{"title":"The perspective for next-generation lung replacement therapies: functional whole lung generation by blastocyst complementation.","authors":"Dai Shimizu, Akihiro Miura, Munemasa Mori","doi":"10.1097/MOT.0000000000001169","DOIUrl":"10.1097/MOT.0000000000001169","url":null,"abstract":"<p><strong>Purpose of review: </strong>Blastocyst complementation represents a promising frontier in next-generation lung replacement therapies. This review aims to elucidate the future prospects of lung blastocyst complementation within clinical settings, summarizing the latest studies on generating functional lungs through this technique. It also explores and discusses host animal selection relevant to interspecific chimera formation, a challenge integral to creating functional human lungs via blastocyst complementation.</p><p><strong>Recent findings: </strong>Various gene mutations have been utilized to create vacant lung niches, enhancing the efficacy of donor cell contribution to the complemented lungs in rodent models. By controlling the lineage to induce gene mutations, chimerism in both the lung epithelium and mesenchyme has been improved. Interspecific blastocyst complementation underscores the complexity of developmental programs across species, with several genes identified that enhance chimera formation between humans and other mammals.</p><p><strong>Summary: </strong>While functional lungs have been generated via intraspecies blastocyst complementation, the generation of functional interspecific lungs remains unrealized. Addressing the challenges of controlling the host lung niche and selecting host animals relevant to interspecific barriers between donor human and host cells is critical to enabling the generation of functional humanized or entire human lungs in large animals.</p>","PeriodicalId":10900,"journal":{"name":"Current Opinion in Organ Transplantation","volume":" ","pages":"340-348"},"PeriodicalIF":1.8,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141987512","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Matthew J Lewis, Kelly H Schlendorf, Leigh C Reardon
{"title":"Integrating risks and benefits: pretransplant assessment and patient selection for heart transplantation in adult congenital heart disease.","authors":"Matthew J Lewis, Kelly H Schlendorf, Leigh C Reardon","doi":"10.1097/MOT.0000000000001170","DOIUrl":"10.1097/MOT.0000000000001170","url":null,"abstract":"<p><strong>Purpose of review: </strong>The number of adult congenital heart disease (ACHD) patients presenting for consideration of heart transplantation continues to grow. Comprehensive pretransplant assessment and thoughtful patient selection are of critical importance to mitigate perioperative and posttransplant morbidity and mortality in this population.</p><p><strong>Recent findings: </strong>There is increasing evidence that patient outcomes after the onset of heart failure in the ACHD population are poor while overall transplant outcomes for ACHD patients have improved over time. Delineation of factors associated with better versus worse posttransplant outcomes is an area of ongoing research. Several studies have found that delayed patient referral, anatomic complexity and the presence of noncardiac organ dysfunction may increase peri-transplant and posttransplant risk.</p><p><strong>Summary: </strong>Pretransplant assessment and patient selection in ACHD patients should focus on mitigating perioperative and early posttransplant risk. Anatomic complexity, noncardiac organ dysfunction, and referral timing after the onset of heart failure can contribute to poor posttransplant outcomes and should inform patient selection.</p>","PeriodicalId":10900,"journal":{"name":"Current Opinion in Organ Transplantation","volume":" ","pages":"305-309"},"PeriodicalIF":1.8,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141855103","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Ethical issues in organ procurement: donation after normothermic regional perfusion in liver transplantation.","authors":"Brian M Nguyen","doi":"10.1097/mot.0000000000001174","DOIUrl":"https://doi.org/10.1097/mot.0000000000001174","url":null,"abstract":"PURPOSE OF REVIEWWith ongoing organ shortages, new perfusion technologies are being embraced to help fill the unmet requirement. Improvement in utilization of donation after cardiac death (DCD) donors has the potential to greatly expand the pool of usable liver allografts. Normothermic regional perfusion (NRP) has been shown to increase usage of DCD donors and improve recipient outcomes. Yet, there remains heterogeneity in its usage worldwide.RECENT FINDINGSResults from the first US multicenter study show improved biliary outcomes with NRP, consistent with prior data from Europe. Internationally, there are wide variations in DCD and NRP usage, highlighting the opportunities for improvement and increased utilization. The ethics of this technique continue to be considered.SUMMARYNRP is a sound technique that can improve utilization for DCD donors, thereby increasing organ supply. Its usage is increasing worldwide. New data continue to show the benefit of this procurement strategy. NRP agrees with the principles of ethics.","PeriodicalId":10900,"journal":{"name":"Current