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The lung microbiome plays a crucial role in the development of chronic lung diseases, which may ultimately lead to the need for lung transplantation. Also, perioperative results seem to be connected with altered lung microbiomes and its dynamic changes providing a possible target for optimizing short-term outcome after transplantation. A literature review using MEDLINE, PubMed Central and Bookshelf was performed. Chronic lung allograft dysfunction (CLAD) seems to be influenced and partly triggered by changes in the pulmonary microbiome and dysbiosis, e.g. through increased bacterial load or abundance of specific species such as Pseudomonas aeruginosa. Additionally, the specific indications for transplantation, with their very heterogeneous changes and influences on the pulmonary microbiome, influence long-term outcome. Next to composition and measurable bacterial load, dynamic changes in the allografts microbiome also possess the ability to alter long-term outcomes negatively. This review discusses the "new" microbiome after transplantation and the associations with direct postoperative outcome. With the knowledge of these principles the impact of alterations in the pulmonary microbiome in hindsight to CLAD and possible therapeutic implications are described and discussed. The aim of this review is to summarize the current literature regarding pre- and postoperative lung microbiomes and how they influence different lung diseases on their progression to failure of conservative treatment. This review provides a summary of current literature for centres looking for further options in optimizing lung transplant outcomes and highlights possible areas for further research activities investigating the pulmonary microbiome in connection to transplantation. [ABSTRACT FROM AUTHOR]

Introduction: Donor-specific antibodies (DSAs) correspond to anti-HLA antibodies of the recipient that are specifically directed to a mismatched antigen of the donor. In the setting of solid organ transplantation DSAs are associated with rejection. Their role is still debated in allogeneic cell transplantation. International guidelines recommend testing patients for DSA before transplant, and if possible, choosing a donor with negative screening. Methods: We collected clinical data of 236 recipients of alloSCT, performed at our institution from March 2019 to October 2023, to evaluate their impact on engraftment. Serum from all patients was tested for DSA. Results: 186 patients (79%) achieved sustained myeloid engraftment within day 30 post alloSCT. Thirty-two out 236 (13%) patients engrafted after day 30 post alloSCT. The median times to neutrophil engraftment and platelet engraftment were respectively 21 days (range 11-121 days) and 19 days (range 10-203 days). Fourteen out 236 patients (6%) experienced PrGF. .Twenty-nine patients (12 %) were DSA-positive. Among 29 patients with DSA positivity, 17 had a haploidentical donor and 12 had a UD donor. DSA positivity directly correlates respectively with neutrophil and platelets engraftment failure at 30 days after alloSCT (p=0.01 and p= 0.0004). Univariate Cox analysis showed that factors, including DSAs positivity, disease type, disease status, donor type, conditioning regimen, patient's age, and CD34+ were correlated with neutrophil and platelet engraftment failure at 30 days after alloSCT. Younger patients with DSA negativity, with acute leukemia, in complete response at the time of transplant, who received a higher dose of CD34+ cells from a sibling donor after a myeloablative conditioning regimen, have a reduced risk of neutrophil and platelet engraftment failure at day +30 post alloSCT.Multivariate analysis confirmed the impact of the presence of DSA only for platelet engraftment, confirming the role of type and status disease, donor type, recipient age, and CD34+ cells infused on engraftment. DSA presence has no impact on TRM, DFS, and OS. Discussion: PrGF has a multifactorial pathogenesis, where DSA is not the only player, but its impact could vary depending on the transplant platform. Thus patient screening may be helpful to choose the best donor and transplant strategy. [ABSTRACT FROM AUTHOR]

Impacts of ischemic time (IT) on pediatric heart transplant outcomes are multifactorial. We aimed to analyze the effect of prolonged IT on graft loss after pediatric heart transplantation. We hypothesized that graft survival with prolonged IT has improved across eras. Patients <18 years old in the Pediatric Heart Transplant Society database were included (N=6,765) and stratified by diagnosis and era (1993-2004, 2005-2009, and 2010-2019). Severe graft failure (SGF) was defined as death, retransplant, or need for mechanical circulatory support in the first 7 days post-transplant. Descriptive statistical methods were used to compare differences between patient characteristics and IT. Kaplan-Meier survival analysis compared freedom from graft loss, rejection, and infection. Multivariable analysis was performed for graft loss and SGF (hazard and logistic regression modeling, respectively). Diagnoses were cardiomyopathy (N = 3,246) and congenital heart disease (CHD; N = 3,305). CHD were younger, more likely to have an IT ≥4.5 hours, and more likely to require extracorporeal membrane oxygenation or mechanical ventilation at transplant (all p < 0.001). Median IT was 3.6 hours (interquartile range 2.98-4.31; range 0-10.5). IT was associated with early graft loss (HR 1.012, 95% CI 1.005-1.019), but not when analyzed only in the most recent era. IT was associated with SGF (OR 1.016 95%CI 1.003-1.030). Donor IT was independently associated with an increased risk of graft loss, albeit with a small effect relative to other risk factors. Graft survival with prolonged IT has improved in the most recent era but the risk of SGF persists. [ABSTRACT FROM AUTHOR]

