Sviluppo di biomarkers per la determinazione e la valutazione prognostica della ripresa funzionale epatica post trapianto, nel fegato marginale e nel non heart beating donor

ABSTRACT Background One of the most crucial issues in liver transplantation is the gap between the increasing number of patients waiting for a transplant and the shortage of available grafts. This limitation has led many liver transplant units to include for surgery organs defined as “marginal” or “sub-optimal” due to hepatic steatosis or sourcing from non-heart-beating donors (NHBD). In turn, the marginality of these organ donors is proportional to a high incidence of liver dysfunction after transplantation due mainly to more severe ischemia-reperfusion injury events. The use of new methods of preservation of hepatic grafts like Machine Perfusion becomes necessary, especially for its ability to reduce the damage of ischaemia-reperfusion in hypothermia. This opens an interest towards the use of alternative methods in preserving hepatic graft as Machine Perfusion, able to reduce this type of insults and allow the dosage of biomarkers that can predict the extent of damage ischemia-reperfusion injury and the quality of functional recovery of the graft after transplantation. The great potential of this system in the context of organ preservation and the numerous studies in the literature led us to investigate this issue. Purpose The aim of our work was to carry out an experimental model of Machine Perfusion (MP) for the preservation of livers procured from non heart-beating donor, as a viable alternative to the traditional Cold storage (CS) at 4°C. A further aim of our project was to identify biomarkers that can be used as predictors of postoperative graft damage. Material and methods We used 10 Landrace pigs of about 20 kg to which we performed, 60 minutes after cardiac arrest, total hepatectomy, thus harvesting the liver. The animals were divided into two groups: in the first group (Group A) 5 livers was preserved for 6 hours in MP at 20° C. In the second group (Group B) 5 livers was stored for 6 hours in CS. In all study groups the period of preservation was followed by reperfusion in normothermic MP (37 °) with whole oxygenated blood previously collected from the donor animal for 2 hours to assess the response to reperfusion. During the experiment blood samples and histological specimens were collected. Results Graft preservation by Machin perfusion at 20°C is superior compared to the Cold Storage, both from biochemical (AST, ALT, LDH, lactate) and histological standpoint (necrosis and congestion). The dose of AST, ALT, LDH and lactate has proven be a reliable parameter for the assessment of organ damage and functional recovery of the graft liver. The dosage of cytokines such as IL1, IL6, TNF alpha showed no significance. Conclusion These experimental evidences highlight the effectiveness of a preservation with continuous perfusion at 20° C on a large animal model. Both from biochemical that histological standpoint, we have observed that Machine Perfusion in moderate hypothermia is beneficial in the preservation of the graft and offers the considerable advantage of being able to test, during perfusion, biomarkers that can predict hepatic graft recovery, before transplant, in order to reduce the incidence of post-transplant graft disfunction

Donor Simvastatin Treatment Is Safe and Might Improve Outcomes After Liver Transplantation: A Randomized Clinical Trial.

BACKGROUND The current curative approaches for ischemia/reperfusion injury on liver transplantation are still under debate for their safety and efficacy in patients with end-stage liver disease. We present the SIMVA statin donor treatment before Liver Transplants study. METHODS SIMVA statin donor treatment before Liver Transplants is a monocentric, double-blind, randomized, prospective tial aiming to compare the safety and efficacy of preoperative brain-dead donors' treatment with the intragastric administration of 80 mg of simvastatin on liver transplant recipient outcomes in a real-life setting. Primary aim was incidence of patient and graft survival at 90 and 180 d post-transplant; secondary end-points were severe complications. RESULTS The trial enrolled 58 adult patients (18-65 y old). The minimum follow-up was 6 mo. No patient or graft was lost at 90 or 180 d in the experimental group (n = 28), whereas patient/graft survival were 93.1% (P = 0.016) and 89.66% (P = 0.080) at 90 d and 86.21% (P = 0.041) and 86.2% (P = 0.041) at 180 d in the control group (n = 29). The percentage of patients with severe complications (Clavien-Dindo ≥IIIb) was higher in the control group, 55.2% versus 25.0% in the experimental group (P = 0.0307). The only significant difference in liver tests was a significantly higher gamma-glutamyl transferase and alkaline phosphatase at 15 d (P = 0.017), (P = 0.015) in the simvastatin group. CONCLUSIONS Donor simvastatin treatment is safe, and may significantly improve early graft and patient survival after liver transplantation, although further research is mandatory

Prevalence, associated factors and outcomes of pressure injuries in adult intensive care unit patients: the DecubICUs study

