Controlled temperatures in cold preservation provides safe heart transplantation results.

BACKGROUND: We aimed to investigate the short-term outcomes of heart transplant patients who underwent SherpaPak™ donor organ preservation. METHOD: We prospectively collected the data of patients who underwent heart transplantation using SherpaPak™ system for donor organ transportation from February 2020 to March 2021. Donor and recipient demographic data, preoperative and postoperative echocardiographic and hemodynamic parameters, total ischemic time and SherpaPak temperatures, vasoactive inotropic scores (VIS), primary graft dysfunction (PGD) status, intensive care unit stay, complications, and mortality during follow-up were assessed. RESULTS: A total of 39 consecutive heart transplant patients with SherpaPak system were included in the study. The mean donor age was 32.2 ± 6.7 (range: 16-46). The mean recipient age was 57.5 ± 12 (range: 19-73). The mean preoperative ejection fraction (EF) was 23.7 ± 15.4 (range: 5-75). All recipients underwent a standard bicaval technique for orthotopic heart implantation. The mean total ischemic time was 230.1 ± 41 (range: 149-342) min. The mean Sherpa temperature was 5.6 ± 0.8°C (range: 3.7-7.5). The mean VIS was 10.2 ± 6.5 (range: 2-32). The number of mild PGD was 5 (14.7%), and moderate PGD was 4 (11.8%). There was no severe PGD. The postoperative EF was 64.3 ± 5.5 (range: 50-78). Mean intubation time was 47.4 ± 64 (range: 8-312, median: 22) h. The mean time of intensive care unit stay was 6.3 ± 5 (range: 2-31, median: 5) days. Two patients required chest revision (5.8%), two patients had lung infection (5.8%). Two patients had a stroke (5.8%). There was no mortality. CONCLUSION: Using the SherpaPak system during heart transplantation is safe and not associated with significant recipient morbidity. None of the recipients experienced significant PGD and mortality.

Methods of Attenuating Ischemia-Reperfusion Injury in Liver Transplantation for Hepatocellular Carcinoma.

Hepatocellular carcinoma (HCC) is one of the most frequent indications for liver transplantation. However, the transplantation is ultimately associated with the occurrence of ischemia-reperfusion injury (IRI). It affects not only the function of the graft but also significantly worsens the oncological results. Various methods have been used so far to manage IRI. These include the non-invasive approach (pharmacotherapy) and more advanced options encompassing various types of liver conditioning and machine perfusion. Strategies aimed at shortening ischemic times and better organ allocation pathways are still under development as well. This article presents the mechanisms responsible for IRI, its impact on treatment outcomes, and strategies to mitigate it. An extensive review of the relevant literature using MEDLINE (PubMed) and Scopus databases until September 2020 was conducted. Only full-text articles written in English were included. The following search terms were used: "ischemia reperfusion injury", "liver transplantation", "hepatocellular carcinoma", "preconditioning", "machine perfusion".

Donor Hepatic Occult Collagen Deposition Predisposes to Peritransplant Stress and Impacts Human Liver Transplantation.

BACKGROUND AND AIMS: Environmentally triggered chronic liver inflammation can cause collagen deposits, whereas early stages of fibrosis without any specific symptoms could hardly be detectable. We hypothesized that some of the human donor grafts in clinical liver transplantation (LT) might possess unrecognizable fibrosis, affecting their susceptibility to LT-induced stress and hepatocellular damage. This retrospective study aimed to assess the impact of occult hepatic fibrosis on clinical LT outcomes. APPROACH AND RESULTS: Human (194) donor liver biopsies were stained for collagen with Sirius red, and positive areas (Sirius red-positive area; SRA) were measured. The body mass index, aspartate aminotransferase/alanine aminotransferase ratio, diabetes score was calculated using 962 cases of the donor data at the procurement. LT outcomes, including ischemia-reperfusion injury (IRI), early allograft dysfunction (EAD), and survival rates, were analyzed according to SRA and BARD scores. With the median SRA in 194 grafts of 9.4%, grafts were classified into low-SRA (<15%; n = 140) and high-SRA (≥15%; n = 54) groups. Grafts with high SRA suffered from higher rates of IRI and EAD (P < 0.05) as compared to those with low SRA. Interestingly, high SRA was identified as an independent risk factor for EAD and positively correlated with the donor BARD score. When comparing low-BARD (n = 692) with high-BARD (n = 270) grafts in the same period, those with high BARD showed significantly higher post-LT transaminase levels and higher rates of IRI and EAD. CONCLUSIONS: These findings from the largest clinical study cohort to date document the essential role of occult collagen deposition in donor livers on LT outcomes. High-SRA and donor BARD scores correlated with an increased incidence of hepatic IRI and EAD in LT recipients. This study provides the rationale for in-depth and prospective assessment of occult fibrosis for refined personalized LT management.

