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Liver graft function is related to the quality of liver transplantation (LT). High-quality perioperative glycemic management is considered hepatoprotective. However, no studies have explored the effects of specialized and staged blood glucose management target ranges on reducing glycemic variability (GV) and early allograft dysfunction (EAD) after LT. In this prospective randomized controlled trial, a total of 188 LT recipients were randomly assigned 1:1 to the less intensive glucose management (LIGM) group and the more intensive glucose management (MIGM) group. They followed goals of 7.8–10.0 mmol/L and 4.5–6.7 mmol/L in the pre-anhepatic and anhepatic phases, respectively, and the goals of 4.1–10.0 mmol/L in the neohepatic phase and postoperatively. The primary outcome was EAD, and the secondary outcomes were GV, incidence of hyperglycemia/hypoglycemia, postoperative liver enzyme levels, 30-day postoperative infection rate, one-year survival rate, and TNF-α, IL-6 and C-reactive protein levels. A total of 182 adult patients (89 in the LIGM group and 93 in the MIGM group) completed the study. The mean age of the recipients was 51.46 ± 10.79 years, and the median MELD score before surgery was 16. The incidence of EAD was significantly lower in the LIGM group than in the MIGM group (10.11 % vs 31.18 %, P < 0.001), with a relative risk (RR) of 0.32 (2-sided 95 % CI 0.110–0.562). There was no statistical difference in the 30-day postoperative infection rate between the two groups (P > 0.05). The one-year survival rate of the LIGM group was higher than that of the MIGM group (92.13 % vs 82.02 %, P = 0.044). Adopting LIGM (7.8–10.0 mmol/L) during the pre-anhepatic and anhepatic phases helps to reduce the incidence of EAD after LT and promotes the recovery of liver function, but does not increase the incidence of postoperative infections. •Provides medical evidence for intraoperative glycemic management targets for LT.•Propose a more feasible intraoperative strict glucose management protocol for LT.•Improved the specialized blood glucose management measures in the LT protection strategy.•Increased the precision of LT blood glucose management measures.

Background In kidney transplantation, the use of Anti-Thymocyte Globulins (ATG) as induction therapy has been described as a possible treatment for reducing the prevalence of Delayed Graft Function (DGF). ATG possesses pharmaceutical proprieties that could help control the lesions caused by ischemia reperfusion injury. However, other studies have questioned this potential protective effect. We hypothesized that the benefits related to ATG for reducing DGF prevalence may be higher and more consistently recognized if only patients with high DGF risk are considered. We recently proposed a scoring system entitled DGFS (Delayed Graft Function Score) for such stratification of kidney transplant recipients according to their risk of DGF. Using the DGFS calculation, we aim to determine whether a short course of ATG can decrease the incidence of DGF in comparison with Basiliximab in kidney transplant recipients with low immunological risk but high DGF risk. Methods We conduct a phase IV, open label, randomized, multicentric and prospective study, to compare ATG in parallel with a control group treated by Basiliximab. The 1:1 randomized allocation of patients between groups is stratified on the clinical center, and on the hypothermic machine-perfusion device. We aimed to include a total of 384 patients to achieve a statistical power at 0.80. The study was initiated at the Nantes University hospital in July 2014, with data collection continuing until April 2018, and publication of the results proposed for 2019. Discussion The main expected benefits of this study are i ) the reduction of unjustified ATG over-prescriptions associated with serious adverse events, ii ) the reduction of chance losses related to ATG under-prescription, iii ) the decrease in the incidence of DGF which was described as a risk factor of graft failure and patient death, and iv ) the reduction in hospitalization duration and number of post transplantation dialysis sessions, both being associated with reduced medical costs. In conclusion, the current study is innovative by proposing a more efficient and personalized induction therapy. Trial registration The study was registered in the Clinical Trials Registry (# NCT02056938 , February 5, 2014), and in the European Clinical Trials Database (EudraCT #2014-000332-42, January 30, 2014).

