Citations

ABSTRACT Background In patients with atrial fibrillation (AF) and heart failure with reduced ejection fraction (HFrEF), atrioventricular node ablation (AVNA) and permanent pacing are often pursued when rhythm control is not pursued. Biventricular pacing (BiVP) has demonstrated benefits over right ventricular pacing, while conduction system pacing (CSP) has emerged as an alternative. However, evidence directly comparing CSP with BiVP in this high‐risk population remains inconsistent. Objective To compare CSP versus BiVP in patients with AF and HFrEF undergoing AVNA, focusing on cardiac function, clinical outcomes, and procedural metrics. Methods Following PRISMA guidelines, we searched PubMed, Scopus, and Web of Science through February 2026 for studies comparing CSP and BiVP in adults with AF and HFrEF undergoing AVNA. Outcomes included all‐cause mortality, heart failure hospitalization (HFH), changes in left ventricular ejection fraction (LVEF), QRS duration, New York Heart Association (NYHA) class, pacing threshold, procedure duration, and fluoroscopy duration. A random‐effects model was used to pool mean differences (MDs) or risk ratios (RRs) with 95% confidence intervals (CIs). Results Six studies (one randomized crossover trial and five observational studies; N = 766 patients: CSP = 356, BiVP = 410) were included. All‐cause mortality was significantly reduced in favor of CSP (RR 0.64 [CI: 0.44 to 0.94], p = 0.02, I 2 = 0%). There was also a trend towards lower HFH, but it marginally missed statistical significance (RR 0.77 [CI: 0.58 to 1.03], p = 0.08; I 2 = 0%). Additionally, CSP decreased NYHA class (MD ‐0.64 [CI: −1.18 to −0.10], p = 0.02; I 2 = 85%) and significantly reduced QRS duration (MD −33.56 ms [CI: −52.36 to −14.76], p = 0.0005; I 2 = 97%). LVEF improvement did not significantly differ between groups (MD 4.51% [95% CI: −1.50 to 10.52], p = 0.14; I 2 = 98%). Procedure duration and fluoroscopy times did not show statistically significant difference between the two groups (MD −11.54 min [CI: −50.05 to 26.97], p = 0.56, I 2 = 96%), and (MD −5.75 min [CI: −13.13 to 1.63], p = 0.13, I 2 = 88%), respectively. Overall pacing thresholds did not significantly differ between CSP and BiVP; however, modality‐specific subgroup analysis showed comparable thresholds between HBP and BiVP, whereas LBBP was associated with significantly lower pacing thresholds than BiVP. Conclusions Among patients with AF and HFrEF undergoing AVNA, CSP may offer symptomatic and electrocardiographic advantages over BiVP, with a possible signal toward improved major clinical outcomes that requires confirmation in larger randomized studies.

Background Surgeons face elevated risks of musculoskeletal disorders due to prolonged operating times, awkward postures, and repetitive tasks, which can impair performance and well-being. Microbreaks have emerged as a potential ergonomic intervention to reduce discomfort and fatigue during surgery. Objective The main goal of this study was to investigate and compare the intraoperative usability and effectiveness of two break scheduling strategies using the OR-Stretch TM Web-App. Furthermore, surgeons’ feedback on the primary barriers to implementation of the OR-Stretch Web-App was recorded. Methods This study used a randomized, within-subjects crossover design. Fourteen surgeons (eight females) performed three surgical procedures with the following microbreak schedules; (1) microbreaks every 30 min with an optional ten-minute snooze (Break-30), (2) microbreaks every 60 min with an optional ten-minute snooze (Break-60), or (3) no microbreaks (Baseline). Outcomes were measured using self-reported subjective surveys (e.g., discomfort, fatigue, workload, and usability). Results Surgeons found both Break-30 and Break-60 conditions aided physical performance, mental focus, body pain/discomfort, and level of fatigue (self-reported improvement between 28.6% and 78.6%). No significant differences were observed in surgeons’ subjective evaluations of the Break-30 and Break-60 conditions; however, the data suggest that Break-60 is preferable to the Break-30 condition. Conclusions This study provides evidence supporting the OR-Stretch Web-App as a potential surgical ergonomic intervention. However, enhancing the Web-App's user-friendliness and developing strategies to synchronize microbreaks with appropriate times during surgeries, to avoid disrupting the surgical workflow, are critical areas for future studies.

