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Background Diagnostic error (DE) is a common problem in clinical practice, particularly in the emergency department (ED) setting. Among ED patients presenting with cardiovascular or cerebrovascular/neurological symptoms, a delay in diagnosis or failure to hospitalise may be most impactful in terms of adverse outcomes. Minorities and other vulnerable populations may be at higher risk of DE. We aimed to systematically review studies reporting the frequency and causes of DE in under-resourced patients presenting to the ED with cardiovascular or cerebrovascular/neurological symptoms. Methods We searched EBM Reviews, Embase, Medline, Scopus and Web of Science from 2000 through 14 August 2022. Data were abstracted by two independent reviewers using a standardised form. The risk of bias (ROB) was assessed using the Newcastle-Ottawa Scale, and the certainty of evidence was evaluated using the Grading of Recommendations Assessment, Development, and Evaluation approach. Results Of the 7342 studies screened, we included 20 studies evaluating 7436,737 patients. Most studies were conducted in the USA, and one study was multicountry. 11 studies evaluated DE in patients with cerebrovascular/neurological symptoms, 8 studies with cardiovascular symptoms and 1 study examined both types of symptoms. 13 studies investigated missed diagnoses and 7 studies explored delayed diagnoses. There was significant clinical and methodological variability, including heterogeneity of DE definitions and predictor variable definitions as well as methods of DE assessment, study design and reporting. Among the studies evaluating cardiovascular symptoms, black race was significantly associated with higher odds of DE in 4/6 studies evaluating missed acute myocardial infarction (AMI)/acute coronary syndrome (ACS) diagnosis compared with white race (OR from 1.18 (1.12–1.24) to 4.5 (1.8–11.8)). The association between other analysed factors (ethnicity, insurance and limited English proficiency) and DE in this domain varied from study to study and was inconclusive. Among the studies evaluating DE in patients with cerebrovascular/neurological symptoms, no consistent association was found indicating higher or lower odds of DE. Although some studies showed significant differences, these were not consistently in the same direction. The overall ROB was low for most included studies; however, the certainty of evidence was very low, mostly due to serious inconsistency in definitions and measurement approaches across studies. Conclusions This systematic review demonstrated consistent increased odds of missed AMI/ACS diagnosis among black patients presenting to the ED compared with white patients in most studies. No consistent associations between demographic groups and DE related to cerebrovascular/neurological diagnoses were identified. More standardised approaches to study design, measurement of DE and outcomes assessment are needed to understand this problem among vulnerable populations. Trial registration number The study protocol was registered in the International Prospective Register of Systematic Reviews PROSPERO 2020 CRD42020178885 and is available from: https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42020178885.

AbstractCoagulation is a crucial biological mechanism in human bodies to prevent blood loss. Abnormal coagulation can cause bleeding diathesis or thrombosis, common pathologic conditions in our clinical practice. Many individuals and organizations have dedicated their efforts in the past decades to understanding the biological and pathological mechanisms of coagulation and developing laboratory testing tools and treatment options to help patients with bleeding or thrombotic conditions. Since 1926, the Mayo Clinic coagulation group has made significant contributions to the clinical and laboratory practice, basic and translational research on various hemostatic and thrombotic disorders, and the education and collaboration to share and advance our knowledge in coagulation through a highly integrated team and practice model. We would like to use this review to share our history and inspire medical professionals and trainees to join the efforts to advance our understanding of coagulation pathophysiology and improve our care for patients with coagulation disorders.

INTRODUCTION: Intrahepatic cholangiocarcinoma (iCCA) is a primary liver malignancy with poor prognosis. Current prognostic methods are most accurate for patients with surgically resectable disease. However, a significant proportion of patients with iCCA are not surgical candidates. We aimed to develop a generalizable staging system based on clinical variables to determine prognosis of all patients with iCCA. METHODS: The derivation cohort included 436 patients with iCCA seen between 2000 and 2011. For external validation, 249 patients with iCCA seen from 2000 to 2014 were enrolled. Survival analysis was performed to identify prognostic predictors. All-cause mortality was the primary end point. RESULTS: Eastern Cooperative Oncology Group status, tumor number, tumor size, metastasis, albumin, and carbohydrate antigen 19-9 were incorporated into a 4-stage algorithm. Kaplan-Meier estimates for 1-year survival were 87.1% (95% confidence interval [CI] 76.1–99.7), 72.7% (95% CI 63.4–83.4), 48.0% (95% CI 41.2–56.0), and 16% (95% CI 11–23.5), respectively, for stages I, II, III, and IV. Univariate analysis yielded significant differences in risk of death for stages II (hazard ratio [HR] 1.71; 95% CI 1.0–2.8), III (HR 3.32; 95% CI 2.07–5.31), and IV (HR 7.44; 95% CI 4.61–12.01) compared with stage I (reference). Concordance indices showed the new staging system was superior to the TNM staging for predicting mortality in the derivation cohort, P < 0.0001. In the validation cohort, however, the difference between the 2 staging systems was not significant. DISCUSSION: The proposed independently validated staging system uses nonhistopathologic data to successfully stratify patients into 4 stages. This staging system has better prognostic accuracy compared with the TNM staging and can assist physicians and patients in treatment of iCCA.

