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.

     

COVID-19 Gender Disparities and Mitigation Recommendations: A Narrative Review

The coronavirus disease 2019 (COVID-19) pandemic has rapidly created widespread impacts on global health and the economy. Data suggest that women are less susceptible to severe illness. However, sex-disaggregated data are incomplete, leaving room for misinterpretation, and focusing only on biologic sex underestimates the gendered impact of the pandemic on women. This narrative review summarizes what is known about gender disparities during the COVID-19 pandemic and the economic, domestic, and health burdens along with overlapping vulnerabilities related to the pandemic. In addition, this review outlines recommended strategies that advocacy groups, community leaders, and policymakers should implement to mitigate the widening gender disparities related to COVID-19.     

The impact of the housing status on clinical outcomes and health care utilization among individuals living with HIV

ABSTRACT

The lack of stable housing can impair access and continuity of care for patients living with human immunodeficiency virus (HIV). This study investigated the relationship between housing status assessed at multiple time points and several core HIV-related outcomes within the same group of HIV patients experiencing homelessness. Patients with consistently stable housing (CSH) during the year were compared to patients who lacked CSH (non-CSH group). The study outcomes included HIV viral load (VL), CD4 counts, and health care utilization. Multivariable and propensity weighted analyses were used to assess outcomes adjusting for potential group differences. Of 208 patients, 88 (42%) had CSH and 120 (58%) were non-CSH. Patients with CSH had significantly higher proportion of VL suppression and higher mean CD4 counts. The frequency of nurse visits in the CSH group was less than a half of that in the non-CSH group. Patients with CSH were less likely to be admitted to the medical respite facility, and if admitted, their length of stay was about a half of that for the non-CSH group. Our study findings show that patients with CSH had significantly better HIV virologic control and immune status as well as improved health care utilization.     

Hip Displacement in Cerebral Palsy: The Role of Surveillance

IntroductionHip displacement is common in cerebral palsy (CP) and is related to the severity of neurological and functional impairment. It is a silent, but progressive disease, and can result in significant morbidity and decreased quality of life, if left untreated. The pathophysiology of hip displacement in CP is a combination of hip flexor-adductor muscle spasticity, abductor muscle weakness, and delayed weight-bearing, resulting in proximal femoral deformities and progressive acetabular dysplasia. Due to a lack of symptoms in the early stages of hip displacement, the diagnosis is easily missed. Awareness of this condition and regular surveillance by clinical examination and serial radiographs of the hips are the key to early diagnosis and treatment.Hip surveillance programmesSeveral population-based studies from around the world have demonstrated that universal hip surveillance in children with CP allows early detection of hip displacement and appropriate early intervention, with a resultant decrease in painful dislocations. Global hip surveillance models are based upon the patients’ age, functional level determined by the Gross Motor Function Classification system (GMFCS), gait classification, standardized clinical exam, and radiographic indices such as the migration percentage (MP), as critical indicators of progressive hip displacement.ConclusionDespite 25 years of evidence showing the efficacy of established hip surveillance programmes, there is poor awareness among healthcare professionals in India about the importance of regular hip surveillance in children with CP. There is a need for professional organizations to develop evidence-based guidelines for hip surveillance which are relevant to the Indian context.     

A Phase I Dose Escalation Study of the Safety,Tolerability, and Pharmacokinetics of Ipilimumab in Chinese Patients with Select Advanced Solid Tumors

Lessons Learned

• The overall safety profiles of ipilimumab 3 mg/kg and 10 mg/kg administered every 3 weeks, were consistent between Chinese patients with solid tumors in the current study and patients from previous U.S. ipilimumab monotherapy studies. No new safety signals were identified.
• The mean systemic exposures to ipilimumab (assessed by first dose area under the curve during the dosing interval and maximum serum concentration) were numerically lower in the Chinese patient population than in U.S. patients for both 3 mg/kg and 10 mg/kg doses; however, the range of serum concentrations in the Chinese and U.S. populations overlapped (3 mg/kg and 10 mg/kg), suggesting that ipilimumab pharmacokinetics was ethnically insensitive in this study.

BackgroundThis phase I, open‐label study assessed ipilimumab safety, tolerability, pharmacokinetics (PK), immunogenicity, and antitumor activity in Chinese patients with unresectable, metastatic, recurrent malignant melanoma (MM) or nasopharyngeal carcinoma (NPC).MethodsOf 39 patients enrolled, 25 received ipilimumab (11 patients received 3 mg/kg, and 14 patients received 10 mg/kg). Reasons for not receiving treatment were withdrawal of consent (3 patients), no longer meeting the criteria (10 patients), and one recorded as “other.” During the induction phase, patients received ipilimumab (3 mg/kg, i.v.), on day 1 of a 3‐week cycle, to a maximum of four doses or progressive disease (PD). During the maintenance phase at week 24, patients received ipilimumab (3 mg/kg, i.v.) on day 1 of a 12‐week cycle, to a maximum of 3 years or PD. Considering the co‐primary safety and PK endpoints, the successive dosing required nine patients with two or fewer dose‐limiting toxicities during the 42‐day observation period to proceed with a new cohort of nine patients at 10 mg/kg.ResultsIpilimumab safety and PK profiles were similar in Chinese and predominantly White populations. Ipilimumab was well tolerated. Most adverse events (AEs) were grades 1–2 and experienced by 11 patients treated with 3 mg/kg and 14 patients treated with 10 mg/kg. There were no new safety concerns. Incidence of anti‐ipilimumab antibodies was low (1 of 10 in the 3 mg/kg patients and 2 of 13 in the 10 mg/kg patients) and without safety implications. In the 3 mg/kg group, 8 of 11 patients had PD. In the 10 mg/kg group (all NPC, 0 MM patients), 11 of 14 patients had PD. Three patients had stable disease (one at 3 mg/kg and two at 10 mg/kg).ConclusionIpilimumab was well tolerated in Chinese patients, showing similar safety and PK to previous studies in predominantly White populations.     

Emerging therapeutic options in inflammatory bowel disease

Inflammatory bowel disease (IBD) is a chronic disease that requires chronic treatment throughout the evolution of the disease, with a complex physiopathology that entails great challenges for the development of new and specific treatments for ulcerative colitis and Crohn´s disease. The anti-tumor necrosis factor alpha therapy has impacted the clinical course of IBD in those patients who do not respond to conventional treatment, so there is a need to develop new therapies and markers of treatment response. Various pathways involved in the development of the disease are known and the new therapies have focused on blocking the inflammatory process at the gastrointestinal level by oral, intravenous, subcutaneous, and topical route. All these new therapies can lead to more personalized treatments with higher success rates and fewer relapses. These treatments have not only focused on clinical remission, but also on achieving macroscopic changes at the endoscopic level and microscopic changes by achieving mucosal healing. These treatments are mainly based on modifying signaling pathways, by blocking receptors or ligands, reducing cell migration and maintaining the integrity of the epithelial barrier. Therefore, this review presents the efficacy and safety of the new treatments that are currently under study and the advances that have been made in this area in recent years.