Survival after Trastuzumab Therapy in Patients with Locally Advanced or Metastatic HER2-Positive Gastric or Gastroesophageal Junction Cancer: A Meta-Analysis of Randomized Controlled Trials.

Background: In the Trastuzumab for Gastric Cancer study, it was found that trastuzumab combined with doublet chemotherapy (fluoropyrimidine and platinum) was the gold-standard treatment for gastroesophageal adenocarcinoma (GEA) that was locally advanced, unresectable, or metastatic (HER2+). Materials and Methods: We performed a meta-analysis of randomized phase II/III studies testing trastuzumab in combination or alone. Results: This meta-analysis's findings involved 2048 patients in total. The treatment arm and hormone receptor status were used to stratify the combined HR. Overall, the PFS (Random model) HR [0.80] and 95% confidence intervals (CI) [0.68-0.95] were significantly higher for regimens containing trastuzumab, fluoropyrimidine, and platinum compared to regimens containing fluoropyrimidine and platinum. Conclusions: The results of this meta-analysis provide additional support for trastuzumab's use in treating HER2-positive GEA, particularly in cases where the disease lacks a HER2+ receptor.

The prevalence of polypharmacy and hyper-polypharmacy among middle-aged vs. older patients in Saudi Arabia: a cross-sectional study.

Introduction: Polypharmacy, the use of multiple medications, is a growing concern among middle-aged and older patients, posing potential risks and challenges in healthcare management. Aim: This study aimed to identify the prevalence of polypharmacy and hyper-polypharmacy among populations of middle-aged vs. older patients and identify its associated common comorbidities and prescribed medications in Qatif Central Hospital (QCH), Saudi Arabia. Methods: Patients aged 40 years or older who presented to an outpatient medical care clinic at QCH, Saudi Arabia, between 1 January and 31 December 2021 were included, and their comorbidities, prescribed medications, and recent clinical laboratory test results were collected. The Charlson comorbidity index (CCI) score was calculated to predict the risk of mortality. Logistic regression was used to compute the association between the prevalence of polypharmacy and patient characteristics. The results were presented as odds ratios (ORs) and 95% confidence intervals (95% CIs). Results: A total of 14,081 patients were included; 31% of the cohort comprised older patients, and 66% of the cohort was identified with polypharmacy. The majority of the polymedicated patients were presented to an internal medicine care unit (34%). The prevalence of polypharmacy was positively associated with CCI (OR = 3.4, 95% CI 3.3-3.6), having a disease related to the musculoskeletal system (MSD) (OR = 4.2, 95% CI 3.8-4.7), and alimentary tract and metabolism (ATM) (OR = 3.8, 95% CI 3.4-4.2). Conversely, the prevalence of polypharmacy was negatively associated with age (OR = 0.9, 95% CI 0.89-0.91) and patients with cardiovascular diseases (OR = 0.6, 95% CI 0.5-0.7). Conclusion: Polypharmacy is still an ongoing concern. Patients, particularly those with diseases related to MSD or ATM, should be considered for reviewing prescriptions by pharmacists to reduce the risk of adverse drug reactions and future consequences of polypharmacy.

Can sodium-glucose co-transporter-2 (SGLT-2) inhibitor reduce the risk of adverse complications due to COVID-19? - Targeting hyperinflammation.

Sodium-glucose co-transporter-2 (SGLT-2) inhibitors are antidiabetic drugs with numerous pleiotropic and positive clinical effects, particularly regarding a reno-cardiovascular protective effect. More recent studies, including from our laboratory, have highlighted some novel anti-inflammatory activity of SGLT-2 inhibitors. This may confer a theoretical advantage in mitigating excessive cytokine production and inflammatory response associated with serious COVID-19 infection. Specifically, earlier research has demonstrated that SGLT-2 inhibitors are associated with a notable decrease in inflammatory indicators, for example, C-reactive protein, ferritin, and interleukin-6. Furthermore, SGLT-2 inhibitors exhibit a favourable impact on the vascular endothelium function; this could pertinence the prophylaxis of the thrombotic issues that arise in SARS-CoV-2. This review provides an overview of the COVID-19 indirect immune response mechanisms impacting the cardiovascular system and the possible effect of SGLT-2 inhibitors on the management of COVID-19.

