Citations

7049 Background: Langerhans cell histiocytosis (LCH) can manifest as single system (SS) disease, multisystem (MS) disease, or pulmonary LCH (smoking-related). There is a paucity of data on prognostic factors including risk organ (RO) involvement (liver, spleen, and bone marrow) in adult LCH, which we sought to address in this study. Methods: Single-center retrospective study of patients ≥18y diagnosed with LCH from 1998 to 2020. Univariate and multivariate analyses for progression free survival (PFS) and overall survival (OS) were conducted using age, sex, organ involvement, LCH subtype, year of diagnosis, BRAF V600E status, and treatments. Results: We included 219 patients with LCH; median age 43y (range 19-88), females 51%, SS unifocal (23%), SS multifocal (6%), pulmonary (31%) and MS (40%). Commonly involved organs included lung (53%), bone (42%), skin (24%), pituitary (16%), and CNS (12%). BRAF V600E was positive in 40/88 (46%). Median follow-up duration was 6.1y (95% CI, 5.1- 7.1). On univariate analysis, factors associated with worse PFS were bone LCH, RO involvement, multifocal/MS LCH, and radiation therapy alone; those with worse OS included RO involvement, MS disease, BRAF V600E+, and age ≥45y at diagnosis. In multivariate analysis, BRAF V600E and age ≥45y at diagnosis were associated with worse mortality (Table). Median PFS was not reached (NR-NR) for SS unifocal LCH, 5mo (0-12.7) for SS multifocal LCH, 110mo (84.7-135.3) for pulmonary LCH, and 27mo (17.2-36.8) for MS LCH. 5-year OS was 97.4% for SS unifocal LCH, 100% for SS multifocal LCH, 96.1% for pulmonary LCH, and 79.9% for MS LCH. 41 (18.7%) developed a second primary malignancy (SPM), of which 11 were hematologic neoplasms. There was a trend towards a higher prevalence of SPMs in patients with BRAF V600E (28% vs. 17%; p = 0.22). Conclusions: In our large single-center study, PFS for multifocal and MS LCH was worse than SS unifocal or pulmonary LCH. RO involvement was not associated with outcomes in multivariate analysis. Overall prognosis was excellent for all subtypes except MS LCH. BRAF V600E and older age were associated with worse OS. The prevalence of SPMs was very high and needs to be explored further.[Table: see text]

Abstract Background MR elastography can determine organ‐related stiffness, which reflects the degree of fibrosis. Liver stiffness increases in cirrhosis, and stiffness increases further post‐prandially due to increased portal blood in‐flow. Non‐selective beta‐blockers (NSBB) reduce the portal venous inflow, but their effect on liver and spleen stiffness are disputed. Aims To assess whether MR elastography of the liver or spleen reflects the severity of cirrhosis, whether treatment with NSBB changes liver and spleen stiffness and whether changes in stiffness can predict the effect of NSBB on portal pressure. Methods Fifty‐two patients with cirrhosis underwent liver vein catheterization and two‐dimensional (2D) MR elastography on separate days. Thirty‐six of the patients had a hepatic venous pressure gradient (HVPG) of ≥12 mmHg and were tested prior to, and after, intravenous infusion of NSBB using HVPG measurement and MR elastography. Results HVPG showed a strong, positive, linear relationship with liver stiffness ( r 2 = 0.92; P < .001) and spleen stiffness ( r 2 = 0.94; P < .001). The cut‐off points for identifying patients with a HVPG ≥ 12 mmHg were 7.7 kPa for liver stiffness (sensitivity 0.78, specificity 0.64) and 10.5 kPa for spleen stiffness (sensitivity 0.8, specificity 0.79). Intravenous administration of NSBB significantly decreased spleen stiffness by 6.9% (CI: 3.5‐10.4, P < .001), but NSBB had no consistent effect on liver stiffness. However, changes in spleen stiffness were not related to the HVPG response ( P = .75). Conclusions Two‐dimensional MR elastographic estimation of liver or spleen stiffness reflects the degree of portal hypertension in patients with liver cirrhosis, but changes in stiffness after NSBB do not predict the effect on HVPG.

