Graft Ischemia Research Articles

Tackling regulated cell death yields enhanced protection in lung grafts.

Background: Effective preservation strategies to ameliorate lung graft ischaemia injury are needed to rescue 'extended criteria' or 'marginal' lung grafts, and to improve recipient outcomes after transplantation. Methods: Lung grafts from male Lewis rats were extracted after 40 min of cardiocirculatory death, and healthy human lung tissues were collected from patients undergoing a lobectomy. Lung samples were then preserved in a 4°C preservation solution supplemented with 0.1 nM Dexmedetomidine (Dex, α2-adrenoceptor agonist) for 16 h. In vitro, human lung epithelial A549 cells were preserved in the 4°C preservation solution with 0.1 nM Dex for 24 h, then re-cultured in the cell culture medium at 37°C to mimic the clinical scenario of cold ischaemia and warm reperfusion. Lung tissues and cells were then analysed with various techniques including western blot, immunostaining and electron microscope, to determine injuries and the protection of Dex. Results: Prolonged warm ischaemia after cardiocirculatory death initiated Rip kinase-mediated necroptosis, which was exacerbated by cold storage insult and enhanced lung graft injury. Dex supplementation significantly reduced necroptosis through upregulating Nrf2 activation and reducing oxidative stress, thereby significantly improving lung graft morphology. Dex treatment also attenuated endoplasmic reticulum stress, stabilised lysosomes and promoted cell membrane resealing function, consequently reducing cell death and inflammatory activation after hypothermic hypoxia-reoxygenation in A549 cells. Conclusions: Inhibition of regulated cell death through Dex supplementation to the graft preservation solution improves allograft quality which may aid to expand the donor lung pool and enhance lung transplant outcomes per se.

What's in a name? Higher risks with donation after cardiac death than public health service increased risk livers

Background: Public health service increased risk donor(IRD) and donation after cardiac death (DCD) livers are utilized to address the organ shortage in liver transplantation, particularly during the opioid epidemic. “Increased risk donor” terminology implies greater risk than DCD by its name, but without direct risk comparison.Objective: The aim of this study was to examine the risks of accepting IRD livers compared to DCD livers during the opioid epidemic.Methods: Retrospective, single center study of 92 recipients of IRD donors and 21 DCD donors(22% and 5% of adult transplants) between 1/2013-5/2017. Median post transplant follow-up was 2.6 years. The primary outcome was the composite of post-transplant risks likely to be greatest in IRD donor and DCD livers, namely, donor viral transmission (HBV, HCV, HIV) and ischemic cholangiopathy. Secondary outcomes were patient and graft survival, biopsy-proven rejection, CMV and EBV viremia. Categorical variables were analyzed using chi square and continuous variables Kruskal-Wallis techniques. Propensity score matched sensitivity analysis was conducted using logistic regression. Cox proportional hazard regression models were used for survival analyses.Results: Ischemic cholangiopathy and graft failure leading to retransplantation occurred in 40% and 14% of DCD recipients but did not occur among IRD recipients(p<0.0001). There were no occurrences of HBV, HCV, HIV transmission. Survival was similar between DCD and IRD groups(90% vs 84% respectively, p=0.23).Conclusion Despite its name, increased risk donors are less risky than DCD livers given lower rates of ischemic cholangiopathy and retransplantation, supporting the recent decision to rename this group of donors to encourage utilization.

Cardiovascular mechanism of donor brain death and heart recipient survival.

Heart donation after donor brain death from cardiac arrest despite successful resuscitation may be associated with worse recipient outcomes due to potential graft ischemia or underlying rhythmic/structural defects. However, selected grafts from such donors often have normal cardiac function and anatomy. We investigated whether a cardiovascular mechanism of donor brain death (CV-DBD) was associated with worse recipient outcomes. We queried the United Network for Organ Sharing (UNOS) database for first-time, single-organ, adult (age 18+) heart transplant recipients and their associated donors between January 2005 and March 2021. Recipients were stratified by donor status (CV-DBD vs. non-CV-DBD). We performed multivariable Cox proportional hazards modeling to ascertain whether receiving a CV-DBD graft was independently associated with mortality. Of 35,833 included recipients, 2,702 (7.5%) received CV-DBD grafts. The associated donors were significantly more likely to be female, older, and have a history of diabetes, hypertension, and substance use (all p < .001). On unadjusted Kaplan-Meier analysis, CV-DBD recipients had a significantly reduced median survival than non-CV-DBD recipients (12.0 vs. 13.1 years, log-rank p = .04). However, after adjusting for donor/recipient age, recipient comorbidities, annualized center volume, and transplantation era, CV-DBD organ status was not associated with recipient mortality (hazard ratio: 1.05, 95% confidence interval: 0.96-1.13, p = .28). In this analysis of over 35,000 heart transplants, CV-DBD status was not associated with adjusted recipient survival. Donor brain death due to cardiac arrest should not be an absolute contraindication to heart donation, although graft function should be carefully assessed before transplantation.

