonstrated minimal and inconsistent changes. Free T4 remained relatively stable across procedures, with limited significant post hoc differences after adjustment. TSH showed significant temporal variability in CABG and AVR but not in PCI. Serum albumin demonstrated marked early decline, most pronounced in CABG, with partial recovery over time, whereas AVR showed delayed long-term suppression. Data availability declined substantially at later timepoints across all biomarkers. Conclusions: In this retrospective exploratory analysis, CABG was associated with the most pronounced early perturbations in thyroid and albumin trajectories, while PCI and AVR demonstrated more heterogeneous temporal patterns. These findings are hypothesis-generating and should be interpreted cautiously given non-protocolized laboratory follow-up, substantial missingness, and potential selection bias.

Itraconazole is the recommended first-line antifungal agent in blastomycosis treatment. However, pharmacokinetic limitations and adverse drug events may necessitate the use of alternative antifungal agents. The primary objective of the study was to retrospectively describe a cohort of patients with blastomycosis who received voriconazole (as partial or complete therapy), for complete or partial treatment, compared to those who received itraconazole alone. Secondary objectives included rationale for voriconazole selection, treatment response, mortality, and adverse drug events. This retrospective multicenter cohort study included adult patients with proven/probable blastomycosis who received itraconazole or voriconazole. Treatment response was evaluated at one year or end of therapy, whichever came first. Mortality outcomes were assessed within 7 days of the last documented azole dose. Propensity score weighting and subgroup analysis were utilized to control confounding variables between cohorts. A total of 119 patients receiving itraconazole and 25 receiving voriconazole as complete or partial treatment were included. Voriconazole was often selected for CNS involvement or after intolerance to alternative azoles. After propensity score weighting, no significant difference in complete or partial treatment response was observed. Rates of all-cause mortality and blastomycosis-related mortality were numerically higher in the voriconazole cohort. Adverse drug event rates were similar between cohorts; however, discontinuation due to adverse events was more common in the voriconazole cohort. Voriconazole was most utilized for the treatment of blastomycosis in cases with CNS involvement or intolerance to other azoles. A statistically significant difference in response rate was not identified between voriconazole-containing or itraconazole-treated patients; however, given limited sample sizes, further data is needed to assess the equivalency of these agents in the treatment of blastomycosis.

Cholangiocytes are specialized epithelial cells that line the intrahepatic and extrahepatic biliary tree and play a critical role in bile modification, liver homeostasis, and response to injury. Cholangiocytes exhibit notable heterogeneity and plasticity, and their dysfunction is central to a spectrum of diseases targeting the bile ducts, collectively called cholangiopathies. These disorders include genetic, infectious, immune-mediated, and malignant diseases, with primary sclerosing cholangitis (PSC) representing one of the most complex and enigmatic of these disorders. PSC is a progressive, fibro-inflammatory disease of the bile ducts that is closely linked to inflammatory bowel disease, carries a heightened risk of cancer, and lacks any approved therapies. This review explores the biology of cholangiocytes, including their development, functional plasticity, and roles in secretion, absorption, and cellular signaling. We provide a detailed examination of cholangiopathies, particularly PSC, a complex cholangiopathy characterized by a paradoxical state of cholangiocyte senescence and hyperproliferation. We describe how immune cell dysfunction, the gut microbiome, genetic predispositions, and environmental factors converge to mediate PSC pathogenesis. We revisit the foundational technologies that empowered early discoveries and shaped the field as we know it today. We also explore how newer techniques such as organoid cultures, single-cell transcriptomics, epigenomics, and spatialomics have transformed our modern understanding of biliary pathophysiology. Finally, we provide an overview of existing rodent models of cholangiopathies and discuss their relevance to human disease. PSC remains therapeutically unaddressed, and thus ongoing multidisciplinary efforts are essential to developing targeted interventions. This review serves as a comprehensive resource for researchers and clinicians navigating the rapidly evolving landscape of cholangiocyte-centered liver disease research.

Circulating extracellular vesicles, proinflammatory/pro-oxidant metabolites, and history of preeclampsia may be used as biomarkers for diagnosis of early CAC in postmenopausal women.