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Introduction:. We assessed ChatGPT-4 vision (GPT-4V)'s performance for image interpretation, diagnosis formulation, and patient management capabilities. We aim to shed light on its potential as an educational tool addressing real-life cases for medical students. Methods:. Ten of the most popular orthopaedic trauma cases from OrthoBullets were selected. GPT-4V interpreted medical imaging and patient information, providing diagnoses, and guiding responses to OrthoBullets questions. Four fellowship-trained orthopaedic trauma surgeons rated GPT-4V responses using a 5-point Likert scale (strongly disagree to strongly agree). Each of GPT-4V's answers was assessed for alignment with current medical knowledge (accuracy), rationale and whether it is logical (rationale), relevancy to the specific case (relevance), and whether surgeons would trust the answers (trustworthiness). Mean scores from surgeon ratings were calculated. Results:. In total, 10 clinical cases, comprising 97 questions, were analyzed (10 imaging, 35 management, and 52 treatment). The surgeons assigned a mean overall rating of 3.46/5.00 to GPT-4V's imaging response (accuracy 3.28, rationale 3.68, relevance 3.75, and trustworthiness 3.15). Management questions received an overall score of 3.76 (accuracy 3.61, rationale 3.84, relevance 4.01, and trustworthiness 3.58), while treatment questions had an average overall score of 4.04 (accuracy 3.99, rationale 4.08, relevance 4.15, and trustworthiness 3.93). Conclusion:. This is the first study evaluating GPT-4V's imaging interpretation, personalized management, and treatment approaches as a medical educational tool. Surgeon ratings indicate overall fair agreement in GPT-4V reasoning behind decision-making. GPT-4V performed less favorably in imaging interpretation compared with its management and treatment approach performance. The performance of GPT-4V falls below our fellowship-trained orthopaedic trauma surgeon's standards as a standalone tool for medical education.

Background: Access to catheter ablation for atrial fibrillation (AF) may vary due to social deprivation. Objectives: This study sought to characterize the correlation between our outcomes of interest (rates of AF diagnoses, ablation referrals, and procedures) and the association between social deprivation and our outcomes. Methods: Rates and correlations of AF diagnoses, ablation referrals, and procedures were reported across 49 census divisions in Ontario, Canada. We used the Ontario Marginalization Index to determine the relationship between dependency, material deprivation, ethnic concentration, and residential instability and our outcomes. Results: Between April 2016 and March 2020, there were 146,366 patients diagnosed with AF; 6,506 patients were referred for ablation; and 4,673 patients underwent de novo ablation. The median age was 72 years (IQR: 61-81 years; 45% female) for the AF cohort and 62 years (IQR: 55-69 years, 33% to 34% female) for the referral and procedure cohorts. There was geographic variation and a weak concordance between AF diagnoses, ablation referrals, and procedures (correlation coefficients 0.33-0.36). Increased material deprivation was associated with more AF diagnoses (rate ratio [RR]: 1.13), but fewer ablation referrals (RR: 0.49) and procedures (RR: 0.48). Increased residential instability was associated with more AF diagnoses (RR: 1.02), but fewer ablation referrals (RR: 0.63) and procedures (RR: 0.64). Higher ethnic concentration was associated with fewer AF diagnoses, ablation referrals, and procedures. Conclusions: In a jurisdiction with universal health care, greater material deprivation and residential instability were associated with more AF diagnoses but less access to ablation, suggesting substantial social gradients in equitable access to AF care.

Introduction: Central nervous system (CNS) metastases remain a common challenge in patients with ALK-positive NSCLC. We previously reported reinduction of CNS responses using dose-intensified alectinib in two patients with CNS progression on standard-dose alectinib. Nevertheless, this strategy has not been assessed in larger cohorts. Methods: Patients were eligible for this retrospective study if they had metastatic ALK-positive NSCLC with CNS relapse on alectinib 600 mg twice daily dosing and subsequently received escalated dosing (900 mg twice daily) of alectinib. CNS efficacy was assessed per the modified Response Evaluation Criteria in Solid Tumors version 1.1. Results: Among 27 patients, median duration of dose-escalated alectinib was 7.7 months (95% confidence interval [CI]: 4.8–10.9), with median overall time-to-progression (TTP) of 7.1 months (95% CI: 4.4–9.6). Among 25 CNS response-assessable patients, CNS objective response rate was 12.0% (95% CI: 2.5–31.2) and CNS disease control rate was 92.0% (95% CI: 74.0–99.0), with median CNS duration of disease control of 5.3 months (95% CI: 3.4–8.3) and median CNS TTP of 7.1 months (95% CI: 4.4–9.6). Among four patients with measurable CNS disease at baseline, three experienced a best intracranial response of stable disease and one experienced intracranial partial response with CNS TTP ranging from 4.1 to 7.7 months. No patient required drug discontinuation due to treatment-related adverse event or experienced grade 3 or higher treatment-related adverse events. Conclusions: Dose-intensified alectinib was found to have tolerability and activity in patients with ALK-positive NSCLC who experienced CNS relapse on standard-dose alectinib and represents one clinically viable strategy for this population.

