Organ Transplantation Research Articles

Effectiveness of ceftazidime/avibactam as a continuous infusion in critically ill patients with OXA-48-producing Klebsiella pneumoniae infection

Introduction. Ceftazidime/avibactam, a novel beta-lactam antibiotic, demonstrates time-dependent bacterial killing; thus, new reports advocate its administration as a continuous infusion, as opposed to bolus or prolonged infusion application. Methods. Critically ill COVID-19 patients (n=10) superinfected with OXA-48-producing Klebsiella pneumoniae susceptible to ceftazidime/avibactam were treated with ceftazidime/avibactam as a continuous infusion for an average of 10 days. The treatment regimen included an initial loading dose, followed by a continuous infusion of ceftazidime/avibactam. These patients were immunocompromised because of severe COVID-19, treatment with corticosteroids, and some solid organ transplant recipients (n=2), all with high disease severity scores. Discussion. Considering the published literature to this date, this is the one of first reports describing the real-life results of using a continuous infusion of ceftazidime/avibactam in the treatment of OXA-48-producing K. pneumoniae superinfection in critically ill COVID-19 patients. Microbiological effectiveness of treatment, evidenced by negativization of microbiological samples, was achieved in eight cases (80%) overall, but in patients with sepsis and urinary tract infection, the cure rate was 100%. Conclusion. The reasons for the low treatment success rates in pneumonia caused by OXA-48-producing K. pneumoniae could be explained by the concurrent severe COVID-19 pneumonia.

The Legality Of Human Organ Transplantation In Maqashidiah Perspective (A Study Of Fazlur Rahman’s Thought)

In the Qur'an, the prohibition of pigs is absolute, but the shari'ah realizes the preservation of Ḥifẓ an-Nafs (preserving life). Through an examination of Fazlur Rahman's thoughts, this study aims to look at the legality of transplantation through the eyes of contextual interpretation and contemporary Muslim thinkers. This research is literature research with qualitative method and sociology of religion approach. The purpose of shari'ah is to safeguard the interests of humans, damaging the honour of corpses is an individual benefit, while maintaining the safety of the living is a general benefit. Fazlur Rahman's understanding of deduction and induction states that reasoning starts from the specific to the general because that is the more general benefit that is prioritised. The benefits that can realise the five elements of the principle of the establishment of a law (Maqashid Sharia), namely the benefits that can protect religion, soul, offspring, mind, and property. The values of Maqashid Sharia are clearly illustrated in Fazlur Rahman's thoughts and decisions in punishing human organ transplants. This legality eliminates doubts in religion which indirectly eliminates doubts from an ethical point of view.

Resenha crítica do livro: “organ transplantation and native peoples: an interdisciplinary approach”

Por ser uma resenha, o trabalho em questão não tem resumo, atendendo a seguinte orientação de submissão: "Todos os artigos submetidos à Revista Saúde.Com, com exceção das contribuições enviadas às seções Resenha ou Cartas, deverão ter resumo na língua portuguesa e em inglês."

A Decade of Organoid Research: Progress and Challenges in the Field of Organoid Technology.

Organoid technology, revolutionizing biomedical research, offers a transformative approach to studying human developmental biology, disease pathology, and drug discovery. Originating from the pioneering work of Henry Van Peters Wilson in 1907 and evolving through subsequent breakthroughs, organoids are three-dimensional structures derived from stem cells or tissue explants that mimic the architecture and function of organs in vitro. With the ability to model various organs such as intestine, liver, brain, kidney, and more, organoids provide unprecedented insights into organ development, disease mechanisms, and drug responses. This review highlights the historical context, generation methods, applications, and challenges of organoid technology. Furthermore, it discusses recent advancements, including strategies to address hypoxia-induced cell death and enhance vascularization within organoids, aiming to refine their physiological relevance and unlock their full potential in personalized medicine and organ transplantation.

Environmental and Climate Impacts on Physiological Aging: Comprehensive Pathways to Enhanced Age-related Resilience.

