Obesity, organ failure, and transplantation: A review of the role of metabolic and bariatric surgery in transplant candidates and recipients.

Obesity is a risk factor for kidney, liver, heart, and pulmonary diseases, as well as failure. Solid organ transplantation remains the definitive treatment for the end-stage presentation of these diseases. Among many criteria for organ transplant, efficient management of obesity is required for patients to acquire transplant eligibility. End-stage organ failure and obesity are 2 complex pathologies that are often entwined. Metabolic and bariatric surgery before, during, or after organ transplant has been studied to determine the long-term effect of bariatric surgery on transplant outcomes. In this review, a multidisciplinary group of surgeons from the Society of American Gastrointestinal and Endoscopic Surgeons and the American Society for Transplant Surgery presents the current published literature on metabolic and bariatric surgery as a therapeutic option for patients with obesity awaiting solid organ transplantation. This manuscript details the most recent recommendations, pharmacologic considerations, and psychological considerations for this specific cohort of patients. Since level one evidence is not available on many of the topics covered by this review, expert opinion was implemented in several instances. Additional high-quality research in this area will allow for better recommendations and, therefore, treatment strategies for these complex patients.

Long-Term Survival Following Primary Graft Dysfunction Development in Lung Transplantation.

INTRODUCTION: Primary graft dysfunction (PGD) is a known risk factor for early mortality following lung transplant (LT). However, the outcomes of patients who achieve long-term survival following index hospitalization are unknown. We aimed to determine the long-term association of PGD grade 3 (PGD3) in patients without in-hospital mortality. METHODS: LT recipients were identified from the United Network for Organ Sharing Database. Patients were stratified based on the grade of PGD at 72 h (No PGD, Grade 1/2 or Grade 3). Groups were assessed with comparative statistics. Long-term survival was evaluated using Kaplan-Meier methods and a multivariable shared frailty model including recipient, donor, and transplant characteristics. RESULTS: The PGD3 group had significantly increased length of stay, dialysis, and treated rejection post-transplant (P < 0.001). Unadjusted survival analysis revealed a significant difference in long-term survival (P < 0.001) between groups; however, following adjustment, PGD3 was not independently associated with long-term survival (hazard ratio: 0.972; 95% confidence interval: 0.862-1.096). Increased mortality was significantly associated with increased recipient age and treated rejection. Decreased mortality was significantly associated with no donor diabetes, bilateral LT as compared to single LT, transplant in 2015-2016 and 2017-2018, and no post-transplant dialysis. CONCLUSIONS: While PGD3 remains a challenge post LT, PGD3 at 72 h is not independently associated with decreased long-term survival, while complications such as dialysis and rejection are, in patients who survive index hospitalization. Transplant providers should be aggressive in preventing further complications in recipients with severe PGD to minimize the negative association on long-term survival.

Early Extubation: Who Qualifies Postoperatively in Lung Transplantation?

INTRODUCTION: Early extubation has been adopted in many settings within cardiothoracic surgery, with several advantages for patients. We sought to determine the association of timing of extubation in lung transplant recipients' short- and long-term outcomes. METHODS: Adult, primary lung transplants were identified from the United Network for Organ Sharing database. Recipients were stratified based on the duration of postoperative ventilation: 1) None (NV); 2) <5 Days (<5D); and 3) 5+ Days (5+D). Comparative statistics were performed, and both unadjusted and adjusted survival were analyzed with Kaplan-Meier Methods and a Cox proportional hazard model. A multivariable model including recipient, donor, and transplant characteristics was created to examine factors associated with NV. RESULTS: 28,575 recipients were identified (NV = 960, <5D = 21,959, 5+D = 5656). The NV group had shorter median length of stay (P < 0.01) and lower incidence of postoperative dialysis (P < 0.01). The NV and <5D groups had similar survival, while 5+D recipients had decreased survival (P < 0.01). The multivariable model demonstrated increased donor BMI, center volume, ischemic time, single lung transplant, and transplantation between 2011 and 2015 were associated with NV (P < 0.01 for all). Use of donation after cardiac death donors and transplantation between 2016 and 2021 was associated with postoperative ventilator use. CONCLUSIONS: Patients extubated early after lung transplantation have a shorter median length of stay without an associated increase in mortality. While not all patients are appropriate for earlier extubation, it is possible to extubate patients early following lung transplant. Further efforts are necessary to help expand this practice and ensure its' success for recipients.