Prediction of donor related lung injury in clinical lung transplantation using a validated ex vivo lung perfusion inflammation score.

BACKGROUND: Ex vivo lung perfusion (EVLP) is an isolated organ assessment technique that has revolutionized the field of lung transplantation and enabled a safe increase in the number of organs transplanted. The objective of this study was to develop a protein-based assay that would provide a precision medicine approach to lung injury assessment during EVLP. METHODS: Perfusate samples collected from clinical EVLP cases performed from 2009 to 2019 were separated into development (n = 281) and validation (n = 57) sets to derive and validate an inflammation score based on IL-6 and IL-8 protein levels in perfusate. The ability of an inflammation score to predict lungs suitable for transplantation and likely to produce excellent recipient outcomes (time on ventilator ≤ 3 days) was assessed. Inflammation scores were compared to conventional clinical EVLP assessment parameters and associated with outcomes, including primary graft dysfunction and patient care in the ICU. RESULTS: An inflammation score accurately predicted the decision to transplant (AUROC 68% [95% CI 62-74]) at the end of EVLP and those transplants associated with short ventilator times (AUROC 73% [95% CI 66-80]). The score identified lungs more likely to develop primary graft dysfunction at 72-hours post-transplant (OR 4.0, p = 0.03). A model comprised of the inflammation score and ∆PO2 was able to determine EVLP transplants that were likely to have excellent recipient outcomes, with an accuracy of 87% [95% CI 83-92]. CONCLUSIONS: The adoption of an inflammation score will improve accuracy of EVLP decision-making and increase confidence of surgical teams to determine lungs that are suitable for transplantation, thereby improving organ utilization rates and patient outcomes.

The Potential Role of Efficacy and Safety Evaluation of N-Acetylcysteine Administration During Liver Procurement. The NAC-400 Single Center Randomized Controlled Trial.

BACKGROUND: N-acetylcysteine infusions have been widely used to reduce ischemia/reperfusion damage to the liver; however, convincing evidence of their benefits is lacking. OBJECTIVE: To perform the largest randomized controlled trial to compare the impact of N-acetylcysteine infusion during liver procurement on liver transplant outcomes. METHODS: Single center, randomized trial with patients recruited from La Fe University Hospital, Spain, from February 2012 to January 2016. A total of 214 grafts were transplanted and randomized to the N-acetylcysteine group (n = 113) or to the standard protocol without N-acetylcysteine (n = 101). The primary endpoint was allograft dysfunction (Olthoff criteria). Secondary outcomes included metabolomic biomarkers of oxidative stress levels, interactions between cold ischemia time and alanine aminotransferase level and graft and patient survival (ID no. NCT01866644). RESULTS: The incidence of primary dysfunction was 34% (31% in the N-acetylcysteine group and 37.4% in the control group [P = 0.38]). N-acetylcysteine administration reduced the alanine aminotransferase level when cold ischemia time was longer than 6 h (P = 0.0125). Oxidative metabolites (glutathione/oxidized glutathione and ophthalmic acid) were similar in both groups (P > 0.05). Graft and patient survival rates at 12 mo and 3 y were similar between groups (P = 0.54 and P = 0.69, respectively). CONCLUSIONS: N-acetylcysteine administration during liver procurement does not improve early allograft dysfunction according to the Olthoff classification. However, when cold ischemia time is longer than 6 h, N-acetylcysteine improves postoperative ALT levels.

Common Criteria for Ex Vivo Lung Perfusion Have No Significant Impact on Posttransplant Outcomes.

