Citations

Abstract Background: Amyloidosis is a complex disease with a multitude of sequalae, particularly with the variants that cause cardiac amyloidosis. There is minimal literature on the types of procedures these patients undergo and the associated postprocedural outcomes. This gap of knowledge makes it difficult for anesthesia providers to risk stratify amyloidosis patients. Methods: This is a single-center, retrospective chart review study performed at a tertiary care medical center that serves as a referral center for patients with amyloidosis. Patients with a known diagnosis of transthyretin (ATTR) or light chain (AL) amyloidosis who underwent procedures requiring anesthesia between January 1, 2018 and October 24, 2024 were included in the study. The primary outcome was 30-day all-cause mortality. Secondary outcomes included other postoperative complications and analysis of types of procedures requiring anesthesia. Results: During the study period, 160 patients underwent a total of 466 procedures requiring anesthesia. Overall, 30-day mortality rate for all encounters was 1.7% (2.7% AL vs 0.5% ATTR, OR 5.71). Endoscopy was the most common procedure, accounting for 26.6% of all procedures. At the patient level, several procedures were more common in ATTR patients including TEE/Cardioversions (21.7% vs 6.6%, p=0.008), electrophysiology (36.2% vs 9.9%, p<0.001), and neurosurgery (13.0% vs 3.3%, p=0.031). Conclusions: In conclusion, patients with amyloid variants that cause cardiac amyloidosis carry substantial postoperative risk when undergoing procedures, with a trend toward increased mortality in patients with AL compared to ATTR. Patients with ATTR are more likely to require neurosurgery and treatment of arrythmias than patients with AL. Additional studies are needed to determine specific diagnostic parameters to help optimize these patients in the future. Trial Registration : Not applicable. Not a clinical trial

Abstract Polycomb group (PcG) proteins form the Polycomb Repressive Complexes 1 and 2 (PRC1/2), which regulate gene expression through histone modifications. Their dysregulation is implicated in cancer. Genomic analysis of prostate cancer datasets revealed a striking divergence: PRC1 genes are frequently amplified in metastatic disease (SU2C), correlating with poor survival, higher tumor mutational burden (TMB), and enhanced androgen receptor (AR) signaling. In contrast, primary prostate cancer (PRAD) is characterized by recurrent deletion of the 3p13 locus, which harbors the gene for the non-canonical PRC1 subunit RYBP. Transcriptomic analysis indicated that RYBP loss derepresses gene expression, consistent with its role in transcriptional repression. Functionally, RYBP expression positively correlates with AR activity and negatively associates with neuroendocrine (NEPC) differentiation. Spatial and single-cell transcriptomics further show that RYBP is enriched in normal epithelial cells but downregulated in tumor cells. Besides, tumors with lower RYBP expression exhibit an immunosuppressive microenvironment, characterized by increased regulatory T cells. Collectively, these findings position RYBP deletion not only as a novel DNA-based biomarker for primary prostate cancer but also as a pivotal epigenetic deregulation event that coordinates oncogenic signaling and lineage plasticity.

Abstract: Urine drug testing (UDT) is an important laboratory tool utilized in various healthcare settings to identify drug or toxic exposures. It has wide clinical applications, including but not limited to detecting substance misuse, monitoring treatment effectiveness and compliance, and identifying substances in affected patients. Depending on the clinical care setting and patient population, the UDT service model and practice are important decisions by the clinical laboratory to meet the needs of the healthcare providers. In addition, clinical laboratories must appreciate the testing process and unique aspects of this toxicology test, from specimen collection and integrity, testing methods, to the result reporting and interpretation. Each phase has specific quality requirements to ensure the accuracy and appropriate interpretation of results. This review aims to summarize the preanalytical, analytical, and postanalytical considerations of clinical laboratories when implementing the test or providing support to clinicians in point-of-care settings. To bring awareness of the limitations inherent to different analytical methodologies, this review discusses important considerations and presents the current gaps, opportunities, and recommendations for quality improvement and standardization. This article may serve as a framework for clinical laboratory directors and other laboratory professionals to review their current provision of UDT and provide recommendations on various important aspects when considering changes to the test service models to meet their local clinical needs, including when introducing new test methods. It may also help physicians and healthcare providers appreciate the complexities of UDT and recognize the challenges in clinical interpretation.