Obesity, organ failure, and transplantation: a review of the role of metabolic and bariatric surgery in transplant candidates and recipients.

Obesity is a risk factor for kidney, liver, heart, and pulmonary diseases, as well as failure. Solid organ transplantation remains the definitive treatment for the end-stage presentation of these diseases. Among many criteria for organ transplant, efficient management of obesity is required for patients to acquire transplant eligibility. End-stage organ failure and obesity are 2 complex pathologies that are often entwined. Metabolic and bariatric surgery before, during, or after organ transplant has been studied to determine the long-term effect of bariatric surgery on transplant outcomes. In this review, a multidisciplinary group of surgeons from the Society of American Gastrointestinal and Endoscopic Surgeons and the American Society for Transplant Surgery presents the current published literature on metabolic and bariatric surgery as a therapeutic option for patients with obesity awaiting solid organ transplantation. This manuscript details the most recent recommendations, pharmacologic considerations, and psychological considerations for this specific cohort of patients. Since level one evidence is not available on many of the topics covered by this review, expert opinion was implemented in several instances. Additional high-quality research in this area will allow for better recommendations and, therefore, treatment strategies for these complex patients.

The impact of ex vivo lung perfusion location on lung transplant outcomes.

BACKGROUND: Ex vivo lung perfusion (EVLP) conducted outside of the transplant center has increased in recent years to mitigate its limitation by resources and expertise. We sought to evaluate EVLP performed at transplant centers and externally. METHODS: Lung transplant recipients were identified from the United Network for Organ Sharing Database. Recipients were then stratified into two groups based where they were perfused: Transplant Program (TP) or External Perfusion Centers (EPC). The groups were assessed with comparative statistics and long-term survival was assessed by Kaplan-Meier method. The groups were then 1:1 propensity and this process was repeated. RESULTS: EPC use was generally restricted to the Southern United States. Following matching, there were no significant differences in post-operative outcomes to include post-operative stroke, dialysis, airway dehiscence, ECMO use, ventilator use or incidence of primary graft dysfunction Grade 3. Adjusted 3-year survival was 68.9% (95% Confidence Interval [CI]: 60.9%-77.9%) for the TP group and 67.6% (95% CI: 61.0%-74.9%) for the EPC group (p = 0.69). In allografts with extended ischemia (14+ h), those in the TP group had significantly longer length of stay, prolonged ventilation and treated rejection in the 1st year, though no significant difference in mid-term survival (p = 0.66). CONCLUSION: EVLP performed at an EPC can be carried out with results and survival similar to allografts undergoing EVLP at a TP. EPCs will extend the valuable resource of EVLP to lung transplant programs without the resources to perform EVLP.

Extended ischemic times during ex vivo lung perfusion is not associated with increased mortality.

BACKGROUND: The purpose of this study was to identify the association of increasing ischemic times in recipients who receive lungs evaluated by ex vivo lung perfusion (EVLP) and their association with outcomes following lung transplantation. METHODS: Lung transplant recipients who received an allograft evaluated by EVLP were identified from the United Network for Organ Sharing (UNOS) Database from 2016-2023. Recipients were stratified into three groups based on total ischemic time (TOT): short TOT (STOT, 0 to <7 h), medium TOT (MTOT, 7> to <14 h), and long TOT (LTOT, +14 h). The groups were assessed with comparative statistics and Kaplan-Meier methods. A Cox regression was created to determine the association of ischemic time in EVLP donors and long-term mortality. RESULTS: Recipients in the LTOT group had significantly longer length of stay and post-operative extracorporeal membrane use at 72 h (p < 0.05 for both). Additionally, they had nonsignificant increases in rate of stroke (4.7%, p = 0.05) and primary graft dysfunction grade 3 (PGD3, 27.5%, p = 0.082). However, there was no significant difference in hospital mortality or mid-term survival (p > 0.05 for both). On multivariable analysis, ischemic time was not associated with increased mortality whereas increasing recipient age, preoperative ECMO use and donation after circulatory death donors were (p < 0.05 for all). CONCLUSIONS: If EVLP technology is available, under certain circumstances, surgeons should not be dissuaded from using an allograft with extended ischemic time.

Monitored Anesthesia Care for Axillary Impella 5.5 Placement: A Feasible Option for Patients With Severe Cardiogenic Shock With Relative Contraindication to Intubation.

