Citations

Previous studies about the COVID-19 pandemic on STEMI patient outcomes have conflicting results. It remains unclear if this may be attributed to regional differences and/or differences during COVID-19 wave periods. Using the American Heart Association Get With The Guidelines–Coronary Artery Disease registry data, we evaluated (1) time metrics related to STEMI system goals and (2) regional variation in STEMI incidence and in-hospital mortality during pandemic wave time periods. The study included all patients 18–100 years old admitted with STEMI (n = 72,516) to 1 of 435 American Heart Association Get With The Guidelines–Coronary Artery Disease hospitals (1 October 2019–31 December 2021). Of these, 70.8% were male and 73.0% non-Hispanic White, with a median age of 63 (IQR 18) years. Compared to pre-pandemic time frames, patients with STEMI had a higher risk profile, delayed time to treatment, were treated with fibrinolytic therapy or primary PCI, and were transferred for primary PCI at similar rates, and had higher adjusted in-hospital mortality (during the second wave in the South and Midwest). Preservation of STEMI systems of care resulted in an overall lower in-hospital mortality rate than predicted, although opportunities exist to improve treatment delays. Regional differences in mortality rates require further study.

Abstract Background and Aims Truncating variants in the TTN gene (TTNtv) are the most common genetic cause of dilated cardiomyopathy (DCM) but also occur as incidental findings in the general population. This study investigated factors associated with the clinical manifestation of TTNtv. Methods An international multicentre retrospective observational study was performed in families with TTNtv-related DCM. Shared frailty models were used to estimate associations of variant characteristics with lifetime risk of DCM, and logistic regression to estimate odds ratios (ORs) for individual-level clinical risk factor profiles (cardiac conditions, cardiovascular comorbidities, lifestyle) and DCM. Results A total of 3158 subjects in 1043 families with TTNtv-related DCM were studied. TTNtv-positive subjects were 21-fold more likely to develop DCM [OR, 21.21; 95% confidence interval (CI), 14.80–30.39]. Disease onset was earlier in males, but was similar for TTNtv of different types and locations. The presence of clinical risk factors was associated with earlier DCM onset (OR, 3.41; 95% CI, 2.06–5.64), with a prior history of atrial fibrillation having a two-fold increased odds of DCM (OR, 2.05; 95% CI, 1.27–3.32). The prevalence of clinical risk factors increased with age; however, the strength of the DCM association was greatest for young-onset (<30 years) disease (OR, 4.75; 95% CI, 2.35–9.60). Administration of beta-adrenergic receptor or renin-angiotensin system-blocking drugs prior to overt DCM was associated with 87% reduced odds of DCM (OR, .13; 95% CI, .08–.23). Conclusions Disease onset in TTNtv-associated familial DCM is dependent on individual patient context and is potentially modifiable by risk factor management and prophylactic therapeutic intervention.

Introduction In moderate to high-risk surgical procedures, 15–25% of patients develop a postoperative surgical site infection. Intraoperative incisional wound irrigation has the potential to reduce surgical site infections, and additional randomised controlled trials are required to provide evidence of effectiveness. Methods and analysis This protocol describes a pragmatic, adaptive, participant and adjudicator-blinded trial at 13 sites in Canada in up to 2500 participants. Participants planned for surgery with an abdominal or groin incision, who are eligible and provide verbal consent through an integrated consent model, are randomised to receive intraoperative incisional wound irrigation with povidone-iodine, saline or no irrigation. The primary outcome is surgical site infection within 30 days postoperatively. Secondary outcomes include quality of life measured 30 days postoperatively and morbidity, mortality and healthcare utilisation within 90 days postoperatively. Ethics and dissemination This trial has been approved by the research ethics board at the participating centres and stopped enrolling participants on May 23, 2025. All participants will provide verbal consent. Results will be disseminated via presentation at conferences, publication and posted on clinicaltrials.gov. Trial registration number The study is registered with http://clinicaltrial.gov ( NCT04548661 ; 14 September 2020).

