Evaluation of birth by cesarean delivery and development of early-onset colorectal cancer

IMPORTANCE: The incidence of early-onset colorectal cancer (CRC), diagnosed younger than 50 years of age, has increased worldwide. Gut dysbiosis throughout the life course is hypothesized as a leading mechanism, yet epidemiologic data are limited. OBJECTIVE: To prospectively examine the association between birth by cesarean delivery and early-onset CRC among offspring. DESIGN, SETTING, AND PARTICIPANTS: In this population-based, nationwide case-control study in Sweden, adults diagnosed with CRC between 18 and 49 years of age from 1991 to 2017 were identified through the Epidemiology Strengthened by Histopathology Reports in Sweden (ESPRESSO) cohort. Up to 5 general population control individuals without CRC were matched with each case on age, sex, calendar year, and county of residence. Pathology-confirmed end points were linked with the Swedish Medical Birth Register and other national registers. Analyses were conducted from March 2022 through March 2023. EXPOSURE: Birth by cesarean delivery. MAIN OUTCOMES AND MEASURES: The primary outcome was development of early-onset CRC in the overall population and by sex. RESULTS: We identified 564 case patients with incident early-onset CRC (mean [SD] age, 32.9 [6.2] years; 284 [50.4%] male) and 2180 matched controls (mean [SD] age, 32.7 [6.3] years; 1104 [50.6%] male). Compared with vaginal delivery, birth by cesarean delivery was not associated with early-onset CRC in the overall population (adjusted odds ratio [aOR], 1.28; 95% CI, 0.91-1.79) after multivariable adjustment for matching and maternal and pregnancy-related factors. A positive association was found for females (aOR, 1.62; 95% CI, 1.01-2.60), but there was no association for males (aOR, 1.05; 95% CI, 0.64-1.72). CONCLUSIONS AND RELEVANCE: In this nationwide, population-based case-control study, birth by cesarean delivery was not associated with early-onset CRC compared with birth by vaginal delivery in the overall population in Sweden. However, females born by cesarean delivery had greater odds of early-onset CRC compared with individuals born through vaginal delivery. This finding suggests that early-life gut dysbiosis may contribute to early-onset CRC in females

CD4 count, viral load and parasite density of HIV positive individuals undergoing malaria treatment with dihydroartemisinin in Benin City, Edo state, Nigeria

Background & objectives: A prospective study on 72 HIV infected and 33 HIV negative individualsundergoing malaria treatment with dihydroartemisinin (Cotecxin) was undertaken to compare CD4cells count, viral load and parasite density at two time-points, a baseline visit and a 9-day posttreatmentvisit.Methods: CD4 count and viral load of the subjects were estimated using Dynabeads T4–T8Quantification Protocol (Dyneal Biotech, Norway) and Amplicor HIV-1 Monitor Test respectively(Roche, United Kingdom).Results: There was a significant decrease in CD4 count at 9-day post-treatment when compared withbaseline value (p 200 cells/μl, a marked significant increase was obtained when the mean viral loadat baseline was compared to the 9-day post-treatment visit value (p <0.05). The mean parasite densityin HIV positive subjects was statistically higher when compared to that of HIV negative individualsat baseline and 9-day post-treatment (p <0.05).Interpretation & conclusion: The study as such may not confirm the impact of malaria infection onprogression to AIDS, incorporating effective malaria control in HIV management programmes mayimprove tremendously the quality of life of HIV infected individuals

Off-the-shelf cell therapy with induced pluripotent stem cell-derived natural killer cells

Cell therapy is emerging as a very promising therapeutic modality against cancer, spearheaded by the clinical success of chimeric antigen receptor (CAR) modified T cells for B cell malignancies. Currently, FDA-approved CAR-T cell products are based on engineering of autologous T cells harvested from the patient, typically using a central manufacturing facility for gene editing before the product can be delivered to the clinic and infused to the patients. For a broader implementation of advanced cell therapy and to reduce costs, it would be advantageous to use allogeneic “universal” cell therapy products that can be stored in cell banks and provided upon request, in a manner analogous to biopharmaceutical drug products. In this review, we outline a roadmap for development of off-the-shelf cell therapy based on natural killer (NK) cells derived from induced pluripotent stem cells (iPSCs). We discuss strategies to engineer iPSC-derived NK (iPSC-NK) cells for enhanced functional potential, persistence, and homing