Citations

Abstract Background Highly modulated radiotherapy delivery demands functional multileaf collimator (MLC) quality assurance (QA) with the ability to measure very low doses during short (<1 s) temporal segments of beam delivery. A radiochromic film with adequate sensitivity in the few‐cGy range is therefore needed. LD‐V1 film was designed for 2–20 cGy measurements in diagnostic kV energy ranges, but its performance for megavoltage (MV) beam qualities has not been well characterized. Purpose To demonstrate the feasibility of LD‐V1 film for low‐dose MV measurements and characterize its signal dependence under conditions relevant for clinical QA. Methods A 6 MV calibration curve was generated using eight dose levels between 0 and 40 cGy and compared with EBT4 film irradiated under identical conditions. Film characteristics evaluated included dose response, scanner and film signal uniformity, scan repeatability, energy dependence, post‐exposure signal evolution, scanning‐orientation dependence, and one‐dimensional (1‐D) profile visualization. Results LD‐V1 demonstrated higher net optical density (OD) and significantly less measurement uncertainty compared to EBT4 at dose levels less than 40 cGy. Significant energy dependence between kV and MV beam qualities was seen. Average net OD differences of 6.3% were seen between landscape and portrait scanning orientations. Post‐irradiation signal growth followed a logarithmic trend, stabilizing at ∼24 h. Scan‐to‐scan variation was <0.1%. Film‐signal uniformity was within 3.9%. 1‐D profiles showed discernible dose fall‐off for doses as low as 10 cGy. Conclusions LD‐V1 demonstrates suitability for low‐dose MV measurements and exhibits improved low‐dose sensitivity relative to EBT4, indicating its potential value for MLC QA in highly dynamic treatment deliveries. Nonetheless, its pronounced energy and scanning‐orientation dependence underscores the need for rigorous and consistent calibration and handling procedures.

Pulsed Electric Field (PEF) ablation is a non-thermal cancer treatment that disrupts tumor cell membranes while preserving the immune microenvironment and promoting immunogenic cell death. We present a case of a patient with metastatic hormone receptor-positive, HER2-low breast cancer who achieved a durable clinical response after PEF in combination with an immune checkpoint inhibitor (pembrolizumab). The patient remained off systemic therapy for 14 months without disease progression. Single-cell spatial molecular imaging (SMI) and gene set enrichment analysis (GSEA) were performed to evaluate immune microenvironment changes pre- and post-PEF treatment. Spatial transcriptomics of the tumor cell compartment revealed a post-PEF enrichment of immune-related pathways, including interferon alpha/beta and gamma signaling and MHC class I antigen processing and presentation, alongside increased infiltration of immune cells: CD8+ T cells, plasmablasts, and monocytes within the tumor neighborhood. This hypothesis-generating case suggests PEF’s potential to reshape the tumor-immune microenvironment when combined with immune checkpoint blockade, warranting further studies on its role in combination immunotherapy strategies.

Effective translation relies on high performance teams integrating diverse disciplines to bring new drugs, medical devices, diagnostics or behavioral interventions into improved health. Despite substantial advancements informed by the Science of Team Science (SciTS), challenges remain in effective translational team (TT) operations, while limited institutional, scholarly, and practitioner legitimacy of team science expertise constrains efforts to address them. Here, we describe an essential member of the TT, the Team Science Professional (TSP). Serving as a team educator and facilitator of team interventions, the TSP plays a pivotal role in facilitating effective team performance. Current challenges faced by this nascent profession are defining career pathways and establishing competencies needed for expert performance. To address these challenges, the authors, representing a spectrum of academic universities organized as a special interest group (SIG) of the Association of Clinical and Translational Science (ACTS), propose a suite of individualized, standardized and pathway-selective micro-credentials (digital badges). Digital badges in “Team Science (TS) Fundamentals,” “TS Practitioner,” “TT Trainer” and “TT Intervention Expert” are described, along with preliminary feasibility and usability evaluations of the submission process. These stackable credentials provide a customizable, portable recognition of skills and help advance career pathways for TSPs. In so doing, the Digital Badge Initiative will enhance the capacity of translational science “Hubs” such as those supported by Clinical and Translational Science Awards to conduct effective and rigorous translation. Moving forward, the ACTS TSP SIG will be examining the impact of digital badging on standardization and its effect on career recognition and retention.

