Organ Donation Research Articles

Nova Scotia's Deemed Consent for Deceased Organ Donation: Family Member Perspectives and Experiences in the ICU Setting.

The purpose of this study was to explore the experience of family members of potential organ donors in the intensive care unit following the change to deemed consent legislation in Nova Scotia. This was a qualitative study with semistructured, in-depth interviews with 17 family members who were asked to make an organ donation decision on behalf of patients admitted to the intensive care unit in Nova Scotia. We analyzed themes using a descriptive approach. Participants were recruited from the organ donation organization in Nova Scotia, Canada. Participant awareness and knowledge of the Human Organ and Tissue Donation Act legislation varied from individuals having no awareness and knowledge of the bill to those who had awareness and optimism that the legislation would be beneficial for increasing organ donation rates in the province. Other themes emerging from the interviews included (1) COVID context, (2) quality of healthcare professional care, (3) family support, and (4) barriers to donation (waiting, consent questionnaire, and patient transfers). The Human Organ and Tissue Donation Act legislation included enhanced support, which was viewed positively by family members. There is a need for continued evaluation as most participants felt it was too early to see the tangible impacts of the newly implemented legislation.

Culture on organ and tissue donation in the community of Medical School, Veracruz Region

Abstract Introduction Organ donation is a life-saving activity, yet there is a disparity between the high number of recipients and the minimal number of donors. Objetives To determine the level of organ and tissue donation culture for transplant purposes among faculty members and undergraduate medical interns at a Medical School Methods A cross-sectional and prospective study was conducted from January 2023 to 2024, including faculty members and undergraduate medical interns from the Medical School at the University of Veracruz - Veracruz Region. The main study variable was the culture of organ and tissue donation for transplant purposes, quantified through three dimensions: knowledge, attitude, and training, assessed using a validated instrument (Cronbach’s alpha: 0.6). The entire described population was included, and they were approached in different areas to invite them to participate in this research. Results 225 subjects (55 faculty members) agreed to participate. 97% of participants expressed support for organ donation. Among those not in favor of donation, 33% feared receiving poor medical care as donors, and 17% viewed donation as a business. Organ donation culture was deemed sufficient in 10.98% and outstanding in 71.76% of participants. The most common level of knowledge was outstanding (52%), 70% of the studied population showed a ‘very positive’ attitude towards organ and tissue donation. Training history was evaluated as an associated factor with knowledge about organ donation (OR/CI95%), identifying an association between lack of training and levels of sufficient knowledge (2.5/1.2-4.9) and outstanding knowledge (0.3/0.1-0.7), as well as with sufficient culture (9.6/1.2-73.0) and outstanding culture (0.1/0.04-0.4) (p < 0.05) Conclusions It is imperative to strengthen training programs for faculty and undergraduate personnel, as quality training enhances knowledge and culture within this essential area of healthcare personnel formation. Key messages • University professors should have accurate information on organ donation and sensitize future physicians on the subject, as this could be a crucial step for future interactions in favor of donation. • It is necessary to eradicate misinformation about organ donation in teachers and students of medical schools, since they are the basis for education and awareness on this issue in the population.

Long-term outcomes of heart re-transplantation from HCV-viremic donors based on UNOS registry