Opinion in Organ Transplantation","volume":"16 1","pages":""},"PeriodicalIF":2.2,"publicationDate":"2024-09-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142264864","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Physical exercise, the immune system and infection risk: implications for prehabilitation and rehabilitation for solid organ transplantation candidates and recipients.","authors":"Nicolette C Bishop","doi":"10.1097/MOT.0000000000001156","DOIUrl":"10.1097/MOT.0000000000001156","url":null,"abstract":"<p><strong>Purpose of review: </strong>Solid organ transplantation recipients have an increased risk of infection, exacerbated by immunosuppressant medications that need to finely balance suppression of the immune system to prevent allograft rejection while avoiding over-suppression leading to infections and malignancy. Exercise modulates immune functions, with moderate-intensity activities particularly associated with enhanced antiviral immunity and reduced infection incidence. However, investigations of the effects of exercise and physical activity on immune function and infection risk posttransplantation are scarce. This review highlights areas where the relationship between exercise, immune function and infection risk has greatest potential for benefit for solid organ transplantation and therefore greatest need for investigation.</p><p><strong>Recent findings: </strong>Moderate and higher intensity exercise do not appear to cause adverse immunological effects in kidney transplantation recipients, although evidence from other organ transplantation is lacking. Evidence from healthy younger and older adults suggests that regular exercise can reduce risk of respiratory infections and latent herpesvirus reactivation and improves antibody responses to vaccination, which is of great importance for organ transplantation recipients.</p><p><strong>Summary: </strong>There is a strong need for research to investigate the role of exercise on immune function and infection risk in solid organ transplantation to improve both allograft survival and long-term health of the recipient.</p>","PeriodicalId":10900,"journal":{"name":"Current Opinion in Organ Transplantation","volume":" ","pages":"271-276"},"PeriodicalIF":1.8,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141283237","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Amelia J Hessheimer, Eva Flores, Jordi Vengohechea, Constantino Fondevila
{"title":"Better liver transplant outcomes by donor interventions?","authors":"Amelia J Hessheimer, Eva Flores, Jordi Vengohechea, Constantino Fondevila","doi":"10.1097/MOT.0000000000001153","DOIUrl":"10.1097/MOT.0000000000001153","url":null,"abstract":"<p><strong>Purpose of review: </strong>Donor risk factors and events surrounding donation impact the quantity and quality of grafts generated to meet liver transplant waitlist demands. Donor interventions represent an opportunity to mitigate injury and risk factors within donors themselves. The purpose of this review is to describe issues to address among donation after brain death, donation after circulatory determination of death, and living donors directly, for the sake of optimizing relevant outcomes among donors and recipients.</p><p><strong>Recent findings: </strong>Studies on donor management practices and high-level evidence supporting specific interventions are scarce. Nonetheless, for donation after brain death (DBD), critical care principles are employed to correct cardiocirculatory compromise, impaired tissue oxygenation and perfusion, and neurohormonal deficits. As well, certain treatments as well as marginally prolonging duration of brain death among otherwise stable donors may help improve posttransplant outcomes. In donation after circulatory determination of death (DCD), interventions are performed to limit warm ischemia and reverse its adverse effects. Finally, dietary and exercise programs have improved donation outcomes for both standard as well as overweight living donor (LD) candidates, while minimally invasive surgical techniques may offer improved outcomes among LD themselves.</p><p><strong>Summary: </strong>Donor interventions represent means to improve liver transplant yield and outcomes of liver donors and grafts.</p>","PeriodicalId":10900,"journal":{"name":"Current Opinion in Organ Transplantation","volume":" ","pages":"219-227"},"PeriodicalIF":1.8,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141087301","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Chase J Wehrle, Chunbao Jiao, Keyue Sun, Mingyi Zhang, Robert L Fairchild, Charles Miller, Koji Hashimoto, Andrea Schlegel
