Citations

ABSTRACT Commercial antimicrobial susceptibility testing (AST) systems for gram-negative bacteria provide operational advantages over reference broth microdilution (BMD) testing, but the results produced by commercial AST systems might not be as accurate as the reference method. Assessing and comparing the performance of AST systems can be informative for clinical microbiology practice. In total, 280 clinical isolates and 100 isolates from the U.S. Centers for Disease Control and Prevention Antimicrobial Resistance Isolate Bank, including Enterobacterales and Pseudomonas aeruginosa, were intended to be tested using disk diffusion (DD) and automated commercial AST systems, such as Selux AST System (Selux Diagnostics), MicroScan (Beckman Coulter), Phoenix (Becton, Dickinson and Company), and Vitek 2 (bioMérieux). These results were compared to BMD as the reference standard. In total, 372 isolates were assessed. For Enterobacterales, the greatest frequency of very major errors was identified with cefepime by Vitek 2 (29.0%) and ertapenem by DD (9.1%); essential agreement less than 90% was identified with the following combinations: aztreonam by MicroScan (86.4%), aztreonam by Vitek 2 (88.9%), cefepime by Selux (86.3%), cefepime by Vitek 2 (76.8%), ceftazidime by Vitek 2 (89.9%), and levofloxacin by MicroScan (83.4%). For P. aeruginosa , essential agreement less than 90% was identified with the following combinations: gentamicin by Selux (87.2%), tobramycin by Selux (86.6%), and ciprofloxacin by Phoenix (88.4%). Overall, antimicrobials that had low demonstrable bias across all automated commercial AST systems included ampicillin, amoxicillin-clavulanate, ceftazidime-avibactam, ertapenem, and trimethoprim-sulfamethoxazole. Comparing commercial testing systems head-to-head against a reference standard provides insight into the strengths and weaknesses of the performance of these test systems, and these insights can subsequently inform local decisions regarding further investigations and potential operational mitigation strategies. IMPORTANCE This study assessed and compared the performance of multiple commercial antimicrobial susceptibility testing (AST) systems and disk diffusion methods. The accuracy of determining minimum inhibitory concentrations or zone diameters of antimicrobials and the associated interpretive categories were studied for 372 isolates of Enterobacterales and Pseudomonas aeruginosa . Performance of the evaluated systems revealed that multiple antimicrobial-organism combinations were below the standards typically required by regulatory agencies and clinical laboratories. These deficiencies varied across the commercial platforms and disk diffusion methods, highlighting the importance of benchmarking studies that compare the performance using identical isolates. These identified performance weaknesses may warrant further study and/or the implementation of mitigation strategies in clinical laboratory operations to prevent the reporting of errant results.

PURPOSE Precision medicine has revolutionized oncology; however, tumor biomarkers are not reflective of the heterogeneous cancer population. We evaluated NRG Oncology prostate cancer (PCa) clinical trials for demographic differences among patients with optional biospecimen collection (BC) consent and biospecimen submission (BSub). METHODS Data from 19 NRG PCa clinical trials closed before 2015 were analyzed. Patients who consented to BC and completed BSub were evaluated by race, ethnicity, median income, area deprivation index (ADI; categorized as highest v lowest three quartiles), age at enrollment, site, and year of enrollment. T/chi-square tests were used for continuous/categorical variables, respectively, followed by logistic regression. RESULTS Of the 15,648 randomized patients eligible for BC, 11,796 (75%) had specimens submitted. In all, 4,598 (82.2%) of 5,597 eligible patients consented for optional BC in nine clinical trials with a separate BC consent process (consent rates by race/ethnicity: 74.1% Black, 72.8% Hispanic/Latino, 83.8% White). A smaller proportion of Black and Hispanic/Latino patients consented to optional BC compared with those who did not (12.1% v 19.5% Black, P < .0001; 3.5% v 5.8% Hispanic, P = .0006). In univariable logistic regression models, high ADI (more socioeconomic disadvantage) was associated with a decreased likelihood for optional BC consent (odds ratio [OR], 0.67 [95% CI, 0.55 to 0.82]; P = .02), but not a decreased likelihood for BSub (OR, 0.74 [95% CI, 0.53 to 1.04]; P = .08). Multivariable models demonstrated that Black/Hispanic/Latino patients were less likely to consent to optional BC, and Black patients were less likely to have BSub ( P < .05 for all). CONCLUSION White/non-Hispanic patients and those with less socioeconomic disadvantage were more likely to consent to optional BC, whereas Black patients were less likely to have BSub. Targeted solutions are needed to improve biorepository representation so that precision medicine approaches better reflect the cancer population.

