Neuropathic Pain After Burn Injury: A Severe and Common Problem in Recovery.

OBJECTIVE: The aim of this study was to address the limited understanding of neuropathic pain (NP) among burn survivors by comprehensively examining its prevalence and related factors on a national scale using the Burn Model System (BMS) National Database. BACKGROUND: NP is a common but underexplored complaint among burn survivors, greatly affecting their quality of life and functionality well beyond the initial injury. Existing data on NP and its consequences in burn survivors are limited to select single-institution studies, lacking a comprehensive national perspective. METHODS: The BMS National Database was queried to identify burn patients responding to NP-related questions at enrollment, 6 months, 12 months, 2 years, and 5 years postinjury. Descriptive statistics and regression analyses were used to explore associations between demographic/clinical characteristics and self-reported NP at different time points. RESULTS: There were 915 patients included for analysis. At discharge, 66.5% of patients experienced NP in their burn scars. Those with NP had significantly higher Patient-Reported Outcomes Measurement Information System 29 (PROMIS-29) pain inference, itch, anxiety, depression, and sleep disturbance scores and were less able to partake in social roles. Multiple logistic regression revealed male sex, % total body surface area, and moderate-to-severe pain as predictors of NP at 6 months. At 12 months, % total body surface area and moderate-to-severe pain remained significant predictors, while ethnicity and employment status emerged as significant predictors at 24 months. CONCLUSIONS: This study highlights the significant prevalence of NP in burn patients and its adverse impacts on their physical, psychological, and social well-being. The findings underscore the necessity of a comprehensive approach to NP treatment, addressing both physical symptoms and psychosocial factors.

Predictors at 6 and 12 Months for Social Participation Outcome at 24 Months in the Adult Burn Injury Population: A Burn Model System National Database Study.

OBJECTIVE: To identify clinical factors (physical and psychological symptoms and post-traumatic growth) that predict social participation outcome at 24-month after burn injury. DESIGN: A prospective cohort study based on Burn Model System National Database. SETTING: Burn Model System centers. PARTICIPANTS: 181 adult participants less than 2 years after burn injury (N=181). INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: Demographic and injury variables were collected at discharge. Predictor variables were assessed at 6 and 12 months: Post-Traumatic Growth Inventory Short Form (PTGI-SF), Post-Traumatic Stress Disorder Checklist Civilian Version (PCL-C), Patient-Reported Outcomes Measurement Information System (PROMIS-29) Depression, Anxiety, Sleep Disturbance, Fatigue, and Pain Interference short forms, and self-reported Heat Intolerance. Social participation was measured at 24 months using the Life Impact Burn Recovery Evaluation (LIBRE) Social Interactions and Social Activities short forms. RESULTS: Linear and multivariable regression models were used to examine predictor variables for social participation outcomes, controlling for demographic and injury variables. For LIBRE Social Interactions, significant predictors included the PCL-C total score at 6 months (ß=-0.27, P<.001) and 12 months (ß=-0.39, P<.001), and PROMIS-29 Pain Interference at 6 months (ß=-0.20, P<.01). For LIBRE Social Activities, significant predictors consisted of the PROMIS-29 Depression at 6 months (ß=-0.37, P<.001) and 12 months (ß=-0.37, P<.001), PROMIS-29 Pain Interference at 6 months (ß=-0.40, P<.001) and 12 months (ß=-0.37, P<.001), and Heat Intolerance at 12 months (ß=-4.55, P<.01). CONCLUSIONS: Post-traumatic stress and pain predicted social interactions outcomes, while depression, pain and heat intolerance predicted social activities outcomes in people with burn injury.

Moderation Effects of Daily Behavior on Associations Between Symptoms and Social Participation Outcomes After Burn Injury: A 6-Month Digital Phenotyping Study.

