Umbilical cord blood: A promising source for allogeneic CAR-T cells.

Chimeric antigen receptor T (CAR-T) cell therapy is an effective treatment for relapsed and refractory acute lymphoblastic leukemia (R/R ALL). However, autologous CAR-T cells derived from patients with B-ALL often show poor amplification ability, exhaustion, and anergy. To overcome these limitations, allogeneic CAR-T cells may be used as effective substitutes; however, which source would be the best substitute is unclear. In this study, we compared the immunophenotype and antitumor efficacy of anti-CD19 CAR-T cells derived from healthy donor cord blood (CB), healthy donor peripheral blood (PB), and PB of B-ALL patients [PB (patient)] in vitro and NOD-Prkdcem26cd52Il2rgem26Cd22/Nju (NCG)-immunodeficient mice, respectively. The results revealed that CAR-T cells derived from healthy donor CB and PB showed a higher proportion of naive T cells and longer tumor suppression in tumor-bearing mice than those of PB (patient). PB (patient) CAR-T cells had a higher proportion of regulatory T cells (Treg cells) and released high levels of interluekin-10 (IL-10), which also suggest a poor prognosis. Thus, CAR-T cells derived from healthy donors have better antitumor efficacy than CAR-T cells derived from PB (patient), and CB may be a good source of allogeneic CAR-T cells.

Comparison of Clinical Features and Outcomes of Appendectomy in Elderly vs. Non-Elderly: A Systematic Review and Meta-Analysis.

Background: The objective of this study is to compare clinical and surgical outcomes of appendectomy among elderly and non-elderly subjects. Methods: A systematic search was conducted on PubMed, Scopus, and Google academic databases. Studies, observational in design, that compared peri-and postoperative outcomes of appendectomy, in patients with acute appendicitis, between elderly and non-elderly/younger subjects were considered for inclusion. Statistical analysis was performed using STATA software. Results: A total of 15 studies were included. Compared to non-elderly patients, those that were elderly had an increased risk of complicated appendicitis [relative risk (RR), 2.38; 95% CI: 2.13, 2.66], peritonitis [RR, 1.88; 95% CI: 1.36, 2.59], and conversion from laparoscopic to open appendectomy [RR, 3.02; 95% CI: 2.31, 3.95]. The risk of overall postoperative complications [RR, 2.59; 95% CI: 2.19, 3.06], intra-abdominal abscess [RR, 1.84; 95% CI: 1.15, 2.96], wound infection [RR, 3.80; 95% CI: 2.57, 5.61], and use of postoperative drainage [RR, 1.14; 95% CI: 1.09, 1.19] was higher among the elderly. The risk of readmission (30 days) [RR, 1.61; 95% CI: 1.16, 2.24] and mortality (30 days) [RR, 12.48; 95% CI: 3.65, 42.7] was also higher among elderly. Conclusions: Findings suggest an increased risk of peri-and postoperative complications among elderly subjects undergoing appendectomy, compared to non-elderly subjects. Systematic Review Registration: https://www.crd.york.ac.uk/prospero/, identifier: CRD42021286157.

[Research Progress on Gene Therapy for ß-thalassemia---Review].

ß-thalassemia is a monogenetic inherited hemolytic anemia, which results in a series of pathophysiological changes due to partial or complete inhibition of the synthesis of ß-globin chain. The curative therapy for this disease is to reconstitute hematopoiesis, and transplantation with genetically modified autologous hematopoietic stem cells can avoid the major difficulties of traditional allogeneic hematopoietic stem cell transplantation，such as HLA matching and immune rejection. ß-thalassemia gene therapy strategies mainly include gene integration and genome editing. The former relies on the development of lentiviral vectors and adds a fully functional HBB gene to the chromosome; the latter rapidly develops with the research of specific nuclease which can repair the HBB gene in situ. In this review, the latest progress of the two strategies in gene therapy of ß-thalassemia is summarized.