BACKGROUND: Unrecognized diabetes mellitus during pregnancy could pose serious maternal and neonatal complications. A hemoglobin A1c level of ≥6.5% was used to diagnose both diabetes mellitus in nonpregnant individuals and diabetes in pregnancy. As the hemoglobin A1c level could be influenced by maternal physiological changes, the optimal cutoff in early pregnancy to detect women with diabetes in pregnancy and associated complications remains unclear. OBJECTIVE: This study aimed to evaluate the diagnostic performance of various hemoglobin A1c levels and the optimal hemoglobin A1c cutoff to identify mothers with diabetes in pregnancy diagnosed by the gold standard 75 g oral glucose tolerance test before 24 weeks of gestation. In addition, the pregnancy and neonatal outcomes were compared using the optimal hemoglobin A1c cutoff. STUDY DESIGN: A retrospective cohort study was conducted between 2004 and 2019. Women with at least 1 risk factor of gestational diabetes mellitus received an oral glucose tolerance test before 24 weeks of gestation. Terminology of hyperglycemia first detected during pregnancy by oral glucose tolerance test was classified as either diabetes in pregnancy or gestational diabetes mellitus following the World Health Organization's recommendation. Women who met the diagnostic criteria of diabetes in pregnancy and early-onset gestational diabetes mellitus (ie, before 24 weeks of gestation) and had a paired hemoglobin A1c measurement within 4 weeks of their early oral glucose tolerance test were studied. Sensitivity, specificity, and positive and negative predictive values at various hemoglobin A1c cutoffs were calculated for the detection of diabetes in pregnancy. The optimal hemoglobin A1c level was identified from the constructed receiver operating characteristic curves. Multivariate binary logistic regression analyses were performed to calculate the unadjusted and adjusted odds ratios for pregnancy complications. RESULTS: There were 63,111 deliveries, and 22,949 women underwent an oral glucose tolerance test before 24 weeks of gestation. A total of 157 and 3210 women met the diagnostic criteria of diabetes in pregnancy and early-onset gestational diabetes mellitus using an oral glucose tolerance test, respectively. Only 346 participants had a paired hemoglobin A1c and oral glucose tolerance test measurement (82 cases with diabetes in pregnancy and 264 cases with early-onset gestational diabetes mellitus). The receiver operating characteristic curve identified an optimal hemoglobin A1c cutoff of 5.7% to diagnose diabetes in pregnancy, with a sensitivity of 64.6%, specificity of 81.1%, positive predictive value of 51.5%, and negative predictive value of 88.1%. A hemoglobin A1c cutoff of either 5.9% or 6.5% could miss 47.6% or 73.2% of women with diabetes in pregnancy. In multivariate logistic regression analysis, a hemoglobin A1c level of ≥5.7% increased the risk of maternal insulin use (adjusted odds ratio, 6.69; 95% confidence interval, 3.44–12.99), macrosomia (adjusted odds ratio, 7.43; 95% confidence interval, 1.90–29.00), and shoulder dystocia (adjusted odds ratio, 6.56; 95% confidence interval, 1.161–37.03). CONCLUSION: The optimal hemoglobin A1c cutoff to detect diabetes in pregnancy diagnosed using an oral glucose tolerance test before 24 weeks of gestation was 5.7%, but this cutoff could not reliably identify diabetes in pregnancy owing to the low sensitivity. However, an early hemoglobin A1c level of ≥5.7% indicated increased risks of pregnancy and neonatal complications.

Purpose: The purpose of this study was to identify factors associated with unanticipated radiation therapy (RT) replanning in stage III non-small cell lung cancer (NSCLC). Methods and Materials: Patients from a single institution with newly diagnosed stage III NSCLC treated with radical RT from January 1, 2016, to December 31, 2019, were retrospectively analyzed. The frequency and reasons for replanning were determined. Logistic regression analysis was used to identify factors associated with replanning. Results: Of 144 patients included in this study, 11% (n = 16) required replanning after the start of RT. The reason for replanning in these 16 patients was changes in the target detected by cone beam computed tomography (shift in 10 patients, shrinkage in 5 patients, and growth in 1 patient). Larger planning target volume (primary and nodal) was statistically predictive of replanning (odds ratio, 2.5; 95% CI, 1.2-5.4; P = .02). The actuarial median overall survival was 33.3 months (95% CI, 10.3-43.9) for the 16 patients who were replanned and 36.3 months (95% CI, 27.4-66.5) for the remaining 128 patients (P = .96). The median time to local recurrence was 25.0 months (95% CI, 10.3-41.3) for those patients who underwent replanning, which was similar to those patients who did not undergo replanning (19.5 months; 95% CI, 11.8-23.2; P = .28). Conclusions: In this study, 11% of patients treated with radical RT for NSCLC required replanning due to changes in the target detected by cone beam computed tomography. A larger planning target volume predicts a higher likelihood of requiring adaptive RT. Overall survival and local control were similar between patients who were replanned compared with those who were not replanned.

Artificial intelligence (AI) and machine learning (ML) have significantly impacted the field of cardiovascular medicine, especially cardiac electrophysiology (EP), on multiple fronts. The goal of this review is to familiarize readers with the field of AI and ML and their emerging role in EP. The current review is divided into 3 sections. In the first section, we discuss the definitions and basics of AI, ML, and big data. In the second section, we discuss their application to EP in the context of detection, prediction, and management of arrhythmias. Finally, we discuss the regulatory issues, challenges, and future directions of AI in EP.

Purpose: To develop a fully-automatic hybrid algorithm to jointly segment and quantify biomarkers of polypoidal choroidal vasculopathy (PCV) on indocyanine green angiography (ICGA) and spectral domain-OCT (SD-OCT) images. Design: Evaluation of diagnostic test or technology. Participants: Seventy-two participants with PCV enrolled in clinical studies at Singapore National Eye Center. Methods: The dataset consisted of 2-dimensional (2-D) ICGA and 3-dimensional (3-D) SD-OCT images which were spatially registered and manually segmented by clinicians. A deep learning-based hybrid algorithm called PCV-Net was developed for automatic joint segmentation of biomarkers. The PCV-Net consisted of a 2-D segmentation branch for ICGA and 3-D segmentation branch for SD-OCT. We developed fusion attention modules to connect the 2-D and 3-D branches for effective use of the spatial correspondence between the imaging modalities by sharing learned features. We also used self-supervised pretraining and ensembling to further enhance the performance of the algorithm without the need for additional datasets. We compared the proposed PCV-Net to several alternative model variants. Main Outcome Measures: The PCV-Net was evaluated based on the Dice similarity coefficient (DSC) of the segmentations and the Pearson’s correlation and absolute difference of the clinical measurements obtained from the segmentations. Manual grading was used as the gold standard. Results: The PCV-Net showed good performance compared to manual grading and alternative model variants based on both quantitative and qualitative analyses. Compared to the baseline variant, PCV-Net improved the DSC by 0.04 to 0.43 across the different biomarkers, increased the correlations, and decreased the absolute differences of clinical measurements of interest. Specifically, the largest average (mean ± standard error) DSC improvement was for intraretinal fluid, from 0.02 ± 0.00 (baseline variant) to 0.45 ± 0.06 (PCV-Net). In general, improving trends were observed across the model variants as more technical specifications were added, demonstrating the importance of each aspect of the proposed method. Conclusion: The PCV-Net has the potential to aid clinicians in disease assessment and research to improve clinical understanding and management of PCV. Financial Disclosure(s): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

A 79-year-old woman with a history of dilated cardiomyopathy who required a permanent peacemaker, recently upgraded to implantable cardioverter-defibrillator cardiac resynchronization therapy, was admitted for right heart failure. On echocardiography, torrential tricuspid regurgitation was noted, with 2 leads across the valve. After multidisciplinary evaluation, a dedicated transcatheter valve replacement was successfully implanted. (Level of Difficulty: Intermediate.)