Interleukin-18 and High-Mobility-Group-Protein B1 are Early and Sensitive Indicators for Cell Damage During Normothermic Machine Perfusion after Prolonged Cold Ischemic Storage of Porcine Liver Grafts.

In the era of organ machine perfusion, experimental models to optimize reconditioning of (marginal) liver grafts are needed. Although the relevance of cytokine signatures in liver transplantation has been analyzed previously, the significance of molecular monitoring during normothermic machine perfusion (NMP) remains elusive. Therefore, we developed a porcine model of cold ischemic liver graft injury after prolonged static cold storage (SCS) and subsequent NMP: Livers obtained from ten minipigs underwent NMP for 6h directly after procurement (control group) or after 20h of SCS. Grafts after prolonged SCS showed significantly elevated AST, ALT, GLDH and GGT perfusate concentrations, and reduced lactate clearance. Bile analyses revealed reduced bile production, reduced bicarbonate and elevated glucose concentrations after prolonged SCS. Cytokine analyses of graft perfusate simultaneously demonstrated an increase of pro-inflammatory cytokines such as Interleukin-1α, Interleukin-2, and particularly Interleukin-18. The latter was the only significantly elevated cytokine compared to controls, peaking as early as 2h after reperfusion (11,012ng/ml vs. 1,493ng/ml; p = 0.029). Also, concentrations of High-Mobility-Group-Protein B1 were significantly elevated after 2h of reperfusion (706.00ng/ml vs. 148.20ng/ml; p < 0.001) and showed positive correlations with AST (r 2 = 0.846) and GLDH (r 2 = 0.918) levels. Molecular analyses during reconditioning of liver grafts provide insights into the degree of inflammation and cell damage and could thereby facilitate future interventions during NMP reducing acute and chronic graft injury.

RESULTS OF THERMAL VISION EXAMINATION BEFORE AND AFTER ORTHOTOPIC LIVER TRANSPLANTATION IN INBRED RATS

This article describes the using of thermal imaging examination in orthotopic liver transplantation in inbred rats. For the experiment, 40 inbred rats of the Vistar line were selected: 20 females, weighing 400–550 g, 20 males, weighing 600–750 g, about a year old. For comparison, we identified the control group, which underwent only an incision of the skin and muscles of the abdominal wall, and then closed the surgical wound, experimental group No. 1, in which the left lateral lobe of the liver was excluded from the bloodstream to create a model of graft ischemia, and experimental group No. 2 who underwent orthotopic transplantation. All manipulations were performed under anesthesia, in compliance with the rules of asepsis and antisepsis. Thermal imaging examination was carried out with a medical thermal imager model ULIRvision Ti120 before the operation, then on the first, third, fifth, seventh day after. When comparing the thermograms of rats from the experimental group No. 2 and the control group, differences were observed on the 3rd day after the operation, then the temperature in the graft area in the experimental group No. 2 was higher than the temperature of the same skin area in the control group. This may be due to a slight ischemia of the graft during its disconnection from the blood flow, as well as to surgical intervention. After conducting research, we came to the conclusion that on the 3rd day in the transplant area there is a local increase in temperature, which is associated with ischemia of the organ due to temporary blockage of blood vessels, which occurs from the moment of explantation of the liver until its subsequent connection to the bloodstream. Rats in which this process affects 33% of the liver die on the first day from developing fulminant sepsis.

