Citations

BACKGROUND: With evolving therapy for heart failure with reduced ejection fraction, the benefits of adding a defibrillator in patients undergoing cardiac resynchronization therapy (CRT) remain unclear, particularly for nonischemic cardiomyopathy (NICM). This study evaluates long-term survival among patients with NICM treated with CRT defibrillator (CRT-D) versus CRT pacemaker (CRT-P). METHODS: DECIDE-CRT (Cardiac Resynchronization With or Without Defibrillator in Non-Ischemic Cardiomyopathy) is a multicenter cohort study across 170 US Veterans Affairs hospitals. We identified patients with NICM receiving primary-prevention CRT-P or CRT-D between January 1, 2006, and December 31, 2020. Using a propensity score approach, we applied inverse probability of treatment weighting to balance baseline characteristics between the CRT-P and CRT-D groups. An inverse probability of treatment weighting–weighted Cox model estimated hazards for all-cause mortality. Secondary outcomes included generator replacement, device-related infections, hospitalization for heart failure, and ventricular arrhythmias. RESULTS: Of 16 609 CRT recipients, 3965 met NICM primary-prevention criteria (CRT-D=3158; CRT- P =807). At baseline, patients with NICM receiving CRT-P were much older, with more cardiovascular and noncardiovascular comorbidities compared with the CRT-D group. During the median follow-up of 5.2 years, the mortality rate for CRT-P versus CRT-D was 9.46 versus 9.21 per 100 person-years (RR, 0.97 [95% CI, 0.71–1.13]; P =0.66). The adjusted hazard ratio for all-cause mortality using the inverse probability of treatment weighting-Cox model was 0.90 (95% CI, 0.71–1.13; P =0.34). There was no difference in adjusted hazard for heart failure hospitalization (hazard ratio, 1.27 [95% CI, 0.86–1.87]), while the CRT-D group had higher rates of generator replacement and device-related infections. CONCLUSIONS: This nationwide observational study from the Veterans Affairs Health system did not demonstrate a clear survival advantage with the addition of a defibrillator among patients with NICM receiving CRT although residual confounding cannot be excluded. Given the uncertainty surrounding the incremental benefit of the defibrillator in this setting, a randomized trial is needed to test the incremental value of CRT-D over CRT-P in NICM.

Abstract INTRODUCTION Associations of arterial stiffness, measured through pulse wave velocity (PWV), with incident dementia may be driven by age‐related structural changes to the arterial wall or by elevated blood pressure. METHODS Dementia‐free White or Black participants in the community‐based Atherosclerosis Risk in Communities (ARIC) cohort study with measures of PWV were examined. The associations of carotid‐femoral PWV (cfPWV) and total, structural, and load‐dependent PWV with dementia were estimated using Poisson regression models and Cox proportional hazards models. Dementia cases were defined by physician‐adjudicated review, telephone interviews, hospitalization records, and death certificates. RESULTS Of 4818 participants included in the study population (mean age: 75 years; 41% male, 21% Black), 1067 (22%) developed dementia over a median follow‐up of 9.0 years. Higher cfPWV, total PWV, structural PWV, and load‐dependent PWV were associated with greater dementia risk. DISCUSSION Both structural and pressure‐related arterial stiffness mechanisms may underlie the link between PWV and dementia.

ABSTRACT Biofilm‐associated staphylococcal infections remain exceptionally difficult to treat due to the presence of resilient staphylococcal biofilms and the limited effectiveness of currently available antibiotics. To combat persistent infections, providers are often forced to use prolonged courses of combination antimicrobial therapies that have significant toxicities with limited effectiveness, leading to increased hospital stays, substantial health care costs and a rise in patient morbidity and mortality. Staphylococcus aureus is a dominant cause of recalcitrant biofilms, for which novel non‐antibiotic therapeutics are critically needed. Lysins, a class of protein‐based antimicrobials, rapidly kill staphylococci, exhibit potent anti‐biofilm activity, have a low propensity of resistance development and synergy with antibiotics. To address this unmet need, we evaluate an extracellular vesicle (EV)‐based delivery platform for the engineered anti‐staphylococcal lysin LYSG101, designed to improve stability and localization at sites of infection. Initial proof‐of‐concept work is provided here, demonstrating that human serum‐derived EVs can be loaded with LYSG101 to exert a potent in vitro antimicrobial effect against both planktonic and biofilm forms of S. aureus . EV‐mediated delivery achieved activity equivalent to free lysin, with additional translational advantages including stability and the potential for sustained intra‐articular retention. This work supports further development of the EV‐mediated lysin delivery as a broadly applicable antimicrobial platform, with potential future applications in biofilm‐associated infections, including prosthetic joint infection (PJI).

