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Donor lung preservation at 10 °C appears to be an innovative and promising method that may improve transplant logistics by extending the cold ischemia time with excellent outcomes. We report the case of two lung transplants from two different donors involving the use of two different preservation methods, highlighting the benefits of using 10 °C lung storage.

BACKGROUND: Heart transplantation is an effective treatment offering the best recovery in both quality and quantity of life in those affected by refractory, severe heart failure. However, transplantation is limited by donor organ availability. The reintroduction of heart donation after the circulatory determination of death (DCD) in 2014 offered an uplift in transplant activity by 30%. Thoraco-abdominal normothermic regional perfusion (taNRP) enables in-situ reperfusion of the DCD heart. The objective of this paper is to assess the clinical outcomes of DCD donor hearts recovered and transplanted from donors undergoing taNRP. METHOD: This was a multicentre retrospective observational study. Outcomes included functional warm ischaemic time, use of mechanical support immediately following transplantation, perioperative and long-term actuarial survival and incidence of acute rejection requiring treatment. 157 taNRP DCD heart transplants, performed between February 2, 2015, and July 29, 2022, have been included from 15 major transplant centres worldwide including the UK, Spain, the USA and Belgium. 673 donations after the neurological determination of death (DBD) heart transplantations from the same centres were used as a comparison group for survival. FINDINGS: taNRP resulted in a 23% increase in heart transplantation activity. Survival was similar in the taNRP group when compared to DBD. 30-day survival was 96.8% ([92.5%-98.6%] 95% CI, n = 156), 1-year survival was 93.2% ([87.7%-96.3%] 95% CI, n = 72) and 5-year survival was 84.3% ([69.6%-92.2%] 95% CI, n = 13). INTERPRETATION: Our study suggests that taNRP provides a significant boost to heart transplantation activity. The survival rates of taNRP are comparable to those obtained for DBD transplantation in this study. The similar survival may in part be related to a short warm ischaemic time or through a possible selection bias of younger donors, this being an uncontrolled observational study. Therefore, our study suggests that taNRP offers an effective method of organ preservation and procurement. This early success of the technique warrants further investigation and use. FUNDING: None of the authors have a financial relationship with a commercial entity that has an interest in the subject. ispartof: ECLINICALMEDICINE vol:58 ispartof: location:England status: published

BACKGROUND: To better define the risk of malignancy transmission through organ transplantation, we review the Spanish experience on donor malignancies. METHODS: We analyzed the outcomes of recipients of organs obtained from deceased donors diagnosed with a malignancy during 2013-2018. The risk of malignancy transmission was classified as proposed by the Council of Europe. RESULTS: Of 10 076 utilized deceased donors, 349 (3.5%) were diagnosed with a malignancy. Of those, 275 had a past (n = 168) or current (n = 107) history of malignancy known before the transplantation of organs into 651 recipients. Ten malignancies met high-risk criteria. No donor-transmitted cancer (DTC) was reported after a median follow-up of 24 (interquartile range [IQR]: 19-25) mo. The other 74 donors were diagnosed with a malignancy after transplantation. Within this group, 64 donors (22 with malignancies of high or unacceptable risk) whose organs were transplanted into 126 recipients did not result in a DTC after a median follow-up of 26 (IQR: 22-37) mo, though a prophylactic transplantectomy was performed in 5 patients. The remaining 10 donors transmitted an occult malignancy to 16 of 25 recipients, consisting of lung cancer (n = 9), duodenal adenocarcinoma (n = 2), renal cell carcinoma (n = 2), extrahepatic cholangiocarcinoma (n = 1), prostate cancer (n = 1), and undifferentiated cancer (n = 1). After a median follow-up of 14 (IQR: 11-24) mo following diagnosis, the evolution was fatal in 9 recipients. In total, of 802 recipients at risk, 16 (2%) developed a DTC, which corresponds to 6 cases per 10 000 organ transplants. CONCLUSIONS: Current standards may overestimate the risk of malignancy transmission. DTC is an infrequent but difficult to eliminate complication.