636. EVOLUTION OF THE INDICATION OF COLONIC INTERPOSITION FOR THE ESOPHAGUS - THE PAST AND THE PRESENT

Abstract Although the stomach is the most common organ used for reconstruction after esophagectomy, some situations precluded its use. The colon is a common alternative. The outcomes of colonic interposition from previous literature were very variable. Our study aims at reviewing the evolution in the indications and outcomes of colonic interposition over the past 38 years. This is a retrospective cohort study of all patients who underwent colonic interposition from November 1982 to October 2021 at our centre. Primary outcomes included 30- and 90-day mortality. Secondary outcomes include surgical complications including anastomotic leakage, anastomotic stricture and graft ischaemia. The major indication of colonic interposition shifted from palliation of esophageal cancer to substitute conduit for curative esophagectomy in the study period. Its use was also extended to the treatment of caustic esophageal injuries in recent years. In terms of surgical techniques, there were significantly higher rates of the retrosternal route of reconstruction and more use of the right colon in recent years. In patients who underwent colonic interposition after curative esophagectomy for esophageal cancer, the 30- and 90-day mortality were 1.9% and 5.7% respectively. The occurrence of anastomotic leakage, stricture and graft ischaemia were 9.6%, 17.3% and 7.7% respectively. Colonic interposition represents a viable option when the stomach cannot be used to replace the diseased esophagus. Despite its complexity, we demonstrated reasonable survival and comparable outcomes of the technique.

Trophism and Homeostasis of Liver Sinusoidal Endothelial Graft Cells during Preservation, with and without Hypothermic Oxygenated Perfusion.

Simple SummaryLittle is known about the functions and intracellular mechanisms of the endothelial cells in liver grafts. In particular, we still know little about the effect of the most recent machine perfusion techniques currently applied to improve liver transplant outcomes. In this study we analyzed different endothelial markers of both immunohistochemical and gene expression in two different biopsies (for each donor). We observed a severe depression of endothelial trophism in liver grafts, which is restored after reperfusion. This is interesting for further studies on liver grafts, especially considering that the execution of HOPE seems to improve this functional recovery. We propose that our results may help improve the knowledge on graft tissues in order to customize the perfusion techniques prior to transplant and, therefore, improve liver transplant outcomes.The aim of the present study was to evaluate the homeostasis and trophism of liver sinusoidal endothelial cells (LSECs) in vivo in different stages of liver graft donation, in order to understand the effects of graft ischemia and perfusion on LSEC activity in liver grafts. Special attention was paid to grafts that underwent hypothermic oxygenated perfusion (HOPE). Forty-seven donors were prospectively enrolled, and two distinct biopsies were performed in each case: one allocation biopsy (at the stage of organ allocation) and one post-perfusion biopsy, performed after graft implant in the recipients. In all biopsies, immunohistochemistry and RT-PCR analyses were carried out for the endothelial markers CD34, ERG, Nestin, and VEGFR-2. We observed an increase in CD34 immunoreactivity in LSEC during the whole preservation/perfusion period (p < 0.001). Nestin and ERG expression was low in allocation biopsies, but increased in post-perfusion biopsies, in both immunohistochemistry and RT-PCR (p < 0.001). An inverse correlation was observed between ERG positivity and donor age. Our results indicate that LSEC trophism is severely depressed in liver grafts, but it is restored after reperfusion in standard conditions. The execution of HOPE seems to improve this recovery, confirming the effectiveness of this machine perfusion technique in restoring endothelial functions.

Favorable, arduous or fatal postoperative pathway within 90 days of lung transplantation

IntroductionThe maximum gain in quality of life after lung transplantation (LT) is expected between six months and one year after LT, as the occurrence of chronic lung allograft dysfunction may mask the beneficial effects beyond one year. Thus, the postoperative period could be the cornerstone of graft success. We sought to describe the factors present before postoperative admission to the ICU and associated with favorable, arduous or fatal pathway within 90 days of LT.Materials and methodsWe conducted a retrospective single-center study between January 2015 and December 2020. Using multinomial regression, we assessed the demographic, preoperative and intraoperative characteristics of patients associated with favorable (duration of postoperative mechanical ventilation < 3 days and alive at Day 90), arduous (duration of postoperative mechanical ventilation ≥ 3 days and alive at Day 90) or fatal (dead at Day 90) pathway within 90 days of LT.ResultsA total of 269 lung transplant patients were analyzed. Maximum graft cold ischemic time ≥ 6 h and intraoperative blood transfusion ≥ 3 packed red blood cells were associated with arduous and fatal pathway at Day 90, whereas intraoperative ECMO was strongly associated with fatal pathway. ConclusionNo patient demographics influenced the postoperative pathway at Day 90. Only extrinsic factors involving graft ischemia time, intraoperative transfusion, and intraoperative ECMO determined early postoperative pathway.