ABSTRACT Prolonged operative time is associated with increased surgical complications, resource utilization, and cost. While factors such as surgeon experience and patient habitus are well recognized, the impact of anatomical anomalies and variations remains poorly quantified. This systematic review evaluates the influence of abdominal structural anomalies and anatomical variations on operative time. Following PRISMA 2020 guidelines, a search of PubMed (2000–2025) identified 82 eligible studies. Operative‐time impact was assessed using added operative time relative to reference benchmarks. The unit of analysis was the procedure‐level observation. Observations were stratified by procedure category and surgical complexity and summarized using median added operative time and range. Among procedure‐level observations with available benchmarks, 13 of 14 (92.9%) structural anomalies, 48 of 54 (88.9%) situs inversus cases, and 10 of 11 (90.9%) other anatomical variants demonstrated increased operative time relative to baseline. Structural anomalies were associated with larger median increases, particularly in colorectal procedures, whereas anatomical variations demonstrated a more heterogeneous effect across procedural systems. Higher‐complexity procedures, including pancreatic operations, showed greater absolute increases in operative time. Preoperative identification of anatomical differences was associated with attenuation of operative delays. Structural anomalies are frequently associated with increased operative duration, whereas anatomical variations demonstrate a more variable and context‐dependent effect. The magnitude of operative time impact is influenced by procedural complexity and preoperative planning. Incorporating anatomical variability into surgical planning may reduce avoidable operative delays and improve operative efficiency.

Abstract Generative AI (Gen AI), Foundation Models (FMs), and Large Language Models (LLMs) are powerful emerging technologies that demonstrate exceptional capabilities in processing vast amounts of unstructured and structured data, including text, voice, images, video and other formats, and adapting to a wide range of specific tasks. Their immense potential to drive meaningful improvements in treatment outcomes is increasingly evident. The advent of these technologies has marked a transformative era in healthcare, including the fields of radiation oncology and medical physics. Specifically, these powerful technologies offer unprecedented opportunities to analyze domain‐specific data, process and synthesize medical images, automate routine tasks, support clinical decision‐making, optimize and streamline clinical workflows, and enhance the quality of clinical trials. While these emerging technologies present new opportunities to revolutionize radiation therapy practice, their implementation also raises important educational, ethical, and regulatory considerations. This scoping review highlights benefits, promises, risks, and challenges, such as interpretability, data privacy, regulatory compliance, reproducibility, hallucination, and integration into existing clinical workflow. Finally, emerging opportunities are outlined to guide future research directions. This review paper provides a timely overview of Gen AI, FMs and LLMs, aiming to inform medical physicists, clinicians, and researchers of the evolving role of these disruptive technologies in shaping the future of radiation therapy.

Abstract Background Lupus nephritis remains a major cause of chronic kidney disease and kidney failure in systemic lupus erythematosus. Glucocorticoids are central to treatment but are limited by systemic toxicity. We evaluated whether a previously characterized collagen IV α3-targeted liposomal nanoparticle formulation carrying low-dose prednisolone could attenuate established lupus nephritis in MRL/lpr mice. Methods Female MRL/lpr mice with disease present at treatment initiation and C57BL/6J control mice received saline or collagen IV α3-targeted prednisolone-loaded nanoparticles (Col4-α3-Pred-NPs). Renal outcomes were assessed by longitudinal proteinuria, glomerular filtration rate (GFR), survival, kidney histopathology, renal IgG and C3d deposition, dUTP/TUNEL-associated injury staining, and renal cytokine/chemokine profiling. Body weight, food and water intake, and blood glucose were monitored as measures of general condition and preliminary tolerability. Results Col4-α3-Pred-NPs improved survival in MRL/lpr mice, reduced cumulative proteinuria burden, and attenuated terminal GFR decline compared with saline-treated MRL/lpr controls. Treatment reduced glomerular and tubulointerstitial injury, lowered composite EGTI histopathology scores, decreased terminal kidney enlargement, reduced glomerular IgG deposition and renal dUTP-positive injury signals, and reduced renal signals for IL-28A/B, IL-7, PD-ECGF, IL-11, CCL6/C10, and IL-15. C3d deposition was not significantly altered. Nanoparticle treatment was not associated with sustained treatment-related increases in blood glucose or body-weight loss during the measured study period. Conclusions Collagen IV α3-targeted liposomal delivery of low-dose prednisolone attenuated established lupus nephritis in MRL/lpr mice and improved renal structural, functional, inflammatory, and survival outcomes. These findings support further evaluation of glomerulus-targeted nanotherapy as a potential strategy to improve the precision and therapeutic index of glucocorticoid treatment in lupus nephritis.

