The therapeutic application of metformin and sirolimus (rapamycin) in longevity-oriented medicine is complicated by substantial interindividual pharmacokinetic variability arising from inherited differences in drug-metabolising enzymes and membrane transporters. Metformin disposition is governed by a coordinated transporter network involving OCT1 (SLC22A1), OCT2 (SLC22A2), MATE1 (SLC47A1), and MATE2-K (SLC47A2), which collectively regulate hepatic uptake and renal elimination. Sirolimus exposure is influenced by CYP3A-mediated metabolism, P-glycoprotein transport, drug–drug interactions, and patient-specific factors, while CYP3A5 expression status (rs776746) may contribute to interindividual pharmacokinetic variability. This structured narrative review critically synthesizes pharmacokinetic, pharmacogenomic, population genetics, and drug–drug interaction evidence to evaluate the mechanistic and clinical basis for genotype-guided dosing of metformin and sirolimus across diverse populations. Targeted literature searches of PubMed/MEDLINE, Embase, and the Cochrane Library informed a structured narrative synthesis of relevant publications from January 1990 to December 2024. Evidence was evaluated according to study design, pharmacokinetic relevance, clinical applicability, and methodological limitations. Additional evidence was obtained from FDA prescribing information, CPIC guidance documents, and the PharmGKB database. Eligible studies included clinical pharmacokinetic investigations, population genetics studies, physiologically based pharmacokinetic (PBPK) models, and pharmacogenomic cohort analyses. CYP3A5 genotype was associated with variability in sirolimus pharmacokinetics, with the magnitude and consistency of genotype-associated differences varying across clinical investigations and pharmacokinetic models. CYP3A5*1 allele frequency varied markedly across populations, ranging from 5 to 15
HPV16/18 positivity is an established marker of cervical precancer risk, but whether its association with histological severity differs according to menopausal status remains uncertain. We evaluated this association among women with cervical intraepithelial neoplasia (CIN). This retrospective cross-sectional study included 254 women with histologically confirmed CIN. Factors associated with CIN2 + were evaluated using multivariable Firth logistic regression adjusting for relevant clinical and demographic covariates. The HPV16/18 × menopause interaction was formally tested, with additional genotype-specific and smoking-stratified sensitivity analyses. HPV16/18 positivity was independently associated with CIN2+ (aOR 3.89; 95
Effective psychosocial support involving religious and spiritual leaders has been shown to enhance quality of life and address psychosocial needs during cancer treatment. However, rigorous evidence quantifying the impact of structured religious or spiritual leader delivered interventions on quality of life remains limited in low- and middle-income countries. Therefore, this randomized controlled trial aims to evaluate the effect of structured messages delivered by religious and spiritual leaders on the quality of life of patients with breast or cervical cancer in southern Ethiopia. A total of 112 patients with breast or cervical cancer will be randomized equally into two groups of 56. Both groups will receive an identical educational video containing general cancer information. On Day 1, the intervention group will additionally receive a video message from a religious leader, followed by a face‑to‑face session at Month 3, and a final video session at Month 6. Data will be collected at chemotherapy initiation and at the sixth month after chemotherapy initiation via the KoboToolbox mobile application, utilizing the EORTC QLQ‑C30, FACIT‑Sp‑12, and adherence measures. The primary outcome is patient‑reported quality of life; spirituality and treatment adherence serve as secondary outcomes, analyzed using Analysis of co variance (ANCOVA). Ethical approval was granted by Hawassa University College of Medicine and Health Sciences and Martin Luther University Halle‑Wittenberg. Our intervention was developed based on existing evidence, and the findings of this study will benefit Ethiopian and African patients, particularly in settings where religious and spiritual considerations have not yet been integrated into medical services. This trial protocol version1.2 was registered at the Pan African Clinical Trial Registry (www.pactr.org) with registration number of PACTR202501810755828.
Chronic myeloid leukemia (CML) is a myeloproliferative neoplasm characterized by the Philadelphia chromosome, BCR–ABL1 fusion gene. Although bleeding manifestations are recognized, spontaneous soft-tissue hematomas are rare. We report a 21-year-old male with chronic-phase CML who developed recurrent spontaneous intramuscular hematomas in the absence of trauma. He presented with hyperleukocytosis and a gluteal hematoma complicated by compartment syndrome requiring surgical decompression. In the absence of identifiable coagulation abnormalities, a multifactorial mechanism, including hyperleukocytosis-associated microvascular dysfunction and possible qualitative platelet abnormalities, may have contributed. This case highlights an uncommon but serious complication of uncontrolled CML.
This narrative review synthesis clinical evidence on vestibular rehabilitation (VR) in vestibular migraine (VM), Vestibular migraine (VM) is the most common cause of recurrent spontaneous vertigo, affecting approximately 1-2.7
