The Advanced Certifying Exam Simulation-Pro assessment instrument: evaluating surgical trainee examsmanship in virtual oral exams.

Purpose: In response to the COVID-19 pandemic, many educational activities in general surgery residency have shifted to a virtual environment, including the American Board of Surgery (ABS) Certifying Exam. Virtual exams may become the new standard. In response, we developed an evaluation instrument, the ACES-Pro, to assess surgical trainee performance with a focus on examsmanship in virtual oral board examinations. The purpose of this study was two-fold: (1) to assess the utility and validity of the evaluation instrument, and (2) to characterize the unique components of strong examsmanship in the virtual setting, which has distinct challenges when compared to in-person examsmanship. Methods: We developed a 15-question evaluation instrument, the ACES-Pro, to assess oral board performance in the virtual environment. Nine attending surgeons viewed four pre-recorded oral board exam scenarios and scored examinees using this instrument. Evaluations were compared to assess for inter-rater reliability. Faculty were also surveyed about their experience using the instrument. Results: Pilot evaluators found the ACES-Pro instrument easy to use and felt it appropriately captured key professionalism metrics of oral board exam performance. We found acceptable inter-rater reliability in the domains of verbal communication, non-verbal communication, and effective use of technology (Guttmann's lambda-2 were 0.796, 0.916, and 0.739, respectively). Conclusions: The ACES-Pro instrument is an assessment with evidence for validity as understood by Kane's framework to evaluate multiple examsmanship domains in the virtual exam setting. Examinees must consider best practices for virtual examsmanship to perform well in this environment. Supplementary Information: The online version contains supplementary material available at 10.1007/s44186-023-00107-7.

Defects in vein valve PROX1/FOXC2 antithrombotic pathway in endothelial cells drive the hypercoagulable state induced by trauma and critical illness.