The Effects of Rapamycin on the Intestinal Graft in a Rat Model of Cold Ischemia Perfusion and Preservation.

Attenuating the rheological and structural consequences of intestinal ischemia-reperfusion-injury (IRI) is important in transplant proceedings. Preconditioning is an often-proposed remedy. This technique uses physical or pharmacological methods to manipulate key ischemia pathways, such as oxidation, inflammation, and autophagy, prior to ischemia. This study determined the time-dependent effects of Rapamycin preconditioning on small-bowel grafts undergoing cold ischemia perfusion and preservation. Our main parameters were mucosa and cell injury and autophagy. A total of 30 male Wistar rats were divided into 5 groups: sham, preservation-control, and 3 treated groups (Rapamycin administered either 0, 30, or 60 min prior to perfusion). After perfusion, the intestines were placed in chilled IGL-1 solution for 12 h. Thereafter, they were reperfused. Histology and bioanalysis (LDH and lactate) were used to ascertain intestinal injury while immunohistochemistry was used for measuring changes in autophagy markers (Beclin-1, LC3B, and p62 proteins). The results show no significant difference amongst the groups after vascular perfusion. However, intestinal injury findings and autophagy changes demonstrate that administering Rapamycin 30 min or 60 min prior was protective against adverse cold ischemia and reperfusion of the intestinal graft. These findings show that Rapamycin is protective against cold ischemia of the small intestine, especially when administered 30 min before the onset.

REPLY: Reply to Kumar and colleagues.

The author reported no conflicts of interest.The Journal policy requires editors and reviewers to disclose conflicts of interest and to decline handling or reviewing manuscripts for which they may have a conflict of interest. The editors and reviewers of this article have no conflicts of interest.In their recent letter to the Editor, Kumar and colleagues1Kumar N. Flores A.S. Hussain N. Ganapathi A.M. Whitson B.A. Essandoh M.K. et al.Ensuring pulmonary artery patency in donor-recipient size mismatch: a collaborative challenge.J Thorac Cardiovasc Surg Tech. 2022; 15: 206-207Scopus (4) Google Scholar provided an important suggestion for additional evaluation of the pulmonary artery anastomosis after lung transplantation with transesophageal echocardiography (TEE) in the operating room. We thank Yokoyama and colleagues2Yokoyama Y. Chen-Yoshikawa T.F. Nakajima D. Ohsumi A. Date H. Various techniques for anastomosis of pulmonary arteries with size mismatch during lung transplantation.J Thorac Cardiovasc Surg Tech. 2021; 9: 192-194Scopus (7) Google Scholar for their previous article on anastomotic techniques that again highlight the importance of a technically optimal operation, which includes an unobstructed pulmonary artery anastomosis. The routine nature of thoracic transplantation might allow a suboptimal pulmonary artery anastomosis after heart or lung transplantation to go undetected as a potential cause of pulmonary graft dysfunction or donor heart right ventricular dysfunction.Kumar and colleagues' suggestion of TEE Doppler interrogation of the flow characteristics across the anastomosis after lung transplantation could provide early evidence of a technical problem. If TEE is not routinely used for lung transplant operations, the anticipation of important pulmonary artery size disparity should at least stimulate consideration with our anesthesia colleagues for insertion of a TEE probe for anastomotic examination. The author reported no conflicts of interest.The Journal policy requires editors and reviewers to disclose conflicts of interest and to decline handling or reviewing manuscripts for which they may have a conflict of interest. The editors and reviewers of this article have no conflicts of interest. The author reported no conflicts of interest. The Journal policy requires editors and reviewers to disclose conflicts of interest and to decline handling or reviewing manuscripts for which they may have a conflict of interest. The editors and reviewers of this article have no conflicts of interest. In their recent letter to the Editor, Kumar and colleagues1Kumar N. Flores A.S. Hussain N. Ganapathi A.M. Whitson B.A. Essandoh M.K. et al.Ensuring pulmonary artery patency in donor-recipient size mismatch: a collaborative challenge.J Thorac Cardiovasc Surg Tech. 2022; 15: 206-207Scopus (4) Google Scholar provided an important suggestion for additional evaluation of the pulmonary artery anastomosis after lung transplantation with transesophageal echocardiography (TEE) in the operating room. We thank Yokoyama and colleagues2Yokoyama Y. Chen-Yoshikawa T.F. Nakajima D. Ohsumi A. Date H. Various techniques for anastomosis of pulmonary arteries with size mismatch during lung transplantation.J Thorac Cardiovasc Surg Tech. 2021; 9: 192-194Scopus (7) Google Scholar for their previous article on anastomotic techniques that again highlight the importance of a technically optimal operation, which includes an unobstructed pulmonary artery anastomosis. The routine nature of thoracic transplantation might allow a suboptimal pulmonary artery anastomosis after heart or lung transplantation to go undetected as a potential cause of pulmonary graft dysfunction or donor heart right ventricular dysfunction. Kumar and colleagues' suggestion of TEE Doppler interrogation of the flow characteristics across the anastomosis after lung transplantation could provide early evidence of a technical problem. If TEE is not routinely used for lung transplant operations, the anticipation of important pulmonary artery size disparity should at least stimulate consideration with our anesthesia colleagues for insertion of a TEE probe for anastomotic examination. Ensuring pulmonary artery patency in donor-recipient size mismatch: A collaborative challengeJTCVS TechniquesVol. 15PreviewThe vascular anastomoses of lung transplantation are a growing area of interest. Anastomosing the donor and recipient pulmonary artery (PA) segments is among the most delicate aspects of the surgery, and proper surgical technique is critical to allograft and patient survival. Obstruction of blood flow through the PA may cause graft ischemia, refractory hypoxemia, right ventricular dysfunction, and even death in affected patients.1 However, the importance of the PA anastomoses has yet to be critically examined in the lung transplant literature. Full-Text PDF Open Access