BACKGROUND: Although it is intense in health care resources, by facilitating assessment and reconditioning, ex vivo lung perfusion (EVLP) has the potential to expand the donor pool and improve lung transplant outcomes. However, inclusion criteria used in EVLP trials have not been validated. METHODS: This retrospective study from 2014 to 2018 reviewed our local state-based donation organization donor records as well as subsequent recipient outcomes to explore the relation between EVLP indications used in clinical trials and recipient outcomes. The primary outcome was primary graft dysfunction grade 3 at 24 hours, with 30-day mortality and posttransplant survival time as secondary outcomes, compared with univariate and multivariate analysis. RESULTS: From 705 lung donor referrals, 304 lung transplantations were performed (use rate of 42%); 212 of recipients (70%) met at least 1 of the commonly cited EVLP initiation criteria. There was no significant difference in primary graft dysfunction grade 3 or 30-day mortality between recipients with or without an EVLP indication (10.2% versus 7.8%, P = .51; and 2.4% versus 0%, P = .14, respectively). Multivariate analyses showed no significant relationship between commonly cited EVLP criteria and primary graft dysfunction grade 3 or survival time. Recipient outcomes were significantly associated with recipient diagnosis. CONCLUSIONS: At least 1 commonly cited criterion for EVLP initiation was present in 70% of the transplanted donors, and yet it did not predict clinical results; acceptable outcomes were seen in both subgroups. To discover the true utility of EVLP beyond good clinical management and focus EVLP on otherwise unacceptable lungs, a reconsideration of EVLP inclusion criteria is required.

Methane supplementation improves graft function in experimental heart transplantation.

BACKGROUND: Maintenance of cell viability during cold storage is a key issue in organ transplantation. Methane (CH4) bioactivity has recently been recognized in ischemia/reperfusion conditions; we therefore hypothesized that cold storage in CH4-enriched preservation solution can provide an increased defense against organ dysfunction during experimental heart transplantation (HTX). METHODS: The hearts of donor Lewis rats were stored for 60 minutes in cold histidine-tryptophan-ketoglutarate (Custodiol [CS]) or CH4-saturated CS solution (CS-CH4) (n = 12 each). Standard heterotopic HTX was performed, and 60 minutes later, the left ventricular (LV) pressure-volume relationships LV systolic pressure (LVSP), systolic pressure increment (dP/dtmax), diastolic pressure decrement, and coronary blood flow (CBF) were measured. Tissue samples were taken to detect proinflammatory parameters, structural damage (by light microscopy), endoplasmic reticulum (ER) stress, and apoptosis markers (CCAAT/enhancer binding protein [C/EBP] homologous protein, GRP78, glycogen synthase kinase-3ß, very low-density lipoprotein receptor, caspase 3 and 9, B-cell lymphoma 2, and bcl-2-like protein 4), whereas mitochondrial functional changes were analyzed by high-resolution respirometry. RESULTS: LVSP and dP/dtmax increased significantly at the largest pre-load volumes in CS-CH4 grafts as compared with the CS group (114.5 ± 16.6 mm Hg vs 82.8 ± 4.6 mm Hg and 3,133 ± 430 mm Hg/s vs 1,739 ± 169 mm Hg/s, respectively); the diastolic function and CBF (2.4 ± 0.4 ml/min/g vs 1.3 ± 0.3 ml/min/g) also improved. Mitochondrial oxidative phosphorylation capacity was more preserved (58.5 ± 9.4 pmol/s/ml vs 27.7 ± 6.6 pmol/s/ml), and cytochrome c release was reduced in CS-CH4 storage. Signs of HTX-caused myocardial damage, level of ER stress, and the transcription of proapoptotic proteins were significantly lower in CS-CH4 grafts. CONCLUSION: The addition of CH4 during 1 hour of cold storage improved early in vitro graft function and reduced mitochondrial dysfunction and activation of inflammation. Evidence shows that CH4 reduced ER stress-linked proapoptotic signaling.

Azithromycin prophylaxis after lung transplantation is associated with improved overall survival.