Introduction: Landmark trials testing immune checkpoint inhibitors (ICIs) in advanced NSCLC are difficult to extrapolate to real-world practice given the exclusion of patients with poor (i.e., ≥2) Eastern Cooperative Oncology Group performance status (ECOG PS). We sought to evaluate the impact of ECOG PS on clinical outcomes and health care utilization in patients with NSCLC treated with ICIs in real-world practice. Methods: Patients with advanced NSCLC who received at least one dose of pembrolizumab or nivolumab were retrospectively identified from the Alberta Immunotherapy Database. The primary outcome was median overall survival, as stratified by ECOG PS. Secondary outcomes included median time-to-treatment failure and metrics of health care utilization, including emergency department visits, hospitalizations, and death in hospital. Results: A total of 790 patients were included, with 29.2% having poor ECOG PS at initiation of ICI. These patients had significantly lower median overall survival (3.3 versus 13.4 mo) and median time-to-treatment failure (1.4 versus 4.9 mo) compared with those with favorable ECOG PS (p < 0.0001 for both outcomes). Patients with poor ECOG PS were also more likely to present to the emergency department, be admitted to the hospital, and die in the hospital during their first admission (risk ratio = 1.6, 2.3–2.7, p < 0.001). Conclusions: Patients with NSCLC with poor ECOG PS treated with ICI had significantly worse survival outcomes and were significantly more likely to use health care services than those with favorable ECOG PS. The large proportion of patients with poor ECOG PS further justifies the urgent need for randomized trials evaluating the efficacy of ICI in this high-risk population.

Introduction: BRAF mutations (present in 2%–3% of NSCLC) are a known oncogenic driver and emerging therapeutic target. There is a scarcity of real-world data describing the clinical characteristics, treatment patterns, and effectiveness of targeted BRAF-inhibiting and immune checkpoint inhibitor (ICI)-based systemic therapies, yet this is required for appropriate treatment decisions that optimize patient outcome. Methods: Demographic, clinical, treatment, and outcome data of patients with BRAF mutation-positive NSCLC diagnosed between 2018 and 2022 were identified from the Glans-Look Lung Cancer Research database and included in this analysis. Results: A total of 53 BRAF mutation-positive patients were identified (V600E, n = 35; non-V600E, n = 18). Furthermore, 46 patients (87%) were diagnosed with metastatic disease, of whom 61% were treated with systemic anticancer therapy, which significantly improved overall survival (34.1 versus 2.2 mo, p = 0.01). ICI-based regimens were found to have effectiveness in the first-line setting for both V600E and non-V600E cohorts (objective response rate: 38%–43%; real-world calculations of median progression-free survival: 10.5–10.8 mo, respectively). Dual-targeted BRAF/MEK inhibition was also found to have effectiveness in the first-line setting for V600E patients (objective response rate: 33%, real-world calculations of median progression-free survival: 15.2 mo). Conclusions: This study of real-world patients with BRAF mutations confirms the importance of effective systemic therapies. Both dual-targeted BRAF/MEK inhibition and ICI-based regimens have evidence of benefit in this population revealing that real-world populations can experience similar clinical response and outcome to clinical trial cohorts on these treatment regimens. Future studies to clarify the role of co-mutations on response to both dual-targeted BRAF/MEK inhibition and ICI-based regimens may be important to treatment selection and optimization of patient outcome.

OBJECTIVES:. Proliferation of COVID-19 research underscored the need for improved awareness among investigators, research staff and bedside clinicians of the operational details of clinical studies. The objective was to describe the genesis, goals, participation, procedures, and outcomes of two research operations committees in an academic ICU during the COVID-19 pandemic. DESIGN:. Two-phase, single-center multistudy cohort. SETTING:. University-affiliated ICU in Hamilton, ON, Canada. PATIENTS:. Adult patients in the ICU, medical stepdown unit, or COVID-19 ward. INTERVENTIONS:. None. MEASUREMENTS AND MAIN RESULTS:. An interprofessional COVID Collaborative was convened at the pandemic onset within our department, to proactively coordinate studies, help navigate multiple authentic consent encounters by different research staff, and determine which studies would be suitable for coenrollment. From March 2020 to May 2021, five non-COVID trials continued, two were paused then restarted, and five were launched. Over 15 months, 161 patients were involved in 215 trial enrollments, 110 (51.1%) of which were into a COVID treatment trial. The overall informed consent rate (proportion agreed of those eligible and approached including a priori and deferred consent models) was 83% (215/259). The informed consent rate was lower for COVID-19 trials (110/142, 77.5%) than other trials (105/117, 89.7%; p = 0.01). Patients with COVID-19 were significantly more likely to be coenrolled in two or more studies (29/77, 37.7%) compared with other patients (13/84, 15.5%; p = 0.002). Review items for each new study were collated, refined, and evolved into a modifiable checklist template to set up each study for success. The COVID Collaborative expanded to a more formal Department of Critical Care Research Operations Committee in June 2021, supporting sustainable research operations during and beyond the pandemic. CONCLUSIONS:. Structured coordination and increased communication about research operations among diverse research stakeholders cultivated a sense of shared purpose and enhanced the integrity of clinical research operations.