The Impella 5.5 left ventricular assist device (LVAD) is typically placed in a hybrid operating room with fluoroscopic and echocardiographic guidance under general anesthesia. In this case report, we describe a patient with severe cardiopulmonary failure necessitating an Impella 5.5 as a bridge to heart/lung transplant. Here, we describe the successful placement of the Impella 5.5 with sedation and local anesthesia in order to avoid general anesthesia and the sequelae of positive pressure ventilation in a fragile patient. Impella placement was confirmed with transesophageal echocardiography. This case report demonstrates a novel strategy for placing the Impella 5.5 and, more importantly, opens the possibility to future prospective studies of this technique.

An Unexpected Partnership: Alexis Carrel, Charles Lindbergh, and Normothermic Machine Perfusion.

Organ transplantation is a triumph of modern medicine which represents a culmination of science and imagination, saving thousands of lives a year. However, transplantation is severely limited by suitable donor allografts. To expand the donor pool and make transplantation achievable for all, normothermic machine perfusion (NMP) is being employed more frequently. Normothermic machine perfusion involves the utilization of a device to approximate the physiology of the human body, preserve organs outside of the donor, and provide a dynamic assessment platform to determine organ suitability for transplantation. As NMP technology advances, it will soon be possible to genetically modify and actively repair these organs. Although its application to the field of transplantation is relatively new, the concept, foundation, and development of NMP can be traced back to the pioneering work of the surgeon-scientist, Alexis Carrel and the famous aviator, Charles Lindbergh in the 1930s. Their collaboration resulted in the Carrel-Lindbergh Perfusion device, an early perfusion device that was able to keep organs alive ex vivo for weeks and is most appropriately viewed as a precursor to modern machine perfusion technologies. As NMP technology becomes more advanced and refined, it is important to acknowledge the historical context in which these technologies emerged.

Does Size Matter? The Effect of Size of Distal Perfusion Catheter on Acute Limb Ischemia: A Meta-Analysis.

Prevention of limb ischemia in patients with venoarterial extracorporeal membrane oxygenation (VA-ECMO) is primarily achieved through the use of distal perfusion catheters (DPC). Our objective was to assess the role of DPC, and specifically the size of the catheter, in reducing the incidence of acute limb ischemia (ALI) through a meta-analysis. Seventeen studies met criteria for analysis. Pooled analysis included a total of 2,040 patients, of which 904 patients received ECMO with DPC and 1,136 patients underwent ECMO without DPC. Compared with ECMO alone, ECMO with DPC, regardless of size, significantly decreased ALI (relative risk [RR]: 0.49, 95% confidence interval [CI]: 0.31-0.77; p = 0.002). When comparing reactive versus prophylactic placement of DPC, prophylactic DPC was associated with significantly decreased ALI (RR: 0.41, 95% CI: 0.24-0.71; p = 0.02). No differences in mortality (RR: 0.89, 95% CI: 0.76-1.03; p = 0.12) and bleeding events (RR: 1.43, 95% CI: 0.41-4.96; p = 0.58) were observed between the two groups. This analysis demonstrates that the placement of DPC, if done prophylactically and regardless of size, is associated with a reduced risk of ALI versus the absence of DPC placement, but is not associated with differences in mortality or bleeding events.

Is Time Scheduling Important? An Analysis of Donor Heart Cross-clamp Times During Heart Transplantation.

