Benefits of surgical treatment within 48†h of proximal femoral fracture in centenarians: a retrospective cohort study.

Introduction: Proximal femoral fractures in aging populations represent a significant concern, with an increasing prevalence among individuals aged ≥100 years. The existing research does not provide robust guidance for clinicians managing older patients aged ≥100 years with proximal femoral fractures. We investigated the safety and efficacy of surgical treatment in patients aged ≥100 years with proximal femoral fractures and evaluated the impact of early surgery on their outcomes. Methods: This retrospective cohort study involved 15 patients aged ≥100 years who underwent surgical treatment of proximal femoral fractures; the control group included 137 patients in their 90s. Data were collected between January 2010 and December 2017. Evaluation items included patient characteristics, surgical details, perioperative complication rates, length of hospital stay, the proportion of patients discharged to the same facility or home, rate of regaining walking ability, and 1-year survival rate. Results: The patients aged ≥100 years and those in their 90s had comparable outcomes. Thus, age alone does not dictate surgical success. Early surgery (≤48 h) was associated with trends toward improved perioperative complications, ambulatory ability, and return to original living environment. Discussion: This study underscores the potential benefits of surgical intervention for proximal femoral fractures in patients aged ≥100 years, indicating the relevance of early surgery (≤48 h). Our findings emphasized the importance of timely intervention and evidence-based decision-making for this demographic. Clinicians, policymakers, and patients could benefit from our insights to enhance fracture management strategies, along with future research endeavors to validate and expand our results in larger multicenter cohorts.

Fine-tuning of nitrogen-containing bisphosphonate esters that potently induce degradation of HMG-CoA reductase.

3-Hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase is the rate-limiting enzyme in the cholesterol biosynthetic pathway, and competitive inhibitors targeting the catalytic domain of this enzyme, so-called statins, are widely used for the treatment of hyperlipidemia. The membrane domain mediates the sterol-accelerated degradation, a post-translational negative feedback mechanism, and small molecules triggering such degradation have been studied as an alternative therapeutic option. Such strategies are expected to provide benefits over catalytic site inhibitors, as the inhibition leads to transcriptional and post-translational upregulation of the enzyme, necessitating a higher dose of the inhibitors and concomitantly increasing the risk of serious adverse effects, including myopathies. Through our previous study on SR12813, a synthetic small molecule that induces degradation of HMG-CoA reductase, we identified a nitrogen-containing bisphosphonate ester SRP3042 as a highly potent HMG-CoA reductase degrader. Here, we performed a systematic structure-activity relationship study to optimize its activity and physicochemical properties, specifically focusing on the reduction of lipophilicity. Mono-fluorination of tert-butyl groups on the molecules was found to increase the HMG-CoA reductase degradation activity while reducing lipophilicity, suggesting the mono-fluorination of saturated alkyl groups as a useful strategy to balance potency and lipophilicity of the lead compounds.