Funder: European Society of Intensive Care Medicine; doi: http://dx.doi.org/10.13039/501100013347Funder: Flemish Society for Critical Care NursesAbstract: Purpose: Intensive care unit (ICU) patients are particularly susceptible to developing pressure injuries. Epidemiologic data is however unavailable. We aimed to provide an international picture of the extent of pressure injuries and factors associated with ICU-acquired pressure injuries in adult ICU patients. Methods: International 1-day point-prevalence study; follow-up for outcome assessment until hospital discharge (maximum 12 weeks). Factors associated with ICU-acquired pressure injury and hospital mortality were assessed by generalised linear mixed-effects regression analysis. Results: Data from 13,254 patients in 1117 ICUs (90 countries) revealed 6747 pressure injuries; 3997 (59.2%) were ICU-acquired. Overall prevalence was 26.6% (95% confidence interval [CI] 25.9–27.3). ICU-acquired prevalence was 16.2% (95% CI 15.6–16.8). Sacrum (37%) and heels (19.5%) were most affected. Factors independently associated with ICU-acquired pressure injuries were older age, male sex, being underweight, emergency surgery, higher Simplified Acute Physiology Score II, Braden score 3 days, comorbidities (chronic obstructive pulmonary disease, immunodeficiency), organ support (renal replacement, mechanical ventilation on ICU admission), and being in a low or lower-middle income-economy. Gradually increasing associations with mortality were identified for increasing severity of pressure injury: stage I (odds ratio [OR] 1.5; 95% CI 1.2–1.8), stage II (OR 1.6; 95% CI 1.4–1.9), and stage III or worse (OR 2.8; 95% CI 2.3–3.3). Conclusion: Pressure injuries are common in adult ICU patients. ICU-acquired pressure injuries are associated with mainly intrinsic factors and mortality. Optimal care standards, increased awareness, appropriate resource allocation, and further research into optimal prevention are pivotal to tackle this important patient safety threat

Correction to: Prevalence, associated factors and outcomes of pressure injuries in adult intensive care unit patients: the DecubICUs study

The original version of this article unfortunately contained a mistake

Prevalence, associated factors and outcomes of pressure injuries in adult intensive care unit patients: the DecubICUs study

Funder: European Society of Intensive Care Medicine; doi: http://dx.doi.org/10.13039/501100013347Funder: Flemish Society for Critical Care NursesAbstract: Purpose: Intensive care unit (ICU) patients are particularly susceptible to developing pressure injuries. Epidemiologic data is however unavailable. We aimed to provide an international picture of the extent of pressure injuries and factors associated with ICU-acquired pressure injuries in adult ICU patients. Methods: International 1-day point-prevalence study; follow-up for outcome assessment until hospital discharge (maximum 12 weeks). Factors associated with ICU-acquired pressure injury and hospital mortality were assessed by generalised linear mixed-effects regression analysis. Results: Data from 13,254 patients in 1117 ICUs (90 countries) revealed 6747 pressure injuries; 3997 (59.2%) were ICU-acquired. Overall prevalence was 26.6% (95% confidence interval [CI] 25.9–27.3). ICU-acquired prevalence was 16.2% (95% CI 15.6–16.8). Sacrum (37%) and heels (19.5%) were most affected. Factors independently associated with ICU-acquired pressure injuries were older age, male sex, being underweight, emergency surgery, higher Simplified Acute Physiology Score II, Braden score 3 days, comorbidities (chronic obstructive pulmonary disease, immunodeficiency), organ support (renal replacement, mechanical ventilation on ICU admission), and being in a low or lower-middle income-economy. Gradually increasing associations with mortality were identified for increasing severity of pressure injury: stage I (odds ratio [OR] 1.5; 95% CI 1.2–1.8), stage II (OR 1.6; 95% CI 1.4–1.9), and stage III or worse (OR 2.8; 95% CI 2.3–3.3). Conclusion: Pressure injuries are common in adult ICU patients. ICU-acquired pressure injuries are associated with mainly intrinsic factors and mortality. Optimal care standards, increased awareness, appropriate resource allocation, and further research into optimal prevention are pivotal to tackle this important patient safety threat

Partial hepatectomy as first-line treatment for patients with hepatocellular carcinoma

Abstract: Background: Partial hepatectomy (PH) and liver transplantation (LT) compete as first-line treatment for hepatocellular carcinoma (HCC). A prospectively collected database was retrospectively reviewed to establish when PH can compete with LT. Methods: Between 1991 and 2002, PH was performed in 131 cases of HCC (Child-Pugh A-B, technically resectable tumor without metastases). To ascertain patient survival after PH, we compared this series with a group of 40 HCC patients (G1-G2 HCC with no gross vascular invasion or metastasis) enlisted for liver transplantation during the same period. Results: The 1-, 3-, and 5-year intention-to-treat survival rates were 75%, 52%, and 31% for resection and 89%, 71%, and 63% for transplantation. Two tumor-related variables (gross vascular invasion and histological grade) and three liver function parameters (Child-Pugh score, bilirubin, Okuda stage) proved to be independent predictors of survival after resection, whereas nodule size and number, and Milan criteria did not. The 5-year survival of the best candidates for resection (favorable tumor biology with very well preserved liver function, n=52) was 58%. On a descriptive basis alone, this result did not differ significantly from the outcome in LT patients. PH patients with a poorly differentiated tumor and/or gross vascular invasion (n=28) had the worst outcome, irrespective of their liver function parameters