Abstract Rationale Primary graft dysfunction (PGD) is the main cause of early morbidity and mortality after lung transplantation. Previous studies have yielded conflicting results for PGD risk factors. Objectives We sought to identify donor, recipient, and perioperative risk factors for PGD. Methods We performed a 10-center prospective cohort study enrolled between March 2002 and December 2010 (the Lung Transplant Outcomes Group). The primary outcome was International Society for Heart and Lung Transplantation grade 3 PGD at 48 or 72 hours post-transplant. The association of potential risk factors with PGD was analyzed using multivariable conditional logistic regression. Measurements and Main Results A total of 1,255 patients from 10 centers were enrolled; 211 subjects (16.8%) developed grade 3 PGD. In multivariable models, independent risk factors for PGD were any history of donor smoking (odds ratio [OR], 1.8; 95% confidence interval [CI], 1.2–2.6; P = 0.002); FiO2 during allograft reperfusion (OR, 1.1 per 10% increase in FiO2; 95% CI, 1.0–1.2; P = 0.01); single lung transplant (OR, 2; 95% CI, 1.2–3.3; P = 0.008); use of cardiopulmonary bypass (OR, 3.4; 95% CI, 2.2–5.3; P < 0.001); overweight (OR, 1.8; 95% CI, 1.2–2.7; P = 0.01) and obese (OR, 2.3; 95% CI, 1.3–3.9; P = 0.004) recipient body mass index; preoperative sarcoidosis (OR, 2.5; 95% CI, 1.1–5.6; P = 0.03) or pulmonary arterial hypertension (OR, 3.5; 95% CI, 1.6–7.7; P = 0.002); and mean pulmonary artery pressure (OR, 1.3 per 10 mm Hg increase; 95% CI, 1.1–1.5; P < 0.001). PGD was significantly associated with 90-day (relative risk, 4.8; absolute risk increase, 18%; P < 0.001) and 1-year (relative risk, 3; absolute risk increase, 23%; P < 0.001) mortality. Conclusions We identified grade 3 PGD risk factors, several of which are potentially modifiable and should be prioritized for future research aimed at preventative strategies. Clinical trial registered with www.clinicaltrials.gov (NCT00552357).

Primary graft dysfunction (PGD) remains the leading cause of early mortality post-heart transplantation. Despite improvements in mechanical circulatory support and critical care measures, the rate of PGD remains significant. A recent consensus statement by the International Society of Heart and Lung Transplantation (ISHLT) has formulated a definition for PGD. Five years on, we look at current concepts and future directions of PGD in the current era of transplantation.

Abstract Rationale Primary graft dysfunction (PGD) is a significant cause of early morbidity and mortality after lung transplant and is characterized by severe hypoxemia and infiltrates in the allograft. The pathogenesis of PGD involves ischemia-reperfusion injury. However, subclinical increases in pulmonary venous pressure due to left ventricular diastolic dysfunction may contribute by exacerbating capillary leak. Objectives To determine whether a higher ratio of early mitral inflow velocity (E) to early diastolic mitral annular velocity (é), indicative of worse left ventricular diastolic function, is associated with a higher risk of PGD. Methods We performed a retrospective cohort study of patients in the Lung Transplant Outcomes Group who underwent bilateral lung transplant at our institution between 2004 and 2014 for interstitial lung disease, chronic obstructive pulmonary disease, or pulmonary arterial hypertension. Transthoracic echocardiograms obtained during evaluation for transplant listing were analyzed for E/é and other measures of diastolic function. PGD was defined as PaO2/FiO2 less than or equal to 200 with allograft infiltrates at 48 or 72 hours after reperfusion. The association between E/é and PGD was assessed with multivariable logistic regression. Measurements and Main Results After adjustment for recipient age, body mass index, mean pulmonary arterial pressure, and pretransplant diagnosis, higher E/é and E/é greater than 8 were associated with an increased risk of PGD (E/é odds ratio, 1.93; 95% confidence interval, 1.02–3.64; P = 0.04; E/é >8 odds ratio, 5.29; 95% confidence interval, 1.40–20.01; P = 0.01). Conclusions Differences in left ventricular diastolic function may contribute to the development of PGD. Future trials are needed to determine whether optimization of left ventricular diastolic function reduces the risk of PGD.