ABSTRACT Background Inflammation plays a critical role in cancer cell proliferation; however, the specific role of inflammasomes, multiprotein complexes that regulate inflammation‐associated signaling pathways, in prostate cancer (PCa) remains insufficiently explored. This study aims to characterize the expression of inflammasome‐related genes in PCa and evaluate their association with clinical outcomes. Methods De‐identified transcriptome data from the Decipher GRID RP, a cohort of 52,266 radical prostatectomy (RP) samples tested (2016–2024) with the Decipher prostate genomic classifier (Veracyte, San Diego, CA), were retrieved from the GRID registry (NCT02609269). Expression analysis of 34 genes involved in inflammatory pathways was conducted to associate their expression with clinical and genomic variables. Outcomes analyses were conducted on a retrospective cohort of 855 patients treated with RP (META855). Results Analysis of inflammasome gene expression in the GRID RP cohort revealed that most genes exhibit low baseline expression, whereas HSP90AB1, APP, TXN, and TXNIP demonstrate strong expression signals. Additionally, higher expression of most genes was associated with Gleason Grade Group 4–5 and very high Decipher scores. On survival analysis of the META855 cohort, higher expressions of AIM2 and HSP90AB1 were significantly associated with worse metastasis‐free survival. Conversely, both high and low expression levels of NLRP3 were associated with better metastasis‐free survival outcomes following RP compared to average expression. On multivariable Cox regression analysis, higher expressions of AIM2 (HR 1.75) and HSP90AB1 (HR 1.60) were significantly associated with shorter time to metastasis following RP. Conclusions There is molecular heterogeneity within pro‐inflammatory genes among patients with PCa. Our findings showed there is a potential association between the expression levels of certain inflammasomes, such as AIM2, HSP90AB1, and NLRP3, and oncological outcomes following RP.

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.

PURPOSE Although outcomes for nonmetastatic cancers have improved since the 1970s, it remains uncertain whether long-term survival has improved among patients presenting with de novo metastatic disease, defined as cancer presenting with distant metastases at the time of initial diagnosis. This study evaluated changes in 5-year survival among patients with de novo metastatic cancer diagnosed in 1976 versus 2015, with a minimum 5-year follow-up through 1981 and 2020, respectively. METHODS Population-based data were obtained from the SEER database. Patients diagnosed with de novo metastatic cancer in 1976 (n = 11,864) and 2015 (n = 26,324) were included. Five-year overall survival (OS) was compared between cohorts, and multivariable logistic regression identified demographic and clinical factors associated with survival. RESULTS The 5-year OS increased significantly from 10.6% in 1976-1981 to 23.6% in 2015-2020 ( P < .001). Survival gains were largest in breast cancer (12.6%-34.2%; P < .001), ovarian cancer (14.4%-32.5%; P < .001), colorectal cancer (3.7%-15.0%; P < .001), and hematologic malignancies (24.3%-53.9%; P < .001). Minimal improvement occurred in pancreatic cancer (0.25%-1.6%; P = .007) and small cell lung cancer (0.8%-3.1%; P = .008). Multivariable analysis demonstrated that older age, male sex, and Black race were associated with lower odds of 5-year survival (all P < .01) CONCLUSION Over the past four decades, long-term survival among patients with de novo metastatic cancer has more than doubled; however, progress remains uneven across cancer types. Gains appear concentrated in malignancies with substantial therapeutic advances, whereas others show persistently poor outcomes. Continued efforts are needed to address disparities and improve survival in resistant cancer types.

Abstract Aims Heart failure (HF) continues to portend significant morbidity and mortality within the USA. Data regarding the efficacy of mineralocorticoid receptor antagonists (MRAs) in HF with preserved ejection fraction (HFpEF) remains unclear. Finerenone, a non-steroidal MRA, has demonstrated reduction in hospitalizations in this population. However, the comparative efficacy of different MRA classes in these patients remains elusive. Methods and results We conducted a retrospective observational cohort study using the TriNetX research network. We applied 1:1 propensity score matching (PSM) to compare patients with HFpEF initiated on finerenone vs. spironolactone. We examined 1-year risks of HF exacerbation, acute kidney injury (AKI), electrolyte derangements, and cardiovascular outcomes. We identified 254,417 patients with HFpEF and MRA use. After PSM, each cohort contained 491 patients. Analysis revealed that finerenone use was associated with a significantly lower risk of HF exacerbation (hazard ratio [HR] = 0.63 [95% confidence interval [CI]: 0.54, 0.74], P &lt; 0.001), all-cause mortality (HR = 0.38 [95% CI: 0.23, 0.64], P &lt; 0.001), and hypokalaemia (HR = 0.58 [95% CI: 0.40, 0.85], P = 0.001). The aforementioned results, along with a reduction in AKI risk, were statistically significant after stratified subgroup analysis by diabetes mellitus and chronic kidney disease. Conclusion In this large real-world HFpEF cohort, finerenone use was associated with lower risks of HF exacerbation and all-cause mortality compared with spironolactone. These observational findings are hypothesis-generating and warrant confirmation in randomized trials.

