The prototypical genetic autoimmune disease is immune dysregulation polyendocrinopathy enteropathy X-linked (IPEX) syndrome, a severe pediatric disease with limited treatment options. IPEX syndrome is caused by mutations in the forkhead box protein 3 (FOXP3) gene, which plays a critical role in immune regulation. As a monogenic disease, IPEX is an ideal candidate for a therapeutic approach in which autologous hematopoietic stem and progenitor (HSPC) cells or T cells are gene edited ex vivo and reinfused. Here, we describe a CRISPR-based gene correction permitting regulated expression of FOXP3 protein. We demonstrate that gene editing preserves HSPC differentiation potential, and that edited regulatory and effector T cells maintain their in vitro phenotype and function. Additionally, we show that this strategy is suitable for IPEX patient cells with diverse mutations. These results demonstrate the feasibility of gene correction, which will be instrumental for the development of therapeutic approaches for other genetic autoimmune diseases.
This narrative review explores the full scope of harmful psychological effects of the COVID-19 (Coronavirus Disease of 2019) pandemic on FLHCWs (Frontline healthcare workers). Additionally, we highlight the risk factors for worse outcomes. A literature review identified 24 relevant papers included in this synthesis. The majority of studies reported a high number of mental health conditions in HCWs (Healthcare workers) overall. Working in the frontline setting was repeatedly identified as an independent risk factor for poorer mental health. Additional risk factors, such as gender, occupational pressure, and low level of support from hospital administration, family, and the community, were also commonly identified. In the past, defined interventions have been shown to mitigate the psychological impact of high-stress situations on frontline workers. This review is aimed at identifying individuals at higher risk to help effectively target preventative measures in future stress situations in our healthcare system.
As SARS-CoV-2 continues to spread across the globe and significantly impacts health-care systems and strains resources, identifying prognostic factors to predict clinical outcome remains essential. We conducted a retrospective cohort study to further explore the prognostic value of serum hypoalbuminemia and other factors in hospitalized COVID-19 patients. The primary endpoint was defined as the risk of in-hospital mortality. 300 patients were included in the analysis, with 56% being male and a mean (±SD) age of 61.5 ± 15.3 years. The mean (±SD) albumin was 2.86 ± 0.5 g/dL. Our analysis showed that patients with in-hospital mortality had lower albumin levels than patients without in-hospital mortality (2.6 ± 0.49 vs. 2.9 ± 0.48 g/dL, respectively, with P value = <0.001). A multivariant logistic regression analysis was subsequently conducted, and after adjustment, the serum albumin level remained a strong predictor of the primary outcome. Based on the data gathered, we were able to create a model predictive of mortality in this patient group based on the serum albumin level and other pertinent factors. In this model, with all other variables remaining constant, each one-unit increase in albumin is estimated to reduce the odds of mortality by 73%. Our results strengthen the current available data on the prognostic value of serum albumin in COVID-19 patients and provide a model to predict in-hospital mortality.
Although the incidence is declining in the western world, Mycobacterium tuberculosis remains one of the most common infectious organisms responsible for significant morbidity and mortality worldwide. Pulmonary tuberculosis (TB) is the most commonly seen presentation; however, TB can affect nearly any of the body's organ systems. Endobronchial TB (EBTB) can complicate pulmonary TB or more rarely present as an isolated finding. It is essential to recognize and treat this condition promptly, as it can develop into tracheobronchial stenosis and chronic respiratory failure. Here we discuss the case of a 43-year-old female with a left upper lobe cavitary lesion who presented with weight loss, dyspnea, and hoarseness. After failing multiple courses of antibiotics, the patient underwent bronchoscopy, and pseudomembranous tracheobronchitis (PMTB) was diagnosed. Cultures of endobronchial samples grew Mycobacterium tuberculosis . Standard anti-TB quadruple therapy was initiated, and the patient clinically improved. Several subtypes of EBTB have been identified earlier. However, to the best of our knowledge, tuberculous PMTB has not previously been reported. This case allows us to consider the diagnostic and therapeutic implications of this condition.
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