Objective: Lipid dysregulation and complement system (CS) activation are 2 important pathophysiology pathways for age-related macular degeneration (AMD). We hypothesized that the relationship between lipids and AMD may also differ according to CS genotype profile. Thus, the objective was to investigate the relationships between lipid-related metabolites and AMD according to CS genotypes. Design: Population-based cross-sectional study. Participants: A total of 6947 participants from Singapore Epidemiology of Eye Diseases study with complete relevant data were included. Methods: We investigated a total of 32 blood lipid–related metabolites from nuclear magnetic resonance metabolomics data including lipoproteins and their subclasses, cholesterols, glycerides, and phospholipids, as well as 4 CS single nucleotide polymorphisms (SNPs): rs10922109 (complement factor H), rs10033900 (complement factor I), rs116503776 (C2-CFB-SKIV2L), and rs2230199 (C3). We first investigated the associations between AMD and the 32 lipid-related metabolites using multivariable logistic regression models. Then, to investigate whether the effect of lipid-related metabolites on AMD differ according to the CS SNPs, we tested the possible interactions between the CS SNPs and the lipid-related metabolites. Main Outcome Measures: Age-related macular degeneration was defined using the Wisconsin grading system. Results: Among the 6947 participants, the prevalence of AMD was 6.1%, and the mean age was 58.3 years. First, higher levels of cholesterol in high-density lipoprotein (HDL) and medium and large HDL particles were associated with an increased risk of AMD, and higher levels of serum total triglycerides (TG) and several very-low–density lipoprotein subclass particles were associated with a decreased risk of AMD. Second, these lipids had significant interaction effects on AMD with 2 CS SNPs: rs2230199 and rs116503776 (after correction for multiple testing). For rs2230199, in individuals without risk allele, higher total cholesterol in HDL2 was associated with an increased AMD risk (odds ratio [OR] per standard deviation increase, 1.20; 95% confidence interval (CI), 1.06–1.37; P = 0.005), whereas, in individuals with at least 1 risk allele, higher levels of these particles were associated with a decreased AMD risk (OR, 0.69; 95% CI, 0.45–1.05; P = 0.079). Conversely, for rs116503776, in individuals without risk allele, higher serum total TG were associated with a decreased AMD risk (OR, 0.84; 95% CI, 0.74–0.95; P = 0.005), whereas, in individuals with 2 risk alleles, higher levels of these particles were associated with an increased risk of AMD (OR, 2.3, 95% CI, 0.99–5.39, P = 0.054). Conclusions: Lipid-related metabolites exhibit opposite directions of effects on AMD according to CS genotypes. This indicates that lipid metabolism and CS may have synergistic interplay in the AMD pathogenesis.

Background: The optimal timing of catheter ablation for the treatment of ventricular tachycardia (VT) in patients with ischemic cardiomyopathy remains unclear. Studies examining the impact of early preventive ablation of VT on rates of implantable cardioverter-defibrillator (ICD) therapies and mortality have been limited by small sample size. Objectives: To conduct a meta-analysis of randomized controlled trials (RCTs) comparing initial catheter ablation and ICD implantation (preventive ablation arm) vs ICD implantation alone (deferred ablation arm) in patients with ischemic cardiomyopathy and VT. Methods: The primary endpoint was the incidence of appropriate ICD therapy during follow-up. Secondary endpoints included appropriate ICD shock, VT storm, procedural complications, and mortality. Sensitivity analysis, meta-regression, and evaluation of bias were performed. Results: Four RCTs (n = 505) fulfilled inclusion criteria. During follow-up (mean >22 months for all RCTs), preventive ablation was associated with a significant reduction in ICD therapies (odds ratio [95% confidence interval]: 0.53 [0.36–0.78]). The occurrence of ICD shocks and VT storm were also significantly reduced in the preventive ablation group. Among patients with left ventricular ejection fraction (LVEF) >30%, preventive ablation was associated with marked reduction in ICD therapy when compared to deferred ablation (odds ratio [95% confidence interval]: 0.37 [0.19–0.72]). Overall, there was no difference in mortality between treatment groups. Conclusions: Preventive catheter ablation in patients with ischemic cardiomyopathy decreases ICD therapies, ICD shocks, and VT storm without increasing complications, particularly in patients with LVEF >30%. However, early preventive ablation is not associated with any benefit in mortality.

Background: Glenoid retroversion and humeral head subluxation have been suggested to lead to inferior outcomes after total shoulder arthroplasty (TSA). There are limited data to support this suggestion. We investigated whether preoperative glenoid retroversion and humeral head subluxation are associated with inferior outcomes after TSA and whether change of retroversion influences outcomes after TSA. Methods: Patients undergoing TSA with minimum 2-year follow-up were included from a prospectively collected institutional shoulder arthroplasty database. Retroversion and humeral head subluxation before and after surgery were measured on axillary radiographs. Postoperative radiographs were -evaluated for glenoid component loosening and compared between groups. Spearman correlations were determined between retroversion measurements and American Shoulder and Elbow Surgeons Standardized Shoulder Assessment Form (ASES) scores. Patients were analyzed in groups based on retroversion and humeral head subluxation. Results: There were 113 patients (50% follow-up rate) evaluated at 4.2 years postoperatively. The mean preoperative retroversion (15.3° ± 7.7°) was significantly higher than postoperative retroversion (10.0° ± 6.8°; P < .0001). There was no correlation between postoperative glenoid version or humeral head subluxation and ASES scores. For patients with preoperative retroversion of >15°, there was no difference in outcome scores based on postoperative retroversion. There were no differences in preoperative or postoperative version for patients with or without glenoid lucencies. Discussion: We observed no significant relationship between postoperative glenoid retroversion or humeral head subluxation and clinical outcomes in patients following TSA. For patients with preoperative retroversion >15°, change of retroversion during TSA had no impact on their clinical outcomes at short-term follow-up.

