Liver transplantation for acute-on-chronic liver failure.

Acute-on-chronic liver failure (AoCLF) represents a newly defined entity in patients with liver disease leading to multiple organ failures and increased mortality. To date, no universally accepted definition exists, and different academic societies developed guidelines on the early diagnosis and classification of AoCLF. Recently published trials focused on factors associated with a poor outcome and on the development of severity scores aimed to identify patients who may benefit for advanced monitoring and treatment. No specific therapies are demonstrated to improve survival, and liver transplantation (LT) remains the only treatment associated with improved outcome. Our review focuses on current evidence for early diagnosis and prognostication of disease in patients with AoCLF, as well of criteria for intensive care unit admission, indication, and futility markers of LT, as well as bridging therapy and optimal timing of surgery

Nonischemic Cardiomyopathy in Liver Transplant Recipients

Nonischemic cardiomyopathy is a collective term, encompassing a spectrum of cardiac comorbidities, accompanying the progressing end-stage liver disease. Alcoholic and cirrhotic cardiomyopathies are the most researched, well-known clinical entities in the list of nonischemic cardiac disorders that bear the most substantial impact on the clinical course, management, and outcomes of liver transplantation in ESLD patients. In this chapter, morphology, pathophysiology, diagnostic criteria, clinical manifestations, and management options of nonischemic cardiomyopathy in liver transplant candidates and recipients, the patients with end-stage liver disease due to advanced stages of cirrhosis, are discussed

Hemodynamic Optimization Strategies in Anesthesia Care for Liver Transplantation

In this chapter, aspects of hemodynamic regulation in the end-stage liver disease (ESLD) patient, factors, contributing to the hemodynamic profile, coagulation-related problems, blood products transfusion tactics and problems, and hemodynamic optimization strategies during different stages of liver transplantation procedure—specifically what, when, and how to correct, with special attention to vasoactive agents use, will be discussed

Best therapeutic practices in the management of obstetric sepsis

Background. Physiological changes that occur during pregnancy make maternal sepsis a difficult condition to diagnose and treat, still having a fairly high mortality rate. Consequently, an early diagnosis and prompt therapeutic management of sepsis can significantly decrease mortality. The purpose of this study is to review literature data that present current practices in the management of obstetric sepsis. Methods. To collect the data required for the study, we performed a search of published articles in the PubMed and Google Scholar databases related to obstetric sepsis. Research paper articles from the period 2012-2022 were included in the analysis. In addition, 145 articles from the period 2012-2022 were evaluated, with the aim of finding out in which situations the risk of maternal death is higher. Thus, the analysis included a total number of 151 articles, which were divided into two distinct stages. Results. The risk of maternal death is higher among patients with the human immunodeficiency virus (HIV), followed by Escherichia coli, genital tract infection, cancer, drug users and in the case of patients with chronic liver disease. Conclusions. After analyzing the data, we found that prompt and focused antibiotic therapy as well as fluid resuscitation are essential to increase the chances of survival of these patients

Challenging Issues in Hepatic Adenoma

Hepatic adenoma is known as a benign lesion encountered mainly in female patients and classically linked to the administration of oral contraceptives. In the last decade, the risk factors for its occurrence have changed and so did the sex ratio. The histopathological classification of hepatic adenomas was found to be related with certain genetic mutations that determine the risk for malignancy. The diagnosis of hepatic tumor is correlated with clinical and imaging data in an effort not only to rule out other tumors but also to distinguish the subtype of adenoma, which is very important for the management of the patient. The ultimate diagnosis is established by pathologists by routine histopathological and specific immunohistochemical staining. There are two major issues that pathologists need to recognize: the presence of β-catenin gene mutation and/or malignant degeneration. The best imaging examination is considered to be MRI. However, along with MRI, ultrasound and computer tomography have proved themselves to be effective not only in evaluating the number, size, localization, and complications of hepatic adenomas, but also in identifying their subtype. A detailed presentation of characteristics of all groups of hepatic adenoma is provided. The means of management of hepatic adenomas are documented and decisional algorithm is explained, based on certain criteria

Obesity is associated with decreased lung compliance and hypercapnia during robotic assisted surgery

