Impact of non-alcoholic fatty liver disease and fibrosis on mortality and kidney outcomes in patients with type 2 diabetes and chronic kidney disease: A multi-cohort longitudinal study.

AIM: To evaluate the impact of non-alcoholic fatty liver disease (NAFLD) presence and fibrosis risk on adverse outcomes in patients with type 2 diabetes and chronic kidney disease. METHODS: Data were sourced from two longitudinal cohorts: 1172 patients from the National Health and Nutrition Examination Survey (NHANES) and 326 patients from the kidney biopsy cohort at the West China Hospital of Sichuan University. Cox regression estimated hazard ratios (HRs) for NAFLD and liver fibrosis concerning adverse clinical outcomes. Subsequently, a two-sample Mendelian randomization study using genome-wide association study statistics explored NAFLD's potential causal link to cardio-cerebrovascular events. RESULTS: In the NHANES cohort, NAFLD stood as an independent risk factor for various outcomes: overall mortality [HR 1.53 (95% confidence interval, CI 1.21-1.95)], mortality because of cardio-cerebrovascular diseases [HR 1.63 (95% CI 1.12-2.37)], heart disease [HR 1.58 (95% CI 1.00-2.49)], and cerebrovascular disease [HR 3.95 (95% CI 1.48-10.55)]. Notably, advanced liver fibrosis, identified by a fibrosis-4 (FIB-4) score >2.67, exhibited associations with overall mortality, cardio-cerebrovascular disease mortality and heart disease mortality. Within the kidney biopsy cohort, NAFLD correlated with future end-stage kidney disease [ESKD; HR 2.17 (95% CI 1.41-3.34)], while elevated FIB-4 or NAFLD Fibrosis Scores predicted future ESKD, following full adjustment. Liver fibrosis was positively correlated with renal interstitial fibrosis and tubular atrophy in biopsies. Further Mendelian randomization analysis supported a causal relationship between NAFLD and cardio-cerebrovascular events. CONCLUSIONS: In patients with type 2 diabetes and chronic kidney disease, the NAFLD presence and elevated FIB-4 scores link to heightened mortality risk and ESKD susceptibility. Moreover, NAFLD shows a causal relationship with cardio-cerebrovascular events.

Causal relationship between renal function and risk of esophageal cancer: insights from Mendelian randomization.

Background: Previous studies have indicated a potential correlation between renal function and risk of cancer. However, establishing a causal relationship is challenging. To address this, we employed Mendelian randomization (MR), a novel method that utilizes genotype data to simulate randomized trial groups, to investigate whether there is a causal correlation between renal function and the esophageal cancer (EC) risk. Methods: MR analysis was conducted with the individual-level data on EC from the UK Biobank published dataset. Genetic instruments were derived from single nucleotide polymorphisms (SNPs) extracted from publicly available genome-wide association studies. Furthermore, leave-one-out sensitivity analysis was performed to assess the impact of individual SNPs. Results: In our MR analysis, we examined 39,475,182 SNPs associated with various renal functional indexes from public databases. Based on the primary causal effects model using MR analyses with the inverse variance weighted method, the genetically predicted cystatin C [odds ratio (OR) =1.0005, 95% confidence interval (CI): 1.0000-1.0009; P=0.05] and creatinine (OR =1.0016, 95% CI: 1.0002-1.0031; P=0.02) demonstrated a significant association with higher risk of EC. However, we found no evidence of an association between urinary albumin and glomerular filtration rate with the risk of EC. Conclusions: Our research provides strong evidence for the association of decreased renal function to a potential risk of EC. However, it is crucial to recognize the necessity for additional large-scale prospective studies to validate this discovery and establish a comprehensive understanding of the causal relationships between renal function and EC. Keywords: Esophageal cancer (EC); renal function; Mendelian randomization (MR); causal association.

Additive impact of diabetes and Helicobacter pylori infection on all-cause mortality, diabetic mortality, and cardiovascular mortality: a longitudinal nationwide population-based study.

