The triglyceride-glucose index: a novel predictor of stroke and all-cause mortality in liver transplantation recipients.

BACKGROUND: The triglyceride-glucose (TyG) index, identified as a reliable indicator of insulin resistance (IR), was reported to be associated with stroke recurrence and morbidity in the general population and critically ill patients. However, the relationship in liver transplantation (LT) recipients remains unknown. This study aimed to investigate the correlation between the TyG index and post-LT stroke along with all-cause mortality and further assess the influence of IR on the LT recipients' prognosis. METHODS: The retrospective cohort study enrolled 959 patients who underwent LT at a university-based medical centre between January 2015 and January 2021. The participants were divided into three groups according to their TyG index tertiles. The primary outcome was post-LT stroke. Multivariate logistic regression, COX proportional hazards regression, and restricted cubic spline RCS were used to examine the association between the TyG index and outcomes in LT recipients. RESULTS: With a median TyG index of 8.23 (7.78-8.72), 780 (87.18% males) patients were eventually included. The incidence of post-LT stroke was 5.38%, and the in-hospital, 1-year, and 3-year mortality rates were 5.54%, 13.21%, and 15.77%, respectively. Multivariate regression analysis showed an independent association between the TyG index and an increased risk of post-LT stroke [adjusted odds ratio (aOR), 3.398 (95% confidence interval [CI]: 1.371-8.426) P = 0. 008], in-hospital mortality [adjusted hazard ratio (aHR), 2.326 (95% CI: 1.089-4.931) P = 0.025], 1-year mortality [aHR, 1.668 (95% CI: 1.024-2.717) P = 0.039], and 3-year mortality [aHR, 1.837 (95% CI: 1.445-2.950) P = 0.012]. Additional RCS analysis also suggested a linear increase in the risk of postoperative stroke with elevated TyG index (P for nonlinearity = 0.480). CONCLUSIONS: The TyG index may be a valuable and reliable indicator for assessing stroke risk and all-cause mortality in patients undergoing LT, suggesting its potential relevance in improving risk stratification during the peri-LT period.

Quantitative Assessment of the in vivo Dissolution Rate to Establish a Modified IVIVC for Isosorbide Mononitrate Tablets.

A modified in vitro-in vivo correlation (IVIVC) of the oral solid dosage forms has been proposed as a linear correlation between in vitro and in vivo dissolution. Nevertheless, the analysis of in vivo dissolution is limited by the lack of available methods. In this proof-of-concept study, a novel pharmacokinetic (PK) model containing the in vivo dissolution process and its quantification was presented to directly estimate the in vivo dissolution rate constant (kd). The new model was validated with a hypothetical oral solution (kd â†’ +∞). The accuracy of the new method was clarified by comparing with the relatively true value of kd from the literature. Isosorbide mononitrate (ISMN) was used as a model drug to explore the practicability of the novel method. The dissolution capacities of ISMN reference and test tablets were discriminated by an improved in vitro dissolution method. Following the human PK studies, the kd values and corresponding in vivo dissolution profiles of two formulations were obtained using the novel method. Finally, a modified level A IVIVC between in vitro and in vivo dissolution of ISMN tablets was established, which is expected to guide the optimization of the tablet formulation containing ISMN.

Investigating a Modified Apparatus to Discriminate the Dissolution Capacity In Vitro and Establish an IVIVC of Mycophenolate Mofetil Tablets in the Fed State.

In this study, a modified dissolution apparatus was developed by equipping a USP apparatus Ⅰ with an open-loop system to discriminate the dissolution capacity in vitro and establish an in vitro and in vivo correlation (IVIVC) for mycophenolate mofetil (MMF) tablets. MMF had strong pH-dependent solubility that could influence the dissolution rate in vivo after the meal. Dissolution tests involving reference (Cellcept®) and test formulations (F1 and F2) were conducted using pH 4.5 acetate buffer to simulate gastric fluids in the fed state. The dissolution profiles of the reference and test formulations were distinguished by using the modified dissolution apparatus and compared with those determined using the USP apparatuses Ⅱ and Ⅳ, and the dissolution capacities of the formulations were discriminated at different sampling time-points. The results of human bioequivalence (BE) studies in the fed state were consistent with in vitro evaluations that the maximum concentrations (Cmax,in vivo) of both F1 and F2 fell below the acceptable range (80.00%). A level A IVIVC between the absorption fraction in vivo and dissolution in vitro, and a level C correlation between Cmax,in vivo and Cmax,in vitro, were established to guide the optimization of the tablet formulation containing MMF.