Citations

Abstract Objective Flares of autoimmune rheumatic diseases (AIRDs) following COVID-19 vaccination are a particular concern in vaccine-hesitant individuals. Therefore, we investigated the incidence, predictors and patterns of flares following vaccination in individuals living with AIRDs, using global COVID-19 Vaccination in Autoimmune Diseases (COVAD) surveys. Methods The COVAD surveys were used to extract data on flare demographics, comorbidities, COVID-19 history, and vaccination details for patients with AIRDs. Flares following vaccination were identified as patient-reported (a), increased immunosuppression (b), clinical exacerbations (c) and worsening of PROMIS scores (d). We studied flare characteristics and used regression models to differentiate flares among various AIRDs. Results Of 15 165 total responses, the incidence of flares in 3453 patients with AIRDs was 11.3%, 14.8%, 9.5% and 26.7% by definitions a–d, respectively. There was moderate agreement between patient-reported and immunosuppression-defined flares (K = 0.403, P = 0.022). Arthritis (61.6%) and fatigue (58.8%) were the most commonly reported symptoms. Self-reported flares were associated with higher comorbidities (P = 0.013), mental health disorders (MHDs) (P < 0.001) and autoimmune disease multimorbidity (AIDm) (P < 0.001). In regression analysis, the presence of AIDm [odds ratio (OR) = 1.4; 95% CI: 1.1, 1.7; P = 0.003), or a MHD (OR = 1.7; 95% CI: 1.1, 2.6; P = 0.007), or being a Moderna vaccine recipient (OR = 1.5; 95% CI: 1.09, 2.2; P = 0.014) were predictors of flares. Use of MMF (OR = 0.5; 95% CI: 0.3, 0.8; P = 0.009) and glucocorticoids (OR = 0.6; 95% CI: 0.5, 0.8; P = 0.003) were protective. A higher frequency of patients with AIRDs reported overall active disease post-vaccination compared with before vaccination (OR = 1.3; 95% CI: 1.1, 1.5; P < 0.001). Conclusion Flares occur in nearly 1 in 10 individuals with AIRDs after COVID vaccination; people with comorbidities (especially AIDm), MHDs and those receiving the Moderna vaccine are particularly vulnerable. Future avenues include exploring flare profiles and optimizing vaccine strategies for this group.

AbstractBackgroundData for proton therapy in high‐risk prostate cancer (HRPC) are limited. Using the Proton Collaborative Group prospective registry, we evaluated outcomes for HRPC patients treated with proton therapy.MethodsA totsl of 605 men with localized HRPC treated with proton therapy from 8/2009 to 3/2019 at nine institutions were selected. Outcomes examined included freedom from progression (FFP), metastasis free survival (MFS), overall survival (OS), and toxicity. Multivariable cox/binomial regression models were used to assess predictors of FFP and toxicity.ResultsMedian age was 71 years. Gleason grade groups 4 (49.4%) and 5 (31.7%) were most common, as were clinical stage T1c (46.1%) and cT2 (41.3%). The median pretreatment prostate specific antigen (PSA) was 9.18 and median International Prostate Symptom Score (IPSS) was 6. Androgen deprivation therapy was given in 63.6%. Median dose was 79.2 GyE in 44 fractions. Pelvic lymph nodes were treated in 58.2% of cases. Pencil beam scanning was used in 54.5%, uniform scanning in 38.8%, and a rectal spacer in 14.2%. At a median followup of 22 months, the 3‐ and 5‐year FFP were 90.7% and 81.4%, respectively. Five‐year MFS and OS were 92.8% and 95.9%, respectively. Independent correlates of FFP included Gleason ≥8, PSA > 10, and cT2 (all p < 0.05). No grade 4 or 5 adverse events were reported. There were 23 (5%) grade 2 and 0 grade 3 gastrointestinal events. Prevalence of late grade 3, late grade 2, acute grade 3, and acute grade 2 genitourinary toxicity was 1.7%, 5.8%, 0%, and 21.8%, respectively. Prevalence of grade 2 and 3 erectile dysfunction at 2 years was 48.4% and 8.4%, respectively.ConclusionsIn the largest series published to date, our results suggest early outcomes using proton therapy for HRPC are encouraging for both safety and efficacy. Further evaluation is needed to determine if an advantage exists to use protons over other radiation techniques in this population.