BACKGROUND: Diabetes mellitus (DM) and Helicobacter pylori infection (HPI) pose increasing public health challenges in aging societies, sharing common pathophysiological mechanisms, and linked to significant health risks. Our study examines their respective impacts on all-cause and cardiovascular mortalities in a comprehensive longitudinal population-based analysis. METHODS: The study analyzed data from the National Health and Nutrition Examination Survey (NHANES) database conducted between 1999 and 2019, which included information on Diabetes mellitus status and Helicobacter pylori infection status. Mortality data were obtained from the same database mentioned above. RESULTS: Among the 2719 participants, 1362 (50.1%) were free of both diabetes mellitus (DM) and Helicobacter pylori infection (HP) (DM -/HP -), 140 (5.1%) had DM alone (DM +/HP -), 1011 (37.2%) had HP alone (DM -/HP +), and 206 (7.6%) had both DM and HP (DM +/HP +). Compared to the DM -/HP - group, the DM +/HP - and DM + /HP + groups demonstrated increased all-cause mortality with adjusted hazard ratios (HRs) of 1.40 (95% [CI] 1.07-1.78) and 1.46 (95% CI 1.15-1.84), respectively. For diabetic mortality, DM +/HP- group and DM + /HP + group showed increased HR of 6.30 (95% CI 1.30-30.43) and 8.56 (95% CI 1.98-36.94), respectively. For cardiovascular mortality, the DM + /HP- group and DM + /HP + group exhibited increased HR of 1.75 (95% CI 1.14-2.69) and 1.98 (95% CI 1.40-2.79), respectively. The DM + /HP + cohort displayed the highest risk of overall mortality (p for trend = 0.003), diabetic mortality (p for trend < 0.0001), an6d cardiovascular mortality (p for trend < 0.0001). CONCLUSIONS: The concurrent presence of DM and Helicobacter pylori infection significantly amplifies the risk of all-cause, cardiovascular, and diabetic mortality. Individuals with either condition may necessitate heightened management to prevent the onset of the other ailment and reduce mortality rates.

Inflammation mechanism and research progress of COPD.

Chronic obstructive pulmonary disease (COPD) is a common respiratory disease characterized by irreversible progressive airflow limitation, often manifested by persistent cough, sputum production and other respiratory symptoms that pose a serious threat to human health and affect the quality of life of patients. The disease is associated with chronic inflammation, which is associated with the onset and progression of COPD, but anti-inflammatory therapy is not first-line treatment. Inflammation has multiple manifestations and phenotypes, and this heterogeneity reveals different patterns of inflammation, making treatment difficult. This paper aims to explore the direction of more effective anti-inflammatory treatment by analyzing the nature of inflammation and the molecular mechanism of disease occurrence and development in COPD patients, and to provide new ideas for the treatment of COPD patients.

Corrigendum: Safety issues of tirzepatide (pancreatitis and gallbladder or biliary disease) in type 2 diabetes and obesity: a systematic review and meta-analysis.

[This corrects the article DOI: 10.3389/fendo.2023.1214334.].

Effects of Organic Soil Amendments on Antimicrobial-Resistant Bacteria in Urban Agriculture Environments.

Biological soil amendments of animal origin (BSAAOs) are widely used in urban agriculture to improve soil quality. Although BSAAO use is regulated due to risks for introducing foodborne pathogens, effects on antimicrobial-resistant (AMR) bacteria are not well established. Here, we aimed to explore the impacts of BSAAOs on levels of resident AMR bacteria in leafy vegetable production environments (i.e., kale, lettuce, chard, cabbage) across urban farms and community gardens in the greater Washington D.C. area (n = 7 sites). Leaf tissue (LT), root zone soil (RZS; amended soil in crop beds), and bulk soil (BS; site perimeter) were collected and analyzed for concentrations of total heterotrophic bacteria (THB), ampicillin (Amp) or tetracycline (Tet) resistant THB, and coliforms. As expected, amended plots harbored significantly higher concentrations of THB than bulk soil (P < 0.001). The increases in total bacteria associated with reduced fractions of Tet-resistant bacteria (P = 0.008), as well as case-specific trends for reduced fractions of Amp-resistant bacteria and coliforms. Site-to-site variation in concentrations of AMR bacteria in soil and vegetable samples reflected differences in land history and crop management, while within-site variation was associated with specific amendment sources, as well as vegetable type and cultivar. Representative isolates of the AMR bacteria and coliforms were further screened for multidrug resistance (MDR) phenotypes, and a high frequency was observed for the former. In amended soils, as the soil pH (range 6.56-7.80) positively correlated with the fraction of Tet-resistant bacteria (rho = 0.529; P < 0.001), crop management strategies targeting pH may have applications to control related risks. Overall, our findings demonstrate that soil amendments promote soil bacteria concentrations and have important implications for limiting the spread of AMR bacteria, at least in the urban landscape.

Systemic immune-inflammation index and all-cause and cause-specific mortality in sarcopenia: a study from National Health and Nutrition Examination Survey 1999-2018.