This perspective article highlights the pressing necessity to focus on heterogeneity in organ-specific aging, emphasizing the influence of environmental and climate changes, as well as social interactions, on the aging process of individual organs. It explores innovative and integrative strategies tailored to the unique aging mechanisms of different organs, aiming to preserve their biological clocks. By emphasizing the importance of addressing organ-specific vulnerabilities, the article calls for transcending traditional pharmacological treatments and organ transplants. It proposes a comprehensive approach that combines environmental management, social support systems, and advanced technological interventions to improve the well-being and longevity of aging populations.

Epidemiology and risk factors of community-acquired pneumonia in patients with different causes of immunosuppression.

Immunosuppression constitutes a significant risk for community-acquired pneumonia (CAP). Nevertheless, specific causes of immunosuppression and their relevance for incidence, etiology and prognosis of CAP are insufficiently investigated.We conducted a population-based cohort study within a statutory health insurance in Germany from 2015 to 2018. CAP was retrieved by ICD-10-GM codes. Episodes of immunosuppression were identified by coded conditions (hematologic neoplasms, stem cell or organ transplantation, neutropenia, HIV, primary immunosuppressive syndromes) or treatments (immunosuppressants, antineoplastic drugs, systemic steroids). Endpoints were defined as occurrence of CAP (primary), hospitalization, 30-day mortality and CAP associated with rare pathogens. Our analysis utilized the Andersen-Gill model adjusted for sex, age, level of long-term care, vaccination status, community type and comorbidities.942,008 individuals with 54,781 CAPs were included (hospitalization 55%, 30-day mortality 14.5%). 6% of individuals showed at least one episode of immunosuppression during the study period with systemic steroids (39.8%) and hematologic neoplasms (26.7%) being most common. Immunosuppression was recorded in 7.7% of CAPs. Besides classical risk factors such as age and level of long-term care, immunosuppressed patients were most prone to CAP (HR 2.4[2.3-2.5]) and consecutive death (HR 1.9[1.8-2.1]). Organ and stem cell transplantation (HR 3.2[2.6-4.0] and 2.8[2.1-3.7], respectively), HIV (HR 3.2[1.9-5.4]) and systemic steroids (> 20mg prednisone daily dose equivalent (HR 2.7[2.4-3.1])) showed the highest risk for contracting CAP. CAP by rare pathogens was strongly associated with immunosuppression (HR 17.1[12.0-24.5]), especially HIV (HR 34.1[7.6-153]) and systemic steroids (HR 8.2[4.6-14.8]).Our study elucidates the relevance of particular immunosuppressive conditions including systemic steroids for occurrence and prognosis of CAP.

Evaluation of QT prolongation in children with cirrhosis and its association with the severity of liver diseases

Summary: Introduction: Prolongation of the QT interval in an electrocardiogram (ECG) is seen in more than 60% of adults with advanced cirrhosis. According to careful research, people with cirrhosis who have their QT intervals prolonged had worse survival rates, more severe disease symptoms, and faster development of their condition. Considering the importance of predicting complications of liver cirrhosis in children and the limited number of studies related to the relationship between prolonged QT and the severity of liver disease in children, in this study, prolonged QT in children with liver cirrhosis and its relationship with the severity of liver disease was investigated. Methods: In the present study, children under 18 years of age with liver cirrhosis were evaluated in the list of liver transplants referred to Abu Ali Sina Organ Transplantation Hospital in Shiraz between 2019 and 2021. QT was calculated based on two pediatric cardiologists‘ 12-lead ECG from liver transplant surgery. Results: In this study, 130 patients with liver cirrhosis with an average age of 7.05±5.34 years were evaluated. The average length of the QT segment was reported as 397±31milliseconds. Only 4 (3%) had a long QT segment in all the studied patients. The comparison of the Meld/ Peld criterion and Child criterion in the two groups of regular QT and prolonged QT showed that the mean of both criteria was signifi cantly longer in the standard QT group (P = 0.018, P = 0.038). Also, prolonged QT showed a signifi cant relationship with the cause of liver cirrhosis (P = 0.003). Conclusion: Our study is one of the fi rst to examine the relationship between QT and severity of cirrhosis in children. Based on the results of this study, prolonged QT is associated with severity of liver disease. Key words: liver – cirrhosis – children – long QT – fi brosis

Does Timepoint of Surgical Procedure Affect the Outcome in Simultaneous Pancreas-Kidney Transplantation? A Retrospective Single-Center Analysis over 20 Years.

