Citations

Current treatments for choroidal neovascularization (CNV) and its associated subretinal fibrosis (SRF), major causes of vision loss, are limited by the need for frequent intravitreal injections and the emergence of drug resistance. This study evaluated the safety and efficacy of the intravitreal administration of engineered humanized anti-vascular endothelial growth factor Nanobodies, including a wild-type Nanobody (WHNb) and two mutated variants (MHNb136 and MHNb256), in a rat model of laser-induced CNV and associated SRF. Safety was assessed through in vivo electrophysiological and histopathological analyses following intravitreal injection of Nanobodies at doses of 12.5, 25, 50, and 100 µg. Efficacy was evaluated in rat models of laser-induced CNV and SRF using double immunohistochemistry for isolectin B4 and anti-collagen type I on sclerochoroidal flat mounts. Mean CNV and SRF areas in Nanobody-treated groups were compared with those in bevacizumab-treated and sham control groups. None of the Nanobodies showed retinal toxicity in safety assessments. Compared with bevacizumab, MHNb136 and MHNb256 reduced the CNV area by 1.72-fold and 1.8-fold, respectively (both p < 0.0001), whereas WHNb showed an effect nearly identical to that of bevacizumab. In addition, 12.5 µg MHNb136 and 100 µg MHNb256 reduced the SRF area by 1.3-fold (p = 0.047) and 1.6-fold (p = 0.0007), respectively, relative to bevacizumab. For CNV reduction, 12.5 µg MHNb136 was comparable to 25 µg MHNb256; both outperformed bevacizumab. For SRF reduction, 12.5 µg MHNb136 was more effective than bevacizumab and comparable to 100 µg MHNb256. These findings suggest that 12.5 µg MHNb136 may represent a cost-effective bioengineered Nanobody candidate for future clinical studies.

Background: The impact of obesity on outcomes following total ankle arthroplasty (TAA) remains unclear, with existing literature reporting mixed results. Although some studies have identified obesity as a risk factor for perioperative complications and poor clinical outcomes, others have found no significant association. Thus, the purpose of this study was to evaluate the association between obesity, across a range of body mass index (BMI) classifications, and postoperative complications after TAA. Methods: Patients undergoing primary TAA were identified from a large national insurance database. Individuals with a BMI ≥30 were identified and matched 1:1 to nonobese controls using propensity score matching based on demographics and comorbidities. Obese patients were further stratified into BMI categories: 30-34.9, 35-39.9, 40-44.9, and ≥45. Ninety-day complications and 2-, 5-, and 10-year surgery-specific outcomes were assessed. Odds ratios (ORs) with 95% CIs and Kaplan-Meier survival analyses were used to evaluate complication risks. Results: After matching, 3364 patients were included in each cohort. No significant differences in 90-day complication rates were observed for patients with BMI 30-44.9 compared with controls. Patients with BMI ≥45 had increased risk of surgical site infection (OR 2.21, 95% CI 1.29-3.79, P = .003), emergency department visits (OR 1.43, 95% CI 1.04-1.96, P = .025), and readmissions (OR 2.31, 95% CI 1.47-3.63, P < .001). The pooled 90-day complication rate was significantly higher in this group as well (12.9% vs 7.6%, OR 1.77, 95% CI 1.26-2.48, P < .001). At 10-year follow-up, Kaplan-Meier analysis demonstrated that patients with a BMI ≥45 had a higher risk of periprosthetic joint infection (PJI compared with controls (hazard ratio 1.75, 95% CI 1.07-2.85, P = .03). Patients with BMI 30-34.9 had a significantly lower risk of aseptic loosening at both 5 years (OR 0.68, 95% CI 0.49-0.94, P = .019) and 10 years (OR 0.65, 95% CI 0.48-0.88, P = .005). Conclusion: BMI ≥45 was associated with higher all-cause health care utilization, including emergency department visits and hospital readmissions, as well as higher long-term risk of PJI following TAA. Level of Evidence: Level III, retrospective cohort study.

