Cardiovascular and mortality outcomes with GLP-1 receptor agonists vs other glucose-lowering drugs in individuals with NAFLD and type 2 diabetes: a large population-based matched cohort study.

AIMS/HYPOTHESIS: We aimed to determine whether the use of glucagon-like peptide-1 receptor agonists (GLP-1RA) in individuals with non-alcoholic fatty liver disease (NAFLD) and type 2 diabetes mellitus decreases the risk of new-onset adverse cardiovascular events (CVEs) and mortality rate compared with other glucose-lowering drugs in a real setting at a population level. METHODS: We conducted a population-based propensity-matched retrospective cohort study using TriNetX. The cohort comprised patients over 20 years old who were newly treated with glucose-lowering drugs between 1 January 2013 and 31 December 2021, and followed until 30 September 2022. New users of GLP-1RAs were matched based on age, demographics, comorbidities and medication use by using 1:1 propensity matching with other glucose-lowering drugs. The primary outcome was the new onset of adverse CVEs, including heart failure, composite incidence of major adverse cardiovascular events (MACE; defined as unstable angina, myocardial infarction, or coronary artery procedures or surgeries) and composite cerebrovascular events (defined as the first occurrence of stroke, transient ischaemic attack, cerebral infarction, carotid intervention or surgery), and the secondary outcome was all-cause mortality. Cox proportional hazards models were used to estimate HRs. RESULTS: The study involved 2,835,398 patients with both NAFLD and type 2 diabetes. When compared with the sodium-glucose cotransporter 2 (SGLT2) inhibitors group, the GLP-1RAs group showed no evidence of a difference in terms of new-onset heart failure (HR 0.97; 95% CI 0.93, 1.01), MACE (HR 0.95; 95% CI 0.90, 1.01) and cerebrovascular events (HR 0.99; 95% CI 0.94, 1.03). Furthermore, the two groups had no evidence of a difference in mortality rate (HR 1.06; 95% CI 0.97, 1.15). Similar results were observed across sensitivity analyses. Compared with other second- or third-line glucose-lowering medications, the GLP-1RAs demonstrated a lower rate of adverse CVEs, including heart failure (HR 0.88; 95% CI 0.85, 0.92), MACE (HR 0.89; 95% CI 0.85, 0.94), cerebrovascular events (HR 0.93; 95% CI 0.89, 0.96) and all-cause mortality rate (HR 0.70; 95% CI 0.66, 0.75). CONCLUSIONS/INTERPRETATION: In individuals with NAFLD and type 2 diabetes, GLP-1RAs are associated with lower incidences of adverse CVEs and all-cause mortality compared with metformin or other second- and third-line glucose-lowering medications. However, there was no significant difference in adverse CVEs or all-cause mortality when compared with those taking SGLT2 inhibitors.

Therapeutic potential of curcumin and its nanoformulations for treating oral cancer.

The global incidence of oral cancer has steadily increased in recent years and is associated with high morbidity and mortality. Oral cancer is the most common cancer in the head and neck region, and is predominantly of epithelial origin (i.e. squamous cell carcinoma). Oral cancer treatment modalities mainly include surgery with or without radiotherapy and chemotherapy. Though proven effective, chemotherapy has significant adverse effects with possibilities of tumor resistance to anticancer drugs and recurrence. Thus, there is an imperative need to identify suitable anticancer therapies that are highly precise with minimal side effects and to make oral cancer treatment effective and safer. Among the available adjuvant therapies is curcumin, a plant polyphenol isolated from the rhizome of the turmeric plant Curcuma longa. Curcumin has been demonstrated to have anti-infectious, antioxidant, anti-inflammatory, and anticarcinogenic properties. Curcumin has poor bioavailability, which has been overcome by its various analogues and nanoformulations, such as nanoparticles, liposome complexes, micelles, and phospholipid complexes. Studies have shown that the anticancer effects of curcumin are mediated by its action on multiple molecular targets, including activator protein 1, protein kinase B (Akt), nuclear factor κ-light-chain-enhancer of activated B cells, mitogen-activated protein kinase, epidermal growth factor receptor (EGFR) expression, and EGFR downstream signaling pathways. These targets play important roles in oral cancer pathogenesis, thereby making curcumin a promising adjuvant treatment modality. This review aims to summarize the different novel formulations of curcumin and their role in the treatment of oral cancer.

Risk of pancreatic cancer in individuals with celiac disease in the United States: A population-based matched cohort study.

