Case report: safety and efficacy of lidocaine infusion for the treatment of intractable zoster-associated neuralgia in solid organ transplant recipients.

Introduction: Solid organ transplant recipients are at high risk for developing severe zoster-associated neuralgia, and the pharmaceutic therapies of pain management for these patients with limited organ function are challenging. Intravenous lidocaine infusion showed positive analgesic effects and is used for the management of neuropathic pain. This case series reports the safety and effectiveness of intravenous lidocaine infusion in the treatment of intractable zoster-associated neuralgia in solid organ transplant recipients. Case series presentation: Five solid organ transplant recipients suffering from refractory zoster-associated neuralgia (numeric rating scale 8-10, despite using high doses of antiepileptic drugs or combined with opioids) were enrolled. Intravenous lidocaine (5 mg/kg ideal bodyweight) was administered over 1.5 h with the monitoring of vital signs. Pain intensity, patient satisfaction, adverse events, typical liver, and kidney function were evaluated. All subjects reported high satisfaction with their treatment and effective pain relief at the 6-month follow-up. One patient experienced short and mild numbness in the mouth and dizziness after the therapy, but no major adverse reactions were reported. Conclusion: This case series provides evidence that intravenous lidocaine infusion provided effective pain relief as an analgesic treatment option for transplant patients with intractable zoster-associated neuralgia.

Simultaneous combined transplantation: Intricacies in immunosuppression management.

Simultaneous combined transplantation (SCT), i.e. the transplantation of two solid organs within the same procedure, can be required when the patients develop more than one end-stage organ failure. The development of SCT over the last 20 years could only be possible thanks to progress in the surgical techniques and in the perioperative management of patients in an ageing population. Performing such major transplant surgeries from the same donor, in a short amount of time, and in critical pathophysiological conditions, is often considered to be counterbalanced by the immune benefits expected from these interventions. However, SCT includes a wide array of different transplant combinations, with each time a different immunological constellation. Recent research offers new insights into the immune mechanisms involved in these different settings. Progress in the understanding of these immunological intricacies help to address the optimal induction and maintenance immunosuppressive treatment strategies. In this review, we summarize the different immunological benefits according to the type of SCT performed. We also incorporate the main outcomes according to the immunological risk at transplantation, and the deleterious impact of preformed or de novo donor-specific antibodies (DSA) in the different types of SCT. Finally, we propose comprehensive and evidence-based induction and maintenance immunosuppression strategies guided by the type of SCT.

A 25-year scoping review of the organ donation system in Malaysia: past, present, and future.

Organ donation and transplantation are integral components of modern medicine. This scoping review thoroughly explores the historical evolution, current status, and future prospects of organ donation and transplantation in Malaysia. Historically, Malaysia faced significant challenges in establishing a robust organ transplantation system, with various factors hindering organ donation efforts. Currently, Malaysia continues to struggle with stagnant donation rates despite collaborative efforts from various sectors. There is an urgent need to amend the 50-year-old Human Tissue Act to strengthen the legal framework for organ donation and address ethical concerns. Looking to the future, Malaysia could adopt a soft opt-out system and prioritize advancements in organ preservation techniques by exploring new sources of organs through the donation after circulatory death program. Continued efforts are necessary to enhance education programs for professionals and the public, dispelling myths about organ donation and effectively educating on the concepts of brain death. Malaysia strives to create a more accessible future for organ transplantation, aligning with the Sustainable Development Goals to reduce the burden of organ failure and improve the population's health and well-being.

TLR4 signalling in ischemia/reperfusion injury: a promising target for linking inflammation, oxidative stress and programmed cell death to improve organ transplantation outcomes.