Background: Sleep deprivation and disturbances in circadian rhythms may hinder surgical performance and decision-making capabilities. Solid organ transplantations, which are technically demanding and often begin at uncertain times, frequently during nighttime hours, are particularly susceptible to these effects. This study aimed to assess how transplant operations conducted during daytime versus nighttime influence both patient and graft outcomes and function. Methods: simultaneous pancreas-kidney transplants (SPKTs) conducted at the University Hospital of Leipzig from 1998 to 2018 were reviewed retrospectively. The transplants were categorized based on whether they began during daytime hours (8 a.m. to 6 p.m.) or nighttime hours (6 p.m. to 8 a.m.). We analyzed the demographics of both donors and recipients, as well as primary outcomes, which included surgical complications, patient survival, and graft longevity. Results: In this research involving 105 patients, 43 SPKTs, accounting for 41%, took place in the daytime, while 62 transplants (59%) occurred at night. The characteristics of both donors and recipients were similar across the two groups. Further, the rate of (surgical) pancreas graft-related complications and reoperations (daytime 39.5% versus nighttime 33.9%; p = 0.552) were also not statistically significant between both groups. In this study, the five-year survival rate for patients was comparable for both daytime and nighttime surgeries, with 85.2% for daytime and 86% for nighttime procedures (p = 0.816). Similarly, the survival rates for pancreas grafts were 75% for daytime and 77% for nighttime operations (p = 0.912), and for kidney grafts, 76% during the day compared to 80% at night (p = 0.740), indicating no significant statistical difference between the two time periods. In a multivariable model, recipient BMI > 30 kg/m2, donor age, donor BMI, and cold ischemia time > 15 h were independent predictors for increased risk of (surgical) pancreas graft-related complications, whereas the timepoint of SPKT (daytime versus nighttime) did not have an impact. Conclusions: The findings from our retrospective analysis at a big single German transplant center indicate that SPKT is a reliable procedure, regardless of the start time. Additionally, our data revealed that patients undergoing nighttime transplants have no greater risk of surgical complications or inferior results concerning long-term survival of the patient and graft. However, due to the small number of cases evaluated, further studies are required to confirm these results.

The risk of solid organ tumors in patients with chronic kidney disease: A narrative review of literature

Chronic kidney disease (CKD) has been correlated with certain pathological conditions such as cardiovascular diseases and other renal-related dysfunctions. Some other reports suggested an association between CKD and the development of certain solid cancers. Therefore, we aimed to generate this narrative review to present the available literature on the risk of solid cancer development in CKD patient populations. We explored the associations between CKD, organ transplantation, and the development of specific solid organ tumors such as kidney, thyroid, lung, breast, bladder, gastric, and prostate cancers. In conclusion, the previous reports showed an increase in the risk of certain solid cancers such as kidney, lung, bladder, and possibly breast cancer in CKD patients and transplant recipients. On the other hand, thyroid, gastric, and prostate cancers showed unclear association with CKD. Despite the suggested impact of smoking and immunosuppression on the development of cancers in CKD patients, more studies are needed to elucidate the mechanism and the risk factors that might be related to the development of cancer in CKD patients.

