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There have been many clinical questions regarding whether the use of proton pump inhibitors (PPIs) could deteriorate the effects of cyclin-dependent kinase inhibitors (CDKIs) in HR+/HER2- advanced breast cancer patients. We performed a systematic review and meta-analysis of this clinical question, including studies enrolling HR+/HER2- metastatic breast cancer patients treated with CDKIs (Palbociclib or Ribociclib) and reporting at least one comparative survival outcome, either overall survival (OS) or progression-free survival (PFS), between concomitant PPI users and non-users. Eight studies met the eligibility criteria, with a total of 2584 patients included (PPI users: 830, PPI non-users: 1754), demonstrating that concomitant PPI use was associated with significantly higher risks of all-cause mortality (HR = 2.03; 95% CI, 1.49 to 2.77; I 2 = 0%) and disease progression (HR = 1.75; 95% CI, 1.26 to 2.43; I 2 = 59%) in breast cancer patients taking Palbociclib. In contrast, there were no significant survival impacts of PPIs on Ribociclib (HR = 1.46; 95% CI, 0.91 to 2.34; I 2 = 36%). Additionally, there was no significant difference in the risk associated with CDKI dose reduction due to drug toxicity (RR = 1.12; 95% CI, 0.97 to 1.29). Therefore, when HR+/HER2- advanced breast cancer patients require the use of PPIs, it may be reasonable to consider using Ribociclib.

Osteoporotic vertebral compression fractures are the most common manifestation of osteoporosis. Percutaneous kyphoplasty (PKP) can lead to both pain improvement and correction of kyphosis secondary to collapsed vertebral bodies. Robot-assisted (RA) PKP has been reported to provide better vertebral body fracture correction than conventional fluoroscopy-assisted (FA) PKP. The aim of this meta-analysis is to compare clinical outcomes of RA PKP versus FA PKP. The Pubmed, Embase, and MEDLINE electronic databases were searched from January 1900 to December 2022, with no language restrictions for relevant articles. We extracted the preoperative and postoperative mean pain score and standard deviation from the included studies and pooled them using an inverse variance method. Statistical analyses were performed using functions available in the metafor package in R software. The results of this meta-analysis were summarized with weighted mean differences (WMDs). Our search strategy identified 181 references from the Pubmed, Embase, and MEDLINE electronic databases. We excluded duplicates and irrelevant references, after screening titles and abstracts. The remaining 12 studies were retrieved for full-text review, and, finally, we included five retrospective cohort studies from 2015 to 2021, comprising 223 patients undergoing RA PKP and 246 patients undergoing FA PKP. No difference was found in subgroup analysis based on the timing of postoperative pain assessment, despite the overall estimate of postoperative pain indicating a significant difference between the RA PKP and FA PKP groups (WMD, -0.22; 95% CI, -0.39 to -0.05). The long-term pain assessment revealed a significantly lower VAS in the RA PKP group than the FA PKP group at six months postoperatively (WMD, -0.15; 95% CI, -0.30 to -0.01), but no difference between the subgroups at three (WMD, 0.06; 95% CI, -0.41 to -0.54) and twelve months (WMD, -0.10; 95% CI, -0.50 to 0.30) postoperatively. Our meta-analysis revealed no significant difference in postoperative pain between RA PKP and FA PKP. Patients undergoing RA PKP had better pain improvement compared to FA PKP at 6 months postoperatively. However, further studies focusing on long-term outcomes in patients undergoing RA PKP are warranted to clarify its benefit, given the small number of included studies.

(1) Although emerging evidence suggests that proton pump inhibitor (PPI)-induced dysbiosis negatively alters treatment response to immune checkpoint inhibitors (ICIs) in cancer patients, no study systematically investigates the association between PPIs, ICIs, and chemotherapy; (2) Cochrane Library, Embase, Medline, and PubMed were searched from inception to 20 May 2022, to identify relevant studies involving patients receiving ICIs or chemotherapy and reporting survival outcome between PPI users and non-users. Survival outcomes included overall survival (OS) and progression-free survival (PFS). Network meta-analyses were performed using random-effects models. p -scores, with a value between 0 and 1, were calculated to quantify the treatment ranking, with a higher score suggesting a higher probability of greater effectiveness. We also conducted pairwise meta-analyses of observational studies to complement our network meta-analysis; (3) We identified 62 studies involving 26,484 patients (PPI = 8834; non-PPI = 17,650), including non-small cell lung cancer (NSCLC), urothelial carcinoma (UC), melanoma, renal cell carcinoma (RCC), hepatocellular carcinoma (HCC), and squamous cell carcinoma (SCC) of the neck and head. Eight post-hoc analyses from 18 randomized-controlled trials were included in our network, which demonstrated that, in advanced NSCLC and UC, patients under ICI treatment with concomitant PPI ( p -score: 0.2016) are associated with both poorer OS (HR, 1.49; 95% CI, 1.37 to 1.67) and poorer PFS (HR, 1.41; 95% CI, 1.25 to 1.61) than those without PPIs ( p -score: 1.000). Patients under ICI treatment with concomitant PPI also had poorer OS (HR, 1.18; 95% CI, 1.07 to 1.31) and poorer PFS (HR, 1.30; 95% CI, 1.14 to 1.48) in comparison with those receiving chemotherapy ( p -score: 0.6664), implying that PPIs may compromise ICI's effectiveness, making it less effective than chemotherapy. Our pairwise meta-analyses also supported this association. Conversely, PPI has little effect on patients with advanced melanoma, RCC, HCC, and SCC of the neck and head who were treated with ICIs; (4) "PPI-induced dysbiosis" serves as a significant modifier of treatment response in both advanced NSCLC and UC that are treated with ICIs, compromising the effectiveness of ICIs to be less than that of chemotherapy. Thus, clinicians should avoid unnecessary PPI prescription in these patients. "PPI-induced dysbiosis", on the other hand, does not alter the treatment response to ICIs in advanced melanoma, RCC, HCC, and SCC of the head and neck.

Milk fat globule-EGF factor 8 (MFG-E8) is an anti-inflammatory glycoprotein that mediates a wide spectrum of pathophysiological processes. MFG-E8 has been studied as a key regulator of cancer cell invasion, migration, and proliferation in different tissues and organs. However, potential roles of MFG-E8 in the growth and progression of liver cancer have not been investigated to date. Here, we analyzed 33 human hepatocellular carcinoma (HCC) samples and found that levels of MFG-E8 expression were significantly higher in HCC cells than in normal liver tissues. In addition, our in vitro gain-of-function study in three different HCC cell lines revealed that overexpression of MFG-E8 promoted the proliferation and migration of HCC cells, as determined by RT-qPCR, MTT assays, and wound healing analyses. Conversely, an MFG-E8 loss-of function study showed that proliferation capacity was significantly reduced by MFG-E8 knockdown in HCC cells. Additionally, MFG-E8 activity-neutralizing antibodies profoundly inhibited both migration and proliferation of HCC cells, attenuating their tumorigenic properties. These reductions in migration and proliferation were rescued by treatment of HCC cells with recombinant MFG-E8 protein. Furthermore, an in vivo HCC xenograft study showed that the number of proliferating HCC cells and tumor volume/weight were all significantly increased by MFG-E8 overexpression, compared to control mice. These results clearly show that MFG-E8 plays an important role in HCC progression and may provide a basis for future mechanistic studies and new strategies for the treatment of liver cancer., Competing Interests: The authors declare no conflict of interest.