Abstract Background The use of hepatitis C virus (HCV) viremic donors increased the heart donor pool, and reduced waitlist time and mortality among first-time single-organ heart transplant (HT) candidates without compromising their post-transplant survival. The outcomes of heart re-transplantation (re-HT) with the use of HCV-viremic donor grafts have not been investigated. Methods Using the United Network of Organ Sharing (UNOS) Registry we analyzed all adult patients who underwent single-organ heart re-HT in the United States between January 1, 2016, and December 31, 2022. HCV-viremic donors were defined by a positive nucleic acid amplification test (NAT+). Graft survival rates between HCV-viremic and HCV-non-viremic donor graft recipients were compared using a log rank test. Results During the study period, of 18,259 HTs performed, 427 (2.3%) constituted single-organ heart re-transplantations. Recipients of NAT+ grafts (n=19) compared to NAT- grafts (n=408) were more often male (84.2% vs 61.3%, p=0.04). Otherwise, there were no significant differences between the two groups in age, ethnicity, BMI, blood type, history of diabetes rates or stroke, creatinine or bilirubin levels, reason for re-HT, hemodynamics, use of mechanical circulatory support, and waitlist time. Ischemic time, frequency of female donors, HLA, ABO, CMV mismatch rates, and calculated panel reactive antibodies levels were comparable across the two groups. There were no significant differences in demographics or comorbidities rates between HCV-viremic and HCV-non-viremic donors apart from the cause of death. Among the donors of HCV-viremic grafts brain anoxia was reported more often (89.5%) than among HCV-non-viremic donors (40%), p <0.01. Rates of acute rejection treated in the first year after re-HT were comparable across the two groups. Over a mean follow-up of 3.0±2.1 and 3.3±1.8 years after re-HT from NAT- and NAT+ organ donors, respectively, graft survival rate at 1 year was 82% vs. 95% (p=0.3) and at 3 years 79% vs. 89%, respectively (p=0.6) (Figure). Conclusion Graft survival rates at 1 and 3 years post-heart re-HT in adult recipients of HCV-viremic donor grafts were comparable to those of recipients of HCV-non-viremic donor grafts. The current study provides compelling preliminary evidence that HCV-viremic donors constitute a viable donor pool for patients in need of heart re-transplantation.

The myocardium of human dilated nonischemic cardiomyopathy harbors unique tissue-resident lymphocyte subsets

Abstract Purpose The etiology of dilated nonischemic cardiomyopathy (NICM) is often unclear, but thought to be multifactorial, involving an interplay between genetic factors and direct myocardial damage caused by infection, autoimmunity, or toxins. Tissue-resident lymphocytes are non-circulating immune cells which are retained within various tissues and play integral roles in maintaining homeostasis, responding to infection, regulating inflammation, and mediating tissue repair. Despite their likely involvement in various cardiac pathologies, the presence of tissue-resident lymphocytes in the human heart has not yet been well-characterized, neither in health nor in disease. Methods Human left ventricular tissue and paired peripheral blood samples were obtained from six adult organ donors with normal heart function who died of noncardiac causes and from the explants of six adult patients with end-stage nonischemic cardiomyopathy. Heart tissue was processed using mechanical and enzymatic digestion. Mononuclear cells were isolated from both heart and paired blood by density centrifugation. Isolated mononuclear cells were surface stained with an antibody cocktail and interrogated using multidimensional flow cytometry. Results The adult human heart contains a diverse immune cell population (Fig 1A). Both healthy and NICM cardiac lymphocytes express distinct phenotypic profiles which resemble those of resident lymphocytes found across various tissues, distinct from those isolated from paired blood. Frequencies of effector memory T (Tem) cells (CD45RA- CCR7-) were higher in heart than in blood among both CD4+ and CD8+ T-cells. In heart compared to blood, significantly more Tem expressed CD69, a canonical marker of tissue-resident memory T (Trm) cells (Fig 1B). Cardiac Trm, especially CD8+ Trm, expressed classical Trm signature markers including integrins CD103 (epithelial binding) and CD49a (collagen binding). NICM Trm expressed more CD49a than healthy heart Trm (Fig 1C). NK-cells also demonstrated higher CD69 expression (trNK) in heart than in blood, with associated expression of CD103, CD49a, and CXCR6 (Fig 1D). Compared to healthy hearts, NICM trNK were predominantly CD56bright/CD16- (Fig 1E and 1F) and expressed less CD57 (Fig 1D), overall indicating a less mature state with lower cytotoxic potential. Confocal imaging of cardiac tissue revealed CD69-expressing tissue-resident lymphocytes within the cardiac interstitium. Conclusions The adult human heart contains diverse populations of lymphocytes which express canonical markers of tissue residency, similar to lymphocytes resident in other tissues. Compared to healthy hearts, NICM hearts have more CD49a+ Trm, perhaps related to greater fibrosis, and also harbor a distinct subset of immature tissue-resident NK cells which may shed light on pathophysiology. Future work is focused on better exploring the functional phenotypes of these resident cells and better localizing them within the myocardium.FA - Figure 1

