Citations

Abstract: Stroke remains a leading cause of global mortality and is projected to become the second-largest contributor to the global disease burden by the year 2050. Despite advancements in medical technology, a definitive cure for stroke is still unavailable, and effective management heavily depends on timely intervention after its occurrence. In recent decades, stroke incidence has declined in developed nations due to improved preventive measures while it has surged in developing regions, particularly among younger populations. This highlights the urgent need for comprehensive prevention strategies to address modifiable factors and reduce long-term disabilities. This review categorizes modifiable stroke risk factors into three key domains: metabolic, behavioral, and environmental. It synthesizes current knowledge and evaluates intervention strategies targeting hypertension, diabetes, smoking, dietary habits, and air pollution, among others. The review also examines emerging evidence on the benefits and limitations of these interventions, providing critical insights into their effectiveness. Notably, the discussion also encompasses the interplay and combined impacts of these risk factors, offering a thorough insight into etiology and emphasizing the importance of adopting a comprehensive strategy for risk management. By providing a general view of stroke prevention efforts, the paper aims to guide future research and support the development of evidence-based, population-level strategies to mitigate stroke risk globally.

The treatment landscape of B-cell lymphomas has significantly evolved in recent years with approval of novel targeted therapies. CD3 × CD20 bispecific antibodies and CD19-directed monoclonal antibodies and antibody–drug conjugates have demonstrated efficacy in relapsed/refractory follicular lymphoma (FL). Bruton tyrosine kinase (BTK) inhibitor–based regimens are emerging as effective treatment options for patients with TP53-mutated classical mantle cell lymphoma (MCL). Results from ongoing clinical trials suggest that the addition of CD3 × CD20 bispecific antibodies to chemoimmunotherapy improves outcomes in patients with relapsed/refractory diffuse large B-cell lymphoma (DLBCL). These NCCN Guideline Insights highlight significant updates to the NCCN Guidelines for B-Cell Lymphomas for the treatment of FL, MCL, and DLBCL.

The NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for Hematopoietic Cell Transplantation (HCT) provide expert, multidisciplinary recommendations for autologous and allogeneic HCT based on current evidence. The NCCN Guidelines focus on pretransplant recipient evaluation, hematopoietic cell mobilization, conditioning, and the diagnosis and management of graft-versus-host disease (GVHD), a common complication of allogeneic HCT that is associated with significant morbidity. This selection from the NCCN Guidelines for HCT focuses on the diagnosis, workup, and management of acute and chronic GVHD, as well as important supportive care considerations.

Background Postoperative atrial fibrillation occurs in ~40% after cardiac surgery. Mineralocorticoid receptor antagonists (MRA) are known to reduce chronic atrial fibrillation (AF) development and burden. We evaluated the association of preoperative MRA use with postoperative atrial fibrillation and investigated atrial cell types modulated by MRAs during cold preservation. Methods We studied 19 042 cardiac surgery patients at Mayo Clinic. Propensity 1:3 matching identified 298 MRA users and 894 non‐users. A subgroup analysis of patients on any preoperative diuretic was performed to isolate cardiac‐specific effects of MRAs, matching 298 MRA users to 894 non‐MRA diuretic users. AF recurrence was assessed for up to 6‐years. Single‐nucleus RNA sequencing (snRNA‐seq) was performed on human donor atria exposed to canrenone (a water‐soluble MRA) during cold preservation with ex‐vivo reperfusion, and expression profiles were compared with atria from patients with AF. Results After matching, preoperative MRA use was associated with a lower incidence of postoperative atrial fibrillation (19.8% versus 31.8%, P <0.001). In the diuretic‐only subgroup, MRA users also had lower postoperative atrial fibrillation (19.8% versus 33.2%, P <0.001). MRA use was associated with a reduced incidence of paroxysmal and chronic AF at 6‐years. snRNA‐seq identified a cardiomyocyte subpopulation, CM2, with high mineralocorticoid receptor expression where canrenone suppressed cold preservation‐induced mineralocorticoid receptor target gene expression, which was conversely elevated in chronic AF. Canrenone also attenuated stress‐response in atrial macrophages and pericytes. Conclusions Preoperative MRAs were associated with reduced postoperative and long‐term AF after cardiac surgery. Mechanistically, our ex‐vivo human atrial model revealed that MRAs suppress mineralocorticoid receptor ‐driven atrial stress responses, particularly in conduction‐relevant cardiomyocytes.

Abstract Background Posaconazole immediate release (IR) suspension is the standard product for enteral feeding tube (EFT) administration but has erratic pharmacokinetic behaviour, often resulting in subtherapeutic concentrations. Limited evidence suggests that posaconazole oral delayed-release (DR) tablets may be crushed. Methods This was a retrospective cohort study of hospitalized adults who received EFT administration of posaconazole IR suspension or crushed DR tablets between 2018 and 2024. Patients were eligible if they had at least one serum drug concentration drawn ≥5 days after posaconazole initiation. The primary outcome was attainment of therapeutic drug concentrations. Secondary outcomes included time to therapeutic serum concentration, adverse drug events, and frequency of occluded EFT. Results Of the included patients, 48 received IR suspension and 100 received DR tablets. Baseline characteristics and severity of illnesses were well balanced. Among IR suspension and crushed DR tablet recipients, 39% and 80% achieved therapeutic concentrations, respectively (P = 0.002). After adjusting for age, sex, BMI, drug interactions, posaconazole indication and malabsorptive conditions, crushed DR tablets were significantly more likely than IR suspension to achieve therapeutic posaconazole concentrations within 30 days (HR 5.22, 95% CI 2.35–11.61). Occluded EFTs were more frequent among crushed DR tablet recipients (27% versus 10%, P = 0.022), while no differences were observed in the occurrence of hepatotoxicity or hypokalaemia. Conclusions With EFT administration, crushed posaconazole DR tablets were associated with a greater likelihood of achieving therapeutic concentrations compared with IR suspension. The optimal technique for administering crushed DR tablets to prevent EFT complications warrants investigation.