ABSTRACTObjectives: Primary graft failure (pGF) after hematopoietic stem-cell transplant is associated with considerable morbidity and mortality. The incidence in haplo-HSCT has been reported to be between 0% and 30%. In 2018, we identified a pGF incidence of 35% in our pediatric haplo-HSCT recipients with hematologic malignancies, which motivated us to enact changes to the conditioning regimen.Methods: We performed a single-center prospective, pre–post study of consecutive patients under 16 years with hematologic malignancies, from January 2015 to December 2022 who received a haplo-HSCT. Twenty-six pediatric patients received a haplo-HSCT before September 2018 (G1) and 36 patients after (G2). The main conditioning regimen for G1 was myeloablative with Flu/Cy/Bu, and for G2 the main regimen was reduced intensity Flu/Cy/Mel/TBI2.Results: Nine patients (35%) in G1 had primary graft failure, while in G2 there were no patients with pGF. The median follow-up for G1 was 15.9 months, and for G2 was 24.8 months, with an estimated overall survival at 12 months of 63% (95% CI 47–76) versus 85% (95% CI 73–93), and at 24 months of 47% (95% CI 31–64) versus 70% (95% CI 54–82) respectively (p = .007).Conclusion: After September 2018 conditioning regimen modifications were implemented with the objective of reducing primary failure, consisting mainly of switching from busulfan to melphalan as the alkylating agent of choice, and adding, when clinically possible TBI. Primary failure has been significantly reduced in our institution since then.

Open in new tab Download slide OBJECTIVES The aim of this study was to compare the outcomes of lung transplantations using grafts from donors aged over 70 years against those performed using younger donors. METHODS This retrospective single-centre analysis includes lung transplants conducted at our institution from January 2014 to June 2022. Lung recipients were classified into 2 groups based on donor age (group A <70 years; group B ≥70 years). Variables regarding demographics, peri and postoperative outcomes and survival were included. The statistical analysis approach included univariable analysis, propensity score matching to address imbalances in donor variables (smoking status), recipient characteristics (sex, age, diagnosis and lung allocation score) and calendar period and survival analysis. RESULTS A total of 353 lung transplants were performed in this period, 47 (13.3%) using grafts from donors aged over 70 years. Donors in group B were more frequently women (70.2% vs 51.6%, P  = 0.017), with less smoking history (22% vs 43%, P  = 0.002) and longer mechanical ventilation time (3 vs 2 days, P  = 0.025). Recipients in group B had a higher lung allocation score (37.5 vs 35, P  = 0.035). Postoperative variables were comparable between both groups, except for pulmonary function tests. Group B demonstrated lower forced expiratory volume 1 s levels (2070 vs 2580 ml, P  = 0.001). The propensity score matching showed a lower chance of chronic lung allograft dysfunction by 12% for group B. One-, three- and five-year survival was equal between the groups. CONCLUSIONS The use of selected expanded-criteria donors aged over 70 years did not result in increased postoperative morbidity, early mortality or survival in this study. [ABSTRACT FROM AUTHOR]

IntroductionDonor-specific antibodies (DSAs) correspond to anti-HLA antibodies of the recipient that are specifically directed to a mismatched antigen of the donor. In the setting of solid organ transplantation DSAs are associated with rejection. Their role is still debated in allogeneic cell transplantation. International guidelines recommend testing patients for DSA before transplant, and if possible, choosing a donor with negative screening.MethodsWe collected clinical data of 236 recipients of alloSCT, performed at our institution from March 2019 to October 2023, to evaluate their impact on engraftment. Serum from all patients was tested for DSA.Results186 patients (79%) achieved sustained myeloid engraftment within day 30 post alloSCT. Thirty-two out 236 (13%) patients engrafted after day 30 post alloSCT. The median times to neutrophil engraftment and platelet engraftment were respectively 21 days (range 11-121 days) and 19 days (range 10-203 days). Fourteen out 236 patients (6%) experienced PrGF. .Twenty-nine patients (12 %) were DSA-positive. Among 29 patients with DSA positivity, 17 had a haploidentical donor and 12 had a UD donor. DSA positivity directly correlates respectively with neutrophil and platelets engraftment failure at 30 days after alloSCT (p=0.01 and p= 0.0004). Univariate Cox analysis showed that factors, including DSAs positivity, disease type, disease status, donor type, conditioning regimen, patient's age, and CD34+ were correlated with neutrophil and platelet engraftment failure at 30 days after alloSCT. Younger patients with DSA negativity, with acute leukemia, in complete response at the time of transplant, who received a higher dose of CD34+ cells from a sibling donor after a myeloablative conditioning regimen, have a reduced risk of neutrophil and platelet engraftment failure at day +30 post alloSCT.Multivariate analysis confirmed the impact of the presence of DSA only for platelet engraftment, confirming the role of type and status disease, donor type, recipient age, and CD34+ cells infused on engraftment. DSA presence has no impact on TRM, DFS, and OS.DiscussionPrGF has a multifactorial pathogenesis, where DSA is not the only player, but its impact could vary depending on the transplant platform. Thus patient screening may be helpful to choose the best donor and transplant strategy.

