THE IMPACT OF ROUTINE CARDIAC TROPONIN I-BASED CARDIOTOXICITY SCREENING ON CLINICAL OUTCOMES IN PATIENTS ON CANCER IMMUNOTHERAPY.

Purpose: Immune checkpoint inhibitors (ICI) used as cancer therapy have been associated with a range of cardiac immune-related adverse events (irAEs), including fulminant myocarditis with a high case fatality rate. Early detection through cardiotoxicity screening by biomarker monitoring can lead to prompt intervention and improved patient outcomes. In this study, we investigate the association between cardiotoxicity screening with routine serial troponin I monitoring in asymptomatic patients receiving ICI, cardiovascular adverse event (CV AE) detection, and overall survival (OS). Methods: We instituted a standardized troponin I screening protocol at baseline and with each ICI dose (every 2-4 weeks) in all patients receiving ICI at our center starting Jan 2019. We subsequently collected data in 825 patients receiving ICI at our institution from January 2018 to October 2021. Of these patients, 428 underwent cardiotoxicity screening with serial troponin I monitoring during ICI administration (Jan 2019-Oct 2021) and 397 patients were unmonitored (Jan 2018-Dec 2018). We followed patients for nine months following their first dose of ICI and compared outcomes of CV AEs and OS between monitored and unmonitored patients. Additionally, we investigated rates of CV AEs, all-cause mortality, and oncologic time-to-treatment failure (TTF) between patients with an elevated troponin I value during the monitoring period versus patients without elevated troponin I. Results: We found a lower rate of severe (grades 4-5) CV AEs, resulting in critical illness or death, in patients who underwent troponin monitoring (0.5%) compared to patients who did not undergo monitoring (1.8%), (HR 0.17, 95% CI 0.02-0.79, p = 0.04). There was no difference in overall CV AEs (grades 3-5) or OS between monitored and unmonitored patients. In the entire cohort, patients with at least one elevated troponin I during the follow up period, during routine monitoring or unmonitored, had a higher risk of overall CV AEs (HR 10.96, 95% CI 4.65-25.85, p<0.001) as well as overall mortality (HR 2.67, 95% CI 1.69 - 4.10, p<0.001) compared to those without elevated troponin. Oncologic time-to-treatment failure (TTF) was not significantly different in a sub-cohort of monitored vs. unmonitored patients. Conclusions: Patients undergoing cardiotoxicity screening with troponin I monitoring during ICI therapy had a lower rate of severe (grade 4-5) CV AEs compared patients who were not screened. Troponin I elevation in screened and unscreened patients was significantly associated with increased CV AEs as well as increased mortality. Troponin I monitoring did not impact oncologic time-to-treatment-failure in a sub-cohort analysis of patients treated with ICI. These results provide preliminary evidence for clinical utility of cardiotoxicity screening with troponin I monitoring in patients receiving ICI therapy.

Competency in Robotic Surgery: Standard Setting for Robotic Suturing Using Objective Assessment and Expert Evaluation.

OBJECTIVE: Surgical skill assessment tools such as the End-to-End Assessment of Suturing Expertise (EASE) can differentiate a surgeon's experience level. In this simulation-based study, we define a competency benchmark for intraoperative robotic suturing using EASE as a validated measure of performance. DESIGN: Participants conducted a dry-lab vesicourethral anastomosis (VUA) exercise. Videos were each independently scored by 2 trained, blinded reviewers using EASE. Inter-rater reliability was measured with prevalence-adjusted bias-adjusted Kappa (PABAK) using 2 example videos. All videos were reviewed by an expert surgeon, who determined if the suturing skills exhibited were at a competency level expected for residency graduation (pass or fail). The Contrasting Group (CG) method was then used to set a pass/fail score at the intercept of the pass and fail cohorts' EASE score distributions. SETTING: Keck School of Medicine, University of Southern California. PARTICIPANTS: Twenty-six participants: 8 medical students, 8 junior residents (PGY 1-2), 7 senior residents (PGY 3-5) and 3 attending urologists. RESULTS: After 1 round of consensus-building, average PABAK across EASE subskills was 0.90 (Range 0.67-1.0). The CG method produced a competency benchmark EASE score of >35/39, with a pass rate of 10/26 (38%); 27% were deemed competent by expert evaluation. False positives and negatives were defined as medical students who passed and attendings who failed the assessment, respectively. This pass/fail score produced no false positives or negatives, and fewer JR than SR were considered competent by both the expert and CG benchmark. CONCLUSIONS: Using an absolute standard setting method, competency scores were set to identify trainees who could competently execute a standardized dry-lab robotic suturing exercise. This standard can be used for high stakes decisions regarding a trainee's technical readiness for independent practice. Future work includes validation of this standard in the clinical environment through correlation with clinical outcomes.

