CAR-T cell therapy: Efficacy in management of cancers, adverse effects, dose-limiting toxicities and long-term follow up.

Chimeric Antigen Receptor T-cell (CAR-T) therapy has emerged as a groundbreaking and highly promising approach for the management of cancer. This paper reviews the efficacy of CAR-T therapy in the treatment of various hematological malignancies, also, with a mention of its effect on solid tumors, for which they have not received FDA approval yet. Different common and uncommon side effects are also discussed in this paper, with attention to the effect of each drug separately. By reviewing the recommendations of the FDA for CAR-T therapy research, we have extensively discussed dose-limiting toxicities. This further highlights the need for precise dosing strategies, striking a balance between therapeutic benefits and potential risks. Additionally, we reviewed the long-term follow-up of patients receiving CAR-T therapy to gain valuable insights into response durability and late-onset effects.

Estimates of the prevalence of male circumcision in sub-Saharan Africa from 2010-2023-A systematic review and meta-analysis.

BACKGROUND: Male circumcision (MC) is a key part of the package of interventions to prevent HIV, the biggest health challenge in sub-Saharan Africa. OBJECTIVE: To estimate the male circumcision prevalence and to evaluate the progress towards meeting WHO targets in sub-Saharan Africa during the period 2010-2023. METHODS: We carried out a systematic review and meta-analysis of studies published during the period 2010-2023. We searched PubMed, Scopus, Cochrane CENTRAL, Google Scholar, WHO and the Demographic and Health Survey for reports on MC prevalence in sub-Saharan Africa. MC prevalence was synthesized using inverse-variance heterogeneity models, heterogeneity using I2 statistics and publication bias using funnel plots. RESULTS: A total of 53 studies were included. The overall prevalence during the study period was 45.9% (95% CI 32.3-59.8), with a higher MC prevalence in Eastern (69.9%, 95%CI 49.9-86.8) compared to Southern African (33.3%, 95%CI 21.7-46.2). The overall prevalence was higher in urban (45.3%, 95%CI 27.7-63.4) compared to rural settings (42.6%, 95% 26.5-59.5). Male circumcision prevalence increased from 40.2% (95% CI 25.0-56.3) during 2010-2015 to 56.2% (95% CI 31.5-79.5) during 2016-2023. Three countries exceeded 80% MC coverage, namely, Ethiopia, Kenya and Tanzania. CONCLUSION: Overall, the current MC prevalence is below 50%, with higher prevalence in Eastern African countries and substantially lower prevalence in Southern Africa. Most of the priority countries need to do more to scale up medical male circumcision programs.

The Contemporary Role of Hematopoietic Stem Cell Transplantation in the Management of Chronic Myeloid Leukemia: Is It the Same in All Settings?

Hematopoietic stem cell transplantation (HSCT) for chronic myeloid leukemia (CML) patients has transitioned from the standard of care to a treatment option limited to those with unsatisfactory tyrosine kinase inhibitor (TKI) responses and advanced disease stages. In recent years, the threshold for undergoing HSCT has increased. Most CML patients now have life expectancies comparable to the general population, and therefore, the goal of therapy is shifting toward achieving treatment-free remission (TFR). While TKI discontinuation trials in CML show potential for achieving TFR, relapse risk is high, affirming allogeneic HSCT as the sole curative treatment. HSCT should be incorporated into treatment algorithms from the time of diagnosis and, in some patients, evaluated as soon as possible. In this review, we will look at some of the recent advances in HSCT, as well as its indication in the era of aiming for TFR in the presence of TKIs in CML.

Male Fertility and Fatherhood in Chronic Myeloid Leukemia: Current Understanding and Future Perspectives.