TAF7, a core subunit of the general transcription factor TFIID, regulates transcription and additionally functions as an RNA chaperone that directs nascent nuclear RNAs to cytoplasmic polysomes, thereby influencing protein synthesis. Here, we identify a set of novel cytoplasmic interactors and a previously unappreciated cytoplasmic role for TAF7 in oncogenesis. BioID-mediated proximity labeling identified STAT3 and the CCT and WASH complexes as prominent cytoplasmic interactors of TAF7. These interactions were validated by co-immunoprecipitation and proximity ligation assays. We further showed that cytoplasmic TAF7 levels increased during oncogenesis in proportion to cancer cell pathogenicity. Notably, TAF7 engagement with STAT3, CCT and WASH complexes is markedly enhanced during cellular transformation, consistent with their functions in cancer progression. Together, these findings reveal a cytoplasmic TAF7 interactome and implicate elevated cytoplasmic TAF7 as associated with oncogenesis.

Cardiac arrest is a leading cause of global mortality, with low survival rates despite advances in resuscitation science. Reported survival ranges from 8% to 34% for out-of-hospital and in-hospital cardiac arrest. Extracorporeal cardiopulmonary resuscitation (ECPR) has emerged as a rescue therapy for patients unresponsive to conventional CPR, leveraging veno-arterial extracorporeal membrane oxygenation (ECMO) to provide artificial circulation, gas exchange, and maintenance of organ perfusion in the absence of spontaneous native circulation. Successful ECPR depends on minimizing time to ECMO initiation and selecting appropriate patients. While several aspects are consistent across countries, ECPR protocols vary in logistics, team composition, cannulation methods, and monitoring, which may influence patient-important outcomes such as survival and neurological recovery. This narrative review explores current global practices in ECPR, and identifies opportunities for standardization while recognizing elements that should remain context specific.

Abstract Technological advancements have increased the number of human spaceflights, including the advent of space tourism and deep space travel. The structure and function of the pulmonary system are gravitationally dependent, highlighting the importance of understanding functional changes within the pulmonary system during transient and sustained microgravity exposure. This systematic review and meta-analysis provide an overview of effects of microgravity (0G) on various functional outcome measures of the human lungs relative to Earth gravity (1G). Twenty-eight studies comprising parabolic flights (~20 seconds), short- (≤30 days) and long-duration spaceflight (>30 days) were assessed. Outcome measures reported in 1G (before flight) and 0G (in-flight) were extracted. Fixed effects models showed microgravity caused a reduction in elastic work and carbon dioxide production, and increases in pulmonary diffusion capacity, compliance, and pulmonary capillary blood volume. Despite this, the effect sizes were small and likely have little clinical significance in healthy individuals. However, they could impact space tourists who have lower health requirements for space travel, and those with underlying obstructive respiratory disorders. The results demonstrate how traditional functional pulmonary testing provides essential physiological benchmarks that complement high-throughput data collection methods, enabling an integrated understanding of how molecular changes translate into functional respiratory outcomes in microgravity.