Liver Graft Hypothermic Static and Oxygenated Perfusion (HOPE) Strategies: A Mitochondrial Crossroads.

Marginal liver grafts, such as steatotic livers and those from cardiac death donors, are highly vulnerable to ischemia–reperfusion injury that occurs in the complex route of the graft from “harvest to revascularization”. Recently, several preservation methods have been developed to preserve liver grafts based on hypothermic static preservation and hypothermic oxygenated perfusion (HOPE) strategies, either combined or alone. However, their effects on mitochondrial functions and their relevance have not yet been fully investigated, especially if different preservation solutions/effluents are used. Ischemic liver graft damage is caused by oxygen deprivation conditions during cold storage that provoke alterations in mitochondrial integrity and function and energy metabolism breakdown. This review deals with the relevance of mitochondrial machinery in cold static preservation and how the mitochondrial respiration function through the accumulation of succinate at the end of cold ischemia is modulated by different preservation solutions such as IGL-2, HTK, and UW (gold-standard reference). IGL-2 increases mitochondrial integrity and function (ALDH2) when compared to UW and HTK. This mitochondrial protection by IGL-2 also extends to protective HOPE strategies when used as an effluent instead of Belzer MP. The transient oxygenation in HOPE sustains the mitochondrial machinery at basal levels and prevents, in part, the accumulation of energy metabolites such as succinate in contrast to those that occur in cold static preservation conditions. Additionally, several additives for combating oxygen deprivation and graft energy metabolism breakdown during hypothermic static preservation such as oxygen carriers, ozone, AMPK inducers, and mitochondrial UCP2 inhibitors, and whether they are or not to be combined with HOPE, are presented and discussed. Finally, we affirm that IGL-2 solution is suitable for protecting graft mitochondrial machinery and simplifying the complex logistics in clinical transplantation where traditional (static preservation) and innovative (HOPE) strategies may be combined. New mitochondrial markers are presented and discussed. The final goal is to take advantage of marginal livers to increase the pool of suitable organs and thereby shorten patient waiting lists at transplantation clinics.