548 Background: PD-L1 and B7-H3 have been found to be overexpressed in urothelial carcinoma (UC) of the urinary bladder. Recent studies have also demonstrated that B7-H3 and PD-L1 can promote resistance to platinum-based drugs but the predictive value of B7-H3 expression in patients treated with platinum-based chemotherapy is unknown. This study aims to investigate the association of PD-L1 and B7-H3 tumor expression with oncological outcomes in patients who underwent radical cystectomy (RC) and received subsequent adjuvant chemotherapy. Methods: Immunohistochemistry was performed on paraffin-embedded sections from bladder and lymph node specimens of 81 patients who had RC for bladder cancer. PD-L1 and B7-H3 expression on tumor cells was assessed by immunohistochemistry in both primary tumors and lymph node specimens. Association with clinicopathologic outcomes was determined using Fisher’s exact test and postoperative survival using Kaplan–Meier survival curves and Cox regression model. Results: B7-H3 expression in cystectomy specimens was more common than PD-L1 expression (72.8% vs. 35.8%). For both markers, no association was found with pathologic tumor stage, lymph node (LN) status, and histological subtype. Similar findings were observed for double-positive tumors (PD-L1+B7-H3+). Concordance between the primary tumor and patient-matched lymph nodes was found in 76.2% and 54.1% of patients for PD-L1 and B7-H3, respectively. PD-L1 tumor expression was not associated with oncologic outcomes. However, B7-H3 expression was associated with recurrence-free survival (HR: 2.38, 95% CI 1.06–5.31, p = 0.035) and cancer-specific survival (HR: 2.67, 95% CI 1.18–6.04, p = 0.019). Conclusions: In our single institutional study, B7-H3 is highly expressed in patients with UC treated with adjuvant chemotherapy and it was associated with decreased recurrence-free survival and cancer-specific survival. Pending further validation in larger cohorts, B7-H3 expression may function as a predictor of response to adjuvant chemotherapy and thus be useful in patient and regimen selection.

AbstractBackgroundAAPM Task Group (TG) 275 was charged with developing practical, evidence‐based recommendations for physics plan and chart review clinical processes for radiation therapy. As part of this charge, and to characterize practices and clinical processes, a survey of the medical physics community was developed and conducted. Detailed analyses and trends based on the survey that exceeded TG report length constraints are presented herein.AimsThe design, development, and detailed results of the TG‐ 275 survey as well as statistical analysis and trends are described in detail. This is complementary material to the TG 275 report.Methods and materialsThe survey consisted of 100 multiple‐choice questions divided into four main sections: 1) Demographics, 2) Initial Plan Check, 3) On‐Treatment, and 4) End‐of‐Treatment Chart Check. The survey was released to all AAPM members who self‐reported working in the radiation oncology field, and it was kept open for 7 weeks. Results were summarized using descriptive statistics. To study practice differences, tests of association were performed using data grouped by four demographic questions: 1) Institution Type, 2) Average number of patients treated daily, 3) Radiation Oncology Electronic Medical Record, and 4) Perceived Culture of Safety.ResultsThe survey captured 1370 non‐duplicate entries from the United States and Canada. Differences across practices were grouped and presented based on Process‐Based and Check‐Specific questions. A risk‐based summary was created to show differences amongst the four demographic questions for checks associated with the highest risk failure modes identified by TG‐275.ConclusionThe TG‐275 survey captured a baseline of practices on initial plan, on‐treatment, and end‐of‐treatment checks across a wide variety of clinics and institutions. The results of test of association showed practice heterogeneities as a function of demographic characteristics. Survey data were successfully used to inform TG‐275 recommendations.