Background The purpose of this study was to assess the clinical benefits of guideline‐directed medical therapy (GDMT) for heart failure (HF) in adults with congenital heart disease and HF with reduced ejection fraction. Methods HF with reduced ejection fraction was defined as stage B/C HF and systemic left ventricular ejection fraction <50%. GDMT score was assessed at baseline encounter (baseline GDMT score) and 1‐year follow‐up. GDMT uptitration was calculated as defined as ∆GDMT score from baseline. Cox regression was used to assess the relationship between HF therapy (baseline and ∆GDMT score) and outcomes (HF hospitalization and mortality). Results Of 778 patients (age 44±16, 480 [62%] males), baseline GDMT score was 2 (1, 3) and ∆GDMT score was 0.62 (95% CI, 0.55–0.69). Of 778, only 258 (33%) had GDMT uptitration (∆GDMT score >0). Higher use of GDMT at baseline (adjusted HR per 1 point increase in GDMT score 0.81, 95% CI, 0.74–0.88, P <0.001), and increased use of GDMT over time (adjusted HR for 1 point increase in ∆GDMT score HR 0.70, 95% CI, 0.61–0.79, P <0.001) were associated with lower risk of HF hospitalization. Higher baseline GDMT score (adjusted HR 0.85, 95% CI, 0.76–0.94, P <0.001), and ∆ GDMT score (adjusted HR 0.82, 95% CI, 0.71–0.94, P <0.000) were also associated with lower mortality. Conclusions GDMT use at baseline and GDMT uptitration were associated with improved outcomes and suggest a dose‐dependent relationship between use of GDMT and risk of adverse outcomes. Furthermore, 67% of patients did not receive GDMT uptitration, suggesting suboptimal therapy, and opportunities for improvement.

Objective The Accreditation Council for Graduate Medical Education (ACGME) introduced Milestones in 2013 to aid the assessment of residents and fellows within the framework of the six core competencies of practice. Feedback from program directors and trainees, clinical competency committee processes, and milestone reporting identified the need for modification. This study represents a consensus-driven educational quality improvement initiative which describes the development, revision process, and key features of Critical Care Anesthesiology (CCA) Milestones 2.0, and provides lessons learned in adapting competency-based assessment to a one-year subspecialty training program. Methods A Critical Care Anesthesiology (CCA) working group was convened by the ACGME in 2021 to revise the content, enhance relevance to training, clarify goals for program leadership, and develop supplemental resources to aid implementation. The group consisted of a diverse group of experienced educators and clinicians from CCA fellowship programs nationwide. A modified Delphi process, stakeholder feedback, Milestones performance data, and public comment were used to iteratively revise Milestones. In addition, a supplemental guide was developed to provide examples and resources to aid the Milestones assessment. Conclusion The Milestones 2.0 simplify the use, implementation, and interpretation of this competency framework for program directors, trainees, faculty, and the American Board of Anesthesiology. The resulting CCA Milestones 2.0 provide updated specialty-specific, competency-based behavioral anchors to guide the developmental progression of competencies and outcomes for CCA fellows and facilitate the design of curricula and the advancement of CCA training programs. Lessons learned in the development of the CCA Milestones 2.0 include the importance of simplification, behavioral specificity, and supplemental.

Abstract Purpose Crisis periods—defined as sustained disruptions to the clinical environment resulting in increased workload, exposure to high-acuity patient care, or limited access to coping resources—can lead to posttraumatic stress disorder (PTSD) among residents and fellows (trainees). By examining self-reported pandemic-related PTSD symptoms, associated risk factors, and their consequences, this study aims to identify vulnerable groups and inform institutional strategies to support trainee well-being during and after crisis events. Method A multi-institutional cross-sectional survey was conducted at 3 U.S. academic medical centers between April and May 2022. Measures included the Primary Care PTSD Screen for DSM-5 (range 0 to 5, scores ≥4 indicate probable PTSD), 4-item PROMIS Social Isolation scale (normed T-score range 0 to 100 scale with higher scores indicating greater isolation), items exploring intent to stay at one’s institution, and demographics. Multivariable analysis adjusted for demographics, specialty, and postgraduate year. Results Of 6,057 eligible trainees, 3,185 (53%) participated in the survey, with 3,109 completing the PTSD screening. A total of 190 (6%) trainees screened positive for self-reported PTSD symptoms. Multivariable analysis revealed that female trainees had a higher odds of screening positive for self-reported PTSD symptoms compared to males (odds ratio [OR] 1.45; 95% confidence interval [CI], 1.03-2.04; P = .03). Greater social isolation was independently associated with increased PTSD risk (OR 1.09; 95% CI, 1.07-1.11; P &lt; .001). Additionally, trainees who did not intend to remain at their institution after training were more likely to screen positive for PTSD (OR 1.74; 95% CI, 1.17-2.58; P = .01). Conclusions Female gender, greater social isolation, and reduced intention to remain at one’s institution are independently associated with self-reported PTSD symptoms in trainees. Recognizing these relationships may enable health care leaders to proactively identify trainees at higher risk during crisis periods and to implement targeted, evidence-based interventions that promote well-being and workforce retention.