OBJECTIVE: To examine the moderation effects of daily behavior on the associations between symptoms and social participation outcomes after burn injury. DESIGN: A 6-month prospective cohort study. SETTING: Community. PARTICIPANTS: Twenty-four adult burn survivors. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: Symptoms and social participation outcomes were assessed weekly using smartphone surveys, including symptoms of pain (Patient-Reported Outcomes Measurement Information System [PROMIS] Pain Intensity and Pain Interference), anxiety (PROMIS Anxiety), and depression (Patient Health Questionnaire), as well as outcomes of social interactions and social activities (Life Impact Burn Recovery Evaluation [LIBRE] Social Interactions and Social Activities). Daily behaviors were automatically recorded by a smartphone application and smartphone logs, including physical activity (steps, travel miles, and activity minutes), sleep (sleep hours), and social contact (number of phone calls and message contacts). RESULTS: Multilevel models controlling for demographic and burn injury variables examined the associations between symptoms and social participation outcomes and the moderation effects of daily behaviors. Lower (worse) LIBRE Social Interactions and LIBRE Social Activities scores were significantly associated with higher (worse) PROMIS Pain Intensity, PROMIS Pain Interference, PROMIS Anxiety, and Patient Health Questionnaire-8 scores (P<.05). Additionally, daily steps and activity minutes were associated with LIBRE Social Interactions and LIBRE Social Activities (P<.05), and significantly moderated the association between PROMIS Anxiety and LIBRE Social Activities (P<.001). CONCLUSIONS: Social participation outcomes are associated with pain, anxiety, and depression symptoms after burn injury, and are buffered by daily physical activity. Future intervention studies should examine physical activity promotion to improve social recovery after burns.

A Comparison of Demographics Across the Burn, Spinal Cord Injury, and Traumatic Brain Injury Model Systems.

OBJECTIVE: This study aims to analyze the demographic profiles of participants in the traumatic brain injury (TBI), burn injury (BI), and spinal cord injury (SCI) Model Systems Databases. DESIGN: Data from the Burn Model System (BMS) National Database, TBI Model Systems (TBIMS) National Database, and SCI Model System (SCIMS) Database was analyzed from 1994 to 2020. SETTING: Not applicable PARTICIPANTS: The study included 16 years and older participants with available data in selected variables, totaling 4,807 BI, 19,127 TBI, and 18,473 SCI participants. INTERVENTIONS: Not applicable MAIN OUTCOME MEASURES: Variables including age, race, ethnicity, sex, education level, primary payor source, family income level, employment status at one-year post-injury, etiology, and mortality at one-year post-injury were analyzed across the database. RESULTS: Median ages at injury for BMS (40.4), TBIMS (40), and SCIMS (38) Database participants were comparable. Males constituted about 75% of participants in BMS, TBIMS, and SCIMS datasets, with approximately 75% having a high school education or lower. The proportion of participants funded by Medicare during initial hospital care varied across the BMS (14%), TBIMS (15.6%), and SCIMS (10.2%). For family income (data available for BMS and SCIMS), roughly 30% of these participants reported a family income below $25,000. Etiology data indicated 49.0% of TBI and 40.7% of SCI cases resulted from vehicular incidents. CONCLUSIONS: An overlapping at-risk population for these injuries appears to be middle-aged males with lower education levels and family incomes, who have access to vehicles. This underscores the need for preventive initiatives tailored to this identified population to mitigate the risk of these injuries.

PET/CT targeted tissue sampling reveals virus specific dIgA can alter the distribution and localization of HIV after rectal exposure.

Human immunodeficiency virus (HIV) vaccines have not been successful in clinical trials. Dimeric IgA (dIgA) in the form of secretory IgA is the most abundant antibody class in mucosal tissues, making dIgA a prime candidate for potential HIV vaccines. We coupled Positron Emission Tomography (PET) imaging and fluorescent microscopy of 64Cu-labeled, photoactivatable-GFP HIV (PA-GFP-BaL) and fluorescently labeled dIgA to determine how dIgA antibodies influence virus interaction with mucosal barriers and viral penetration in colorectal tissue. Our results show that HIV virions rapidly disseminate throughout the colon two hours after exposure. The presence of dIgA resulted in an increase in virions and penetration depth in the transverse colon. Moreover, virions were found in the mesenteric lymph nodes two hours after viral exposure, and the presence of dIgA led to an increase in virions in mesenteric lymph nodes. Taken together, these technologies enable in vivo and in situ visualization of antibody-virus interactions and detailed investigations of early events in HIV infection.

Preliminary Exploration of Long-Term Patient Outcomes After Tracheostomy in Burns: A Burn Model System Study.