Cancer risk in people living with HIV and solid organ transplant recipients: a systematic review and meta-analysis

Systematic evaluations of cancer risk in people living with HIV or AIDS (PLHIV) and solid organ transplant recipients provide unique insights into the role of the immune system in cancer development. In this systematic review and meta-analysis, we expand previous analyses of cancer risk for these two immunocompromised populations. We considered studies published in English and listed on PubMed or Embase up to July 1, 2022. Studies were eligible for inclusion if they used population-based registries and compared cancer incidence in PLHIV or solid organ transplant recipients with the general population in the same geographical area. We extracted the number of observed site-specific cancers and expected cases and calculated meta-standardised incidence ratios for cancer within PLHIV and solid organ transplant recipients. In solid organ transplant recipients meta-standardised incidence ratios were compared by organ type. This project is registered on PROSPERO, CRD42022366679. 46 studies in PLHIV and 67 in solid organ transplant recipients were included in the analysis. Meta-standardised incidence ratios for cancers associated with human papillomavirus were increased in both populations; the highest meta-standardised incidence ratio in PLHIV was anal cancer (37·28 [95% CI 23·65-58·75], I2=97·4%), and in solid organ transplant recipients was cutaneous squamous cell carcinoma (45·87 [31·70-66·38], I2=99·0%). Meta-standardised incidence ratios were significantly increased for most non-HPV viral-infection-related cancers in both populations; the highest standard incidence ratios were for Kaposi sarcoma (PLHIV: 801·52 [95% CI 200·25-3208·13], I2=100·0%; solid organ transplant recipients: 47·31 [23·09-96·95], I2=87·7%) and non-Hodgkin lymphoma (32·53 [19·64-53·87], I2=99·8%; 10·24 [8·48-12·35], I2=94·9%). Eight types of cancer with no known viral cause showed an increased risk in solid organ transplant recipients only; no cancer type showed increased risk in PLHIV only. Cancer risk was increased for a range of infection-related cancers in both PLHIV and solid organ transplant recipients, but divergent results in these and other cancers have emerged. The cancer risk patterns probably reflect variances in the degree of impaired immunity, exposure to carcinogenic viruses, and perhaps exposure to carcinogenic immunosuppressive agents. US National Cancer Institute, National Institutes of Health.

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

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. 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 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. 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.

Tacrolimus-induced posterior reversible encephalopathy syndrome following liver transplantation

Tacrolimus-induced posterior reversible encephalopathy syndrome following liver transplantation

Donor-derived infections in the United States: Opportunities to learn from the Disease Transmission Advisory Committee's experience.

The Disease Transmission Advisory Committee (DTAC) of the Organ Procurement and Transplantation Network focuses on issues related to the transmission of disease through organ transplantation. Providing a review of potential cases of transmission, translating aggregate data into actionable education and guidance for the transplant community, and providing input for policy development, DTAC aims to improve the safety of organ transplantation through a reduction in donor-derived transmission events. Through its nearly 20-year history, DTAC has provided education, guidance, and policy, addressed numerous emerging infections, and continuously focused on the community's understanding of risk assessment related to donor-derived transmission. By updating the DTAC mission to both decrease transmission and safely expand the donor pool with additional guidance to safely use organs previously not considered for transplantation due to transmission concerns, the Committee's role will remain critical.

Conhecimento ético e deontológico dos estudantes de medicina sobre a doação de órgãos e tecidos no Brasil

Organ donation and transplantation have been taking place in Brazil for decades, acting as an effective alternative for individuals who do not benefit from conventional treatments. This requires a regulatory framework that allows for organ removal while respecting bioethical and legal standards. This study aims to assess the knowledge of future health professionals regarding the ethical and deontological issues involved in organ and tissue donation. This descriptive and qualitative study was carried out with medical students from the first to the fifth year at a university in the west of the state of Paraná, Brazil, with a sample of 131 participants. The results showed 84.7% of students had never attended classes on the subject during their undergraduate years. Despite this lack of formal education, 53.4% correctly identified the concept of brain death. Additionally, 94.7% expressed willingness to donate their organs and 31% believed certain groups should be excluded from the transplant list. The findings suggest a gap in university curricula regarding the subject, yet students are actively seeking alternative ways to gain knowledge. Moreover, there was a high acceptance rate among students for post-mortem organ donation. Opinions diverged significantly on ethical and individual issues such as the exclusion of people from the transplant list.