Transplantations represent the principal therapeutic interventions for terminal organ failure, a procedure that has salvaged myriad lives annually. Ischemia/reperfusion injury (IRI) is frequently correlated with an unfavourable prognosis and is relevant for early graft dysfunction and graft survival. IRI constitutes a complex pathological state influenced by a series of factors such as oxidative stress, metabolic stress, leukocytic infiltration, programmed cell death pathways, and inflammatory immune responses. Reducing ischemia/reperfusion injury is one of the main directions of transplantation research. Toll-like receptors (TLRs) are important pattern-recognition receptors expressed on various organs that orchestrate the immune responses upon recognising PAMPs and DAMPs. Targeting the TLR4 signalling has recently been suggested as a promising approach for alleviating IRI by affecting inflammation, oxidative stress and programmed cell death (PCD). In this minireview, we summarise the role of TLR4 signalling in regulating inflammation, oxidative stress and PCD in organ transplantation and discuss their interactions during IRI. A detailed understanding of the multiple functions of TLR4 in IRI provides novel insights into developing therapies to improve organ transplantation outcomes.

In Defense of Normothermic Regional Perfusion.

Normothermic regional perfusion (NRP) is a relatively new approach to procuring organs for transplantation. After circulatory death is declared, perfusion is restored to either the thoracoabdominal organs (in TA-NRP) or abdominal organs alone (in A-NRP) using extracorporeal membrane oxygenation. Simultaneously, surgeons clamp the cerebral arteries, causing a fatal brain injury. Critics claim that clamping the arteries is the proximate cause of death in violation of the dead donor rule and that the procedure is therefore unethical. We disagree. This account does not consider the myriad other factors that contribute to the death of the donor, including the presence of a fatal medical condition, the decision to withdraw life support, and the physician's actions in withdrawing life support and administering medication that may hasten death. Instead, we claim that physicians play a causative role in many of the events that lead to a patient's death and that these actions are often ethically and legally justified. We advance an "all things considered" view according to which TA-NRP may be considered ethically acceptable insofar as it avoids suffering and respects the wishes of the patient to improve the lives of others through organ donation. We conclude with a series of critical questions related to the practice of NRP and call for the development of national consensus on this issue in the United States.

Assessing the Brain Death/Death by Neurologic Criteria Determination Process in Korea: Insights from 10-Year Noncompleted Donation Data.

BACKGROUND: This study aimed to analyze the current status of brain death/death by neurologic criteria (BD/DNC) determination in Korea over a decade, identifying key areas for improvement in the process. METHODS: We conducted a retrospective analysis of data from the Korea Organ Donation Agency spanning 2011 to 2021, focusing on donors whose donations were not completed. The study reviewed demographics, medical settings, diagnoses, and outcomes, with particular emphasis on cases classified as nonbrain death and those resulting in death by cardiac arrest during the BD/DNC assessment. RESULTS: Of the 5047 patients evaluated for potential brain death from 2011 to 2021, 361 were identified as noncompleted donors. The primary reasons for noncompletion included nonbrain death (n = 68, 18.8%), cardiac arrests during the BD/DNC assessment process (n = 80, 22.2%), organ ineligibility (n = 151, 41.8%), and logistical and legal challenges (n = 62, 17.2%). Notably, 25 (36.8%) of them failed to meet the minimum clinical criteria, and 7 of them were potential cases of disagreement between the two clinical examinations. Additionally, most cardiac arrests (n = 44, 55.0%) occurred between the first and second examinations, indicating management challenges in critically ill patients during the assessment period. CONCLUSIONS: Our study highlights significant challenges in the BD/DNC determination process, including the need for improved consistency in neurologic examinations and the management of critically ill patients. The study underscores the importance of refining protocols and training to enhance the accuracy and reliability of brain death assessments, while also ensuring streamlined and effective organ donation practices.

LiverColor: An Artificial Intelligence Platform for Liver Graft Assessment.