INTRODUCTION: Upper airway management is crucial to burn care. Endotracheal intubation is often performed in the setting of inhalation injury, burns of the face and neck, or large burns requiring significant resuscitation. Tracheostomy may be necessary in patients requiring prolonged ventilatory support. This study compares long-term, patient-reported outcomes in burn patients with and without tracheostomy. MATERIALS AND METHODS: Data from the Burn Model System Database, collected from 2013 to 2020, were analyzed. Demographic and clinical data were compared between those with and without tracheostomy. The following patient-reported outcomes, collected at 6-, 12-, and 24-mo follow-up, were analyzed: Veterans RAND 12-Item Health Survey (VR-12), Satisfaction with Life, Community Integration Questionnaire, Patient-Reported Outcomes Measurement Information System 29-Item Profile Measure, employment status, and days to return to work. Regression models and propensity-matched analyses were used to assess the associations between tracheostomy and each outcome. RESULTS: Of 714 patients included in this study, 5.5% received a tracheostomy. Mixed model regression analyses demonstrated that only VR-12 Physical Component Summary scores at 24-mo follow-up were significantly worse among those requiring tracheostomy. Tracheostomy was not associated with VR-12 Mental Component Summary, Satisfaction with Life, Community Integration Questionnaire, or Patient-Reported Outcomes Measurement Information System 29-Item Profile Measure scores. Likewise, tracheostomy was not found to be independently associated with employment status or days to return to work. CONCLUSIONS: This preliminary exploration suggests that physical and psychosocial recovery, as well as the ability to regain employment, are no worse in burn patients requiring tracheostomy. Future investigations of larger scale are still needed to assess center- and provider-level influences, as well as the influences of various hallmarks of injury severity. Nonetheless, this work should better inform goals of care discussions with patients and families regarding the use of tracheostomy in burn injury.

Anatomic Distribution of Intravenously Injected IgG Takes Approximately 1 Week to Achieve Stratum Corneum Saturation in Vaginal Tissues.

i.v. injected Abs have demonstrated protection against simian HIV infection in rhesus macaques, paving the way for the Antibody Mediated Prevention trial in which at-risk individuals for HIV received an i.v. infusion of the HIV broadly neutralizing Ab VRC01. However, the time needed for these Abs to fully distribute and elicit protection at mucosal sites is still unknown. In this study, we interrogate how long it takes for Abs to achieve peak anatomical levels at the vaginal surface following i.v. injection. Fluorescently labeled VRC01 and/or Gamunex-C were i.v. injected into 24 female rhesus macaques (Macaca mulatta) with vaginal tissues and plasma acquired up to 2 wk postinjection. We found that Ab delivery to the vaginal mucosa occurs in two phases. The first phase involves delivery to the submucosa, occurring within 24 h and persisting beyond 1 wk. The second phase is the delivery through the stratified squamous epithelium, needing ∼1 wk to saturate the stratum corneum. This study has important implications for the efficacy of immunoprophylaxis targeting pathogens at the mucosa.

Longitudinal Trends in Severe Traumatic Brain Injury Inpatient Rehabilitation.

OBJECTIVE: The goal of this study is to describe national trends in inpatient rehabilitation facility (IRF) discharges for the most severely disabled cohort of patients with traumatic brain injury (TBI). METHODS: Data from the Uniform Data System for Medical Rehabilitation for patients discharged from an IRF between January 1, 2002, and December 31, 2017, with a diagnosis of TBI and an admission Functional Independence Measure of 18, the lowest possible score, were obtained and analyzed. RESULTS: Of the 252 112 patients with TBI discharged during the study period, 10 098 met the study criteria. From 2002 to 2017, the number of patients with an IRF admission Functional Independence Measure of 18 following TBI discharged from IRFs annually decreased from 649 to 488, modeled by a negative regression (coefficient = -2.97; P = .001), and the mean age (SD) increased from 43.0 (21.0) to 53.7 (21.3) years (coefficient = 0.70; P < .001). During the study period, the number of patients with the most severe disability on admission to IRF who were discharged annually as a proportion of total patients with TBI decreased from 5.5% to 2.5% (odds ratio = 0.95; P < .001) and their mean length of stay decreased from 41.5 (36.2) to 29.3 (24.9) days (coefficient = -0.83; P < .001]. CONCLUSION: The number and proportion of patients with the most severe disability on IRF admission following TBI who are discharged from IRFs is decreasing over time. This may represent a combination of primary prevention, early mortality due to withdrawal of life-sustaining treatment, alternative discharge dispositions, or changes in admitting and reimbursement practices. Furthermore, there has been a decrease in the duration of IRF level care for these individuals, which could ultimately lead to poorer functional outcomes, particularly given the importance of specialized rehabilitative care in this population.