When COVID-19 caused worldwide cancellations of summer research immersion programs in 2020, Mayo Clinic rallied to create an alternate virtual experience called Summer Foundations in Research (SFIR). SFIR was designed not only to ensure the continuance of science pathways training for undergraduate scientists but also to support undergraduate mental wellbeing, given the known pandemic stressors. A total of 170 participants took part in the program and were surveyed pre-post for outcomes in biomedical research career knowledge, biomedical research career interest, research skills confidence, and three dimensions of mental wellbeing. Knowledge of and interest in careers involving biomedical research rose significantly following participation in SFIR. The participants’ mean research skills confidence also rose between 0.08 and 1.32 points on a 7-point scale across 12 items from the Clinical Research Appraisal Inventory. Success in science pathways support was accompanied by positive shifts in participant mental wellbeing. Measurable decreases in stress (Perceived Stress Scale, p < 0.0001) accompanied gains in resilience (Brief Resilience Scale, p < 0.0001) and life satisfaction (Satisfaction with Life Scale, p = 0.0005). Collectively, the data suggest that core objectives of traditional in-person summer research programming can be accomplished virtually and that these programs can simultaneously impact student wellbeing. This theoretical framework is particularly salient during COVID-19, but the increased accessibility of virtual programs such as SFIR can continue to bolster science education pathways long after the pandemic is gone.

AbstractMycobacterium is a large, clinically relevant bacterial genus made up of the agents of tuberculosis and leprosy and hundreds of species of saprophytic nontuberculous mycobacteria (NTM). Pathogenicity, clinical presentation, epidemiology, and antimicrobial susceptibilities are exceptionally diverse between species. Patients with end-stage lung disease and recipients of lung transplants are at a higher risk of developing NTM colonization and disease and of severe manifestations and outcomes of tuberculosis. Data from the past three decades have increased our knowledge of these infections in lung transplant recipients. Still, there are knowledge gaps to be addressed to further our understanding of risk factors and optimal treatments for mycobacterial infections in this population.

Purpose The purpose of the present study was to investigate body mass index, multi-morbidity, and COVID-19 Risk Score as predictors of severe COVID-19 outcomes. Patients Patients from this study are from a well-characterized patient cohort collected at Mayo Clinic between January 1, 2020 and May 23, 2020; with confirmed COVID-19 diagnosis defined as a positive result on reverse-transcriptase-polymerase-chain-reaction (RT-PCR) assays from nasopharyngeal swab specimens. Measures Demographic and clinical data were extracted from the electronic medical record. The data included: date of birth, gender, ethnicity, race, marital status, medications (active COVID-19 agents), weight and height (from which the Body Mass Index (BMI) was calculated, history of smoking, and comorbid conditions to calculate the Charlson Comorbidity Index (CCI) and the U.S Department of Health and Human Services (DHHS) multi-morbidity score. An additional COVID-19 Risk Score was also included. Outcomes included hospital admission, ICU admission, and death. Results Cox proportional hazards models were used to determine the impact on mortality or hospital admission. Age, sex, and race (white/Latino, white/non-Latino, other, did not disclose) were adjusted for in the model. Patients with higher COVID-19 Risk Scores had a significantly higher likelihood of being at least admitted to the hospital (HR = 1.80; 95% CI = 1.30, 2.50; P < .001), or experiencing death or inpatient admission (includes ICU admissions) (HR = 1.20; 95% CI = 1.02, 1.42; P = .028). Age was the only statistically significant demographic predictor, but obesity was not a significant predictor of any of the outcomes. Conclusion Age and COVID-19 Risk Scores were significant predictors of severe COVID-19 outcomes. Further work should examine the properties of the COVID-19 Risk Factors Scale.