National trends of left ventricular assist device therapy in Germany

Abstract Background The prevalence of advanced heart failure (HF) is increasing and prognosis remains poor. Although heart transplantation is still considered to be the gold standard for the treatment of advanced HF in selected patients, its use is limited by organ donor shortage and a growing burden of cormorbidities among potential recipients. The 2021 European Society of Cardiology (ESC) guidelines recommend consideration of long-term mechanical circulatory support with a left ventricular assist device (LVAD) in eligible patients with advanced heart failure (HF) who are refractory to medical/device therapy. Purpose The purpose of this study was to evaluate the national trends of LVAD in Germany. The main hypothesis was that LVAD therapy is still underutilized. Methods From the national database of the German Federal Statistical Office (DESTATIS), we identified all patients who underwent LVAD implantation in Germany between January 2011 and December 2022 (n = 9,232). We compared temporal trends and in-hospital outcomes. Results From 2011 to 2022, number of LVAD implantation was highest in the year 2017 (n = 914) and steadily decreased over the following years (2022: n = 617). Mean age of LVAD recipients was 56.2 years (2011-2015) and increased to 58.4 years (2020-2022). The majority of LVAD recipients are male (84,8 %), and this trend has been stable during the entire time period. In-hospital mortality after LVAD remains high, but has been decreasing (25.8% during 2011-2015 compared to 20.2% during 2020-2022). Conclusion Although LVAD is recommended in eligible patients with advanced HF, our study suggests an underutilization of LVAD in this patient population and especially in female patients.

Organ Donation Process for Transplantation: A Scoping Review

Objectives: To identify studies in the literature that address the strategies used in the organ donation process. Method: Scoping review based on the Joanna Briggs Institute ( JBI) methodology, in the databases Medical Literature and Retrieval System Online (MEDLINE), Scopus, Web of Science, Latin American and Caribbean Literature in Health Sciences (LILACS), and Embase via the Virtual Health Library (VHL), following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses Extension for Scoping Reviews (PRISMA-ScR) checklist, carried out from August to December 2023. Results:"irty-three studies were eligible, which showed that the donation process must happen systematically, following the steps: 1) identi#cation of patients suspected of having brain death (BD); 2) opening the protocol and notifying organizations; 3) con#rmation of the diagnosis of BD; 4) communicating the death to the family; 5) conducting the interview; 6) consent to donation; 7) donor maintenance; 8) procurement and allocation of organs; 9) transplant; and 10) follow-up. Conclusion: Donation requires a multifaceted approach, including awareness, investment, evaluation and research.

Optimized partial freezing protocol enables 10-day storage of rat livers

Preserving organs at subzero temperatures with halted metabolic activity holds the potential to prolong preservation and expand the donor organ pool for transplant. Our group recently introduced partial freezing, a novel approach in high-subzero storage at -15 °C, enabling 5-day storage of rodent livers through precise control over ice nucleation and unfrozen fraction. However, increased vascular resistance and tissue edema suggested a need for improvements to extend viable preservation. Here, we describe an optimized partial freezing protocol with key optimizations, including an increased concentration of polyethylene glycol (PEG) to enhance membrane stability while minimizing shear stress during cryoprotectant unloading with an acclimation period and a maintained osmotic balance through an increase in bovine serum albumin (BSA). These approaches ensured the viability during preservation and recovery processes, promoting liver function and ensuring optimal preservation. This was evidenced by increased oxygen consumption, decreased vascular resistance, and edema. Ultimately, we show that using the optimized protocol, livers can be stored for 10 days with comparable vascular resistance and lactate levels to 5 days, outperforming the viability of time-matched static cold stored (SCS) livers as the current gold standard. This study represents a significant advancement in expanding organ availability through prolonged preservation, thereby revolutionizing transplant medicine.