Importance Pathologic complete response (pCR) is increasingly used as a surrogate end point for survival in randomized clinical trials (RCTs) in the field of gastrointestinal oncology. Although this approach has been endorsed by the US Food and Drug Administration, it is still novel and incompletely verified. Objective To evaluate the trial-level association between pCR and survival in rectal cancer RCTs examining the effectiveness of neoadjuvant therapy. Data Sources A meta-analysis was conducted to identify eligible RCTs in PubMed, EMBASE, and Cochrane databases published between database inception to January 3, 2024. Study Selection RCTs evaluating neoadjuvant therapies in patients with rectal cancer who underwent subsequent surgical resection and reported pCR, overall survival (OS), and disease-free survival (DFS) were included. Data Extraction and Synthesis Two investigators extracted the data, which were verified by a third author. The risk of bias and the certainty of the evidence were evaluated using the Cochrane Risk of Bias Tool, version 2, and the Grading of Recommendations Assessment, Development, and Evaluation tool, respectively. Adjusted odds and hazard ratios with their 95% CIs were extracted. Weighted linear regression was used to assess the correlation between pCR and both OS and DFS. Main Outcomes and Measures Trial-level correlation between pCR and both OS and DFS. Results Twenty-five RCTs, including 11 882 patients, met the inclusion criteria. On meta-regression analysis, pCR was not correlated with OS (β = 0.37; 95% CI, −0.98 to 1.71; P = .57). Similarly, pCR was not correlated with DFS (β = −0.84; 95% CI, −2.55 to 0.87; P = .32). Two studies (8%) used in the meta-analysis had high risk of bias. On sensitivity analysis excluding these studies, pCR was still not associated with OS or DFS. Subgroup analysis of RCTs using total neoadjuvant therapies was not possible due to limited sample size. Conclusions and Relevance In this systematic review and meta-analysis of RCTs comparing neoadjuvant therapies in rectal cancer, there was no trial-level association between pCR and survival. These results suggest that the use of pCR as a surrogate end point for survival should be reexamined and used more cautiously.

Objective To explore if observations on nasopharyngoscopy influence the surgical procedure selected for the management of velopharyngeal insufficiency (VPI). Design Cross-sectional survey. Participants Seventeen surgeons with experience treating VPI. Interventions Review of twenty-four nasopharyngoscopy videos with a combination of velopharyngeal closure patterns and gap sizes. Main Outcome Measures Surgical procedure was selected after watching a nasopharyngoscopy video. Chi-square tests were used to evaluate if, for each surgeon, procedure selection varied based on closure pattern and gap size combination. Variable importance scores were obtained from a random forest analysis to quantify contribution of nasopharyngoscopy observations on procedure selection. Results Four procedures accounted for 86% of all surgeries selected: Furlow double-opposing Z-Plasty (33%), palatal lengthening using buccal myomucosal flaps (20%), pharyngeal flap (19%), and sphincter pharyngoplasty (14%). Four surgeons (23.5%) significantly varied their surgical selection when different closure pattern and gap size combinations were shown on nasopharyngoscopy. Ten surgeons (58%) selected the same procedure in ≥ 50% of the 24 nasopharyngoscopy videos. Individual surgeon preference was the strongest predictor of surgical selection, accounting for 57.9% of surgical selection variance. Velopharyngeal gap size accounted for 36.5% of the variance in surgical selection, yet the specific surgeries selected based on gap size varied widely across surgeons. Closure pattern was a weak predictor, contributing 5.6% to surgical selection variance. Conclusions Nasopharyngoscopy findings influence VPI surgical procedure selection in a highly individualized, surgeon-specific manner. Among factors observed on nasopharyngoscopy, velopharyngeal gap size has a much larger influence on procedure selection than closure pattern.

