Citations

The NCCN Guidelines for Bladder Cancer provide strategies for the diagnosis, treatment, and follow-up of patients with bladder cancer, which is the sixth most common cancer in the United States. Bladder cancer can be divided into 3 categories along a clinical spectrum: (1) non–muscle-invasive bladder cancer; (2) muscle-invasive bladder cancer; and (3) metastatic bladder cancer, with most patients falling into the category of non–muscle-invasive disease. Thus, the selected content featured in this issue specifically covers the clinical presentation and workup of and subsequent management recommendations for non–muscle-invasive bladder cancer.

The NCCN Guidelines for Prostate Cancer include recommendations for staging and risk assessment after a prostate cancer diagnosis and for the care of patients with localized, regional, recurrent, and metastatic disease. These NCCN Guidelines Insights summarize the panel’s discussions on select 2026 updates to the guidelines regarding nonmetastatic disease: the elimination of the very-low-risk group, updates to the Principles of Active Surveillance, and caution in the use of focal therapy in newly diagnosed patients.

Abstract Background T cell activation and polarization drive atherosclerosis. Among the mediators underlying T cell polarization, the epigenetic enzyme EZH2 catalyses the repressive mark H3K27me3. In humans, EZH2 is upregulated in T cells in advanced atherosclerosis, whereas its deficiency in T cells in mice limits plaque formation via an anti-inflammatory response. Emerging evidence indicates that EZH2 can also regulate lncRNAs and miRNAs by depositing H3K27me3 at their loci, repressing transcription. Purpose We hypothesize that EZH2 governs lncRNAs and miRNAs expression in T cells in the context of atherogenesis. Methods CD4+ T cells were isolated from spleens of atherosclerosis-prone T cell-specific Ezh2 (Ezh2cd4)-KO mice and WT littermates. Small RNA-seq (SMARTer® smRNA-Seq) and transcriptomic profiling (Prime-seq) were performed. Differential expression was assessed using edgeR. Selected miRNAs were validated by RT-qPCR. Putative miRNA targets were retrieved from miRTarBase (v. 8) and TargetScan, and gene ontology enrichment was performed using Metascape. Results In CD4+ T cells from Ezh2cd4-KO mice, 41 out of 2,950 mature miRNAs were differentially expressed (log2FC > |0.8|, FDR < 0.05), with 27 upregulated and 14 downregulated. Top upregulated miRNAs included miR-125a-5p, miR-130a-3p, miR-744-5p, miR-181a-5p, miR-181b-5p, miR-374b-5p, miR-99b, miR-3085, and miR-7049-3p. RT-qPCR confirmed that expression of miR-125a-5p, miR-181a-5p, miR-181b-5p, and miR-99b-5p were upregulated in Ezh2-deficient murine CD4+ T cells. GO enrichment analysis of downregulated genes revealed enrichment of IL-4, IL-9, IL-10, and TGF-β pathways, suggesting their relevance in T-cell function and differentiation. In human Jurkat T cells, pharmacological EZH2 inhibition using GSK126 or tazemetostat resulted only in the upregulation of miR-125a-5p and miR-99b-5p, confirming the conservation of the mechanisms in humans. Integration of our Prime-seq transcriptomics and smallRNAseq datasets with human and mouse predicted and experimentally validated targets of miR-125a-5p and miR-99b-5p identified six conserved target genes: STAT1, FAM169B, NDRG3, PSMB9, TRIB1, and RAB3IP. Conclusions Our findings indicate that Ezh2 represses miRNA expression in T cells during atherogenesis, thereby possibly promoting differentiation toward pro-atherogenic subsets while restraining anti-atherogenic transcriptional programs. Further research is needed to elucidate the underlying mechanisms. Ezh2-regulated miRNAs may represent promising targets to direct T cell plasticity to combat atherosclerosis.