Hepatic steatosis, characterized by excess fat in the liver, is the main reason for discarding livers intended for transplantation due to its association with increased postoperative complications. The current gold standard for evaluating hepatic steatosis is liver biopsy, which, despite its accuracy, is invasive, costly, slow, and not always feasible during liver procurement. Consequently, surgeons often rely on subjective visual assessments based on the liver's colour and texture, which are prone to errors and heavily depend on the surgeon's experience. The aim of this study was to develop and validate a simple, rapid, and accurate method for detecting steatosis in donor livers to improve the decision-making process during liver procurement. We developed LiverColor, a co-designed software platform that integrates image analysis and machine learning to classify a liver graft into valid or non-valid according to its steatosis level. We utilized an in-house dataset of 192 cases to develop and validate the classification models. Colour and texture features were extracted from liver photographs, and graft classification was performed using supervised machine learning techniques (random forests and support vector machine). The performance of the algorithm was compared against biopsy results and surgeons' classifications. Usability was also assessed in simulated and real clinical settings using the Mobile Health App Usability Questionnaire. The predictive models demonstrated an area under the receiver operating characteristic curve of 0.82, with an accuracy of 85%, significantly surpassing the accuracy of visual inspections by surgeons. Experienced surgeons rated the platform positively, appreciating not only the hepatic steatosis assessment but also the dashboarding functionalities for summarising and displaying procurement-related data. The results indicate that image analysis coupled with machine learning can effectively and safely identify valid livers during procurement. LiverColor has the potential to enhance the accuracy and efficiency of liver assessments, reducing the reliance on subjective visual inspections and improving transplantation outcomes.

Psychological Health of the Adolescent Transplant Recipient.

BACKGROUND: Solid organ transplant recipients experience a period of unique vulnerability during adolescence, when normative developmental changes intersect with health-related variables to influence psychological health. METHODS: This article builds on previous reviews of psychological health in solid organ transplant recipients and proposes opportunities for clinical intervention during adolescence. RESULTS: Transplant recipients often experience neurocognitive changes, particularly with respect to executive functions, that impact health management tasks and autonomous care. Recipients should be monitored for the development of anxiety, depression, and posttraumatic stress symptoms during adolescence, which in turn can negatively impact adherence to immunosuppression. Recent research in posttraumatic growth and resiliency factors may represent a promising avenue of intervention, leveraging normative developmental processes during this time period. CONCLUSIONS: As pediatric transplant providers, adolescence represents a developmental period for targeted interventions to foster adjustment and adherence and promote a successful transition to adult care.

Clinical characteristics and risk factor analysis of recipients with multidrug-resistant bacterial bloodstream infections after liver transplantation: a single-centre retrospective study.

Background: The clinical characteristics and associated risk factors for recipients who experience multidrug-resistant organism (MDRO) bloodstream infections after liver transplantation are poorly understood. This study aimed to analyse the clinical characteristics and epidemiology of pathogenic bacteria and identify associated risk factors in patients who underwent MDRO after liver transplantation. Method: We retrospectively collected data on recipients who developed bloodstream infections after liver transplantation between 2018 and 2023. Recipients were divided into MDRO and non-MDRO groups based on blood culture results. We explored the risk factors for MDRO bloodstream infections post-transplantation and summarised the clinical features, pathogen epidemiology, and prognosis. A multivariate logistic regression analysis was conducted to identify significant risk factors. Results: A total of 463 liver transplant recipients were studied, and 73 developed blood infections. There were 29 MDRO cases. The mean duration of the episodes was 26 days (range: 1-474 days). Among these patients, 22 (30.1%) developed blood infections without fever (temperature < 37.3°C), and 33 patients (45.2%) had a white blood cell count between 4 and 10 × 109/L. Among the 108 positive blood cultures, 29 genera were detected, predominantly gram-negative bacilli (n = 64, 58.2%). The detection rate for multidrug-resistant bacilli was 31.8% (35/110), with the abdomen being the most common site of origin (21.3%). Factors such as a history of preoperative intensive care unit (ICU) hospitalisation (p < 0.001) and a preoperative international normalised ratio (INR) > 2 (p < 0.048) were identified as risk factors in multivariate regression analysis. Conclusion: Multidrug-resistant bacterial bloodstream infections after liver transplantation tend to occur early in the postoperative period (<30 days) and are associated with high mortality and a lack of specific clinical manifestations. A history of preoperative intensive care unit (ICU) hospitalisation and an international normalised ratio (INR) > 2 may be risk factors for multidrug-resistant bacterial bloodstream infections after liver transplantation.

Immune response against bacterial infection in organ transplant recipients.

