Clinical features, laboratory characteristics, and outcome of ETP and TCRA/D aberrations in pediatric patients with T-acute lymphoblastic leukemia.

BACKGROUND: T-cell acute lymphoblastic leukemia (T-ALL) is an aggressive malignancy with few accepted prognostic factors that limit the efficiency of therapy. The aim of the current study was to assess the clinical and laboratory features of T-cell receptor (TCR) aberrations and early T-cell precursor (ETP) subtype as well as their outcome to therapy. METHODS: Sixty-three newly diagnosed pediatric T-ALL patients were assessed for the ETP status using immunophenotyping. Screening of TCRA/D aberrations was done by fluorescent in situ hybridization (FISH). The data were correlated to the patients' clinical features, response to treatment, and survival rates. RESULTS: Seven patients (11%) had ETP-ALL. The ETP-ALL patients were older (P = 0.013), presented with lower white blood cell (WBC) count (P = 0.001) and lower percentage of peripheral blood (PB) blast cells (P = 0.037), more likely to have hyperdiploid karyotype (P = 0.009), and had been associated with TCRA/D gene amplification (P = 0.014) compared to other T-ALL patients. Of note, the same associations had been significantly observed in patients with TCRA/D gene amplification. Patients with TCRA/D amplification frequently coincided with TCRß aberrations (P = 0.025). TCR-ß aberrations were significantly associated with negative MRD at the end of induction compared to TCR-ß-negative patients. There was a nonsignificant trend of ETP-positive cases to have lower overall survival (OS) (P = 0.06). Patients with TCR aberrations had no significant differences regarding disease-free survival (DFS) or OS rates compared to those with normal TCR. CONCLUSION: ETP-ALL patients tend to have increased mortalities. There was no significant impact of TCR aberrations on the survival rates of the patients.

Efficacy of different salvage regimens in progressive unresectable pediatric low-grade glioma.

Multiple salvage chemotherapy regimens are used in progressive low-grade glioma (LGG), with no single regimen being more effective than any other. In the present study, different salvage therapies were compared with regard to the response rate, overall survival (OS) rate, event-free survival (EFS) rate and visual outcome in 70 patients with pediatric LGG. Age was found to significantly affect the EFS and OS rates (P<0.001). The visual outcome was the same between the three regimens. The 2-year EFS and OS rates of the vincristine/carboplatin, monthly carboplatin and weekly vinblastine regimens were 64.7 and 70.6%, 71.0 and 85.0%, and 56.0 and 62.7%, respectively (P=0.6 for EFS; P=0.56 for OS). Overall, the present study demonstrated that age had a significant impact on survival. The three salvage regimens used were equally effective with regard to the radiological response and visual outcome. However, further randomized controlled trials are required to detect the optimal salvage therapy.

Impact of low-protein diet on cardiovascular risk factors and kidney function in diabetic nephropathy: A systematic review and meta-analysis of randomized-controlled trials.

AIM: To assess the efficacy of low-protein diets (LPD) on cardiovascular risk factors and kidney function in diabetic nephropathy (DN) based on randomized controlled trials (RCTs). METHODS: A comprehensive systematic search was undertaken in PubMed/MEDLINE, Web of Science, SCOPUS and Embase databases from inception until January 2022 without using time or language restrictions. RCTs which reported the effects of LPD on cardiovascular risk factors and kidney function in DN were considered. RESULTS: The results of the present study showed that a LPD significantly reduces urinary urea (WMD: -244.49 g/day, 95 % CI: -418.83, -70.16, P = 0.006) and HbA1c (WMD: -0.20, 95 % CI: -0.39, -0.01, P = 0.036) levels. However, the results did not show neither significant nor beneficial effect on other renal function and cardiovascular risk factors. Furthermore, the results of subgroup analysis showed LPD caused a further decrease in HbA1c during the follow-up period of ≤ 24 weeks, protein intake less than 0.8 g/kg/d and in individuals younger than 50 years. Albuminuria also showed a greater reduction in people under the age of 50 with type 1 diabetes (DMT1) following a LPD. CONCLUSION: The results of the present study showed that LPD significantly reduces urinary urea and HbA1c.

The effect of tamoxifen on the lipid profile in women: A systematic review and meta-analysis of randomized controlled trials.