{"title":"Machine perfusion in liver transplantation: recent advances and coming challenges.","authors":"Chase J Wehrle, Chunbao Jiao, Keyue Sun, Mingyi Zhang, Robert L Fairchild, Charles Miller, Koji Hashimoto, Andrea Schlegel","doi":"10.1097/MOT.0000000000001150","DOIUrl":"10.1097/MOT.0000000000001150","url":null,"abstract":"<p><strong>Purpose of review: </strong>Machine perfusion has been adopted into clinical practice in Europe since the mid-2010s and, more recently, in the United States (US) following approval of normothermic machine perfusion (NMP). We aim to review recent advances, provide discussion of potential future directions, and summarize challenges currently facing the field.</p><p><strong>Recent findings: </strong>Both NMP and hypothermic-oxygenated perfusion (HOPE) improve overall outcomes after liver transplantation versus traditional static cold storage (SCS) and offer improved logistical flexibility. HOPE offers additional protection to the biliary system stemming from its' protection of mitochondria and lessening of ischemia-reperfusion injury. Normothermic regional perfusion (NRP) is touted to offer similar protective effects on the biliary system, though this has not been studied prospectively.The most critical question remaining is the optimal use cases for each of the three techniques (NMP, HOPE, and NRP), particularly as HOPE and NRP become more available in the US. There are additional questions regarding the most effective criteria for viability assessment and the true economic impact of these techniques. Finally, with each technique purported to allow well tolerated use of riskier grafts, there is an urgent need to define terminology for graft risk, as baseline population differences make comparison of current data challenging.</p><p><strong>Summary: </strong>Machine perfusion is now widely available in all western countries and has become an essential tool in liver transplantation. Identification of the ideal technique for each graft, optimization of viability assessment, cost-effectiveness analyses, and proper definition of graft risk are the next steps to maximizing the utility of these powerful tools.</p>","PeriodicalId":10900,"journal":{"name":"Current Opinion in Organ Transplantation","volume":" ","pages":"228-238"},"PeriodicalIF":1.8,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140897495","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Damiano Patrono, Nicola De Stefano, Renato Romagnoli
{"title":"Liver transplantation for tumor entities.","authors":"Damiano Patrono, Nicola De Stefano, Renato Romagnoli","doi":"10.1097/MOT.0000000000001149","DOIUrl":"10.1097/MOT.0000000000001149","url":null,"abstract":"<p><strong>Purpose of review: </strong>Tumor entities represent an increasing indication for liver transplantation (LT). This review addresses the most contentious indications of LT in transplant oncology.</p><p><strong>Recent findings: </strong>Patient selection based on tumor biology in LT for colorectal cancer liver metastases (CRLM) demonstrated promising long-term outcomes and preserved quality of life despite high recurrence rates. In selected cases, LT for intrahepatic cholangiocarcinoma (iCCA) is feasible, with acceptable survival even in high-burden cases responsive to chemotherapy. LT following a strict neoadjuvant protocol for perihilar cholangiocarcinoma (pCCA) resulted in long-term outcomes consistently surpassing benchmark values, and potentially outperforming liver resection.</p><p><strong>Summary: </strong>While preliminary results are promising, prospective trials are crucial to define applications in routine clinical practice. Molecular profiling and targeted therapies pave the way for personalized approaches, requiring evolving allocation systems for equitable LT access.</p>","PeriodicalId":10900,"journal":{"name":"Current Opinion in Organ Transplantation","volume":" ","pages":"255-265"},"PeriodicalIF":1.8,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140876123","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Stephen Possick, Vandana Khungar, Ranjit Deshpande
{"title":"Cardiac evaluation of the liver transplant candidate.","authors":"Stephen Possick, Vandana Khungar, Ranjit Deshpande","doi":"10.1097/MOT.0000000000001122","DOIUrl":"10.1097/MOT.0000000000001122","url":null,"abstract":"<p><strong>Purpose of review: </strong>This review aims to summarize recent changes in the cardiac evaluation of adult liver transplant candidates. Over the last several years, there have been significant advances in the use of coronary computed tomography angiography (CCTA) with and without fractional flow reserve (FFR) and increasingly widespread availability of coronary calcium scoring for risk stratification for obstructive coronary artery disease. This has led to novel strategies for risk stratification in cirrhotic patients being considered for liver transplant and an updated American Heart Association (AHA) position paper on the evaluation of liver and kidney transplant candidates. The diagnosis of cirrhotic cardiomyopathy has been refined. These new diagnostic criteria require that specific echocardiographic parameters are evaluated in all patients. The definition of pulmonary hypertension on echocardiography has been altered and no longer utilizes right atrium (RA) pressure estimates based on inferior vena cava (IVC) size and collapse. This provides more volume neutral estimates of pulmonary pressure.</p><p><strong>Recent findings: </strong>Although CCTA has outstanding negative predictive value, false positive results are not uncommon and often lead to further testing. Revised diagnostic criteria for cirrhotic cardiomyopathy improve risk stratification for peri-operative volume overload and outcomes. Refined pulmonary hypertension criteria provide improved guidance for right heart catheterization (RHC) and referral to subspecialists. There are emerging data regarding the safety and efficacy of TAVR for severe aortic stenosis in cirrhotic patients.