High-fat diet and caffeine interact to modulate bone microstructure and biomechanics in mice

peer reviewedAims: Although excessive fat and caffeine intake are independent risk factors for bone microstructural and functional disturbances, their association remains overlooked. Thus, we investigated the impact of high-fat diet (HFD) and caffeine alone and combined on serum lipid profile, bone microstructure, mi- cromineral distribution and biomechanical properties. Methods: Forty female C57BL/6 mice were randomized into 4 groups daily treated for seventeen weeks with standard diet (SD) or HFD (cafeteria diet) alone or combined with 50 mg/kg caffeine. Key findings: The association between HFD and caffeine reduced the weight gain compared to animals re- ceiving HFD alone. Caffeine alone or combined with HFD increases total and HDL cholesterol circulating levels. HFD also reduced calcium, phosphorus and magnesium bone levels compared to the groups receiv- ing SD, and this reduction was aggravated by caffeine coadministration. From biomechanical assays, HFD combined with caffeine increased bending strength and stiffness of tibia, a finding aligned with the marked microstructural remodeling of the cortical and cancellous bone in animals receiving this combina- tion. Significance: Our findings indicated that HFD and caffeine interact to induce metabolic changes and bone microstructural remodeling, which are potentially related to bone biomechanical adaptations in response to HFD and caffeine coadministration

Evaluation of a quality improvement intervention to reduce anastomotic leak following right colectomy (EAGLE): pragmatic, batched stepped-wedge, cluster-randomized trial in 64 countries

Background Anastomotic leak affects 8 per cent of patients after right colectomy with a 10-fold increased risk of postoperative death. The EAGLE study aimed to develop and test whether an international, standardized quality improvement intervention could reduce anastomotic leaks. Methods The internationally intended protocol, iteratively co-developed by a multistage Delphi process, comprised an online educational module introducing risk stratification, an intraoperative checklist, and harmonized surgical techniques. Clusters (hospital teams) were randomized to one of three arms with varied sequences of intervention/data collection by a derived stepped-wedge batch design (at least 18 hospital teams per batch). Patients were blinded to the study allocation. Low- and middle-income country enrolment was encouraged. The primary outcome (assessed by intention to treat) was anastomotic leak rate, and subgroup analyses by module completion (at least 80 per cent of surgeons, high engagement; less than 50 per cent, low engagement) were preplanned. Results A total 355 hospital teams registered, with 332 from 64 countries (39.2 per cent low and middle income) included in the final analysis. The online modules were completed by half of the surgeons (2143 of 4411). The primary analysis included 3039 of the 3268 patients recruited (206 patients had no anastomosis and 23 were lost to follow-up), with anastomotic leaks arising before and after the intervention in 10.1 and 9.6 per cent respectively (adjusted OR 0.87, 95 per cent c.i. 0.59 to 1.30; P = 0.498). The proportion of surgeons completing the educational modules was an influence: the leak rate decreased from 12.2 per cent (61 of 500) before intervention to 5.1 per cent (24 of 473) after intervention in high-engagement centres (adjusted OR 0.36, 0.20 to 0.64; P < 0.001), but this was not observed in low-engagement hospitals (8.3 per cent (59 of 714) and 13.8 per cent (61 of 443) respectively; adjusted OR 2.09, 1.31 to 3.31). Conclusion Completion of globally available digital training by engaged teams can alter anastomotic leak rates. Registration number: NCT04270721 (http://www.clinicaltrials.gov)