CD19 + CD21lo/neg cells are increased in systemic sclerosis-associated interstitial lung disease

Interstitial lung disease (ILD) represents a significant cause of morbidity and mortality in systemic sclerosis (SSc). The purpose of this study was to examine recirculating lymphocytes from SSc patients for potential biomarkers of interstitial lung disease (ILD). Peripheral blood mononuclear cells (PBMCs) were isolated from patients with SSc and healthy controls enrolled in the Vanderbilt University Myositis and Scleroderma Treatment Initiative Center cohort between 9/2017–6/2019. Clinical phenotyping was performed by chart abstraction. Immunophenotyping was performed using both mass cytometry and fluorescence cytometry combined with t-distributed stochastic neighbor embedding analysis and traditional biaxial gating. This study included 34 patients with SSc-ILD, 14 patients without SSc-ILD, and 25 healthy controls. CD21^lo/neg cells are significantly increased in SSc-ILD but not in SSc without ILD (15.4 ± 13.3% vs. 5.8 ± 0.9%, p = 0.002) or healthy controls (5.0 ± 0.5%, p < 0.0001). While CD21^lo/neg B cells can be identified from a single biaxial gate, tSNE analysis reveals that the biaxial gate is comprised of multiple distinct subsets, all of which are increased in SSc-ILD. CD21^lo/neg cells in both healthy controls and SSc-ILD are predominantly tBET positive and do not have intracellular CD21. Immunohistochemistry staining demonstrated that CD21^lo/neg B cells diffusely infiltrate the lung parenchyma of an SSc-ILD patient. Additional work is needed to validate this biomarker in larger cohorts and longitudinal studies and to understand the role of these cells in SSc-ILD.

     

Left Ventricular Unloading Before Percutaneous Coronary Intervention is Associated With Improved Survival in Patients With Acute Myocardial Infarction Complicated by Cardiogenic Shock: A Systematic Review and Meta-Analysis

BackgroundLeft ventricular unloading with Impella may improve survival outcomes in patients with acute myocardial infarction complicated by cardiogenic shock (AMI-CS). However, the optimal timing to initiate left ventricular unloading has yet to be established. Therefore, we conducted a systematic review and meta-analysis to compare survival in patients with AMI-CS who were supported with Impella prior to PCI (pre-PCI) to those in whom support was initiated following PCI (post-PCI).MethodsAll studies that evaluated the impact of pre-PCI versus post-PCI Impella placement in patients with AMI-CS were included. Primary endpoints included in-hospital, 30-day, and 6-month survival rates.ResultsWe identified five observational studies comparing outcomes in 432 patients with AMI-CS, of which 173 patients were treated with Impella pre-PCI and 259 patients post-PCI. Patients in the pre-PCI group had lower in-hospital mortality compared to patients in the post-PCI group (RR 0.62, 95% CI: 0.50–0.76, I² = 0%). The lower mortality rate in the pre-PCI group remained evident at 30 days (HR 0.60, 95% CI: 0.47–0.78, I² = 0%) and at 6 months (HR 0.66, 95% CI: 0.44–0.97, I² = 0%). There was no difference in the risk of adverse events including reinfarction, stroke, major bleeding, acute ischemic limb, access site bleeding, and hemolysis.ConclusionsIn this meta-analysis of studies evaluating survival among AMI-CS patients with left ventricular unloading initiated pre- versus post-PCI, Impella placement prior to PCI was associated with improved survival.     

