Number of Local Regional Therapies for Hepatocellular Carcinoma and Peri-Operative Outcomes after Liver Transplantation.

The wait times for patients with hepatocellular carcinoma (HCC) listed for liver transplant are longer than ever, which has led to an increased reliance on the use of pre-operative LRTs. The impact that multiple rounds of LRTs have on peri-operative outcomes following transplant is unknown. This was a retrospective single center analysis of 298 consecutive patients with HCC who underwent liver transplant (January 2017 to May 2021). The data was obtained from two institution-specific databases and the TransQIP database. Of the 298 patients, 27 (9.1%) underwent no LRTs, 156 (52.4%) underwent 1-2 LRTs, and 115 (38.6%) underwent ≥3 LRTs prior to LT. The patients with ≥3 LRTs had a significantly higher rate of bile leak compared to patients who received 1-2 LRTs (7.0 vs. 1.3%, p = 0.014). Unadjusted and adjusted regression analyses demonstrated a significant association between the total number of LRTs administered and bile leak, but not rates of overall biliary complications. The total number of LRTs was not significantly associated with any other peri-operative or post-operative outcome measure. These findings support the aggressive use of LRTs to control HCC in patients awaiting liver transplant, with further evaluation needed to confirm the biliary leak findings

Serum from patients with cirrhosis undergoing liver transplantation induces permeability in human pulmonary microvascular endothelial cells ex vivo

IntroductionPatients with cirrhosis undergoing liver transplantation frequently exhibit systemic inflammation, coagulation derangements, and edema, indicating endothelial dysfunction. This syndrome may worsen after ischemia-reperfusion injury of the liver graft, coincident with organ dysfunction that worsens patient outcomes. Little is known about changes in endothelial permeability during liver transplantation. We hypothesized that sera from these patients would increase permeability in cultured human endothelial cells ex vivo.MethodsAdults with cirrhosis presenting for liver transplantation provided consent for blood collection during surgery. Sera were prepared at five time points spanning the entire operation. The barrier function of human pulmonary microvascular endothelial cells in culture was assessed by transendothelial resistance measured using the ECIS ZΘ system. Confluent cells from two different endothelial cell donors were stimulated with human serum from liver transplant patients. Pooled serum from healthy men and purified inflammatory agonists served as controls. The permeability response to serum was quantified as the area under the normalized resistance curve. Responses were compared between time points and analyzed for associations with clinical characteristics of liver transplant patients and their grafts.ResultsLiver transplant sera from all time points during surgery-induced permeability in both endothelial cell lines. The magnitude of permeability change was heterogeneous between patients, and there were differences in the effects of sera on the two endothelial cell lines. In one of the cell lines, the severity of liver disease was associated with greater permeability at the start of surgery. In the same cell line, serum collected 15 min after liver reperfusion induced significantly more permeability as compared to that collected at the start of surgery. Early postreperfusion sera from patients undergoing living donor transplants induced more permeability than sera from deceased donor transplants. Sera from two exemplary cases of patients on preoperative dialysis, and one patient with an unexpectedly long warm ischemia time of the liver graft, induced exaggerated and prolonged endothelial permeability.DiscussionSerum from patients with cirrhosis undergoing liver transplantation induces permeability of cultured human pulmonary microvascular endothelial cells. Increased endothelial permeability during liver transplantation may contribute to organ injury and present a target for future therapeutics

Serum From Patients With Cirrhosis Undergoing Liver Transplantation Induces Permeability in Human Pulmonary Microvascular Endothelial Cells