Space exploration exposes astronauts to unique conditions such as microgravity and space radiation, potentially influencing gene expression and triggering carcinogenesis. Paradoxically, these extreme environments could uncover other pro-treatment aspects of cancer biology. Despite numerous reviews addressing these aspects in isolation, a comprehensive synthesis of the effects of space stressors on cancer development is incomplete. This scoping review aims to provide a holistic perspective on the influence of spaceflight and associated stressors—including gravitation (hyper- and microgravity), radiation, and vibration—on the potential for cancer development and altered cellular mechanisms. We adhered to the PRISMA-ScR checklist for our review. A multitiered search strategy was employed in English, starting with a preliminary keyword identification in Google Scholar and PubMed. Subsequently, the main search was conducted across five databases—Cochrane, Embase, PubMed, Scopus, and Web of Science—until 22 February 2024. All included studies were thoroughly assessed by two independent reviewers. Of the 15,553 identified articles, 158 were deemed eligible. The majority (92%) were experimental studies, predominantly cell-based (74.17%). Breast (15.19%), thyroid (13.92%), and hematopoietic (11.40%) cancers were the most frequently examined. Spaceflight stressors could affect different biological systems variably, with microgravity impacting spatial growth and metastasis, and cosmic radiation exerting both tumor-suppressive and mutagenic effects. Our findings highlight the need for large-scale, prolonged analog studies mimicking space conditions to enhance mission safety and shed light on the nuanced effects of space stressors on cancer. Additionally, further extensive studies need to be performed in the true weightlessness of spaceflight, both animal-based and on human tissue (cell cultures and potentially whole perfusion organ models), in addition to crew pre/intra/post-flight long-duration evaluations. Furthermore, this unique research avenue may reveal cancer cell sensitivities to these stressors, opening new pathways for innovative therapeutic strategies in cancer treatment.

Introduction Despite growing evidence to characterise cancer-associated cognitive decline (CACD) in women with breast cancer, interventions to mitigate CACD are limited. Emerging evidence suggests aerobic exercise may enhance cognition after breast cancer diagnosis and treatment; yet, CACD remains an understudied outcome of exercise, and few high-quality studies have been conducted. In addition to knowledge gaps in effectiveness, the translation of exercise interventions to community settings remains challenging. The Breast cancer Reasoning and Activity INtervention (BRAIN) investigates the effectiveness of aerobic exercise training, delivered in a community-based setting, for improving cognitive function in women with breast cancer and gathers information on the implementation success of the intervention. Methods and analysis This Hybrid Type I effectiveness–implementation study is conducted at an academic medical centre in the southwestern United States in partnership with a non-profit, community health and wellness organisation. The study enrols 160 women diagnosed with stage I–IIIa breast cancer and within 3–36 months of treatment completion into a 1:1 randomised controlled trial. Individuals randomised to the exercise group receive a 6-month, individually tailored aerobic exercise programme delivered by exercise trainers employed at local community fitness centres. The programme is progressive in nature and designed to help participants achieve aerobic exercise levels consistent with guidelines for cancer survivors. Individuals randomise to the control group receive a 6-month health education control intervention delivered virtually by hospital-based health educators. Cognitive performance (primary), self-reported cognition, patient-reported outcomes, physical activity and cardiorespiratory fitness are measured at baseline, 6 months (postintervention) and 12 months (follow-up). Brain structure and function are measured via magnetic resonance imaging (MRI) at baseline and 6 months. Implementation outcomes are defined by the RE-AIM framework, which includes reach, effectiveness, adoption, implementation and maintenance. RE-AIM outcomes are measured at baseline, 6 months, 12 months and ongoing during the study. Ethics and dissemination This study was approved by the Mayo Clinic Institutional Review Board (#23-000020). All participants provide informed consent prior to participation. Findings will be disseminated to scientific, clinical and community audiences through manuscripts, presentations and newsletters. Trial registration number NCT04816006.

ABSTRACT Clinical and Laboratory Standards Institute (CLSI) recommends a blood culture contamination (BCC) threshold of <3%, with ≤1% considered optimal. However, there is not a standardized definition of BCC, and the effect of multiple definitions on BCC rates or what definitions laboratories use remain unknown. We surveyed 52 hospitals and analyzed 362,078 blood cultures (BCx) collected 1 September 2019 to 31 August 2021 from 62 intensive care units (ICUs) and 231 wards from 48 of these hospitals. We calculated and compared BCC rates using the College of American Pathologists (CAP) or CLSI criteria (both utilize a limited number of skin commensals to define BCC) and the comprehensive National Healthcare Safety Network (NHSN) commensal list. We characterized factors associated with BCC and related outcomes (central-line associated bloodstream infection [CLABSI] and vancomycin use). BCC, BCx positivity, and single BCx rates were monitored by 100%, 39%, and 21% of hospitals, respectively. Hospitals used CAP (65%), CLSI (17%), and NHSN (17%) criteria to define BCC. Mean BCC rate by CAP (CAP-BCC) was 1.38% for ICUs and 0.96% for wards. BCC rates remained similar by CLSI criteria but increased when using NHSN list. Sharing BCC data outside of the laboratory, measuring additional BCx quality indicators, and limiting central catheter-drawn BCx were associated with lower BCC rates. BCC was associated with higher CLABSI rates in ICUs. This study demonstrated variability in laboratory practices and opportunities to optimize BCx stewardship. IMPORTANCE Blood culture contamination (BCC) is associated with patient harm and unnecessary use of healthcare resources. BCC thresholds have been established; however, multiple BCC definitions exist. There is limited data on how BCC rates differ depending on the BCC definition used, what definitions laboratories most commonly use, or their approach to other blood cultures (BCx) quality indicators such as single rates or BCx positivity. A cross-sectional multicenter survey and analysis of BCx data from intensive care unit and wards revealed that most laboratories did not track single BCx or BCx positivity rates and that there was variability in how BCC was defined. Additionally, BCC rates were influenced by the definition used. BCC was associated with increased central-line associated bloodstream infection rates.