Digital Interventions for Social Participation in Adults with Long-term Physical Conditions: A Systematic Review.

This review aims to identify and evaluate digital interventions for social participation in the growing population of adults with long-term physical conditions. Articles were sourced from MEDLINE, EMBASE, CINAHL and PsycINFO databases using subject headings and keywords related to "social participation" and "digital technology". Studies that adopted digital technology interventions to improve social participation in adults with long-term physical conditions were included. Data on study methodology, participant and digital intervention characteristics, and findings related to social participation were extracted. The search yielded a total of 4646 articles and 14 articles met criteria for final review with five randomized controlled trials, two non-randomized clinical trials and seven one-group pretest-posttest clinical trials. Studies were organized based on the digital intervention strategy implemented to improve social participation: group support (n = 4), individual skill training or counseling (n = 6), education and support (n = 3), and mixed intervention (n = 1). The group support interventions developed a social network among participants through videoconference, app, or virtual reality platform. Three studies reported positive improvements in different aspects of social participation. Individual skill training or counseling mainly utilized phone calls to help participants cope with activity participation and interpersonal relationship issues. Only two studies demonstrated benefits for social participation. The education and support intervention, which used messages and website information to increase participants' knowledge and provide support, showed positive findings in three studies. This review suggests digital interventions for improving social participation in adults with long-term physical conditions are feasible and the effectiveness of different strategies may vary.Registration: This review was prospectively registered on the International Prospective Register of Systematic Reviews (PROSPERO) (registry number: CRD42021254105).

Divergent Antibody Repertoires Found for Omicron versus Wuhan SARS-CoV-2 Strains Using Ig-MS.

SARS-CoV-2 Omicron (B.1.1.529) and its subvariants are currently the most common variants of concern worldwide, featuring numerous mutations in the spike protein and elsewhere that collectively make Omicron variants more transmissible and more resistant to antibody-mediated neutralization provided by vaccination, previous infections, and monoclonal antibody therapies than their predecessors. We recently reported the creation and characterization of Ig-MS, a new mass spectrometry-based serology platform that can define the repertoire of antibodies against an antigen of interest at single proteoform resolution. Here, we applied Ig-MS to investigate the evolution of plasma antibody repertoires against the receptor-binding domain (RBD) of SARS-CoV-2 in response to the booster shot and natural viral infection. We also assessed the capacity for antibody repertoires generated in response to vaccination and/or infection with the Omicron variant to bind to both Wuhan- and Omicron-RBDs. Our results show that (1) the booster increases antibody titers against both Wuhan- and Omicron- RBDs and elicits an Omicron-specific response and (2) vaccination and infection act synergistically in generating anti-RBD antibody repertoires able to bind both Wuhan- and Omicron-RBDs with variant-specific antibodies.

Next-Generation Serology by Mass Spectrometry: Readout of the SARS-CoV-2 Antibody Repertoire.

Methods of antibody detection are used to assess exposure or immunity to a pathogen. Here, we present Ig-MS, a novel serological readout that captures the immunoglobulin (Ig) repertoire at molecular resolution, including entire variable regions in Ig light and heavy chains. Ig-MS uses recent advances in protein mass spectrometry (MS) for multiparametric readout of antibodies, with new metrics like Ion Titer (IT) and Degree of Clonality (DoC) capturing the heterogeneity and relative abundance of individual clones without sequencing of B cells. We applied Ig-MS to plasma from subjects with severe and mild COVID-19 and immunized subjects after two vaccine doses, using the receptor-binding domain (RBD) of the spike protein of SARS-CoV-2 as the bait for antibody capture. Importantly, we report a new data type for human serology, that could use other antigens of interest to gauge immune responses to vaccination, pathogens, or autoimmune disorders.