Background Sex and hormones influence immune responses to ischemia reperfusion (IR) and could, therefore, cause sex-related differences in lung transplantation (LTx) outcomes. We compared men’s and women’s clinical and molecular responses to post-LTx IR. Methods In 203 LTx patients, we used the 2016 International Society for Heart and Lung Transplantation guidelines to score primary graft dysfunction (PGD). In a subgroup of 40 patients with blood samples collected before LTx (T0) and 6, 24, 48 (T48), and 72 h (T72) after lung reperfusion, molecular response to IR was examined through serial analysis of circulating cytokine expression. Results After adjustment, women had less grade 3 PGD than men at T48, but not at T72. PGD grade decreased from T0 to T72 more often in women than men. The evolution of PGD (the difference in mean PGD between T72 and T0) was greater in men. However, the evolution of IL-2, IL-7, IL-17a, and basic fibroblast growth factor levels was more often sustained throughout the 72 h in women. In the full cohort, we noted no sex differences in secondary clinical outcomes, but women had significantly lower peak lactate levels than men across the 72 h. Conclusions Men and women differ in the evolution of PGD and cytokine secretion after LTx: Women have a more sustained proinflammatory response than men despite a greater reduction in PGD over time. This interaction between cytokine and PGD responses warrants investigation. Additionally, there may be important sex-related differences that could be used to tailor treatment during or after transplantation.

Purpose of Review This review summarizes the current literature on primary graft dysfunction highlighting the current definition, reviewing epidemiology, and describing donor, recipient, and perioperative risk factors in the contemporary era. Recent Findings PGD, in its most severe form, complicates 8% of heart transplants and portends a 1-year mortality of close to 40%. PGD is multifactorial and heterogeneous with contributions from donor and recipient risk as well as organ recovery and preservation modalities. Biomarkers may enhance risk stratification and lend insight into the underlying mechanism of PGD. Temperature-controlled storage and hypothermic oxygenation perfusion systems, in particular, may have significant potential to mitigate PGD risk. Summary PGD is a devastating early complication of heart transplantation that is both complex and multifactorial. Despite its incidence and impact the underlying biology of PGD remains poorly understood. Future studies mechanistic studies are needed to address the underlying pathophysiology of PGD to develop targeted prophylactic and/or therapeutic interventions.

Primary graft dysfunction (PGD) is the main cause of early morbidity and mortality after lung transplantation. Previous studies have yielded conflicting results for PGD risk factors. Herein, we carried out a systematic review and meta-analysis of published literature to identify recipient-related clinical risk factors associated with PGD development. A systematic search of electronic databases (PubMed, Embase, Web of Science, Cochrane CENTRAL, and Scopus) for studies published from 1970 to 2013 was performed. Cohort, case-control, or cross-sectional studies that examined recipient-related risk factors of PGD were included. The odds ratios (ORs) or mean differences (MDs) were calculated using random-effects models. Thirteen studies involving 10042 recipients met final inclusion criteria. From the pooled analyses, female gender (OR 1.38, 95% CI 1.09 to 1.75), African American (OR 1.82, 95%CI 1.36 to 2.45), idiopathic pulmonary fibrosis (IPF) (OR 1.78, 95% CI 1.49 to 2.13), sarcoidosis (OR 4.25, 95% CI 1.09 to 16.52), primary pulmonary hypertension (PPH) (OR 3.73, 95%CI 2.16 to 6.46), elevated BMI (BMI≥25 kg/m2) (OR 1.83, 95% CI 1.26 to 2.64), and use of cardiopulmonary bypass (CPB) (OR 2.29, 95%CI 1.43 to 3.65) were significantly associated with increased risk of PGD. Age, cystic fibrosis, secondary pulmonary hypertension (SPH), intra-operative inhaled nitric oxide (NO), or lung transplant type (single or bilateral) were not significantly associated with PGD development (all P>0.05). Moreover, a nearly 4 fold increased risk of short-term mortality was observed in patients with PGD (OR 3.95, 95% CI 2.80 to 5.57). Our analysis identified several recipient related risk factors for development of PGD. The identification of higher-risk recipients and further research into the underlying mechanisms may lead to selective therapies aimed at reducing this reperfusion injury.