Background: Sarcopenia, common in the elderly, often linked to chronic diseases, correlates with inflammation.The association between SII and mortality in sarcopenia patients is underexplored, this study investigates this relationship in a U.S. adult cohort. Methods: We analyzed 1999-2018 NHANES data, focusing on 2,974 adults with sarcopenia. Mortality outcomes were determined by linking to National Death Index (NDI) records up to December 31, 2019. Using a weighted sampling design, participants were grouped into three groups by the Systemic Immune-Inflammation Index (SII). We used Cox regression models, adjusting for demographic and clinical variables, to explore SII's association with all-cause and cause-specific mortality in sarcopenia, performing sensitivity analyses for robustness. Results: Over a median follow-up of 9.2 years, 829 deaths occurred. Kaplan-Meier analysis showed significant survival differences across SII groups. The highest SII group showed higher hazard ratios (HRs) for all-cause and cause-specific mortality in both crude and adjusted models. The highest SII group had a higher HR for all-cause(1.57, 1.25-1.98), cardiovascular(1.61, 1.00-2.58), cancer(2.13, 1.32-3.44), and respiratory disease mortality(3.21, 1.66-6.19) in fully adjusted models. Subgroup analyses revealed SII's association with all-cause mortality across various demographics, including age, gender, and presence of diabetes or cardiovascular disease. Sensitivity analyses, excluding participants with cardiovascular diseases, those who died within two years of follow-up, or those under 45 years of age, largely reflected these results, with the highest SII group consistently demonstrating higher HRs for all types of mortality in both unadjusted and adjusted models. Conclusion: Our study is the first to demonstrate a significant relationship between SII and increased mortality risks in a sarcopenia population.

Safety issues of tirzepatide (pancreatitis and gallbladder or biliary disease) in type 2 diabetes and obesity: a systematic review and meta-analysis.

Purpose: A systematic review and meta-analysis was conducted to synthesize the available data from clinical trials and assess the safety issues of tirzepatide (pancreatitis and gallbladder or biliary disease) in type 2 diabetes (T2D) and obesity. Methods: A systematic search was conducted in three electronic databases, namely Embase, PubMed, and the Cochrane Library, up until March 1, 2023, to identify randomized controlled trials (RCTs) comparing tirzepatide to either placebo or active hypoglycemic drugs in individuals with T2D and obesity. Heterogeneity was assessed using the I2 value and Cochran's Q test, and a fixed effects model was employed to estimate the safety profile of tirzepatide. The safety outcomes of interest, including pancreatitis, the composite of gallbladder or biliary diseases, cholecystitis, and cholelithiasis and biliary diseases, were evaluated. (The composite of gallbladder or biliary diseases incorporated cholelithiasis, cholecystitis, other gallbladder disorders, and biliary diseases.). Results: A total of nine trials with 9871 participants (6828 in the tirzepatide group and 3043 in the control group) that met the pre-specified criteria were included. When compared to all control groups consisting of basal insulin (glargine or degludec), selective GLP1-RA (dulaglutide or semaglutide once weekly), and placebo, an increased risk of pancreatitis was not found to be significantly associated with tirzepatide (RR 1.46, [95% CI] 0.59 to 3.61; I2 = 0.0%, p = 0.436). For gallbladder or biliary disease, the composite of gallbladder or biliary disease was significantly associated with tirzepatide compared with placebo or basal insulin (RR 1.97, [95% CI] 1.14 to 3.42; I2 = 0.0%, p = 0.558), but not with the risk of cholelithiasis, cholecystitis or biliary diseases. Conclusion: Based on the currently available data, tirzepatide appears to be safe regarding the risk of pancreatitis. However, the increased risk of the composite outcome of gallbladder or biliary diseases observed in RCTs warrants further attention from physicians in clinical practice. Systematic review registration: https://www.crd.york.ac.uk/PROSPERO, identifier CRD42023412400.

A new insight into synergistic effects between endogenous phenolic compounds additive and α-tocopherol for the stability of olive oil.

Investigation of edible oil stability involves interactions between additive polyphenols and the inherent tocopherols. The work aimed to identify endogenous polyphenols to produce the synergistic effect with α-tocopherol in olive oil and to find the right action ratio. Caffeic acid and quercetin were selected from the 15 main endogenous phenolic compounds in olive oil. Quercetin had the strongest synergistic effect with α-tocopherol at 2:1 in the olive oil model. The rate of 2:1 also was the turning point of the change of synergism. Furthermore, the addition of quercetin and α-tocopherol at 2:1 to olive oil resulted in lower POV, K232, K270, and secondary oxidation products such as (E, E)-2,4-decadienal and 2-pentylfuran than the olive oil model with a single antioxidant in three months of accelerated oxidation. The dynamic changes of antioxidants during oxidation in olive oil indicated that their synergistic effect was the repair and regeneration of α-tocopherol by quercetin.