A multicenter observational study to establish practice for circulatory death declaration for organ donation in South Korea

Background This study aimed to determine the proportion of organ donors suitable for donation after circulatory death and investigate the current process followed by critical care physicians for declaring circulatory death to establish organ donation. Methods This observational study involved potential organ donors who had recently died after discontinuation of life support. We conducted an online survey of intensivists to determine how these deaths were confirmed. Results Among the 177 patients who died after withdrawal of life-sustaining treatment across 19 intensive care units in 11 institutions, 49 (27.7%) were considered potential donors. According to general medical criteria for organ donation, 20 (11.3%) patients were identified as medically suitable donors. Notably, 116 (73.9%) patients exhibited a flat electrocardiogram within 5 min after the loss of pulse. In the survey, 90 physicians (59.2%) agreed to implement the concept of the 5-min no-touch period for the declaration of circulatory death. Conclusions This study found that 11.3% of the patients who died following the withdrawal of life-sustaining treatment in the intensive care units were identified as suitable donors after circulatory death. Most of critical care physicians agree with the concept of a 5-min no-touch period for the declaration of circulatory death.

Future directions in transmasculine genital gender-affirming surgery: tissue substitutes and transplant.

The present study reviews contemporary literature focused on transplantation and tissue substitutes for the purposes of masculinizing genital gender affirming surgery. Additional background is provided for both topics to provide a more comprehensive understanding of the modern applications. Genitourinary vascularized composite allotransplantation has become a reality in recent years with several cases reported worldwide in cisgender men with promising reports of urinary and sexual function. A natural extension might be to apply these techniques to gender affirming surgery (GAS). Technical barriers include anatomic differences between vasculature supporting penoscrotal and vulvovaginal anatomy as well as size discrepancies between the corporal bodies which complicate the required anastomoses. Whether the smaller caliber of biologic female pelvic vasculature can support erection of a neophallus is another obstacle. Ethically, resource allocation, elective immunosuppression, society response to organ donation and gender identity, as well as the psychosocial safety of the patient given charged public opinion must all be considered.Tissue substitutes have long been used in urologic reconstruction but more recently applied to masculinizing gender affirmation surgery which has traditionally relied on autografting. The focus has been on restoring form and function to the donor site as well as facilitating treatment of urethral stricture and wound complications after phalloplasty. Furthermore, aesthetic applications have also been described, most recently for glans atrophy. The field of masculinizing gender affirmation surgery represents an exciting frontier for surgeons and patients alike. Given the relative nascency of the specialty and its propensity to draw techniques from various surgical disciplines there exists a unique opportunity for rapid innovation to overcome challenging problems posed by these complex procedures as evidenced by discussions around applying penile transplantation and the use of novel tissue grafting techniques.

HeartMate III Autonomy Assistant in a Hemiplegic Left Ventricular Assist Device Patient: A Case Report.

Terminal heart failure presents challenges, requiring cardiac transplantation, or mechanical circulatory support. Limited donor organ availability has made mechanical support crucial. Advances in centrifugal-flow systems, compared to axial-flow, have improved patient outcomes by reducing adverse events. Rehabilitation is vital for patient independence postimplantation. We developed a tool to aid hemiplegic patients in managing power sources. A 44 year old male with tritroncular ischemic heart disease and a 15% ejection fraction. He underwent a double bypass and left ventricular assist device (LVAD) implantation while awaiting a transplant. Postsurgery, the patient suffered a stroke, leading to left motor impairments. To assist in managing LVAD power sources, an autonomous tool with a Woodcast support base and antislip surface was developed. The tool improves autonomy and quality of life for motor-impaired patients. It is designed to be portable, adaptable, supporting various mobility levels. Real-world evidence shows it reduces time and alarms for battery changes, proving effective in home settings. The tool significantly enhances hemiparetic patients' self-care and independence, showing promise for motor-impaired individuals. Further research is needed to evaluate long-term benefits and challenges.

What Does the Evaluation of the Organ Donation (Deemed Consent) Act 2019 in England Tell Us About the Effectiveness of Deemed Consent Systems for Deceased Organ Donation?

What Does the Evaluation of the Organ Donation (Deemed Consent) Act 2019 in England Tell Us About the Effectiveness of Deemed Consent Systems for Deceased Organ Donation?