Background: Outcomes in heart transplantation are affected by a variety of variables and patient factors. However, the impact of circadian rhythms, gene expression, and transcription remain underexplored. We thus evaluated the potential role of donor heart cross-clamp times on short-term and long-term outcomes after heart transplantation. Methods: A total of 31 713 heart transplants were identified from the United Network for Organ Sharing Database. Patients were first stratified on the basis of time of donor procurement: 12 am to 12 pm or 12 pm to 12 am. To evaluate a possible effect of circadian rhythms, donor time was further divided into 5 groups based on preclinical data: 4 am to 8 am; 8 am to 11 am; 11 am to 5 pm; 5 pm to 10 pm; 10 pm to 4 am. Groups were assessed with comparative statistics. Long-term survival was evaluated using Kaplan-Meier methods and a multivariate Cox proportional hazard model. Results: Patients who received hearts recovered between 12 am and 12 pm had significantly higher survival than those who received hearts recovered between 12 pm and 12 am. This survival difference was observed in both unadjusted (P = 0.002) and adjusted analyses (hazard ratio [HR]: 0.93; 95% confidence interval [CI], 0.89-0.97; P < 0.001). On unadjusted analysis, the survival difference among the 5 groups was insignificant (P = 0.07). Following adjustment, the periods of 11 am to 5 pm (HR: 1.09, 95% CI, 1.02-1.17; P = 0.012), 5 pm to 10 pm (HR: 1.11; 95% CI, 1.04-1.19; P = 0.002), and 10 pm to 4 am (HR: 1.07; 95% CI, 1.01-1.15; P = 0.034), were all independently associated with increased long-term mortality. Notably, the time of 8 am to 11 am was not associated with a change in survival (HR: 1.04; 95% CI, 0.96-1.14; P = 0.3). Conclusions: Given the independent association of donor timing and survival after adjustment in a large national cohort, further investigation into the role of donor circadian rhythm and donor procurement time is warranted in preclinical and clinical studies. Understanding the underlying mechanisms of this observation could potentially lead to the development of effective treatments and donor procurement processes that prepare the organs for transplantation in a better condition.

Polymerized Human Hemoglobin-Based Oxygen Carrier Preserves Lung Allograft Function During Normothermic Ex Vivo Lung Perfusion.

Normothermic ex vivo lung perfusion (EVLP) can resuscitate marginal lung allografts to increase organs available for transplantation. During normothermic perfusion, cellular metabolism is more active compared with subnormothermic perfusion, creating a need for an oxygen (O 2 ) carrier in the perfusate. As an O 2 carrier, red blood cells (RBCs) are a scarce resource and are susceptible to hemolysis in perfusion circuits, thus releasing cell-free hemoglobin (Hb), which can extravasate into the tissue space, thus promoting scavenging of nitric oxide (NO) and oxidative tissue damage. Fortunately, polymerized human Hb (PolyhHb) represents a synthetic O 2 carrier with a larger molecular diameter compared with Hb, preventing extravasation, and limiting adverse reactions. In this study, a next-generation PolyhHb-based perfusate was compared to both RBC and asanguinous perfusates in a rat EVLP model. During EVLP, the pulmonary arterial pressure and pulmonary vascular resistance were both significantly higher in lungs perfused with RBCs, which is consistent with RBC hemolysis. Lungs perfused with PolyhHb demonstrated greater oxygenation than those perfused with RBCs. Post-EVLP analysis revealed that the PolyhHb perfusate elicited less cellular damage, extravasation, iron tissue deposition, and edema than either RBCs or colloid control. These results show promise for a next-generation PolyhHb to maintain lung function throughout EVLP.

Exploring Alternative Perfusion Solutions Using Next-Generation Polymerized Hemoglobin-Based Oxygen Carriers in a Model of Rat Ex Vivo Lung Perfusion.

Lung transplantation is hampered by the lack of suitable donors. Previously, donors that were thought to be marginal or inadequate were discarded. However, new and exciting technology, such as ex vivo lung perfusion (EVLP), offers lung transplant providers extended assessment for marginal donor allografts. This dynamic assessment platform has led to an increase in lung transplantation and has allowed providers to use donors that were previously discarded, thus expanding the donor pool. Current perfusion techniques use cellular or acellular perfusates, and both have distinct advantages and disadvantages. Perfusion composition is critical to maintaining a homeostatic environment, providing adequate metabolic support, decreasing inflammation and cellular death, and ultimately improving organ function. Perfusion solutions must contain sufficient protein concentration to maintain appropriate oncotic pressure. However, current perfusion solutions often lead to fluid extravasation through the pulmonary endothelium, resulting in inadvertent pulmonary edema and damage. Thus, it is necessary to develop novel perfusion solutions that prevent excessive damage while maintaining proper cellular homeostasis. Here, we describe the application of a polymerized human hemoglobin (PolyhHb)-based oxygen carrier as a perfusate and the protocol in which this perfusion solution can be tested in a model of rat EVLP. The goal of this study is to provide the lung transplant community with key information in designing and developing novel perfusion solutions, as well as the proper protocols to test them in clinically relevant translational transplant models.

Racial and Ethnic Disparities in Peri-and Post-operative Cardiac Surgery.