Transplantation of a beating heart: A first in man

SummaryBackgroundIn the current practice, graft ischaemia and reperfusion injury (IRI) is considered an inevitable component in organ transplantation, contributes to compromised organ quality, inferior graft survival and limitations in organ availability. Among all the donor organs, the heart is most vulnerable to IRI and the tolerated ischaemic time is the shortest.MethodsBy combining adapted surgical techniques and normothermic machine perfusion (NMP), we performed the first case of ischaemia-free beating heart transplantation (IFBHT) in man. The donor heart was procured after an in situ NMP circuit was established, then underwent ex situ NMP and implanted under NMP support. The post-transplant graft function was monitored.FindingsThe donor heart was procured, preserved, and implanted under a continuously perfused, normothermic, oxygenated, beating state. During ex situ NMP, the donor heart beat with sinus rhythm and adequate ventricular contraction, consumed oxygen and lactate, suggesting a good cardiac function. The dynamic electrocardiogram demonstrated an absence of ischaemic injury of the donor heart during the entire procedure. The echocardiogram showed an immediate graft function with a left ventricle ejection fraction (LVEF) of 70%. The patient was discharged on post-transplantation day 20 and was followed up for 8 months with normal cardiac function and life.InterpretationThis study shows the feasibility of IFBHT procedure, which might be able to completely avoid graft IRI, has thus the potential to improve transplant outcome while increasing organ utilization.FundingThis study was funded by National Natural Science Foundation of China, Guangdong Provincial Key Laboratory Construction Projection on Organ Donation and Transplant Immunology, and Guangdong Provincial International Cooperation Base of Science and Technology.

Abdominal normothermic regional perfusion in controlled donation after circulatory determination of death liver transplantation: Outcomes and risk factors for graft loss

Postmortem normothermic regional perfusion (NRP) is a rising preservation strategy in controlled donation after circulatory determination of death (cDCD). Herein, we present results for cDCD liver transplants performed in Spain 2012-2019, with outcomes evaluated through December 31, 2020. Results were analyzed retrospectively and according to recovery technique (abdominal NRP [A-NRP] or standard rapid recovery [SRR]). During the study period, 545 cDCD liver transplants were performed with A-NRP and 258 with SRR. Median donor age was 59years (interquartile range 49-67years). Adjusted risk estimates were improved with A-NRP for overall biliary complications (OR 0.300, 95% CI 0.197-0.459, p<.001), ischemic type biliary lesions (OR 0.112, 95% CI 0.042-0.299, p<.001), graft loss (HR 0.371, 95% CI 0.267-0.516, p<.001), and patient death (HR 0.540, 95% CI 0.373-0.781, p=.001). Cold ischemia time (HR 1.004, 95% CI 1.001-1.007, p=.021) and re-transplantation indication (HR 9.552, 95% CI 3.519-25.930, p<.001) were significant independent predictors for graft loss among cDCD livers with A-NRP. While use of A-NRP helps overcome traditional limitations in cDCD liver transplantation, opportunity for improvement remains for cases with prolonged cold ischemia and/or technically complex recipients, indicating a potential role for complimentary ex situ perfusion preservation techniques.

Outcome of Redo Transplantation Compared to First Lung Transplantation in a Cystic Fibrosis Cohort

<h3>Purpose</h3> Improve of long-term survival after lung transplantation have increase the number of chronic rejections, especially in cystic fibrosis, usually young at the time of the first lung transplantation. They present the same systemic disease but with a new end-stage lung disease. <h3>Methods</h3> After ethical approval, we retrospectively collected the perioperative data of cystic fibrosis patients who underwent primary lung transplantation (LgTx group) or redo transplantation (RedoLgTx group) from January 2012 to June 2021. We aimed to compared perioperative data and outcome up to first hospital discharge. Results are presented as number (percentage) and median and were compared using Chi-square or Fischer test and, Mann Whitney Wilcoxon test. <h3>Results</h3> A total of 280 patients were included in the study: 257 in the LgTx group and 23 in the RedoLgTx group. There were no statistical difference between groups concerning 90-days survival (Log Rank; p=0.114), neither concerning early postoperative outcome (table 1). Demographic characteristics were not significantly different. In the RedoLgTx group, 2nd graft ischemia duration (494min vs. 422min; p=0.02), fluid support (2.8L vs 3.7L; p=0.003) and lactatemia at the end of the surgery (2.8mmol/L vs 4.2mmol/L; p=0.01) were higher. However, intraoperative ECMO requirement (45.7% vs 47.8%; p=0.84) and blood loss (1.5L vs. 1L; p=0.07) were not statistically different between groups. <h3>Conclusion</h3> Early outcome after redo lung transplantation for cystic fibrosis did not appeared to be more perjorative than first transplantation, even though surgery was more complex.