Diuretics and risk of lower extremity amputation amongst patients with insulin-treated type 2 diabetes - exploring the mechanism of possible sodium glucose co-transporter 2 inhibitor induced risk of lower extremity amputations.

AIMS AND BACKGROUND: Sodium-glucose cotransporter-2 (SGLT2) inhibitor has been linked to an increased risk of lower extremity amputation (LEA) in patients with Type 2 Diabetes (T2D) and is known to induce volume depletion through osmotic diuresis. We investigated the potential association between diuretics use and the LEA risk in insulin-treated T2D patients. METHODS AND MATERIALS: A retrospective cohort study was conducted on 10,320 insulin-treated T2D patients within the UK population. Cox proportional hazard models were utilised to estimate LEA hazard ratios. Amputation risk was compared between a propensity score-matched cohort of diuretics users versus non-users over a 20-year period. RESULTS: Among 10,320 subjects, 6454 (52.3%) were on diuretics. In the full cohort, diuretic-treated patients had significantly higher risk of LEA than the non-diuretic individuals (HR: 1.89; 95%CI: 1.34-2.68). When adjusting for possible confounding effects, a 2.3-fold higher risk of amputation was observed (aHR: 2.45; 95%CI: 1.63-3.69). In the matched cohort (n = 580), this association is marginally significant (HR: 3.33; 95%CI: 1.17-18.9; p = .029). CONCLUSION: While diuretic use appeared to be associated with an increased risk of LEA among insulin-treated T2D patients, this association is marginally significant after controlling for confounding factors by cohort matching. These results suggest that volume depletion may be a factor in increasing the risk of LEA amongst high-risk T2D patients, but the strength of this association is weak when adjusted for all other risk factors. Thus, patient selection is crucial when determining the safe use of agents that induce volume depletion in high risk patients with T2D.

Effect of Sodium-Glucose Cotransporter-2 Inhibitors on Endothelial Function: A Systematic Review of Preclinical Studies.

INTRODUCTION: While the beneficial effects of sodium-glucose cotransporter-2 (SGLT-2) inhibitors on cardiovascular and renal outcomes are recognized, their direct effects on endothelial function remain unclear. We, therefore, undertook a systematic review to evaluate the current literature in this area. METHODS: Electronic databases (PubMed, EMBASE, and Medline) were systematically searched using PRISMA guidelines for studies involving the in vitro, in vivo, or ex vivo administration of SGLT-2 inhibitors to animals, vascular tissue, or vascular endothelial cells. RESULTS: Of 144 retrieved publications, 24 experimental studies met the inclusion criteria. Reporting of possible sources of bias were poor, making the overall risk of bias difficult to assess. Within the 24 studies, the SGLT-2 inhibitors canagliflozin, ipragliflozin, empagliflozin, dapagliflozin, tofogliflozin, and luseogliflozin were assessed as interventions. Animal model studies (n = 17) demonstrated that all SGLT-2 inhibitors prevented endothelial dysfunction and enhanced endothelium-dependent vasorelaxation in diabetic and non-diabetic models. In vitro studies (n = 9) using human endothelial cells indicated a direct anti-inflammatory effect of dapagliflozin (1-100 nM) and canagliflozin, (10 µM), while empagliflozin (1 and 10 µM) improved viability of hyperglycemic cells. Potential mechanisms of action of the SGLT-2 inhibitors include a reduction in oxidative stress, modulation of adhesion molecules and reductions in pro-inflammatory cytokines. CONCLUSIONS: Preclinical studies indicate that SGLT-2 inhibitors attenuate vascular dysfunction in preclinical models via a combination of mechanisms that appear to act independently of glucose-lowering benefits.