BACKGROUND AND AIM: The effect of tamoxifen administration on serum lipids in females remains unclear. The studies which have explored this topic have produced conflicting results, probably due to discrepancies in the length of the intervention, differences in baseline variables or other factors. To answer this research question, we decided to conduct this systematic review and meta-analysis to assess the effects of tamoxifen on the lipid profile in women. METHODS: A comprehensive search was conducted in Web of Science, Scopus, PubMed/Medline and Embase, from the inception of these databases up to June 2021. We used a random effects meta-analysis to generate the combined results. RESULTS: The overall findings were generated from 18 eligible trials. As compared to placebo, tamoxifen led to a notable reduction of the total cholesterol (TC) (WMD: -23.03 mg/dL, 95% CI: -25.94 to -20.12, P˂0.001), and the low-density lipoprotein-cholesterol (LDL-C) (WMD: -18.68 mg/dL, 95% CI: -24.31 to -13.04, P˂0.001). However, tamoxifen did not alter triglycerides (TG) concentrations (WMD: +1.06 mg/dL, 95% CI: -11.08 to 13.20, P = 0.864) significantly. A pronounced reduction of the high-density lipoprotein-cholesterol (HDLC) was noted in the RCTs with a duration of ≤52 weeks (WMD: -2.06 mg/dL) and when tamoxifen was administered in participants with a BMI ≥25 kg/m2 (WMD: -1.42 mg/dL). Notable reductions in TC (WMD: -23.57 mg/dL) and LDL-C (WMD: -19.21 mg/dL) was detected when the dose of tamoxifen was ≥20 mg/day. Moreover, a significant reduction of TC (WMD: -20.23 mg/dL) and LDL-C (WMD: -24.13 mg/dL) was observed in the RCTs with a duration of ≤52 weeks. CONCLUSION: Tamoxifen can alter the lipid profile in females, particularly by decreasing TC, LDL-C and HDLC. Tamoxifen can further reduce TC and LDL-C if the dose of administration is ≥20 mg/day, the treatment duration is ≤52 weeks and if it prescribed in subjects with dyslipidemia.

Effect of saffron supplementation on liver enzymes: A systematic review and meta-analysis of randomized controlled trials.

BACKGROUND AND AIMS: Possible protective effects of saffron (Crocus sativus L) have been reported in several randomized clinical trials (RCTs). Current systematic review was performed to summarize the efficacy of saffron intake on liver enzymes. METHODS: An electronic database search was conducted on PubMed/Medline, Scopus, Web of Science, and Cochrane for RCTs comparing effect of saffron and placebo on liver enzymes from inception to July 2021. There was no restriction in language of included studies and we calculated the standardized mean difference (SMD) and 95% Confidence Intervals (CI) for each variable. Random-effect model was used to calculate effect size. RESULTS: Eight studies (n = 463 participants) were included in the systematic review. The saffron intake was associated with a statistically significant decrease in aspartate aminotransferase (AST) (SMD: -0.18; 95% CI: -0.34, -0.02; I2 = 0%) in comparison to placebo intake. Our results also indicated that saffron consumption did not have a significant effect on alanine aminotransferase (ALT) (SMD: -0.14; 95% CI: -0.36, 0.09; I2 = 47.0%) and alkaline phosphatase (ALP) levels (SMD: 0.14; 95% CI: -0.18, 0.46; I2 = 42.9%) compared to placebo. CONCLUSIONS: Saffron intake showed beneficial impacts on circulating AST levels. However, larger well-designed RCTs are still needed to clarify the effect of saffron intake on these and other liver enzymes.

Duplication 1q is highly correlated with poor prognosis in high hyperdiploid pediatric B-acute lymphoblastic leukemia.

BACKGROUND: The role of structural abnormalities in high hyperdiploidy (HeH) has been debatable, with few studies that addressed recurrent translocations with concurrent HeH (t-HeH). We aimed at the characterization of HeH cases in pediatric B-acute lymphoblastic leukemia (B-ALL) patients with special emphasis on the structural abnormalities including t-HeH. PATIENTS AND METHODS: Our study included all patients diagnosed with HeH over the period from January 2016 to April 2019 presenting to the Pediatric Oncology Department, National Cancer Institute, Cairo University. RESULTS: Among 480 de novo B-ALL pediatric patients, HeH was detected in eighty (16.7%) cases with a median age of 5 years. t-HeH was identified in 17/480 (3.5%) cases: 9(1.9%) with t(12;21), 7(1.5%) with t(9;22), and 1(0.2%) with t(4;11). Duplication (1q) was the most prevalent structural abnormality in c-HeH (hyperdiploidy without recurrent translocations) (n = 12,15%). Children ≥10 years or presenting with white blood cells (WBC) ≥50 × 109 /L) had an inferior 3 year-overall survival as compared to younger children (P = .003), and to lower WBC (P = .02). Duplication (1q) was an independent adverse parameter on the disease-free survival (DFS) of c-HeH patients (P = .004). CONCLUSIONS: Older age and WBC ≥ 50 × 109 /L were adverse prognostic factors. Duplication (1q) is correlated with lower DFS in c-HeH patients. t-HeH has distinct patterns of chromosomal gain.