Introduction: Orthotopic cardiac xenotransplantation has seen notable improvement, leading to the first compassionate use in 2022. However, it remains challenging to define the clinical application of cardiac xenotransplantation, including the back‐up strategy in case of xenograft failure. In this regard, the heterotopic thoracic technique could be an alternative to the orthotopic procedure. We present hemodynamic data of heterotopic thoracic pig‐to‐baboon transplantation experiments, focusing on perioperative xenograft dysfunction and xenograft overgrowth. Methods: We used 17 genetically modified piglets as donors for heterotopic thoracic xenogeneic cardiac transplantation into captive‐bred baboons. In all animals, pressure probes were implanted in the graft's left ventricle and the recipient's ascending aorta and hemodynamic data (graft pressure, aortic pressure and recipient's heart rate) were recorded continuously. Results: Aortic pressures and heart rates of the recipients' hearts were postoperatively stable in all experiments. After reperfusion, three grafts presented with low left ventricular pressure indicating perioperative cardiac dysfunction (PCXD). These animals recovered from PCXD within 48 h under support of the recipient's heart and there was no difference in survival compared to the other 14 ones. After 48 h, graft pressure increased up to 200 mmHg in all 17 animals with two different time‐patterns. This led to a progressive gradient between graft and aortic pressure. With increasing gradient, the grafts stopped contributing to cardiac output. Grafts showed a marked weight increase from implantation to explantation. Conclusion: The heterotopic thoracic cardiac xenotransplantation technique is a possible method to overcome PCXD in early clinical trials and an experimental tool to get a better understanding of PCXD. The peculiar hemodynamic situation of increasing graft pressure but missing graft's output indicates outflow tract obstruction due to cardiac overgrowth. The heterotopic thoracic technique should be successful when using current strategies of immunosuppression, organ preservation and donor pigs with smaller body and organ size. [ABSTRACT FROM AUTHOR]

Objective To evaluate the effect of body mass index (BMI) on early prognosis of the recipients after lung transplantation. Methods Clinical data of 307 lung transplant recipients were retrospectively analyzed. According to preoperative BMI, all recipients were divided into the low (BMI <18.5 kg/m2, n=114), normal (18.5 kg/m2 İBMI <24 kg/m2, n=145) and high (BMIı24.0 kg/m2, n=48) BMI groups, respectively. Baseline data including age, sex, blood type, BMI, preoperative complications, preoperative pulmonary hypertension, and intraoperative use of extracorporeal membrane oxygenation (ECMO) of all recipients were compared among three groups. The survival rate of all recipients was estimated by Kaplan-Meier curve and the survival curve was delineated. The differences of survival rate were analyzed by log-rank test. The 30-, 90- and 180-d mortality risk of all recipients after lung transplantation in different BMI groups was compared by multivariate Cox regression analysis. Results There were significant differences in age and sex of recipients among three groups (both P<0.05). There was a significant difference regarding the 180-d survival rate after lung transplantation among different BMI groups (P<0.05). Multivariate Cox regression analysis showed that the 90-d mortality risk after lung transplantation in the high BMI group was 2.295 times higher than that in the normal BMI group [hazard ratio (HR) 2.295, 95% confidence interval (CI) 1.064-4.947, P=0.034]. In the high BMI group, the 180-d mortality risk after lung transplantation was 2.783 times higher compared with that in the normal BMI group (HR 2.783, 95%CI 1.333- 5.810, P=0.006), and the 180-d mortality risk in the low BMI group was 2.181 times higher than that in the normal BMI group (HR 2.181, 95%CI 1.124-4.232, P=0.021). Conclusions Compared with the recipients with normal BMI, their counterparts with high and low preoperative BMI have higher mortality risk early after lung transplantation. Adjusting preoperative BMI to normal range contributes to improving early prognosis of lung transplant recipients. [ABSTRACT FROM AUTHOR]

Bharat Gurnani,1 Kirandeep Kaur,2 Vaitheeswaran Ganesan Lalgudi,3 Koushik Tripathy4 1Department of Cornea and Refractive Surgery, Sadguru Netra Chikitsalaya, Shri Sadguru Seva Sangh Trust, Janaki-kund, Madhya Pradesh, India; 2Department of Pediatric Ophthalmology, Sadguru Netra Chikitsalaya, Shri Sadguru Seva Sangh Trust, Janaki-kund, Madhya Pradesh, India; 3Department of Cornea, The Ottawa Hospital, University of Ottawa Eye Institute, Ontario, Canada; 4Department of Vitreoretinal and Cataract, ASG Eye Hospital, Kolkata, West Bengal, IndiaCorrespondence: Bharat Gurnani, Consultant, Cataract, Cornea, External Diseases, Trauma, Ocular Surface, Uvea and Refractive Surgery, Sadguru Netra Chikitsalaya, Shri Sadguru Seva Sangh Trust, Janaki-kund, Madhya Pradesh, 485334, India, Tel +919080523059, Email drgurnanibharat25@gmail.comAbstract: Descemet membrane endothelial keratoplasty (DMEK) is a corneal endothelial transplantation procedure with selective removal of a patient’s defective Descemet membrane and endothelium. It is replaced with a healthy donor Descemet membrane and endothelium without a stromal component. Corneal graft rejection can be at the level of epithelium, stroma as well endothelium. DMEK graft rejection is relatively less common than rejection with DSAEK or penetrating keratoplasty, and a good outcome may be achieved with prompt management. The clinical picture of DMEK rejection is usually similar to endothelial rejection in Descemet Stripping Endothelial Keratoplasty (DSEK/DSAEK), which generally manifests as pain, redness, reduction in visual acuity, stromal edema, endothelial rejection line, keratic precipitates at the back of the cornea and corneal neovascularization. However, more subtle forms of rejection or immune reactions are more common in DMEK compared to DSAEK eyes. Early clinical diagnosis, prompt intervention, and meticulous management safeguard visual acuity and graft survival in these cases. Intensive topical steroids form the mainstay in the management of DMEK rejection. Sometimes, oral or intravenous steroids or other systemic immunomodulators may be required. DMEK graft failure can be primary or secondary, and failure usually requires a second procedure in the form of repeat DMEK or DSEK or penetrating keratoplasty (PKP). A detailed literature search was performed using search engines such as Google Scholar, PubMed, and Google books, and a comprehensive review on DMEK rejection was found to be lacking. This review is a comprehensive update on the risk factors, pathophysiology, primary and secondary graft failure, recent advances in diagnosis, prevention of rejection, and updates in the management of DMEK rejection. The review also discusses the differential diagnosis of DMEK failure and rejection, prognosis, and future perspectives considering DMEK failure and rejection.Keywords: descemet membrane endothelial keratoplasty, DMEK rejection, primary graft failure, secondary graft failure, rebubbling