Background: Metabolic-associated fatty liver disease (MAFLD) affects approximately 30% of the global population and is associated with obesity and metabolic syndrome. Anthropometric indices such as body mass index (BMI), waist circumference (WC), and weight are crucial markers for evaluating the progression of MAFLD. Curcumin, a bioactive compound with anti-inflammatory and antioxidant properties, has been investigated for its potential to improve metabolic outcomes. This umbrella review aimed to systematically evaluate the effects of curcumin supplementation on anthropometric indices in patients with MAFLD, considering epidemiological strength and power analysis. Methods: An umbrella review of meta-analyses from randomized controlled trials was conducted. PubMed, Scopus, and Web of Science were searched up to September 2024. Meta-analyses assessing curcumin’s effects on BMI, weight, and WC in MAFLD patients were included. Quality was assessed using the A Measurement Tool to Assess Systematic Reviews version (AMSTAR-2) tool, and heterogeneity was evaluated using the I 2 statistic. Statistical analyses were performed using R and Stata 18 software. Results: Curcumin supplementation had no significant effect on BMI (standardized mean difference [SMD]: −0.01; 95% confidence interval [CI]: −0.24 to 0.21, P = .91) with low power (1-β = 0.03) and a low epidemiological grade according to GRADE criteria. Similarly, curcumin showed no significant effect on WC (SMD: −0.27; 95% CI: −0.57 to 0.04, P = .08) with high power (1-β = 0.96) but low epidemiological strength. However, curcumin significantly reduced weight (SMD: −0.12; 95% CI: −0.19 to −0.04, P < .01) with moderate power (1-β = 0.56) and moderate epidemiological strength. No significant effect of dose or effect of supplementation duration was found. Conclusion: Curcumin supplementation may result in a statistically detectable but clinically modest reduction in body weight in patients with MAFLD, while showing limited or no efficacy on BMI and waist circumference. The epidemiological strength of the evidence varies across outcomes and is of low to moderate quality. Further well-designed, high-quality randomized controlled trials are needed to confirm the clinical relevance of curcumin’s effects on anthropometric indices.

Abstract Through emerging interpretations of individual “medical freedoms,” a panoply of state legislative bills seeks to undermine long-standing public health and health care requirements including recommendations to test, screen, treat, and vaccinate persons. To the extent these bills could upend decades of laws and policies protecting individual and communal health, especially among vulnerable individuals, they threaten the health — and freedoms — of all persons.

Introduction Historic series have demonstrated the importance of construct rigidity in the treatment of pelvic discontinuities, but there remains limited data comparing different constructs, especially contemporary cup-cages and custom triflange components. The aim of this study was to evaluate reconstructive constructs with emphasis on implant survivorship, radiographic results, complications, and clinical outcomes. Methods We reviewed 184 revision THAs with unilateral pelvic discontinuity at a single institution between 1998–2022. Mean age was 66 years, 83% were female, and mean BMI was 29 kg/m2. Constructs included uncemented cup and plating (n=66, 36%), cup-cages (n=59, 32%), jumbo uncemented acetabular components (n=30, 16%), conventional antiprotrusio cages (n=16, 9%), and custom triflanges (n=13, 7%). Since 2013, 73% of cases were treated with either a cup-cage or custom triflange. Acetabular distraction (n=36, 20%) and porous augments (n=33, 18%) were used as adjuncts. Mean follow-up was 8 years. Results The 5-year survivorships free of revision for aseptic loosening, any revision, and any reoperation were 92%, 79%, and 75%. Of 43 revisions, the most common indications were aseptic loosening (n=15) and dislocation (n=15). For each construct, the 5-year survivorships free of revision for aseptic loosening were 100% (triflange), 94% (cup-cage), 92% (uncemented jumbo acetabular component), 90% (plating), and 86% (conventional anti-protrusio cage). Radiographic analysis demonstrated discontinuity healing in 85% of unrevised patients. Of the 15 re-revisions for aseptic loosening, 92% involved loss of fixation from inferior hemipelvis. There were 63 complications with dislocation (n=32), nerve palsy (n=10), and wound problems (n=9) most common. Mean Harris hip scores improved from 51 to 70 at 5 years. Conclusion In this series, the 5-year survivorship free from aseptic loosening was very good (92%), especially with contemporary techniques like custom triflange (100%) and cup-cage constructs (94%). Survivorship free from any revision (79%) and reoperation (75%) remain lower due to dislocation and infection.