Introduction: Adequate bladder distention is critical for safe and efficient transurethral morcellation during endoscopic prostate enucleation. Traditional assessment methods are subjective and may compromise safety and efficiency. We evaluated the feasibility and impact of continuous intravesical pressure (IVP) monitoring using a handheld pressure meter during morcellation compared with conventional manual bladder assessment. Material and Methods: In this prospective, randomized pilot study, 30 patients undergoing transurethral morcellation after bipolar prostate enucleation were randomized 1:1 to continuous IVP monitoring with a handheld pressure meter (Group A) or manual suprapubic bladder assessment by a urology fellow (Group B). In Group A, morcellation was performed while IVP remained within a predefined safe range (15–60 mmHg), with pauses for pressure correction as needed. The primary outcome was the number of morcellation pauses. Secondary outcomes included morcellation time, morcellation efficiency (g/min), total operative time, hemoglobin deficit, complications, and functional outcomes (International Prostate Symptom Score, maximum urinary flow rate, and post-void residual) at 3 and 6 months. Results: Baseline characteristics were comparable between groups. Morcellation time was significantly shorter in Group A (8.9 ± 3.7 vs 13.3 ± 2.1 minutes; p = 0.0008), with fewer morcellation pauses (3.3 ± 0.7 vs 5.7 ± 1.2; p < 0.0001) and higher morcellation efficiency (9.9 ± 2.0 vs 5.9 ± 0.6 g/min; p < 0.0001). Enucleation time, total operative time, tissue weight, and hemoglobin deficit were similar. No bladder injuries or postoperative fever occurred. Functional outcomes at 3 and 6 months were comparable. Conclusion: Continuous IVP monitoring using a handheld pressure meter during transurethral morcellation is feasible, reduces interruptions, and significantly improves morcellation efficiency without compromising safety or functional outcomes. This inexpensive technique may be a valuable safety adjunct, particularly for less experienced surgeons, and merits evaluation in larger randomized trials.

The growing population of older cancer survivors faces an elevated risk of accelerated cognitive decline due to the combined effects of aging and cancer-related cognitive impairment. Loneliness and social isolation have also been linked to poorer cognitive outcomes and increased risk of Alzheimer’s Disease and Related Dementias (ADRD). At the same time, regular physical activity and social support interventions may improve cognitive function and reduce risk of cognitive decline. Despite these parallel lines of evidence, few interventions have addressed these modifiable risk factors simultaneously, particularly among older cancer survivors. In this perspective, we propose that group-based exercise may provide synergistic benefits for cognitive health by addressing both physical activity and social engagement. We present a conceptual model in which participation in group exercise promotes exercise-induced neurobiological adaptations that support cognitive function while simultaneously enhancing social connectedness. These processes may reduce loneliness and social isolation, promoting cognitive engagement. We also highlight key considerations for future research, including the potential for virtual or remotely delivered group exercise to increase accessibility, the importance of group dynamics in fostering social support, and the need to incorporate validated measures of loneliness, social isolation, and cognitive function in intervention studies.

ABSTRACT Background Predictors of complications and length of stay (LOS) in patients requiring brief inpatient stays after total thyroidectomy remain poorly understood. We identify preoperative risk factors for complications, differentiate predictors of overnight versus two‐day stays and estimate associated hospital costs. Methods The National Inpatient Sample for 2016–2021 was used to analyse adult patients undergoing total thyroidectomy with LOS = 1 or 2 days. Multivariate regressions identified predictors of complications and LOS. Costs were transformed logarithmically. Results Of 26 560 patients, 70% had an overnight stay. Two‐day stays were associated with higher complication rates, comorbidity index, neck dissection and increased cost. Hispanic and Asian or Pacific Islander race, comorbidity and surgery in a rural hospital increased the risk of any thyroidectomy‐specific complication. Two‐day stays had a 29% higher cost than overnight stays. Conclusions Preoperative characteristics can help predict complications and LOS following total thyroidectomy. Risk stratification supports cost‐effective, patient‐centred care planning.

Abstract Background Machine learning models for chest X‐ray (CXR)‐based tuberculosis (TB) detection often suffer from performance drops when deployed across institutions due to domain shifts caused by differences in patient populations, imaging protocols, and equipment. Domain adaptation has been widely studied to address the problem, but privacy regulations restrict data sharing, making conventional approaches infeasible. Purpose We aim to enhance TB detection performance when a detector model is shared across multiple clinical sites without accessing any source data or statistics. This problem is related to source‐free domain adaptation (SFDA) but requires special designs for imbalanced binary classification. Methods We propose two methods for TB detection, which are based on Source HypOthesis Transfer (SHOT) and SFDA via source Distribution Estimation (SFDA‐DE), respectively. As the main ideas of our methods, we propose ranking‐based pseudo‐labeling and selective fine‐tuning of network layers to address severe class imbalance and prevent overfitting. Results On six unseen target domains with high class imbalance, our proposed SFDA methods significantly improved the average F1 score and AUROC compared to non‐adapted models, all without accessing source data during adaptation. Conclusions Our methods offer a privacy‐preserving and effective strategy to improve the generalization of TB detection models across institutions, addressing domain shifts while complying with data‐sharing restrictions.