Do acting interns need residents? A comparison of acting intern experience on hospital medicine resident versus nonresident teams.

BACKGROUND: The clinical demands for hospitalist groups have grown at academic medical centers, without similar growth of teaching opportunities for faculty. Traditional resident teaching teams are often crowded with learners which can limit acting intern (or subintern) patient encounters. Medical students are often placed on nonresident teaching teams, although there are few studies on learner experience on a nonresident teaching team model. METHODS: To address these concerns, we created two nonresident teaching teams composed of one attending and two acting interns. We compared acting intern experience on the nonresident teaching teams to the traditional resident teams to determine if there were significant differences in student experience by reviewing course evaluation data on the two team models. RESULTS: Of the 276 students who completed the Internal Medicine Acting Internship from 2019 to 2023, 224 students (81%) completed the course evaluation. The course was highly rated, and the ratings were similar in both models demonstrating that the nonresident teaching team model is an effective option for acting interns. CONCLUSION: The nonresident teaching team model can offload crowded teaching teams, add additional acting intern experiences, and add teaching opportunities for hospital medicine attendings.

Detection and Characterization of Endplate Structural Defects on CT: A Diagnostic Accuracy Study.

STUDY DESIGN: Diagnostic test study. OBJECTIVE: To determine the reliability and validity or diagnostic accuracy of two previously described endplate structural defect (EPSD) assessment methods. SUMMARY OF BACKGROUND DATA: Studies of EPSD may further the understanding of pathoanatomical mechanisms underlying back pain. However, clinical imaging methods used to document EPSD have not been validated, leaving uncertainty about what the observations represent. METHODS: Using an evaluation manual, 418 endplates on CT sagittal slices obtained from 19 embalmed cadavers (9 men and 10 women, aged 62-91 y) were independently assessed by two experienced radiologists and a novice for EPSD using the two methods. The corresponding micro-CT (µCT) from the harvested T7-S1 spines were assessed by another independent rater with excellent intra-rater reliability (Kappa=0.96). RESULTS: Inter-rater reliability was good for presence (Kappa=0.60-0.69) and fair for specific phenotypes (Kappa=0.43-0.58) of EPSD. Erosion, for which the Brayda-Bruno classification lacked a category, was mainly (82.8%) classified as wavy/irregular, while many notched defects (n=15, 46.9%) and Schmorl's nodes (n=45, 79%) were recorded as focal defects using Feng's classification. When compared to µCT, endplate fractures (n=53) and corner defects (n=28) were routinely missed on CT. Endplates classified as wavy/irregular on CT corresponded to erosion (n=29, 21.2%), jagged defects (n=21, 15.3%), calcification (n=19, 13.9%), and other phenotypes on µCT. Some focal defects on CT represented endplate fractures (n=21, 27.6%) on µCT. Overall, with respect to the presence of an EPSD, there was a sensitivity of 70.9% and specificity of 79.1% using Feng's method, and 79.5% and 57.5% using Brayda-Bruno's. Poor to fair inter-rater reliability (k=0.26-0.47) was observed for defect dimensions. CONCLUSION: There was good inter-rater reliability and evidence of criterion validity supporting assessments of EPSD presence using both methods. However, neither method contained all needed EPSD phenotypes for optimal sensitivity, and specific phenotypes were often misclassified.

Development of A Standardized Opsonophagocytosis Killing Assay for Group B Streptococcus and Assessment in an Interlaboratory Study.

The placental transfer of antibodies that mediate bacterial clearance via phagocytes is likely important for protection against invasive group B Streptococcus (GBS) disease. A robust functional assay is essential to determine the immune correlates of protection and assist vaccine development. Using standard reagents, we developed and optimized an opsonophagocytic killing assay (OPKA) where dilutions of test sera were incubated with bacteria, baby rabbit complement (BRC) and differentiated HL60 cells (dHL60) for 30 min. Following overnight incubation, the surviving bacteria were enumerated and the % bacterial survival was calculated relative to serum-negative controls. A reciprocal 50% killing titer was then assigned. The minimal concentrations of anti-capsular polysaccharide (CPS) IgG required for 50% killing were 1.65-3.70 ng/mL (depending on serotype). Inhibition of killing was observed using sera absorbed with homologous CPS but not heterologous CPS, indicating specificity for anti-CPS IgG. The assay performance was examined in an interlaboratory study using residual sera from CPS-conjugate vaccine trials with international partners in the Group B Streptococcus Assay STandardisatiON (GASTON) Consortium. Strong correlations of reported titers between laboratories were observed: ST-Ia r = 0.88, ST-Ib r = 0.91, ST-II r = 0.91, ST-III r = 0.90 and ST-V r = 0.94. The OPKA is an easily transferable assay with accessible standard reagents and will be a valuable tool to assess GBS-specific antibodies in natural immunity and vaccine studies.