Burden and Management of Multi-Drug Resistant Organism Infections in Solid Organ Transplant Recipients Across the World: A Narrative Review

Solid organ transplant (SOT) recipients are particularly susceptible to infections caused by multidrug-resistant organisms (MDRO) and are often the first to be affected by an emerging resistant pathogen. Unfortunately, their prevalence and impact on morbidity and mortality according to the type of graft is not systematically reported from high-as well as from low and middle-income countries (HIC and LMIC). Thus, epidemiology on MDRO in SOT recipients could be subjected to reporting bias. In addition, screening practices and diagnostic resources may vary between countries, as well as the availability of new drugs. In this review, we aimed to depict the burden of main Gram-negative MDRO in SOT patients across HIC and LMIC and to provide an overview of current diagnostic and therapeutic resources.

Estimation of Immunosuppressants by Liquid Chromatography Tandem Mass Spectrometry in Clinical Laboratories

Immunosuppressive drugs or Immunosuppressants have contributed significantly to the success of organ transplantation by preventing graft rejection. They inhibit the activity of the immune system by reducing the proliferation and function of cells associated with immune reactions.

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.

Calcineurin Inhibitor in NEuRoloGically deceased donors to decrease kidney delayed graft function study: study protocol of the CINERGY Pilot randomised controlled trial

IntroductionMost solid organ transplants originate from donors meeting criteria for death by neurological criteria (DNC). Within the organ donor, physiological responses to brain death increase the risk of ischaemia reperfusion...

Fueling the success of transplantation through nutrition: recent insights into nutritional interventions, their interplay with gut microbiota and cellular mechanisms

Purpose of review: The role of nutrition in organ health including solid organ transplantation is broadly accepted, but robust data on nutritional regimens remains scarce calling for further investigation of specific dietary approaches at the different stages of organ transplantation. This review gives an update on the latest insights into nutritional interventions highlighting the potential of specific dietary regimens prior to transplantation aiming for organ protection and the interplay between dietary intake and gut microbiota. Recent findings: Nutrition holds the potential to optimize patients’ health prior to and after surgery, it may enhance patients’ ability to cope with the procedure-associated stress and it may accelerate their recovery from surgery. Nutrition helps to reduce morbidity and mortality in addition to preserve graft function. In the case of living organ donation, dietary preconditioning strategies promise novel approaches to limit ischemic organ damage during transplantation and to identify the underlying molecular mechanisms of diet-induced organ protection. Functioning gut microbiota are required to limit systemic inflammation and to generate protective metabolites such as short-chain fatty acids or hydrogen sulfide. Summary: Nutritional intervention is a promising therapeutic concept including the pre- and rehabilitation stage in order to improve the recipients’ outcome after solid organ transplantation.

European Society for Organ Transplantation (ESOT) Consensus Statement on the Use of Non-invasive Biomarkers for Cardiothoracic Transplant Rejection Surveillance.

While allograft rejection (AR) continues to threaten the success of cardiothoracic transplantation, lack of accurate and repeatable surveillance tools to diagnose AR is a major unmet need in the clinical management of cardiothoracic transplant recipients. Endomyocardial biopsy (EMB) and transbronchial biopsy (TBBx) have been the cornerstone of rejection monitoring since the field's incipience, but both suffer from significant limitations, including poor concordance of biopsy interpretation among pathologists. In recent years, novel molecular tools for AR monitoring have emerged and their performance characteristics have been evaluated in multiple studies. An international working group convened by ESOT has reviewed the existing literature and provides a series of recommendations to guide the use of these biomarkers in clinical practice. While acknowledging some caveats, the group recognized that Gene-expression profiling and donor-derived cell-free DNA (dd-cfDNA) may be used to rule out rejection in heart transplant recipients, but they are not recommended for cardiac allograft vasculopathy screening. Other traditional biomarkers (NT-proBNP, BNP or troponin) do not have sufficient evidence to support their use to diagnose AR. Regarding lung transplant, dd-cfDNA could be used to rule out clinical rejection and infection, but its use to monitor treatment response is not recommended.