Abstract In recent years, there has been increasing interest in the possible prognostic impact of concomitant medications in patients with cancer treated with immunotherapy combinations. This real‐world analysis aims to evaluate the impact of concomitant medications on survival outcomes in patients with advanced biliary tract cancer (BTCs) treated with cisplatin, gemcitabine and durvalumab (CGD) therapy. The study cohort included patients with a diagnosis of advanced BTCs who were taking concomitant medications for their comorbidities before the start of CGD. The primary objectives were overall survival (OS) and progression‐free survival (PFS). The initial population consisted of 666 patients, who were retrospectively collected from 41 sites in 12 countries. Data on concomitant medications were available for 493 patients. After a median follow‐up of 8.8 months (95% CI: 7.8–9.8), patients who did not take steroids (prednisone >10 mg/day or equivalent) or nonsteroidal anti‐inflammatory drugs (NSAIDs) and opioids, before the start of CGD, had longer OS and PFS in univariate analysis. The multivariate analysis confirmed longer OS for patients who did not take steroids. Patients who did not take steroids had an OS of 14.8 months (95% CI: 13.1–29.1) versus 5.0 months (95% CI: 2.14–11.32) of patients who took prednisone >10 mg/day or equivalent. No differences were reported in terms of overall response rate (ORR), disease control rate (DCR) ( p = 1.0 and p = .16, respectively), and safety profile between the two groups. Our analysis suggests that patients who did not receive steroids before the start of GCD had longer survival and highlighted the relevance of balancing concomitant medications and chemoimmunotherapy.

Abstract Purpose The objective of this quality improvement process was to identify quality gaps in compliance with regulatory requirements and reduce the loss of revenue resulting from noncompliance with documentation of single-dose vial waste. Methods This quality improvement initiative employed process mapping and quality gap identification to address challenges related to compliance and revenue generation. A fishbone diagram and the 5 whys technique were used to identify and analyze the root causes of missed waste documentation and workflow inconsistencies. These root causes were categorized into key areas: missing documentation, divergent workflows, inconsistencies, insufficient surveillance, and staffing issues. Leveraging these insights, we developed comprehensive educational resources such as quick reference guides and updated on-the-job training materials for the pharmacy department. Additionally, reliable, reproducible reports were created to monitor waste documentation, facilitating timely interventions whereby technicians were contacted to complete missing documentation within the 96-hour charge capture window. Results This study evaluated a total of 5,801 orders placed from October 1, 2022, to March 31, 2023, for the preimplementation period. Of these 5,801 orders, 803 (13.8%) were missing waste documentation, resulting in a total revenue loss of $362,594 when converted to the average sales price (ASP). For the postimplementation period from April 1 to September 30, 2023, a total of 10,464 orders were inspected for missing waste documentation. Only 181 orders (1.7%) were found to have incomplete waste documentation, resulting in a total revenue loss of $44,343 when converted to ASP. The postimplementation period yielded a revenue capture of $318,250, representing significant improvement in compliance with waste documentation. Conclusion This quality improvement initiative significantly reduced revenue loss from noncompliance with waste documentation for compounded sterile products. Comprehensive education and reliable reporting increased adherence to waste documentation workflows and regulatory compliance.