This comprehensive review delves into the intricate dynamics between the immune system and bacterial infections in organ transplant recipients. Its primary objective is to fill existing knowledge gaps while critically assessing the strengths and weaknesses of current research. The paper accentuates the delicate balance that must be struck between preventing graft rejection through immunosuppression and maintaining robust immunity against bacterial threats. In this context, personalized medicine emerges as a transformative concept, offering the potential to revolutionize clinical outcomes by tailoring immunosuppressive regimens and vaccination strategies to the unique profiles of transplant recipients. By emphasizing the pivotal role of continuous monitoring, the review underscores the necessity for vigilant surveillance of transplant recipients to detect bacterial infections and associated immune responses early, thereby reducing the risk of severe infections and ultimately improving patient outcomes. Furthermore, the study highlights the significance of the host microbiome in shaping immune responses, suggesting that interventions targeting the microbiome hold promise for enhancing bacterial immunity in transplant recipients, both in research and clinical practice. In terms of future research directions, the review advocates for large-scale, longitudinal studies encompassing diverse patient cohorts to provide more comprehensive insights into post-transplant immune responses. It also advocates integrating multi-omics approaches, including genomics, transcriptomics, proteomics, and microbiome data, to understand immune responses and their underlying mechanisms. In conclusion, this review significantly enriches our understanding of immune responses in transplant recipients. It paves the way for more effective and personalized approaches to managing infections in this complex setting.

Culturally Safe Care Barriers and Facilitators in Organ Transplantation and Donation According to First Nations and Health Professionals in Quebec, Canada.

Introduction: First Nations are most at risk of developing end-stage kidney disease. Kidney transplantation is the best treatment option for these patients; however, First Nations donors are underrepresented. The aim of this study was to describe and understand barriers and facilitators of culturally safe organ transplantation and donation from the perspective of First Nations and Health Professionals in the Province of Quebec, Canada. Methods/Approach: This was a qualitative descriptive study using the decolonizing Two-Eyed Seeing approach. The sample consisted of First Nations people and health professionals living in Quebec, Canada, who have had an experience of organ transplantation or donation. Semi-structured interviews were conducted between May and September 2021 with 11 people, including 5 healthcare professionals and 6 First Nations people. Findings: This study enrolled 11 participants. Several individual and contextual factors influencing culturally safe organ transplantation and donation among First Nations people were identified: language barrier, impacts of relocation, lack of knowledge about transplantation, mistrust of the healthcare system, family support and accompaniment, and transplant testimonials. Discussion: This study identified several avenues for reinforcing culturally safe transplantation and donation among First Nations, including the presence of a companion in medical consultations, focusing on access to culturally safe accommodation and sharing transplant testimonials. Further work in partnership with First Nations is needed to improve access to culturally safe organ transplantation.

Knowledge and willingness to donate kidney for transplantation among general population in Saudi Arabia.

INTRODUCTION: Kidney transplantation is the preferred treatment for end-stage renal disease (ESRD), offering a superior quality of life and extended survival compared to other renal replacement therapies. As the number of ESRD patients grows, so does the demand for organ transplants. The prevalence of ESRD is anticipated to escalate further due to the rising rates of diabetes mellitus (DM), hypertension (HTN), and obesity. Organ donation, particularly from living donors, remains the main source of transplants in the region, despite the notable underutilization of potential deceased donors' organs. The objective of this research is to assess the level of knowledge, attitudes, and willingness to donate kidneys among the general population, a pivotal step in addressing the organ shortage crisis. METHODS: This cross-sectional study was conducted in the Aseer region of Saudi Arabia using a previously validated questionnaire. The questionnaire collected demographic data and insights into general attitudes, knowledge, and beliefs about organ donation. Logistic regression was used to identify predictors of knowledge and willingness to donate. RESULTS: The study involved 705 participants, predominantly young adults with a high level of education. Awareness of kidney donation was high, and knowledge about donation was broad, especially regarding religious permissibility and awareness of the donor registry. However, only 25% expressed willingness to donate their kidneys, and a 4% were already registered as donors. Furthermore, higher educational level was not associated with higher odds of knowledge or willingness to donate. CONCLUSION: Despite the considerable awareness, actual donor registration rates were low, highlighting the necessity for targeted educational interventions and a deeper understanding of the cultural and socioeconomic barriers that exist.