OBJECTIVES: Deep venous thrombosis (DVT) causes significant morbidity and mortality after trauma. Recently, we have shown that blood flow patterns at vein valves induce oscillatory stress genes, which maintain an anticoagulant endothelial phenotype that inhibits spontaneous clotting at vein valves and sinuses, is lost in the presence of DVT in human pathological samples, and is dependent on expression of the transcription factor FOXC2. We describe an assay, modifying our mouse multiple injury system, which shows evidence of clinically relevant microthrombosis and hypercoagulability applicable to the study of spontaneous DVT in trauma without requiring direct vascular injury or ligation. Finally, we investigated whether these model findings are relevant to a human model of critical illness by examining gene expression changes by quantitative polymerase chain reaction and immunofluorescence in veins collected from critically ill. METHODS: C57/Bl6 mice were subjected to a modified mouse multiple injury model with liver crush injury, crush and pseudofracture of a single lower extremity, and 15% total blood volume hemorrhage. Serum was assayed for d-dimer at 2, 6, 24, and 48 hours after injury by enzyme-linked immunosorbent assay. For the thrombin clotting assay, veins of the leg were exposed, 100 µL of 1 mM rhodamine (6 g) was injected retro-orbitally, and 450 µg/mL thrombin was then applied to the surface of the vein with examination of real-time clot formation via in vivo immunofluorescence microscopy. Images were then examined for percentage area of clot coverage of visible mouse saphenous and common femoral vein. Vein valve specific knockout of FOXC2 was induced with tamoxifen treatment in PROX1 Ert2Cre FOXC2 fl/fl mice as previously described. Animals were then subjected to a modified mouse multiple injury model with liver crush injury, crush and pseudofracture of a single lower extremity, and 15% total blood volume hemorrhage. Twenty-four hours after injury, we examined the valve phenotype in naive versus multiple injury animals, with and without loss of the FOXC2 gene from the vein valve (FOXC2 del ) via the thrombin assay. Images were then examined for proximity of clot formation to the valve present at the junction of the mouse saphenous, tibial, and superficial femoral vein and presence of spontaneous microthrombi present in the veins before exposure to thrombin. Human vein samples were obtained from excess tissue preserved after harvest for elective cardiac surgery and from organ donors after organ procurement. Sections were submitted for paraffin embedding and then assayed by immunofluorescence for PROX1, FOXC2, thrombomodulin, endothelial protein C receptor, and von Willebrand's factor. All animal studies were reviewed and approved by the Institutional Animal Care and Use Committee, and all human studies reviewed and approved by the institutional review board. RESULTS: After mouse multiple injuries, enzyme-linked immunosorbent assay for d-dimer showed evidence of products of fibrin breakdown consistent with formation of clot related to injury, fibrinolysis, and/or microthrombosis. The thrombin clotting assay demonstrated higher percentage area of vein covered with clot when exposed to thrombin in the multiple injury animals compared with uninjured (45% vs. 27% p = 0.0002) consistent with a phenotype of hypercoagulable state after trauma in our model system. Unmanipulated FoxC2 knockout mice manifest increased clotting at the vein valve as compared with unmanipulated wild type animals. After multiple injuries, wild type mice manifest increase clotting at the vein after thrombin exposure ( p = 0.0033), and equivalent to that of valvular knockout of FoxC2 (FoxC2del), recapitulating the phenotype seen in FoxC2 knockout animals. The combination of multiple injuries and FoxC2 knockout resulted in spontaneous microthrombi in 50% of the animals, a phenotype not observed with either multiple injuries or FoxC2 deficiency alone (χ 2 , p = 0.017). Finally, human vein samples demonstrated the protective vein valve phenotype of increased FOXC2 and PROX1 and showed decreased expression in the critically ill organ donor population by immunofluorescence imaging in organ donor samples. CONCLUSION: We have established a novel model of posttrauma hypercoagulation that does not require direct restriction of venous flow or direct injury to the vessel endothelium to assay for hypercoagulability and can generate spontaneous microthrombosis when combined with valve-specific FOXC2 knockout. We find that multiple injuries induce a procoagulant phenotype that recapitulates the valvular hypercoagulability seen in FOXC2 knockout and, in critically ill human specimens, find evidence for loss of oscillatory shear stress-induced gene expression of FOXC2 and PROX1 in the valvular endothelium consistent with potential loss of DVT-protective valvular phenotype.

Cellular immunophenotype of major spine surgery in adults.

PURPOSE: ASD reconstructions are a major, sterile traumatic insult, likely causing perturbations to the immune systems. The immune response to surgery is associated with outcomes. The purpose of this study was to examine for a detectable immune signature associated with ASD surgery. METHODS: Consecutive patients undergoing ASD surgery were approached and enrolled. Peripheral blood was drawn before incision, 4 h after, and 24 h after incision. Blood was stabilized and comprehensive flow cytometric immunophenotyping performed. Leukocyte population frequency, absolute number and activation marker expression were defined. Immunologic features were defined and analyzed by hierarchical clustering and principal component analysis (PCA). Changes over time were evaluated by repeated measures ANOVA (RMANOVA) and were corrected for a 1% false discovery rate. Post hoc testing was by Dunn's test. p values of < = 0.05 were considered significant. RESULTS: Thirteen patients were enrolled; 11(85%) F, 65.4 years (± 7.5), surgical duration 418 ± 83 min, EBL 1928 ± 1253 mL. Hierarchical clustering and PCA found consistent time from incision-dependent changes. HLA-DR and activating co-stimulatory molecule CD86 were depressed at 4 h and furthermore at 24 h on monocyte surfaces. CD4 + HLA-DR + T cells, but not CD8 +, increased over time with increased expression of PD-1 at 4 and 24 h. CONCLUSIONS: Despite surgery and patient heterogeneity, we identified an immune signature associated with the sterile trauma of ASD surgery. Circulating leukocyte populations change in composition and signaling protein expression after incision and persisting to 24 h after incision, suggesting an immunocompromised state. Further work may determine relationships between this state and poor outcomes after surgery.