</p><p><strong>Summary: </strong>Increased utilization of noninvasive testing, including CCTA and/or coronary calcium scoring, can improve the negative predictive value of testing for obstructive coronary artery disease and potentially reduce reliance on coronary angiography. Application of the 2020 criteria for cirrhotic cardiomyopathy will improve systolic and diastolic function assessment and subsequent perioperative risk stratification. The use of global strain scores is emphasized, as it provides important information beyond ejection fraction and diastolic parameters. A standardized one-parameter echo cut-off for elevated pulmonary pressures simplifies both evaluation and follow-up. Innovative transcutaneous techniques for valvular stenosis and regurgitation offer new options for patients at prohibitive surgical risk.</p>","PeriodicalId":10900,"journal":{"name":"Current Opinion in Organ Transplantation","volume":" ","pages":"299-304"},"PeriodicalIF":1.8,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138298615","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Roberto Broere, Stefan H Luijmes, Jeroen de Jonge, Robert J Porte
{"title":"Graft repair during machine perfusion: a current overview of strategies.","authors":"Roberto Broere, Stefan H Luijmes, Jeroen de Jonge, Robert J Porte","doi":"10.1097/MOT.0000000000001151","DOIUrl":"10.1097/MOT.0000000000001151","url":null,"abstract":"<p><strong>Purpose of review: </strong>With changing donor characteristics (advanced age, obesity), an increase in the use of extended criteria donor (ECD) livers in liver transplantation is seen. Machine perfusion allows graft viability assessment, but still many donor livers are considered nontransplantable. Besides being used as graft viability assessment tool, ex situ machine perfusion offers a platform for therapeutic strategies to ameliorate grafts prior to transplantation. This review describes the current landscape of graft repair during machine perfusion.</p><p><strong>Recent findings: </strong>Explored anti-inflammatory therapies, including inflammasome inhibitors, hemoabsorption, and cellular therapies mitigate the inflammatory response and improve hepatic function. Cholangiocyte organoids show promise in repairing the damaged biliary tree. Defatting during normothermic machine perfusion shows a reduction of steatosis and improved hepatobiliary function compared to nontreated livers. Uptake of RNA interference therapies during machine perfusion paves the way for an additional treatment modality.</p><p><strong>Summary: </strong>The possibility to repair injured donor livers during ex situ machine perfusion might increase the utilization of ECD-livers. Application of defatting agents is currently explored in clinical trials, whereas other therapeutics require further research or optimization before entering clinical research.</p>","PeriodicalId":10900,"journal":{"name":"Current Opinion in Organ Transplantation","volume":" ","pages":"248-254"},"PeriodicalIF":1.8,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11224572/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140897493","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Nicholas Bourgeois, Catherine M Tansey, Tania Janaudis-Ferreira
{"title":"Exercise training in solid organ transplant candidates and recipients.","authors":"Nicholas Bourgeois, Catherine M Tansey, Tania Janaudis-Ferreira","doi":"10.1097/MOT.0000000000001158","DOIUrl":"10.1097/MOT.0000000000001158","url":null,"abstract":"<p><strong>Purpose of review: </strong>Exercise training programs are an integral part of the management of solid organ transplantation (SOT) candidates and recipients. Despite this, they are not widely available and specific guidelines on exercise parameters for each type of organ are not currently provided. A review of this topic could help clinicians to prescribe appropriate exercise regimens for their patients.</p><p><strong>Recent findings: </strong>In this narrative review, we discuss the physical impairments of SOT candidates and recipients and how these affect their physical function and transplant outcomes. We examine recent systematic reviews, statements, and randomized controlled trials on exercise training in SOT candidates and recipients and present the current available evidence while providing some practical recommendations for clinicians based on the frequency, intensity, time, and type principle.</p><p><strong>Summary: </strong>While randomized controlled trials of better methodology quality are needed to strengthen the evidence for the effects of exercise training and for the optimal training characteristics, the available evidence points to beneficial effects of many different types of exercise. The current evidence can provide some guidance for clinicians on the prescription of exercise training for transplant candidates and recipients.</p>","PeriodicalId":10900,"journal":{"name":"Current Opinion in Organ Transplantation","volume":" ","pages":"277-283"},"PeriodicalIF":1.8,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141260480","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}