Background: Primary graft failure (PGF) remains the most common cause of short-term mortality after heart transplantation. The main objective was to develop and validate a risk model for prediction of short-term mortality due to PGF after heart transplantation using the ISHLT Heart Transplant Registry. Methods: We developed a non-linear artificial neural networks (ANN) model to evaluate the association between recipient-donor variables and post-transplant PGF. Patients in the ISHLT registry were randomly divided into derivation and an independent internal validation cohort. The primary endpoint was PGF defined as death within 30 days due to Graft failure or Cardiovascular causes or retransplant within 30 days for causes other than rejection. Results: Among 64,964 adult recipients transplanted between 1994 and 2013, mean age was 51 years and 22% were female. The incidence of PGF up to 30 days was 3.7%. The ANN model selected 33 of 77 risk variables as relevant for PGF prediction. The C-index in the test cohort was 0.70 (95% CI: 0.68-0.71). The risk variables which most influenced the PGF were underlying HF diagnosis, ischemia time and sex, while renal function had a lower influence. Conclusion: An ANN model to predict primary graft dysfunction was derived and independently validated. The good discrimination of the ANN model likely results from its flexibility to model potentially non-linear relationships and interactions. Whether this model with improved discrimination can assist in clinical decisions at the time of transplant should be tested.

Introduction and importance: This report details the clinical features and management in a case of Descemet stripping automated endothelial keratoplasty (DSAEK) which had primary graft failure (PGF) due to an inverted yet attached lenticule. Presentation of case: A 66-year-old gentleman had poor visual recovery in the right eye after undergoing cataract surgery 12 years prior to presentation. The visual acuity was counting fingers and examination revealed endothelial decompensation. The patient underwent a DSAEK and postoperatively had a well attached lenticule. However, the cornea was edematous three weeks after the surgery and optical coherence tomography (OCT) revealed a reversed lenticule. The patient underwent a repeat DSAEK and had an uneventful postoperative course. The visual acuity was 20/40 after 7 months with a clear cornea and a well attached graft. Discussion: PGF is a rare complication following DSAEK which occurs due to poor endothelial function of the donor graft. Insertion of a reversed lenticule may get overlooked as a cause of PGF unless the graft edge profile is examined on an OCT scan. The graft in the current case was well attached despite its inverted position suggesting that graft adherence is perhaps not a function of the corneal endothelial pumps in isolation and may be driven by factors such as the intraocular pressure. Conclusion: A reversed DSAEK lenticule may have normal adherence to the host stroma and must be considered in cases with PGF. OCT of the graft edge is required for diagnosis before performing a repeat keratoplasty.

Introduction and importance: This report details the clinical features and management in a case of Descemet stripping automated endothelial keratoplasty (DSAEK) which had primary graft failure (PGF) due to an inverted yet attached lenticule. Presentation of case: A 66-year-old gentleman had poor visual recovery in the right eye after undergoing cataract surgery 12 years prior to presentation. The visual acuity was counting fingers and examination revealed endothelial decompensation. The patient underwent a DSAEK and postoperatively had a well attached lenticule. However, the cornea was edematous three weeks after the surgery and optical coherence tomography (OCT) revealed a reversed lenticule. The patient underwent a repeat DSAEK and had an uneventful postoperative course. The visual acuity was 20/40 after 7 months with a clear cornea and a well attached graft. Discussion: PGF is a rare complication following DSAEK which occurs due to poor endothelial function of the donor graft. Insertion of a reversed lenticule may get overlooked as a cause of PGF unless the graft edge profile is examined on an OCT scan. The graft in the current case was well attached despite its inverted position suggesting that graft adherence is perhaps not a function of the corneal endothelial pumps in isolation and may be driven by factors such as the intraocular pressure. Conclusion: A reversed DSAEK lenticule may have normal adherence to the host stroma and must be considered in cases with PGF. OCT of the graft edge is required for diagnosis before performing a repeat keratoplasty.