Dysregulation of the leukocyte signaling landscape during acute COVID-19.

The global COVID-19 pandemic has claimed the lives of more than 750,000 US citizens. Dysregulation of the immune system underlies the pathogenesis of COVID-19, with inflammation mediated tissue injury to the lung in the setting of suppressed systemic immune function. To define the molecular mechanisms of immune dysfunction in COVID-19 we utilized a systems immunology approach centered on the circulating leukocyte phosphoproteome measured by mass cytometry. We find that although COVID-19 is associated with wholesale activation of a broad set of signaling pathways across myeloid and lymphoid cell populations, STAT3 phosphorylation predominated in both monocytes and T cells. STAT3 phosphorylation was tightly correlated with circulating IL-6 levels and high levels of phospho-STAT3 was associated with decreased markers of myeloid cell maturation/activation and decreased ex-vivo T cell IFN-γ production, demonstrating that during COVID-19 dysregulated cellular activation is associated with suppression of immune effector cell function. Collectively, these data reconcile the systemic inflammatory response and functional immunosuppression induced by COVID-19 and suggest STAT3 signaling may be the central pathophysiologic mechanism driving immune dysfunction in COVID-19.

Standardized oral examinations allow for assessment of medical student clinical knowledge and decrease racial grading differences in a surgery clerkship.

BACKGROUND: Oral examinations are not consistently included in third-year medical student clerkships. When included, they are often unstructured, leaving room for variations in difficulty or scoring. Previous research has demonstrated differences in clinical grade achievement, with underrepresented in medicine students receiving significantly lower grades than White students. METHODS: We designed a structured oral examination for third-year medical students on the surgery clerkship. Students completed 2 oral examination scenarios and were evaluated on their ability to complete a history and diagnostic workup, interpret laboratory and imaging results, and devise a treatment plan. Scores from our examination were compared to previous, unstructured oral examination scores and to student demographics. Students and faculty were surveyed regarding their experience. RESULTS: Third-year medical students demonstrated strong knowledge of multiple surgical diseases. The greatest number of errors occurred in treatment planning (P < .001). Third-year medical students receiving honors clerkship grades achieved higher percentages of correct items on their oral examination. (94.8% vs 90.4%) (P = .02). Evaluation of prior unstructured oral examinations found underrepresented in medicine students received lower scores than White students (P = .04). After implementation of our structured examination, no difference was seen between the scores of underrepresented in medicine and White students (P = .99). CONCLUSION: We implemented a standardized oral examination for third-year medical students on the surgery clerkship with student and faculty satisfaction and demonstrated the ability to determine domains of knowledge weakness. The application of our structured oral examination helped to address nonspecific grading practices and eliminate oral examination grade differences between underrepresented in medicine and White students.

Evaluating chief resident readiness for the teaching assistant role: The Teaching Evaluation assessment of the chief resident (TEACh-R) instrument.

BACKGROUND: The American Board of Surgery has mandated chief residents complete 25 cases in the teaching assistant (TA) role. We developed a structured instrument, the Teaching Evaluation and Assessment of the Chief Resident (TEACh-R), to determine readiness and provide feedback for residents in this role. METHODS: Senior (PGY3-5) residents were scored on technical and teaching performance by faculty observers using the TEACh-R instrument in the simulation lab. Residents were provided with their TEACh-R scores and surveyed on their experience. RESULTS: Scores in technical (p < 0.01) and teaching (p < 0.01) domains increased with PGY. Higher technical, but not teaching, scores correlated with attending-rated readiness for operative independence (p 0.02). Autonomy mismatch was inversely correlated with teaching competence (p < 0.01). Residents reported satisfaction with TEACh-R feedback and desire for use of this instrument in operating room settings. CONCLUSION: Our TEACh-R instrument is an effective way to assess technical and teaching performance in the TA role.