OBJECTIVES Bronchial anastomotic complications remain a major concern in lung transplantation. We aim to compare 2 different techniques, continuous suture (CS) versus interrupted suture (IS) by analysing airway complications requiring intervention. METHODS Lung transplantations between January 2015 and December 2020 were included. Airway complications requiring intervention were classified following the 2018 International Society for Heart and Lung Transplantation consensus and analysed comparing 3 groups of patients according to surgical technique: group A, both anastomosis performed with CS; group B, both with interrupted; and group C, IS for 1 side and CS for the contralateral side. RESULTS A total of 461 anastomoses were performed in 245 patients. The incidence of airway complications requiring intervention was 5.7% [95% confidence interval (CI): 2.8–8.6] per patient (14/245) and 3.7% (95% CI: 2.0–5.4) per anastomosis (17/461). Complications that required intervention were present in 5 out of 164 (3.1%) anastomosis with interrupted technique, and in 12/240 (5%) with CS. No significant differences were found between techniques (P = 0.184). No statistical differences were found among group A, B or C in terms of incidence of anastomotic complications, demographics, transplant outcomes or overall survival (log-rank P = 0.513). In a multivariable analysis, right laterality was significantly associated to complications requiring intervention (OR 3.7 [95% CI: 1.1–12.3], P = 0.030). Endoscopic treatment was successful in 12 patients (85.7%). Retransplantation was necessary in 2 patients. CONCLUSIONS In summary, although it seems that anastomotic complications requiring intervention occur more frequently with CS, there are no statistical differences compared to IS. Endoscopic treatment offers good outcomes in most of the airway complications after lung transplantation.

17 páginas, 6 figuras, Background and aims: Hepatic ischemia-reperfusion injury (IRI) is the leading cause of early posttransplantation organ failure as mitochondrial respiration and ATP production are affected. A shortage of donors has extended liver donor criteria, including aged or steatotic livers, which are more susceptible to IRI. Given the lack of an effective treatment and the extensive transplantation waitlist, we aimed at characterizing the effects of an accelerated mitochondrial activity by silencing methylation-controlled J protein (MCJ) in three preclinical models of IRI and liver regeneration, focusing on metabolically compromised animal models. Approach and results: Wild-type (WT), MCJ knockout (KO), and Mcj silenced WT mice were subjected to 70% partial hepatectomy (Phx), prolonged IRI, and 70% Phx with IRI. Old and young mice with metabolic syndrome were also subjected to these procedures. Expression of MCJ, an endogenous negative regulator of mitochondrial respiration, increases in preclinical models of Phx with or without vascular occlusion and in donor livers. Mice lacking MCJ initiate liver regeneration 12 h faster than WT and show reduced ischemic injury and increased survival. MCJ knockdown enables a mitochondrial adaptation that restores the bioenergetic supply for enhanced regeneration and prevents cell death after IRI. Mechanistically, increased ATP secretion facilitates the early activation of Kupffer cells and production of TNF, IL-6, and heparin-binding EGF, accelerating the priming phase and the progression through G1 /S transition during liver regeneration. Therapeutic silencing of MCJ in 15-month-old mice and in mice fed a high-fat/high-fructose diet for 12 weeks improves mitochondrial respiration, reduces steatosis, and overcomes regenerative limitations. Conclusions: Boosting mitochondrial activity by silencing MCJ could pave the way for a protective approach after major liver resection or IRI, especially in metabolically compromised, IRI-susceptible organs.

OBJECTIVES Controlled donation after circulatory death (cDCD) donors are becoming a common source of organs for transplantation globally. However, the graft survival rate of cDCD abdominal organs is inferior to that of organs from brain-dead donors. The rapid retrieval (RR) technique is used by most donor organ procurement teams. The abdominal normothermic regional perfusion (A-NRP) technique has been implemented to minimize warm ischaemic damage to the abdominal organs. However, there is limited information on the effect of A-NRP on the quality of the donor lungs. This study aimed to compare lung transplantation outcomes using lungs procured from cDCD donors using the A-NRP and abdominal RR techniques. METHODS A single-centre retrospective analysis of consecutive transplant recipients of cDCD lungs from June 2013 to December 2019 was performed. The recipients were divided into 2 cohorts according to the abdominal procurement technique used. The recipient and donor characteristics (age, sex, cause of brain injury, warm ischaemic time, diagnosis, lung allocation score and other factors), incidence of primary graft dysfunction and early survival were monitored. RESULTS Twenty-eight consecutive lung transplantation recipients were identified (median age 59 years; 61% male); 14 recipients received lungs using the A-NRP and 14 using abdominal RR for abdominal organ retrieval. There were no significant differences in the baseline characteristics, primary graft dysfunction (P = 0.70), hospital mortality (P = 1.0) and 1-year survival rate (P = 1.0) between the 2 groups. CONCLUSIONS No difference was observed in lung transplantation outcomes irrespective of the abdominal organ procurement technique used (A-NRP or abdominal RR).