BACKGROUND: Azithromycin prophylaxis (AP) in lung transplant recipients has been shown to reduce the composite end-point of death or chronic lung allograft dysfunction (CLAD) onset but without a clear effect on overall survival. Our program began using AP in 2010. We sought to evaluate the association between AP and survival and the risk of CLAD and baseline lung allograft dysfunction (BLAD). METHODS: We studied double lung recipients transplanted between 2004 and 2016. We defined AP as chronic use of azithromycin initiated before CLAD onset. We analyzed the association between AP and death or retransplant using Cox regression with adjustment for potential confounders. We further used Cox and logistic models to assess the relationship between AP and post-transplant CLAD onset and BLAD, respectively. RESULTS: A total of 445 patients were included, and 344 (77%) received AP (median time from transplant: 51 days). Patients receiving AP were more likely to receive induction with interleukin-2 receptor antagonists (57% vs 35%; p < 0.001). AP was associated with improved survival (hazard ratio [HR]: 0.59; 95% confidence interval [CI]: 0.42-0.82; p = 0.0020) in our fully adjusted model, with a reduced adjusted risk of BLAD (odds ratio: 0.53; 95% CI: 0.33-0.85; p = 0.0460) but no clear reduction in the adjusted risk of CLAD (HR: 0.69; 95% CI: 0.47-1.03; p = 0.0697). CONCLUSIONS: AP is associated with improved survival after lung transplantation, potentially through improved baseline function. These findings build on prior trial results and suggest that AP is beneficial for lung transplant recipients.

Ex vivo lung perfusion for donor lung assessment and repair: a review of translational interspecies models.

For patients with end-stage lung disease, lung transplantation is a lifesaving therapy. Currently however, the number of patients who require a transplant exceeds the number of donor lungs available. One of the contributing factors to this is the conservative mindset of physicians who are concerned about transplanting marginal lungs due to the potential risk of primary graft dysfunction. Ex vivo lung perfusion (EVLP) technology has allowed for the expansion of donor pool of organs by enabling assessment and reconditioning of these marginal grafts before transplant. Ongoing efforts to optimize the therapeutic potential of EVLP are underway. Researchers have adopted the use of different large and small animal models to generate translational preclinical data. This includes the use of rejected human lungs, pig lungs, and rat lungs. In this review, we summarize some of the key current literature studies relevant to each of the major EVLP model platforms and identify the advantages and disadvantages of each platform. The review aims to guide investigators in choosing an appropriate species model to suit their specific goals of study, and ultimately aid in translation of therapy to meet the growing needs of the patient population.

Study design of the DAS-OLT trial: a randomized controlled trial to evaluate the impact of dexmedetomidine on early allograft dysfunction following liver transplantation.

BACKGROUND: Perioperative ischemia/reperfusion (I/R) injury during liver transplantation is strongly associated with early allograft dysfunction (EAD), graft loss, and mortality. Hepatic I/R injury also causes remote damage to other organs including the renal and pulmonary systems. Dexmedetomidine (DEX), a selective α2-adrenoceptor agonist which is used as an adjuvant to general anesthesia, has been shown in preclinical studies to provide organ protection by ameliorating the effects of I/R injury in a range of tissues (including the liver). However, prospective clinical evidence of any potential benefits in improving outcomes in liver transplantation is lacking. This study aimed to verify the hypothesis that the application of dexmedetomidine during the perioperative period of liver transplantation can reduce the incidence of EAD and primary graft non-function (PNF). At the same time, the effects of dexmedetomidine application on perioperative renal function and lung function were studied. METHODS: This is a prospective, single-center, randomized, parallel-group study. Two hundred participants (18-65 years) scheduled to undergo liver transplantation under general anesthesia will be included in this study. For participants in the treatment group, a loading dose of DEX will be given after induction of anesthesia (1 µg/kg over 10 min) followed by a continuous infusion (0.5 µg/kg /h) until the end of surgery. For participants in the placebo group, an equal volume loading dose of 0.9% saline will be given after the induction of anesthesia followed by an equal volume continuous infusion until the end of surgery. All other supplements, e.g., opioids, sedatives, and muscle relaxant, will be identical in both arms and administered according to routine clinical practice. DISCUSSION: The present trial will examine whether DEX confers organoprotective effects in the liver, in terms of reducing the incidence of EAD and PNF in orthotopic liver transplantation recipients. TRIAL REGISTRATION: ClinicalTrials.gov NCT03770130. Registered on 10 December 2018. https://clinicaltrials.gov/ct2/show/NCT03770130.