Robotic assisted surgery (RAS) represents a great challenge for anesthesiology due to the increased intraabdomial pressures required for surgical optimal approach. The changes in lung physiology are difficult to predict and require fast decision making in order to prevent altered gas exchange. The aim of this study was to document the combined effect of patient physical status, medical history and intraoperative position during RAS on lung physiology and to determine perioperative risk factors for hypercapnia. We prospectively analyzed 62 patients who underwent elective RAS. Age, co-morbidities and body mass index (BMI) were recorded before surgery. Ventilatory parameters and arterial blood gas analysis were determined before induction of anesthesia, after tracheal intubation and on an hourly basis until the end of surgery. In RAS, the induction of pneumoperitoneum was associated with a significant decrease in lung compliance from a mean of 42.5–26.7 ml cm H(2)O(−1) (p = 0.001) and an increase in plateau pressure from a mean of 16.1 mmHg to a mean of 23.6 mmHg (p = 0.001). Obesity, demonstrated by a BMI over 30, significantly correlates with a decrease in lung compliance after induction of anesthesia (p = 0.001). A significant higher increase in arterial CO(2) tension was registered in patients undergoing RAS in steep Trendelenburg position (p = 0.05), but no significant changes in end-tidal CO(2) were recorded. A higher arterial to end-tidal CO(2) tension gradient was observed in patients with a BMI > 30 (p < 0.001). In conclusion, patients’ physical status, especially obesity, represents the main risk factor for decreased lung compliance during RAS and patient positioning in either Trendelenburg or steep Trendelenburg during surgery has limited effects on respiratory physiology

Medical and psychological management of patients with a history of surgical treatment for pancreatic diseases

Background. Pancreatic cancer, known for its high mortality rate and late diagnosis, remains a significant health concern. Surgery offers a potential therapeutic remedy, but it is only valid in the early stage of detection. Increasing risk factors and an aging population are expected to raise the incidence of pancreatic cancer, further challenging healthcare systems. Methods. The general objective of this study was to analyze doctors' experiences regarding the health status of patients with benign pancreatic pathology who underwent surgery and were admitted to CF2 Clinical Hospital in Bucharest. The research involved a specialized questionnaire addressing various aspects of patient health, including mobility, pain intensity, psycho-emotional state, and prognosis. The study also included a protocol evaluating patients based on criteria like symptomatology, treatment, and postoperative complications. Results. The findings show significant discrepancies between patients' perceptions and doctors' evaluations in quality-of-life domains, with some positive correlations. The statistical analysis, including reliability, alpha, mean, and standard deviation, underscores these differences. Respondents reported a relatively good perception of their overall health state, and a moderate perception of their level of social functioning. The correlation between patients' perceptions and medical evaluations of mental health was 0.423, indicating a moderate but not necessarily significant relationship. Conclusions. The study reveals that physicians recognize the multifaceted challenges faced by patients with surgically treated pancreatic diseases. It emphasizes the need for a comprehensive approach to patient care, addressing physical, emotional, and social aspects. The study also highlights the importance of early detection and the complexity of doctor-patient interactions in pancreatic cancer treatment

Hemoadsorption in ‘liver indication’: analysis of 109 patients’ data from the CytoSorb international registry

Background: Our aim is to report the results of the ‘liver indication’ subset of patients in the CytoSorb International Registry. Methods: Structured data were recorded. Treatment characteristics and changes from T1 (start of hemoadsorption) to T2 (termination) were evaluated with a special focus on bilirubin, C-reactive protein, procalcitonin, interleukin-6, platelet levels, SOFA scores, mortality, and subjective assessment by the attending physicians. Results: Until January 2021, from the total 1434 patients, 109 (age: 49.2 ± 17.1 years, 57.8% males) received treatment for hyperbilirubinemia. APACHE II-predicted mortality was 49.6 ± 26.8%. In the study, 91% of patients were alive at the termination of hemoadsorption and improvement was observed by the physicians in 75 cases. Overall, 65 (59.6%) patients died in the hospital, and 60 (55.0%) died in the ICU. Patients received a median of two treatments for a median of 43 h (interquartile range: 24–72 h) in total. Serum bilirubin levels reduced significantly to −4.6 (95% CI: −6.329 to −2.8) mg/dL. Thrombocytopenia was reported in four patients as an adverse event. Conclusions: We report the largest case series on hemoadsorption for ‘liver indication’ from the CytoSorb International Registry. The finding of significant bilirubin removal observed in our study could have substantial impact in designing and executing further studies on the effects of hemoadsorption in liver dysfunction, which are certainly warranted

Continuous renal replacement therapy in cytokine release syndrome following immunotherapy or cellular therapies?

