Influence of donor age on liver transplantation outcomes: A multivariate analysis and comparative study.

BACKGROUND: The growing disparity between the rising demand for liver transplantation (LT) and the limited availability of donor organs has prompted a greater reliance on older liver grafts. Traditionally, utilizing livers from elderly donors has been associated with outcomes inferior to those achieved with grafts from younger donors. By accounting for additional risk factors, we hypothesize that the utilization of older liver grafts has a relatively minor impact on both patient survival and graft viability. AIM: To evaluate the impact of donor age on LT outcomes using multivariate analysis and comparing young and elderly donor groups. METHODS: In the period from April 2013 to December 2018, 656 adult liver transplants were performed at the University Hospital Merkur. Several multivariate Cox proportional hazards models were developed to independently assess the significance of donor age. Donor age was treated as a continuous variable. The approach involved univariate and multivariate analysis, including variable selection and assessment of interactions and transformations. Additionally, to exemplify the similarity of using young and old donor liver grafts, the group of 87 recipients of elderly donor liver grafts (≥ 75 years) was compared to a group of 124 recipients of young liver grafts (≤ 45 years) from the dataset. Survival rates of the two groups were estimated using the Kaplan-Meier method and the log-rank test was used to test the differences between groups. RESULTS: Using multivariate Cox analysis, we found no statistical significance in the role of donor age within the constructed models. Even when retained during the entire model development, the donor age's impact on survival remained insignificant and transformations and interactions yielded no substantial effects on survival. Consistent insignificance and low coefficient values suggest that donor age does not impact patient survival in our dataset. Notably, there was no statistical evidence that the five developed models did not adhere to the proportional hazards assumption. When comparing donor age groups, transplantation using elderly grafts showed similar early graft function, similar graft (P = 0.92), and patient survival rates (P = 0.86), and no significant difference in the incidence of postoperative complications. CONCLUSION: Our center's experience indicates that donor age does not play a significant role in patient survival, with elderly livers performing comparably to younger grafts when accounting for other risk factors.

Use of machine learning models for identification of predictors of survival and tumour recurrence in liver transplant recipients with hepatocellular carcinoma.

Background: Hepatocellular carcinoma (HCC) is one of the leading indications for liver transplantation (LT) however, selection criteria remain controversial. We aimed to identify survival factors and predictors for tumour recurrence using machine learning (ML) methods. We also compared ML models to the Cox regression model. Methods: Thirty pretransplant donor and recipient general and tumour specific parameters were analysed from 170 patients who underwent orthotopic liver transplantation for HCC between March 2013 and December 2019 at the University Hospital Merkur, Zagreb. Survival rates were calculated using the Kaplan-Meier method and multivariate analysis was performed using the Cox proportional hazards regression model. Data was also processed through Coxnet (a regularized Cox regression model), Random Survival Forest (RSF), Survival Support Vector Machine (SVM) and Survival Gradient Boosting models, which included pre-processing, variable selection, imputation of missing data, training and cross-validation of the models. The cross-validated concordance index (CI) was used as an evaluation metric and to determine the best performing model. Results: Kaplan-Meier curves for 5-year survival time showed survival probability of 80% for recipient survival and 82% for graft survival. The 5-year HCC recurrence was observed in 19% of patients. The best predictive accuracy was observed in the RSF model with CI of 0.72, followed by the Survival SVM model (CI 0.70). Overall ML models outperform the Cox regression model with respect to their limitations. Random Forest analysis provided several relevant outcome predictors: alpha fetoprotein (AFP), donor C-reactive protein (CRP), recipient age and neutrophil to lymphocyte ratio (NLR). Cox multivariate analysis showed similarities with RSF models in identifying detrimental variables. Some variables such as donor age and number of transarterial chemoembolization treatments (TACE) were pointed out, but these were not influential in our RSF model. Conclusions: Using ML methods in addition to classical statistical analysis, it is possible to develop sufficient prognostic models, which, compared to established risk scores, could help us quantify survival probability and make changes in organ utilization.

Constrictive pericarditis as a cause of refractory ascites after liver transplantation: A case report.

BACKGROUND: Refractory ascites is a rare complication following orthotopic liver transplantation (OLT). The broad spectrum of differential diagnosis often leads to delay in diagnosis. Therapy depends on recognition and treatment of the underlying cause. Constrictive pericarditis is a condition characterized by clinical signs of right-sided heart failure. In the advanced stages of the disease, hepatic congestion leads to formation of ascites. In patients after OLT, cardiac etiology of ascites is easily overlooked and it requires a high degree of clinical suspicion. CASE SUMMARY: We report a case of a 55-year-old man who presented with a refractory ascites three months after liver transplantation for alcoholic cirrhosis. Prior to transplantation the patient had a minimal amount of ascites. The transplant procedure and the early postoperative course were uneventful. Standard post-transplant work up failed to reveal any typical cause of refractory post-transplant ascites. The function of the graft was good. Apart from atrial fibrillation, cardiac status was normal. Eighteen months post transplantation the patient developed dyspnea and severe fatigue with peripheral edema. Ascites was still prominent. The presenting signs of right-sided heart failure were highly suggestive of cardiac etiology. Diagnostic paracentesis was suggestive of cardiac ascites, and further cardiac evaluation showed typical signs of constrictive pericarditis. Pericardiectomy was performed followed by complete resolution of ascites. On the follow-up the patient remained symptom-free with no signs of recurrent ascites and with normal function of the liver graft. CONCLUSION: Refractory ascites following liver transplantation is a rare complication with many possible causes. Broad differential diagnosis needs to be considered.

[Adrenal myelolipoma--report of 15 patients]. / Mijelolipomi nadbubrezne zlijezde--prikaz serije od 15 bolesnika.

Myelolipoma is a rare, benign, non-functioning tumor most frequently located in the adrenal cortex. It consists of mature fatty tissue with components of hematopoietic tissue in different proportions. There are certain ambiguities related to the diagnosis and therapy of myelolipoma, and it is therefore important to keep in view all the aspects of the lesion and the circumstances in which it develops. This paper presents a series of 15 patients with myelolipoma diagnosed at the Ljudevit Jurak Department of Pathology, Sestre milosrdnice University Hospital Center. Out of 15 patients, 10 were men (one of them with bilateral tumor) aged 41 to 73, and 5 were women aged 51 to 54. Macroscopically, the tumors were oval, encapsulated, yellowish, soft masses located in the adrenal glands. The diameter of the tumors ranged between 0.5 and 13.9 cm. Microscopically, they consisted of multiplied mature adipose cells combined with myeloid tissue composed largely of megakaryocytes, erythroid cells and lymphocytes. In all patients, the postoperative course was uneventful with no recurrences.

Extraction of Lutein Diesters from Tagetes Erecta using Supercritical CO2 and Liquid Propane.

The efficiency of high pressure extraction of lutein diesters from marigold (Tagetes erecta) flower petals has been investigated. The solvents used for extraction were supercritical carbon dioxide and liquid propane. Operating parameters were 300 bar and 40, 60 and 80 °C for CO2 and 100, 150, 200 bar and 40 and 60 °C for propane, respectively. The influence of process parameters on the total yield of extraction and content of lutein diesters in the extracts was investigated. The results show, that solvent power of propane for lutein diesters is approximately 3.5 times higher than of CO2. The calculation procedure based on the Fick's second law was applied to determine the diffusivities of lutein diesters during extraction from marigold flower petals for both extraction stages: a constant rate stage followed by a stage of decreasing rate. The mathematical model based on the Fick's second law well described the experimental extraction results.