Assessing Knowledge, Attitudes, and Perceptions of Medical Students Toward Emergency Preparedness and Disaster Medicine in Singapore.

OBJECTIVE: Despite rising incidences of global disasters, basic principles of disaster medicine training are barely taught in Singapore's 3 medical schools. The aim of this study was to evaluate the current levels of emergency preparedness, attitudes, and perceptions of disaster medicine education among medical students in Singapore. METHODS: The Emergency Preparedness Information Questionnaire (EPIQ) was provided to enrolled medical students in Singapore by means of an online form, from March 6, 2020, to February 20, 2021. A total of 635 (25.7%) responses were collated and analyzed. RESULTS: Mean score for overall familiarity was low, at 1.50 ± 0.74, on a Likert scale of 1 for not familiar to 5 for very familiar. A total of 90.6% of students think that disaster medicine is an important facet of the curriculum, and 93.1% agree that training should be provided for medical students. Although 77.3% of respondents believe that they are unable to contribute to a disaster scenario currently, 92.8% believe that they will be able to contribute with formal training. CONCLUSIONS: Despite low levels of emergency preparedness knowledge, the majority of medical students in Singapore are keen for adaptation of disaster medicine into the current curriculum to be able to contribute more effectively. This can arm future health-care professionals with the confidence to respond to any potential emergency.

Using Real-time Feedback To Improve Surgical Performance on a Robotic Tissue Dissection Task.

Background: There is no standard for the feedback that an attending surgeon provides to a training surgeon, which may lead to variable outcomes in teaching cases. Objective: To create and administer standardized feedback to medical students in an attempt to improve performance and learning. Design setting and participants: A cohort of 45 medical students was recruited from a single medical school. Participants were randomly assigned to two groups. Both completed two rounds of a robotic surgical dissection task on a da Vinci Xi surgical system. The first round was the baseline assessment. In the second round, one group received feedback and the other served as the control (no feedback). Outcome measurements and statistical analysis: Video from each round was retrospectively reviewed by four blinded raters and given a total error tally (primary outcome) and a technical skills score (Global Evaluative Assessment of Robotic Surgery [GEARS]). Generalized linear models were used for statistical modeling. According to their initial performance, each participant was categorized as either an innate performer or an underperformer, depending on whether their error tally was above or below the median. Results and limitations: In round 2, the intervention group had a larger decrease in error rate than the control group, with a risk ratio (RR) of 1.51 (95% confidence interval [CI] 1.07-2.14; p = 0.02). The intervention group also had a greater increase in GEARS score in comparison to the control group, with a mean group difference of 2.15 (95% CI 0.81-3.49; p < 0.01). The interaction effect between innate performers versus underperformers and the intervention was statistically significant for the error rates, at F(1,38) = 5.16 (p = 0.03). Specifically, the intervention had a statistically significant effect on the error rate for underperformers (RR 2.23, 95% CI 1.37-3.62; p < 0.01) but not for innate performers (RR 1.03, 95% CI 0.63-1.68; p = 0.91). Conclusions: Real-time feedback improved performance globally compared to the control. The benefit of real-time feedback was stronger for underperformers than for trainees with innate skill. Patient summary: We found that real-time feedback during a training task using a surgical robot improved the performance of trainees when the task was repeated. This feedback approach could help in training doctors in robotic surgery.

