Abnormal thrombosis and neutrophil activation increase hospital-acquired sacral pressure injuries and morbidity in COVID-19 patients.

Hospitalized patients have an increased risk of developing hospital-acquired sacral pressure injury (HASPI). However, it is unknown whether SARS-CoV-2 infection affects HASPI development. To explore the role of SARS-CoV-2 infection in HASPI development, we conducted a single institution, multi-hospital, retrospective study of all patients hospitalized for ≥5 days from March 1, 2020 to December 31, 2020. Patient demographics, hospitalization information, ulcer characteristics, and 30-day-related morbidity were collected for all patients with HASPIs, and intact skin was collected from HASPI borders in a patient subset. We determined the incidence, disease course, and short-term morbidity of HASPIs in COVID-19(+) patients, and characterized the skin histopathology and tissue gene signatures associated with HASPIs in COVID-19 disease. COVID-19(+) patients had a 63% increased HASPI incidence rate, HASPIs of more severe ulcer stage (OR 2.0, p<0.001), and HASPIs more likely to require debridement (OR 3.1, p=0.04) compared to COVID-19(-) patients. Furthermore, COVID-19(+) patients with HASPIs had 2.2x increased odds of a more severe hospitalization course compared to COVID-19(+) patients without HASPIs. HASPI skin histology from COVID-19(+) patients predominantly showed thrombotic vasculopathy, with the number of thrombosed vessels being significantly greater than HASPIs from COVID-19(-) patients. Transcriptional signatures of a COVID-19(+) sample subset were enriched for innate immune responses, thrombosis, and neutrophil activation genes. Overall, our results suggest that immunologic dysregulation secondary to SARS-CoV-2 infection, including neutrophil dysfunction and abnormal thrombosis, may play a pathogenic role in development of HASPIs in patients with severe COVID-19.

Factors associated with matching into research-focused dermatology residency programs.

Although dermatology is one of the most competitive specialties to match into, there is limited transparency in the residency match process. In this retrospective cohort study of 2234 allopathic medical graduates, we identify applicant characteristics associated with matching into research oriented dermatology programs. Many of the statistically significant variables in our study, including PhD/MD status, graduating from a Top-25 NIH funded medical school, increasing total number of pre-residency publications (PRPs), and increasing number of high-impact PRPs, correlate with future academic employment. Although literature shows an association between an increasing number of first author PRPs and future academic employment, we did not find number of first or last author PRPs to be predictive of matching into a research oriented residency program. A more comprehensive evaluation of an applicant's research output, considering both the final products of an applicant's research endeavors and an applicant's role in various projects, may better approximate an applicant's commitment to academics.

Trends of Research Output of Allopathic Medical Students Matching Into Dermatology, 2007-2018.

IMPORTANCE: According to the National Residency Matching Program's biennial Charting Outcomes in the Match (NRMP ChOM) reports, the mean number of research items of matched allopathic dermatology applicants has nearly tripled since 2007, rising from 5.7 to 14.7. Research items are self-reported by applicants and serve as an approximation of research output. Because the NRMP research items field is unverified and reported as an aggregate of several different research pursuits, it may not be an accurate representation of applicant research output. OBJECTIVE: To determine if the rise in NRMP-reported data is associated with a rise in verifiable, indexed publications from matched allopathic dermatology applicants from 2007 to 2018. DESIGN, SETTING, AND PARTICIPANTS: Cross-sectional study including a bibliometric analysis on accepted applicant research output among 2234 matched allopathic dermatology applicants, with a total of 6229 publications, in dermatology residency programs for the years 2007, 2009, 2011, 2014, 2016, and 2018. MAIN OUTCOME AND MEASURES: The primary outcomes were the mean number of peer-reviewed indexed publications and mean number of NRMP ChOM research items. Secondary outcomes assessed the quality of indexed publications by analyzing article type and journal of publication. RESULTS: From 2007 to 2018, the mean number of indexed publications per matched dermatology applicant increased from 1.6 to 4.7 (203% increase). Indexed publications consistently compose a minority of NRMP ChOM research items (28.8% across the 6 years of the study). Nonindexed research items increased at more than double the rate of indexed publications. Bibliometric analysis showed that all other types of publications are increasing at a rate of 6 to 9 times that of basic science publications, dermatology-related publications increased at 5 times the rate of non-dermatology publications, and publications in lower-impact factor dermatology journals increased at 4 times the rate of publications in higher-impact factor dermatology journals. CONCLUSIONS AND RELEVANCE: This cross-sectional study provides data on the research output of matched dermatology applicants. Indexed publications compose a minority of NRMP research items. Medical student self-reports of research output may emphasize research quantity over quality.

