Cumulative effects of excess high-normal alanine aminotransferase levels in relation to new-onset metabolic dysfunction-associated fatty liver disease in China.

BACKGROUND: Within the normal range, elevated alanine aminotransferase (ALT) levels are associated with an increased risk of metabolic dysfunction-associated fatty liver disease (MAFLD). AIM: To investigate the associations between repeated high-normal ALT measurements and the risk of new-onset MAFLD prospectively. METHODS: A cohort of 3553 participants followed for four consecutive health examinations over 4 years was selected. The incidence rate, cumulative times, and equally and unequally weighted cumulative effects of excess high-normal ALT levels (ehALT) were measured. Cox proportional hazards regression was used to analyse the association between the cumulative effects of ehALT and the risk of new-onset MAFLD. RESULTS: A total of 83.13% of participants with MAFLD had normal ALT levels. The incidence rate of MAFLD showed a linear increasing trend in the cumulative ehALT group. Compared with those in the low-normal ALT group, the multivariate adjusted hazard ratios of the equally and unequally weighted cumulative effects of ehALT were 1.651 [95% confidence interval (CI): 1.199-2.273] and 1.535 (95%CI: 1.119-2.106) in the third quartile and 1.616 (95%CI: 1.162-2.246) and 1.580 (95%CI: 1.155-2.162) in the fourth quartile, respectively. CONCLUSION: Most participants with MAFLD had normal ALT levels. Long-term high-normal ALT levels were associated with a cumulative increased risk of new-onset MAFLD.

Association between TyG index trajectory and new-onset lean NAFLD: a longitudinal study.

Objective: The purpose of this manuscript is to identify longitudinal trajectories of changes in triglyceride glucose (TyG) index and investigate the association of TyG index trajectories with risk of lean nonalcoholic fatty liver disease (NAFLD). Methods: Using data from 1,109 participants in the Health Management Cohort longitudinal study, we used Latent Class Growth Modeling (LCGM) to develop TyG index trajectories. Using a Cox proportional hazard model, the relationship between TyG index trajectories and incident lean NAFLD was analyzed. Restricted cubic splines (RCS) were used to visually display the dose-response association between TyG index and lean NAFLD. We also deployed machine learning (ML) via Light Gradient Boosting Machine (LightGBM) to predict lean NAFLD, validated by receiver operating characteristic curves (ROCs). The LightGBM model was used to create an online tool for medical use. In addition, NAFLD was assessed by abdominal ultrasound after excluding other liver fat causes. Results: The median age of the population was 46.6 years, and 440 (39.68%) of the participants were men. Three distinct TyG index trajectories were identified: "low stable" (TyG index ranged from 7.66 to 7.71, n=206, 18.5%), "moderate stable" (TyG index ranged from 8.11 to 8.15, n=542, 48.8%), and "high stable" (TyG index ranged from 8.61 to 8.67, n=363, 32.7%). Using a "low stable" trajectory as a reference, a "high stable" trajectory was associated with an increased risk of lean-NAFLD (HR: 2.668, 95% CI: 1.098-6.484). After adjusting for baseline age, WC, SBP, BMI, and ALT, HR increased slightly in "moderate stable" and "high stable" trajectories to 1.767 (95% CI:0.730-4.275) and 2.668 (95% CI:1.098-6.484), respectively. RCS analysis showed a significant nonlinear dose-response relationship between TyG index and lean NAFLD risk (χ2 = 11.5, P=0.003). The LightGBM model demonstrated high accuracy (Train AUC 0.870, Test AUC 0.766). An online tool based on our model was developed to assist clinicians in assessing lean NAFLD risk. Conclusion: The TyG index serves as a promising noninvasive marker for lean NAFLD, with significant implications for clinical practice and public health policy.

Association of the triglyceride-glucose index with the occurrence and recurrence of colorectal adenomas: a retrospective study from China.

