Long-term outcome following liver transplantation of patients with ACLF grade 3.

BACKGROUND AND AIMS: Utility, a major principle for allocation in the context of transplantation, is questioned in patients with acute-on chronic liver failure grade 3 (ACLF-3) who undergo liver transplantation (LT). We aimed to explore long-term outcomes of patients included the three-center retrospective French experience published in 2017. METHOD: All patients with ACLF-3 (n=73) as well as their transplanted matched controlled with ACLF-2 (n=145), 1 (n=119) and no ACLF (n=292) that have participated in the princeps study published in 2017 were included. We explored 5- and 10-year patient and graft survivals, causes of death and their predictive factors. RESULTS: Median follow-up of patients ACLF-3 patients was 7.5 years. At LT, median MELD was 40. In patients with ACLF-3, 2, 1 and no ACLF, 5-year patients' survivals were respectively 72.6% vs. 69.7% vs. 76.4% vs. 77.0% (p=0.31). Ten-year patients' survival ACLF-3 was 56.8% and was not different other groups (p=0.37) Leading causes of death in ACLF-3 patients were infections (33.3%), and cardiovascular events (23.3%). After exclusion of early death, UCLA futility risk score, age-adjusted Charlson comorbidity index and Chronic Liver Failure Consortium ACLF score were independently associated with 10-year patients' survival. Long-term grafts' survivals were not different across the groups. Clinical frailty scale and WHO performance status improved over time in patients alive after 5 years. CONCLUSION: 5- and 10-year patients' and grafts' survivals in ACLF-3 patients were not different from their controls. 5-year patients' survival is higher than that of the 50%-70% threshold defining the utility of liver graft. Efforts should focus on candidates' selection based on comorbidities as well as the prevention of infection and cardiovascular events standing as the main cause of death. IMPACT AND IMPLICATIONS: While short-term outcomes following liver transplantation in the most severely ill cirrhotic patients (ACLF-3) are known, long-term data are limited, raising questions about the utility of graft allocation in the context of scarce medical resources. This study provides a favorable long-term update, confirming no differences in 5- and 10-year patient and graft survival following liver transplantation in ACLF-3 patients compared to matched ACLF-2, ACLF-1, and no-ACLF patients. The study highlights the risk of dying from infection and cardiovascular causes in the long-term and identifies scores including comorbidities evaluation, such as the age-adjusted Charlson Comorbidity Index, as independently associated with long-term survival. Therefore, physicians should consider the cumulative burden of comorbidities when deciding to transplant these patients. Additionally, after transplantation, the study encourages mitigating infectious risk with tailored immunosuppressive regimens and managing tightly cardiovascular risk over time.

Sedation vs. general anesthesia in stone ureteroscopy: Comparison of efficacy and safety, a post COVID-19 report.

INTRODUCTION: Ureterorenoscopy (URS) for ureteral or renal stones is traditionally performed under general anesthesia (GA). Sedation is an alternative to GA, allowing control of the level of consciousness, spontaneous ventilation, and faster recovery. Our aim was to compare sedation and GA for patients undergoing ureterorenoscopy. Endpoints were stone-free rate (SFR) and complication rates. METHOD: Monocentric comparative retrospective study including all consecutive ureterorenoscopies for ureteral or renal stone. The inclusion period was dichotomized in two 6-months periods due to the COVID-19 pandemic: from January 1 to July 1, 2019 (URS under GA) and from January 1 to July 1, 2021 (URS under GA or sedation). Stone-free (SF) status was defined as the absence of stone or fragment>4mm after the first ureterorenoscopy. Complication rates were assessed according to the Satava (perioperative complications) and Clavien-Dindo (postoperative complications) classifications. Statistical analysis was performed by Chi-square test. RESULTS: A total of 185 patients were included for a total of 206 ureterorenoscopies; 82 underwent ureterorenoscopy under GA and 103 under sedation. The median stone size was 10 [7-16] mm. In all, 150 (81%) patients had at least one intrarenal stone. The SFR was similar between the two groups (67% GA group, 69% sedation group, P=0.912). In the sedation group, the mean SFR in ureter was 83.7% vs. 92.5% in the GA group. In renal cavities, the mean SFR was 46.4% in the sedation group vs. 42.5% in the GA group. Satava grade I, IIa, and IIb complications were 5 (6%), 5 (6%), and 1 (1%) in the GA group and 6 (6%), 1 (1%), and 3 (3%) in the sedation group, respectively (P=0.214). The grade I, II, III, and IV Clavien complications were 6 (7%), 3 (4%), 0 (0%), and 2 (2%) in the GA group and 6 (6%), 4 (4%), 1 (1%), and 4 (4%) in the sedation group, respectively (P=0.928). CONCLUSION: Our post COVID-19 study showed no difference in efficacy and safety between ureterorenoscopy under sedation and GA for patients with renal stones. Our results confirm the interest of the sedation procedure, particularly in the context of outpatient surgery.

Combination of a propofol emulsion with alpha-2 adrenergic receptor agonists used for multimodal analgesia or sedation in intensive care units: a physicochemical stability study.

OBJECTIVES: To assess the physicochemical stability of the combination of a propofol emulsion with an alpha-2 (α2) adrenergic receptor agonist (α2A; clonidine or dexmedetomidine) under conditions mimicking routine practice in an intensive care unit or in multimodal analgesia procedures. METHODS: We developed and validated three stability-indicating methods based on high-performance liquid chromatography with ultraviolet (HPLC-UV) detection. Eight different conditions per combination were evaluated in triplicate, with variations in the simulated, bodyweight-adjusted dose level and the drugs' flow rate. The drugs were mixed in clinically relevant concentrations and proportions and then stored unprotected from light, in clear glass vials at room temperature for 96 hours. At each sampling point, we assessed the chemical stability (the HPLC-UV drug level, pH, and osmolality) and physical compatibility (visual aspect, zeta potential (ZP), mean droplet diameter (MDD, Z-average) and polydispersity index (PDI)). We validated our stability findings in positive and negative control experiments. RESULTS: Over the 96-hour test, the concentrations of propofol, clonidine and dexmedetomidine did not fall below 90% of the initial value, and the pH and osmolality were stable. The visual aspect of the mixed propofol emulsions did not change. The MDD remained below 500 nm (range 165-195 nm). The PDI was always below 0.4; 78.7% of the measurements were below 0.1 and 21.3% were between 0.1 and 0.4. The ZP measurements (-31.3 to -42.9 mV) suggested that the emulsion was stable. The MDD and PDI increased slightly at 96 hours under some conditions, which might indicate early destabilisation of the emulsion. Given that the MDD remained below 500 nm, these emulsions are compatible with intravenous administration. CONCLUSIONS: Our results demonstrate the chemical and physical compatibility of propofol-α2 agonist mixtures at concentrations and in proportions representative of standard protocols when stored unprotected from light at room temperature for 96 hours.