Citations

Abstract Background and Aims In the VICTOR trial (NCT05093933), vericiguat was neutral for the primary composite endpoint of cardiovascular death or hospitalization for heart failure (HF). VICTOR was powered to independently assess cardiovascular death. This study reports detailed analysis on the effects of vericiguat on mortality. Methods VICTOR, a double-blind, placebo-controlled, randomized trial, enrolled 6105 ambulatory patients with HF and reduced ejection fraction (HFrEF) without recent worsening and randomized them to vericiguat or placebo. The main outcome for this analysis was the pre-specified secondary endpoint of cardiovascular death. All-cause death, sudden cardiac death, and death related to HF were also assessed. Results Over a median of 19.7 months (inter-quartile range 14.6–25.4), cardiovascular deaths occurred in 292 patients (5.7 deaths per 100 patient-years) and 346 patients (6.8 deaths per 100 patient-years) in the vericiguat and placebo groups, respectively (hazard ratio [HR] 0.83, 95% confidence interval [CI] 0.71–0.97; P = .020). Risk of death from any cause was lower with vericiguat vs placebo (377 [7.3 deaths per 100 patient-years] vs 440 [8.6 deaths per 100 patient-years]; HR 0.84, 95% CI 0.74–0.97; P = .015). Sudden cardiac death and HF-related deaths were lower with vericiguat vs placebo (1.6 vs 2.2 events per 100 patient-years; HR 0.75, 95% CI 0.56–0.99; P = .042 and 1.7 vs 2.4 events per 100 patient-years; HR 0.71, 95% CI 0.54–0.94; P = .016, respectively). Lower mortality rates were consistent across subgroups including baseline therapy. Consistent cardiovascular and all-cause mortality benefit was seen across baseline N-terminal pro-B-type natriuretic peptide levels. Conclusions In ambulatory well-treated participants with HFrEF, vericiguat was associated with clinically meaningful reductions in the key secondary outcome of cardiovascular death, as well as all-cause mortality.

Abstract Purpose To describe the systemic benefits of sugammadex as a reversal agent for neuromuscular blockade. Summary Sugammadex is the preferred reversal agent for neuromuscular blockade as recommended in guidelines from the American Society of Anesthesiology. This recommendation is primarily based on a faster time to recovery from neuromuscular blockade as compared to that seen with neostigmine. Systemic adverse effects of neostigmine are often mitigated by the administration of glycopyrrolate. However, glycopyrrolate is an antimuscarinic agent that may be associated with its own adverse effects when used as part of a reversal strategy for neuromuscular blockade. This review describes the potential systemic benefits of sugammadex, compared to an acetylcholinesterase/anticholinergic strategy, related to postoperative nausea and vomiting, urinary retention, bowel recovery, and cognitive dysfunction while also discussing its role in enhanced recovery after surgery protocols. Conclusion Sugammadex is associated with a reduction in systemic effects when compared to combinations of neostigmine and glycopyrrolate. Further research is needed on important clinical and economic outcomes associated with a reduction in these adverse effects.

The integration of artificial intelligence (AI) in medical imaging has revolutionized diagnostic capabilities, yet the black-box nature of deep learning models poses significant challenges for clinical adoption. Current explainable AI (XAI) approaches, including SHAP, LIME, and Grad-CAM, predominantly focus on post hoc explanations that may inadvertently undermine clinical decision-making by providing misleading confidence in AI outputs. This paper presents a systematic review and meta-analysis of 67 studies (covering 23 radiology, 19 pathology, and 25 ophthalmology applications) evaluating XAI fidelity, stability, and performance trade-offs across medical imaging modalities. Our meta-analysis of 847 initially identified studies reveals that LIME achieves superior fidelity (0.81, 95% CI: 0.78–0.84) compared to SHAP (0.38, 95% CI: 0.35–0.41) and Grad-CAM (0.54, 95% CI: 0.51–0.57) across all modalities. Post hoc explanations demonstrated poor stability under noise perturbation, with SHAP showing 53% degradation in ophthalmology applications (ρ = 0.42 at 10% noise) compared to 11% in radiology (ρ = 0.89). We demonstrate a consistent 5–7% AUC performance penalty for interpretable models but identify modality-specific stability patterns suggesting that tailored XAI approaches are necessary. Based on these empirical findings, we propose a comprehensive three-pillar accountability framework that prioritizes transparency in model development, interpretability in architecture design, and a cautious deployment of post hoc explanations with explicit uncertainty quantification. This approach offers a pathway toward genuinely accountable AI systems that enhance rather than compromise clinical decision-making quality and patient safety.