The rise and fall of troponin in a patient with polymyositis.

Troponins are an excellent sensitive marker for myocardial ischaemic damage. However, there are several non-ischaemic cardiac and non-cardiac reasons for troponin elevation. Many cases of troponin T elevation and some troponin I cases have been reported in the literature due to inflammatory muscle disease. Here, we report a woman in her 50s who initially presents with fatigue and weakness, and is found to have elevated troponin T. The patient was appropriately worked up for cardiac causes with ECG and echocardiogram. She had positive antinuclear antibodies, antineutrophil cytoplasmic antibody and myositis panel. The elevation of troponins was attributed to polymyositis and treated with methotrexate and prednisone with recovery of patient's symptoms. This article emphasises the struggle of diagnosis in a patient with no reported medical history, having low to moderate risk of silent myocardial infarction.

A Program of Assessment Model for Point-of-Care Ultrasound Training for Pediatric Critical Care Providers: A Comprehensive Approach to Enhance Competency-Based Point-of-Care Ultrasound Training.

Point-of-care ultrasound (POCUS) is increasingly accepted in pediatric critical care medicine as a tool for guiding the evaluation and treatment of patients. POCUS is a complex skill that requires user competency to ensure accuracy, reliability, and patient safety. A robust competency-based medical education (CBME) program ensures user competency and mitigates patient safety concerns. A programmatic assessment model provides a longitudinal, holistic, and multimodal approach to teaching, assessing, and evaluating learners. The authors propose a fit-for-purpose and modifiable CBME model that is adaptable for different institutions' resources and needs for any intended competency level. This educational model drives and supports learning, ensures competency attainment, and creates a clear pathway for POCUS education while enhancing patient care and safety.

Cardiac Point-of-Care Ultrasound and Multi-Disciplinary Improvement Opportunities in Acute Systolic Heart Failure Management in a Pediatric Emergency Center.

Cardiac point-of-care ultrasound (POCUS) has the ability to rapidly assess function and identify systolic heart failure (HF), an often-missed diagnosis. POCUS has the potential to expedite medical intervention, improving overall outcomes. There have been limited studies describing pediatric emergency center (EC) utilization of cardiac POCUS and its impact on outcomes in pediatric patients. Authors performed a retrospective chart review at a tertiary children's hospital to identify all patients admitted from the EC to the Cardiac Intensive Care Unit (CICU) with acute systolic HF between January 2017 and August 2019. Outcome measures included EC length of stay (LOS), CICU LOS, and time until first IV HF medicine was administered. A total of 21 patients and 24 encounters meeting criteria were identified. Cardiac POCUS agreed with standard echocardiography in 8 of 9 cases. Patients who had a cardiac POCUS in the EC seemed more likely to receive their first dose of intravenous heart failure medication while in the Emergency Center (70% vs 43%). There was a trend toward significance, but it did not reach statistical significance (p = 0.1). EC and CICU LOS were not significantly different between POCUS and non-POCUS groups. Cardiac POCUS has the potential to have a valuable role in the early diagnosis of acute systolic HF in children. However, early diagnosis by POCUS did not translate into shorter EC or CICU LOS. This pilot data serves as a baseline for efforts to promote earlier clinical recognition of acute HF and more efficient collaboration between clinical services.

Adequacy Rate of Magnesium Citrate Bowel Preparation in a Large Retrospective Cohort.

INTRODUCTION: Magnesium Citrate (MC) is not FDA approved as a colonoscopy preparation. Advantages include low cost, small volume and accessibility without prescription. We retrospectively evaluated bowel preparations used in a private gastroenterology practice. The sample size is the largest for any similar studies (n =19,173). METHODS: Electronic Medical Records were queried for colonoscopies between 2010-2016. Bowel preps, indications (screening vs. other) and preparation adequacy were all recorded. Adequacy rates were calculated and compared using generalized linear modeling. Data were analyzed using SAS. RESULTS: The most common prep used was MC 2 bottles; screening (n=6,064, with 98.94% adequacy) and non-screening (n=3,251, with 99.29% adequacy), followed by MC 3 bottles; screening (n=2,757 with 90.35% adequacy), and non-screening (n=1,925 with 92.92% adequacy). CONCLUSION: MC bowel preparation is adequate, well tolerated, and inexpensive. In a large retrospective analysis, it compares favorably to other preparations.