The Impact of Burn Size on Community Participation: A Life Impact Burn Recovery Evaluation (LIBRE) Study.

OBJECTIVE: To assess the association of burn size and community participation as measured by the LIBRE Profile. SUMMARY OF BACKGROUND DATA: Burn size is an established clinical predictor of survival after burn injury. It is often a factor in guiding decisions surrounding early medical interventions; however, literature is inconclusive on its relationship to quality of life outcomes. METHODS: This is a secondary data analysis of a cross-sectional survey of adult burn survivors. Self-reported data were collected between October 2014 and December 2015 from 601 burn survivors aged ≥18 years with ≥5% total body surface area (TBSA) or burns to critical areas. Sociodemographic characteristics were compared between participants with small burns (≤40% TBSA burned) and large burns (>40% TBSA burned). Ordinary least squares regression models examined associations between burn size and LIBRE Profile scale scores with adjustments for sex, current work status, burns to critical areas, and time since burn injury. RESULTS: The analytic sample comprised 562 participants with data available for burn size. 42% of respondents had large burns (>40% TBSA burned) and 58% reported smaller burns (TBSA ≤40%). In adjusted regression models, patients with large burns tended to score lower on the Social Activities and Work & Employment scales ( P < 0.05) and higher on the Family & Friends scale ( P < 0.05). Participants with burns >40% TBSA scored lower for several individual items in the Social Activities scale and one item in the Work & Employment scale ( P < 0.05). CONCLUSIONS: Increasing burn size was found to be negatively associated with selected items of Work & Employment and Social Activities, but positively associated with aspects of Family & Friend Relationships. Future longitudinal studies are necessary to assess and understand the long-term social impact of burn injuries on adult populations.

De novo emergence of SARS-CoV-2 spike mutations in immunosuppressed patients.

BACKGROUND: The continuing evolution of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants with decreased susceptibility to neutralizing antibodies is of clinical importance. Several spike mutations associated with immune escape have evolved independently in association with different variants of concern (VOCs). How and when these mutations arise is still unclear. We hypothesized that such mutations might arise in the context of persistent viral replication in immunosuppressed hosts. METHODS: Nasopharyngeal specimens were collected longitudinally from two immunosuppressed patients with persistent SARS-CoV-2 infection. Plasma was collected from these same patients late in disease course. SARS-CoV-2 whole genome sequencing was performed to assess the emergence and frequency of mutations over time. Select Spike mutations were assessed for their impact on viral entry and antibody neutralization in vitro. RESULTS: Our sequencing results revealed the intrahost emergence of spike mutations that are associated with circulating VOCs in both immunosuppressed patients (del241-243 and E484Q in one patient, and E484K in the other). These mutations decreased antibody-mediated neutralization of pseudotyped virus particles in cell culture, but also decreased efficiency of spike-mediated cell entry. CONCLUSIONS: These observations demonstrate the de novo emergence of SARS-CoV-2 spike mutations with enhanced immune evasion in immunosuppressed patients with persistent infection. These data suggest one potential mechanism for the evolution of VOCs and emphasize the importance of continued efforts to develop antiviral drugs for suppression of viral replication in hospitalized settings.

For-Profit and Not-for-Profit Inpatient Rehabilitation in Traumatic Brain Injury: Analysis of Demographics and Outcomes.

OBJECTIVE: To describe differences in characteristics and outcomes of patients with traumatic brain injury by inpatient rehabilitation facility (IRF) profit status. DESIGN: Retrospective database review using the Uniform Data System for Medical Rehabilitation. SETTING: IRFs. PARTICIPANTS: Individual discharges (N=53,630) from 877 distinct rehabilitation facilities for calendar years 2016 through 2018. INTERVENTION: Not applicable. MAIN OUTCOME MEASURES: Patient demographic data (age, race, primary payer source), admission and discharge FIM, FIM gain, length of stay efficiency, acute hospital readmission from for-profit and not-for-profit IRFs within 30 days, and community discharges by facility profit status. RESULTS: Patients at for-profit facilities were significantly older (69.69 vs 64.12 years), with lower admission FIM scores (52 vs 57), shorter lengths of stay (13 vs 15 days), and higher discharge FIM scores (88 vs 86); for-profit facilities had higher rates of community discharges (76.8% vs 74.6%) but also had higher rates of readmission (10.3% vs 9.9%). CONCLUSIONS: The finding that for-profit facilities admit older patients who are reportedly less functional on admission and more functional on discharge, with higher rates of community discharge but higher readmission rates than not-for-profit facilities is an unexpected and potentially anomalous finding. In general, older, less functional patients who stay for shorter periods of time would not necessarily be expected to make greater functional gains. These differences should be further studied to determine if differences in patient selection, coding and/or billing, or other unreported factors underlie these differences.

