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Transplantation Aug 2023Solid organ transplant recipients are at high risk for Staphylococcus aureus bacteremia, but the risks before and after transplantation require further research.
BACKGROUND
Solid organ transplant recipients are at high risk for Staphylococcus aureus bacteremia, but the risks before and after transplantation require further research.
METHODS
We performed a population-based retrospective self-controlled study using the State Inpatient Database from 10 states in the United States. Adult and pediatric patients who had solid organ transplantation from 2004 to 2018 were tracked longitudinally for 1 y before and after transplantation outside of the immediate peritransplant periods. The exposure of interest was solid organ transplantation, and the outcome of interest was hospitalization with S. aureus bacteremia.
RESULTS
Of 75 549 patients, 581 (0.77%) and 239 (0.32%) were hospitalized with S. aureus bacteremia in the pretransplant and posttransplant periods, respectively ( P < 0.001). Overall, the odds of hospitalization with S. aureus bacteremia increased from 7 to 12 mo to 1 to 6 mo before transplantation (odds ratio, 1.24; 95% confidence interval, 1.05-1.46) and then decreased following transplantation (odds ratio, 0.35; 95% confidence interval, 0.28-0.45; 7-12 mo after transplantation). The decreased rate after transplantation was driven by the cases associated with central line-associated bloodstream infections and endocarditis among kidney and heart transplant recipients. Odds of hospitalization with S. aureus bacteremia did not change after liver transplantation, whereas they increased after lung transplantation.
CONCLUSIONS
In addition to immunosuppression, the reversal of organ failure and associated requirements for organ support following transplantation may play an important role in the risk of S. aureus bacteremia in solid organ transplant recipients. These results can guide infection prevention approaches and future research on S. aureus infections in transplant patients.
Topics: Adult; Humans; Child; United States; Staphylococcus aureus; Retrospective Studies; Organ Transplantation; Staphylococcal Infections; Bacteremia; Risk Factors
PubMed: 36959162
DOI: 10.1097/TP.0000000000004590 -
Transplant International : Official... 2023The reporting of serious adverse events (SAE) and serious adverse reactions (SAR) is an essential part of an effective vigilance and surveillance system (V&S) in organ...
The reporting of serious adverse events (SAE) and serious adverse reactions (SAR) is an essential part of an effective vigilance and surveillance system (V&S) in organ donation and transplantation. All SAE and SAR reported to the German organ procurement organization (DSO) between 2016 and 2022 were analyzed. In case of a possible transmission of a disease to one or more recipients, an assessment of imputability was done according to the grading system of the US Disease Transmission Advisory Committee (DTAC). 543 SAE and SAR cases were reported to the DSO and analyzed in detail. 53 of the 543 reports (9.8%) were proven or probable (P/P) transmissions of infectious diseases, malignancies or other diseases to 75 recipients. Infections were the most frequently reported P/P disease transmission occurrences (30/53, 57%). In case of disease transmission, the mortality of the recipients was high (17/75, 23%), especially when a malignant disease was transmitted (11/22, 50 %). Donor-Derived disease transmission is a rare event (53/8,519; 0.6 %), but when it occurs can lead to significant morbidity and mortality.
Topics: Humans; Organ Transplantation; Tissue and Organ Procurement; Tissue Donors; Germany; Probability
PubMed: 37745644
DOI: 10.3389/ti.2023.11610 -
Experimental and Clinical... Dec 2023As a result of recent biomedical advancements, organ donation continues to save and enhance countless lives globally.Yet,the gap between the organ supply and demand... (Review)
Review
OBJECTIVES
As a result of recent biomedical advancements, organ donation continues to save and enhance countless lives globally.Yet,the gap between the organ supply and demand persists, leading to approximately 17 people dying each day waiting for an organ transplant and another person being added to the transplant waiting list every 9 minutes. This gap persists, in part, because of ethical and practical concerns arising from ambiguities surrounding death determination before donation and the dead donor rule. In this study, we discuss challenges related to defining death in the context of organ donation, critical and tolerant views on the dead donorrule, and possible avenues by which some of the ambiguities and ethicaltensions related to organ donation may be resolved.
MATERIALS AND METHODS
We reviewed literature opinions and data pertaining to cultural and religious influences affecting societal attitudes toward death determination and organ donation and examined the future of deceased organ donation.
RESULTS
Cultural and religious influences affect societal attitudes toward death determination and organ donation. There is a plurality of views on the matter that may be assuaged to an extent by standardized death determination criterion that could be implemented globally or by identifying alternative therapies other than human organ transplant.
