Safe and potent anti-CD19 CAR T-cells with shRNA-IL-6 gene silencing element in patients with refractory or relapsed B-cell acute lymphoblastic leukemia.

Severe cytokine release syndrome (sCRS) and immune effector cell-associated neurotoxicity syndrome (ICANS) have limited the widespread use of chimeric antigen receptor T (CAR T)-cell therapy. We designed a novel anti-CD19 CAR (ssCART-19) with a small hairpin RNA (shRNA) element to silence the interleukin-6 (IL-6) gene, hypothesizing it could reduce sCRS and ICANS by alleviating monocyte activation and proinflammatory cytokine release. In a post hoc analysis of two clinical trials, we compared ssCART-19 with common CAR T-cells (cCART-19) in relapsed/refractory B-cell acute lymphoblastic leukemia (r/r B-ALL). Among 87 patients, 47 received ssCART-19 and 40 received cCART-19. Grade ≥3 CRS occurred in 14.89% (7/47) of the ssCART-19 group versus 37.5% (15/40) in the cCART-19 group (p = 0.036). ICANS occurred in 4.26% (2/47) of the ssCART-19 group (all grade 1) compared to 15% (2/40) of the cCART-19 group. Patients in the ssCART-19 group showed comparable rates of treatment response (calculated with rates of complete remission and incomplete hematological recovery) were 91.49% (43/47) for ssCART-19 and 85% (34/40) for cCART-19 (p = 0.999). With a median follow-up of 21.9 months, cumulative nonrelapse mortality was 10.4% for ssCART-19 and 13.6% for cCART-19 (p = 0.33). Median overall survival was 37.17 months for ssCART-19 and 32.93 months for cCART-19 (p = 0.40). Median progression-free survival was 24.17 months for ssCART-19 and 9.33 months for cCART-19 (p = 0.23). These data support the safety and efficacy of ssCART-19 for r/r B-ALL, suggesting its potential as a promising therapy.

[Effect of glucose pretreatment on the effect of rapid rehabilitation surgery in patients undergoing hip replacement].

OBJECTIVE: To explore the effect of glucose pretreatment in the rapid rehabilitation surgery of hip replacement patients, and to provide reference for the future clinical treatment. METHODS: From June 2016 to June 2018, 168 patients (100 males, 68 females) were treated with hip replacement. The patients were divided into control group and observation group, 84 cases in each group, aged 25 to 90 (52.05±5.73) years old. Both groups were treated with the concept of rapid rehabilitation surgery, the control group was given traditional fasting water deprivation before operation, and the observation group was given glucose pretreatment before operation. The levels of fasting blood glucose(FBG), C-peptide, fasting insulin(FINS), IgG, IgM, IgA and total lymphocyte count (TLC) were compared before and after operation, and the sensitivity of thirst, nausea, fatigue, sweating, stomach discomfort, anxiety, hunger and dizziness were compared. RESULTS: All the 168 patients were followed up. There was no significant difference in FBG, C-peptide and fins levels between the observation group and the control group (P>0.05). The levels of FBG, C-peptide and fins in the observation group were higher than those in the control group (P<0.05). There was no significant difference in the serum IgG, IgM, IgA and TLC levels between the observation group and the control group(P>0.05);the serum IgG, IgM, IgA and TLC levels after operation were higher than those before operation, and the observation group was higher than the control group(P<0.05). There was no significant difference in the degree of thirst, nausea, fatigue, sweating and stomach discomfort between the observation group and the control group (P>0.05);the degree of anxiety, hunger and dizziness in the observation group was less than that in the control group (P<0.05). CONCLUSION: Glucose pretreatment before hip replacement can relieve insulin resistance, improve immunity and change energy storage under fasting, which can be widely used in clinic.

Radiomics score: a potential prognostic imaging feature for postoperative survival of solitary HCC patients.

BACKGROUND: Radiomics is an emerging field in oncological research. In this study, we aimed at developing a radiomics score (rad-score) to estimate postoperative recurrence and survival in patients with solitary hepatocellular carcinoma (HCC). METHODS: A total of 319 solitary HCC patients (training cohort: n = 212; validation cohort: n = 107) were enrolled. Radiomics features were extracted from the artery phase of preoperatively acquired computed tomography (CT) in all patients. A rad-score was generated by using the least absolute shrinkage and selection operator (lasso) logistic model. Kaplan-Meier and Cox's hazard regression analyses were used to evaluate the prognostic significance of the rad-score. Final nomograms predicting recurrence and survival of solitary HCC patients were established based on the rad-score and clinicopathological factors. C-index and calibration statistics were used to assess the performance of nomograms. RESULTS: Six potential radiomics features were selected out of 110 texture features to formulate the rad-score. Low rad-score positively correlated with aggressive tumor phenotypes, like larger tumor size and vascular invasion. Meanwhile, low rad-score was significantly associated with increased recurrence and reduced survival. In addition, multivariate analysis identified the rad-score as an independent prognostic factor (recurrence: Hazard ratio (HR): 2.472, 95% confident interval (CI): 1.339-4.564, p = 0.004;survival: HR: 1.558, 95%CI: 1.022-2.375, p = 0.039). Notably, the nomogram integrating rad-score had a better prognostic performance as compared with traditional staging systems. These results were further confirmed in the validation cohort. CONCLUSIONS: The preoperative CT image based rad-score was an independent prognostic factor for the postoperative outcome of solitary HCC patients. This score may be complementary to the current staging system and help to stratify individualized treatments for solitary HCC patients.