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.

     

The Transmission of Trauma from Mother to Infant: Radioactive Residues and Counter-Transference in the Case of a Haitian Mother and Her Two-Year-Old Son*

ABSTRACT

Close observation of the interactions between a traumatised mother and her infant son provides information on the modes of transmission of psychic trauma in the mother–infant dyad. Following the presentation of a current literature review on the theme, the subject of “radioactive residue” and counter-transference in the transmission of psychic trauma from mother to infant will be illustrated through a clinical case study that focuses on a Haitian mother and her two-year-old infant son who has been referred to a “transitional care nursery” in urban Paris. The encounter with this mother–infant dyad is analysed through observing the quality of the interactions that take place between the mother and infant in order to determine how a particularly traumatic narrative impacts the mother–infant relationship, in addition to relations with the clinician. Mother and infant respond to one another through the emission and reception of “radioactive residues” as hypothesized by Gampel. This clinical case study shows that there is a need to consider transcultural factors and collective experience and history when analysing traumatic events. Additionally, the case study shows that counter-transference can be an effective clinical tool for gaining access to an infant's experience as the recipient of a traumatic narrative.     

Ethanol upregulates the P2X7 purinergic receptor in human macrophages

Alcohol consumption is considered to be the third leading cause of death in the United States. In addition to its direct toxicity, ethanol has two contrasting effects on the immune system: the nucleotide oligomerization domain‐like receptor pyrin domain‐containing‐3 (NLRP3) inflammasome is inhibited by acute ethanol exposure but activated by chronic ethanol exposure. Purinergic receptors (especially the P2X7 receptor) are able to activate the NLRP3 inflammasome and are involved in many ethanol‐related diseases (such as gout, pulmonary fibrosis, alcoholic steatohepatitis, and certain cancers). We hypothesized that ethanol regulates purinergic receptors and thus modulates the NLRP3 inflammasome's activity. In experiments with monocyte‐derived macrophages, we found that interleukin (IL)‐1β secretion was inhibited after 7 h of exposure (but not 48 h of exposure) to ethanol. The disappearance of ethanol's inhibitory effect on IL‐1β secretion after 48 h was not mediated by the upregulated production of IL‐1β, IL‐1α, IL‐6 or the inflammasome components NLRP3, apoptosis‐associated speck‐like protein containing a caspase recruitment domain, and caspase 1. P2X7R expression was upregulated by ethanol, whereas expression of the P2X4 and P2X1 receptors was not. Taken as a whole, our results suggest that ethanol induces NLRP3 inflammasome activation by upregulating the P2X7 receptor. This observation might have revealed a new mechanism for inflammation in ethanol‐related diseases.     

Step UP! To Stamp Out Stigma: adapting and testing a bystander intervention to reduce HIV-related stigma

Aim

HIV-related stigma is a traumatizing experience operating across socioecological levels. Few interventions have combined multiple methods of stigma reduction into a comprehensive approach. This study adapted bystander training to the context of HIV-related stigma and pilot tested the model.

Subjects and methods

The study drew upon the team’s prior research to create an adapted bystander intervention. Thirty-nine participants met in three separate workshop sessions, which consisted of didactic training, group discussions, and contact between people living with HIV (PLHIV) and their friends/family members, and healthcare workers. Participants completed pre-/post-intervention questionnaires that included demographic characteristics and standardized measures of stigma and empowerment. A person living openly with HIV served as the moderator. The study’s principal investigator led a discussion to evaluate the workshop model.

Results

The workshops were associated with decreased feelings of powerlessness but did not show any immediate effects on feelings of stigmatization. Subjects unanimously recommended requiring the training for all healthcare providers.

Conclusion

The study showed the feasibility of adapting a bystander approach to HIV-related stigma. Interactive participation across different stakeholder groups allows for addressing various types of stigma and incorporating multiple evidence-based approaches to stigma reduction. Future research will incorporate further adaptations and test the approach using a large-scale randomized controlled trial.

     

Anticoagulation in the cardiac patient: A concise review

Anticoagulation has multiple roles in the treatment of cardiovascular disease, including in management of acute myocardial infarction, during percutaneous coronary intervention, as stroke prophylaxis in patients with atrial arrhythmias, and in patients with mechanical heart valves. Clinical anticoagulation choices in the aforementioned diseases vary widely, due to conflicting data to support established agents and the rapid evolution of evidence‐based practice that parallels more widespread use of novel oral anticoagulants. This review concisely summarizes evidence‐based guidelines for anticoagulant use in cardiovascular disease, and highlights new data specific to direct oral anticoagulants.     

The incidence of negative intraoperative findings after unsuccessful hydrostatic reduction of ileocolic intussusception in children: A retrospective analysis

Background

There is a lack of studies addressing the occurrence of negative intraoperative findings (that is the absence of intussusception) after an unsuccessful hydrostatic reduction of an ileocolic intussusception. The aim of this study is to determine the incidence of negative intraoperative findings after unsuccessful hydrostatic reduction of ileocolic intussusception.