CONCLUSIONS
The debate regarding death and the acceptability of dead donor organs fortransplant does not have a straightforward solution, and efforts are needed to overcome social, cultural and religious objections.
Topics: Humans; Tissue Donors; Organ Transplantation; Tissue and Organ Procurement
PubMed: 38263778
DOI: 10.6002/ect.2023.0247 -
Xenotransplantation 2024Organ transplant is a crucial therapeutic strategy offering a life-saving and transformative medical intervention. It provides an opportunity to improve their quality of... (Review)
Review
Organ transplant is a crucial therapeutic strategy offering a life-saving and transformative medical intervention. It provides an opportunity to improve their quality of life and increase their lifespan. The shortage of organs remains a critical global challenge, leading to a prolonged waiting times for organ receivers, which contributes to an increase in morbidity and mortality rates. Hence, xenotransplantation offered a promising solution to the global shortage of organs through the use of animal organs, leading to an increase in donor availability, reducing waiting times, minimizing organ trafficking, improving genetic engineering advancements, and driving scientific innovation. Even though xenotransplantation has many benefits in the clinical setting, it has many barriers that are hindering its achievements and constraining its occurrence. Some barriers to xenotransplant are general, such as the immunological barrier, while others are specific to certain regions due to local causes. The Arab region exhibits disparities in clinical settings compared to the global context, marked by the huge economic crisis and a shortage of trained healthcare professionals. Considering the huge resources and advancements needed in the field of xenotransplantation, this review aims to explore the specific barriers toward xenotransplantation in the Arab countries, highlighting the challenges to overcome these barriers.
Topics: Animals; Humans; Transplantation, Heterologous; Arab World; Quality of Life; Organ Transplantation; Tissue Donors
PubMed: 38526015
DOI: 10.1111/xen.12852 -
Transplant Infectious Disease : An... Aug 2023Cytomegalovirus (CMV) is a frequent infectious complication following solid organ transplantation (SOT). Considering significant differences in healthcare systems, a...
Epidemiology, management, and burden of cytomegalovirus in solid organ transplant recipients in selected countries outside of Europe and North America: A systematic review.
BACKGROUND
Cytomegalovirus (CMV) is a frequent infectious complication following solid organ transplantation (SOT). Considering significant differences in healthcare systems, a systematic review was conducted to describe the epidemiology, management, and burden of CMV post-SOT in selected countries outside of Europe and North America.
METHODS
MEDLINE, Embase, and Cochrane databases were searched for observational studies in SOT recipients across 15 countries in the regions of Asia, Pacific, and Latin America (search period: January 1, 2011 to September 17, 2021). Outcomes included incidence of CMV infection/disease, recurrence, risk factors, CMV-related mortality, treatment patterns and guidelines, refractory and/or resistant CMV, patient-reported outcomes, and economic burden.
RESULTS
Of 2708 studies identified, 49 were eligible (n = 43/49; 87.8% in adults; n = 34/49, 69.4% in kidney recipients). Across studies, selection of CMV preventive strategy was based on CMV serostatus. Overall, rates of CMV infection (within 1 year) and CMV disease post-SOT were respectively, 10.3%-63.2% (9 studies) and 0%-19.0% (17 studies). Recurrence occurred in 35.4%-41.0% cases (3 studies) and up to 5.3% recipients died of CMV-associated causes (11 studies). Conventional treatments for CMV infection/disease included ganciclovir (GCV) or valganciclovir. Up to 4.4% patients were resistant to treatment (3 studies); no studies reported on refractory CMV. Treatment-related adverse events with GCV included neutropenia (2%-29%), anemia (13%-48%), leukopenia (11%-37%), and thrombocytopenia (13%-24%). Data on economic burden were scarce.
CONCLUSION
Outside of North America and Europe, rates of CMV infection/disease post-SOT are highly variable and CMV recurrence is frequent. CMV resistance and treatment-associated adverse events, including myelosuppression, highlight unmet needs with conventional therapy.
Topics: Adult; Humans; Cytomegalovirus; Cytomegalovirus Infections; Europe; North America; Ganciclovir; Organ Transplantation; Leukopenia
PubMed: 37254966
DOI: 10.1111/tid.14070 -
Human Immunology May 2024The intestines have been considered the "forbidden organ" for years, and intestinal failure became the last organ failure recognized as such in the medical field. The...