INTRODUCTION: Patients with cirrhosis undergoing liver transplantation frequently exhibit systemic inflammation, coagulation derangements, and edema, indicating endothelial dysfunction. This syndrome may worsen after ischemia-reperfusion injury of the liver graft, coincident with organ dysfunction that worsens patient outcomes. Little is known about changes in endothelial permeability during liver transplantation. We hypothesized that sera from these patients would increase permeability in cultured human endothelial cells METHODS: Adults with cirrhosis presenting for liver transplantation provided consent for blood collection during surgery. Sera were prepared at five time points spanning the entire operation. The barrier function of human pulmonary microvascular endothelial cells in culture was assessed by transendothelial resistance measured using the ECIS ZΘ system. Confluent cells from two different endothelial cell donors were stimulated with human serum from liver transplant patients. Pooled serum from healthy men and purified inflammatory agonists served as controls. The permeability response to serum was quantified as the area under the normalized resistance curve. Responses were compared between time points and analyzed for associations with clinical characteristics of liver transplant patients and their grafts. RESULTS: Liver transplant sera from all time points during surgery-induced permeability in both endothelial cell lines. The magnitude of permeability change was heterogeneous between patients, and there were differences in the effects of sera on the two endothelial cell lines. In one of the cell lines, the severity of liver disease was associated with greater permeability at the start of surgery. In the same cell line, serum collected 15 min after liver reperfusion induced significantly more permeability as compared to that collected at the start of surgery. Early postreperfusion sera from patients undergoing living donor transplants induced more permeability than sera from deceased donor transplants. Sera from two exemplary cases of patients on preoperative dialysis, and one patient with an unexpectedly long warm ischemia time of the liver graft, induced exaggerated and prolonged endothelial permeability. DISCUSSION: Serum from patients with cirrhosis undergoing liver transplantation induces permeability of cultured human pulmonary microvascular endothelial cells. Increased endothelial permeability during liver transplantation may contribute to organ injury and present a target for future therapeutics

Gender and Racial Disparity Among Liver Transplantation Professionals: Report of a Global Survey.

Equality, diversity, and inclusion (EDI) are fundamental principles. Little is known about the pattern of practice and perceptions of EDI among liver transplant (LT) providers. International Liver Transplant Society (ILTS) EDI Committee survey around topics related to discrimination, mentorship, and gender. Answers were collected and analyzed anonymously. Worldwide female leadership was also queried via publicly available data. The survey was e-mailed to 1312 ILTS members, 199 responses (40.7% female) were collected from 38 countries (15.2% response rate). Almost half were surgeons (45.7%), 27.6% hepatologists and 26.6% anesthetists. Among 856 LT programs worldwide, 8.2% of leadership positions were held by females, and 22% of division chiefs were female across all specialties. Sixty-eight of respondents (34.7%) reported some form of discrimination during training or at their current position, presumably related to gender/sexual orientation (20.6%), race/country of origin (25.2%) and others (7.1%). Less than half (43.7%) received mentorship when discrimination occurred. An association between female responses and discrimination, differences in compensation, and job promotion was observed. This survey reveals alarmingly high rate of experience with racial and gender disparity, lack of mentorship, and very low rates of female leadership in the LT field and calls to action to equity and inclusion

Addressing the Burden and Management Strategies for Disparities and Inequities Among Liver Transplant Professionals: The ILTS Experience.

Medical professional environments are becoming increasingly multicultural, international, and diverse in terms of its specialists. Many transplant professionals face challenges related to gender, sexual orientation or racial background in their work environment or experience inequities involving access to leadership positions, professional promotion, and compensation. These circumstances not infrequently become a major source of work-related stress and burnout for these disadvantaged, under-represented transplant professionals. In this review, we aim to 1) discuss the current perceptions regarding disparities among liver transplant providers 2) outline the burden and impact of disparities and inequities in the liver transplant workforce 3) propose potential solutions and role of professional societies to mitigate inequities and maximize inclusion within the transplant community

Angiotensin II in liver transplantation (AngLT-1): protocol of a randomised, double-blind, placebo-controlled trial.

