Obesity is a chronic, relapsing disease with multifactorial origins and significant global health implications. Historically, bariatric surgery has been the most effective intervention for achieving sustained weight loss and metabolic improvement, especially in individuals with moderate to severe obesity. However, the therapeutic landscape is rapidly evolving. Recent advances in pharmacotherapy—including GLP-1 receptor agonists, dual and triple incretin agonists, and amylin-based combination therapies—have demonstrated unprecedented efficacy, with some agents inducing 15–25% weight loss, approaching outcomes once exclusive to surgical intervention. These developments challenge the continued applicability of existing bariatric surgery criteria, which were established in an era of limited medical alternatives. In this narrative review, we examine the evolution of surgical eligibility thresholds and critically assess the potential role of novel pharmacotherapies in redefining treatment algorithms. By comparing the efficacy, safety, metabolic benefits, and cost-effectiveness of surgery versus next-generation drugs, we explore whether a more stepwise, pharmacotherapy-first approach may now be justified, particularly in patients with BMI 30–40 kg/m². We also discuss future directions in obesity management, including personalized treatment strategies, perioperative drug use, and the integration of pharmacologic agents into long-term care pathways. As the field advances, a paradigm shift toward individualized, minimally invasive interventions appears inevitable—necessitating a timely re-evaluation of current bariatric surgery guidelines to reflect the expanding potential of medical therapy.

Background and Objectives: Pulmonary hypertension (PH) is a major contributor to morbidity and mortality in sickle cell disease (SCD), yet reliable and accessible biomarkers for cardiopulmonary risk stratification remain limited. This study aimed to evaluate whether the platelet-to-neutrophil ratio (PNR) is independently associated with echo-estimated PH (ePH) in adolescents and adults with SCD and to compare its predictive value with hemoglobin composition and genotype. Materials and Methods: A retrospective cohort study was conducted at King Fahd Hospital of the University, Al Khobar, Saudi Arabia (January 2019–January 2025). Clinical, laboratory, and echocardiographic data from 114 patients with confirmed SCD who underwent transthoracic echocardiography (TTE) were analyzed. ePH was defined as tricuspid regurgitant velocity (TRV) ≥ 2.5 m/s or pulmonary artery acceleration time (PAAT) ≤ 105 ms. Multivariable logistic and linear regression models were used to assess associations between PNR, hemoglobin fractions, genotype, and pulmonary pressure estimates. Results: Overall, 43% of patients met the criteria for ePH. PNR was not independently associated with ePH or TRV in adjusted analyses. In contrast, higher fetal hemoglobin (HbF) levels were independently associated with lower odds of ePH (adjusted OR 0.92 per 1% increase, 95% CI 0.86–0.98) and lower TRV values. The HbS/β⁰ genotype was significantly associated with increased odds of ePH (adjusted OR 5.44, 95% CI 1.37–24.0). Exploratory analyses demonstrated an inverse association between PNR and lactate dehydrogenase, suggesting that PNR reflects hemolytic activity rather than pulmonary vascular involvement. Conclusions: In this retrospective cohort of patients with SCD, PNR was not independently associated with ePH or TRV after multivariable adjustment. In contrast, hemoglobin composition and genotype, particularly higher HbF and the HbS/β⁰ genotype, were significantly associated with pulmonary pressure estimates.