Abstract Background Hospitalists work in complex clinical environments with rising patient acuity and competing demands. Uncertainty is an inescapable part of this work, yet little is known about how hospitalists experience and manage clinical uncertainty. Objectives To explore how hospitalists experience and manage uncertainty in clinical practice. Methods We conducted a single‐center qualitative study using reflexive thematic analysis within a constructivist paradigm. We interviewed hospitalist attending physicians during and/or after their work week and analyzed data inductively, drawing on literature about uncertainty in other clinical contexts. To strengthen rigor and trustworthiness, we held return‐of‐findings feedback sessions with participants. Results We interviewed 12 hospitalists between April 2023 and September 2024. Across diverse clinical situations, participants framed uncertainty through the lens of hospital discharge, using it as an anchor for decision‐making. Managing uncertainty required cognitive and emotional resources and was influenced by participants’ “bandwidth,” or perceived capacity to manage competing professional and personal demands. Perceived bandwidth shaped participants’ responses to uncertainty. Adequate bandwidth encouraged uncertainty engagement, while limited bandwidth prompted deferral or offloading. Participants described how they attempted to ease the burden of uncertainty for their oncoming colleagues by adjusting their documentation and care plans during handoffs. Conclusions Hospitalists experience uncertainty as a routine part of clinical practice and manage it pragmatically to advance patients toward discharge. Their approaches are shaped by their perceived bandwidth. The influences of uncertainty should be considered when assessing workload, organizing clinical service, and planning handoffs.

SignificanceCurrent clinical care following ischemic stroke provides intermittent assessments, potentially missing early detection of neurological deterioration. Optical imaging offers the potential for a continuous, portable alternative to the current combination of physical exams and radiological imaging. However, optical imaging technology has lacked the crucial combination of portability, resolution, and coverage required to assess spatially distributed brain function.AimHere, we present a proof-of-principle study that applies recent advancements in portable high-density diffuse optical tomography (HD-DOT) instrumentation and a functional connectivity analysis strategy to assess spatially distributed brain connectivity. Point-of-care brain health assessments with these tools may inform clinical care and our understanding of brain injury throughout acute stages of stroke recovery.ApproachWe measured spatially distributed cortical oxygenation with HD-DOT within the intensive care unit in N=13 patients with ischemic stroke within the first 72-h since last known normal. To assess brain function integrity, we developed a Similarity metric of functional connectivity (FC) through comparisons to FC in a healthy young adult population. To assess the sensitivity of this FC Similarity metric to disruptions caused by stroke, we compared these data with FC Similarity assessed in an older healthy cohort. We administered the NIH Stroke Scale to stroke patients to evaluate the potential of the FC Similarity metric to inform the severity of functional disruptions.ResultsThe FC Similarity metric applied to HD-DOT data in both acute stroke patients and healthy older controls exhibited a significant sensitivity to the presence of a stroke (Cohen’s d=1.5, p=1.2×10−3) and a significant relationship with the degree of neurological disruption as measured by the NIH Stroke Scale (R2=0.69, p=4.7×10−4).ConclusionsWe present a proof-of-principle for HD-DOT and the FC Similarity metric for assessing brain function during the acute stage of ischemic stroke recovery at the point-of-care.