Cryptococcus neoformans fungemia in a liver transplant patient: Case report and literature review.

Cryptococcus neoformans is an environmental fungus that can frequently cause life-threatening meningitis and fungemia in acquired immunodeficiency syndrome patients. In recent years, cases of these fungal infections are increasingly identified in HIV-negative patients especially in solid organ transplantation (SOT) patients. Cryptococcal fungemia can often clinically present as life-threatening disseminated disease from subclinical colonization. This is a factor that affects survival, especially in patients with decompensated liver cirrhosis and SOT recipients. Early diagnosis and appropriate treatment are important for the course of the disease. This report describes the cryptococcal fungemia that developed in an HIV-negative patient after SOT due to alcohol-related liver cirrhosis.

Incidence of de novo malignancy and all-cause mortality among heart transplant recipients.

BACKGROUND: Heart transplant recipients develop cancer at two-times the rate compared to the general population. However, the incidence and mortality rates and the adjusted association between cancer and mortality remains unclear. METHODS: We estimated the incidence and mortality rates and the adjusted association between developing cancer (any, skin, hematologic, and solid tumor subtypes) and the all-cause mortality rates among adult heart transplant recipients from the Scientific Registry of Transplant Recipients from October 1, 1987, until June 28, 2020. RESULTS: Among 51,597 adult heart transplant recipients, 13,191 (25.6%) were diagnosed with de novo malignancy throughout the follow-up period. The cumulative incidence cancer at years 1, 5, 10, and 20 was 3%, 16.4%, 32.8%, and 56.6%, respectively. Among those with cancer, the cumulative mortality was 17.5%, 42.3%, 65%, and 91% at years 1, 5, 10, and 20, respectively. The incidence rate of any de novo malignancy was 38.7 cases per 1000 person-years and the mortality rate (for those with cancer) was 115.2 cases per 1000 person-years. Compared to those without cancer, those with cancer had a higher adjusted mortality association [HR: 2.14 (2.07, 2.21)]. The strongest associations were estimated for pancreatic [10.63 (8.34, 13.54)], leukemia [8.06 (4.33, 15.00)], and esophagus [6.94 (5.43, 8.87)] malignancies. The association between de novo malignancies and mortality was higher in the earlier years of follow-up. CONCLUSION: Compared to not developing cancer, those with de novo malignancy have a 2-fold higher mortality rate, on average. The strength of the association varies by cancer subtype and by follow-up time.

Characterization of the Antibody Response to SARS-CoV-2 Infection in COVID-19 Transplant versus Nontransplant Recipients by Ig-MS.

Solid organ transplant recipients with immunosuppressant regimens to prevent rejection are less able to mount effective immune responses to pathogenic infection. Here, we apply a recently reported mass spectrometry-based serological approach known as Ig-MS to characterize immune responses against infection with SARS-CoV-2 in cohorts of transplant recipients and immunocompetent controls, both at a single early time point following COVID-19 diagnosis as well as over the course of one-month postdiagnosis. We found that the antibody repertoires generated by transplant recipients against SARS-CoV-2 do not differ significantly compared to immunocompetent individuals with regard to repertoire titer, clonality, or glycan composition. Importantly, our study is the first to characterize the evolution of antibody glycan profiles in transplant recipients with COVID-19 disease, presenting evidence that the evolution of glycan composition in these immunocompromised individuals is similar to that in immunocompetent people.

The potential for therapeutic drug monitoring of belatacept and other biologicals in solid organ transplantation.

