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.

     

A systematic review of the methodological quality of economic evaluations in genetic screening and testing for monogenic disorders

PurposeUnderstanding the value of genetic screening and testing for monogenic disorders requires high-quality, methodologically robust economic evaluations. This systematic review sought to assess the methodological quality among such studies and examined opportunities for improvement.MethodsWe searched PubMed, Cochrane, Embase, and Web of Science for economic evaluations of genetic screening/testing (2013-2019). Methodological rigor and adherence to best practices were systematically assessed using the British Medical Journal checklist.ResultsAcross the 47 identified studies, there were substantial variations in modeling approaches, reporting detail, and sophistication. Models ranged from simple decision trees to individual-level microsimulations that compared between 2 and >20 alternative interventions. Many studies failed to report sufficient detail to enable replication or did not justify modeling assumptions, especially for costing methods and utility values. Meta-analyses, systematic reviews, or calibration were rarely used to derive parameter estimates. Nearly all studies conducted some sensitivity analysis, and more sophisticated studies implemented probabilistic sensitivity/uncertainty analysis, threshold analysis, and value of information analysis.ConclusionWe describe a heterogeneous body of work and present recommendations and exemplar studies across the methodological domains of (1) perspective, scope, and parameter selection; (2) use of uncertainty/sensitivity analyses; and (3) reporting transparency for improvement in the economic evaluation of genetic screening/testing.     

Recurrent Oral and Genital Ulcers in an Infant: Neonatal Presentation of Pediatric Behçet Disease

Behçet disease is a complex, multisystem disease characterized by recurrent oral and genital ulcerations. It rarely occurs in infants or children. Neonatal Behçet disease has been reported in infants whose ulcers resolve at or before 9 weeks of age. Few cases of neonatal Behçet disease persisting into childhood have previously been reported. We report the case of a 1‐month‐old infant who presented with severe recurrent genital ulcerations and at 6 months developed recurrent oral ulcerations. Her orogenital ulcerations continue to recur. Human leukocyte antigen testing revealed HLA‐B51 and B44 positivity. This is a case of pediatric Behçet disease in the neonatal period. Behçet disease should be considered in the differential diagnosis of recurrent genital and oral ulcerations in infants and children.     

克拉屈滨治疗经典型毛细胞白血病致间质性肺炎一例报道并文献复习

毛细胞白血病（HCL）是一种以脾大、全血细胞减少、骨髓组织增生等为临床表现的罕见慢性B淋巴细胞增殖性疾病。克拉屈滨作为其一线药物，对HCL的完全缓解率很高。本文报道了2017-09-04绍兴市人民医院收治的1例经典型HCL患者在克拉屈滨治疗期间，出现严重粒细胞缺乏伴高热，合并全身皮疹及间质性肺炎，经大剂量激素等治疗后好转的诊疗过程。并结合文献回顾了HCL的诊断及治疗方法，简述了克拉屈滨治疗HCL致间质性肺炎这一少见并发症的诊疗思路，以提高临床医师对该毒副作用的认识，为临床工作提供帮助。