No association between proton pump inhibitor use and risk of dementia: Evidence from a meta-analysis.

BACKGROUND AND AIM: A growing body of literature suggests the association between dementia risk and proton pump inhibitor (PPI) use. Therefore, we aimed to investigate the association between PPI use and dementia risk. METHODS: An extensive literature search was performed in PubMed, Embase, and Cochrane till March 31, 2019. All the studies (cohort and case-control) assessing the association between PPI use and dementia risk were eligible for inclusion. Articles were selected based on the screening of title and abstract, data were extracted, and risk of bias was assessed using Newcastle-Ottawa scale. The primary outcome was pooled risk of dementia among PPI user as compared with non-PPI user. Secondary outcomes include dementia risk based on subgroups. Statistical analysis was performed using review manager software. RESULTS: Twelve studies (eight cohort and four case-control) were found to be eligible for inclusion. Majority of the studies were of high quality. Dementia was diagnosed based on International Classification of Diseases 9/10 codes in majority of the included studies. PPI use was not associated with the dementia risk, with a pooled relative risk (RR) of 1.05 (95% confidence interval [CI]: 0.96-1.15), P = 0.31. Subgroup analysis based on study design (cohort: P = 0.14; case-control: P = 0.14), sex (RR 1.25 [95% CI: 0.97-1.60], P = 0.08), histamine 2 receptor antagonist blockers (P = 0.93), and Alzheimer's disease (RR 1.00 [95% CI: 0.91-1.09], P = 0.93) revealed no significant association between PPI use and dementia risk. CONCLUSION: We found no significant association between PPI use and the risk of dementia or Alzheimer's disease.

Amputation Risk in Type II Diabetes Mellitus Patients Treated with SGLT-2 Inhibitors: A Systematic Literature Review of Randomized Clinical Trials.

BACKGROUND: SGLT-2 inhibitors, prescribed for type 2 diabetes, have a heightened risk of amputation. The FDA issued a warning in May 2017, leading to the inclusion of a cautionary label. Vigilance is essential for patients and healthcare providers to promptly identify and address potential limb complications associated with the use of SGLT-2 inhibitors. METHOD: A comprehensive search of electronic databases was conducted, covering the period from inception to May 2024. This systematic literature review adhered to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. The quality of the included studies was assessed using the Cochrane risk of bias (ROB) tool. Inclusion and exclusion criteria were predefined, and data extraction was performed to summarize the findings. RESULT: A total of 12 randomized control trial (RCT) studies were included in the present systematic review. 37,657 (54.89%) participants were randomly assigned to receive the different interventions of SGLT-2 inhibitor, whereas 30,959 (45.11%) received a placebo. Overall, 618 events were reported in the treatment group, whereas 396 events were reported in the placebo group. CONCLUSION: In conclusion, patients treated with SGLT-2 inhibitors did not have any significant difference in amputation occurrences compared to placebo across various studies. However, canagliflozin usage has led to higher amputation events in certain trials.

Interleukin-6 serves as a critical factor in various cancer progression and therapy.

Interleukin-6 (IL-6), a pro-inflammatory cytokine, plays a crucial role in host immune defense and acute stress responses. Moreover, it modulates various cellular processes, including proliferation, apoptosis, angiogenesis, and differentiation. These effects are facilitated by various signaling pathways, particularly the signal transducer and activator of transcription 3 (STAT3) and Janus kinase 2 (JAK2). However, excessive IL-6 production and dysregulated signaling are associated with various cancers, promoting tumorigenesis by influencing all cancer hallmarks, such as apoptosis, survival, proliferation, angiogenesis, invasiveness, metastasis, and notably, metabolism. Emerging evidence indicates that selective inhibition of the IL-6 signaling pathway yields therapeutic benefits across diverse malignancies, such as multiple myeloma, prostate, colorectal, renal, ovarian, and lung cancers. Targeting key components of IL-6 signaling, such as IL-6Rs, gp130, STAT3, and JAK via monoclonal antibodies (mAbs) or small molecules, is a heavily researched approach in preclinical cancer studies. The purpose of this study is to offer an overview of the role of IL-6 and its signaling pathway in various cancer types. Furthermore, we discussed current preclinical and clinical studies focusing on targeting IL-6 signaling as a therapeutic strategy for various types of cancer.

Impact of Bariatric Surgery in Reducing Macrovascular Complications in Severely Obese T2DM Patients.

BACKGROUND: Evidence from real-world studies have suggested a reduced rate of macrovascular complications following bariatric surgery. We undertook this meta-analysis to investigate the impact of bariatric surgery on macrovascular disease outcomes in severely obese type 2 diabetes mellitus (T2DM) patients. METHODS: An extensive literature search was performed in PubMed from inception until March 2020. All cohort studies assessing the association between bariatric surgery and macrovascular complications in severely obese T2DM patients were included. Two independent reviewers screened the articles, extracted data, and assessed the quality using the Newcastle-Ottawa Scale. The primary outcome was to assess the impact of bariatric surgery and the risk of macrovascular complications. Statistical analysis was performed using Review Manager 5.3. RESULTS: This meta-analysis comprised of five studies including 49,211 participants (75% female), of which 14,434 underwent bariatric surgery and 34,777 underwent usual care. Participants who underwent bariatric surgery had a significantly lower risk of macrovascular complications as compared to those with non-surgical interventions (RR: 0.50 [95% CI: 0.35-0.73], p = 0.0003). In the subgroup analysis, based on the geographical regions, studies conducted in the USA showed a higher reduction (RR: 0.41 [95% CI: 0.32-0.53], p < 0.00001) in macrovascular complications as compared to other parts of the world. The risk of all-cause mortality was also significantly lower in patients with bariatric surgery (RR 0.39 [95% CI: 0.30-0.50], p < 0.00001). CONCLUSION: Bariatric surgery was associated with a 50% reduction in macrovascular complications along with 61% reduction in risk of all-cause mortality in morbidly obese T2DM patients.