Abstract Diagnosis of interstitial lung disease (ILD) requires a multidisciplinary discussion approach that includes clinicians, radiologists, and pathologists. Surgical lung biopsy (SLB) is currently the recommended standard in obtaining pathologic specimens for patients with ILD requiring a tissue diagnosis. The increased diagnostic confidence and accuracy provided by microscopic pathology assessment of SLB specimens must be balanced with the associated risks in patients with ILD. This document was developed by the SLB Working Group of the Pulmonary Fibrosis Foundation, composed of a multidisciplinary group of ILD physicians, including pulmonologists, radiologists, pathologists, and thoracic surgeons. In this document, we present an up-to-date literature review of the indications, contraindications, risks, and alternatives to SLB in the diagnosis of fibrotic ILD; outline an integrated approach to the decision-making around SLB in the diagnosis of fibrotic ILD; and provide practical information to maximize the yield and safety of SLB.

Background Patients with restless legs syndrome (RLS) have increased silent microvascular disease by magnetic resonance imaging. However, there has been no previous autopsy confirmation of these magnetic resonance imaging findings. RLS is also frequently associated with inflammatory and immunologically mediated medical disorders. The postmortem cortex in patients with RLS was therefore evaluated for evidence of microvascular and immunological changes. Methods and Results Ten microvascular injury samples of precentral gyrus in 5 patients with RLS (3 men, 2 women; mean age, 81 years) and 9 controls (2 men, 7 women; mean age, 90 years) were studied by hematoxylin and eosin stains in a blinded fashion. None of the subjects had a history of stroke or neurologic insults. In a similar manner, the following immunohistochemistry stains were performed: (1) glial fibrillary acidic protein (representing gliosis, reactive change of glial cells in response to damage); (2) CD3 (a T‐cell marker); (3) CD19 (a B‐cell marker); (4) CD68 (a macrophage marker); and (5) CD117 (a mast cell marker). Patients with RLS had significantly greater silent microvascular disease ( P =0.015) and gliosis ( P =0.003). T cells were increased in RLS compared with controls ( P =0.009) and tended to colocalize with microvascular disease ( P =0.003). Other markers did not differ. There was no correlation between microvascular lesion load and RLS severity or duration. Conclusions Patients with RLS had statistically significantly more silent cerebral microvascular disease and gliosis than controls compatible with previous magnetic resonance imaging studies and with studies showing a link between RLS and hypertension, clinical stroke, and cardiovascular disease. T‐cell invasion may be a secondary phenomenon.

Background Several animal studies have demonstrated that mechanical thrombectomy (MT) for acute ischemic stroke (AIS) may cause vessel wall injury (VWI). However, the histological changes in human cerebral arteries following MT are difficult to determine. Objective To investigate the occurrence of VWI during MT by histological and immunohistochemical evaluation of AIS clots. Methods As part of the multicenter STRIP registry, 277 clots from 237 patients were analyzed using Martius Scarlett Blue stain and immunohistochemistry for CD34 (endothelial cells) and smooth muscle actin (smooth muscle cells). Results MT devices used were aspiration catheters (100 cases), stentriever (101 cases), and both (36 cases). VWI was found in 33/277 clots (12%). There was no significant correlation between VWI and MT device. The degree of damage varied from grade I (mild intimal damage, 24 clots), to grade II (relevant intimal and subintimal damage, 3 clots), and III (severe injury, 6 clots). VWI clots contained significantly more erythrocytes (p=0.006*) and less platelets/other (p=0.005*) than non-VWI clots suggesting soft thrombus material. Thrombolysis correlated with a lower rate of VWI (p=0.04*). VWI cases showed a significantly higher number of passes (2 [1–4] vs 1 [1–3], p=0.028*) and poorer recanalization outcome (p=0.01*) than cases without VWI. Conclusions Histological markers of VWI were present in 12% of AIS thrombi, suggesting that VWI might be related to MT. VWI was associated with soft thrombus consistency, higher number of passes and poorer revascularization outcome. There was no significant correlation between VWI and MT device.