Introduction Controlled donation after circulatory-death donors (cDCD) are becoming a frequent source of lungs grafts worldwide. Conversely, lung transplantations (LTx) from uncontrolled donors (uDCD) are sporadically reported. We aimed to review our institutional experience using both uDCD and cDCD and compare to LTx from brain death donors (DBD). Methods This is a retrospective analysis of all LTx performed between January 2013- December 2019 in our institution. Donor and recipient characteristics were collected and univariate, multivariate and survival analyses were carried out comparing the three cohorts of donors. Results A total of 239 (84.7%) LTx were performed from DBD, 29 (10.3%) from cDCD and 14 (5%) from uDCD. There were no statistically significant differences in primary graft dysfunction grade 3 at 72 hours, 30- and 90-day mortality, need for extracorporeal membrane oxygenation after procedure, ICU and hospital length of stay, airway complications, CLAD incidence or survival at 1 and 3 years after transplant (DBD: 87.1% and 78.1%; cDCD: 89.7% and 89.7%; uDCD: 85.7% and 85.7%, respectively; p=0.42). Short- and mid-term outcomes are comparable between the three types of donors. Conclusions These findings may encourage and reinforce all types of donation after circulatory-death programmes as a valid and growing source of suitable organs for transplantation.

Normothermic Regional Perfusion (NRP) allows the in situ perfusion of organs with oxygenated blood in donation after the circulatory determination of death (DCDD). We aimed at evaluating the impact of NRP on the short-term outcomes of kidney transplants in controlled DCDD (cDCDD). This is a multicenter, nationwide, retrospective study comparing cDCDD kidneys obtained with NRP versus the standard rapid recovery (RR) technique. During 2012-2018, 2,302 cDCDD adult kidney transplants were performed in Spain using NRP (n=865) or RR (n=1,437). The study groups differed in donor and recipient age, warm and cold ischemic time and use of ex situ machine perfusion. Transplants in the NRP group were more frequently performed in high-volume centers (=90 transplants/year). Through matching by propensity score, two cohorts with a total of 770 patients were obtained. After the matching, no statistically significant differences were observed between the groups in terms of primary non function (p=0.261) and mortality at one year (p=0.111). However, the RR of kidneys was associated with a significantly increased odds of delayed graft function (OR 1.97 [95%CI 1.43-2.72]; p

Heart transplantation from controlled donation after the circulatory determination of death (cDCDD) may help to increase the availability of hearts for transplantation. During 2020, four heart transplants were performed at three different Spanish hospitals based on the use of thoraco-abdominal normothermic regional perfusion (TA-NRP) followed by cold storage (CS). All donors were young adults

Background Controlled donation after circulatory death (cDCD) has emerged as one of the main strategies for increasing the organ donor pool. Because of the ischemic injury that follows the withdrawal of life-sustaining therapies, hearts from cDCD donors have not been considered for transplantation until recently. The ex-situ perfusion of hearts directly procured from cDCD donors has been used to allow the continuous perfusion of the organ and the assessment of myocardial viability prior to transplantation. Based on our experience with abdominal normothermic regional perfusion in cDCD, we designed a protocol to recover and validate hearts from cDCD donors using thoraco-abdominal normothermic regional perfusion without the utilization of an ex-situ device. Case presentation We describe the first case of a cDCD heart transplant performed with this approach in Spain. The donor was a 43-year-old asthmatic female diagnosed with severe hypoxic encephalopathy. She was considered a potential cDCD donor and a suitable candidate for multiorgan procurement including the heart via thoraco-abdominal normothermic regional perfusion. The heart recipient was a 60-year-old male diagnosed with amyloid cardiomyopathy. Cold ischemia time was 55 min. The surgery was uneventful. Conclusions This case report, the first of its kind in Spain, supports the feasibility of evaluating and successfully transplanting cDCD hearts without the need for ex-situ perfusion based on the use of thoraco-abdominal normothermic regional perfusion opening the way for multiorgan donation in cDCD.

