(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.

Aims: The 2023 ESC guidelines for acute coronary syndrome note that contemporary data are heterogenous regarding beta-blocker (BB) use post-myocardial infarction (MI) in patients without reduced ejection fraction (EF) or heart failure (HF). We aimed to address the heterogeneity in contemporary data around BB post-MI in this population. Methods and results: We searched six databases from 1 January 2000 to 1 September 2024 to identify contemporary studies enrolling MI patients without reduced EF (≤40%) or history of HF receiving BB at index MI and comparing outcomes between BB users and non-users. The primary outcome was all-cause mortality. Secondary outcomes included major adverse cardiac and cerebrovascular events (MACCE) and cardiovascular (CV) mortality. Random-effects meta-analysis was conducted using the restricted maximum likelihood method. There were 24 studies including 290 349 patients enrolled in the contemporary era. Overall, BB use was associated with a significant 11% reduction in all-cause mortality [hazard ratio (HR), 0.89; 95% confidence interval (CI), 0.81–0.97; I2 = 40], however with moderate-to-high statistical heterogeneity. Pre-specified subgroup analyses demonstrate comparable all-cause mortality (HR, 0.99; 95% CI, 0.94–1.06; I2 = 0%), CV mortality (HR, 0.99; 95% CI, 0.85–1.15; I2 = 0%), and MACCE (HR, 1.24; 95% CI, 1.01–1.52; I2 = 0%) in patients with a 1-year event-free period, defined as no death, recurrent MI, or HF while on BB following index MI. In patients with no event-free period, meta-regression revealed that BB mortality benefits were modified by the study inclusion period (P = 0.01), reflecting a temporal trend of decreasing BB mortality benefits over time. Based on the temporal trend, in patients with preserved EF post-2010, BB exhibited no reduction in all-cause mortality (HR, 0.97; 95% CI, 0.90–1.04; I2 = 0%), but a non-significant trend towards increased CV mortality (HR, 1.29; 95% CI, 0.96–1.72; I2 = 0%) and a significant increase in MACCE (HR, 1.24; 95% CI, 1.01–1.52; I2 = 0%). Conclusion: In the contemporary reperfusion era, BB may not confer additional mortality benefits beyond a 1-year event-free period post-MI in patients without reduced EF. Moreover, post-MI BB use was associated with detrimental effects in patients with preserved EF.

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.

Lay Summary: Glucagon-like peptide 1 agonists may reduce the risk of major adverse cardiovascular events, heart failure, and all-cause mortality among patients with multiple myeloma and Type 2 diabetes mellitus receiving proteasome inhibitors. The use of glucagon-like peptide 1 agonist is associated with a reduction in cardiovascular events and mortality among patients with multiple myeloma and Type 2 diabetes mellitus receiving proteasome inhibitors. The use of glucagon-like peptide 1 agonist is not associated with an increased risk of adverse events among patients with multiple myeloma and Type 2 diabetes mellitus receiving proteasome inhibitors.

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; I² = 0%) and disease progression (HR = 1.75; 95% CI, 1.26 to 2.43; I² = 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; I² = 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.

Introduction: Inclisiran is a novel drug that employs ribonucleic acid (RNA) interference to lower the levels of the proprotein convertase subtilisin/kexin type 9 (PCSK9) protein. It has demonstrated a significant reduction in LDL cholesterol levels compared to a placebo. We aim to comprehensively evaluate the safety of using Inclisiran in patients with dyslipidemia and ASCVD or an ASCVD risk equivalent. Methods: Four electronic databases, namely, Pubmed/MEDLINE, Web of Science, Embase, and ClinicalTrials.gov, were searched from inception to June 2024 to identify relevant randomized controlled trials (RCTs) comparing safety profiles of Inclisiran and the control group. The outcomes investigated were all-cause mortality, major adverse cardiovascular events (MACEs), injection-site adverse events, new-onset or worsening type 2 diabetes mellitus (T2DM), and nasopharyngitis. The effect estimates of outcomes were assessed using the risk ratio (RR) with a 95% confidence interval (CI). Random-effects meta-analysis was conducted using the restricted maximum likelihood method. Subgroup analysis was performed based on different dosing regimens. Results: The study included 7 RCTs, enrolling 4790 patients (age 63.8 ± 9.7 years, 33.2% females) who received Inclisiran. Compared to the control group, Inclisiran use did not yield a significant effect on all-cause mortality (RR, 0.92; 95% CI, 0.54 to 1.54; I² = 0%), MACEs (RR, 0.98; 95% CI, 0.82 to 1.17; I² = 0%), nasopharyngitis (RR, 1.10; 95% CI, 0.83 to 1.45; I² = 0%), and T2DM (RR, 1.02; 95% CI, 0.85 to 1.21; I² = 0%). However, Inclisiran use demonstrated a significant increase in injection-site adverse events (RR, 6.50; 95% CI, 3.20 to 13.20; I² = 29%). Conclusions: Inclisiran use significantly increased injection-site reactions, with no increase in mortality, T2DM, or nasopharyngitis. It demonstrates a generally favorable safety profile, making it a promising option for lipid management in individuals at high cardiovascular risk, such as those with ASCVD or equivalent conditions. While it effectively improves dyslipidemia, decision-makers should be aware of an increased incidence of injection-site reactions, which, though typically mild, warrant consideration in clinical practice. Further trials are required to assess the safety of Inclisiran, particularly the association of the severity of injection-site adverse events over longer treatment durations.