Introduction: Myocardial infarction is an inflammatory condition that leads to scar deposition and cardiac remodeling. Stem cells (SC) are an alternative to prevent cardiac remodeling, but have poor survival after transplanted to an pro-inflammatory ischemic myocardium. Polymeric biocompatible scaffolds are biomaterials that can improve SC retention and survival, with the goal to improve regional cardiac function. Methods: We electrospun fibers of a) uniaxial polycaprolactone (PCL) and b) coaxial PCL (core) and gelatin methacrylate (sheath), an anti-inflammatory substance. We first tested the SC retention of each scaffold. Then, adipose derived mesenchymal SCs (MSCs) were co-cultured with M1 macrophages (pro-inflammatory) with and without scaffold and we measure the expression of inflammatory-related genes (RT-PCR). Lastly, PCL+GelMA scaffolds with and without MSCs (3.5x10 3 MSCs) were implanted after myocardial ischemia/reperfusion (IR) and followed for 2 weeks. Results: The average diameter of PCL and PCL+GelMA fibers were 730±40nm and 1110±50nm, respectively. PCL+GelMA scaffolds increased MSCs adhesion compared to PCL (absorbance: 0.09±.03 for PCL and 0.24±0.02 for coaxial, p<0.05). Figure A shows that MSCs in presence of M1 macrophages had a significant increase in inflammatory genes, which was significantly ameliorated in the presence of GelMA. In preliminary animal studies (n=1-4), MSCs delivered in a PCL+GelMA scaffold had partial preservation of regional function parameteres compared to IR only or IR+PCL+GelMA (no MSCs) (Figure B). Conclusion: Coaxially PCL+gelMA scaffolds attenuate the pro-inflammatory milieu of MSCs under ischemic-like conditions, and may improve regional cardiac remodeling.

OBJECTIVES: To compare clinical characteristics and outcomes of children admitted to the PICU for severe acute respiratory syndrome coronavirus 2–related illness with or without multisystem inflammatory syndrome in children. The secondary objective was to identify explanatory factors associated with outcome of critical illness defined by a composite index of in-hospital mortality and organ system support requirement. DESIGN: Retrospective cohort study. SETTING: Thirty-eight PICUs within the Viral Infection and Respiratory Illness Universal Study registry from March 2020 to January 2021. PATIENTS: Children less than 18 years with severe acute respiratory syndrome coronavirus 2–related illness with or without multisystem inflammatory syndrome in children. MEASUREMENTS AND MAIN RESULTS: Of 394 patients, 171 (43.4%) had multisystem inflammatory syndrome in children. Children with multisystem inflammatory syndrome in children were more likely younger (2–12 yr vs adolescents; p < 0.01), Black (35.6% vs 21.9%; p < 0.01), present with fever/abdominal pain than cough/dyspnea (p < 0.01), and less likely to have comorbidities (33.3% vs 61.9%; p < 0.01) compared with those without multisystem inflammatory syndrome in children. Inflammatory marker levels, use of inotropes/vasopressors, corticosteroids, and anticoagulants were higher in multisystem inflammatory syndrome in children patients (p < 0.01). Overall mortality was 3.8% (15/394), with no difference in the two groups. Diagnosis of multisystem inflammatory syndrome in children was associated with longer duration of hospitalization as compared to nonmultisystem inflammatory syndrome in children (7.5 d[interquartile range, 5–11] vs 5.3 d [interquartile range, 3–11 d]; p < 0.01). Critical illness occurred in 164 patients (41.6%) and was more common in patients with multisystem inflammatory syndrome in children compared with those without (55.6% vs 30.9%; p < 0.01). Multivariable analysis failed to show an association between critical illness and age, race, sex, greater than or equal to three signs and symptoms, or greater than or equal to two comorbidities among the multisystem inflammatory syndrome in children cohort. Among nonmultisystem inflammatory syndrome in children patients, the presence of greater than or equal to two comorbidities was associated with greater odds of critical illness (odds ratio 2.95 [95% CI, 1.61–5.40]; p < 0.01). CONCLUSIONS: This study delineates significant clinically relevant differences in presentation, explanatory factors, and outcomes among children admitted to PICU with severe acute respiratory syndrome coronavirus 2–related illness stratified by multisystem inflammatory syndrome in children.