Tailored Feedback Based on Clinically Relevant Performance Metrics Expedites the Acquisition of Robotic Suturing Skills-An Unblinded Pilot Randomized Controlled Trial.

PURPOSE: Previously, we identified 8 objective suturing performance metrics highly predictive of urinary continence recovery after robotic-assisted radical prostatectomy. Here, we aimed to test the feasibility of providing tailored feedback based upon these clinically relevant metrics and explore the impact on the acquisition of robotic suturing skills. MATERIALS AND METHODS: Training surgeons were recruited and randomized to a feedback group or a control group. Both groups completed a baseline, midterm and final dry laboratory vesicourethral anastomosis (VUA) and underwent 4 intervening training sessions each, consisting of 3 suturing exercises. Eight performance metrics were recorded during each exercise: 4 automated performance metrics (derived from kinematic and system events data of the da Vinci® Robotic System) representing efficiency and console manipulation competency, and 4 suturing technical skill scores. The feedback group received tailored feedback (a visual diagram+verbal instructions+video examples) based on these metrics after each session. Generalized linear mixed model was used to compare metric improvement (Δ) from baseline to the midterm and final VUA. RESULTS: Twenty-three participants were randomized to the feedback group (11) or the control group (12). Demographic data and baseline VUA metrics were comparable between groups. The feedback group showed greater improvement than the control group in aggregate suturing scores at midterm (mean Δ feedback group 4.5 vs Δ control group 1.1) and final VUA (Δ feedback group 5.3 vs Δ control group 4.9). The feedback group also showed greater improvement in the majority of the included metrics at midterm and final VUA. CONCLUSIONS: Tailored feedback based on specific, clinically relevant performance metrics is feasible and may expedite the acquisition of robotic suturing skills.

An Assessment Tool to Provide Targeted Feedback to Robotic Surgical Trainees: Development and Validation of the End-To-End Assessment of Suturing Expertise (EASE).

Purpose: To create a suturing skills assessment tool that comprehensively defines criteria around relevant sub-skills of suturing and to confirm its validity. Materials and Methods: 5 expert surgeons and an educational psychologist participated in a cognitive task analysis (CTA) to deconstruct robotic suturing into an exhaustive list of technical skill domains and sub-skill descriptions. Using the Delphi methodology, each CTA element was systematically reviewed by a multi-institutional panel of 16 surgical educators and implemented in the final product when content validity index (CVI) reached ≥0.80. In the subsequent validation phase, 3 blinded reviewers independently scored 8 training videos and 39 vesicourethral anastomoses (VUA) using EASE; 10 VUA were also scored using Robotic Anastomosis Competency Evaluation (RACE), a previously validated, but simplified suturing assessment tool. Inter-rater reliability was measured with intra-class correlation (ICC) for normally distributed values and prevalence-adjusted bias-adjusted Kappa (PABAK) for skewed distributions. Expert (≥100 prior robotic cases) and trainee (<100 cases) EASE scores from the non-training cases were compared using a generalized linear mixed model. Results: After two rounds of Delphi process, panelists agreed on 7 domains, 18 sub-skills, and 57 detailed sub-skill descriptions with CVI ≥ 0.80. Inter-rater reliability was moderately high (ICC median: 0.69, range: 0.51-0.97; PABAK: 0.77, 0.62-0.97). Multiple EASE sub-skill scores were able to distinguish surgeon experience. The Spearman's rho correlation between overall EASE and RACE scores was 0.635 (p=0.003). Conclusions: Through a rigorous CTA and Delphi process, we have developed EASE, whose suturing sub-skills can distinguish surgeon experience while maintaining rater reliability.

Tooth autotransplantation in a patient with rapidly progressing periodontitis aided by 3D printing.