Purpose: To establish the safety and efficacy of gantry-mounted linear accelerator-based stereotactic body radiation therapy (SBRT) for low- and intermediate-risk prostate cancer. Methods: We pooled 921 patients enrolled on 7 single-institution prospective phase II trials of gantry-based SBRT from 2006 to 2017. The cumulative incidences of biochemical recurrence (defined by the Phoenix definition) and physician-scored genitourinary (GU) and gastrointestinal (GI) toxicities (defined per the original trials using Common Terminology Criteria for Adverse Events) were estimated using a competing risk framework. Multivariable logistic regression was used to evaluate the relationship between late toxicity and prespecified covariates: biologically effective dose, every other day versus weekly fractionation, intrafractional motion monitoring, and acute toxicity. Results: Median follow-up was 3.1 years (range, 0.5-10.8 years). In addition, 505 (54.8%) patients had low-risk disease, 236 (25.6%) had favorable intermediate-risk disease, and 180 (19.5%) had unfavorable intermediate-risk disease. Intrafractional motion monitoring was performed in 78.0% of patients. The 3-year cumulative incidence of biochemical recurrence was 0.8% (95% confidence interval [CI], 0-1.7%), 2.2% (95% CI, 0-4.3%), and 5.1% (95% CI, 1.0-9.2%) for low-, favorable intermediate-, and unfavorable intermediate-risk disease. Acute grade ≥2 GU and GI toxicity occurred in 14.5% and 4.6% of patients, respectively. Three-year cumulative incidence estimates of late grade 2 GU and GI toxicity were 4.1% (95% CI, 2.6-5.5%) and 1.3% (95% CI, 0.5-2.1%), respectively, with late grade ≥3 GU and GI toxicity estimates of 0.7% (95% CI, 0.1-1.3%) and 0.4% (95% CI, 0-0.8%), respectively. The only identified significant predictors of late grade ≥2 toxicity were acute grade ≥2 toxicity (P < .001) and weekly fractionation (P < .01), although only 12.4% of patients were treated weekly. Conclusions: Gantry-based SBRT for prostate cancer is associated with a favorable safety and efficacy profile, despite variable intrafractional motion management techniques. These findings suggest that multiple treatment platforms can be used to safely deliver prostate SBRT.

Post-explant (ex vivo) evaluation of medical devices is an essential part of quality assurance, quality improvement, and further device development. Central to this is detailed pathological analysis. Here, we provide the first such evaluation of an explanted Tiara transcatheter mitral valve prosthesis. (Level of Difficulty: Advanced.)

Objectives: This study evaluates the impact of socioeconomic status (SES) on utilization of mechanical circulatory support (MCS) devices and outcomes in cardiogenic shock (CS). Background: CS is associated with significant mortality. There is increasing use of temporary MCS devices in CS, and its impact on outcomes is currently under investigation. There is a lack of data on the effect of SES on the utilization of MCS devices in CS. Methods: CS hospitalizations were obtained from the State Inpatient Databases in 2016 from 9 states representing various regions in the United States. The study had exempt institutional review board status as the database includes deidentified data. Hospitalizations were separated into SES cohorts based on the median household income of the patient residence zip code. Utilization of MCS devices and revascularization procedures along with clinical outcomes with CS were compared across the quartiles. Results: There were 38,520 hospitalizations identified with CS, 42.6% of which were secondary to acute myocardial infarction. Patients from higher SES areas were significantly older but had lower burden of comorbidities. Utilization of temporary MCS devices was higher for hospitalizations from higher SES regions (frequency from the lowest SES quartile to the highest SES quartile: 21.3%, 21.5%, 23.5, and 24.1%, P

Introduction: The real-world data evaluating treatment outcomes of atezolizumab plus carboplatin-etoposide chemotherapy (atezolizumab) for extensive-stage SCLC (ESCLC) are lacking. Our objective was to evaluate real-world outcomes of ESCLC treated with atezolizumab. Methods: A retrospective analysis of provincial patients with ESCLC who started first-line (1L) systemic treatment was conducted. We primarily evaluated the progression-free survival (PFS) and overall survival (OS) outcomes in association with atezolizumab compared with platinum-etoposide chemotherapy (chemotherapy) while adjusting for relevant demographic and clinical factors. Adverse events (AEs) during 1L were evaluated. Results: A total of 67 patients were identified. Of the 34 patients who received atezolizumab, 24% had Eastern Cooperative Oncology Group performance status greater than or equal to 2, approximately 50% were more than or equal to 65 years, 21% received cisplatin-etoposide chemotherapy before atezolizumab, and 12% had thoracic radiation (tRT).Within the atezolizumab versus chemotherapy group, the median PFS equals to 6.0 versus 4.3 months (p = 0.03) whereas OS = 12.8 versus 7.1 months (p = 0.01). Relative to chemotherapy, the hazard ratio (95% confidence interval) for PFS was 0.53 (0.28–1.02) and OS was 0.42 (0.20–0.88) with atezolizumab. tRT compared with no tRT receipt correlated with reduced death risk (hazard ratio [95% confidence interval] = 0.33 [0.13–0.88]).AE-related treatment withdrawal with atezolizumab was 32% and 15% with chemotherapy (p = 0.02). Within the tRT subgroup, 25% versus 20% in atezolizumab versus chemotherapy group, respectively, discontinued 1L owing to AE. Conclusions: This is the first real-world study revealing comparable survival with that in the IMpower133 trial. Treatment discontinuation from AEs was higher with atezolizumab among Canadian patients with ESCLC. Our data suggest safe use of tRT and chemoimmunotherapy, but its efficacy for ESCLC warrants further study.