Transplant Outcomes in Hearts with Moderate to Severe Left Ventricular Hypertrophy After the 2018 OPTN/UNOS Allocation Changes

<h3>Purpose</h3> After the 2018 OPTN/UNOS heart transplant (HT) allocation changes, there has been an increase in graft ischemia time, a factor shown to worsen HT outcomes in recipients of hearts with left ventricular hypertrophy (LVH). We compare HT outcomes in moderate to severe LVH defined by left ventricular wall thickness ≥ 1.4cm and non-LVH hearts and determine if there were changes in LVH HT outcomes after 2018. <h3>Methods</h3> The UNOS database was queried for all HT recipients ages >18 from 2016 to 2020. Multi-organ transplants were excluded. Demographic, donor, and recipient information were compared between LVH and non-LVH hearts. The primary outcome was post-transplant survival with secondary outcomes of rejection, cardiac allograft vasculopathy (CAV), and post-transplant ejection fraction, all at one year. Comparisons were made using Chi-squared and Wilcoxon rank-sum. Multiple logistic and linear regression models were used to discern the predictors of survival and the effect of LVH on outcomes. <h3>Results</h3> 10,175 HTs were analyzed: 491 LVH and 9784 non-LVH. After the 2018 changes, compared to non-LVH HT donors, LVH HT donors were older, had higher BMI, more often had HTN, were male, and had kidney disease. LVH HT recipients were older, higher BMI, and had greater HLA mismatch. Graft ischemia time, survival, and secondary outcomes were similar. Examining the LVH cohort specifically before and after the 2018 changes, there were no differences in survival or most secondary outcomes (decrease in CAV) despite increases in recipient BMI, recipient prior cardiac surgery, and graft ischemia time, which were independent predictors of worse outcomes in the overall cohort. LVH was not a predictor of survival or any secondary outcome. <h3>Conclusion</h3> Outcomes for recipients of hearts with moderate to severe LVH were not negatively impacted by the 2018 OPTN/UNOS changes despite longer graft ischemia time, and outcomes for recipients of LVH hearts were similar to those receiving hearts without LVH.

Cell-Free DNA in the Early Course After Heart Transplantation

<h3>Purpose</h3> Cell-free DNA (cfDNA) has been used as a marker of rejection after heart transplantation (HTx). The commonly reported outcome is donor fraction (DF). However, cfDNA from donor (dd-cfDNA) and recipient (rd-cfDNA) can be quantified separately. We aimed to investigate the influence of donor and recipient-derived factors as well as intraoperative measures on levels of cfDNA. <h3>Methods</h3> Blood samples were collected in parallel to the first endomyocardial biopsy in 45 patients (8 children, 37 adults) after HTx. Levels of rd- and dd-cfDNA and DF were determined using digital PCR. Regression analyses were performed with respect to the influence of donor- (age, body surface area (BSA), gender) and recipient-derived factors (age, BSA, gender, kidney function pre-HTx, ventricular assist device (VAD) pre-HTx, previous heart operation) as well as perioperative measures (operation time, ischemic graft time, early rejection, presence of acute kidney injury). <h3>Results</h3> The first biopsy was taken on a mean of 11 days after HTx (median 10, range 5-14, IQR 9-12). Mean ischemic time was 180 min (median 180, range 62-394, IQR 118-215), mean operation time was 376 min (median 333, range 174-745, IQR 239-510). Mean rd-cf-DNA levels were 190,000 copies/μl (median 140,000, range 33,000-1,400,000, IQR 83,000-200,000), mean dd-cfDNA-levels 700 copies/μl (median 400, range 150-7000, IQR 270-620). Mean DF was 0.48 (median 0.33, range 0.09-5.3, IQR 0.2-0.5). In a multiple regression model, ischemic graft time was the only factor with a statistically significant impact on levels of dd-cfDNA, but not on DF. The biggest influence on rd-cfDNA-levels was the use of a VAD pre-HTx, but this was not statistically significant. Strong correlations were seen between age and BSA of donor and recipient. <h3>Conclusion</h3> The separate quantification of both rd- and dd-cfDNA, in contrast to solely reporting DF, allows for the distinction of factors mainly influencing the recipient (such as the pre-HTx use of VAD) and the donor (such as ischemic graft time). In this proof-of-concept study, most of the investigated measures did not reach statistical significance. The correlation of ischemic graft time and dd-cfDNA (but not DF), however, shows the possibility of precisely detecting graft injury

Multimodality Imaging after Liver Transplant: Top 10 Important Complications.