BACKGROUND: Resection of colorectal adenoma (CRA) prevents colorectal cancer; however, recurrence is common. We aimed to assess the association of the triglyceride-glucose (TyG) index with CRA occurrence and recurrence. METHODS: Data from 3392 participants at a hospital in China from 2020 to 2022 were analyzed. Logistic regression was used to estimate odds ratios (ORs) and 95% confidence intervals (CIs). A restricted cubic spline was used to fit TyG index dose‒response curves to recurrent adenomas. The discriminatory power of TyG index for predicting later recurrence was assessed with the area under the receiver operating characteristic (ROC) curve in 170 patients with a TyG index at initial adenoma diagnosis. RESULTS: One thousand five hundred ninety-six adenoma and 1465 normal participants were included in the occurrence analysis, and 179 recurrent and 152 nonrecurrent participants were included in the recurrence analysis. The TyG mutation was an independent risk factor for CRA occurrence and recurrence. After adjusting for confounders, the risk of adenoma in the participants in Q2, Q3, and Q4 groups of TyG was 1.324 (95% CI 1.020-1.718), 1.349 (95% CI 1.030-1.765), and 1.445 (95% CI 1.055-1.980) times higher than that of the Q1, respectively, and the risk of recurrence in the Q3 and Q4 groups was 2.267 (95% CI 1.096-4.691) and 2.824 (95% CI 1.199-6.648) times in Q1 group. Multiple logistic regression showed that the highest quartile of the TyG index was associated with a greater risk of advanced adenoma recurrence (OR 4.456, 95% CI 1.157-17.164), two or more adenomas (OR 5.079, 95% CI 1.136-22.714 [after removal of TyG index extreme values]), and proximal colon or both adenomas (OR 3.043, 95% CI 1.186-7.810). Subgroup analysis revealed that the association was found to be present only in participants of all age groups who were either male or without obesity, hyperglycemia, hypertension, or dyslipidemia (p < 0.05). ROC curves illustrated that the TyG index had good predictive efficacy for identifying recurrence, especially for patients with two or more adenomas (AUC 0.777, 95% CI 0.648-0.907). CONCLUSIONS: An increase in the TyG index is associated with an increased risk of adenoma occurrence and recurrence, with a stronger association with the latter.

Efficacy and Safety of Novel Oral Antivirals in Hospitalized COVID-19 Patients: A Network Meta-Analysis of Randomized Clinical Trials.

Objective: Numerous pharmacological interventions are now under investigation for the treatment of the 2019 coronavirus pandemic (COVID-19), and the evidence is rapidly evolving. Our aim is to evaluate the comparative efficacy and safety of these drugs. Methods: We searched for randomized clinical trials (RCTs) on the efficacy and safety of novel oral antivirals for the treatment of hospitalized COVID-19 patients until November 30, 2022, including baricitinib, ivermectin (IVM), favipiravir (FVP), chloroquine (CQ), lopinavir and ritonavir (LPV/RTV), hydroxychloroquine (HCQ), and hydroxychloroquine plus azithromycin (HCQ+AZT). The main outcomes of this network meta-analysis (NMA) were in-hospital mortality, adverse event (AE), recovery time, and improvement in peripheral capillary oxygen saturation (SpO2). For dichotomous results, the odds ratio (OR) was used, and the 95% confidence interval (CI) was determined. We also used meta-regression to explore whether different treatments affected efficacy and safety. STATA 15.0 was used to conduct the NMA. The research protocol was registered with PROSPERO (#CRD 42023415743). Results: Thirty-six RCTs, with 33,555 hospitalized COVID-19 patients, were included in this analysis. First, we compared the efficacy of different novel oral antivirals. Baricitinib (OR 0.56, 95% CI: 0.35 to 0.90) showed the highest probability of being the optimal probiotic species in reducing in-hospital mortality and suggested that none of the interventions reduced AE better than placebo. In terms of safety outcomes, IVM ranked first in improving the recovery time of hospitalized COVID-19 patients (mean difference (MD) -1.36, 95% CI: -2.32 to -0.39). In addition, patients were most likely to increase SpO2 (OR 1.77, 95% CI: 0.09 to 3.45). The meta-regression revealed no significant differences between participants using different novel oral antivirals in all outcomes in hospitalized COVID-19 patients. Conclusion: Currently, baricitinib has reduced in-hospital mortality in hospitalized COVID-19 patients, with moderate certainty of evidence. IVM appeared to be a safer option than placebo in improving recovery time, while FVP was associated with increased SpO2 safety outcomes. These preliminary evidence-based observations should guide clinical practice until more data are made public.

Efficacy and safety of Omega-3 polyunsaturated fatty acids in adjuvant treatments for colorectal cancer: A meta-analysis of randomized controlled trials.