INTRODUCTION: Catecholamine vasopressors such as norepinephrine are the standard drugs used to maintain mean arterial pressure during liver transplantation. At high doses, catecholamines may impair organ perfusion. Angiotensin II is a peptide vasoconstrictor that may improve renal perfusion pressure and glomerular filtration rate, a haemodynamic profile that could reduce acute kidney injury. Angiotensin II is approved for vasodilatory shock but has not been rigorously evaluated for treatment of hypotension during liver transplantation. The objective is to assess the efficacy of angiotensin II as a second-line vasopressor infusion during liver transplantation. This trial will establish the efficacy of angiotensin II in decreasing the dose of norepinephrine to maintain adequate blood pressure. Completion of this study will allow design of a follow-up, multicentre trial powered to detect a reduction of organ injury in liver transplantation. METHODS AND ANALYSIS: This is a double-blind, randomised clinical trial. Eligible subjects are adults with a Model for End-Stage Liver Disease Sodium Score ≥25 undergoing deceased donor liver transplantation. Subjects are randomised 1:1 to receive angiotensin II or saline placebo as the second-line vasopressor infusion. The study drug infusion is initiated on reaching a norepinephrine dose of 0.05 µg kg ETHICS AND DISSEMINATION: The trial protocol was approved by the local Institutional Review Board (#20-30948). Results will be posted on ClinicalTrials.gov and published in a peer-reviewed journal. TRIAL REGISTRATION NUMBER: ClinicalTrials.govNCT04901169

Perioperative coagulation test methods to identify patients at risk for peri- and postoperative bleeding complications