Abstract Background Primary graft dysfunction (PGD) is the main cause of death in the first 30 days after heart transplantation (HTX), accounting for approximately 40% of mortality. The study’s primary aim was to assess the incidence of PGD, following the International Society for Heart and Lung Transplantation consensus, and to compare it with the incidence of significant postoperative hypotension despite administration of high-dose inotropes and vasoconstrictors. The secondary aim of the study was to determine changes in biochemical markers that accompany the phenomenon. Methods Forty-five patients who underwent HTX between 2010 and 2015 were enrolled in this study, and detailed hemodynamic and metabolic data from the first 48 postoperative hours were collected and analyzed. Hemodynamic instability was defined as significant postoperative hypotension (mean arterial pressure (MAP) 10). Data for long-term mortality were obtained from the population registration office. Results PGD incidence was relatively low (17.8%); however, hemodynamic instability was common (40%). Among unstable patients, MAP was insufficient for end-organ perfusion (51.4 ± 9.5 mmHg) but no decrease in left ventricular function was observed (cardiac index, 2.65 ± 0.6 l/min/m2; left ventricular ejection fraction, 52.9 ± 15.5%). Within this group, mean systemic vascular resistance index (961 ± 288 dyn*s*m2/cm5) was low despite receiving high doses of vasoactive agent (norepinephrine 0.21 (0.06-0.27) μg/kg/min during first 24 h postoperatively and 0.21 (0.01-0.27) μg/kg/min during next 24 h postoperatively). After HTX, serum lactate levels were initially significantly higher in patients with hemodynamic instability (p = 0.002); however, impaired lactate clearance was not observed (p = 0.366), and lactate levels normalized within the first 24 h postoperatively. Postoperative hemodynamic instability altered the long-term outcome and increased 5-year mortality after HTX (p = 0.034). Conclusions Hemodynamic instability is a more common phenomenon than PGD. Only early postoperative serum lactate levels correspond with hemodynamic instability following HTX. Postoperative hemodynamic instability is associated with poor long-term survival among HTX recipients.

Objectives: Primary graft failure (pGF) after hematopoietic stem-cell transplant is associated with considerable morbidity and mortality. The incidence in haplo-HSCT has been reported to be between 0% and 30%. In 2018, we identified a pGF incidence of 35% in our pediatric haplo-HSCT recipients with hematologic malignancies, which motivated us to enact changes to the conditioning regimen. Methods: We performed a single-center prospective, pre-post study of consecutive patients under 16 years with hematologic malignancies, from January 2015 to December 2022 who received a haplo-HSCT. Twenty-six pediatric patients received a haplo-HSCT before September 2018 (G1) and 36 patients after (G2). The main conditioning regimen for G1 was myeloablative with Flu/Cy/Bu, and for G2 the main regimen was reduced intensity Flu/Cy/Mel/TBI2. Results: Nine patients (35%) in G1 had primary graft failure, while in G2 there were no patients with pGF. The median follow-up for G1 was 15.9 months, and for G2 was 24.8 months, with an estimated overall survival at 12 months of 63% (95% CI 47-76) versus 85% (95% CI 73-93), and at 24 months of 47% (95% CI 31-64) versus 70% (95% CI 54-82) respectively ( p  = .007). Conclusion: After September 2018 conditioning regimen modifications were implemented with the objective of reducing primary failure, consisting mainly of switching from busulfan to melphalan as the alkylating agent of choice, and adding, when clinically possible TBI. Primary failure has been significantly reduced in our institution since then.

Introduction and Objectives: Heart transplant (HT) represents a major physiological stress, resulting in elevated levels of analytical biomarkers. This study aimed to determine whether changes in biomarker levels after HT can identify patients with a poor prognosis., Methods: A prospective longitudinal noninterventional study was conducted in 149 consecutive patients undergoing HT from July 2017 to July 2023. Biomarkers were assessed before HT and at 6, 24, 48, 72, and 96hours after HT. The biomarkers analyzed were high-sensitivity troponin T, N-terminal pro-B-type natriuretic peptide (NT-proBNP), creatinine, and lactic acid. The primary outcome was a composite of death and severe primary graft failure (PGF)., Results: NT-proBNP and troponin levels remained highly elevated throughout the period and stabilized from the first 24hours post-HT. Lactate levels stabilized after the first 24hours, and creatinine from the second day onward. Exitus occurred in 23 (15%) of the patients, and severe PGF in 26 (17%). All biomarkers were significantly associated with the incidence of the combined event (P <.0001). Receiver operating characteristic curve analysis at 24hours showed significant areas under the curve (P=.0001). The greatest discriminatory power was observed for the NT-proBNP curve. A value of 10 000 pg/mL had a sensitivity of 90% and specificity of 80%., Conclusions: A significant elevation of post-HT analytical biomarkers was associated with mortality and/or severe PGF. Among the biomarkers analyzed, NT-proBNP was the most accurate in classifying patients., (Copyright © 2024 Sociedad Española de Cardiología. Published by Elsevier España, S.L.U. All rights reserved.)