Chronic myeloid leukemia (CML), while traditionally a disease of the elderly, has recently risen in incidence among younger patients. Hence, fertility concerns have emerged considering the disease process and treatments, especially with the current scarce and conflicting recommendations. This review explores the impact of CML treatments including the first-line tyrosine kinase inhibitors (TKIs) and other treatments on male fertility in chronic myeloid leukemia (CML) patients. The aim of this review was to compile the available evidence on male fertility to ultimately tailor treatment plans for male CML patients for whom fertility and future chances for conception pose a concern. The data available on the conventional and newer TKIs to address fertility concerns were reviewed, particularly the potential long- and short-term effects. Also, the possible side effects on subsequent generations were a crucial focus point of this review to reach a more comprehensive CML management approach. We found and compared the evidence on TKIs approved to treat CML. We also reported the effects of hydroxyurea, interferon, and transplantation, which are considered second-line treatments. Our findings suggest that these drugs might have an undiscovered effect on fertility. More research with larger sample sizes and longer follow-up periods is essential to solidify our understanding of these effects.

Association between Diabetes and Levels of Micronutrients in Qatar-A Case-Control Study.

OBJECTIVE: The objectives of this study were to investigate associations between micronutrient levels and diabetes and to explore the association in individuals with controlled and uncontrolled diabetes. METHODS: A case-control study, matched on age and gender, was performed on participants with (cases) and without diabetes (controls), who were Qatari or long-term residents (≥15 years of residence). Participants with diabetes were divided into those with controlled and uncontrolled diabetes using an HbA1c cutoff of 7%. Levels of micronutrients were measured from serum and categorized into normal and abnormal levels. RESULTS: A total of 1118 participants (374 cases and 744 controls) were included with a mean age of 41.7 years (SD 9.9), of whom 53.9% were female. Of those with diabetes, 229 had controlled diabetes and 145 had uncontrolled diabetes. Compared to those without diabetes, participants with diabetes had significantly lower mean magnesium (0.80 mmol/L (SD 0.07) vs. 0.84 mmol/L (SD 0.06), respectively, p < 0.001). Lower magnesium and iron were observed in participants with uncontrolled compared to participants with controlled diabetes. After multivariable logistic regression, diabetes was associated with hypomagnesemia (OR 3.2, 95% CI 3.4-213.9) and low iron (OR 1.49, 95% CI 1.03-2.15). Uncontrolled diabetes showed stronger odds of association with hypomagnesemia (OR 5.57, 95% CI 3.65-8.52). CONCLUSION: In an affluent setting in the MENA region, diabetes was associated with low magnesium and low iron, and this association was stronger in individuals with uncontrolled diabetes.

Does colchicine reduce mortality in patients with COVID-19 clinical syndrome? An umbrella review of published meta-analyses.

Background: Despite significant improvements in both treatment and prevention strategies, as well as multiple commissioned reviews, there remains uncertainty regarding the survival benefit of repurposed drugs such as colchicine in patients with Coronavirus Disease 2019 (COVID-19) clinical syndrome. Methods: In this umbrella review, we carried out a comprehensive search of PubMed, EMBASE, Cochrane Database of Systematic Reviews, Science Citation Index, and the Database of Abstracts of Reviews of Effectiveness between January 1, 2020 and January 31, 2023 for systematic reviews and meta-analyses evaluating the mortality-reducing benefits of colchicine in patients with COVID-19. This was to ascertain the exact relationship between colchicine exposure and mortality outcomes in these cohorts of patients. We utilized A Measurement Tool to Assess systematic Reviews-2 (AMSTAR-2) to conduct an exhaustive methodological quality and risk of bias assessment of the included reviews. Results: We included eighteen meta-analyses (n = 199,932 participants) in this umbrella review. Colchicine exposure was associated with an overall reduction of about 32% in the risk of mortality (odds ratio 0.68, confidence interval [CI] 0.58-0.78; I2 = 94%, p = 0.001). Further examination of pooled estimates of mortality outcomes by the quality effects model (corrected for the methodological quality and risk of bias of the constituent reviews) reported similar point estimates (OR 0.73; CI 0.59 to 0.91; I2 = 94%). Conclusion: In a pooled umbrella evaluation of published meta-analyses of COVID-19 patient cohorts, exposure to colchicine was associated with a reduction in overall mortality. Although it remains uncertain if this effect could potentially be attenuated or augmented by COVID-19 vaccination.