Objective: This study is a comprehensive review of the clinical pharmacology, pharmacokinetics, efficacy, safety, and clinical applicability of amivantamab-vmjw for metastatic non-small cell lung cancer (NSCLC) with epidermal growth factor receptor (EGFR) exon 20 insertion (exon20ins) mutation. Data Synthesis: The literature search to identify clinical trials returned only the CHRYSALIS phase 1 study. In a phase I trial, amivantamab-vmjw was associated with an overall response rate (ORR) of 40% (95% CI, 29–51) in the EGFR exon20ins NSCLC patient population (n = 81) after platinum-based chemotherapy. There were 3 complete responses (CRs) and 29 partial responses (PRs). The median duration of response (DOR) was 11.1 months (95% CI, 6.9—not reached; NR). The median progression-free survival (PFS) was 8.3 months (95% CI, 6.5–10.9), and overall survival (OS) was 22.8 months (95% CI, 14.6—NR). Application to Clinical Practice: This review summarizes the pharmacology, clinical evidence, and use of amivantamab-vmjw for patients with locally advanced or metastatic NSCLC with EGFR exon20ins mutation. Conclusion: The FDA approval of amivantamab-vmjw, the first bispecific antibody to target the exon20ins mutation, represents an important advancement in the treatment of patients with NSCLC with limited effective treatment options. The initial findings of the CHRYSALIS trial demonstrate an overall tumor response benefit with an acceptable safety profile.

Abstract Background Over the past decade, the use of technology‐enhanced simulation in emergency medicine (EM) education has grown, yet we still lack a clear understanding of its effectiveness. This systematic review aims to identify and synthesize studies evaluating the comparative effectiveness of technology‐enhanced simulation in EM. Methods We searched MEDLINE, EMBASE, PsycINFO, CINAHL, ERIC, Web of Science, and Scopus to identify EM simulation research that compares technology‐enhanced simulation with other instructional modalities. Two reviewers screened articles for inclusion and abstracted information on learners, clinical topics, instructional design features, outcomes, cost, and study quality. Standardized mean difference (SMD) effect sizes were pooled using random effects. Results We identified 60 studies, enrolling at least 5279 learners. Of these, 23 compared technology‐enhanced simulation with another instructional modality (e.g., living humans, lecture, small group), and 37 compared two forms of technology‐enhanced simulation. Compared to lecture or small groups, we found simulation to have nonsignificant differences for time skills (SMD 0.33, 95% confidence interval [CI] −0.23 to 0.89, n = 3), but a large, significant effect for non–time skills (SMD 0.82, 95% CI 0.18 to 1.46, n = 8). Comparison of alternative types of technology‐enhanced simulation found favorable associations with skills acquisition, of moderate magnitude, for computer‐assisted guidance (compared to no computer‐assisted guidance), for time skills (SMD 0.50, 95% CI −1.66 to 2.65, n = 2) and non–time skills (SMD 0.57, 95% CI 0.33 to 0.80, n = 6), and for more task repetitions (time skills SMD 1.01, 95% CI 0.16 to 1.86, n = 2) and active participation (compared to observation) for time skills (SMD 0.85, 95% CI 0.25 to 1.45, n = 2) and non–time skills (SMD 0.33 95% CI 0.08 to 0.58, n = 3). Conclusions Technology‐enhanced simulation is effective for EM learners for skills acquisition. Features such as computer‐assisted guidance, repetition, and active learning are associated with greater effectiveness.

475 Background: Emerging evidence supports use of neoadjuvant chemotherapy (NAC) prior to radical nephroureterectomy (RNU) for appropriately selected patients with upper tract urothelial carcinoma (UTUC). However, oncologic outcomes have not been well characterized for patients with residual muscle-invasive disease after NAC. Methods: We used a multi-institutional cohort from 24 centers in the U.S., Europe, and Japan to retrospectively identify patients who underwent RNU for UTUC from 1985-2022 and had high-grade muscle-invasive disease. We stratified the cohort based on receipt of NAC (>ypT2 vs. >pT2). Exclusion criteria included receipt of adjuvant chemotherapy, concurrent cystectomy with RNU, and distant metastatic disease. Baseline characteristics were compared between groups. Kaplan-Meier survival analysis with log-rank test was used to compare differences in recurrence-free survival (RFS), overall survival (OS), and cancer-specific survival (CSS). Multivariable Cox regression and Fine-Gray competing risk regression were used to determine predictors of these outcomes. Results: A total of 1,233 patients were included, 62 of whom received NAC prior to RNU. A platinum-based regimen was used in 90% of NAC recipients, and the median number of cycles administered was 4 (IQR: 3-5). Median follow-up time among all patients was 22 months (IQR: 8-47 mo.). NAC recipients were more likely to have pathologic node positivity (35% vs. 13%) and less likely to have positive tumor margins (8% vs. 28%). On Kaplan-Meier analysis, NAC recipients with residual >ypT2 disease had poorer outcomes than those with >pT2 disease (2-year RFS [NAC vs. no NAC]: 52% vs. 80%, p<0.001; 2-year OS: 60% vs. 78%, p=0.003; 2-year CSS: 61% vs. 86%, p<0.001). Multivariable analyses also showed a statistically significant association between residual muscle-invasive disease after NAC and poorer RFS, OS, and CSS (Table). Conclusions: NAC recipients with >ypT2 disease at RNU after exhibit poorer outcomes than stage-matched chemotherapy naïve counterparts. This may reflect effects of occult micrometastatic disease or chemoresistant primary tumors in non-responders. Our data highlight the need to improve prospective identification of candidates most likely to respond to NAC prior to RNU for UTUC in order to maximize its therapeutic benefit. [Table: see text]