Background: Primary graft dysfunction (PGD) is the main cause of death in the first 30 days after heart transplantation (HTX), accounting for approximately 40% of mortality. The study's primary aim was to assess the incidence of PGD, following the International Society for Heart and Lung Transplantation consensus, and to compare it with the incidence of significant postoperative hypotension despite administration of high-dose inotropes and vasoconstrictors. The secondary aim of the study was to determine changes in biochemical markers that accompany the phenomenon. Methods: Forty-five patients who underwent HTX between 2010 and 2015 were enrolled in this study, and detailed hemodynamic and metabolic data from the first 48 postoperative hours were collected and analyzed. Hemodynamic instability was defined as significant postoperative hypotension (mean arterial pressure (MAP) < 60 mmHg) combined with a high inotrope score (> 10). Data for long-term mortality were obtained from the population registration office. Results: PGD incidence was relatively low (17.8%); however, hemodynamic instability was common (40%). Among unstable patients, MAP was insufficient for end-organ perfusion (51.4 ± 9.5 mmHg) but no decrease in left ventricular function was observed (cardiac index, 2.65 ± 0.6 l/min/m2; left ventricular ejection fraction, 52.9 ± 15.5%). Within this group, mean systemic vascular resistance index (961 ± 288 dyn*s*m2/cm5) was low despite receiving high doses of vasoactive agent (norepinephrine 0.21 (0.06-0.27) μg/kg/min during first 24 h postoperatively and 0.21 (0.01-0.27) μg/kg/min during next 24 h postoperatively). After HTX, serum lactate levels were initially significantly higher in patients with hemodynamic instability (p = 0.002); however, impaired lactate clearance was not observed (p = 0.366), and lactate levels normalized within the first 24 h postoperatively. Postoperative hemodynamic instability altered the long-term outcome and increased 5-year mortality after HTX (p = 0.034). Conclusions: Hemodynamic instability is a more common phenomenon than PGD. Only early postoperative serum lactate levels correspond with hemodynamic instability following HTX. Postoperative hemodynamic instability is associated with poor long-term survival among HTX recipients. [ABSTRACT FROM AUTHOR]

This study sought to determine the utility of donor left ventricular function assessment by echocardiographic left ventricular global longitudinal strain (LV GLS) in predicting primary graft failure (PGF) after orthotopic heart transplantation (HT). Retrospective, observational study. Tertiary referral hospital. Adult patients (>18 years) who underwent isolated HT. Demographic, clinical, and echocardiographic data were collected on 100 patients who underwent HT between January 2010 and December 2019 at the authors' institution. The respective donor variables, as well as procedural factors, were reviewed and analyzed to assess their independent association with PGF. Standard donor echocardiographic measurements were supplemented by two-dimensional speckle-tracking echocardiography to obtain LV GLS. PGF was defined as per the International Society for Heart and Lung Transplantation 2014 consensus statement. PGF occurred in 40 of the 100 patients (40%). Initial univariate analysis found that RADIAL score, donor ejection fraction, and donor LV GLS were associated with PGF. However, in a multivariate Cox regression analysis, only RADIAL score and donor LV GLS remained significant predictors of PGF, with a p < 0.001. By receiver operating characteristic curve analysis, LV GLS at a cut-off value of –11.5% showed the greatest area under the curve (area under the curve = 0.889; 95% confidence interval, 0.826-0.952) and predicted PGF with 92.5% sensitivity and 65% specificity. Impaired donor LV GLS was proven to be an independent predictor of PGF after HT. [ABSTRACT FROM AUTHOR]

Background Previous studies suggest that infant heart transplant (HT) recipients are at higher risk of developing severe primary graft dysfunction (PGD) than older children. We sought to identify risk factors for developing severe PGD in infant HT recipients. Methods and Results We identified all HT recipients aged

Objective To analyze the prediction efficiency of scoring models at home and abroad on delayed graft function (DGF) after renal transplantation in China. Methods The clinical data of 112 donors and 220 recipients undergoing renal transplantation were prospectively analyzed. The DGF predicted by KDRI model, Jeldres model, and model of our center was compared with actual DGF incidence of renal transplant recipients. The prediction efficiency of each model was analyzed. The predictive accuracy was compared by the area under curve (AUC) of receiver operating characteristic (ROC) curve. Results The DGF incidence of 220 renal transplant recipients was 14.1% (31/220). DGF prediction using KDRI model showed that 41 cases were high risk donors, the AUC was 0.57, the sensitivity was 0.37, the specificity was 0.66, and the positive predictive value was 22%. DGF prediction using Jedres model showed that 22 cases were high risk recipients, the AUC was 0.56, the sensitivity was 0.13, the specificity was 0.92 and the positive predictive value was 20%. DGF prediction using the model of our center showed that 25 cases were high risk donors, the AUC was 0.80, the sensitivity was 0.53, the specificity was 0.84, the positive predictive value was 40%. Conclusions Compared with the KDRI and Jedres models, the prediction model of our center has higher AUC and sensitivity with a better prediction efficiency on DGF. Therefore, it is a suitable evaluation system of donors from donation after citizen s death in Chinese. [ABSTRACT FROM AUTHOR]

Previous reports of primary graft dysfunction (PGD) in pediatric heart transplant (HT) recipients are limited to descriptive series of children who required extracorporeal membrane oxygenation (ECMO) support shortly after HT. In this study we sought to determine the incidence, risk factors, and survival after severe PGD in pediatric HT recipients. We identified all children <18 years old who underwent HT in the United States during 1996 to 2015 using the Organ Procurement and Transplant Network database and then identified those who developed severe PGD by linking patient variables to Extracorporeal Life Support Organization registry data. Logistic regression models were used to assess risk factors for developing severe PGD. The overall incidence of severe PGD was 4.7% over 20 years (95% confidence interval 4.2% to 5.3%). The incidence was 4.1%, 4.5%, 5.3%, and 4.6%, respectively, in consecutive 5-year periods (p for trend = 0.48). Independent risk factors for developing severe PGD were younger age, congenital heart disease, HT while supported on ECMO, higher serum bilirubin, and graft ischemic time ≥4 hours. Ventricular assist device support as bridge to HT and available donor variables were not associated. Death (or graft loss) before discharge occurred in 40.6% of children with PGD (105 deaths, 7 re-transplants) and in 5.6% of children without PGD. Severe PGD remains an important clinical morbidity in pediatric HT recipients in the current era and is associated with high mortality. These findings highlight the need for research in preventing and treating PGD in pediatric HT recipients for improving overall post-transplant survival. [ABSTRACT FROM AUTHOR]