Introduction Stressful experiences may generate persistent emotional distress that could interfere with daily life. Early intervention is key to reducing those emotional disturbances and potentially preventing the development of more severe pyschopathology. The present research consists of two studies that evaluate the effects of the PASER technique on levels of emotional disturbance. Methodology In study 1, a quasi-experimental repeated-measures within-group design was used, with four assessments conducted through the APEEM inventory in relation to a non-pathological stressful situation selected by each participant. The first three measurements were mediated solely by brief imaginal exposure (inherent to the APEEM instrument) in order to control for the cumulative effects of exposure and habituation over time. Following each of these assessments, a 15-min distractor task was administered. The fourth measurement was conducted after the group application of the PASER technique. In study 2, an experimental design was conducted, assessing the effects of the variables “measurement time point” (baseline and post-test), “sex” and “intervention condition” (control vs. PASER). Results The results showed a progressive reduction in emotional disturbance as time progressed in both studies. Participants receiving PASER exhibited a significantly greater reduction in emotional disturbance than those in the control condition. These findings support the effectiveness of PASER in reducing emotional disturbance beyond the effects attributable to repeated exposure and the passage of time. Conclusions These results suggest that PASER produces an effect greater than simple exposure-based desensitization, potentially promoting memory reconsolidation processes. Longitudinal studies are recommended to confirm the stability of these effects.

Background and Goals: Spontaneous bacterial peritonitis (SBP) is a serious complication in patients with cirrhosis and ascites, with additional risks posed by multidrug-resistant organisms (MDRO). This real-world study evaluated clinical outcomes in patients with SBP and the impact of MDRO. Methods: This study identified US adults with SBP receiving guideline-recommended treatment with antibiotics and albumin from January 2012 to June 2022. Antibiotic utilization trends, health care resource utilization, and clinical outcomes [in-hospital and ICU mortality and hospital and ICU length of stay (LOS)] were assessed and stratified by MDRO status. Results: A total of 10,956 patients with 12,570 encounters were identified. Median age was 57.0 years (IQR=49.0 to 65.0), and 62.4% were male; suspected MDRO infections occurred in 15% of encounters. Third-generation cephalosporins were used in 71.6%, 49.2% had acute kidney injury, and 20.0% and 7.2% had hepatorenal syndrome and hepatic encephalopathy, respectively. Median hospital LOS was 7.2 days (IQR=4.3 to 12.9), with 17.7% in-hospital mortality. ICU care was required in 14.5% of encounters, with a median ICU LOS of 3.6 days (IQR=1.7 to 6.7) and ICU mortality of 29.7%. MDRO infections were associated with increased in-hospital mortality (OR=2.24, P <0.001) and decreased hazard of hospital discharge (ie, prolonged LOS; HR=0.43, P <0.001). Receiving albumin within 24 hours of admission was associated with a 72% higher hazard of hospital discharge (ie, shorter LOS; HR=1.72, P <0.001). Conclusion: This study highlights the clinical and resource burden of SBP, emphasizing the impact of MDRO infections and the importance of timely albumin administration concordant with clinical guidelines.

Abstract Standard of care RPT may result in dose-limiting side effects of the salivary glands include sialadenitis and xerostomia that are inconsistent with outcomes from external beam for equivalent ADs. This work develops a parametrizable ‘Macro-to-Micro’ (M2μ) model that demonstrates the consideration of small-scale dosimetry in comparison to conventional methods that typically assume uniform voxel or organ-level uptake. Anatomical features of the salivary gland are represented by annular structures (a centralized branching network of ducts, including excretory, lobar, interlobular) and small-scale voxels (intralobular ducts and acinar cells) with dimensions set to reproduce ex-vivo murine histopathology measurements and scaled up in size for extrapolation to humans. Simulations were performed by scoring and recording S-value histograms to the target ductal and acinar cells, for two beta emitters (177Lu, 131I) and one alpha emitter (225Ac). Four idealized activity distributions were created to assign activity to surface and volumes of the annuli, and GEANT4 v11 was used for radiation transport calculations. Comparisons against whole gland uniform spherical self-dose S-value calculations were conducted to validate the radiation transport and to highlight differences between M2μ and conventional dosimetry approaches. Analyses for both models showed greater S-value variation in comparison to the homogeneously distributed activity S-value calculation. The most notable result was that the calculated S-values differed between different branches, depending on the geometric size of the annuli. For the surrounding acinar cells, S-values from ductal cells decreased as a function of distance from the branching structures. High variability of S-values, depending on ductal cell dimensions as well as within the acinar cell distribution of the salivary gland highlights the potential clinical utility of small-scale approaches to RPT salivary gland dosimetry, contingent on clinical translation and validation. To this end, future work should further refine the model and incorporate small-scale activity distributions from pre-clinical and translational studies.