Predictors of Acute Transfer and Mortality Within 6 Months From Admission to an Inpatient Rehabilitation Facility for Patients With Brain Tumors.

OBJECTIVE: To obtain useful information for clinicians in evaluating patients with brain tumors for transfer to and subsequent care in inpatient rehabilitation facilities (IRFs). DESIGN: Retrospective chart review. SETTING: Inpatient rehabilitation facility. PARTICIPANTS: A total of 208 adults with either initial or recurrent brain tumors who were admitted to an IRF between January 2017 and December 2018 after an acute hospitalization. INTERVENTIONS: None MAIN OUTCOME MEASURES: Transfer from an IRF to an acute care hospital and mortality within 6 months from admission to an IRF. RESULTS: Of the 208 patients who met inclusion criteria, 20.2% were transferred to an acute care hospital during the IRF stay, which was associated with prior chemotherapy, steroid use, and laterality of tumor. In total, 36.9% of patients with brain tumors died within 6 months of an IRF admission that was associated with recurrent tumor diagnosis, prior chemotherapy, prior neurosurgical intervention, prior neurostimulant use, use of steroids, isocitrate dehydrogenase and O6-methyl-guanyl-methyl-transferase biomarkers, and laterality and location of tumor. CONCLUSIONS: Patients with brain tumors have a notable potential for acute hospital transfer and mortality within 6 months of IRF stay, with several tumor- and treatment-related risk factors. This information can help identify functional goals, identify high risk patients, enable closer clinical monitoring, and facilitate focused care discussions at IRFs.

An Elusive Case of Tuberculous Meningitis in a Young Man With Altered Mental Status.

BACKGROUND: Tuberculous meningitis (TBM) is a rare, frequently elusive diagnosis, often characterized by vague symptoms and associated with high rates of morbidity and mortality. CASE REPORT: We present a case of TBM in a young man with a headache and altered mental status. In addition, we provide a brief history of TBM, review the pathophysiology of the disease, discuss clinical and radiologic features, and detail the management of TBM both emergently and throughout our patient's hospital course. WHY SHOULD AN EMERGENCY PHYSICIAN BE AWARE OF THIS?: Our patient's lack of pulmonary symptoms, initially unremarkable head computed tomography, and two prior emergency department evaluations for headache without concerning historical features or physical examination findings collectively highlight the challenges of diagnosing TBM early in its symptom course. We encourage emergency physicians to consider TBM in appropriate patients, particularly those with risk factors for tuberculosis infection.

A MUC16 IgG Binding Activity Selects for a Restricted Subset of IgG Enriched for Certain Simian Immunodeficiency Virus Epitope Specificities.