Abstract Rationale Cognitive and psychiatric impairments are threats to functional independence, general health, and quality of life. Evidence regarding these outcomes after lung transplantation is limited. Objectives Determine the frequency of cognitive and psychiatric impairment after lung transplantation and identify potential factors associated with cognitive impairment after lung transplantation. Methods In a retrospective cohort study, we assessed cognitive function, mental health, and health-related quality of life using a validated battery of standardized tests in 42 subjects post-transplantation. The battery assessed cognition, depression, anxiety, resilience, and post-traumatic stress disorder (PTSD). Cognitive function was assessed using the Montreal Cognitive Assessment, a validated screening test with a range of 0 to 30. We hypothesized that cognitive function post-transplantation would be associated with type of transplant, cardiopulmonary bypass, primary graft dysfunction, allograft ischemic time, and physical therapy post-transplantation. We used multivariable linear regression to examine the relationship between candidate risk factors and cognitive function post-transplantation. Measurements and Main Results Mild cognitive impairment (score, 18–25) was observed in 67% of post-transplant subjects (95% confidence interval [CI]: 50–80%) and moderate cognitive impairment (score, 10–17) was observed in 5% (95% CI, 1–16%) of post-transplant subjects. Symptoms of moderate to severe anxiety and depression were observed in 21 and 3% of post-transplant subjects, respectively. No transplant recipients reported symptoms of PTSD. Higher resilience correlated with less psychological distress in the domains of depression (P < 0.001) and PTSD (P = 0.02). Prolonged graft ischemic time was independently associated with worse cognitive performance after lung transplantation (P = 0.001). The functional gain in 6-minute-walk distance achieved at the end of post-transplant physical rehabilitation (P = 0.04) was independently associated with improved cognitive performance post-transplantation. Conclusions Mild cognitive impairment was present in the majority of patients after lung transplantation. Prolonged allograft ischemic time may be associated with cognitive impairment. Poor physical performance and cognitive impairment are linked, and physical rehabilitation post-transplant and psychological resilience may be protective against the development of long-term impairment. Further study is warranted to confirm these potential associations and to examine the trajectory of cognitive function after lung transplantation.

Purpose Early Allograft Dysfunction (EAD) is a serious complication following liver transplantation. With more marginal donors and critical recipients, identifying EAD risk factors and their impact on long-term outcomes is crucial. Methods We reviewed all liver transplants performed between 2007 and 2017 at our institution, excluding pediatric recipients, combined thoracic transplants, and retransplants in the same hospital stay. EAD was defined as either: (i) AST/ALT > 2000 IU/l in first 7 postoperative days (POD), (ii) Bilirubin ≥ 10 mg/dl on POD 7, (iii) INR ≥ 1.6 on POD 7. Results Of the 621 cases analyzed, the EAD rate was 53.6%. Multivariate analysis identified only donor-dependent variables as independent risk factors for the onset of EAD: donor age ( p  = 0.012), donor serum sodium ( p  = 0.021), cold ischemic time ( p  = 0.007) and graft weight ( p  < 0.001). EAD significantly impaired graft survival (69.2% vs. 86.2% after 1 year; p  = 0.005) but did not impact long-term patient survival (76.3% vs. 87.6% after 1 year; p  = 0.162). Of the EAD components, elevated INR proved to be the only reliable predictor of patient mortality. Additionally, an AST/ALT concentration of > 4000 IU/l significantly improved the predictive value of the EAD definition for patient survival ( p  = 0.002). Conclusions EAD risk factors are primarily donor-based and significantly impair graft but not patient survival. The high EAD rates and increased use of marginal grafts suggest the need to adjust conventional EAD definitions to optimize graft allocation in the future