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.

     

African-American Adolescents’ Weight Loss Skills Utilization: Effects on Weight Change in a Sequential Multiple Assignment Randomized Trial

Objective

Successful weight loss interventions for African-Americans adolescents are lacking. Cognitive-behavioral interventions seek to develop weight loss skills (e.g., counting calories, goal setting, managing one's environment). Little is known about how well adolescents implement such skills in their daily lives. Study aims were to (1) examine weight loss skills utilization at midpoint and end of a 6-month cognitive-behavioral/motivational interviewing weight loss sequential multiple assignment randomized trial (SMART), and (2) determine if greater skill utilization predicted weight loss at treatment end and 3 months post-treatment.

Low-dose hydrocortisone in patients with COVID-19 and severe hypoxia (COVID STEROID) trial—Protocol and statistical analysis plan

Introduction

Severe acute respiratory syndrome coronavirus-2 has caused a pandemic of coronavirus disease (COVID-19) with many patients developing hypoxic respiratory failure. Corticosteroids reduce the time on mechanical ventilation, length of stay in the intensive care unit and potentially also mortality in similar patient populations. However, corticosteroids have undesirable effects, including longer time to viral clearance. Clinical equipoise on the use of corticosteroids for COVID-19 exists.

Methods

The COVID STEROID trial is an international, randomised, stratified, blinded clinical trial. We will allocate 1000 adult patients with COVID-19 receiving ≥10 L/min of oxygen or on mechanical ventilation to intravenous hydrocortisone 200 mg daily vs placebo (0.9% saline) for 7 days. The primary outcome is days alive without life support (ie mechanical ventilation, circulatory support, and renal replacement therapy) at day 28. Secondary outcomes are serious adverse reactions at day 14; days alive without life support at day 90; days alive and out of hospital at day 90; all-cause mortality at day 28, day 90, and 1 year; and health-related quality of life at 1 year. We will conduct the statistical analyses according to this protocol, including interim analyses for every 250 patients followed for 28 days. The primary outcome will be compared using the Kryger Jensen and Lange test in the intention to treat population and reported as differences in means and medians with 95% confidence intervals.

Discussion

The COVID STEROID trial will provide important evidence to guide the use of corticosteroids in COVID-19 and severe hypoxia.

     

Ductal Carcinoma In Situ with Microinvasion on Core Biopsy: Evaluating Tumor Upstaging Rate,Lymph Node Metastasis Rate,and Associated Predictive Variables

Annals of Surgical Oncology - The role of sentinel lymph node biopsy (SLNB) when ductal carcinoma in situ with microinvasion (DCISM) is identified on core biopsy is unclear. Our aim was to assess...     

Symptom occurrence, symptom distress, and quality of life in renal transplant recipients.

The growing number of persons who have successful renal transplants and the challenges they undergo as they adjust to changed lifestyles increases the need for knowledge of the recipient's view of the changes resulting from the transplantation process. One area for exploration is the recipient's perception of the symptoms that occur after transplantation. The purpose of this study was to determine symptom occurrence and symptom distress following renal transplantation and their relationships to quality of life in patients with renal transplants.     

An Evaluation of a Mixed-Gender Sexual Assault Prevention Program

This study evaluated the short-term effectiveness of a mixed-gender sexual assault prevention program developed for college students. Program participants (n = 177) were compared to non-program participants (n = 132) prior to the program and during a 2-week follow-up period on measures of rape myths, victim empathy, perceived negative consequences and estimated likelihood of committing rape, sexual communication, sexual assault awareness, and risky dating behavior. The prevention program was effective at increasing men’s victim empathy and decreasing their adherence to rape myths but ineffective at changing women’s assault-related knowledge, participation in risky dating behaviors, and sexual communication strategies. Limitations of the study and directions for future research in sexual assault prevention are addressed. Editors’ Strategic Implications: This study provides an important example of the limitations of a single session prevention programming approach (even if it is well designed and executed) in addressing a systemic and pervasive problem like sexual assault on college campuses.     

Arterial and Venous Pharmacokinetics of Ropivacaine with and without Epinephrine after Thoracic Paravertebral Block

Background: Animal and volunteer studies indicate that ropivacaine is associated with less neurologic and cardiac toxicity than bupivacaine. Ropivacaine may offer advantages when used for thoracic paravertebral block. This study was designed to describe the pharmacokinetics of ropivacaine after thoracic paravertebral block.

Methods: Twenty female patients undergoing elective unilateral breast surgery were randomly assigned to receive a single bolus thoracic paravertebral injection of 2 mg/kg ropivacaine, with or without 5 [mu]g/ml epinephrine. Simultaneous arterial and venous blood samples were obtained for plasma ropivacaine assay. Data were analyzed with NONMEM, using two possible absorption models: conventional first-order absorption and absorption following the inverse gaussian density function.

Results: Epinephrine reduced the peak plasma concentrations and delayed the time of peak concentration of ropivacaine in both the arterial and venous blood. The time course of drug input into the systemic circulation was best described by two inverse gaussian density functions. The median bioavailability of the rapid component was approximately 20% higher when epinephrine was not used. The mean absorption times were 7.8 min for the rapid absorption phase and 697 min for the slow absorption phase, with wide dispersion of the absorption function for the acute phase. The half-time of arterial-venous equilibration was 1.5 min.