Interleukin-7 Reverses Lymphopenia and Improves T-Cell Function in Coronavirus Disease 2019 Patient With Inborn Error of Toll-Like Receptor 3: A Case Report.

BACKGROUND: Immunotherapy treatment for coronavirus disease 2019 combined with antiviral therapy and supportive care remains under intense investigation. However, the capacity to distinguish patients who would benefit from immunosuppressive or immune stimulatory therapies remains insufficient. Here, we present a patient with severe coronavirus disease 2019 with a defective immune response, treated successfully with interleukin-7 on compassionate basis with resultant improved adaptive immune function. CASE SUMMARY: A previously healthy 43-year-old male developed severe acute respiratory distress syndrome due to the severe acute respiratory syndrome coronavirus 2 virus with acute hypoxemic respiratory failure and persistent, profound lymphopenia. Functional analysis demonstrated depressed lymphocyte function and few antigen-specific T cells. Interleukin-7 administration resulted in reversal of lymphopenia and improved T-cell function. Respiratory function and clinical status rapidly improved, and he was discharged home. Whole exome sequencing identified a deleterious autosomal dominant mutation in TICAM1, associated with a dysfunctional type I interferon antiviral response with increased severity of coronavirus disease 2019 disease. CONCLUSIONS: Immunoadjuvant therapies to boost host immunity may be efficacious in life-threatening severe coronavirus disease 2019 infections, particularly by applying a precision medicine approach in selecting patients expressing an immunosuppressive phenotype.

Maintaining Effective Senior Resident-Led Intern Education through Virtual Curricular Transition.

OBJECTIVE: The COVID-19 pandemic has resulted in a significant shift to virtual resident education. While novel methods for virtual resident training have been described, many of these demonstrate a substantial change from previous instructional methods and their efficacy cannot be directly compared to in-person teaching. We sought to determine if the conversion of our intern "summer school" from an in-person to online format (a) impacted the knowledge acquisition of interns, and (b) their preferences for senior resident-led didactics. DESIGN: A senior-resident led intern summer curriculum was started in an in-person format with the 2019-2020 academic year. Interns underwent assessments of their knowledge and surveys of changes in subject confidence. After the COVID-19 pandemic, the curriculum was shifted to an online format for the academic year 2020-2021. SETTING: Washington University in St. Louis, an academic medical center located in St. Louis, Missouri PARTICIPANTS: PGY1 general surgery residents during academic year 2019-2020 (n = 13) and 2020-2021 (n = 14). RESULTS: In both years, interns demonstrated significant increases in confidence pre- and post-summer school in all domains (p <0.01). This was no different between the in-person and the virtual administration of the bootcamp (p 0.76). In both virtual and in-person curricula, interns demonstrated increased knowledge as measured by multiple choice, boards-style question quizzes. There were no significant differences between virtual and in-person formats. In both formats, interns reported a preference for senior residents as teachers (81% v. 77%) and increased comfort in asking questions in senior resident-led vs. attending-led didactics (91% v 100%). CONCLUSION: Virtual senior-resident led intern educational sessions are equally as effective as in-person sessions for knowledge acquisition and improving confidence in intern-specific domains. In both virtual and in-person settings, interns prefer senior resident teachers to attendings. Virtual senior resident-led education is an effective and simple method for intern instruction, regardless of the format/approach.

Dysregulation of the Leukocyte Signaling Landscape during Acute COVID-19.

The global COVID-19 pandemic has claimed the lives of more than 450,000 US citizens. Dysregulation of the immune system underlies the pathogenesis of COVID-19, with inflammation mediated local tissue injury to the lung in the setting of suppressed systemic immune function. To define the molecular mechanisms of immune dysfunction in COVID-19 we utilized a systems immunology approach centered on the circulating leukocyte phosphoproteome measured by mass cytometry. COVID-19 is associated with wholesale activation of a broad set of signaling pathways across myeloid and lymphoid cell populations. STAT3 phosphorylation predominated in both monocytes and T cells and was tightly correlated with circulating IL-6 levels. High levels of STAT3 phosphorylation was associated with decreased markers of myeloid cell maturation/activation and decreased ex-vivo T cell IFN-gamma production, demonstrating that during COVID-19 dysregulated cellular activation is associated with suppression of immune effector cell function. Collectively, these data reconcile the systemic inflammatory response and functional immunosuppression induced by COVID-19 and suggest STAT3 signaling may be the central pathophysiologic mechanism driving immune dysfunction in COVID-19.