Efficacy of Thalidomide Treatment in Children With Transfusion Dependent ß-Thalassemia: A Retrospective Clinical Study.

Background: Thalidomide has been reported as a promising treatment for reducing transfusion volume in adults with ß-thalassemia. However, the evidence about the safety and efficacy of thalidomide on children with transfusion dependent ß-thalassemia (TDT) is scarce. Methods: Seventy-seven children with TDT treated with thalidomide at least for 6 months were included and retrospectively analyzed. Oral dose was started at 2.5 mg·kg-1·d-1. Blood volume for maintenance of hemoglobin above 90 g·L-1 compared with pre-treatment volume is the evaluation index for response. Results: After the sixth month treatment, 51/77 (66.2%) maintained Hb over 90 g·L-1 without transfusion. Adverse events were reported in 48 (63.2%) patients. Age, sex, genotype category, dosage, and transfusion interval before thalidomide treatment were not correlated to treatment response. The AUC was 0.806 for the HbF at the third month of treatment in predicting probability of major responders at the sixth month treatment. Based on Youden's index algorithm in the ROC curve, 47.298 g·L-1 was the optimal cut-off value of the HbF at the third month of treatment in predicting major responders at the sixth month treatment, with sensitivity of 67.5% and specificity of 93.3%. Conclusions: The dose of thalidomide between 2.5 mg·kg-1·d-1 and 3.6 mg·kg-1·d-1 is effective in TDT children. Severe side effects are uncommon. HbF concentration of 47.298 g·L-1 at the third month is recommended as the predictor for further major responders.

Plasma visfatin, associated with a genetic polymorphism -1535C>T, is correlated with C-reactive protein in Chinese Han patients with traumatic brain injury.

Visfatin is a newly identified pro-inflammatory adipokine and a genetic polymorphism -1535 C>T located in the visfatin gene promoter has been suggested to be associated with the regulation of visfatin expression in some inflammatory illness. However, there were some conflicting results regarding whether this variant is functional or not. This study aimed to examine the relations of the -1535 C>T single nucleotide polymorphism (SNP) of visfatin gene to the plasma visfatin and C-reactive protein concentrations in traumatic brain injury (TBI). 318 Chinese Han patients with TBI were recruited in this study. Plasma visfatin and C-reactive protein levels were significantly different between the genotypes in the SNP-1535 C>T even after adjustment for age, sex and body mass index. The genotype C-C had the highest plasma visfatin and C-reactive protein concentrations. The plasma visfatin and C-reactive protein concentrations between the variant genotypes C-T and T-T did not differ significantly. Plasma visfatin level was significantly associated with plasma C-reactive protein level using multivariate linear regression. Thus, the SNP-1535 C>T of visfatin gene seemed to be potentially involved in the inflammatory component of TBI through a decreased production of visfatin.

Change in plasma visfatin level after severe traumatic brain injury.

Higher plasma visfatin concentration has been associated with ischemic stroke. Thus, we sought to investigate change in plasma visfatin level after traumatic brain injury and to evaluate its relation with disease outcome. Seventy-six healthy controls and 98 patients with acute severe traumatic brain injury were recruited. Twenty-seven patients (27.6%) died and 48 patients (49.0%) suffered from unfavorable outcome (Glasgow outcome scale score of 1-3) in 6 months. On admission, plasma visfatin level was increased in patients than in healthy controls and was highly correlated with Glasgow Coma Scale score. A multivariate analysis identified plasma visfatin level as an independent predictor for 6-month mortality and unfavorable outcome. According to receiver operating characteristic curve analysis, the predictive value of the plasma visfatin concentration was similar to Glasgow Coma Scale score's. In a combined logistic-regression model, visfatin did not improve the predictive value of Glasgow Coma Scale score. Thus, increased plasma visfatin level is associated with 6-month clinical outcomes after severe traumatic brain injury.