Importance Sex and racial or ancestral disparities in Alzheimer disease remain incompletely understood; autopsy studies that examine amyloid, tau, and genetic factors are scarce. Objective To test whether neuritic plaque burden and cognitive outcomes differ by sex and whether sex modifies the effects of apolipoprotein E ε4 ( APOEε4 ), informant-reported race, and African ancestry. Design, Setting, and Participants This was a cross-sectional study using postmortem neuropathological data from the Biobank for Aging Studies, University of São Paulo, São Paulo, Brazil. A total of 2268 autopsies from a population-based, diverse clinicopathological sample were collected between April 2004 and March 2025. Exposures Sex, informant-reported race (Black, White), African ancestry proportion, and APOEε4 carrier status. Main Outcomes and Measures Neuritic plaque burden (Consortium to Establish a Registry for Alzheimer’s Disease [CERAD] score), and cognitive function (Clinical Dementia Rating–Sum of Boxes [CDR-SB]). Ordinal logistic regression examined association of sex with CERAD scores and 2- and 3-way interactions among sex, race, ancestry, and APOEε4 ; adjusting for age, education, vascular factors, and Braak stages. Linear models related pathology to CDR-SB, adding copathologies. Results The analysis included 2268 autopsies (median [IQR] age, 74.8 [63.8-83.3] years; 1152 [51% male] and 1116 [49%] female; 802 [35%] Black and 1466 [65%] White; other race groups not included owing to small numbers); female individuals were older than male individuals and more likely to exhibit cognitive impairment (CDR global score ≥0.5). Female individuals had higher plaque burden than male individuals (unadjusted odds ratio [OR], 1.97; 95% CI, 1.67-2.29; P &amp;lt; .001), and this association remained significant in adjusted models for sociodemographic and vascular factors and APOEε4 status (adjusted OR, 1.65; 95% CI, 1.33-2.20; P &amp;lt; .001). APOEε4 carriers of both sexes had an approximately 4-fold greater odds of plaques. Significant 2-way interactions were found between sex, APOEε4 status, race, and ancestry on CERAD scores. Black noncarriers (OR, 0.47; 95% CI, 0.34-0.67) and noncarriers of African ancestry (OR, 0.57; 95% CI, 0.43-0.76) were least likely to have high plaque burden, whereas this protection was weakened in ε4 carriers. No significant 3-way interaction was detected. Among individuals with a CERAD score of 2 or higher, female individuals were more likely than male individuals to reach Braak stage V-VI than male individuals (probability ratio, 1.25; 95% CI, 1.13-1.38; P = .002). Adding Braak stage to multivariable models attenuated the female-male difference in plaques and interaction of sex and plaque on CDR-SB was no longer significant. Conclusions and Relevance The findings indicate that female sex, APOEε4 , and both race and African ancestry were jointly associated with amyloid in this study population. Excess amyloid among women may partly explain their greater tau burden and steeper cognitive decline. These findings highlight the importance of incorporating sex, race, and ancestry into biomarker thresholds, risk stratification, and the design of preventive or disease-modifying trials for Alzheimer disease.

Background: Stroke is a leading cause of mortality and long-term disability, and aphasia is among its most common and debilitating sequelae. Diffusion tensor imaging (DTI) and advanced diffusion imaging techniques enable the assessment of white matter integrity and provide clinically relevant measures in post-stroke aphasia. Methods: We conducted a comprehensive review of studies applying DTI or advanced diffusion imaging to investigate structural connectivity in adults with post-stroke aphasia (PSA). PubMed, CENTRAL, Ovid MEDLINE, and Embase were searched, and eligible studies were synthesized according to their diagnostic, prognostic, or therapeutic focus. Results: Ninety-five studies were included. Of these, 59 were classified as diagnostic, 17 as prognostic, and 19 as therapeutic. Most studies employed conventional DTI (n = 77), while a growing body of research utilized advanced diffusion models, including CSD, DSI, and DKI (n = 18). Conclusions: This comprehensive synthesis demonstrates the evolution of diffusion imaging in PSA research. While conventional DTI has provided foundational insights, advanced diffusion methods offer superior characterization of complex fiber architecture and improved clinical–anatomical correlation. Diffusion-derived markers of dorsal and ventral language pathways were consistently associated with language performance, while connectome-level analyses highlighted the importance of preserved global network architecture for recovery. Continued efforts are needed to translate diffusion imaging findings into clinical applicable biomarkers to guide personalized aphasia rehabilitation, with greater use of advanced methods.

Modulation of the gut microbiota represents a promising approach to counteract diet-induced metabolic alterations, with microalgae emerging as potential interventions. Building on our previous in vivo evidence that dietary supplementation with the marine microalga Tisochrysis lutea F&M-M36 (T. lutea) positively modulates selected metabolic alterations under high-fat feeding, the present study aimed to identify potential associations between these metabolic changes and coordinated modifications of the gut microbiota. Animals were fed normal-fat (NF), high-fat (HF), or HF supplemented with 5% T. lutea (HFTiso) diets for three months. Gut microbial profiles were analyzed by 16S rRNA sequencing and correlated with plasma lipids, glucose, blood pressure, fecal lipid excretion, and adiponectin levels. T. lutea supplementation was associated with significant modulation of selected metabolic parameters and coherent alterations in gut microbial communities. Multivariate analyses revealed treatment-dependent clustering of metabolic profiles, with HFTiso forming an intermediate group between HF and NF diets. Beta-diversity analyses showed marked treatment-specific shifts, while alpha-diversity remained stable. Linear discriminant analysis identified 31 discriminative genera, with the HFTiso group enriched in taxa associated with fermentative metabolism and lipid-related metabolic pathways including Anaerotruncus, Marvinbryantia, and Eubacterium coprostanoligenes, while the HF group was linked to Clostridium sensu stricto 1 and Terrisporobacter. Positive correlations between HFTiso-associated taxa and adiponectin levels were consistent with microbiota-associated metabolic signatures. In parallel, T. lutea supplementation was associated with downregulation of colonic Niemann-Pick C1-like 1 (NPC1L1) mRNA expression, a key mediator of intestinal cholesterol uptake. The bioactivity of T. lutea likely reflects its content of polyunsaturated fatty acids, oleic acid, phytosterols, and fucoxanthin; however, whether these components act synergistically or whether specific bioactive compounds are primarily responsible remains to be clarified. Together, these findings indicate that T. lutea supplementation is associated with coordinated changes in gut microbiota composition and transcriptional modulation of the intestinal cholesterol transporter NPC1L1 in the context of selected early-stage metabolic alterations under high-fat feeding. While direct extrapolation to humans remains limited, these results suggest potential translational relevance of T. lutea as a nutraceutical approach targeting early-stage metabolic dysregulation. Future studies will be required to determine the mechanistic contribution of individual bioactive components and to assess whether microbiota- and gene expression-associated changes play a causal role in mediating the observed metabolic outcomes, thereby informing the rational development of T. lutea-derived interventions.

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.