BACKGROUND: The performance of estimated glomerular filtration rate (eGFR) among patients with heart failure (HF) may be worse than in the general population due to a higher prevalence of confounding factors affecting creatinine and cystatin C. Studies in this area are scarce and not stratified by type of HF. We evaluated the performance of current creatinine and cystatin C equations (eGFRcr, eGFRcys, and eGFRcrcys) compared with measured GFR (mGFR) among patients with HF stratified by ejection fraction. METHODS: We pulled data on Mayo Clinic patients with an mGFR performed for clinical indications from 2011 to 2023, with serum creatinine and cystatin C measured within 7 days and an echocardiogram performed up to 1 year before the mGFR date. HF was identified by the presence of International Classification of Diseases codes within 1 year before the mGFR and subgrouped into ejection fraction (EF) ≥50% (HFEF≥50%, n=182) or <50% (HFEF<50%, n=115) and compared with no-HF controls (n=1871). CKD-EPI (and EKFC) eGFRcr, eGFRcys, and eGFRcrcys equations were calculated and compared for bias (mGFR minus eGFR) and accuracy (1-P30, proportion of people with ≥30% difference between eGFR and mGFR). CIs were generated by bootstrapping. RESULTS: The HF groups were characterized by older age, higher proportion of males, more diabetes, higher creatinine, and higher cystatin C than controls. In terms of bias, eGFRcr overestimated mGFR to a greater extent in both HF groups compared with controls, whereas eGFRcys and eGFRcrcys showed similar bias in both HF groups and controls. In the HF groups, cystatin C-based equations were more accurate than eGFRcr, particularly within HFEF<50% (1-P30 of 28% and 34% for CKD-EPI eGFRcys and eGFRcrcys, respectively, versus 60% for eGFRcr), whereas eGFRcrcys was more accurate in controls. The CKD-EPI and EKFC equations were overall convergent, showing similar results. CONCLUSIONS: Among patients with HF, eGFRcr demonstrates inferior performance (more bias and less accuracy) compared with cystatin C-based eGFRs, with this effect being more pronounced in those with HFEF<50%.

Purpose: To evaluate the role of women physicians in thyroid eye disease (TED) research and clinical care and describe relevance for academic medicine and patient access. Methods: A cross-sectional study of TED-related publications indexed on PubMed in 2000, 2010, and 2020, and of completed or currently active clinical trials was conducted. Author, journal, and principal investigator (PI) characteristics were noted. Author/PI gender was determined from institutional profile or subsequently via a previously described Google-based algorithm. American Society of Ophthalmic Plastic and Reconstructive Surgery (ASOPRS), American Board of Ophthalmology (ABO), and American Thyroid Association (ATA) information was obtained via direct communication. Trends in participation of men and women were evaluated. Results: A total of 444 manuscripts (61 from 2000; 117 from 2010; 266 from 2020) were included. The percentage of women as first and senior authors increased from 2000 to 2020 (p < 0.0001 and p = 0.0003, resp.). First author gender distribution was near equal in 2020 (52.6% men, 47.4% women [p = 0.39]), whereas senior authors remained mostly men (68.0% men, 32.0% women [p < 0.0001]). As of 2020, the gender imbalance of senior authors was greater on multidisciplinary author teams (74.8% men, 25.2% women) compared with single specialty author teams (62.2% men, 37.8% women). Of the 98 TED-related clinical trials included, 34 had women PIs (35%). The percentage of women as members in ASOPRS, ABO, and ATA all increased significantly from 2000 to 2020, but remained disproportionately men in 2020 (all p < 0.0001). Conclusion: Gender-based discrepancies persist in TED research, especially among senior authors, who determine research direction, and on multidisciplinary teams, which reflect the preferred model of care. Further efforts are required to determine whether these findings affect patients with TED.

Due to extensive pathophysiological changes in critically ill patients, standard dosing of antibiotics may lead to inadequate drug exposure. This is concerning, as insufficient plasma drug concentrations may lead to treatment failure, whereas excessive drug exposure may increase the risk of toxic adverse events. The role of inflammation as a factor influencing the pharmacokinetics (PK) and pharmacodynamics (PD) of antibiotics remains largely unknown. PK/PD target attainment of antibiotics can be improved through therapeutic drug monitoring, i.e., measurement of drug concentrations in the blood with subsequent dosage adjustment to reach a certain target. Besides, population PK models may be used to predict drug exposure and tailor dosing in an individual patient (model‐informed precision dosing). Inflammatory biomarkers have been proposed to measure inflammation levels and guide antibiotic treatment. However, their potential to guide antibiotic dosing is unclear. This narrative review describes associations between inflammation and PK/PD of antibiotics in critically ill patients, and the role of biomarkers, therapeutic drug monitoring and model‐informed precision dosing in improving antibiotic dosing. A focus of future research should be on the interplay between inflammation and PK/PD of antibiotics by including inflammatory biomarkers in PK/PD models and using big data to predict antibiotic exposure in critically ill patients.

