Prognostic Value of Mitral Annular Calcification in Liver Transplant Patients: Implication in Posttransplant Outcomes.

BACKGROUND: With the rise of metabolic diseases and aging in liver transplant (LT) candidates, mitral annular calcification (MAC) is more recognizable. Despite cardiovascular risk becoming a leading cause of mortality in LT recipients, the influence of MAC remains unexamined. This study investigates the prevalence, related factors, and impact of MAC on LT outcomes. METHODS: We explored 4148 consecutive LT patients who underwent routine pretransplant echocardiography from 2008 to 2019. Multivariate logistic analysis and the tree-based Shapley additive explanation scores in machine learning were used to evaluate the significant and important related factors. The primary outcome was 30-d major adverse cardiac events (MACE), and the secondary outcome was a median of 5-y cumulative all-cause mortality. RESULTS: MAC was found in 123 (3.0%) patients. Significant and important related factors included age, alcoholic liver disease, chronic kidney disease, hyperuricemia, hypertension, and coronary artery disease. The MACE rate was higher in patients with MAC compared with those without MAC at 30 d (P < 0.001, adjusted hazard ratio 1.67; 95% confidence interval, 1.08-2.57). Patients with MAC had poorer cumulative overall survival probability compared with those without MAC (P = 0.0016; adjusted hazard ratio 1.47; 95% confidence interval, 1.01-2.15). Specifically, women with MAC had a poorer survival probability compared with men without MAC (65.0% versus 80.7%, P < 0.001) >10 y post-LT. CONCLUSIONS: The presence of MAC before LT was linked to increased 30-d MACE and lower long-term survival rates, especially in women. Identification and management of MAC and potential risk factors are crucial for improving post-LT survival.

Effect of dexmedetomidine on the incidence of postoperative acute kidney injury in living donor liver transplantation recipients: A randomized controlled trial.

BACKGROUND: Acute kidney injury (AKI) is one of the most common complications after living-donor liver transplantation (LDLT) that has great impact on recipient and graft outcomes. Dexmedetomidine is reported to decrease the incidence of AKI. In the current study, we investigated whether intraoperative dexmedetomidine infusion would reduce the AKI following LDLT. MATERIAL AND METHODS: In total, 205 adult patients undergoing elective LDLT were randomly assigned to the dexmedetomidine group (n=103) or the control group (n=102). Dexmedetomidine group received continuous dexmedetomidine infusion at a rate of 0.4 mcgÖ¼/kg/hr after the anesthesia induction until 2 hours after graft reperfusion. The primary outcome was to compare the incidence of AKI. Secondary outcomes included serial lactate levels during surgery, chronic kidney disease, major adverse cardiovascular events, early allograft dysfunction, graft failure, overall mortality, duration of mechanical ventilation, ICU and hospital length of stay. Intraoperative hemodynamic parameters were also collected. RESULTS: Of 205 recipients, 42.4% (n=87) developed AKI. The incidence of AKI was lower in the dexmedetomidine group (35.0%, n=36/103) compared with the control (50.0%, n=51/102) ( P =0.042). There were significantly lower lactate levels in the dexmedetomidine group after reperfusion (4.39 [3.99-4.8] vs 5.02 [4.62-5.42], P =0.031) until the end of surgery (4.23 [3.73-4.73] vs 5.35 [4.84-5.85], P =0.002). There were no significant differences in the other secondary outcomes besides lactate. Also, intraoperative mean blood pressure, cardiac output, and systemic vascular resistance did not show any difference. CONCLUSION: Our study suggests that intraoperative dexmedetomidine administration was associated with significantly decreased AKI incidence and lower intraoperative serum lactate levels in LDLT recipients, without untoward hemodynamic effects.

Impact of preoperative nonselective beta-blocker use on acute kidney injury after living donor liver transplantation: Propensity score analysis.