ABSTRACT Introduction Right ventricular pacing (RVP) has long been the standard therapy for bradyarrhythmias but may induce ventricular dyssynchrony and adverse cardiac remodeling. Physiologic pacing strategies that preserve the native conduction system, particularly left bundle branch area pacing (LBBAP), have emerged as promising alternatives. This study aimed to evaluate the comparative efficacy and safety of LBBAP versus RVP through an updated meta‐analysis. Methods Following PRISMA guidelines, we systematically searched PubMed, Cochrane CENTRAL, and ClinicalTrials.gov for relevant studies published through June 2025. Studies comparing LBBAP and RVP in patients undergoing pacemaker implantation were included. Pooled estimates were calculated using random‐effects models. Results A total of 40 studies comprising 8290 patients were included. LBBAP was associated with significantly shorter QRS duration compared with RVP (30 studies, n = 5510; MD −35.56 ms, 95% CI −41.88 to −29.24; p < 0.0001). Structural remodeling also favored LBBAP, with greater improvement in left ventricular ejection fraction (16 studies, n = 1693; MD +3.77%, 95% CI 2.43–5.12; p < 0.0001) and greater reduction in left ventricular end‐diastolic diameter (13 studies, n = 1666; MD −2.33 mm, 95% CI −3.59 to −1.07; p < 0.0001). Clinically, LBBAP was associated with lower heart failure hospitalization (RR 0.38, 95% CI 0.29–0.52; p < 0.0001) and reduced all‐cause mortality (RR 0.55, 95% CI 0.41–0.72; p < 0.0001), along with greater reduction in NT‐proBNP levels. Conclusion LBBAP provides superior electrical synchrony, improved cardiac remodeling, and favorable clinical outcomes compared with RVP, while maintaining a comparable procedural safety profile.

Objective To comprehensively examine hypertension- and heart failure–related mortality rates in the United States to develop a targeted approach to health policy development. Methods We analyzed death certificates from the Centers for Disease Control and Prevention Wide-Ranging Online Data for Epidemiologic Research database, focusing on mortality caused by hypertensive heart failure in adults aged ≥25 years from 2006 to 2020. Age-adjusted mortality rates per 1,000,000 and annual percent changes were calculated and categorized by year, sex, race, urban status, age group, and census region. Results A total of 268,545 deaths occurred due to hypertensive heart failure between 2006 and 2020. The overall age-adjusted mortality rates increased from 60.5 in 2006 to 134.9 in 2020. Males had higher age-adjusted mortality rates than women (76.6 vs. 73.8). Older-aged people exhibited significantly higher age-adjusted mortality rates than young and middle-aged adults. Age-adjusted mortality rates were highest in non-Hispanic Blacks/African Americans and lowest in non-Hispanic Asians/Pacific Islanders (126.8–43.6). Furthermore, age-adjusted mortality rates were highest in individuals from nonmetropolitan areas and the Western region. Conclusion Following a period of decline, the age-adjusted mortality rates increased until 2020. The highest age-adjusted mortality rates were observed in non-Hispanic Blacks and nonmetropolitan areas. An urgent restructuring of healthcare policy is needed to reduce heart failure-associated mortality.

Abstract The Bridging the Gaps (BTG) in Leukemia, Lymphoma and Multiple Myeloma Consensus Conference 2025 brought together a multidisciplinary group of oncology experts to address the complexities of lymphoma management, focusing on mantle cell lymphoma (MCL), chronic lymphocytic leukemia (CLL), and diffuse large B‐cell lymphoma (DLBCL). This article presents consensus recommendations developed through a modified Delphi process, which emphasize the need for tailored therapeutic strategies in light of recent advancements in treatment options. Key recommendations include the screening for high‐risk features in MCL, use of the BOVen regimen (zanubrutinib, obinutuzumab, and venetoclax) for TP53 ‐aberrant cases, and integration of chimeric antigen receptor T‐cell therapy for patients with mantle cell lymphoma that is refractory to covalent Bruton tyrosine kinase inhibitors. For CLL, recommendations include consideration of time‐limited therapies for younger patients and a “watch and wait” strategy for asymptomatic patients despite the improved activity and safety of current treatment regimens. For DLBCL, this article highlights the challenges in treatment sequencing and the role of circulating tumor DNA and minimal residual disease testing in monitoring disease progression. Overall, the conference describes the importance of ongoing research to refine management strategies and improve patient outcomes in lymphoma care, addressing the gaps in clinical practice where high‐level evidence is lacking.