There is an increased clinical use of elbow orthoses. It is important to consider patient experiences in their use. Patient-reported outcome measures (PROMs) serve as essential tools for gathering patient perspectives. This review provides a comprehensive list of PROMs used in clinical trials of elbow orthoses, and documents their properties, uses, and quality. A systematic literature search across PubMed, Scopus, Embase, Cumulative Index to Nursing and Allied Health Literature, and Web of Science identified 31 clinical trials of elbow orthoses that used PROMs as outcome measures. Subsequently, manual searches were conducted to report on each PROM's characteristics. A total of 15 different PROMs were used as outcome measurements in clinical trials that used an elbow orthosis as an intervention for 11 different conditions. Researchers can use this review to aid in making informed decisions about which PROMs to use for future clinical trials.

Abstract Clinical question What are the benefits and harms of medications for adults with type 2 diabetes at varied risks of cardiovascular and kidney related complications? Context Emerging clinical trials of novel medications have demonstrated benefits on cardiovascular, kidney, and weight related outcomes in people with type 2 diabetes. Dynamically updated practice guidelines adhering to standards of trustworthiness are necessary in response to a rapidly evolving evidence base and the availability of multiple medication alternatives. This living practice guideline incorporates the latest available medications and evidence and provides recommendations stratified by risks of cardiovascular and kidney complications to inform diabetes management. Recommendations The panel issued risk-stratified recommendations regarding four prioritised medications for adults with type 2 diabetes (SGLT-2 inhibitors, GLP-1 receptor agonists, finerenone and tirzepatide): • Lower risk (three or fewer cardiovascular risk factors without established cardiovascular disease (CVD) or chronic kidney disease (CKD)): weak recommendation against SGLT-2 inhibitors or GLP-1 receptor agonists. • Moderate risk (more than three cardiovascular risk factors without established CVD or CKD; or established CVD and/or CKD at lower risk of complications): weak recommendation in favour of SGLT-2 inhibitors or GLP-1 receptor agonists; and a weak recommendation against finerenone in adults with CKD. • Higher risk (established CVD and/or CKD at higher risk of complications, or established heart failure): strong recommendation in favour of SGLT-2 inhibitors or GLP-1 receptor agonists; and a weak recommendation in favour of finerenone in adults with CKD. • Across risk strata: weak recommendation in favour of tirzepatide in adults with obesity. About this guideline and how it was created An international panel including two patient partners, clinicians, and methodologists produced these recommendations. The panel followed standards for trustworthy guidelines and used the GRADE approach, explicitly considering the balance of benefits, harms and burdens of treatment from an individual patient perspective. Recommendations were informed by a linked living systematic review and network meta-analysis evaluating relative benefits and harms updated to 31 July 2024; and by linked systematic reviews addressing risk prediction models and values and preferences of adults with type 2 diabetes. Candidate therapeutics are prioritised based on availability of sufficient randomised trial data, relevance to a global audience and likelihood of changing practice. This is the first version of the living guideline. The guideline is part of the BMJ Rapid Recommendations series. MAGICapp displays the most recent version of the guideline and full content including evidence summaries and decision aids; major updates will be published in The BMJ . We encourage re-use, adaptation and translation of these living guidelines, and recognise that the lack of availability or high costs of some medications may be prohibitive and will impact on how these recommendations are implemented across different health care systems.

Abstract Monomorphic posttransplant lymphoproliferative disorders (PTLDs) beyond diffuse large B-cell lymphoma (DLBCL) are rare, biologically heterogeneous entities with limited prospective data to guide treatment. DLBCL-PTLD, which comprises most cases, is managed using approaches informed by prospective phase 2 studies, including reduction in immunosuppression and a risk-adapted sequential immunochemotherapy approach. In contrast, non-DLBCL subtypes such as Burkitt lymphoma, PTLDs of T/NK-cell origin, and plasmacytic variants are less common and are typically treated using strategies extrapolated from established treatment algorithms used in immunocompetent patients and sporadic case reports. Classic Hodgkin lymphoma PTLD, although not classified as monomorphic, represents another distinct and clinically relevant subtype. This review summarizes the epidemiology, clinical features, treatment strategies, and outcomes associated with these less common PTLDs, aiming to provide a practical framework for their management.