Sentinel lymph node biopsy guideline concordance in melanoma: Analysis of the National Cancer Database.

BACKGROUND AND OBJECTIVES: This study investigated the impact of treating facility type on guideline-concordant sentinel lymph node biopsy (SLNB) management in T1a* (defined as a Breslow depth <0.76 mm without ulceration or mitoses) and T2/T3 melanoma. METHODS: This was a retrospective cohort study utilizing the National Cancer Database from 2012 to 2016. RESULTS: Our cohort included 109,432 patients. For T1a* melanomas, 85% of patients received guideline-concordant SLNB management at community and academic facilities versus 75% of patients at integrated network facilities (p < .001). Over 83% of patients with T2/T3 melanoma treated at an academic facility received guideline-concordant SLNB management versus 77% treated at a community facility (p < .001). Adjusting for demographic and clinical factors, integrated (adjusted odds ratio, aOR = 0.54), and comprehensive community (aOR = 0.74) facilities were less likely to provide guideline-concordant SLNB management in patients with T1a* melanoma compared to academic facilities. Community facilities (aOR = 0.72) were less likely to provide guideline-concordant SLNB management in patients with T2/T3 melanoma compared to academic facilities. CONCLUSION: Academic facilities provide the highest rate of guideline-concordant sentinel lymph node management. Comparatively, community programs may underutilize SLNB in T2/T3 disease, while integrated and comprehensive community facilities may over-utilize SLNB in T1a* disease.

Development of sacral/buttock retiform purpura as an ominous presenting sign of COVID-19 and clinical and histopathologic evolution during severe disease course.

Retiform purpura has been described as a relatively frequent cutaneous finding in patients with coronavirus disease 2019 (COVID-19). The etiology is hypothesized to be related to thrombotic vasculopathy based on lesional biopsy specimen findings, but the pathogenesis of the vasculopathy is not completely understood. Here, we present a case of a retiform purpuric patch on the sacrum/buttocks in a hospitalized patient prior to subsequent diagnosis of COVID-19 and an eventual fatal disease course. Two lesional biopsy specimens at different time points in the disease course revealed thrombotic vasculopathy, despite therapeutic anticoagulation. Detailed histopathologic evaluation using immunohistochemical markers suggest the etiology of the vasculopathy involves both persistent complement activation and platelet aggregation, which possibly promote ongoing thrombus formation. This case highlights that sacral/buttock retiform purpuric patches may be a presenting sign of infection with SARS-CoV-2 virus and may represent an ominous sign supporting a future severe disease course. In addition, biopsy specimen findings at separate time points demonstrate that cutaneous vasculopathy may persist despite adequate systemic anticoagulation, possibly due to the combination of persistent complement and platelet activation. Finally, occlusive thrombi in sacral/buttock retiform purpuric patches may contribute to future ulceration and significant cutaneous morbidity in patients who survive COVID-19.

D-dimer can help differentiate suspected pulmonary embolism patients that require anti-coagulation.