INTRODUCTION AND OBJECTIVES: Acute kidney injury (AKI) is prevalent and has deleterious effects on postoperative outcomes following liver transplantation (LT). The impact of nonselective beta-blockers (NSBBs) in patients with liver cirrhosis remains controversial. This study investigated the association between preoperative NSBB use and AKI after living donor LT (LDLT). PATIENTS AND METHODS: We evaluated 2,972 adult LDLT recipients between January 2012 and July 2022. The patients were divided into two groups based on the preoperative NSBB use. Propensity score matched (PSM) and inverse probability of treatment weighting (IPTW) analyses were performed to evaluate the association between preoperative NSBB use and postoperative AKI. Multiple logistic regression analyses were also used to identify the risk factors for AKI. RESULTS: The overall incidence of AKI was 1,721 (57.9%) cases. The NSBB group showed a higher incidence of AKI than the non-NSBB group (62.4% vs. 56.7%; P = 0.011). After PSM and IPTW analyses, no significant difference in the incidence of AKI was found between the two groups (Odds ratio, OR 1.13, 95% confidence interval, CI 0.93-1.37, P = 0.230, PSM analysis; OR 1.20, 95% CI 0.99-1.44, P = 0.059, IPTW analysis). In addition, preoperative NSBB use was not associated with AKI after multivariate logistic regression analysis (OR 1.16, 95% CI 0.96-1.40, P = 0.118). CONCLUSIONS: Preoperative NSBB use was not associated with AKI after LDLT. Further studies are needed to validate our results.

Liver transplantation using grafts of living donors with isolated unconjugated hyperbilirubinemia: a matched case-control study.

Unconjugated bilirubin has shown both cytotoxic and cytoprotective effects, acting as either an oxidant or an antioxidant. Elevated unconjugated bilirubin with otherwise normal, so-called isolated unconjugated hyperbilirubinemia (IUHB), is encountered frequently in living liver donor evaluation. However, the significance of IUHB on transplantation-related outcomes has not been clarified in donors and recipients. Forty-six living donors with IUHB were matched 1:1 with the control donors and 43 recipients who received grafts from donors with IUHB were matched 1:1 with the control recipients. Matched variables included donor/recipient age, residual liver volume, steatosis, cold ischemic time, graft versus recipient weight ratio, the MELD score and others. Donors in the control and IUHB group were comparable regarding the maximum postoperative transaminase concentrations, postoperative complications, and hospital stay. Recipients in the control and IUHB group were comparable regarding primary graft dysfunction, major postoperative complications, long-term ICU/hospital stay, 1-year mortality, and rejection rate, as well as recipient/graft survival rates. Recipients' unconjugated bilirubin concentration at 3 years after transplantation was higher in IUHB group with otherwise comparable liver function. It was concluded that living donor liver transplantation is safe for donors with IUHB and their recipients.

Lipase and protease double-deletion mutant of Pseudomonas fluorescens suitable for extracellular protein production.

Pseudomonas fluorescens, a widespread Gram-negative bacterium, is an ideal protein manufacturing factory (PMF) because of its safety, robust growth, and high protein production. P. fluorescens possesses a type I secretion system (T1SS), which mediates secretion of a thermostable lipase (TliA) and a protease (PrtA) through its ATP-binding cassette (ABC) transporter. Recombinant proteins in P. fluorescens are attached to the C-terminal signal region of TliA for transport as fusion proteins to the extracellular medium. However, intrinsic TliA from the P. fluorescens genome interferes with detection of the recombinant protein and the secreted recombinant protein is hydrolyzed, due to intrinsic PrtA, resulting in decreased efficiency of the PMF. In this research, the lipase and protease genes of P. fluorescens SIK W1 were deleted using the targeted gene knockout method. Deletion mutant P. fluorescens ΔtliA ΔprtA secreted fusion proteins without TliA or protein degradation. Using wild-type P. fluorescens as an expression host, degradation of the recombinant protein varied depending on the type of culture media and aeration; however, degradation did not occur with the P. fluorescens ΔtliA ΔprtA double mutant irrespective of growth conditions. By homologous expression of tliA and the ABC transporter in a plasmid, TliA secreted from P. fluorescens ΔprtA and P. fluorescens ΔtliA ΔprtA cells was found to be intact, whereas that secreted from the wild-type P. fluorescens and P. fluorescens ΔtliA cells was found to be hydrolyzed. Our results demonstrate that the P. fluorescens ΔtliA ΔprtA deletion mutant is a promising T1SS-mediated PMF that enhances production and detection of recombinant proteins in extracellular media.