Primary graft failure (PGF) is a lethal complication that occurs early after allogeneic stem cell transplantation (allo-SCT). Cord blood transplantation (CBT) is a potential re-transplantation option. Total body irradiation (TBI) is often incorporated into the pre-salvage CBT conditioning regimen following PGF; however, patients experiencing PGF are not always amenable to TBI, and non-TBI regimens for salvage CBT should be established. Here, we report five patients with hematologic malignancies who received salvage CBT for PGF following a non-TBI regimen using fludarabine (Flu), melphalan (Mel), and low-dose anti-thymocyte globulin (ATG). The median intervals between the failed allo-SCT and salvage CBT, as well as between the diagnosis of PGF and salvage CBT, were 37 days and 8 days, respectively. The median neutrophil recovery period was 21 days (range 18-21 days). Four of five patients achieved neutrophil engraftment following salvage CBT; all four exhibited sustained engraftment with complete donor chimerism. Three of the five patients were alive after a median follow-up time of 907 days (range 315-909 days) post-salvage CBT; two patients died of causes unrelated to recurrence. These data suggest that CBT following the non-TBI regimen described here is feasible in patients with PGF. [ABSTRACT FROM AUTHOR]

BACKGROUND Primary graft dysfunction (PGD) remains a significant cause of post-transplant morbidity and mortality. The exact mechanism and risk factors for this phenomenon remain unknown in the contemporary era. METHODS In this study we reviewed adult patients undergoing heart transplantation (HT) at our institution between 2009 and 2017. Severe PGD was defined as the need for mechanical circulatory support (MCS) within the first 24 hours after HT. Multivariate logistic regression analysis was used to identify risk factors for severe PGD, focusing on those bridged to transplant (BTT) with a continuous-flow left ventricular assist device (CF-LVAD). RESULTS Fifty-six of 480 (11.7%) HT patients experienced severe PGD. Eighty percent of the severe PGD patients were BTT with a CF-LVAD (odds ratio [OR] 3.86, 95% confidence interval [CI] 1.94 to 7.68, p < 0.001). Among the BTT patients, significant associations between >1 year of CF-LVAD support (OR 2.48, 95% CI 1.14 to 5.40, p = 0.022), pre-HT creatinine (OR 3.35, 95% CI 1.42 to 7.92, p = 0.006), elevated central venous pressure/pulmonary capillary wedge pressure (CVP/PCWP) ratio (OR 3.32, 95% CI 1.04 to 10.60, p = 0.043), use of amiodarone before HT (OR 2.69, 95% CI 1.20 to 6.20, p = 0.022), and severe PGD were identified. RADIAL score did not accurately predict severe PGD in this contemporary cohort. Those patients who developed severe PGD had decreased 1-year post-transplant survival (78.3% vs 91.8%, p = 0.007). CONCLUSIONS Use of CF-LVAD as BTT is associated with an increased risk of severe PGD. Increased time on device support, renal dysfunction, right ventricular dysfunction as assessed by CVP/PCWP ratio, and pre-transplant amiodarone may identify those patients at high risk. Further research is warranted focusing on optimal timing of device implantation and transplantation, as well as the underlying mechanisms of PGD. [ABSTRACT FROM AUTHOR]

Objective To explore the protective effect of extracorporeal membrane oxygenation (ECMO) on donor kidneys from non-controllable donation after cardiac death (DCD). Methods A total of 60 non-controllable DCD donors were selected and divided into 3 groups randomly based on the in vivo perfusion time of ECMO: test group 1 received EMCO perfusion for 2 h, test group 2 for 4 h and test group 3 for 6 h, with 20 cases in each group. Corresponding recipients were also divided into 3 groups, with 20 cases in each group. Meanwhile, 20 recipients from donation after brain death (DBD) with stable circulatory function were randomly selected as control group. Incidence of delayed graft function (DGF), primary graft failure (PNF) and acute rejection of the recipients in different groups were compared. The indexes including graft function recovery time, urine volume on day 1 and graft function within 1 year after renal transplantation were compared for the recipients in different groups. And 1-year survival rate of the recipients and grafts after renal transplantation was compared. Results Compared with the control group, various test groups presented no significant differences in the incidence of PNF, DGF and acute rejection (all P>0.05). Compared with the control group, graft function recovery time prolonged significantly in each test group, which presented statistically significant differences (all P<0.05), while the urine volume on day 1 and graft function within 1 year after renal transplantation presented no statistically significant difference in each test group (all P>0.05). The 1-year survival rate of the recipients and grafts after renal transplantation was 100% in test groups and control group, which presented no statistically significant difference (all P>0.05). Conclusions ECMO can protect donor kidneys effectively through assisting the circulatory or respiratory function of non-controllable DCD, and improve their utilization rate. [ABSTRACT FROM AUTHOR]