Solutions to Address Inequity in Diabetes Technology Use in Type 1 Diabetes: Results from Multidisciplinary Stakeholder Co-creation Workshops.

Background: Racial-ethnic inequity in type 1 diabetes technology use is well documented and contributes to disparities in glycemic and long-term outcomes. However, solutions to address technology inequity remain sparse and lack stakeholder input. Methods: We employed user-centered design principles to conduct workshop sessions with multidisciplinary panels of stakeholders, building off of our prior study highlighting patient-identified barriers and proposed solutions. Stakeholders were convened to review our prior findings and co-create interventions to increase technology use among underserved populations with type 1 diabetes. Stakeholders included type 1 diabetes patients who had recently onboarded to technology; endocrinology and primary care physicians; nurses; diabetes educators; psychologists; and community health workers. Sessions were recorded and analyzed iteratively by multiple coders for common themes. Results: We convened 7 virtual 2-h workshops for 32 stakeholders from 11 states in the United States. Patients and providers confirmed prior published studies highlighting patient barriers and generated new ideas by co-creating solutions. Common themes of proposed interventions included (1) prioritizing more equitable systems of offering technology, (2) using visual and hands-on approaches to increase accessibility of technology and education, (3) including peer and family support systems more, and (4) assisting with insurance navigation and social needs. Discussion: Our study furthers the field by providing stakeholder-endorsed intervention ideas that propose feasible changes at the patient, provider, and system levels to reduce inequity in diabetes technology use in type 1 diabetes. Multidisciplinary stakeholder engagement in disparities research offers unique insight that is impactful and acceptable to the target population.

Generation of a Universal Human Complement Source by Large-Scale Depletion of IgG and IgM from Pooled Human Plasma.

Complement is a key component of functional immunological assays used to evaluate vaccine-mediated immunity to a range of bacterial and viral pathogens. However, standardization of these assays is complicated due to the availability of a human complement source that lacks existing antibodies acquired either through vaccination or natural circulation of the pathogen of interest. We have developed a method for depleting both IgG and IgM in 200 mL batches from pooled hirudin-derived human plasma by sequential affinity chromatography using a Protein G Sepharose column followed by POROS™ CaptureSelect™ IgM Affinity resin. The production of large IgG- and IgM-depleted batches of human plasma that retains total hemolytic and alternative pathway activities allows for improved assay standardization and comparison of immune responses in large clinical trials.

Spontaneous Remission of Metastatic Castration-Resistant Prostate Cancer: Coley's Toxin Revisited?

Metastatic castration-resistant prostate cancer (mCRPC) is an incurable disease associated with poor survival outcomes. Immunotherapy was first pioneered by William Coley in the early 20th century with the injection of live and heat-killed bacteria. Despite the recent emergence of cancer immunotherapy, mCRPC remains an elusive immune target. Spontaneous remission of mCRPC following microbial infection has not been described in the literature to date. We present evidence of spontaneous biochemical and radiologic regression in a patient with mCRPC following multiple episodes of sepsis.

mRNA vaccination in people over 80 years of age induces strong humoral immune responses against SARS-CoV-2 with cross neutralization of P.1 Brazilian variant.

Age is the major risk factor for mortality after SARS-CoV-2 infection and older people have received priority consideration for COVID-19 vaccination. However, vaccine responses are often suboptimal in this age group and few people over the age of 80 years were included in vaccine registration trials. We determined the serological and cellular response to spike protein in 100 people aged 80-96 years at 2 weeks after the second vaccination with the Pfizer BNT162b2 mRNA vaccine. Antibody responses were seen in every donor with high titers in 98%. Spike-specific cellular immune responses were detectable in only 63% and correlated with humoral response. Previous SARS-CoV-2 infection substantially increased antibody responses after one vaccine and antibody and cellular responses remained 28-fold and 3-fold higher, respectively, after dual vaccination. Post-vaccine sera mediated strong neutralization of live Victoria infection and although neutralization titers were reduced 14-fold against the P.1 variant first discovered in Brazil they remained largely effective. These data demonstrate that the mRNA vaccine platform delivers strong humoral immunity in people up to 96 years of age and retains broad efficacy against the P.1 variant of concern.

Immunological and pathological outcomes of SARS-CoV-2 challenge following formalin-inactivated vaccine in ferrets and rhesus macaques.