Patients who have undergone liver transplant are now regularly seen in day-to-day radiology practice. All surgical techniques for liver transplant require arterial, portal venous, hepatic venous and caval, and biliary anastomoses. This review is focused on the 10 "not to be missed" complications of liver transplant that affect the health and life of the graft and graft recipient. Arterial complications are the most common and devastating. Early hepatic artery thrombosis may be catastrophic because the biliary tree is solely dependent on the hepatic artery after transplant and collateral vessels have not yet formed. In contrast, delayed hepatic artery thrombosis may be more insidious as collateral arteries develop. US findings of delayed hepatic artery thrombosis may be similar to those of hepatic artery stenosis and celiac artery stenosis. Splenic artery steal syndrome is an increasingly recognized cause of graft ischemia. Venous complications are much less common. Hepatic venous and caval complications are notable for their increased incidence in living-donor and pediatric transplants. Biliary complications often result from arterial ischemia. Biliary cast syndrome is a notable example in which ischemic biliary mucosa sloughs into and obstructs the duct lumens. Neoplasms also may occur within the hepatic graft and may be due to recurrent malignancy, posttransplant lymphoproliferative disorder, or metastases. US is the initial imaging modality of choice, particularly in the acute postoperative setting. Further evaluation with contrast-enhanced US, CT, or MRI; catheter angiography; endoscopic retrograde cholangiopancreatography; and/or nuclear medicine studies is performed as needed. An invited commentary by Bhargava is available online. Online supplemental material is available for this article. ©RSNA, 2022.

Diagnosis and treatment of splenic artery steal syndrome after liver transplantation

AbstractIntroductionSplenic artery steal syndrome is a phenomenon which cause graft ischaemia and dysfunction after liver transplantation.Case PresentationA 31 year old women underwent living donor liver transplantation (LDLT) with a diagnosis of cryptogenic liver cirrhosis. In postoperative follow‐up liver enzymes were elevated. Dynamic computed tomography and digital subtraction angiography revealed splenic artery steal syndrome. Splenic artery ligation was performed for treatment.DiscussionThe diagnosis of splenic artery steal syndrome is made by the presence of slowed hepatic artery flow compared to the splenic artery without hepatic artery thrombosis or stenosis on digital subtraction angiography.ConclusionAlthough interventional radiological procedures are the first‐line treatment method, surgical treatment methods (splenectomy, splenic artery ligation) are successful in increasing hepatic artery flow.

Quantifying and Characterizing Angiogenesis Using the Postnatal Mouse Retina.

Angiogenesis refers to the expansion of blood vessels from a preexisting vascular plexus, and it is a fundamental process for organ development, the female reproductive system, and wound healing, but it is also a common denominator in several diseases such as cancer and neovascular eye disease. For these reasons, shedding light on the molecular and cellular mechanisms of angiogenesis has the potential to devise new therapeutic strategies to refrain pathological vessel growth or even promote new vessel formation in ischemic conditions and organ grafts. The mouse postnatal retina provides an excellent and widely adopted model to study physiological angiogenesis in vivo, and this chapter outlines a detailed protocol for its dissection, staining, and analysis of the vasculature.

Liver Transplantation: Analysis of Preservation Solutions in the Andalusian Registry

The initial objective of this study is to analyze the impact on survival of the preservation solution used. Secondarily, the influence of donor age, underlying pathology, and graft ischemia time is investigated. A multicenter retrospective analytical observational study has been carried out. A population of 1822 liver transplant recipients is studied in 4 Andalusian hospitals between 1995 and 2014. Survival of the patient and graft is analyzed by groups based on the conservation solution used, the age of the donor, the pathology indicated for transplant and the ischemia time, and the relationship between the variables through a bivariate study. A descriptive and predictive multivariate analysis of the variables was performed. Comparison of the graft and patient survival functions for each preservation solution did not differ significantly. The bivariate analysis shows a significantly higher utilization of Celsior and histidine-tryptophan-ketoglutarate solution in graft loss. The comparison between donor age groups showed significant differences in favor of donor grafts younger than 50 years. In the multivariate analysis of patient and graft survival, the donor age obtained a hazard ratio of 1.008 (P < .005) with donors older than 47.6 and 47.5 years, respectively. Survival analysis between pathology groups found significant differences, not obtaining predictive power for patient or graft survival in the multivariate study. No significant differences were found in survival according to ischemia time, but there was a relationship between early graft loss and longer mean cold ischemia times up to 18 hours.