BackgroundControlled donation after circulatory death (cDCD) has emerged as one of the main strategies for increasing the organ donor pool. Because of the ischemic injury that follows the withdrawal of life-sustaining therapies, hearts from cDCD donors have not been considered for transplantation until recently. The ex-situ perfusion of hearts directly procured from cDCD donors has been used to allow the continuous perfusion of the organ and the assessment of myocardial viability prior to transplantation. Based on our experience with abdominal normothermic regional perfusion in cDCD, we designed a protocol to recover and validate hearts from cDCD donors using thoraco-abdominal normothermic regional perfusion without the utilization of an ex-situ device.Case presentationWe describe the first case of a cDCD heart transplant performed with this approach in Spain. The donor was a 43-year-old asthmatic female diagnosed with severe hypoxic encephalopathy. She was considered a potential cDCD donor and a suitable candidate for multiorgan procurement including the heart via thoraco-abdominal normothermic regional perfusion. The heart recipient was a 60-year-old male diagnosed with amyloid cardiomyopathy. Cold ischemia time was 55 minutes. The surgery was uneventful.ConclusionsThis case report, the first of its kind in Spain, supports the feasibility of evaluating and successfully transplanting cDCD hearts without the need for ex-situ perfusion based on the use of thoraco-abdominal normothermic regional perfusion opening the way for multiorgan donation in cDCD.

OBJECTIVES Most transplant centres use donation after brain death (DBD) criteria to assess the quality of controlled donation after circulatory death (cDCD) lungs. However, research on the relationship between DBD extended criteria and cDCD lung transplantation outcomes is limited. We investigated the outcomes of using DBD extended criteria donor organs in cDCD lung transplantation, compared to the standard criteria cDCD lung transplantation. METHODS A retrospective chart review of consecutive cDCD lung referrals to Hospital Universitario Puerta de Hierro-Majadahonda from June 2013 to December 2019 was undertaken. Donors were divided into standard and extended criteria groups. Early outcomes after lung transplant were compared between these groups using the Kaplan–Meier method and log-rank test. RESULTS Thirty out of 91 cDCD donor lung offers were accepted for transplantation, of which 11 were from standard criteria donors and 19 were extended criteria donors. The baseline characteristics of the 2 recipient groups were similar. There were no differences in the rates of grade 3 primary graft dysfunction at 72 h after lung transplantation (21% vs 18%), duration of mechanical ventilation (48 h vs 36 h), total intensive care unit stay (10 days vs 7 days) and 1-year survival (89% vs 90%). CONCLUSIONS Carefully selecting cDCD lungs from outside the standard acceptability criteria may expand the existing donor pool with no detrimental effects on lung transplantation outcomes.

Normothermic regional perfusion (NRP) in controlled donation after circulatory death is becoming a popular method due to the favorable results of the grafts procured under this technique. This procedure requires experience, and, sometimes, the availability of extracorporeal membrane oxygenation (ECMO) machines to implement NRP is limited to tertiary hospitals. In order to provide support with NRP in controlled donation after circulatory death across the different hospitals of the Autonomous Community of Madrid, a mobile NRP team was created. In the first 18 months since its creation, the mobile NRP team participated in 33 procurements across nine different hospitals, representing 72% of all controlled donations after circulatory death in the Autonomous Community of Madrid. NRP was successfully performed in 29 (88%) cases, with a mean duration of 69 ± 27 minutes. A total of 39 kidneys, 12 livers, and 5 bilateral lungs were recovered and transplanted. None of the livers were discarded due to an elevation in transaminases during NRP. A mobile NRP team is a feasible option and, in our series, aided in the optimization and recovery of organs from donors after controlled circulatory death in centers where ECMO technology was not available.

To describe the characteristics and the evolution of patients with solid tumours admitted to the ICU and to identify factors associated with hospital mortality and to evaluate three illness severity scores.Descriptive study including 132 patients with solid tumour admitted to the ICU (2010-2016). Demographics and cancer-related data, organ failures, life-supporting therapies and severity scores: APACHE II, SOFA and ICU Cancer Mortality Model (ICMM) were collected.There were 58 patients admitted for medical reasons and 74 for scheduled surgery. The ICU and hospital mortality rate were 12.9% and 19.7%, respectively. The medical reason for admission, the number of organ failures, and the need of life-supporting therapies were significantly associated with a higher mortality (p0.05). In the logistic regression analysis, the three severity scores: SOFA (OR 1.18, 95% IC 1.14-1.48), APACHE II (OR 1.11, 95% CI 1.09-1.27), and ICMM (OR 1.03, 95% CI 1.02-1.07) were independently associated with a higher mortality (p0.05). To evaluate the discrimination, the area under the receiver operating characteristics curves (AUROC) were calculated: APACHE II (0.795, 95% CI 0.69-0.9), SOFA (0.77, 95% CI 0.69-0.864) and ICMM (0.794, 95% CI 0.697-0.891). The comparison of AUC ROC after DeLong's test showed no difference between them.Hospital mortality was associated with the type and severity of acute illness. The three severity scores were useful to assess outcome and accurate in the discrimination, but we did not find a significant difference between them.