Saphenous vein graft disease, pathophysiology, prevention, and treatment. A review of the literature.

BACKGROUND: The saphenous vein remains the most frequently used conduit for coronary artery bypass grafting, despite reported unsatisfactory long-term patency rates. Understanding the pathophysiology of vein graft failure and attempting to improve its longevity has been a significant area of research for more than three decades. This article aims to review the current understanding of the pathophysiology and potential new intervention strategies. METHODS: A search of three databases: MEDLINE, Web of Science, and Cochrane Library, was undertaken for the terms "pathophysiology," "prevention," and "treatment" plus the term "vein graft failure." RESULTS: Saphenous graft failure is commonly the consequence of four different pathophysiological mechanisms, early acute thrombosis, vascular inflammation, intimal hyperplasia, and late accelerated atherosclerosis. Different methods have been proposed to inhibit or attenuate these pathological processes including modified surgical technique, topical pretreatment, external graft support, and postoperative pharmacological interventions. Once graft failure occurs, the available treatments are either surgical reintervention, angioplasty, or conservative medical management reserved for patients not eligible for either procedure. CONCLUSION: Despite the extensive amount of research performed, the pathophysiology of saphenous vein graft is still not completely understood. Surgical and pharmacological interventions have improved early patency and different strategies for prevention seem to offer some hope in improving long-term patency.

Histidine-Tryptophan-Ketoglutarate Solution for Donor Heart Preservation Is Safe for Transplantation.

BACKGROUND: Various solutions are used for donor heart preservation. We examined the outcomes in our heart transplant population where histidine-tryptophan-ketoglutarate (HTK) solution has been used for heart preservation since 2004. METHODS: This was a retrospective review of the United Network for Organ Sharing (UNOS) database (2004-2016) comparing our heart transplant outcomes with other national centers. Propensity matching in a 1:3 ratio was performed to adjust for preoperative recipient variables. RESULTS: After propensity matching comparing UNOS outcomes (n = 1080) with our institutional data (n = 360), there was no difference in matched preoperative variables. Donor hearts were similar for donor age, sex, donor-to-recipient size ratio, LVEF, and ischemic time. Our HTK cohort had a larger proportion with donor cardiac arrest (26.3% vs 6.1%, P < .001) and longer cardiac arrest duration (22.1 ± 16.0 vs 17.2 ± 14.0 minutes, P = .052). Our primary graft dysfunction (PGD) rate requiring mechanical support was 4.2% (n = 1). Postoperative mechanical support use for PGD included extracorporeal membrane oxygenation in 9 (60.0%), intraaortic balloon pump in 4 (26.7%), right ventricular assist device in 3 (20%), and biventricular assist device in 3 (20%). Overall survival at our institution was similar to the national average (P = .649). Survival at 1, 5, and 10 years with HTK was 92.2%, 81.3%, and 70.8%, and for the UNOS population was 91.6%, 80.3%, and 62.0%, respectively. CONCLUSIONS: Use of HTK solution for donor hearts was associated with a low rate of severe PGD. Overall survival was not significantly different from other institutions using a variety of preservation solutions in the UNOS database during the same period. HTK solution is efficacious for preservation of donor hearts.

Warm retrograde perfusion can remove more fat from lung grafts with fat embolism in a porcine model.

OBJECTIVE: In lung transplantation, unexpected pulmonary emboli, including thrombi and fat, have been observed with high probability and are associated with potential primary graft dysfunction. We evaluated a new perfusion method using warm retrograde flushing that removes more fat than conventional cold retrograde flushing. METHODS: We developed a novel porcine donor model for pulmonary fat embolism by administering autologous fat in the left pulmonary artery. The left pulmonary artery and the left superior and inferior pulmonary veins were cannulated for flushing and collecting these solutions. After flushing, the left lung was reperfused under observation for 3 h. Two groups underwent warm and cold additional retrograde flush (WS; warm solution group, CS; cold solution group). RESULTS: The fat removal rate in the antegrade flush was equal in both groups (3.0 ± 0.6% vs 3.0 ± 0.4%, p = 0.46); however, the rate was significantly greater in the WS group in retrograde flush (25.2 ± 3.2% vs 8.0 ± 1.4%, p = 0.01). Histology with Oil Red O staining and its software analysis showed more residual fat in the CS group (0.12 ± 0.01% vs 0.38 ± 0.07%, p = 0.01). There was no significant difference in the pulmonary function and hemodynamics during the 3-h period after reperfusion. CONCLUSION: Warm retrograde perfusion can remove more fat from lung grafts with fat embolism in a porcine donor model.