There is an urgent requirement for safe and effective vaccines to prevent COVID-19. A concern for the development of new viral vaccines is the potential to induce vaccine-enhanced disease (VED). This was reported in several preclinical studies with both SARS-CoV-1 and MERS vaccines but has not been reported with SARS-CoV-2 vaccines. We have used ferrets and rhesus macaques challenged with SARS-CoV-2 to assess the potential for VED in animals vaccinated with formaldehyde-inactivated SARS-CoV-2 (FIV) formulated with Alhydrogel, compared to a negative control vaccine. We showed no evidence of enhanced disease in ferrets or rhesus macaques given FIV except for mild transient enhanced disease seen 7 days after infection in ferrets. This increased lung pathology was observed at day 7 but was resolved by day 15. We also demonstrate that formaldehyde treatment of SARS-CoV-2 reduces exposure of the spike receptor binding domain providing a mechanistic explanation for suboptimal immunity.

ChAdOx1 nCoV-19 protection against SARS-CoV-2 in rhesus macaque and ferret challenge models.

Vaccines against SARS-CoV-2 are urgently required, but early development of vaccines against SARS-CoV-1 resulted in enhanced disease after vaccination. Careful assessment of this phenomena is warranted for vaccine development against SARS CoV-2. Here we report detailed immune profiling after ChAdOx1 nCoV-19 (AZD1222) and subsequent high dose challenge in two animal models of SARS-CoV-2 mediated disease. We demonstrate in rhesus macaques the lung pathology caused by SARS-CoV-2 mediated pneumonia is reduced by prior vaccination with ChAdOx1 nCoV-19 which induced neutralising antibody responses after a single intramuscular administration. In a second animal model, ferrets, ChAdOx1 nCoV-19 reduced both virus shedding and lung pathology. Antibody titre were boosted by a second dose. Data from these challenge models on the absence of enhanced disease and the detailed immune profiling, support the continued clinical evaluation of ChAdOx1 nCoV-19.

Diagnosing Acute Heart Failure in the Pediatric Emergency Department Using Point-of-Care Ultrasound.

BACKGROUND: Acute heart failure (AHF) in children is associated with significant disease burden with high rates of morbidity, mortality, and resource utilization. These children often present to the emergency department with clinical features that mimic common childhood illnesses. Cardiac point-of-care ultrasound (POCUS) can be an effective tool for rapidly identifying abnormal cardiac function. CASE REPORTS: This case series documents 10 children presenting with AHF between 2016 and 2019 and demonstrates how pediatric emergency physicians used cardiac POCUS to expedite their diagnosis, management, and disposition. All cardiac POCUS was performed before comprehensive echocardiograms were completed. One case is described in detail; the other cases are summarized in a Table. WHY SHOULD AN EMERGENCY PHYSICIAN BE AWARE OF THIS?: Early recognition of AHF is critical to reduce pediatric morbidity and mortality. With proper training, cardiac POCUS can be an effective adjunct and should be considered for the early diagnosis and treatment of infants and children with AHF.

Quantification of SARS-CoV-2 neutralizing antibody by wild-type plaque reduction neutralization, microneutralization and pseudotyped virus neutralization assays.

Virus neutralization assays measure neutralizing antibodies in serum and plasma, and the plaque reduction neutralization test (PRNT) is considered the gold standard for measuring levels of these antibodies for many viral diseases. We have developed procedures for the standard PRNT, microneutralization assay (MNA) and pseudotyped virus neutralization assay (PNA) for severe acute respiratory syndrome coronavirus 2. The MNA offers advantages over the PRNT by reducing assay time, allowing increased throughput and reducing operator workload while remaining dependent upon the use of wild-type virus. This ensures that all severe acute respiratory syndrome coronavirus 2 antigens are present, but Biosafety Level 3 facilities are required. In addition to the advantages of MNA, PNA can be performed with lower biocontainment (Biosafety Level 2 facilities) and allows for further increases in throughput. For each new vaccine, it is critical to ensure good correlation of the neutralizing activity measured using PNA against the PRNT or MNA. These assays have been used in the development and licensure of the ChAdOx1 nCoV-19 (AstraZeneca; Oxford University) and Ad26.COV2.S (Janssen) coronavirus disease 2019 vaccines and are critical for demonstrating bioequivalence of future vaccines.

Comparison of rhesus and cynomolgus macaques as an infection model for COVID-19.

A novel coronavirus, SARS-CoV-2, has been identified as the causative agent of the current COVID-19 pandemic. Animal models, and in particular non-human primates, are essential to understand the pathogenesis of emerging diseases and to assess the safety and efficacy of novel vaccines and therapeutics. Here, we show that SARS-CoV-2 replicates in the upper and lower respiratory tract and causes pulmonary lesions in both rhesus and cynomolgus macaques. Immune responses against SARS-CoV-2 are also similar in both species and equivalent to those reported in milder infections and convalescent human patients. This finding is reiterated by our transcriptional analysis of respiratory samples revealing the global response to infection. We describe a new method for lung histopathology scoring that will provide a metric to enable clearer decision making for this key endpoint. In contrast to prior publications, in which rhesus are accepted to be the preferred study species, we provide convincing evidence that both macaque species authentically represent mild to moderate forms of COVID-19 observed in the majority of the human population and both species should be used to evaluate the safety and efficacy of interventions against SARS-CoV-2. Importantly, accessing cynomolgus macaques will greatly alleviate the pressures on current rhesus stocks.