Background Reverse total shoulder arthroplasty (rTSA) offers tremendous promise for the treatment of complex pathologies beyond the scope of anatomic total shoulder arthroplasty but is associated with a higher rate of major postoperative complications. We aimed to design and validate a machine learning (ML) model to predict major postoperative complications or readmission following rTSA. Methods We retrospectively reviewed California's Office of Statewide Health Planning and Development database for patients who underwent rTSA between 2015 and 2017. We implemented logistic regression (LR), extreme gradient boosting (XGBoost), gradient boosting machines, adaptive boosting, and random forest classifiers in Python and trained these models using 64 binary, continuous, and discrete variables to predict the occurrence of at least one major postoperative complication or readmission following primary rTSA. Models were validated using the standard metrics of area under the receiver operating characteristic (AUROC) curve, area under the precision–recall curve (AUPRC), and Brier scores. The key factors for the top-performing model were determined. Results Of 2799 rTSAs performed during the study period, 152 patients (5%) had at least 1 major postoperative complication or 30-day readmission. XGBoost had the highest AUROC and AUPRC of 0.681 and 0.129, respectively. The key predictive features in this model were patients with a history of implant complications, protein-calorie malnutrition, and a higher number of comorbidities. Conclusion Our study reports an ML model for the prediction of major complications or 30-day readmission following rTSA. XGBoost outperformed traditional LR models and also identified key predictive features of complications and readmission.

Objective Recent reports have shown that outpatient shoulder arthroplasty (SA) may be a safe alternative to inpatient management in appropriately selected patients. The purpose was to review the literature reporting on outpatient SA. Methods A systematic review of publications on outpatient SA was performed. Included publications discussed patients who were discharged on the same calendar day or within 23 hours from surgery. Articles were categorized by discussions on complications, readmissions, and safety, patient selection, pain management strategies, cost effectiveness, and patient and surgeon satisfaction. Results Twenty-six articles were included. Patients undergoing outpatient SA were younger and with a lower BMI than those undergoing inpatient SA. Larger database studies reported more medical complications for patients undergoing inpatient compared to outpatient SA. Articles on pain management strategies discussed both single shot and continuous interscalene blocks with similar outcomes. Both patients and surgeons reported high levels of satisfaction following outpatient SA, and cost analysis studies demonstrated significant cost savings for outpatient SA. Conclusion In appropriately selected patients, outpatient SA can be a safe, cost-saving alternative to inpatient care and may lead to high satisfaction of both patients and physicians, though further studies are needed to clarify appropriate utilization of outpatient SA.

Summary: Background: Coronary artery calcium (CAC) score is a clinically validated marker of cardiovascular disease risk. We developed and validated a novel cardiovascular risk stratification system based on deep-learning-predicted CAC from retinal photographs. Methods: We used 216 152 retinal photographs from five datasets from South Korea, Singapore, and the UK to train and validate the algorithms. First, using one dataset from a South Korean health-screening centre, we trained a deep-learning algorithm to predict the probability of the presence of CAC (ie, deep-learning retinal CAC score, RetiCAC). We stratified RetiCAC scores into tertiles and used Cox proportional hazards models to evaluate the ability of RetiCAC to predict cardiovascular events based on external test sets from South Korea, Singapore, and the UK Biobank. We evaluated the incremental values of RetiCAC when added to the Pooled Cohort Equation (PCE) for participants in the UK Biobank. Findings: RetiCAC outperformed all single clinical parameter models in predicting the presence of CAC (area under the receiver operating characteristic curve of 0·742, 95% CI 0·732–0·753). Among the 527 participants in the South Korean clinical cohort, 33 (6·3%) had cardiovascular events during the 5-year follow-up. When compared with the current CAC risk stratification (0, >0–100, and >100), the three-strata RetiCAC showed comparable prognostic performance with a concordance index of 0·71. In the Singapore population-based cohort (n=8551), 310 (3·6%) participants had fatal cardiovascular events over 10 years, and the three-strata RetiCAC was significantly associated with increased risk of fatal cardiovascular events (hazard ratio [HR] trend 1·33, 95% CI 1·04–1·71). In the UK Biobank (n=47 679), 337 (0·7%) participants had fatal cardiovascular events over 10 years. When added to the PCE, the three-strata RetiCAC improved cardiovascular risk stratification in the intermediate-risk group (HR trend 1·28, 95% CI 1·07–1·54) and borderline-risk group (1·62, 1·04–2·54), and the continuous net reclassification index was 0·261 (95% CI 0·124–0·364). Interpretation: A deep learning and retinal photograph-derived CAC score is comparable to CT scan-measured CAC in predicting cardiovascular events, and improves on current risk stratification approaches for cardiovascular disease events. These data suggest retinal photograph-based deep learning has the potential to be used as an alternative measure of CAC, especially in low-resource settings. Funding: Yonsei University College of Medicine; Ministry of Health and Welfare, Korea Institute for Advancement of Technology, South Korea; Agency for Science, Technology, and Research; and National Medical Research Council, Singapore.

Objective Coronavirus disease 2019 (COVID-19) is associated with olfactory dysfunction, but the evolution of the olfactory loss and timeline to recovery are largely unknown. This study examines changes in smell sensitivity in COVID-19–positive (COVID+) and COVID-19–negative (COVID–) viral illness during the initial weeks after infection. Study Design Cross-sectional cohort comparison. Setting National anonymous surveys. Methods Survey participants were queried about smell sensitivity and general health status at the time of COVID-19 testing and in the weeks that followed. Results In total, 375 (174 COVID+, 201 COVID–) participants completed the survey and 132 (62 COVID+, 70 COVID–) participants completed the 2-week follow-up survey. Normal smell in the COVID+ cohort was less frequent at the time of testing and at follow up ( P < .05). Dynamic changes in smell sensitivity in the COVID+ cohort were more frequent in the initial weeks ( P < .001). In those with normosmia at the start of infection, 38% of the COVID+ cohort reported worsening smell compared to only 8% in the COVID– cohort ( P < .05). Recovery of overall health was associated with normosmia at the time of infection and improvement of smell sensitivity within weeks of infection. Conclusion The COVID+ cohort showed greater dynamic change in smell sensitivity and a higher rate of persistent olfactory dysfunction in the weeks after infection. Normal smell at the time of COVID-19 infection may still worsen before recovery. Overall health recovery after viral illness is associated with improvement in smell sensitivity and the absence of initial anosmia or hyposmia.