Mitigation of Primary Graft Dysfunction in Lung Transplantation: Current Understanding and Hopes for the Future.

Primary graft dysfunction (PGD) is a form of acute lung injury that develops within the first 72 hours after lung transplantation. The overall incidence of PGD is estimated to be around 30%, and the 30-day mortality for grade 3 PGD around 36%. PGD is also associated with the development of bronchiolitis obliterans syndrome, a specific form of chronic lung allograft dysfunction. In this article, we will discuss perioperative strategies for PGD prevention as well as possible future avenues for prevention and treatment.

Fatores de risco para disfunção e para não função primária do fígado transplantado em um contexto brasileiro / Risk factors for dysfunction and primary non-function of the transplanted liver in a Brazilian context

A disfunção precoce do enxerto é descrita como mau funcionamento inicial, função marginal ou retardo na função e incide entre 7% e 27% dos pacientes transplantados de fígado. A não função primária é a perda do enxerto e incide entre 1,4% e 8,4% nessa população. O presente estudo foi conduzido para analisar fatores de risco para disfunção e para não função primária de fígados transplantados. Foram pesquisados fatores do doador, do enxerto, do paciente e da logística do transplante. Trata-se de um estudo epidemiológico, tipo coorte histórica conduzido com 180 prontuários de pacientes transplantados e admitidos na Unidade de Terapia Intensiva, cujos doadores estavam em morte encefálica. Todos os transplantes foram realizados no Hospital das Clínicas da Universidade Federal de Minas Gerais, Belo Horizonte, Brasil, entre 2012 e 2018. Análises estatísticas descritiva, bivariada e multivariada foram realizadas usando o método de Kaplan-Meier e o teste Log-rank. Associação entre os fatores de risco e os desfechos foi estabelecida aplicando a regressão de Cox e o processo de seleção Backward, ajustada pelo Hazard ratio. Verificou-se que os receptores de fígado tinham idade média de 52,1 anos; em sua maioria homens brancos. As indicações do transplante foram: doença alcoólica, 31,7%; doença metabólica e Hepatite viral, 26,1%; tumor, 22,2%; doença colestática, 17,8% e doença vascular, 2,8%. Índice de Massa Corporal igual ou superior a 30 kg/m² foi encontrado em 3,9%. O escore médio do Model for End-Stage Liver Disease foi de 23 e a creatinina sérica média foi de 1,35mg/dl. Em relação aos doadores, a idade média foi de 37,6 anos, sendo 39,4% do sexo feminino. As causas da morte encefálica foram acidente vascular cerebral em 86 (47,8%), traumatismo craniano em 77 (42,8%) e por outras causas 17 (9,4%). A aspartato aminotransferase foi, em média, 77,20 UI/L, a alanina aminotransferase foi, em média, 60,42 UI/L. Sódio sérico >160 mmol/l ocorreu em 18,6% e a Gamaglutamiltransferase média foi de 77 UI/L. O Índice de Risco do Doador médio foi de 1,476. Quanto ao enxerto verificou-se que sua origem foi local em 37,8%; regional, em 56,7% e nacional, em 5,5% dos casos. O tempo de isquemia fria (>10 horas) ocorreu em 58 (32,2%). O tempo de isquemia quente (> 60 minutos) ocorreu em 14 (9,9%) % dos transplantes e o tempo médio da cirurgia do receptor foi de 6,1 horas. Estes receberam, em média, 4 U de plaquetas e 5 (2.8%) receberam Plasma Fresco Congelado > 30U. O Equilíbrio do Risco médio foi de 10. A evolução clínica9 normal ocorreu em 66 (36,7%) dos pacientes. A disfunção precoce do enxerto foi identificada em 104 (57,8%) e a não função primária em 10 (5,5%). Encontrou-se que o doador do sexo feminino, o tempo de isquemia quente do enxerto superior a 60 minutos e o consumo de Plasma Fresco Congelado > 30 U pelo receptor, constituem risco aumentado para disfunção precoce do enxerto nesta amostra. O fator de risco para a não função primária foi o volume de plaquetas consumido pelo receptor. O controle desses fatores de risco contribui para a função adequada do fígado após o transplante e melhora da sobrevida dos enxertos e dos pacientes.