Patients with rapidly progressing periodontitis may require extractions of teeth with poor periodontal prognosis. Although replacement with a dental implant is a popular choice, teeth autotransplantation remains a viable option. Herein, we report a case of a 23-year-old patient with rapidly progressing periodontitis resulting in severe clinical attachment loss on the left maxillary first molar, which required extraction. The tooth was replaced by tooth autotransplantation of the unerupted immature left mandibular third molar, which was delivered carefully without compromising the periodontal ligament. Cone beam computed tomography and three-dimensional printing of the third molar donor tooth significantly aided the tooth autotransplantation procedure. Recovery was uneventful. At the 1-year follow-up, healthy periodontal parameters and radiographic features were noted, and the autotransplanted tooth remained vital. This case showed that tooth autotransplantation is a viable option for replacing tooth loss due to rapidly progressing periodontitis.

Pulmonary contusions in patients with rib fractures: The need to better classify a common injury.

BACKGROUND: Pulmonary contusions are common injuries. Computed tomography reveals vast contused lung volume spectrum, yet pulmonary contusions are defined dichotomously (unilateral vs bilateral). We assessed whether there is stepwise increased risk of pulmonary complications among patients without, with unilateral, and with bilateral pulmonary contusion. METHODS: We identified adults admitted with rib fractures using the largest US inpatient database. After propensity-score-matching patients without vs with unilateral vs bilateral pulmonary contusions and adjusting for residual confounders, we compared risk for pneumonia, ventilator-associated pneumonia (VAP), respiratory failure, intubation, and mortality. RESULTS: Among 148,140 encounters of adults with multiple rib fractures, 19% had concomitant pulmonary contusions. Matched patients with pulmonary contusions had increased risk of pneumonia 19% [95%CI:16-33%], respiratory failure 40% [95%CI: 31-50%], and intubation 46% [95%CI: 33-61%]. Delineation showed bilateral contusions, not unilateral contusions, attributed to increased risk of complications. CONCLUSIONS: There is likely a correlation between contused lung volume and risk of pulmonary complications; dichotomously classifying pulmonary contusions is insufficient. Better understanding this correlation requires establishing the clinically significant contusion volume and a correspondingly refined classification system.

Clinical Trial Outcomes in Urology: Assessing Early Discontinuation, Results Reporting and Publication in ClinicalTrials.Gov Registrations 2007-2019.

PURPOSE: Clinical trials require significant resources, but benefits are only realized after trial completion and dissemination of results. We comprehensively assessed early discontinuation, registry results reporting, and publication by trial sponsor and subspecialty in urology trials. MATERIALS AND METHODS: We assessed trial registrations from 2007 to 2019 on ClinicalTrials.gov and publication data from PubMed®/MEDLINE®. Associations between sponsor or subspecialty with early discontinuation were assessed using Cox proportional hazards and results reporting or publication with logistic regression at 3 years after completion. RESULTS: Of 8,636 trials 3,541 (41.0%) were completed and 999 (11.6%) were discontinued. Of completed trials 26.9% reported results and 21.6% were published. Sponsors included academic institutions (53.1%), industry (37.1%) and the U.S. government (9.8%). Academic-sponsored (adjusted HR 0.81, 95% CI 0.69-0.96, p=0.012) and government-sponsored trials (adjusted HR 0.62, 95% CI 0.49-0.78, p <0.001) were less likely than industry to discontinue early. Government-sponsored trials were more likely to report (adjusted OR 1.72, 95% CI 1.17-2.54, p=0.006) and publish (adjusted OR 1.89, 95% CI 1.23-2.89, p=0.004). Academic-sponsored trials were less likely to report (adjusted OR 0.65, CI:0.48-0.88, p=0.006) but more likely to publish (adjusted OR 1.72, 95% CI 1.25-2.37, p <0.001). These outcomes were similar across subspecialties. However, endourology was more likely to discontinue early (adjusted HR 2.00, 95% CI 1.53-2.95, p <0.001), general urology was more likely to report results (adjusted OR 1.54, 95% CI 1.13-2.11, p=0.006) and andrology was less likely to publish (adjusted OR 0.53, 95% CI 0.35-0.81, p=0.003). CONCLUSIONS: Sponsor type is significantly associated with trial completion and dissemination. Government-sponsored trials had the best performance, while industry and academic-sponsored trials lagged in completion and results reporting, respectively. Subspecialty played a lesser role. Lack of dissemination remains a problem for urology trials.