Background A contemporary, comprehensive risk score for the prediction of in‐hospital fatal and nonfatal adverse events after percutaneous coronary intervention has been recently developed, albeit its external validation in patients with acute coronary syndrome is lacking. The objective of this study is to validate the Mayo Clinic integer risk score in a large cohort of patients with acute coronary syndrome undergoing percutaneous coronary intervention from the MATRIX (Minimizing Adverse Haemorrhagic Events by Transradial Access Site and Systemic Implementation of Angiox) trial. Methods The risk score is composed of a common set of 23 clinical and procedural variables (model A) and 18 preprocedural variables (model B). The primary objective was to appraise the receiver‐operator characteristics of both models for in‐hospital mortality, bleeding, contrast‐associated acute kidney injury, and stroke. The impact of risk score categories on 1‐year outcomes was also investigated. Results Among the 6724 patients undergoing percutaneous coronary intervention in the MATRIX trial, the receiver‐operator characteristics—area under the curves for in‐hospital mortality, bleeding, contrast‐associated acute kidney injury, and stroke were 0.88 (95% CI, 0.85–0.91), 0.66 (95% CI, 0.63–0.69), 0.70 (95% CI, 0.67–0.72), and 0.65 (95% CI, 0.52–0.78) for model A and 0.88 (95% CI, 0.84–0.92), 0.63 (95% CI, 0.60–0.66), 0.66 (95% CI, 0.63–0.69), and 0.65 (95% CI, 0.52–0.78) for model B, respectively. Mortality (model A), bleeding, and stroke risks were well calibrated, whereas mortality (model B) and contrast‐associated acute kidney injury risk were underestimated. There was a gradual risk increase for 1‐year mortality and bleeding as a function of the risk score tertile using both models. Conclusions The risk score identifies patients with acute coronary syndrome at incremental risk of in‐hospital mortality, bleeding, contrast‐associated acute kidney injury, and stroke, representing a valuable tool for mitigation of modifiable risk factors. Registration URL: https://www.clinicaltrials.gov ; Unique Identifier: NCT01433627.

ABSTRACT Background and Aim This study aimed to provide updated nationwide data on outcomes in heart transplantation for amyloid cardiomyopathy (ACM) compared with other cardiomyopathy etiologies. Methods United Network for Organ Sharing data for patients over 18 who underwent heart transplant for ACM, and other cardiomyopathies including DCM, ICM, RCM, and CHD were reviewed from 2001 through 2022. The data were analyzed with a propensity score‐matched analysis comparing ACM patients with transplant for the cardiomyopathies to measure primary outcomes, including 5‐year, 10‐year, and all‐cause mortality accounting for differences at baseline. Results Of 21 457 heart transplant recipients who met eligibility criteria, there was a 100% increase in the number of heart transplants for ACM from 2010 to 2020 ( p < 0.001). The unadjusted mortality did not differ significantly among ACM, DCM, ICM, RCM, and CHD groups, and 5‐year mortality was comparable between ACM and DCM patients. ACM patients had a significantly lower incidence of postoperative stroke ( p = 0.044), and risk factors for ACM transplant mortality were identified as mechanical ventilation at the time of transplant (HR: 3.8, p = 0.023) and older donor age (HR: 1.1, p = 0.015). Conclusions The number of heart transplants for ACM has increased in recent years, and overall outcomes in these ACM transplants have been similar compared to those for other cardiomyopathies. Despite historical concerns regarding poor prognosis and amyloid recurrence, carefully screened ACM patients can benefit from heart transplantation. Further research and optimization of ACM patient eligibility criteria alongside investigation of concurrent adjunctive therapies could optimize treatment of ACM with heart transplantation.

Objectives: To quantify the effects of geared wheelchair wheels on energy expenditure during manual wheelchair propulsion in individuals with spinal cord injury (SCI). Methods: Eleven adult manual wheelchair users with SCI propelled their personal manual wheelchairs, which were equipped with a pair of geared wheels, on a passive wheelchair ergometer in low-gear and standard-gear conditions for six minutes. The energy cost of transport, distance traveled, rate of oxygen consumption (SCI MET), rate of perceived exertion, heart rate, and stroke cycle frequency were measured and compared across the gear conditions. Results: The distance traveled and SCI MET were significantly lower (p = 0.003) and cost of transport was significantly higher under the low-gear condition compared with the standard-gear condition. Gear condition exerted a moderate effect on the level of exertion; however, the decrease in the rate of perceived exertion under the low-gear condition was not statistically significant. Gear condition did not significantly affect heart rate and stroke cycle frequency. Conclusions: Geared manual wheelchair propulsion was significantly more energy-demanding, but less intense (easier) under the low-gear condition than the standard-gear condition. Using geared wheels may be beneficial for manual wheelchair users to independently accomplish strenuous propulsion tasks during typical activities of daily living, such as propulsion on carpeted floor. However, the small sample size and inclusion of only male participants limit the generalizability of these findings, and future studies with larger and more diverse cohorts are warranted.