To access publisher's full text version of this article, please click on the hyperlink in Additional Links field or click on the hyperlink at the top of the page marked DownloadRecently, an increasing number of novel drugs were approved in oncology and hematology. Nevertheless, pharmacology progress comes with a variety of side effects, of which cytokine release syndrome (CRS) is a potential complication of some immunotherapies that can lead to multiorgan failure if not diagnosed and treated accordingly. CRS generally occurs with therapies that lead to highly activated T cells, like chimeric antigen receptor T cells or in the case of bispecific T-cell engaging antibodies. This, in turn, leads to a proinflammatory state with subsequent organ damage. To better manage CRS there is a need for specific therapies or to repurpose strategies that are already known to be useful in similar situations. Current management strategies for CRS are represented by anticytokine directed therapies and corticosteroids. Based on its pathophysiology and the resemblance of CRS to sepsis and septic shock, as well as based on the principles of initiation of continuous renal replacement therapy (CRRT) in sepsis, we propose the rationale of using CRRT therapy as an adjunct treatment in CRS where all the other approaches have failed in controlling the clinically significant manifestations.School of Doctoral Studies - Iuliu Hatieganu University Romanian Government Ion Chiricuta Oncology Institute Cluj Napoca Iuliu Hatieganu University of Medicine and Pharmacy Cluj Napoca European Economic Spac

Randomized-controlled trial of the DIALIVE liver dialysis device vs. standard of care in patients with acute-on-chronic liver failure

BACKGROUND AND AIMS: Acute on chronic liver failure (ACLF) is characterized by severe systemic inflammation, multi-organ failure and high mortality rates. Its treatment is an urgent unmet need. DIALIVE is a novel liver dialysis device that aims to exchange d ysfunctional albumin and remove damage- and pathogen-associated molecular patterns. This first-in-man randomized, controlled clinical trial was performed with the primary aim of assessing its safety in ACLF patients with secondary aims to evaluate its clinical effects, device performance and effect on pathophysiologically-relevant biomarkers. METHODS: 32 alcoholic cirrhosis patients with ACLF were included. Patients were treated with DIALIVE for up to 5-days and end points were assessed at Day-10. Safety was assessed in all patients (n=32). The secondary aims were assessed in a pre-specified subgroup that had at least 3-treatment sessions with DIALIVE (n=30). RESULTS: There were no significant differences in 28-day mortality or occurrence of serious adverse events between the groups. Significant reduction in the severity of endotoxemia and improvement in albumin function was observed in DIALIVE group, which translated into a significant reduction in the CLIF-C (Chronic Liver Failure consortium) organ failure (p=0.018) and CLIF-C ACLF scores (p=0.042) at Day-10. Time to resolution of ACLF was significantly faster in DIALIVE group (p=0.036). Biomarkers of systemic inflammation such as IL-8 (p=0.006), cell death [cytokeratin-18: M30 (p=0.005) and M65 (p=0.029)], endothelial function [asymmetric dimethylarginine (p=0.002)] and, ligands for toll-like receptor 4 (p=0.030) and inflammasome (p=0.002) improved significantly in DIALIVE group. CONCLUSIONS: These data indicate that DIALIVE appears to be safe and impacts positively on prognostic scores and pathophysiologically relevant biomarkers in patients with ACLF. Larger, adequately powered studies are warranted to further confirm its safety and efficacy. LAY SUMMARY: This is the first-in-man clinical trial which tested DIALIVE, a novel liver dialysis device for the treatment of liver cirrhosis and acute on chronic liver failure, a condition associated with severe inflammation, organ failures and a high risk of death. The study met the primary end point confirming DIALIVE system to be safe. Additionally, it reduced inflammation with improved clinical parameters. It did not, however, reduce mortality in this small study and requires further larger clinical trials to re-confirm its safety and evaluate efficacy. CLINICAL TRIAL NUMBER: NCT03065699