Purpose of Review: Despite efforts to curtail its impact on medical care, race remains a powerful risk factor for morbidity and mortality following cardiac surgery. While patients from racial and ethnic minority groups are underrepresented in cardiac surgery, they experience a disproportionally elevated number of adverse outcomes following various cardiac surgical procedures. This review provides a summary of existing literature highlighting disparities in coronary artery bypass surgery, valvular surgery, cardiac transplantation, and mechanical circulatory support. Recent Findings: Unfortunately, specific causes of these disparities can be difficult to identify, even in large, multicenter studies, due to the complex relationship between race and post-operative outcomes. Current data suggest that these racial/ethnic disparities can be attributed to a combination of patient, socioeconomic, and hospital setting characteristics. Summary: Proposed solutions to combat the mechanisms underlying the observed disparate outcomes require deployment of a multidisciplinary team of cardiologists, anesthesiologists, cardiac surgeons, and experts in health care equity and medical ethics. Successful identification of at-risk populations and the implementation of preventive measures are necessary first steps towards dismantling racial/ethnic differences in cardiac surgery outcomes.

Ex Vivo Lung Perfusion and Primary Graft Dysfunction Following Lung Transplantation: A Contemporary United Network for Organ Sharing Database Analysis.

Background: Primary graft dysfunction (PGD) has detrimental effects on recipients following lung transplantation. Here, we determined the contemporary trends of PGD in a national database, factors associated with the development of PGD grade 3 (PGD3) and ex vivo lung perfusion's (EVLP) effect on this harmful postoperative complication. Methods: The United Network for Organ Sharing database was queried from 2015 to 2023, and recipients were stratified into No-PGD, PGD1/2, or PGD3. The groups were analyzed with comparative statistics, and survival was determined with Kaplan-Meier methods. Multivariable Cox regression was used to determine factors associated with increased mortality. PGD3 recipients were then stratified based on EVLP use prior to transplantation, and a 3:1 propensity match was performed to determine outcomes following transplantation. Finally, logistic regression models based on select criteria were used to determine risk factors associated with the development of PGD3 and mortality within 1 year. Results: A total of 21.4% of patients were identified as having PGD3 following lung transplant. Those with PGD3 suffered significantly worse perioperative morbidity, mortality, and had worse long-term survival. PGD3 was also independently associated with increased mortality. Matched EVLP PGD3 recipients had significantly higher use of ECMO postoperatively; however, they did not suffer other significant morbidity or mortality as compared to PGD3 recipients without EVLP use. Importantly, EVLP use prior to transplantation was significantly associated with decreased likelihood of PGD3 development, while having no significant association with early mortality. Conclusions: EVLP is associated with decreased PGD3 development, and further optimization of this technology is necessary to expand the donor pool.

Ex vivo lung perfusion in donation after circulatory death: A post hoc analysis of the Normothermic Ex Vivo Lung Perfusion as an Assessment of Extended/Marginal Donors Lungs trial.

OBJECTIVE: Donation after circulatory death (DCD) donors offer the ability to expand the lung donor pool and ex vivo lung perfusion (EVLP) further contributes to this ability by allowing for additional evaluation and resuscitation of these extended criteria donors. We sought to determine the outcomes of recipients receiving organs from DCD EVLP donors in a multicenter setting. METHODS: This was an unplanned post hoc analysis of a multicenter, prospective, nonrandomized trial that took place during 2011 to 2017 with 3 years of follow-up. Patients were placed into 3 groups based off procurement strategy: brain-dead donor (control), brain-dead donor evaluated by EVLP, and DCD donors evaluated by EVLP. The primary outcomes were severe primary graft dysfunction at 72 hours and survival. Secondary outcomes included select perioperative outcomes, and 1-year and 3-years allograft function and quality of life measures. RESULTS: The DCD EVLP group had significantly higher incidence of severe primary graft dysfunction at 72 hours (P = .03), longer days on mechanical ventilation (P < .001) and in-hospital length of stay (P = .045). Survival at 3 years was 76.5% (95% CI, 69.2%-84.7%) for the control group, 68.3% (95% CI, 58.9%-79.1%) for the brain-dead donor group, and 60.7% (95% CI, 45.1%-81.8%) for the DCD group (P = .36). At 3-year follow-up, presence observed bronchiolitis obliterans syndrome or quality of life metrics did not differ among the groups. CONCLUSIONS: Although DCD EVLP allografts might not be appropriate to transplant in every candidate recipient, the expansion of their use might afford recipients stagnant on the waitlist a viable therapy.