Effect of Community and Academic Surgical Rotation Sites on Medical Student Performance Outcomes and Career Choices.

OBJECTIVE: We hypothesize that students exposed to both academic and community surgery clerkship sites will have higher National Board of Medical Examiners Subject Exam in Surgery (NBME SES) scores and be more likely to pursue a career in a surgical specialty. DESIGN: The NBME surgery subject exam scores and National Resident Matching Program (NRMP) results were collected for all medical students rotating through the surgery clerkship over 4 years. Permutations of sites were analyzed against exam scores and match rates into surgical and nonsurgical specialties. SETTING: This study was performed at the Tulane University School of Medicine, in New Orleans, Louisiana, United States of America. PARTICIPANTS: Data for a total of 910 students rotating through the surgery clerkship over a period of 4 years was collected and analyzed. RESULTS: There was no statistical difference in NBME subject exam scores (p = 0.44) or match rates into a surgical specialty (p = 0.13) as stratified by site placement. Average NBME surgery subject exam scores were higher for those pursuing a surgical specialty (p < 0.001). CONCLUSIONS: The combination of sites experienced during the surgery clerkship did not affect NBME surgery subject exam scores nor lead to a tendency to match into a surgical specialty.

An Unusual Cause of Frequent, Sudden, Transient, Unexplained Falls and New-Onset Status Epilepticus: Case Report and Mini-Review.

We report a 14-year old adolescent Caucasian female, who presented with frequent, sudden, transient, and unexplained falls leading to multiple serious injuries to her head and extremities requiring several visits to the emergency department. She was evaluated numerous times and imaging studies, echocardiogram, electrocardiogram, and electroencephalogram studies were all normal. She eventually presented to outside emergency department with dystonic posturing and status epilepticus and was transferred to our pediatric intensive care unit for further management. She was diagnosed with an uncommon, underrecognized and underdiagnosed condition. To our knowledge there is no such previous report in a pediatric patient.

Nanoclusters self-assembled from conformation-stabilized influenza M2e as broadly cross-protective influenza vaccines.

Influenza vaccines with broad cross-protection are urgently needed. The highly conserved ectodomain of the influenza matrix protein 2 (M2e) can be a promising candidate if its low immunogenicity was overcome. In this study, we generated protein nanoclusters self-assembled from conformation-stabilized M2e tetramers (tM2e) to improve its immunogenicity. The resulting nanoclusters showed an average hydrodynamic diameter of 227 nm. Vaccination with the nanoclusters by an intranasal route elicited high levels of serum antigen-specific IgG in mice (approximately 100-fold higher than that obtained with soluble tM2e), as well as antigen-specific T cell and mucosal antibody responses. The immunity conferred complete protection against lethal challenge with homo- as well as heterosubtypic viruses. These results demonstrate that nanoclusters assembled from conformation-stabilized M2e are promising as a potential universal influenza A vaccine. Self-assembly into nanoclusters represents a novel approach for increasing the immunogenicity of vaccine antigens. FROM THE CLINICAL EDITOR: In order to develop more effective influenza vaccination, the highly conserved ectodomain of M2e could be a promising candidate. Unfortunately, it is a weak antigen for vaccination purposes. In this study, self-assembled protein nanoclusters of tM2e were generated and tested. The nanoclusters demonstrated superior vaccination properties, with complete protection against lethal challenge in the studied rodent model, raising hope for the introduction of similar vaccines to challenge human influenza outbreaks.