ABSTRACT Background and Aim Determining the location of gastrointestinal (GI) bleeding is critical for guiding diagnostic and therapeutic strategies but often results in patients receiving pan‐endoscopy with upper endoscopy, colonoscopy, and small bowel capsule endoscopy, which can be unnecessary, costly, and waste limited healthcare resources. The blood urea nitrogen‐to‐creatinine ratio (BUN/Cr) may help discriminate between upper GI bleeding (UGIB) and lower GI bleeding (LGIB). This study aims to assess the diagnostic performance of the BUN/Cr in distinguishing UGIB from LGIB. Methods A literature search was conducted in MEDLINE, EMBASE, and Cochrane Library to identify diagnostic test accuracy studies published from inception through January 31, 2025, which evaluated BUN/Cr in patients with UGIB versus LGIB. A linear mixed‐effects model meta‐analysis was conducted using the “diagmeta” package. The pooled sensitivity, specificity, diagnostic odds ratio, and area under the summary receiver operating characteristic curve (AUC) were estimated, and optimal threshold was determined using the Youden index. Results Seventeen studies were included in this meta‐analysis. The pooled mean difference in BUN/Cr between UGIB and LGIB patients was 11.44 (95% confidence interval [95% CI] 8.35–14.52). At a threshold of > 30, pooled sensitivity was 38.8% (95% CI 28.1%–50.8%) and specificity was 89.3% (95% CI 81.0%–94.2%). At the optimal cut‐off of 22, sensitivity was 66.2% (95% CI 57.8%–73.7%), specificity was 71.0% (95% CI 58.5%–81.0%), and AUC was 0.740 (95% CI 0.683–0.794). Conclusion BUN/Cr demonstrates moderate diagnostic accuracy for distinguishing UGIB from LGIB, particularly at a threshold of ≥ 22. This readily accessible and inexpensive blood test may assist in early clinical triage and assessment of the location of GI bleeding, particularly in those patients where the clinical presentation is obscure.

Importance The ideal duration of androgen deprivation therapy (ADT) for treating localized prostate cancer is unknown due to variable adherence and treatment durations tested in clinical trials. Objective To determine the ideal duration of ADT for patients with prostate cancer treated with radiotherapy. Data Sources This individual patient data meta-analysis of 13 randomized phase 3 clinical trials evaluated the use of radiotherapy alone or with ADT. It included patients with a median follow-up of 11.3 (IQR, 9.5-14.5) years and ADT duration of 0 to 36 months. Most patients (7392 [72%]) included had National Comprehensive Cancer Network high-risk or very high-risk disease. Study Selection For this meta-analysis, a systematic literature search from 1980 to 2020 was performed in trial registries (Cochrane Central Register of Controlled Trials and ClinicalTrials.gov), MEDLINE (1966-2020), Embase (1982-2020), Web of Science, and Scopus to identify trials. Data Extraction and Synthesis Intention-to-treat and as-treated analyses were performed. The number needed to treat to prevent 1 distant metastasis at 10 years was calculated based on prognostic risk group. The analyses were conducted from January 5 to August 15, 2023. Main Outcomes and Measures The primary end point for this study was overall survival, defined as time to death or last follow-up from randomization. Secondary end points included biochemical recurrence, distant metastasis (DM), prostate cancer–specific mortality, and other-cause mortality. Results The median (IQR) age among the 10 266 male patients was 70 (65-74) years. Longer durations of ADT were associated with nonlinear improvement in relative benefits of DM, prostate cancer–specific mortality, and overall survival, with reduced estimated benefits beyond 9 to 12 months of ADT based on the end point. There was a near-linear increase in other-cause mortality associated with long-term ADT use (hazard ratio, 1.28; 95% CI, 1.09-1.50; P = .002 for 28 vs 0 months of ADT). The optimal ADT duration based on 10-year DM was 0, 6, 12 months, and undefined for patients with 1 intermediate-risk factor, 2 or more intermediate-risk factors, and National Comprehensive Cancer Network high-risk and very high-risk disease, respectively. Conclusions and Relevance The results of this meta-analysis suggest that, for men with localized prostate cancer treated with definitive radiotherapy and ADT, there are relative and absolute benefits from increasing durations of ADT that help provide individualized risk estimates.

The NCCN Guidelines for Prostate Cancer provide a framework on which to base decisions for patients with prostate cancer across the disease spectrum. The Guidelines sections included in this article focus on metastatic castration-sensitive prostate cancer (mCSPC), nonmetastatic castration-resistant prostate cancer (CRPC), and metastatic CRPC (mCRPC). For patients with mCSPC, disease characteristics, such as whether metastases arose synchronously or metachronously and the degree of metastatic burden, impact therapy decisions, including how much treatment intensification is appropriate and when prostate-directed and/or metastasis-directed therapy should be considered. In the mCRPC setting, androgen deprivation therapy is continued with the sequential or concurrent addition of certain androgen receptor pathway inhibitors, chemotherapies, immunotherapies, radiopharmaceuticals, and/or targeted therapies. The NCCN Prostate Cancer Panel emphasizes a shared decision-making approach in all disease settings based on patient preferences, prior treatment exposures, biomarkers, the extent and location of metastases, symptoms, and potential side effects.