Dose-dependent response to infection with SARS-CoV-2 in the ferret model and evidence of protective immunity.

There is a vital need for authentic COVID-19 animal models to enable the pre-clinical evaluation of candidate vaccines and therapeutics. Here we report a dose titration study of SARS-CoV-2 in the ferret model. After a high (5 × 106 pfu) and medium (5 × 104 pfu) dose of virus is delivered, intranasally, viral RNA shedding in the upper respiratory tract (URT) is observed in 6/6 animals, however, only 1/6 ferrets show similar signs after low dose (5 × 102 pfu) challenge. Following sequential culls pathological signs of mild multifocal bronchopneumonia in approximately 5-15% of the lung is seen on day 3, in high and medium dosed groups. Ferrets re-challenged, after virus shedding ceased, are fully protected from acute lung pathology. The endpoints of URT viral RNA replication & distinct lung pathology are observed most consistently in the high dose group. This ferret model of SARS-CoV-2 infection presents a mild clinical disease.

Privileged Modality Distillation for Vessel Border Detection in Intracoronary Imaging.

Intracoronary imaging is a crucial imaging technology in coronary disease diagnosis as it visualizes the internal tissue morphologies of coronary arteries. Vessel border detection in intracoronary images (VBDI) is desired because it can help the succeeding procedures of computer-aided disease diagnosis. However, existing VDBI methods suffer from the challenge of vessel-environment variability (i.e. high intra- and inter-subject diversity of vessels and their surrounding tissues appeared in images). This challenge leads to the ineffectiveness in the vessel region representation for hand-crafted features, in the receptive field extraction for deeply-represented features, as well as performance suppression derived from clinical data limitation. To solve this challenge, we propose a novel privileged modality distillation (PMD) framework for VBDI. PMD transforms the single-input-single-task (SIST) learning problem in the single-mode VBDI to a multiple-input-multiple-task (MIMT) problem by using the privileged image modality to help the learning model in the target modality. This learns the enriched high-level knowledge with similar semantics and generalizes PMD on diversity-increased low-level image features for improving the model adaptation to diverse vessel environments. Moreover, PMD refines MIMT to SIST by distilling the learned knowledge from multiple to one modality. This eliminates the reliance on privileged modality in the test phase, and thus enables the applicability to each of different intracoronary modalities. A structure-deformable neural network is proposed as an elaborately-designed implementation of PMD. It expands a conventional SIST network structure to the MIMT structure, and then recovers it to the final SIST structure. The PMD is validated on intravascular ultrasound imaging and optical coherence tomography imaging. One modality is the target, and the other one can be considered as the privileged modality owing to their semantic relatedness. The experiments show that our PMD is effective in VBDI (e.g. the Dice index is larger than 0.95), as well as superior to six state-of-the-art VBDI methods.

Accurate automated Cobb angles estimation using multi-view extrapolation net.

Accurate automated quantitative Cobb angle estimation that quantitatively evaluates scoliosis plays an important role in scoliosis diagnosis and treatment. It solves the problem of the traditional manual method, which is the current clinical standard for scoliosis assessment, but time-consuming and unreliable. However, it is very challenging to achieve highly accurate automated Cobb angle estimation because it is difficult to utilize the information of Anterior-posterior (AP) and Lateral (LAT) view X-rays efficiently. We therefore propose a Multi-View Extrapolation Net (MVE-Net) that provides accurate automated scoliosis estimation in multi-view (both AP and LAT) X-rays. The MVE-Net consists of three parts: Joint-view net learning AP and LAT angles jointly based on landmarks learned from joint representation; Independent-view net learning AP and LAT angles independently based on landmarks learned from unique independent feature of AP or LAT angles; Inter-error correction net learning a combination function adaptively to offset the first two nets' errors for accurate angle estimation. Experimental results on 526 X-rays show 7.81 and 6.26 Circular Mean Absolute Error in AP and LAT angle estimation, which shows the MVE-Net provides an accurate Cobb angle estimation in multi-view X-rays. Our method therefore provides effective framework for automated, accurate, and reliable scoliosis estimation.