OBJECTIVES: Determine whether D-dimer concentration in the absence of imaging can differentiate patients that require anti-coagulation from patients who do not require anti-coagulation. METHODS: Data was obtained retrospectively from 366 hemodynamically stable adult ED patients with suspected pulmonary embolism (PE). Patients were categorized by largest occluded artery and aggregated into: 'Require anti-coagulation' (main, lobar, and segmental PE), 'Does not require anti-coagulation' (sub-segmental and No PE), 'High risk of deterioration' (main and lobar PE), and 'Not high risk of deterioration' (segmental, sub-segmental, and No PE) groups. Wilcoxon rank-sum test was used for 2 sample comparisons of median D-dimer concentrations. Receiver operating characteristic (ROC) curve analysis was utilized to determine a D-dimer cut-off that could differentiate 'Require anti-coagulation' from 'Does not require anti-coagulation' and 'High risk of deterioration' from 'Low risk of deterioration' groups. RESULTS: The 'Require anti-coagulation' group had a maximum area under the curve (AUC) of 0.92 at an age-adjusted D-dimer cut-off of 1540 with a specificity of 86% (95% CI, 81-91%), and sensitivity of 84% (79-90%). The 'High risk of deterioration' group had a maximum AUC of 0.93 at an age-adjusted D-dimer cut-off of 2500 with a specificity of 90% (85-93%) and sensitivity of 83% (77-90%). CONCLUSIONS: An age-adjusted D-dimer cut-off of 1540 ng/mL differentiates suspected PE patients requiring anti-coagulation from those not requiring anti-coagulation. A cut-off of 2500 differentiates those with high risk of clinical deterioration from those not at high risk of deterioration. When correlated with clinical outcomes, these cut-offs can provide an objective method for clinical decision making when imaging is unavailable.

Financial Conflicts of Interest Among Emergency Medicine Journals' Editorial Boards.

STUDY OBJECTIVE: We aim to characterize the prevalence of financial conflicts of interest among emergency medicine journal editorial board members. METHODS: We conducted a cross-sectional study of editorial board members of leading peer-reviewed emergency medicine journals. A list of highly cited emergency medicine journals was curated with Journal Citation Reports and Google Scholar Metrics. Financial conflicts of interest were obtained by curating the Centers for Medicare & Medicaid Services' Open Payments database for the most recently available data (2017). The outcomes of this study were prevalence of financial conflicts of interest and frequency of disclosure on each journal's Web site. RESULTS: Editorial boards of the top 5 journals were analyzed. Of the 198 unique US-based physician-editors, 60 (30.3%) had a financial conflict of interest documented as general or research-based payments. The 52 editors with general payments had a median of 2 payments (interquartile range [IQR] 1 to 8.25), with a median of $202 (IQR $69 to $7,386); the maximum general payment was $115,730 received from industry. For research payments, 26 editors (13.1%) had a median 4 payments (IQR 2 to 9), with a median of $47,095 (IQR $5,328 to $126,025) and maximum of $3,590,000 received from industry. Seven editors in one of the emergency medicine journals included in this study publicly disclosed competing interests; dollar amounts were not reported. CONCLUSION: Nearly one third of US-based editors at leading emergency medicine journals had financial conflicts of interest, although only one journal publicly disclosed the presence of payments. Public disclosure of editorial board members' financial relationships with industry may allow for more transparency related to the content published in these journals.

Quantitative analysis of the impact of a human pathogenic mutation on the CCT5 chaperonin subunit using a proxy archaeal ortholog.

The human chaperonin complex is a ~ 1 MDa nanomachine composed of two octameric rings formed from eight similar but non-identical subunits called CCT. Here, we are elucidating the mechanism of a heritable CCT5 subunit mutation that causes profound neuropathy in humans. In previous work, we introduced an equivalent mutation in an archaeal chaperonin that assembles into two octameric rings like in humans but in which all subunits are identical. We reported that the hexadecamer formed by the mutant subunit is unstable with impaired chaperoning functions. This study quantifies the loss of structural stability in the hexadecamer due to the pathogenic mutation, using differential scanning calorimetry (DSC) and isothermal titration calorimetry (ITC). The disassembly of the wild type complex, which is tightly coupled with subunit denaturation, was decoupled by the mutation without affecting the stability of individual subunits. Our results verify the effectiveness of the homo-hexadecameric archaeal chaperonin as a proxy to assess the impact of subtle defects in heterologous systems with mutations in a single subunit.