Background: Colorectal cancer (CRC) ranks third globally. There are many adverse reactions to treatments such as surgeries and post-surgical chemotherapy, which affect patients' prognosis and reduce their life quality. Omega-3 polyunsaturated fatty acids (O3FAs) have become an essential part of immune nutrition due to their anti-inflammatory properties, which improve body immunity and have attracted widespread attention. A systematic review focused on the efficacy and safety of O3FAs for patients undergoing surgeries in combination with chemotherapy or a surgery alone is lacking. Objectives: To evaluate the efficacy of O3FAs in the adjuvant treatment of CRC, a meta-analysis was conducted on patients with CRC who underwent surgeries in combination with chemotherapy or a surgery alone. Methods: As of March 2023, publications have been obtained using search terms from digital databases such as PubMed, Web of Science, Embase and Cochrane Library. Only randomized clinical trials (RCTs) evaluating the efficacy and safety of O3FAs following adjuvant treatments for CRC were included in the meta-analysis. Key outcomes were tumor necrosis factor-alpha (TNF-α), C-reactive protein (CRP), interleukin-6 (IL-6), interleukin-1beta (IL-1ß), albumin, body mass index (BMI), weight, the rate of infectious and non-infectious complications, the length of hospital stay (LOS), CRC mortality and life quality. Results: After screening 1,080 studies, 19 RCTs (n = 1,556) with O3FAs in CRC were included, in all of which at least one efficacy or safety outcome was examined. Compared to the control group, the level of TNF-α (MD = -0.79, 95% CI: 1.51 to -0.07, p = 0.03) and IL-6 was reduced due to O3FA-enriched nutrition during the perioperative period (MD = -4.70, 95% CI: 6.59 to -2.80, p < 0.00001). It also reduces LOS (MD = 9.36, 95% CI: 2.16 to 16.57, p = 0.01). No significant differences were found in CRP, IL-1ß, albumin, BMI, weight, the rate of infectious and non-infectious complications, CRC mortality or life quality. The inflammatory status of patients with CRC undergoing adjuvant therapies decreased after a total parenteral nutrition (TPN) O3FA supplementation (TNF-α, MD = -1.26, 95% CI: 2.25 to -0.27, p = 0.01, I 2 = 4%, n = 183 participants). The rate of infectious and non-infectious complications was reduced among patients with CRC undergoing adjuvant therapies after a parenteral nutrition (PN) O3FA supplementation (RR = 3.73, 95% CI: 1.52 to 9.17, p = 0.004, I 2 = 0%, n = 76 participants). Conclusion: Our observations suggest that supplementation with O3FAs has little or no effect on patients with CRC undergoing adjuvant therapies and that a prolonged inflammatory state may be modified. To validate these findings, well-designed, large-scale, randomized and controlled studies on homogeneous patient populations are expected.

Effectiveness of COVID-19 vaccines against SARS-CoV-2 variants of concern in real-world: a literature review and meta-analysis.

Knowing vaccine effectiveness (VE) against variants of concern (VOCs) in the real-world setting is essential for public health decision-making. A systematic landscape of the VE against a series of clinical outcomes caused by the VOCs in the real-world setting is needed. We systematically searched for studies that evaluated VE against VOCs in the real-world setting and collected individual data. We identified 113 studies meeting the eligibility criteria. We found full vaccination provided strong protection against each clinical outcome with summary VE ranging from 86.8% to 96.0% Alpha, moderate protection against infection caused by Beta, Gamma and Delta with summary VE ranging from 70.9% to 72.8%, strong protection against severe disease caused by Delta with summary VE ranging from 84.9% to 90.3%, limited protection with summary VE of 23.5% (95% CI, 17.0-29.5) against infection and moderate protection with summary VE ranging from 56.5% to 82.4% against severe diseases caused by Omicron. Booster vaccination can provide a substantial improvement in protection against Delta and Omicron, but not as much as the Delta. The meta-regression analysis showed that the VE against the Omicron wanned over time, and the VE against hospitalization declined relatively slowly, compared to against infection. Those findings supported the need for public health measures, increasing booster vaccination coverage in response to current and new infectious waves driven by variants and developing broadly protective vaccines to confront virus evolution.