The failure of anti-CD20 antibody (Rituximab) as therapy for lupus may be attributed to the transient and incomplete B cell depletion achieved in clinical trials. Here, using an alternative approach, we report that complete and sustained CD19+ B cell depletion is a highly effective therapy in lupus models. CD8+ T cells expressing CD19-targeted chimeric antigen receptors (CARs) persistently depleted CD19+ B cells, eliminated autoantibody production, reversed disease manifestations in target organs, and extended life spans well beyond normal in the (NZB × NZW) F1 and MRLfas/fas mouse models of lupus. CAR T cells were active for 1 year in vivo and were enriched in the CD44+CD62L+ T cell subset. Adoptively transferred splenic T cells from CAR T cell–treated mice depleted CD19+ B cells and reduced disease in naive autoimmune mice, indicating that disease control was cell-mediated. Sustained B cell depletion with CD19-targeted CAR T cell immunotherapy is a stable and effective strategy to treat murine lupus, and its effectiveness should be explored in clinical trials for lupus.

ObjectivesThe rising burden of preventable risk factors for non-communicable diseases (NCDs) among adolescents is a major public health challenge worldwide. We identified the preventable risk factors for NCDs in adolescents.MethodsIn a school-based study, pre-tested structured questionnaires were completed by 414 adolescents (14 to 17 years) at six schools in three cities in Pakistan. The chi-squared test and adjusted odds ratio (aOR) with 95% confidence interval (CI) were calculated in a multinomial logistic regression analysis.ResultsOver 80% of the adolescents had unhealthy diets, and 54% were physically inactive. Most adolescents were exposed to passive smoking, and 14% were also current smokers. More than one-third of participants chewed betel nut, and one-quarter used oral tobacco. More girls were physically inactive (OR, 4.07; 95% CI, 2.69 to 6.17), whereas a greater proportion of boys were current smokers (OR, 2.17; 95% CI, 1.19 to 3.91), exposed to passive smoking (OR, 2.57; 95% CI, 1.72 to 3.83), and using betel nut (OR, 2.03; 95% CI, 1.34 to 3.06). Only 3.1% of the participants were without any preventable lifestyle risk factor for NCDs, and over 80% had ≥2 factors. Co-existence of risk factors was independently associated with fathers being blue-collar workers (aOR, 3.57; 95% CI, 1.07 to 11.92) and parents not treating their child fairly (aOR, 5.05; 95% CI, 1.29 to 19.78).ConclusionsMost of the adolescents studied had preventable risk factors for NCDs. These results warrant comprehensive and integrated interventions to prevent lifestyle risk factors, and parents are front-line stakeholders.

Background:Adolescents are at substantial risk of acquiring behaviors which might influence their health status. This study was aimed to assess the proportion of school going adolescents (both males and females) with poor self-perceived health and its associated factors.Methodology:A cross-sectional study was conducted in three major cities of Pakistan i.e. Karachi, Lahore and Quetta. From each city, six (6) secondary schools were randomly selected (3 public and 3 private). Pre-tested, self-administered questionnaire was distributed to students. Binary logistic regression analysis was conducted to determine independent factors associated with poor self-perceived health.Results:Approximately 29% adolescents (119/414) reported poor self-perceived health. Individual and parental factors significantly associated with poor self-perceived health were being male (AOR = 1.75, 95% CI: 1.09 – 2.79), living in extended family (AOR = 2.65, 95% CI: 1.66 – 4.22), unskilled employment of father (AOR = 2.17, 95% CI: 1.35 – 3.48), lack of parental-child communication (AOR = 1.74, 95% CI: 1.03 – 2.91) and unfair treatment by parents (AOR = 1.80, 95% CI: 1.09 – 2.96). Life style factors such as use of smokeless tobacco (AOR = 2.14, 95% CI: 1.26 – 3.96) and unhealthy diet (AOR = 3.60, 95% CI: 1.76 – 7.33) were associated with poor self-perceived health.Conclusion:Better employment opportunities for father, parental counseling and increase awareness for adolescents about healthy diet are recommended to improve adolescent self-perceived health in Pakistan.

BackgroundSimultaneous advances in gene editing, T cell engineering and biotechnology currently provide an opportunity for rapid progress in medicine. The approval of chimeric antigen receptor (CAR) T cell therapies by the US Food and Drug Administration (FDA) and the European Commission have generated substantial momentum for these first-in-class therapies to be used in patients with B cell malignancies.Main bodyConsiderable efforts focus on improved outcomes and reduced side effects of the newly approved therapies. Using innovative strategies, researchers aim to extend CAR T cell use to tackle difficulties inherent in solid tumors. Efforts are underway to broaden the applications of CAR T cells, and the strategy has been successful in chronic viral infections and preclinical models of autoimmunity. Research is in progress to generate “off-the-shelf” CAR T cells, an advance, which would greatly increase patient availability and reduce treatment cost.ConclusionsIn this thematic review, we highlight advances that may help develop genetically engineered cells into a new category of medical therapies.

A consecutive series of 34 patients with congenital diaphragmatic hernia are reported from a tertiary neonatal care unit in the Eastern Province. All the patients presented within the first 24 hours of life with left-sided defect. The overall mortality (56%) and postoperative mortality (44%) are comparable with reports from other centers. The outcome of treatment correlated well with the age on presentation, the size of the defect, and preoperative blood gas results. Our approach to management has been modified lately, in the light of recent experience from other centers. The surgery is delayed until the neonate is stabilized with biochemical values of PaCO 2 = 45 torr or less; pH = 7.2 or higher; and PaO 2 = 50 torr or more. This management policy did not adversely affect overall survival. The problems encountered with patient transfer and the need for continued improvement in the organization of regionalized care are highlighted.