Perioperative Blutungskomplikationen können für den einzelnen Patienten / die einzelne Patientin schwerwiegende Folgen haben. Es ist daher notwendig, Patienten / Patientinnen mit erhöhtem Risiko für schwere Blutungen früh zu identifizieren, idealerweise bereits vor dem chirurgischen Eingriff. Die Therapie mit den direkten oralen Antikoagulantien Apixaban und Rivaroxaban kann ohne Messung der Wirkspiegel durchgeführt werden. In bestimmten Situationen, wie beim Auftreten von Blutungskomplikationen oder vor ungeplanten Eingriffen kann die Bestimmung der Wirkspiegel jedoch notwendig werden. Aktuell gibt es keine Methode zur patientennahen Bestimmung der Wirkspiegel von Apixaban und Rivaroxaban. Postoperative Blutungskomplikationen sind die häufigste Ursache für Morbidität und Mortalität nach neurochirurgischen Eingriffen.^ ^Niedrige Fibrinogen- und Faktor XIII- Spiegel sind mögliche Risikofaktoren für das Auftreten von Nachblutungen in der Neurochirurgie. Die Ziele dieser Dissertation waren (a), die Anwendbarkeit zweier modifizierter Thromboelastometrie-Verfahren zur Bestimmung des Effekts von Rivaroxaban und Apixaban zu prüfen, und (b), einen möglichen Zusammenhang zwischen perioperativen Fibrinogen- und Faktor XIII-Spiegel und Blutungskomplikationen nach elektiven neurochirurgischen Eingriffen zu finden. Um den Effekt von Apixaban und Rivaroxaban mittels Thromboelastometrie zu bestimmen, wurden Vollblutproben von 20 Probanden mit aufsteigenden Konzentrationen von Apixaban und Rivaroxaban versetzt.^ Zur Messung der Proben wurde ein spezieller, bisher nicht kommerziell erhältlicher ROTEM® Testansatz mit geringerer Tissue Factor Konzentration (lowTF) verwendet. Um die Assoziation zwischen perioperativen Fibrinogen- und Faktor XIII-Spiegel und dem Auftreten postoperativer Blutungen zu evaluieren wurden Fibrinogen- und Faktor XIII-Spiegel in 290 Patienten während elektiver intrakranieller Eingriffen gemessen. Die Spiegel wurden vor dem Hautschnitt sowie zum Zeitpunkt der Hautnaht bestimmt.^ Es besteht eine dosisabhängige Korrelation zwischen Apixaban und Rivaroxaban Plasmaspiegeln und den LowTF ROTEM® Parametern clotting time und time to maximum velocity. Patienten / Patientinnen mit postoperativer Nachblutung hatten signifikant niedrigere Fibrinogen-Spiegel zum Zeitpunkt der Hautnaht im Vergleich zu denen ohne Blutungskomplikationen. Die vorliegenden Daten weisen darauf hin, dass LowTF ROTEM® als initialer, patientennaher Screeningtest den Effekt von Apixaban und Rivaroxaban nachweisen kann und niedrige Fibrinogen-Spiegel nach neurochirugischen Eingriffen ein möglicher modifizierbarer Risikofaktor für postoperative Nachblutungen sind.Background: Bleeding complications during and after surgery can have detrimental consequences. Patients at risk for major bleeding must be identified early, ideally before they go into surgery. Routine drug monitoring is not required in patients treated with the direct oral anticoagulants apixaban and rivaroxaban. But certain clinical situations such as bleeding or if a patient needs to undergo emergency surgery can necessitate rapid testing for the residual effect of these anticoagulants. There is currently no point of care test to determine the effect of apixaban or rivaroxaban. Bleeding complications in patients undergoing neurosurgical procedures are among the most common causes of postoperative morbidity and mortality.^ ^Low levels of fibrinogen and factor XIII have been proposed as potential risk factors for postoperative bleeding. The aims of this thesis were 1) to evaluate the applicability of two modified rotational thromboelastometry assays to detect the effect of apixaban and rivaroxaban at the point of care and 2) to assess the association of perioperative levels of fibrinogen and factor XIII with postoperative bleeding complications in patients undergoing elective neurosurgical procedures. Methods: To detect the effect of apixaban and rivaroxaban using rotational thromboelastometry (ROTEM®), blood samples of 20 volunteers were spiked with increasing concentrations of apixaban and rivaroxaban. The ROTEM® test modifications LowTF ROTEM® and PiCT® - ROTEM® were used to determine effect of apixaban and rivaroxaban.^ To evaluate the association of perioperative fibrinogen and factor XIII levels on postoperative bleeding, fibrinogen and factor XIII levels were prospectively assessed in 290 patients undergoing elective craniotomies. Coagulation factors were determined prior to skin incision and at the time of skin closure. Results: There was a dose depended correlation between apixaban and rivaroxaban plasma levels and the LowTF ROTEM® test parameters clotting time and time to maximum velocity. Patients who developed postoperative hematoma after craniotomies had lower fibrinogen plasma concentrations at the time of skin closure compared to patients without bleeding complications. Conclusion: We propose two methods to identify patients with increased risk for perioperative bleeding: LowTF ROTEM® might be used as an initial screening tool to detect the effect of apixaban and rivaroxaban at the point of care.^ Low plasma fibrinogen levels in patients undergoing neurosurgery are a potentially modifiable risk factor for postoperative bleeding complications.submitted by Dieter AdelmannMedizinische Universität Wien, Diss., 201

Central venous pressure monitoring in living donor kidney recipients does not affect immediate graft function: A propensity score analysis

BACKGROUND:During kidney transplantation, intraoperative fluid management can affect post-transplant graft function. It is unclear whether or not central venous pressure (CVP) monitoring is required to guide fluid therapy during kidney transplantation. METHODS:We compared post-transplant graft function in recipients of living donor kidney transplants between August 2006 and March 2009 based on the use or absence of intraoperative CVP monitoring. Graft function, assessed using the creatinine reduction ratio on postoperative day 2 (CCR2), was evaluated by multivariable linear regression analysis and in a propensity-matched cohort. RESULTS:Two hundred and ninety patients were included in the analysis. Central venous pressure was monitored in 84 patients (29%). There was no difference in post-transplant graft function, as measured by CCR2, between patients with and without CVP monitoring in both unadjusted and multivariable-adjusted analyses. There were also no statistically significant differences in CCR2, delayed graft function, or 3-month renal function between those monitored with CVP and those without, in the propensity-matched cohort. CONCLUSIONS:In this single-center analysis, immediate post-transplant renal function was not associated with the use of intraoperative CVP monitoring