Prevalence and associated factors of vitamin D deficiency after Roux-en-Y gastric bypass: a systematic review and meta-analysis.

OBJECTS: To estimate the prevalence and associated factors of vitamin D deficiency (VDD) after Roux-en-Y gastric bypass (RYGB). METHODS: PubMed, EMBASE, and CENTRAL were searched for relevant records from inception to 17 March 2023, using search terms: vitamin D, vitamin D3, vitamin D deficiency, hypovitaminosis D, gastric bypass, and RYGB. Studies were eligible for inclusion if they provided related data on VDD prevalence after RYGB. RESULTS: Of the 1119 screened studies, 72 studies involving 7688 individuals were enrolled in the final analysis. The prevalence estimates of VDD after RYGB were 42%. Subgroup analyses suggested the pooled prevalence of postoperative VDD was 35% for follow-up duration less than or equal to 1 year, 43% for greater than 1 and less than or equal to 5 years, and 54% for greater than 5 years. Meta-regression showed that VDD prevalence was positively correlated with follow-up time. Also, the prevalence was higher in studies with inadequate vitamin D supplementation than in those with adequate supplementation and in Asia population than in those from South America, Europe, and North America. Other factors associated with high VDD prevalence after RYGB included high presurgical VDD prevalence, noncompliant patients, and black populations. No significant association existed between VDD and alimentary length. CONCLUSION: VDD presented a high prevalence in patients following RYGB. It occurred more frequently with longer postoperative follow-up time. Population-specific vitamin D supplementation measures, targeted treatment for presurgical VDD, improved patient compliance, and periodical follow-ups were necessary to reduce VDD and other adverse outcomes.

Caveolin-mediated cytosolic delivery of spike nanoparticle enhances antitumor immunity of neoantigen vaccine for hepatocellular carcinoma.

Rationale: Although neoantigen-based cancer vaccines have shown promise in various solid tumors, limited immune responses and clinical outcomes have been reported in patients with advanced disease. Cytosolic transport of neoantigen and adjuvant is required for the activation of intracellular Toll-like receptors (TLRs) and cross-presentation to prime neoantigen-specific CD8+T cells but remains a significant challenge. Methods: In this study, we aimed to develop a virus-like silicon vaccine (V-scVLPs) with a unique spike topological structure, capable of efficiently co-delivering a hepatocellular carcinoma (HCC)-specific neoantigen and a TLR9 agonist to dendritic cells (DCs) to induce a robust CD8+T cell response to prevent orthotopic tumor growth. We evaluated the antitumor efficacy of V-scVLPs by examining tumor growth and survival time in animal models, as well as analyzing tumor-infiltrating CD8+T cells and cytokine responses in the tumor microenvironment (TME). To evaluate the synergistic efficacy of V-scVLPs in combination with α-TIM-3 in HCC, we used an orthotopic HCC mouse model, a lung metastasis model, and a tumor rechallenge model after hepatectomy. Results: We found that V-scVLPs can efficiently co-deliver the hepatocellular carcinoma (HCC)-specific neoantigen and the TLR9 agonist to DCs via caveolin-mediated endocytosis. This advanced delivery strategy results in efficient lymph node draining of V-scVLPs to activate lymphoid DC maturation for promoting robust CD8+T cells and central memory T cells responses, which effectively prevents orthotopic HCC tumor growth. However, in the established orthotopic liver tumor models, the inhibitory receptor of TIM-3 was significantly upregulated in tumor-infiltrating CD8+T cells after immunization with V-scVLPs. Blocking the TIM-3 signaling further restored the antitumor activity of V-scVLPs-induced CD8+T cells, reduced the proportion of regulatory T cells, and increased the levels of cytokines to alter the tumor microenvironment to efficiently suppress established orthotopic HCC tumor growth, and inhibit lung metastasis as well as recurrence after hepatectomy. Conclusion: Overall, the developed novel spike nanoparticles with efficient neoantigen and adjuvant intracellular delivery capability holds great promise for future clinical translation to improve HCC immunotherapy.

Prevalence and associated factors of secondary hyperparathyroidism after Roux-en-Y gastric bypass: A meta-analysis.

This study aimed to investigate the prevalence and factors associated with secondary hyperparathyroidism (SHPT) after Roux-en-Y gastric bypass (RYGB). We searched PubMed, EMBASE, and CENTRAL for relevant studies using search terms gastric bypass, RYGB and hyperparathyroidism. Thirty-four cohort studies with 4331 patients were incorporated into the final meta-analysis. Overall estimates of the prevalence of SHPT following RYGB were 39%. Subgroup analyses indicated the pooled prevalences of SHPT were 25%, 42%, 48%, and 54% for ≤1 year, >1 and ≤5 years, >5 and ≤10 years, and >10 years, respectively, after RYGB. Meta-regression showed that SHPT occurred was positively related to follow-up durations (p = 0.001). Additionally, SHPT prevalence was higher in studies in which calcium and vitamin D supplementation were considered inadequate than in those which were adequate (p = 0.002). SHPT is highly prevalent in individuals with obesity after RYGB. It seems to progress with time after surgery. Routine calcium and vitamin D supplementation post-RYGB together with targeted treatment of vitamin D deficiency, reasonable adjustment of the doses of supplementation with regular follow-up, and improved patient compliance, as well as long-term screening, are necessary to prevent the development of SHPT.