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Characterization of B-cell receptor clonality and immunoglobulin gene usage at multiple time points during active SARS-CoV-2 infection.

Although monoclonal antibodies to the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) are known, B-cell receptor repertoire and its change in patients during coronavirus disease-2019 (COVID-19) progression is underreported. We aimed to study this molecularly. We used immunoglobulin heavy chain (IGH) variable region (IGHV) spectratyping and next-generation sequencing of peripheral blood B-cell genomic DNA collected at multiple time points during disease evolution to study B-cell response to SARS-CoV-2 infection in 14 individuals with acute COVID-19. We found a broad distribution of responding B-cell clones. The IGH gene usage was not significantly skewed but frequencies of individual IGH genes changed repeatedly. We found predominant usage of unmutated and low mutation-loaded IGHV rearrangements characterizing naïve and extrafollicular B cells among the majority of expanded peripheral B-cell clonal lineages at most tested time points in most patients. IGH rearrangement usage showed no apparent relation to anti-SARS-CoV-2 antibody titers. Some patients demonstrated mono/oligoclonal populations carrying highly mutated IGHV rearrangements indicating antigen experience at some of the time points tested, including even before anti-SARS-CoV-2 antibodies were detected. We present evidence demonstrating that the B-cell response to SARS-CoV-2 is individual and includes different lineages of B cells at various time points during COVID-19 progression.

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Open Access
Characterization of B-cell receptor clonality and immunoglobulin gene usage at multiple time points during active SARS-CoV-2 infection

Purpose Although monoclonal antibodies specific to the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are known, information about the B-cell receptor (BCR) repertoire and its change in patients during COVID-19 disease progression is underreported. Methods We used immunoglobulin heavy chain (IGH) variable region (IGHV) spectratyping and next-generation sequencing of peripheral blood B-cell genomic DNA collected at multiple time points during disease evolution to study B-cell response to SARS-CoV-2 infection in 14 individuals with acute COVID-19. Results We found a broad distribution of responding B-cell clones. The IGH gene usage was not significantly skewed but frequencies of individual IGH genes changed repeatedly. We found predominant usage of unmutated and low mutation-loaded IGHV rearrangements characterizing naïve and extrafollicular B-cells among the majority of expanded peripheral B-cell clonal lineages at most tested time points in most patients. IGH rearrangement usage showed no apparent relation to anti-SARS-CoV-2 antibody titers. Some patients demonstrated mono/oligoclonal populations carrying highly mutated IGHV rearrangements indicating antigen experience at some of the time points tested, including even before anti-SARS-CoV-2 antibodies were detected. Conclusion We present evidence demonstrating that the B-cell response to SARS-CoV-2 is individual and includes different lineages of B-cells at various time points during COVID-19 progression.

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Critical Care Staffing in Pandemics and Disasters: A Consensus Report From a Subcommittee of the Task Force for Mass Critical Care – Systems Strategies to Sustain the Health Care Workforce

The COVID-19 pandemic has led to unprecedented mental health disturbances, burnout, and moral distress among health-care workers, affecting their ability to care for themselves and their patients. The Workforce Sustainment subcommittee of the Task Force for Mass Critical Care (TFMCC) utilized a consensus development process, incorporating evidence from literature review with expert opinion through a modified Delphi approach to determine factors affecting mental health, burnout, and moral distress in health-care workers, to propose necessary actions to help prevent these issues, and enhance workforce resilience, sustainment, and retention. Consolidation of evidence gathered from literature review and expert opinion resulted in 197 total statements that were synthesized into 14 major suggestions. These suggestions were organized into three categories: (1) mental health and well-being for staff in medical settings; (2) system-level support and leadership; and (3) research priorities and gaps. Suggestions include both general and specific occupational interventions to support health-care worker basic physical needs, psychological distress, reduce moral distress and burnout, and foster mental health and resilience. The Workforce Sustainment subcommittee of the TFMCC offers evidence-informed operational strategies to assist health-care workers and hospitals plan, prevent, and treat the factors affecting health-care worker mental health, burnout, and moral distress to improve resilience and retention following the COVID-19 pandemic.

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Open Access
Review of Autologous Fat Grafting in Postmastectomy Reconstruction Patients: Nonroutine Diagnostics and Oncologic Safety.