Clinical effect of early administration of tocilizumab following the initiation of corticosteroid therapy for patients with COVID-19

IntroductionSevere acute respiratory syndrome coronavirus 2 (SARS-CoV-2) first broke out in Wuhan in December 2019, and has since caused a global pandemic. The efficacy of several drugs has been evaluated, and it is now evident that tocilizumab has a beneficial effect, especially combined with corticosteroids, in patients with Coronavirus Disease 2019 (COVID-19). However, the optimal timing of tocilizumab administration has not yet been established. The goal of the present study was to determine the optimal timing of tocilizumab administration after starting corticosteroid therapy in patients with COVID-19.MethodsWe retrospectively analyzed the clinical characteristics of patients who were hospitalized for COVID-19 and treated with tocilizumab and corticosteroids in our hospital. The patients were divided into concurrent and sequential groups. The concurrent group received tocilizumab ≤24 h after corticosteroids, and the sequential group received tocilizumab >24 h after corticosteroid administration.ResultsThe baseline clinical characteristics of tocilizumab administration were similar between the two groups. White blood cell counts were significantly lower and C-reactive protein levels were significantly higher in the concurrent group than the sequential group. In the concurrent group, tocilizumab administration led to a significant decrease in maximum body temperature. In addition, there were significantly more oxygen-free days in the concurrent group than in the sequential group. However, survival rate was not significantly different between the concurrent and the sequential groups.ConclusionsIn the combination therapy with tocilizumab and corticosteroids, early administration of tocilizumab after starting corticosteroid treatment is effective when treating COVID-19.     

桦木酸对大鼠肺纤维化模型肺组织的影响＊

目的 探讨桦木酸对大鼠肺纤维化模型肺组织中NF-κB、β-arrestin2表达的影响。方法 15只SPF级雄性SD大鼠分为对照组、模型组、桦木酸组，每组5只。对照组予以单次气管内注射1 mL·kg^-1 0.9%生理盐水，模型组和桦木酸组予单次气管内快速注射5 mg·kg^-1博来霉素建立大鼠肺纤维化模型。造模1天后，对照组及模型组给予10 mL·kg^-1 1%可溶性淀粉溶液，桦木酸组给予50 mg·kg^-1的桦木酸悬浮液，持续21天。HE、Masson染色方法观察肺组织病理改变。酶联免疫吸附法（ELISA）检测肺组织匀浆IL-6的水平。免疫组化法检测肺组织中NF-κB、β-arrestin2、IκBα的表达。结果 与对照组相比，模型组肺组织匀浆中IL-6水平升高，NF-κB、β-arrestin2、IκBα蛋白表达均上调（P<0.05）。与模型组相比，桦木酸组肺组织匀浆中IL-6水平降低，肺组织中NF-κB、β-arrestin2、IκBα蛋白表达均下调（P<0.05）。结论 桦木酸可减轻肺部炎症、减慢肺纤维化的发生发展，可能与下调肺组织中NF-κB、β-arrestin2有关。     

Rationale for a Clinical Trial That Compares Acute Stroke Rehabilitation at Inpatient Rehabilitation Facilities to Skilled Nursing Facilities: Challenges and Opportunities

In the United States, approximately 400,000 patients with acute stroke are discharged annually to inpatient rehabilitation facilities (IRFs) or skilled nursing facilities (SNFs). Typically, IRFs provide time-intensive therapy for an average of 2-3 weeks, whereas SNFs provide more moderately intensive therapy for 4-5 weeks. The factors that influence discharge to an IRF or SNF are multifactorial and poorly understood. The complexity of these factors in combination with subjective clinical indications contributes to large variations in the use of IRFs and SNFs. This has significant financial implications for health care expenditure, given that stroke rehabilitation at IRFs costs approximately double that at SNFs. To control health care spending without compromising outcomes, the Institute of Medicine has stated that policy reforms that promote more efficient use of IRFs and SNFs are critically needed. A major barrier to the formulation of such policies is the highly variable and low-quality evidence for the comparative effectiveness of IRF- vs SNF-based stroke rehabilitation. The current evidence is limited by the inability of observational data to control for residual confounding, which contributes to substantial uncertainty around any magnitude of benefit for IRF- vs SNF-based care. Furthermore, it is unclear which specific patients would receive the most benefit from each setting. A randomized controlled trial addresses these issues, because random treatment allocation facilitates an equitable distribution of measured and unmeasured confounders. We discuss several measurement, practical, and ethical issues of a trial and provide our rationale for design suggestions that overcome some of these issues.