Background:. Implant-related symptoms are the most common reason for reoperation after open reduction and internal fixation (ORIF) of midshaft clavicular fractures. Dual mini-fragment plate fixation is a relatively new solution that may decrease implant prominence while maintaining fixation strength and function. There are minimal published data comparing reoperation rates and clinical outcomes between single, superior-plate constructs and dual mini-fragment plate constructs in the fixation of midshaft clavicular fractures. We hypothesized that reducing plate size with the use of dual mini-fragment plating compared with standard, 3.5-mm, superior plating would minimize implant symptoms and the corresponding need for reoperation while still providing sufficient fixation to allow fracture-healing and return to function. Methods:. We retrospectively reviewed the cases of 44 consecutive patients who underwent ORIF of displaced midshaft clavicular fractures utilizing either a single, 3.5-mm, superior plate construct (21 patients) or a dual, 2.7-mm and 2.4-mm, plate construct (23 patients). Outcomes at a minimum of 2 years were assessed. Primary outcome measures included reoperation for any reason and the American Shoulder and Elbow Surgeons (ASES) Standardized Shoulder Assessment Form, patient self-report section. Results:. There was a 100% union rate in both groups. None (0%) of the 23 patients who received the dual (2.7-mm and 2.4-mm) plate construct and 6 (29%) of the 21 patients who received the single (3.5-mm) plate construct underwent reoperation for implant-related symptoms. Using a Fisher exact test, the rate of reoperation was compared between the groups, and the difference was found to be significant (p = 0.008). Using an unpaired t test, the difference in mean ASES scores was not significant (p = 0.138) between the dual-plate group (98 of 100) and the single superior plate group (96 of 100) with retained implants. Conclusions:. In our comparative retrospective series, dual fixation utilizing a 2.7-mm superior plate and a 2.4-mm anterior plate for the treatment of displaced midshaft clavicular fractures was associated with a significantly lower rate of reoperation when compared with single, 3.5-mm, superior plate fixation. Level of Evidence:. Therapeutic Level III. See Instructions for Authors for a complete description of levels of evidence.

Background There are limited data on the effect of glenoid retroversion in clinical outcomes following reverse total shoulder arthroplasty (RTSA). The purpose of this study was to evaluate if surgical correction of retroversion affects outcomes following RTSA. Methods An institutional database was utilized to identify 177 patients (mean age: 68.2 ± 10.1 years) with minimum 2-year follow-up after primary RTSA. Glenoid version was measured on preoperative and postoperative radiographs. American Shoulder and Elbow Surgeons (ASES) scores and range of motion were collected before and after RTSA. Change in retroversion was determined by comparing preoperative and postoperative glenoid retroversion on radiographs using paired Wilcoxon signed-rank test. Spearman’s rank correlation was used to investigate relationships between ASES scores and glenoid retroversion. Results The mean postoperative ASES composite score (75.5 ± 22.7) was significantly higher than preoperative (36.8 ± 19.2; P

Solitary fibrous tumors/hemangiopericytomas (SFT/HPC) are soft tissue tumors that can arise from the abdomen, pleura, head and neck, or extremities. We report an unusual case of recurrent hemangiopericytoma in a 67-year-old female presenting with a painless and palpable mass within her right posterior neck. Eight years after initial resection of the mass, a follow-up MRI showed multiple enlarging calvarial lesions. A whole body FDG-PET/CT revealed not only hypermetabolic calvarial lesions but also numerous hypermetabolic axillary node and osseous metastases. Though the majority of these soft tissue tumors exhibit benign behavior and carry a favorable prognosis, patients with these slow growing tumors are at risk for local recurrence and distant metastases which demonstrate substantial FDG avidity. Additional studies are needed to clarify the role of whole body FDG-PET/CT in the surveillance of SFT/HPC to detect recurrent or metastatic lesions. Keywords: Solitary fibrous tumor, Hemangiopericytoma, Metastases

ABSTRACT: Objective: Gorham-Stout disease (GSD), otherwise known as vanishing bone disease, is a rare disorder that is associated with bone destruction resulting in massive osteolysis secondary to proliferation of vascular channels. The exact etiology and mechanism of bone resorption is unknown. The disease process can be benign and self-limiting or progressive and life-threatening. The optimal initial evaluation, follow-up, and treatment procedures have not yet been defined. Various treatments and modalities have been suggested and include bisphosphonates, alpha-2β interferon, external beam radiation therapy, and surgery.Methods: Systematic literature searches were performed using the PubMed and EMBASE databases.Results: We present the case of a 20-year-old, asymptomatic man with incidentally noted lucency of the T3, T4, and T5 posterior ribs on chest radiograph. Follow-up imaging identified progressive osteolysis consistent with a diagnosis of GSD. Initial workup revealed a significantly low level of 25-hydroxyvitamin D (9 ng/mL; adequate is >30 ng/mL) and mild elevation of the bone formation markers pro-collagen 1 intact N-terminal peptide (102 μg/L; reference range is 22 to 87 μg/L) and bone-specific alkaline phosphatase (23 μg/L; reference range is 0 to 20 μg/L). His C-telopeptide level was normal (521 pg/mL; reference range is 90 to 750 pg/mL) but was higher than the median of the reference range. He was started on cholecalciferol at 2,000 IU daily and treated with a 5-mg, intravenous infusion of zoledronic acid.Conclusion: The initial presentation of GSD can provoke significant anxiety in both patients and their clinicians given the potential significant outcomes and paucity of data on the evaluation and management of this disease. Here we propose a method for initial diagnostic workup and follow-up.Abbreviations: CT computed tomography GSD Gorham-Stout disease

The B-cell lymphoma 2–associated anthanogene (BAG3) protein is expressed most prominently in the heart, the skeletal muscle, and in many forms of cancer. In the heart, it serves as a co-chaperone with heat shock proteins in facilitating autophagy; binds to B-cell lymphoma 2, resulting in inhibition of apoptosis; attaches actin to the Z disk, providing structural support for the sarcomere; and links the α-adrenergic receptor with the L-type Ca2+ channel. When BAG3 is overexpressed in cancer cells, it facilitates prosurvival pathways that lead to insensitivity to chemotherapy, metastasis, cell migration, and invasiveness. In contrast, in the heart, mutations in BAG3 have been associated with a variety of phenotypes, including both hypertrophic/restrictive and dilated cardiomyopathy. In murine skeletal muscle and vasculature, a mutation in BAG3 leads to critical limb ischemia after femoral artery ligation. An understanding of the biology of BAG3 is relevant because it may provide a therapeutic target in patients with both cardiac and skeletal muscle disease.