PURPOSE Approximately three quarters of patients with sarcoma report financial toxicity, defined as the psychosocial and economic burden of cancer care. The Comprehensive Score for Financial Toxicity (COST) is a screening questionnaire validated in patients with cancer. However, its use is not widespread in sarcoma care, likely in part due to its complexity. This study aimed to characterize financial toxicity in patients with sarcoma and evaluate whether shorter screening tools can identify high-risk patients. METHODS We conducted a survey and retrospective cohort study of patients treated for sarcoma at a large, academic sarcoma center in 2016-2024. Patients completed the COST questionnaire (11 graded questions, each scored on a five-point Likert scale from 0 to 4) and the shorter, four-question Worry about Affording Healthcare Scale (WAHS). We obtained clinical information from the electronic health record. We used descriptive statistics to summarize responses to COST, Pearson's correlation coefficient to assess the association between WAHS and COST, and stepwise Spearman correlations to evaluate whether an abbreviated (1-4 question) version of COST correlated highly with total COST score. RESULTS Among 205 participants, the mean COST score was 20/44 (standard deviation = 6; lower scores indicate greater financial toxicity). Respondents worried most about job loss (mean COST: 0.99) and family finances (mean COST: 1.11). WAHS was weakly correlated with COST (r = 0.47, P < .01). A four-item abbreviated COST tool was strongly correlated with the total COST (ρ = 0.906, P < .0001) and demonstrated high sensitivity (96%) and moderate specificity (75%). CONCLUSION An abbreviated four-item COST tool could act as a clinically feasible, accurate screening tool after external validation. Routine financial toxicity screening could facilitate timely detection and referral to essential financial navigation resources.

PURPOSE Hepatopancreatobiliary (HPB) cancers—including hepatocellular carcinoma (HCC), cholangiocarcinoma (CCA), pancreatic ductal adenocarcinoma (PDAC), and gallbladder cancer—are aggressive malignancies with limited treatment options and poor prognosis. The emergence of personalized liquid biopsy technologies, particularly bespoke circulating tumor DNA (ctDNA), offers new opportunities for improving clinical management. Traditional methods like imaging and tumor markers may miss early recurrence or evolving disease. This study explores the real-world application of ctDNA in HPB cancers, focusing on its use for surveillance, diagnostic clarification, treatment monitoring, and recurrence detection. Methods We retrospectively analyzed the use of a personalized ctDNA assay (Signatera, Natera) in 54 patients with HPB cancers at a single academic cancer center. The cohort included PDAC (22/54), HCC (11/54), and CCA (21/54). ctDNA was assessed longitudinally for surveillance, treatment monitoring, or diagnostic clarification. Concordance with imaging and tumor markers, as well as lead time to recurrence detection, was descriptively analyzed. RESULTS ctDNA was evaluable in 37/54 patients (84.6%), with ctDNA positivity in 22/37 (59.5%). Success rates by tumor type were 16/22 (72.7%) in PDAC, 10/11 (90.9%) in HCC, and 11/21 (52.4%) in CCA. ctDNA concordance with imaging was observed in 69/85 assessments (72.6%) and with tumor markers (carbohydrate antigen 19-9 or alpha fetoprotein) in 39/95 (41%). Clinical applications included disease surveillance (21/54, 38.9%), treatment monitoring (24/54, 44.4%), and diagnostic clarification (16/54, 29.6%). In patients with recurrence, ctDNA detected disease before imaging in several cases, with a median lead time of 28 days (range, 1 month to 7 months). CONCLUSION Personalized ctDNA testing demonstrated meaningful utility across HPB cancers, enabling early recurrence detection and guiding clinical decision making as a complementary tool in multidisciplinary care.

Background and importance Emergency tracheal intubation in critically ill adults is associated with a high risk of peri-intubation adverse events, making first-attempt success a key safety target. Objective This study aimed to evaluate whether the use of neuromuscular blocking agents (NMBAs) improves the proportion of first-attempt success and reduces adverse events during emergent intubations outside the operating room. Methods This was a systematic review and meta-analysis of randomized clinical trials or nonrandomized studies comparing sedative-hypnotic plus NMBA versus sedative-hypnotic alone in critically ill adults undergoing emergency endotracheal intubation in nonoperative settings. Animal, cadaveric, manikin/simulation, and pediatric studies were excluded. Articles were screened on 21 August 2025, in Ovid MEDLINE, Ovid Embase, Ovid Cochrane Central Register of Controlled Trials, and the Web of Science Core Collection. Main results Of 4736 screened citations, 13 studies (8 cohort; 5 before-after studies) were included in the quantitative analysis, with 14 072 participants. NMBA use was associated with higher first-attempt success, which ranged from 69 to 92% (pooled odds ratio, 2.72; 95% onfidence interval: 1.42–5.21; low-certainty evidence). Secondary outcomes related to adverse events were rated as very low certainty due to sparse data, inconsistent reporting, and serious imprecision. Conclusion NMBA use during emergency intubation was associated with improved first-attempt success, although the certainty of evidence was low.