In solid organ transplantation (SOT), biologicals such as recombinant therapeutic proteins, monoclonal antibodies, fusion proteins and conjugates are increasingly used for immunosuppression, desensitization, ABO (blood group) incompatibility, antibody-mediated rejections and atypical haemolytic uremic syndrome. In this paper, we review the medical evidence available for biologicals used in SOT and the potential for improvement by the application of therapeutic drug monitoring (TDM) and model-informed precision dosing. Biologicals are used for off-label indications within the field of SOT, building on the experience from their use on labelled indications. Dosing is currently mostly standard, and experience vs. effect and toxicity is limited. Pharmacokinetic characteristics of these large, partly also immunogenic molecules differ from those of traditional small molecules. Individualization by concentration measurements and modelling has mostly been proof-of-concept or feasibility studies that lack the power to provide evidence for improvement in clinical outcome. For some drugs such as alemtuzumab, eculizumab, rituximab, tocilizumab and belatacept, studies have demonstrated significant interindividual variability in pharmacokinetics. Variability in absorption from subcutaneous administration may increase interindividual variability. There is also an economic aspect of appropriate dosing that needs to be pursued. Available assays and models to refine interpretation are in place, but trials of adequate size to document the usefulness of TDM and MIPD are scarce. Collaboration within the TDM community seems mandatory to establish studies of sufficient strength to provide evidence for the use of biologicals that are currently used off-label in SOT and furthermore to identify the settings where TDM may be beneficial.

Perception and Willingness Regarding Organ Transplantation/donation among Medical Students of Maharajgunj Medical Campus: A Cross-sectional Study.

BACKGROUND: Organ transplant is the procedure of replacing a failing or damaged organ with a functioning one. Positive attitude and awareness about donation are a must for donor organs to be available. This study explored the level of knowledge, perception and willingness regarding organ donation among medical students in Nepal. METHODS: A descriptive cross-sectional study was conducted with 180 medical students using a self-administered questionnaire. Descriptive statistics were used, and Pearson correlation was applied to examine the relationship between knowledge and perception of organ transplantation. Independent samples t-test and ANOVA was used to compare scores among year of study and gender. RESULTS: Results indicated that 86.1% of participants were aware of the need for organ donation, and 83.3% knew that both living and deceased individuals could be donors. While 93.9% believed in the need for effective laws, 72.8% perceived risks for donors. However, only 74.4% were willing to donate their organs, though 91.7% expressed willingness to promote organ donation among friends and family. Participants showed a positive perception towards organ donation. CONCLUSIONS: Despite a high level of awareness and knowledge regarding organ donation, participants exhibited a lower level of willingness to donate organs. Perceived risks for donors and a lack of robust laws and regulations presented significant barriers. Nevertheless, an inclination to promote organ donation was observed. This underlines the need for enhanced education and policy reform to increase organ donation rates.

Perspectives on biovigilance and transmission of infection of donor origin in deceased organ donation-The evolving scenario in the United Kingdom.

BACKGROUND: A biovigilance program that has oversight of the entire organ and tissue donation and transplantation pathways underpins the quality and safety system in the United Kingdom. METHOD: A synopsis of the microbiological characterization of potential deceased organ donors and the processes for notification and investigation of possible donor-derived infections are described. A summary of the outcome of investigations performed over a 10-year period and a subset data frame of 5 years showing the proportion of infection incidents in relation to other incident types are also presented. CONCLUSION: A single, centralized system overseeing the entire donation and transplantation pathway has become an essential part of transplantation practice across the United Kingdom. Revision of processes and management options, awareness of clinical conditions, and review of guidance are some examples of benefits gained over time. Transmission figures provided reflect the UK setting; these should be interpreted in context, as donor and recipient epidemiology differs across regions and nations. Despite a well-established system in place, under reporting of cases continues to occur, with ongoing efforts to reassure professionals and patients of the true benefits of biovigilance in driving improvements in practice and patient outcomes.

Real-World Experience With Maribavir for Treatment of Cytomegalovirus Infection in High-Risk Solid Organ Transplant Recipients.

We evaluated use of maribavir (MBV) for treatment of 15 episodes of refractory/resistant cytomegalovirus infection in 13 solid organ transplant recipients. Treatment failure due to treatment-emergent MBV resistance or early virological recurrence after MBV discontinuation occurred in 7 (47%) episodes. Sustained viral clearance was achieved in 6 (40%) episodes.