Enhancing differentiation and functionality of insulin-producing cells derived from iPSCs using esterified collagen hydrogel for cell therapy in diabetes mellitus

BackgroundIslet transplantation is a recommended treatment for type 1 diabetes but is limited by donor organ shortage. This study introduces an innovative approach for improving the differentiation and functionality of insulin-producing cells (IPCs) from iPSCs using 3D spheroid formation and hydrogel matrix as an alternative pancreatic islet source. The extracellular matrix (ECM) is crucial for pancreatic islet functionality, but finding the ideal matrix for β-cell differentiation has been challenging. We aimed to advance IPC differentiation and maturation through an esterified collagen hydrogel, comparing its effectiveness with conventional basement membrane extract (BME) hydrogels.MethodsiPSCs were differentiated into IPCs using a small molecule-based sequential protocol, followed by spheroid formation in concave microwells. Rheological analysis, scanning electron microscopy, and proteomic profiling were used to characterize the chemical and physical properties of each matrix. IPCs, both in single-cell form and as spheroids, were embedded in either ionized collagen or BME hydrogels, which was followed by assessments of morphological changes, pancreatic islet-related gene expression, insulin secretion, and pathway activation using comprehensive analytical techniques.ResultsEsterified collagen hydrogels markedly improved the structural integrity, insulin expression, and cell-cell interactions in IPC spheroids, forming densely packed insulin-expressing clusters, in contrast to the dispersed cells observed in BME cultures. Collagen hydrogel significantly enhanced the mRNA expression of crucial endocrine markers and maturation factors, with IPC spheroids showing accelerated differentiation from day 5, suggesting a faster differentiation compared to single cells in hydrogel encapsulation. Insulin secretion in response to glucose in collagen environments, with a GSIS index of 2.46 ± 0.05, exceeded those in 2D and BME, demonstrating superior pancreatic islet functionality. Pathway analysis highlighted enhanced insulin secretion capabilities, evidenced by the upregulation of genes like Secretogranin III and Chromogranin A in collagen cultures. In vivo transplantation results showed that collagen hydrogel enhanced cluster integrity, tissue integration, and insulin secretion compared to non-embedded IPCs and BME groups.ConclusionEsterified collagen hydrogels demonstrated superior efficacy over 2D and BME in promoting IPC differentiation and maturation, possibly through upregulation of the expression of key secretion pathway genes. Our findings suggest that using collagen hydrogels presents a promising approach to enhance insulin secretion efficiency in differentiating pancreatic β-cells, advancing cell therapy in diabetes cell therapy.

Supporting Financial Neutrality in Donation of Organs, Cells, and Tissues.

The avoidance of financial gain in the human body is an international ethical standard that underpins efforts to promote equity in donation and transplantation and to avoid the exploitation of vulnerable populations. The avoidance of financial loss due to donation of organs, tissues, and cells is also now recognized as an ethical imperative that fosters equity in donation and transplantation and supports the well-being of donors and their families. Nevertheless, there has been little progress in achieving financial neutrality in donations in most countries. We present here the findings of an international ethics working group convened in preparation for the 2023 Global Summit on Convergence in Transplantation, held in Santander, Spain, which was tasked with formulating recommendations for action to promote financial neutrality in donation. In particular, we discuss the potential difficulty of distinguishing interventions that address donation-related costs from those that may act as a financial incentive for donation, which may inhibit efforts to cover costs. We also outline some practical strategies to assist governments in designing, implementing, and evaluating policies and programs to support progress toward financial neutrality in donation.

Developing and Expanding Deceased Organ Donation to its Maximum Therapeutic Potential: An Actionable Global Challenge From the 2023 Santander Summit.