BACKGROUND: Celiac disease (CD) has been associated with gastrointestinal malignancies. However, the magnitude of the risk of pancreatic cancer (PC) associated with CD is much less clear, and risks have not been estimated from large populations. AIM: To assess the risk of PC in CD patients. METHODS: We conducted a population-based, multicenter, propensity score-matched cohort study with consecutive patients diagnosed with CD using the TriNeTx research network platform. We examined the incidence of PC in patients with CD compared with a matched cohort of patients without CD (non-CD, controls). Each patient in the main group (CD) was matched to a patient in the control group using 1:1 propensity score matching to reduce confounding effects. The incidence of PC was estimated using a Cox proportional hazards model with a hazard ratio (HR) and 95% confidence interval (CI). RESULTS: A total of 389980 patients were included in this study. Among them, 155877 patients had a diagnosis of CD, and the remaining 234103 individuals without CD were considered a control cohort. The mean duration of follow-up for patients in the CD and control cohorts was 5.8 ± 1.8 and 5.9 ± 1.1 years, respectively. During the follow-up, 309 patients with CD developed PC, whereas 240 patients developed PC in the control group (HR = 1.29; 95%CI: 1.09-1.53). In the secondary analyses in the first year after diagnosis of CD, patients with CD were at a significant increase in risk for PC; 151 patients with CD had an incidence of PC compared with 96 incidences of PC among the patients in the non-CD control group (HR = 1.56; 95%CI: 1.20-2.01) and sensitivity analysis showed similar magnitude to the one generated in the primary and secondary analysis. CONCLUSION: Patients with CD are at increased risk of PC. Risk elevation persists beyond the first year after diagnosis to reference individuals without CD from the general population.

Clinical characteristics and outcomes of COVID-19 in patients with autoimmune hepatitis: A population-based matched cohort study.

BACKGROUND: Patients with autoimmune hepatitis (AIH) require life-long immunosuppressive agents that may increase the risk of poor coronavirus disease 2019 (COVID-19) outcomes. There is a paucity of large data at the population level to assess whether patients with AIH have an increased risk of severe diseases. AIM: To evaluate the impact of pre-existing AIH on the clinical outcomes of patients with COVID-19. METHODS: We conducted a population-based, multicenter, propensity score-matched cohort study with consecutive adult patients (≥ 18 years) diagnosed with COVID-19 using the TriNeTx research network platform. The outcomes of patients with AIH (main group) were compared to a propensity score-matched cohort of patients: (1) Without chronic liver disease (CLD); and (2) Patients with CLD except AIH (non-AIH CLD) control groups. Each patient in the main group was matched to a patient in the control group using 1:1 propensity score matching to reduce confounding effects. The primary outcome was all-cause mortality, and secondary outcomes were hospitalization rate, need for critical care, severe disease, mechanical ventilation, and acute kidney injury (AKI). For each outcome, the risk ratio (RR) and confidence intervals (CI) were calculated to compare the association of AIH with the outcome. RESULTS: We identified 375 patients with AIH, 1647915 patients with non-CLD, and 15790 patients with non-AIH CLD with COVID-19 infection. Compared to non-CLD patients, the AIH cohort had an increased risk of all-cause mortality (RR = 2.22; 95%CI: 1.07-4.61), hospitalization rate (RR = 1.78; 95%CI: 1.17-2.69), and severe disease (RR = 1.98; 95%CI: 1.19-3.26). The AIH cohort had a lower risk of hospitalization rate (RR = 0.72; 95%CI: 0.56-0.92), critical care (RR = 0.50; 95%CI: 0.32-0.79), and AKI (RR = 0.56; 95%CI: 0.35-0.88) compared to the non-AIH CLD patients. CONCLUSION: Patients with AIH are associated with increased hospitalization risk, severe disease, and all-cause mortality compared to patients without pre-existing CLD from the diagnosis of COVID-19. However, patients with AIH were not at risk for worse outcomes with COVID-19 than other causes of CLD.

Nanocurcumin in Oral Squamous Cancer Cells and Its Efficacy as a Chemo-Adjuvant.

