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 vanguard randomised feasibility trial comparing three regimens of peri-operative oxygen therapy on recovery after major surgery

International recommendations encourage liberal administration of oxygen to patients having surgery under general anaesthesia, ostensibly to reduce surgical site infection. However, the optimal oxygen regimen to minimise postoperative complications and enhance recovery from surgery remains uncertain. The hospital operating theatre randomised oxygen (HOT-ROX) trial is a multicentre, patient- and assessor-blinded, parallel-group, randomised clinical trial designed to assess the effect of a restricted, standard care, or liberal peri-operative oxygen therapy regimen on days alive and at home after surgery in adults undergoing prolonged non-cardiac surgery under general anaesthesia. Here, we report the findings of the internal vanguard feasibility phase of the trial undertaken in four large metropolitan hospitals in Australia and New Zealand that included the first 210 patients of a planned overall 2640 trial sample, with eight pre-specified endpoints evaluating protocol implementation and safety. We screened a total of 956 participants between 1 September 2019 and 26 January 2021, with data from 210 participants included in the analysis. Median (IQR [range]) time-weighted average intra-operative F_iO₂ was 0.30 (0.26–0.35 [0.20–0.59]) and 0.47 (0.44–0.51 [0.37–0.68]) for restricted and standard care, respectively (mean difference (95%CI) 0.17 (0.14–0.20), p < 0.001). Median time-weighted average intra-operative F_iO₂ was 0.83 (0.80–0.85 [0.70–0.91]) for liberal oxygen therapy (mean difference (95%CI) compared with standard care 0.36 (0.33–0.39), p < 0.001). All feasibility endpoints were met. There were no significant patient adverse events. These data support the feasibility of proceeding with the HOT-ROX trial without major protocol modifications.     

Randomized prospective trial of fractionated stereotactic radiosurgery with chemotherapy versus chemotherapy alone for bevacizumab-resistant high-grade glioma

Journal of Neuro-Oncology - Outcomes for patients with recurrent high-grade glioma (HGG) progressing on bevacizumab (BEV) are dismal. Fractionated stereotactic radiosurgery (FSRS) has been shown to...     

Editorial Commentary: Rotator Cuff Repair: How Much Tension Can a Tendon Stand? If It Hurts My Finger,It's Probably Hurting the Tendon

Rotator cuff repairs may fail anatomically because of greater-than-needed tension to approximate the tendon to the greater tuberosity during repair. Surgeons should make every effort to minimize the tension when reapproximating a torn rotator cuff.