Abstract Background The intra‐fraction motion of tumors during radiation therapy can be monitored using imaging systems based on X‐ray imaging (e.g., kV/MV radiography or CBCT) or magnetic resonance imaging (MRI). However, these techniques have limitations, including additional ionizing radiation dose and the need for complex, expensive equipment. Hence, a non‐invasive, lower‐cost motion‐tracking approach that does not add radiation would be beneficial for routine clinical applications. Purpose To study the feasibility of tracking the dynamic motion of a small gold marker in water by using Cherenkov photons produced by MV photon beams, through Monte Carlo simulations and experiments. Methods The GAMOS Monte Carlo code, which includes an optical simulation module, was used to calculate the deposited dose and Cherenkov‐light yield in a water phantom. Phase‐space files for 6, 10, 15, and 10 MV flattening filter‐free (FFF) beams served as photon sources. The simulation setup consisted of a 20 × 20 × 20 cm 3 water phantom with an 8 × 12 × 0.25 mm 3 gold planar implant at its center. Percent depth dose (PDD) and Cherenkov‐light yield were evaluated throughout the phantom and near the gold implant. For experimental validation, a 20 × 20 × 20 cm 3 glass water tank was placed on a programmable platform executing sinusoidal, sawtooth, and sharkfin motions (± 20 mm amplitude; 10‐ and 60‐s cycles). A 5 × 5 cm 2 10 MV FFF beam (2400 MU/min) irradiated the gold implant. A scientific CMOS camera (f/2.0) positioned at 80 cm from the implant captured Cherenkov images. Repeatability was quantified by the standard deviation (SD) across motion cycles. The accuracy was assessed as the absolute difference between the bright‐room reference position and the Cherenkov‐derived position. Images of the implant in sinusoidal motion were also acquired during delivery of a two‐arc brain volumetric modulated arc therapy (VMAT) plan (Arc A and Arc B). Results Monte Carlo simulations showed that Cherenkov light yield throughout the phantom closely correlated with the PDD for all beam energies. The Cherenkov light yield upstream of the gold implant increased by 6.12%, 7.16%, 9.11%, and 7.01% compared to the Cherenkov light yield without the gold implant for 6, 10 FFF, 10, and 15 MV beams, respectively. Experiments confirmed that the beam‐facing side of the gold implant appeared brighter than the opposite side, indicating enhanced backscattered electron production. Cherenkov‐based positional measurements of the periodically moving implant showed close agreement with bright‐room references. For static beams, accuracy across motion patterns was < 0.70 mm with repeatability < 0.2 mm. For the VMAT plan, the accuracies were < 0.50 mm (Arc A) and < 0.70 mm (Arc B). Conclusion The Cherenkov‐light yield was strongly correlated with the deposited dose and showed a notable enhancement around the gold implant. Cherenkov light imaging successfully tracked the dynamic motion of a gold implant in water under high‐dose rate conditions, demonstrating its potential for real‐time fiducial tracking in radiation therapy without additional radiation exposure.

Abstract Hemorrhagic shock is a common emergency that accounts for more than 10% of global mortality and up to 40% of trauma-related mortality. The Advanced Trauma Life Support (ATLS) guidelines outline resuscitation strategies in patients with massive hemorrhage based on clinical trial and observational data. Early intervention with fluids and/or blood products is recommended during resuscitation as key to maintaining vascular patency, stabilizing a patient’s blood pressure, maintaining tissue oxygenation, and limiting shock. From a transfusion perspective, there is wide heterogeneity in the quality of blood products due to donor and manufacturing variation. The optimal transfusion strategy for massive hemorrhage remains unclear. In silico models of resuscitation may offer a means to evaluate the effectiveness and safety of various resuscitation protocols. Here we describe a stochastic multicompartment model of fluid balance and resuscitation that includes (i) cardiovascular hemodynamics, (ii) body fluid compartments and capillary solute exchange, (iii) the ability to alter hemorrhage, resuscitation, and hemostasis parameters, and (iv) tissue oxygenation and capillary-alveolar gas exchange. Building upon deterministic frameworks, this stochastic model more faithfully reflects the clinical heterogeneity of bleeding patients at a level I trauma center. This allows for a proof of concept in silico trial comparing crystalloids, conventional component therapy (CCT), i.e. red cell, platelet and plasma components, to cold-stored low titer group O whole blood (LTOWB). In an in silico cohort of ATLS class III (>30% and ≤40% blood volume lost) hemorrhage, LTOWB resuscitation reduced the time spent in the critical hemostatic window (platelet count <50x109/L, INR≥2, hemoglobin (Hgb) <8 g/dL and fibrinogen <150 mg/dL) compared with CCT (90.59 vs. 147.62 minutes; p=0.04), with no difference in predicted event-free survival (t = 240 minutes; cardiac < 1.5, fluid overload > 10% or SBP > 150% of the starting SBP, or Hgb < 3.0 g/dL). In a separate cohort of ATLS class IV (>40% blood volume lost) hemorrhage, LTOWB yielded a higher predicted event-free survival (74%) versus the CCT arm (69%, p < 0.01). We demonstrate how this in silico platform can function as a digital twin for hemorrhagic trauma enabling precision transfusion strategies, and in parallel, an operational twin to support blood banks to forecast blood product demand and inform massive transfusion protocols and clinical trial design.