A retrospective chart review was performed for all patients undergoing FG at a multi-site single health system between 2015 to 2018. A total of 228 eligible breasts from 155 patients were identified using Current Procedural Terminology codes. Patients were divided by reconstructive technique. Bivariate analyses compared baseline characteristics and post-FG outcomes. Mean age for patients undergoing ABR (129 breasts) was 52.8 years compared to 48.6 years for those undergoing IBR (99 breasts; P = 0.002). A heavier volume of fat was grafted per ABR breast (143.8mL) than per IBR breast (102.2mL; P = 0.002). Forty-seven (20.6%) breasts required FG revision, more frequently in ABR breasts (31.0%) than IBR breasts (7.1%; P < 0.001). Following FG, 17.5% of patients experienced a palpable mass, and 18.9% of breasts underwent nonroutine diagnostics or procedures, with no difference between ABR and IBR groups. Most biopsies noted benign findings such as fat necrosis (2.2%) or a benign mass (0.9%), with recurrence only noted in two patients (0.9%). Mean follow-up was 20.4 months. FG is a safe, surgically simple procedure more commonly performed in ABR breasts. FG use in ABR and IBR breasts is oncologically safe, with no impairment in breast surveillance and low rates of locoregional recurrence, but possibly increased incidence of nonroutine imaging and biopsies.

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Open Access
Characteristics of Primary Care Providers' Consultations With a Statewide Child Psychiatry Access Program Regarding Autism Spectrum Disorder.

Child Psychiatry Access Programs (CPAPs) provide consultative support for pediatric primary care providers (PCPs) to treat co-morbid mental health (MH) symptoms among patients with Autism Spectrum Disorder (ASD). We examined differences in illness severity, comorbidity, and psychotropic medication use between patients with and without ASD for whom primary care providers sought consultation from Maryland's CPAP. We examined N=3641 Maryland's CPAP consultations from 2012 to 2019; n=311 were consultations for ASD. Demographics, treatment recommendations, diagnoses, and Clinical Global Impression-Severity scores were collected. Patients who received psychotropic medication or psychotherapy by any mental health provider were defined as comanaged. Descriptive statistics and logistic regression were conducted. Sample size for regression was N=1854. Compared with non-ASD, patients with consults for ASD were more often male (P < 0.001), aged 0-5 years (P < 0.001), severely ill (Clinical Global Impression-Severity > 4) (P < 0.001), and prescribed stimulants, nonstimulant attention-deficit hyperactivity disorder medications, and antipsychotic medications (P < 0.001). Controlling for key covariates, consultations for youth displaying aggression were 3.02 times (P < 0.001) more likely, with Clinical Global Impression-Severity > 4 were 2.36 times (P < 0.001) more likely, and prescribed antipsychotics were 4.30 times more likely to concern an ASD patient (P<0.001). A larger proportion of ASD patients (vs. non-ASD) had comorbid psychiatric diagnoses of attention-deficit hyperactivity disorder, a learning disability, and disruptive behavior disorder vs. a smaller proportion with major depressive disorder. ASD patients for whom primary care providers sought Maryland's CPAP consultation were more severe and complex than non-ASD patients in terms of comorbid diagnoses and medication regimen.

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Open Access
Evaluating Medic Performance in Combat Casualty Care Simulation and Training: A Scoping Review of Prospective Research.

Combat medics are required to perform highly technical medical procedures in austere environments with minimal error. Effective means to quantify medic performance in field and simulated environments are critical to optimize medic training procedures as well as to evaluate the influence of medical equipment and other supportive technologies on medic performance. Human performance evaluation in combat casualty care presents many unique challenges due to the unique environment (battlefields) and population (medics) that must be represented. Recent advances in simulation and measurement technology have presented opportunities to improve simulation fidelity and measurement quality; however, it is currently unclear to what extent these advances have been adopted in this domain. In this work, a scoping review of recent (2011-2021) prospective research on Army medic (68 W and Special Operations) performance is presented. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews guidelines served as the framework for the review. The goal of this work was to summarize recent trends and practices and to illuminate opportunities for future work. Two human factors experts performed an exhaustive review of relevant, peer-reviewed literature and systematically identified articles for inclusion in the final analysis. The articles were examined in detail, and data elements of interest were extracted. Forty-eight articles were identified based on the defined inclusion criteria. Thirty three of the articles focused on technological evaluation, 25 focused on medic training procedures, and 5 focused on evaluating medical techniques. Study contributions were predominantly related to medic training materials/procedures and simulator technology. Supportive medical technologies, including telemedical systems, hemorrhage control devices, and ultrasound devices, also received significant attention. Timing was the most common metric used to quantify medic performance, followed by skill pass/fail ratings. There was a notable lack of neurophysiological data used to examine medic physical/cognitive workload during procedures, a growing practice in many other related domains. The most commonly simulated procedures were hemorrhage control, airway management, and thoracostomy. Notable limitations cited across articles were insufficient simulation fidelity, inadequate sample size or sample representativeness, and poor study design. This work provided a summary of recent peer-reviewed research related to medic simulation and training, and performance evaluation. This article should be used to contextualize existing research and inspire new research questions. Expanding and advancing research on medic simulation and training will help to ensure optimal casualty care at the front lines.

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Open Access