Purpose: Quantitative biomarkers from chest computed tomography (CT) can facilitate the incidental detection of important diseases. Atrial fibrillation (AFib) substantially increases the risk for comorbid conditions including stroke. This study investigated the relationship between AFib status and left atrial enlargement (LAE) on CT. Materials and Methods: A total of 500 consecutive patients who had undergone nongated chest CTs were included, and left atrium maximal axial cross-sectional area (LA-MACSA), left atrium anterior-posterior dimension (LA-AP), and vertebral body cross-sectional area (VB-Area) were measured. Height, weight, age, sex, and diagnosis of AFib were obtained from the medical record. Parametric statistical analyses and receiver operating characteristic curves were performed. Machine learning classifiers were run with clinical risk factors and LA measurements to predict patients with AFib. Results: Eighty-five patients with a diagnosis of AFib were identified. Mean LA-MACSA and LA-AP were significantly larger in patients with AFib than in patients without AFib (28.63 vs. 20.53 cm2, P<0.000001; 4.34 vs. 3.5 cm, P<0.000001, respectively), both with area under the curves (AUCs) of 0.73. Multivariable logistic regression analysis including age, sex, and VB-Area with LA-MACSA improved the AUC for predicting AFib (AUC=0.77). An LA-MACSA threshold of 30 cm2 demonstrated high specificity for AFib diagnosis at 92% and sensitivity of 48%, and LA-AP threshold at 4.5 cm demonstrated 90% specificity and 42% sensitivity. A Bayesian machine learning model using age, sex, height, body surface area, and LA-MACSA predicted AFib with an AUC of 0.743. Conclusions: LA-MACSA or LA-AP can be rapidly measured from routine chest CT, and when >30 cm2 and >4.5 cm, respectively, are specific indicators to predict patients at increased risk for AFib.

AbstractIntroductionIn October 2021, the American Society of Transplantation (AST) hosted a virtual consensus conference aimed at identifying and addressing barriers to the broader, safe expansion of living donor liver transplantation (LDLT) throughout the United States (US).MethodsA multidisciplinary group of LDLT experts convened to address issues related to financial implications on the donor, transplant center crisis management, regulatory and oversight policies, and ethical considerations by assessing the relative significance of issues in preventing LDLT growth, with proposed strategies to overcome barriers.ResultsLiving liver donors endure multiple obstacles including financial instability, loss of job security, and potential morbidity. These concerns, along with other center, state, and federal specific policies can be perceived as significant barriers to expanding LDLT. Donor safety is of paramount importance to the transplant community; however, regulatory and oversight policies aimed at ensuring donor safety can be viewed as ambiguous and complicated leading to time‐consuming evaluations that may deter donor motivation and program expansion.ConclusionTransplant programs need to establish appropriate crisis management plans to mitigate potential negative donor outcomes and ensure program viability and stability. Finally, ethical aspects, including informed consent for high‐risk recipients and use of non‐directed donors, can be perceived as additional barriers to expanding LDLT.

AbstractBackgroundPatients with gastroparesis (Gp) may need enteral nutrition (EN) or exclusive parenteral nutrition (PN). Among patients with Gp, we aimed to (1) identify the frequency of EN and exclusive PN use and (2) explore characteristics of patients using EN and/or exclusive PN compared with those using oral nutrition (ON), including changes over 48 weeks.MethodsPatients with Gp underwent history and physical examination, gastric emptying scintigraphy, water load satiety testing (WLST), and questionnaires assessing gastrointestinal symptoms and quality of life (QOL). Patients were observed 48 weeks.ResultsOf 971 patients with Gp (idiopathic, 579; diabetic, 336; post–Nissen fundoplication, 51), 939 (96.7%) were using ON only, 14 (1.4%) using exclusive PN, and 18 (1.9%) using EN. Compared with patients receiving ON, patients receiving exclusive PN and/or EN were younger, had lower body mass index, and had greater symptom severity. Patients receiving exclusive PN and/or EN had lower physical QOL but not mental QOL or Gp‐related QOL scores. Patients receiving exclusive PN and/or EN ingested less water during WLST but did not have worse gastric emptying. Of those who had been receiving exclusive PN and/or EN, 50% and 25%, respectively, resumed ON at 48‐week follow‐up.ConclusionsThis study describes patients with Gp requiring exclusive PN and/or EN for nutrition support, who represent a small (3.3%) but important subset of patients with Gp. Unique clinical and physiological parameters are associated with this subset and provide insight into the use of nutrition support in Gp.