ABSTRACT Objective: To identify and describe characteristics of patients with sepsis who could be treated with minimally invasive sepsis (MIS) approach without intensive care unit (ICU) admission and to develop a prediction model to select candidates for MIS approach. Methods: A secondary analysis of the electronic database of patients with sepsis at Mayo Clinic, Rochester, MN. Candidates for the MIS approach were adults with septic shock and less than 48 hours of ICU stay, who did not require advanced respiratory support and were alive at hospital discharge. Comparison group consisted of septic shock patients with an ICU stay of more than 48 hours without advanced respiratory support at the time of ICU admission. Results: Of 1795 medical ICU admissions, 106 patients (6%) met MIS approach criteria. Predictive variables (age >65 years, oxygen flow >4 L/min, temperature <37°C, creatinine >1.6 mg/dL, lactate >3 mmol/L, white blood cells >15 × 109/L, heart rate >100 beats/min, and respiration rate >25 breaths/min) selected through logistic regression were translated into an 8-point score. Model discrimination yielded the area under the receiver operating characteristic curve of 79% and was well fitted (Hosmer-Lemeshow P = 0.94) and calibrated. The MIS score cutoff of 3 resulted in a model odds ratio of 0.15 (95% confidence interval, 0.08–0.28) and a negative predictive value of 91% (95% confidence interval, 88.69–92.92). Conclusions: This study identifies a subset of low-risk septic shock patients who can potentially be managed outside the ICU. Once validated in an independent, prospective sample our prediction model can be used to identify candidates for MIS approach.

Abstract Background CERTAIN (Checklist for Early Recognition and Treatment of Acute Illness and iNjury) education program was developed to accelerate the global dissemination of a standardized, systemic, structured approach to critical care delivery. The coronavirus disease (COVID-19) pandemic prompted the evolution of this program from a live in-person course to a blended synchronous and asynchronous learning experience, including virtual simulation. Objectives We describe our experience and insights gained through this digital program transformation and highlight areas in need of further research to advance the delivery of high-quality online education offerings to global interprofessional audiences. Methods The CERTAIN education program was delivered to a broad international audience first in person (2016–2019) and then virtually during the COVID-19 global pandemic (2020–present). During this transition, we adopted a flipped classroom model to deliver the core content asynchronously using an online learning management system, supplemented by a novel synchronous online experience to provide learners with the opportunity to apply these concepts using a series of simulated clinical cases. Results A total of 400 participants attended 11 CERTAIN courses. We transitioned our 10-hour live course to a 3-hour virtual workshop. The duration of simulation activities (admission, rounding, and shared decision-making) remained constant. Didactic lectures were eliminated from the synchronous online course and presented as recorded videos in precourse materials. We collected 306 postcourse surveys (response rate, 76.5%). The majority of the overall course ratings were excellent (147 [49.5%]) and very good (97 [32.7%]), and learner responses were similar to live and online courses. Simulation activities were consistently the most popular elements of our program. Access to digital learning platforms and language barriers during simulation activities proved to be the greatest challenges during our transition. Delivering mobile-friendly online content and close coordination between dedicated bilingual faculty and local champions helped overcome these challenges. Conclusion Critical care education and case-based simulation workshops can be delivered to international interprofessional audiences with similar, high degrees of learner satisfaction to in-person offerings.

Abstract Objective To describe the technique, safety profile, and outcome of computed tomography (CT)–guided atlanto-axial lateral articulation injections performed at our institution. Methods Consecutive cases of all CT-guided atlanto-axial injections performed from January 2017 to April 2022 at our institution were searched in the electronic medical records. Patient charts were reviewed for demographics, characterization of pain, potential altered anatomy, pain level before and immediately after the procedure, procedure technique, complications, and follow-up outcomes, if available. Results Forty-five injections in 40 different patients were included. The average age was 67.4 years, and 28 (70%) of the patients were female. Of the 45 injections, 43 (96%) were technically successful. The average change in pain score (0–10) from immediately before to immediately after the injection was –3.36 (SD = 2.87, range = –8 to +3). Of all injections, 14 (31%) had a postprocedural pain score of zero. In 2 cases (4%), patients reported an increase in pain score immediately after the injection. In 3 cases (7%), transient non–vertebral artery vascular uptake of contrast was documented during the procedure, which could be cleared with needle repositioning. There were no complications. Conclusion CT-guided atlanto-axial lateral articulation injection is a safe procedure with a high technical success rate. It allows for direct visualization of vital structures and provides an alternative option to the traditional fluoroscopic guidance, especially in cases of prior technically unsuccessful fluoroscopically guided injection or altered anatomy.