AIMS The aim of this study was to evaluate the effectiveness of local low-dose urokinase thrombolysis (LLDUT) in haemodynamically stable pulmonary embolism with right ventricular dysfunction (RVD). METHODS AND RESULTS This was a prospective study. LLDUT with a 200,000 IU bolus followed by a 100,000 IU/hr infusion was given. Treatment duration was determined through radiological control performed 48-72 hrs into treatment. A follow-up echocardiogram was performed within seven days after LLDUT completion. Evolution of thrombus burden, pulmonary artery pressures (PAP) and RVD were studied, and haemorrhagic complications and mortality were recorded. Eighty-seven patients were included (62.5±16.5 years). In 67 patients (77%), the baseline echocardiogram showed mild-to-severe RVD, a dilated right ventricle (diameter: 44.4±6.2 mm) and a decreased tricuspid annular plane systolic excursion (14 mm [12-17]). Seventy-six patients (87.4%) experienced radiological improvement. Initially high PAP (mmHg) decreased after LLDUT: systolic 52.4 vs. 35.2 (17.2 [95% CI: 14.5-19.9]; p

Although the number of lung transplants in Spain is increasing annually, more organs are required to ease waiting lists. Controlled non-heart beating donors (cNHBD) (Maastricht III) are a reality at international level, and contribute significantly to increasing donor numbers. In this study, we present our cNHBD protocol and the initial experience in Spain using lung grafts from this type of donor. Three bilateral lung transplants were performed between January 2012 and December 2014. Preservation was by ex vivo lung perfusion in 2 cases and by traditional cold perfusion in the other. None of the patients developed grade 3 primary graft dysfunction, no in-hospital mortality was recorded and 1-year survival was 100%. These initial results, and international experience, should help to develop similar protocols to encourage the use of controlled non-heart beating donors.

Although the number of lung transplants in Spain is increasing annually, more organs are required to ease waiting lists. Controlled non-heart beating donors (NHBD) (Maastricht III) are a reality at international level, and contribute significantly to increasing donor numbers. In this study, we present our NHBD protocol and the initial experience in Spain using lung grafts from this type of donor. Three bilateral lung transplants were performed between January 2012 and December 2014. Preservation was by ex-vivo lung perfusion in 2 cases and by traditional cold ischemia in the other. None of the patients developed grade 3 primary graft dysfunction, no in-hospital mortality was recorded and 1-year survival was 100%. These initial results, and international experience, should help to develop similar protocols to encourage the use of controlled non-heart beating donors.

Resumen Objetivo Estudiar el impacto en la mortalidad y morbilidad en pacientes criticos de las bacteriemias primarias (BP) y relacionadas con cateteres intravasculares (BRC) causadas por Staphylococcus coagulasa negativo (SCN). Diseno Doble analisis con datos del registro ENVIN-HELICS (1997 a 2008): 1) analizar las caracteristicas clinicas de pacientes con BP/BRC causadas por SCN, comparandolas con las de los pacientes con BP/BRC causadas por otros patogenos; y 2) analizar mediante un estudio casos-controles (1:4) el impacto de BP/BRC por SCN en pacientes sin otras infecciones nosocomiales frente a pacientes sin ninguna infeccion nosocomial. Ambito Ciento sesenta y siete UCI espanolas. Pacientes Pacientes ingresados en UCI mas de 24 horas. Intervencion Ninguna. Variables de interes Estancia en UCI y mortalidad. Resultados Dos mil doscientos cincuenta y dos pacientes presentaron BP/BRC de los que 1.133 casos fueron por SCN. La mortalidad de los pacientes con BP/BRC causadas por patogenos distintos de SCN fue superior (29,8% vs. 25,9%; p = 0,039), debido exclusivamente a la mortalidad de pacientes con candidemia (mortalidad: 45,9%). En pacientes sin otras infecciones nosocomiales, la BP/BRC por SCN (414 pacientes) es un factor independiente de riesgo de tener una estancia superior a la media (OR 5,81; IC 95%: 4,31-7,82; p Conclusion La mortalidad cruda de los pacientes que padecieron BP/BRC causada por SCN es similar a la de los pacientes con BP/BRC causada por otras bacterias, pero inferior a la de los pacientes con candidemia. Comparandolo con la estancia en UCI de pacientes sin infecciones nosocomiales, la BP/BRC por SCN es un factor apreciable de prolongacion de estancia.