Background The presence of pre-formed IgA anti–β 2 -glycoprotein I antibodies (IgA-aB2GP1ab) has been related to early graft loss after kidney transplant. Because β 2 -glycoprotein I is produced in both the kidney and heart, we aimed to assess whether the presence of these antibodies may also be associated with poor outcomes after heart transplantation (HT). Methods A 2-year follow-up retrospective analysis of 151 consecutive patients who underwent HT between 2004 and 2012 was performed to assess the role of this pre-formed antibody type in HT. The population was divided into 2 groups according to the presence of IgA: Group 1 was positive for IgA-aB2GP1ab (47 patients, 31.1%), and Group 2 was negative for IgA-Ab2GP1ab (104 patients, 68.9%). Results Early mortality rates within the first 3 months were higher in Group 1 (27.7%) than in Group 2 (9.6%). No differences in donor and recipient characteristics or in causes of death were observed between groups. Multivariate analysis identified the presence of IgA-aB2GP1ab, female gender and blood type A as independent risks factors for early mortality after HT. A greater incidence of thrombotic events during the first 3 months post-HT in Group 1 (23.4% vs 5.8%) and a greater presence of risk factors for thrombotic events, which may have exacerbated them, were observed. After this period, no increase in mortality or in thrombotic events was found when the 2 groups were compared. Conclusion Pre-transplant presence of IgA-aB2GP1ab is associated with both increased early mortality rates and higher thrombotic events after HT. [ABSTRACT FROM AUTHOR]

Background: Left ventricular systolic dysfunction (LVSD) accounts for almost 25% of nonacceptance of potential donor hearts. Previous smaller, single-center studies showed that LVSD following brain death may be transient, and such hearts can be successfully resuscitated with resolution of LVSD, then transplanted.Objectives: This study evaluated outcomes of donor hearts with LVSD on initial transthoracic echocardiogram (TTE) that resolved during donor management.Methods: We reviewed echocardiograms of all cardiac donors in the United Network of Organ Sharing database that were transplanted from January 1, 2007, to September 30, 2015, and identified 472 donor hearts with LVSD (left ventricular ejection fraction [LVEF] ≤40%) on initial TTE that resolved (LVEF ≥50%) during donor management on a subsequent TTE. These patients comprised the improved donor LVEF group. These were compared with donor hearts with normal LVEF (LVEF ≥55%) on the initial TTE for recipient mortality, cardiac allograft vasculopathy (CAV), and primary graft failure (PGF).Results: There was no significant difference in recipient mortality at 30 days, 1 year, 3 years, and 5 years of follow-up, nor any difference in rates of PGF at 90 days and CAV at 5 years between recipients of donor hearts with improved LVEF and recipients of donor hearts with initially normal LVEF. Post-transplant length of stay was also similar between the 2 groups. Using propensity scores, 461 transplants in the improved-donor LVEF group were matched to 461 transplants in the normal-donor LVEF group. There was no significant difference in PGF at 90 days or recipient mortality after up to 5 years of follow-up.Conclusions: In the largest analysis of donor hearts with transient LVSD, we found that such hearts can be successfully resuscitated and transplanted without increasing recipient mortality, CAV, or PGF. These results underscore the importance of appropriate donor management and should help to increase utilization of donor hearts with transient LVSD. [ABSTRACT FROM AUTHOR]

Cord blood transplantation (CBT) recipients are at increased risk for delayed engraftment and primary graft failure, complications that are often indistinguishable early post-transplantation. Current assays fail to accurately identify recipients with slow hematopoietic recovery and distinguish them from those with pending graft failure. To address this, we prospectively examined the kinetics of immune cell subset recovery in the peripheral blood of 39 patients on days +7 and +14 after double-unit CBT (dCBT) by multiparametric flow cytometry analysis, which we term real-time immunophenotyping (RTIP). RTIP analysis at day +14 revealed distinctive patterns of reconstitution and, importantly, identified patients with slow hematopoietic recovery who went on to engraft. Strikingly, higher absolute numbers of circulating monocytes and natural killer cells at day +14 were predictive of engraftment, but only the absolute number of circulating monocytes was significantly correlated with time to engraftment. This is the first evidence that RTIP on patient peripheral blood mononuclear cells early after dCBT is technically feasible and can be used as a “signature” for predicting the kinetics of hematopoietic recovery. Furthermore, RTIP is a time- and cost-efficient methodology that has the potential to become a clinically feasible diagnostic tool to guide therapeutic interventions in high-risk patients; therefore, its utility should be evaluated in a large cohort of patients. [ABSTRACT FROM AUTHOR]

Early allograft dysfunction ( EAD) following liver transplantation ( LT) remains a challenge for patients and clinicians. We retrospectively analyzed the effect of pre-defined EAD on outcomes in a 10-year cohort of deceased-donor LT recipients with clearly defined exclusion criteria. EAD was defined by at least one of the following: AST or ALT >2000 IU/L within first-week post- LT, total bilirubin ≥10 mg/ dL, and/or INR ≥1.6 on post-operative day 7. Ten patients developed primary graft failure and were analyzed separately. EAD occurred in 86 (36%) recipients in a final cohort of 239 patients. In univariate and multivariate analyses, EAD was significantly associated with mechanical ventilation ≥2 days or death on days 0, 1, PACU/ SICU stay >2 days or death on days 0-2 and renal failure ( RF) at time of hospital discharge (all P<.05). EAD was also significantly associated with higher one-year graft loss in both uni- and multivariate Cox hazard analyses ( P=.0203 and .0248, respectively). There was no difference in patient mortality between groups in either of the Cox proportional hazard models. In conclusion, we observed significant effects of EAD on short-term post- LT outcomes and lower graft survival. [ABSTRACT FROM AUTHOR]