Early graft dysfunction is described as initial malfunction, marginal function or delayed function, and it affects between 7% and 27% of liver transplant patients. The primary nonfunction is graft loss, and it affects between 1.4% and 8.4% of this population. The present study was conducted to analyze risk factors for dysfunction and non-primary function of transplanted livers. Donor, graft, patient, and transplant logistics factors were researched. This is an epidemiological study, with a historical cohort conducted with 180 medical records of transplanted patients admitted to the Intensive Care Unit, whose donors were brain dead. All transplants were performed at the Hospital das Clínicas, Federal University of Minas Gerais, Belo Horizonte, Brazil, between 2012 and 2018. Descriptive, bivariate, and multivariate statistical analyzes were performed using the Kaplan-Meier method and the Log-rank test. Association between risk factors and outcomes was assessed by Cox regression and the Backward selection process, adjusted by the Hazard ratio. The liver receptors were mostly white males with an average age of 52.1 years. Transplant indications were: alcoholic disease, 31.7%; metabolic disease and viral hepatitis, 26.1%; tumor, 22.2%; cholestatic disease, 17.8% and vascular disease, 2.8%. Body Mass Index equal to or greater than 30 kg / m² occurred 3.9%. The average score for the Model for End-Stage Liver Disease was 23, and the mean serum creatinine was 1.35mg / dl. Regarding donors, the average age was 37.6 years, with 39.4% being female. The causes of brain death were stroke in 86 (47.8%), head injury in 77 (42.8%), and for other causes in 17 (9.4%). Aspartate aminotransferase was, on average, 77.20 UI/L. Alanine aminotransferase was, on average, 60.42 UI/L. Serum sodium > 160 mmol/l occurred in 18.6%, and the mean Gamaglutamiltransferase was 77 IU / L. The average Donor Risk Index was 1.476. As for the graft, it was found that its origin was local in 37.8%; regional, in 56.7%; and national, in 5.5% of cases. The cold ischemia time (> 10 hours) occurred in 58 (32.2%), the warm ischemia time (> 60 minutes) occurred in 14 (9.9%) of the transplants. The average time of the recipient's surgery was 6.1 hours, who received 4 U of platelets on average. 5 (2.8%) received fresh frozen plasma > 30 U. The average Balance of risk was 10. The normal clinical evolution occurred in 66 (36.7%) of the patients. Early graft dysfunction occurred in 104 (57.8%), and primary non-function in 10 (5.5%). The risk factors for early graft dysfunction were the female donor, the graft warm ischemia time greater than 60 minutes, and the11 consumption of fresh frozen plasma > 30 U by the recipient. The risk factor for primary nonfunction was the volume of platelets consumed by the recipient. The control of these risk factors contributes to the adequate function of the liver after transplantation and to improve grafts and patient's survival

Pirfenidone exerts beneficial effects in patients with IPF undergoing single lung transplantation.