On November 9 and 10, 2023, the Organización Nacional de Trasplantes (ONT), under the Spanish Presidency of the Council of the European Union, convened in Santander a Global Summit entitled "Towards Global Convergence in Transplantation: Sufficiency, Transparency and Oversight." This article summarizes two distinct but related challenges elaborated at the Santander Summit by Working Group 2 that must be overcome if we are to develop and expand deceased donation worldwide and achieve the goal of self-sufficiency in organ donation and transplantation. Challenge 1: the need for a unified concept of death based on the permanent cessation of brain function. Working group 2 proposed that challenge 1 requires the global community to work toward a uniform, worldwide definition of human death, conceptually unifying circulatory and neurological criteria of death around the cessation of brain function and accepting that permanent cessation of brain function is a valid criterion to determine death. Challenge 2: reducing disparities in deceased donation and increasing organ utilization through donation after the circulatory determination of death (DCDD). Working group 2 proposed that challenge 2 requires the global community to work toward increasing organ utilization through DCDD, expanding DCDD through in situ normothermic regional perfusion, and expanding DCDD through ex situ machine organ perfusion technology. Recommendations for implementation are described.

Expanding Opportunities for Living Donation: Recommendations From the 2023 Santander Summit to Ensure Donor Protections, Informed Decision Making, and Equitable Access

A strategic vision toward global convergence in transplantation must encourage and remove barriers to living organ donation and transplantation. Here, we discuss deliberations of a working group of the 2023 Santander Summit charged with formulating recommendations for the safe expansion of living donor kidney transplantation and living donor liver transplantation worldwide. Living donor kidney transplantation has grown to be the preferred treatment for advanced kidney failure. Living donor liver transplantation emerged more recently as a strategy to reduce waitlist mortality, with adoption influenced by cultural factors, regional policies, clinical team experience, and the maturity of regional deceased donor transplant systems. Barriers to living donor transplantation span domains of education, infrastructure, risk assessment/risk communication, and financial burden to donors. Paired donor exchange is a growing option for overcoming incompatibilities to transplantation but is variably used across and within countries. Effectively expanding access to living donor transplantation requires multifaceted strategies, including improved education and outreach, and measures to enhance efficiency, transparency, and shared decision making in donor candidate evaluation. Efforts toward global dissemination and vigilant oversight of best practices and international standards for the assessment, informed consent, approval, and monitoring of living donors are needed. Fostering greater participation in paired exchange requires eliminating disincentives and logistical obstacles for transplant programs and patients, and establishing an ethical and legal framework grounded in World Health Organization Guiding Principles. Sharing of best practices from successful countries and programs to jurisdictions with emerging practices is vital to safely expand the practice of living donation worldwide and bring the field together globally.

Reinforcing Global Oversight of Organ Transplantation: Activity and Outcome Monitoring Through the Development of Registries.

Establishing transparency and oversight of organ transplantation by regulatory agencies is of paramount importance to assure ethical, legal, and clinically robust transplantation practices. Registries reporting activity and outcome data of the donor and recipient, including donor source (living or deceased), must be developed for each transplant and should be a mandatory requirement to achieve accreditation to perform transplant surgeries. Collected data for the living organ donor must include the nationality, the nature of their relationship with the recipient, and the complications encountered by living donors that result in prolonged morbidity or mortality. Long-term patient and graft survival must be reported for the recipient with the underlying reasons for mortality or graft loss. To retain the authorization to perform organ transplantation, a facility must ensure that it reports this required information regarding every organ transplant.

Recent Progress on Organic Electron Donors (OEDs) Enabled Radical Reactions

Over the past few decades, organic transformations facilitated by small organic molecules have witnessed considerable advancements. Small organic molecules have been widely applied to the construction of various skeletons. However, reduction as one of the fundamental reactions is generally initiated by metal‐containing reducing agents, although the initial progress of organic electron donors (OEDs) enabled reductive cleavage of some chemical bonds had been achieved in 1990s. Due to their structural diversity and tunability, OEDs can overcome the limitations of metal‐based reducing agents, such as low selectivity and poor functional group tolerance as well as the environmental problems caused by substantial inorganic waste after reactions. Building on a brief historical overview of OED research, this review focuses on the rencent advancements of the OEDs promoted radical reactions. It covers the reduction of C‐X (X =C, O, N etc.) single bonds, radical cyclization, intermolecular radical addition to unsaturated bonds, radical coupling, functionalization of aromatics, and C‐H bond activation. Additionally, the mechanistic insights of the typical reactions are highlighted for well understanding of the reaction mode involving OEDs.

