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.

     

Tranexamic acid through intravenous,intramuscular and oral routes: an individual participant data meta‐analysis of pharmacokinetic studies in healthy volunteers

Tranexamic acid (TXA) is an antifibrinolytic drug that reduces surgical blood loss and death due to bleeding after trauma and post‐partum haemorrhage. One key issue for treatment success is early administration. While usually given intravenously, oral and intramuscular use would be useful in specific circumstances. Therefore, an understanding of TXA pharmacokinetics when given via different routes is valuable. The aim of this study was to perform an individual participant data meta‐analysis of pharmacokinetic studies with TXA given to healthy volunteers via different routes. We searched the following databases: PubMed, Web of Science, Wiley Online Library, Elsevier Science Direct and J‐STAGE. Individual subject data were extracted when available, otherwise arithmetic means were used. A population pharmacokinetic model was developed using nonlinear mixed effect modelling. Seven studies were included in the analysis with data from 10 patients for the IV route, six patients for the IM route and 114 patients for the oral route. The pharmacokinetics was ascribed to a two‐compartment model, and the main covariate was allometrically scaled bodyweight. Oral and IM bioavailabilities were 46 and 105%, respectively. For a 70 kg bodyweight, the population estimates were 7.6 L/h for clearance, 17.9 L for the volume of the central compartment, 2.5 L/h for the diffusional clearance and 16.6 L for the peripheral volume of distribution. Larger well‐designed studies are needed to describe the pharmacokinetics of TXA when given IM or as an oral solution before these can be recommended as alternatives to IV.     

Inclusion cyst of the tunica albuginea: Demonstration by ultrasound

A 35-year-old man discovered a 1-cm nodule at the upper pole of the left testicle after blunt focal trauma. While the pain, tenderness, and location suggested hematoma or appendiceal torsion, the demonstration by ultrasound of the size, cystic nature, and extraparenchymal location was consistent with the rarely documented cyst of the tunica albuginea.     

Missed opportunities for participation in prevention of mother to child transmission programmes: Simplicity of nevirapine does not necessarily lead to optimal uptake, a qualitative study

Background  

The objective of this study was to examine missed opportunities for participation in a prevention of mother-to-child transmission (PMTCT) programme in three sites in South Africa. A rapid anthropological assessment was used to collect in-depth data from 58 HIV-positive women who were enrolled in a larger cohort study to assess mother-to-child HIV transmission. Semi-structured interviews were conducted with the women in order to gain an understanding of their experiences of antenatal care and to identify missed opportunities for participation in PMTCT.     

A study of patients referred from A&E for coroners post-mortem.

A review of 179 autopsies was undertaken over a 1-year period to determine if clinically useful information was obtainable from coroners post mortems performed on patients referred from the A&E department. Fifty-six patients had undergone unsuccessful resuscitation. The leading causes of death were heart disease and trauma. Discrepancies between the diagnosis made during resuscitation and the cause of death found at autopsy were revealed especially in those dying from noncardiac causes. Iatrogenic trauma from resuscitation attempts occurred in a significant number of cases. It is suggested that review of selected Coroners post mortems should be part of departmental audit, with a view to improving clinical skills.     

Exercise metabolism during 1 hour of treadmill walking while taking high and low doses of propranolol,metoprolol, or placebo

Aerobic exercise and beta-blocking drugs are regularly prescribed as treatment for hypertension and as a prophylactic for patients at risk from coronary heart disease and for those recovering from an infarct. Some beta blockers, particularly non-beta₁-selective drugs, may make exercise more difficult, possibly by interfering with substrate metabolism during exercise. This study examined the effects of low and high doses of a beta₁-selective blocker, metoprolol, and a nonselective beta blocker, propranolol, on exercise metabolism. The study involved 20 healthy subjects (10 men, 10 women) who walked on a treadmill at 50% of their maximal oxygen uptake for 1 h on five occasions, separated by 7 days. On each of the five occasions they received one of the following treatments, given in random order: placebo, metoprolol 50 mg, metoprolol 100 mg, propranolol 40 mg, or propranolol 80 mg, all taken twice daily. Fat oxidation, expressed as a percentage of total energy expenditure, was significantly lower than with placebo for all of the active treatments except metoprolol 50 mg (placebo: 42.7 ± 11.6%; metoprolol 50 mg: 38.7 ± 14.1%, p = NS; metoprolol 100 mg: 36.3 ± 13.7%, p = 0.05; propranolol 40 mg: 31.2 ± 9.3%, p = 0.01; propranolol 80 mg: 29.5 ± 10.9%, p = 0.01); and significantly lower with propranolol than with metoprolol (propranolol 40 mg: p = 0.0036; propranolol 80 mg: p = 0.01). Plasma ammonia concentration was significantly higher than with placebo with propranolol 40 mg, propranolol 80 mg, and metoprolol 100 mg (p = 0.01 for all); with metoprolol 50 mg, there was no difference from placebo (p = NS). Both beta blockers in this study reduced fat metabolism and increased perceived exertion to some degree. Additional inhibition of fat oxidation occurred with the nonselective drug, probably in intramuscular rather than adipose lipolysis, and was probably beta₂ mediated. The results of this study suggest that a selective beta blocker has less of an adverse effect on substrate metabolism than does a nonselective beta blocker. Beta₁-selective drugs may offer advantages in patients who undertake regular aerobic exercise.