Pirfenidone demonstrated pleiotropic antiinflammatory effects in various experimental and clinical settings. The aim of this study was to assess the impact of previous treatment with pirfenidone on short-term outcomes after single lung transplantation (SLTx). Therefore, patients with idiopathic pulmonary fibrosis (IPF) who were undergoing SLTx were screened retrospectively for previous use of pirfenidone and compared to respective controls. Baseline parameters and short-term outcomes were recorded and analyzed. In total, 17 patients with pirfenidone were compared with 26 patients without antifibrotic treatment. Baseline characteristics and severity of disease did not differ between groups. Use of pirfenidone did not increase blood loss, wound-healing, or anastomotic complications. Severity of primary graft dysfunction at 72 hours was less (0.3 ± 0.6 vs 1.4 ± 1.3, P = .002), and length of mechanical ventilation (37.5 ± 34.8 vs 118.5 ± 151.0 hours, P = .016) and intensive care unit (ICU) stay (6.6 ± 7.1 vs 15.6 ± 20.3, P = .089) were shorter in patients with pirfenidone treatment. An independent beneficial effect of pirfenidone was confirmed by regression analysis while controlling for confounding variables (P = .016). Finally, incidence of acute cellular rejections within the first 30 days after SLTx was lower in patients with previous pirfenidone treatment (0.0% vs 19.2%; P = .040). Our data suggest a beneficial role of previous use of pirfenidone in patients with IPF who were undergoing SLTx.

EVLP: Ready for Prime Time?

Ex vivo lung perfusion implies perfusion and ventilation of a donor lung outside of the human body. The 2 most clinically relevant and commercially available devices currently in clinical trials are XVIVO Perfusion System (XPS Perfusion, Goteborg, Sweden) and Organ Care System (Transmedics, Andover, MA). Our review focuses on the needs met by ex vivo lung perfusion, and the clinical literature on both devices.

A single-nucleotide polymorphism in a gene modulating glucocorticoid sensitivity is associated with the decline in total lung capacity after lung transplantation.

PURPOSE: Glucocorticoids are used to prevent chronic lung allograft dysfunction (CLAD) after lung transplantation (LT). Our study was aimed at assessing the association between the glucocorticoid-induced transcript 1 gene (GLCCI1) variant, which modulates glucocorticoid sensitivity, and the postoperative lung function and development of CLAD after LT. METHODS: A total of 71 recipients of LT were genotyped for the GLCCI1 variant (rs37972) and divided into three groups: the homozygous mutant allele (TT) group, the heterozygous mutant allele (CT) group, and the wild-type allele (CC) group. The results of pulmonary function tests were compared with the postoperative baseline values. RESULTS: The total lung capacity (TLC) in the TT group was significantly lower than that in the CC group at 3 years after LT (P = 0.029). In the recipients of cadaveric LT, the TLC and forced expiratory volume in 1 s in the TT group were significantly lower than those in the CC groups, resulting in a significant worse CLAD-free survival at 3 years after LT (P = 0.016). CONCLUSION: The GLCCI1 variant was associated with a significant decrease of the TLC at 3 years after LT and the development of CLAD at 3 years, especially in patients undergoing cadaveric LT.

Intraoperative extracorporeal membrane oxygenation and the possibility of postoperative prolongation improve survival in bilateral lung transplantation.

OBJECTIVES: The value of intraoperative extracorporeal membrane oxygenation (ECMO) in lung transplantation remains controversial. In our department, ECMO has been used routinely for intraoperatively unstable patients for more than 15 years. Recently, we have extended its indication to a preemptive application in almost all cases. In addition, we prolong ECMO into the early postoperative period whenever graft function does not meet certain quality criteria or in patients with primary pulmonary hypertension. The objective of this study was to review the results of this strategy. METHODS: All standard bilateral lung transplantations performed between January 2010 and June 2016 were included in this single-center, retrospective analysis. Patients were divided into 3 groups: group I-no ECMO (n = 116), group II-intraoperative ECMO (n = 343), and group III-intraoperative and prolonged postoperative ECMO (n = 123). The impact of different ECMO strategies on primary graft function, short-term outcomes, and patient survival were analyzed. RESULTS: The use of intraoperative ECMO was associated with improved 1-, 3-, and 5-year survival compared with non-ECMO patients (91% vs 82%, 85% vs 76%, and 80% vs 74%; log-rank P = .041). This effect was still evident after propensity score matching of both cohorts. Despite the high number of complex patients in group III, outcome was excellent with higher survival rates than in the non-ECMO group at all time points. CONCLUSIONS: Intraoperative ECMO results in superior survival when compared with transplantation without any extracorporeal support. The concept of prophylactic postoperative ECMO prolongation is associated with excellent outcomes in recipients with pulmonary hypertension and in patients with questionable graft function at the end of implantation.