Oral squamous cell carcinoma is the sixth most common cancer worldwide. Despite the available treatment, the survival rate is poor. The addition of agents to make chemotherapeutics safer and more effective is important. Curcumin is a common Indian spice that has shown anticarcinogenic properties. It has been possible to overcome its poor bio-availability using nanotechnology. We aimed to investigate the adjuvant effect of nanocurcumin (NC ~ 200 nm size) treatment on cetuximab (epidermal growth factor receptor inhibitor) in oral squamous cancer cells (KB 3-1 cell). Cancer cells were cultured and treated for 24 hours with cetuximab and NC, in various doses to find the drugs' half-maximal inhibitory concentration (IC50). Experiments were conducted with a combination dose of both and sensitization treatment with NC before cetuximab with cytotoxicity assessment by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. One-way analysis of variance (ANOVA) was used to compare different treatment groups. We found a concentration-dependent cancer cell death with NC, which was significant compared to cetuximab (p <0.001). The combination treatment group had highly significant cell death (p <0.0001) compared to a single drug, and the NC sensitization caused substantial cell death compared to a single cetuximab treatment (p<0.01). Our study findings indicate the potential chemo-adjuvant effect of NC in oral cancer.

Comparative Study of Risk Factors and Cognitive Profile of Small- and Large-Vessel Vascular Dementia - A Clinic Based Study.

Background: Vascular dementia (VaD) is a clinically heterogeneous entity. There is a dearth of studies for comparison of the cognitive profile of cerebral small-vessel disease (SVD) with large-vessel disease. Objective: We planned to evaluate and compare the cognitive profile of SVD and large-vessel VaD and evaluate various risk factors associated with them. Materials and Methods: Patients of VaD were recruited after excluding mixed and ambiguous cases. Patients were classified into SVD and large-vessel VaD and analyzed for their clinic-epidemiological and cognitive profiles. Results: Among 76 patients, 48 (62.5%) have SVD and 28 (37.5%) have large-vessel disease. Hypertension (93.4%) was the commonest risk factor, followed by smoking (34.21%), hyperlipidemia (26.31%), and diabetes mellitus (DM, 22.36%). Hypertension (P < 0.05) and DM were common in SVD, whereas smoking, hyperlipidaemia, and cardiac diseases were common in large-vessel disease. Attention (77.1% vs 25%), executive function (68.8% vs 28.6%), and calculation (58.3% vs 32.1%) were significantly more impaired in SVD compared to large-vessel disease, whereas visuoperceptual (21.4% vs 6.3%), praxis (28.6% vs 4.2%), and gnosis (14.3% vs 2.1%) were significantly more impaired in large-vessel disease than in SVD. Disruption of frontal-subcortical connection was responsible for the cognitive profile in SVD, but in large-vessel disease, it resulted from the cumulative loss of function from different lesions. Conclusions: Despite having common vascular risk factors, few are more common in SVD than in large-vessel disease. The different clinical and cognitive profile is due to the diverse anatomical lesions in these two subclasses of VaD.

Association of Gut Microbiome and Vitamin D Deficiency in Knee Osteoarthritis Patients: A Pilot Study.

BACKGROUND: Few preclinical studies have shown that Knee osteoarthritis (KOA) is linked to gut microbiome dysbiosis and chronic inflammation. This pilot study was designed to look at the gut microbiome composition in KOA patients and normal individuals with or without vitamin D deficiency (VDD, serum vitamin D <30 ng/mL). METHODS: This pilot study was conducted prospectively in 24 participants. The faecal samples of all the participants were taken for DNA extraction. The V3-V4 region of 16s rRNA was amplified, and the library was prepared and sequenced on the Illumina Miseq platform. RESULTS: The mean (±SD) age was 45.5 (±10.2) years with no defined comorbidities. Of 447 total Operational Taxonomic Units (OTUs), a differential abundance of 16 nominally significant OTUs between the groups was observed. Linear discriminate analysis (LEfSe) revealed a significant difference in bacteria among the study groups. Pseudobutyrivibrio and Odoribacter were specific for VDD, while Parabacteroides, Butyricimonas and Gordonibacter were abundant in the KOA_VDD group, and Peptococcus, Intestimonas, Delftia and Oribacterium were abundant in the KOA group. About 80% of bacterial species were common among different groups and hence labelled as core bacterial species. However, the core microbiome of KOA and VDD groups were not seen in the KOA_VDD group, suggesting that these bacterial groups were affected by the interaction of the KOA and VDD factors. CONCLUSION: Parabacteroides, Butyricimonas, Pseudobutyrivibrio, Odoribacter and Gordonibacter are the predominant bacteria in vitamin D deficient patients with or without KOA. Together these results indicate an association between the gut microbiome, vitamin D and knee osteoarthritis.