AI for biofabrication.

Biofabrication is an advanced technology that holds great promise for constructing highly biomimetic in vitro three-dimensional human organs. Such technology would help address the issues of immune rejection and organ donor shortage in organ transplantation, aiding doctors in formulating personalized treatments for clinical patients and replacing animal experiments. Biofabrication typically involves the interdisciplinary application of biology, materials science, mechanical engineering, and medicine to generate large amounts of data and correlations that require processing and analysis. Artificial intelligence (AI), with its excellent capabilities in big data processing and analysis, can play a crucial role in handling and processing interdisciplinary data and relationships and in better integrating and applying them in biofabrication. In recent years, the development of the semiconductor and integrated circuit industries has propelled the rapid advancement of computer processing power. An AI program can learn and iterate multiple times within a short period, thereby gaining strong automation capabilities for a specific research content or issue. To date, numerous AI programs have been applied to various processes around biofabrication, such as extracting biological information, designing and optimizing structures, intelligent cell sorting, optimizing biomaterials and processes, real-time monitoring and evaluation of models, accelerating the transformation and development of these technologies, and even changing traditional research patterns. This article reviews and summarizes the significant changes and advancements brought about by AI in biofabrication, and discusses its future application value and direction.&#xD.

Locoregional Therapies and Interventional Radiology in Managing Hepatocellular Carcinoma: A Comprehensive Approach to Bridging, Downstaging, and Liver Transplantation

AbstractHepatocellular carcinoma (HCC) remains a significant global health challenge, particularly for patients awaiting liver transplants (LTs) due to the scarcity of donor organs. During the waiting period, a multidisciplinary approach becomes crucial to optimize tumor treatment and preserve liver function. In recent years, interventional radiology has emerged as an integral part of treatment strategies. It has played a pivotal role in bridging and downstaging patients on the path to transplantation. Interventional radiologists administer minimally invasive locoregional therapies to HCC patients on LT waiting lists. Additionally, they address complications such as portal hypertension and portal vein thrombosis, which can lead to clinical deterioration and jeopardize transplant candidacy. This article examines the pivotal role of interventional radiology in the management of HCC, highlighting recent studies and advancements within the field. Additionally, it provides a concise review of the eligibility criteria for LT in patients with HCC, alongside a discussion of the surgical techniques employed in LT for these patients.

Cold ischemia time alters cell-type specific senescence leading to loss of cellular integrity in mouse lungs

Purpose: Ischemia-reperfusion injury (IRI) is a major challenge in lung transplantation often causing graft dysfunction and chronic airway illnesses in recipients. To prevent potential transplant related complications, strict guidelines were put in place to choose viable donor lungs with minimal risk of IRI. These regulations deem most of the donor organs unfit for transplant which then are donated for research to understand the mechanisms of health and diseases in human. However, resected organs that are being transported undergo cold ischemia that can negatively affect the tissue architecture and other cellular functions under study. Thus, it is important to assess how cold ischemia time (CIT) affects the physiological mechanism. In this respect, we are interested in studying how CIT affects cellular senescence in normal aging and various pulmonary pathologies. We thus hypothesized that prolonged CIT exhibits cell-type specific changes in lung cellular senescence in mice. Methods: Lung lobes from C57BL/6J (n = 5–8) mice were harvested and stored in UW Belzer cold storage solution for 0, 4-, 9-, 12-, 24-, and 48-h CIT. Lung cellular senescence was determined using fluorescence (C12FdG) assay and co-immunolabelling was performed to identify changes in individual cell types. Results: We found a rapid decline in the overall lung cellular senescence after 4-h of CIT in our study. Co-immunolabelling revealed the endothelial cells to be most affected by cold ischemia, demonstrating significant decrease in the endothelial cell senescence immediately after harvest. Annexin V-PI staining further revealed a prominent increase in the number of necrotic cells at 4-h CIT, thus suggesting that most of the cells undergo cell death within a few hours of cold ischemic injury. Conclusions: We thus concluded that CIT significantly lowers the cellular senescence in lung tissues and must be considered as a confounding factor for mechanistic studies in the future.