We have recently shown that MUC16, a component of the glycocalyx of some mucosal barriers, has elevated binding to the G0 glycoform of the Fc portion of IgG. Therefore, IgG from patients chronically infected with human immunodeficiency virus (HIV), who typically exhibit increased amounts of G0 glycoforms, showed increased MUC16 binding compared to uninfected controls. Using the rhesus macaque simian immunodeficiency virus SIVmac251 model, we can compare plasma antibodies before and after chronic infection. We find increased binding of IgG to MUC16 after chronic SIV infection. Antibodies isolated for tight association with MUC16 (MUC16-eluted antibodies) show reduced FcγR engagement and antibody-dependent cellular cytotoxicity (ADCC) activity. The glycosylation profile of these IgGs was consistent with a decrease in FcγR engagement and subsequent ADCC effector function, as they contain a decrease in afucosylated bisecting glycoforms that preferentially bind FcγRs. Testing of the SIV antigen specificity of IgG from SIV-infected macaques revealed that the MUC16-eluted antibodies were enriched for certain specific epitopes, including regions of gp41 and gp120. This enrichment of specific antigen responses for fucosylated bisecting glycoforms and the subsequent association with MUC16 suggests that the immune response has the potential to direct specific epitope responses to localize to the glycocalyx through interaction with this specific mucin.IMPORTANCE Understanding how antibodies are distributed in the mucosal environment is valuable for developing a vaccine to block HIV infection. Here, we study an IgG binding activity in MUC16, potentially representing a new IgG effector function that would concentrate certain antibodies within the glycocalyx to trap pathogens before they can reach the underlying columnar epithelial barriers. These studies reveal that rhesus macaque IgG responses during chronic SIV infection generate increased antibodies that bind MUC16, and interestingly, these MUC16-tethered antibodies are enriched for binding to certain antigens. Therefore, it may be possible to direct HIV vaccine-generated responses to associate with MUC16 and enhance the antibody's ability to mediate immune exclusion by trapping virions within the glycocalyx and preventing the virus from reaching immune target cells within the mucosa. This concept will ultimately have to be tested in the rhesus macaque model, which is shown here to have MUC16-targeted antigen responses.

Program Administrator Burnout in Graduate Medical Education: a Longitudinal Study.

BACKGROUND: Little is known about the level of burnout among program administrators (PAs) in medical education and its impact on the trainee environment. OBJECTIVE: To investigate variations in burnout levels over a 1-year period among a national cohort of PAs and examine any associations between perceived support and isolation. DESIGN: A 1-year longitudinal study conducted to assess burnout levels among PAs across the USA. The Copenhagen Burnout Inventory (score range, 0-100) was used to measure burnout over one academic year (July 2017-June 2018). The generalized estimating equations model was used to measure changes in burnout levels from the start of the academic year. To explore the differences in burnout scores across question response levels, a one-way ANOVA test was utilized and reported as least squares means ± SD. PARTICIPANTS: Individuals who self-identified as PAs in a graduate medical education training program. Among the 1084 persons nationwide who expressed interest, 904 (83%) completed the baseline survey; 29 of the 42 (69%) local administrators completed the survey. "Clients" defined as interns, residents/fellows, and medical students. MAIN MEASURES: Change in burnout score using the validated tool. Hypothesis formulated prior to data collection. KEY RESULTS: Among the 931 participants, the 3rd quarter (March 2018) marked the lowest average personal burnout score (change from the start of academic year, - 3.67; p < 0.001, 95% CI - 5.77 to - 1.58) and work-related burnout score (change, - 3.03; p < 0.001, 95% CI - 5.01 to - 1.06). Client-related burnout was the lowest in September 2017 (change, - 1.46; p = 0.491; 95% CI - 3.54 to 0.62). June 2018: those who strongly agreed to feeling isolated in their current position had an increased personal (69.1 ± 18.4 SD), work-related (72.5 ± 20.8 SD), and client-related (42.3 ± 23.7 SD) burnout score. CONCLUSIONS: PA burnout levels fluctuate over the academic year and are shown to increase as feelings of isolation grow.

Considerations for the Management of Oncology Patients During the COVID-19 Pandemic.

Worldwide incidence and mortality due to the coronavirus disease 2019 (COVID-19) pandemic is greatest in the United States, with the initial epicenter in New York. In Nassau County, New York, where we practice, our institution has had more than 2500 cases and has discharged from the hospital more than 1000 patients. As many academic and private institutions have swiftly shifted their clinical and research priorities to address the pandemic, data are emerging regarding both the impact of malignancy on COVID-19 outcomes as well as the challenges faced in assuring that cancer care remains unimpeded. Of concern, recent studies of cancer patients primarily in China and Italy have suggested that advanced malignancy is associated with increased susceptibility to severe COVID-19 infection. At present, more than 500 clinical trials are underway investigating the pathogenesis and treatment of COVID-19, including expanded use of oncology drugs, such as small molecular inhibitors of cytokine pathways. Here, we begin by reviewing the latest understanding of COVID-19 pathophysiology and then focus our attention on the impact of this virus on hematologic and oncologic practice. Finally, we highlight ongoing investigational treatment approaches that are so relevant to the care of oncology patients during this extraordinary pandemic.