We present a case of adult-onset Kawasaki disease shock syndrome complicated by coronary aneurysms, in which profound hypotension and reduced left ventricular ejection fraction were treated successfully with intravenous immunoglobulin. The diagnosis of Kawasaki disease shock syndrome should be considered in cases of rapidly developing shock, particularly in young adults with an infectious prodrome, in whom it may be under-recognized. We advocate for early identification to minimize delays in treatment with intravenous immunoglobulin, which reverses left ventricular dysfunction and decreases risk of long-term sequelae such as coronary artery aneurysms. Résumé: Nous présentons un cas de syndrome de choc dans la maladie de Kawasaki survenu à l'âge adulte et compliqué par des anévrismes des artères coronaires, chez lequel l'injection d'immunoglobulines par voie intraveineuse a permis de traiter avec succès une hypotension prononcée et une fraction d'éjection ventriculaire gauche réduite. Le diagnostic de syndrome de choc dans la maladie de Kawasaki devrait être envisagé dans les cas de choc évoluant rapidement, en particulier chez les jeunes adultes en phase prodromique d'une infection, chez lesquels cette affection peut passer inaperçue. Nous préconisons un diagnostic précoce afin de réduire au minimum les délais du traitement aux immunoglobulines par voie intraveineuse qui a pour effet d'inverser la dysfonction ventriculaire gauche et de diminuer le risque de séquelles à long terme, comme l'anévrisme des coronaires.

Mutations in Bcl-2–associated athanogene 3 (BAG3) were associated with skeletal muscle dysfunction and dilated cardiomyopathy. Retro-orbital injection of an adeno-associated virus serotype 9 expressing BAG3 (rAAV9-BAG3) significantly (p < 0.0001) improved left ventricular ejection fraction, fractional shortening, and stroke volume 9 days post-injection in mice with cardiac dysfunction secondary to a myocardial infarction. Furthermore, myocytes isolated from mice 3 weeks after injection showed improved cell shortening, enhanced systolic [Ca2+]i and increased [Ca2+]i transient amplitudes, and increased maximal L-type Ca2+ current amplitude. These results suggest that BAG3 gene therapy may provide a novel therapeutic option for the treatment of heart failure.

Background: Tenofovir (TDF)-based highly active antiretroviral therapy (HAART), as recommended by the World Health Organization guidelines for HIV-naive patients, has been limited in resource-constrained settings. The aim of this study was to evaluate the effectiveness of zidovudine-(ZDV) versus TDF-based HAART in the Yi minority region of Sichuan Province, China at a single HIV treatment center. Methods: The primary end point was the attainment of an HIV viral load

Background: Numerous population-based studies of age-related macular degeneration have been reported around the world, with the results of some studies suggesting racial or ethnic differences in disease prevalence. Integrating these resources to provide summarised data to establish worldwide prevalence and to project the number of people with age-related macular degeneration from 2020 to 2040 would be a useful guide for global strategies. Methods: We did a systematic literature review to identify all population-based studies of age-related macular degeneration published before May, 2013. Only studies using retinal photographs and standardised grading classifications (the Wisconsin age-related maculopathy grading system, the international classification for age-related macular degeneration, or the Rotterdam staging system) were included. Hierarchical Bayesian approaches were used to estimate the pooled prevalence, the 95% credible intervals (CrI), and to examine the difference in prevalence by ethnicity (European, African, Hispanic, Asian) and region (Africa, Asia, Europe, Latin America and the Caribbean, North America, and Oceania). UN World Population Prospects were used to project the number of people affected in 2014 and 2040. Bayes factor was calculated as a measure of statistical evidence, with a score above three indicating substantial evidence. Findings: Analysis of 129 664 individuals (aged 30–97 years), with 12 727 cases from 39 studies, showed the pooled prevalence (mapped to an age range of 45–85 years) of early, late, and any age-related macular degeneration to be 8·01% (95% CrI 3·98–15·49), 0·37% (0·18–0·77), and 8·69% (4·26–17·40), respectively. We found a higher prevalence of early and any age-related macular degeneration in Europeans than in Asians (early: 11·2% vs 6·8%, Bayes factor 3·9; any: 12·3% vs 7·4%, Bayes factor 4·3), and early, late, and any age-related macular degeneration to be more prevalent in Europeans than in Africans (early: 11·2% vs 7·1%, Bayes factor 12·2; late: 0·5% vs 0·3%, 3·7; any: 12·3% vs 7·5%, 31·3). There was no difference in prevalence between Asians and Africans (all Bayes factors

Background: Conventional autologous skin grafts are associated with significant donor-site morbidity. This study was conducted to determine feasibility, safety, and efficacy of a new strategy for skin grafting based on harvesting small columns of full-thickness skin with minimal donor-site morbidity. Methods: The swine model was used for this study. Hundreds of full-thickness columns of skin tissue (~700 µm diameter) were harvested using a custom-made harvesting device, and then applied directly to excisional skin wounds. Healing in donor and graft sites was evaluated over 3 months by digital photographic measurement of wound size and blinded, computer-aided evaluation of histological features and compared with control wounds that healed by secondary intention or with conventional split-thickness skin grafts (STSG). Results: After harvesting hundreds of skin columns, the donor sites healed rapidly without scarring. These sites reepithelialized within days and were grossly and histologically indistinguishable from normal skin within 7 weeks. By contrast, STSG donor sites required 2 weeks for reepithelialization and retained scar-like characteristics in epidermal and dermal architecture throughout the experiment. Wounds grafted with skin columns resulted in accelerated reepithelialization compared with ungrafted wounds while avoiding the “fish-net” patterning caused by STSG. Conclusion: Full-thickness columns of skin can be harvested in large quantities with negligible long-term donor-site morbidity, and these columns can be applied directly to skin wounds to enhance wound healing.