The intestines have been considered the "forbidden organ" for years, and intestinal failure became the last organ failure recognized as such in the medical field. The impossibility of providing adequate nutritional support, turned these patients into recipients of just palliative comfort. In the 1960's, parenteral nutrition appeared as the most reasonable replacement therapy, but the initial success obtained with clinical kidney, heart, liver, lung and pancreas transplantation served as background to explore intestinal transplantation. The first clinical report of an isolated intestinal transplant was done by Richard Lillihei in 1967; in 1983, Thomas Starzl, performed the first multi visceral transplant, and in 1990, David Grant performed the first combined liver-intestinal transplant in an adult recipient in Canada. Since then, advances in immunosuppressive therapies and surgical innovations have allowed not only a continuous increase in indications, but also a worldwide application of all procedures, bringing clinical intestinal transplantation to reality. In this historical account, the most important contributions have been summarized, thus describing the steady progress, expansion and novelties developed over the last 56 years, since the first attempt. Clinical intestinal transplantation remains a complex and evolving field; ongoing research and technological advancements will continue shaping its future.
Topics: Humans; History, 20th Century; History, 21st Century; Intestinal Failure; Intestines; Organ Transplantation
PubMed: 38519405
DOI: 10.1016/j.humimm.2024.110788 -
HEC Forum : An Interdisciplinary... Jun 2024The stipulation of living organ transplantation policy and practice in Bangladesh is family-oriented, with relatives being the only people legally eligible to donate...
The stipulation of living organ transplantation policy and practice in Bangladesh is family-oriented, with relatives being the only people legally eligible to donate organs. There have been very few transplantations of bone marrows, liver lobes, and kidneys from related-living donors in Bangladesh. The major question addressed in this study is why Bangladesh is not getting adequate organs for transplantation. In this study, I examin the stipulations of the policy and practice of living organ donation through the lens of 32 key stakeholders including physicians and nurses, a health administrator, organ donors and recipients, and their family members, as they can shed light on the realities and problems of organ donation for transplantation in Bangladesh. My ethnography reveals that the family members are always encouraged to donate organs for transplantation, and saving the lives of relatives through organ donation is seen as a moral obligation. Many view saving the life of a relative by donating one's organs as equivalent to saving one's own life. An assessment of the dynamics of biomedicine, religion, and culture leads to the conclusion that the family-oriented organ donation policy and practice have been widely endorsed and accepted in Bangladesh, and Islamic ethical principles and collective family ethos undergird that policy and practice. However, the unavailability of medical resources, lack of post-operative coverage for organ donors, religious misconceptions and unawareness of the general public, and the absence of posthumously donated vital organs for transplantation are perceived to be the most common barriers to a successful living donor-recipient pair organ transplantation. By overcoming these obstacles, Bangladesh can develop a successful living donor-recipient pair organ transplantation program that will ensure improved healthcare outcomes, promote altruism and solidarity among Bangladeshi families, and protect the poor from having their organs sold to wealthy patients.
Topics: Humans; Bangladesh; Tissue and Organ Procurement; Living Donors; Organ Transplantation; Family
PubMed: 36355267
DOI: 10.1007/s10730-022-09500-z -
Current Opinion in Organ Transplantation Apr 2024Regulatory dendritic cells (DCregs; also 'tolerogenic DCs'), innate immune cells that regulate the alloimmune response, are a novel cellular therapy for organ... (Review)
Review
PURPOSE OF REVIEW
Regulatory dendritic cells (DCregs; also 'tolerogenic DCs'), innate immune cells that regulate the alloimmune response, are a novel cellular therapy for organ transplantation. Preliminary results from early-phase clinical trials in live donor kidney and liver transplantation are promising. This follows many years of research elucidating mechanisms of action and utility of DCregs. Herein, we review early-phase clinical trial observations and recent advances in the production, modification, and future-trajectory of DCreg in organ transplantation.
RECENT FINDINGS
Preclinical work has demonstrated the ability of adoptively transferred DCreg to abrogate ischemia-reperfusion injury and promote long-term allograft survival. Good Manufacturing Practice-grade DCregs have been generated in adequate numbers for early-phase trials of autologous DCregs in kidney transplantation and donor-derived DCreg in liver transplantation. These trials have demonstrated feasibility and safety, with preliminary evidence of an influence on host immune reactivity. In both kidney and liver transplantation, reduced effector CD8 + T-cells have been noted, together with other changes that may be conducive to reduced dependence on immunosuppressive therapy.
SUMMARY
Substantial progress has been made in bringing DCreg to clinical testing in organ transplantation. Additional clinical and mechanistic studies are now needed to further explore and garner the full potential of DCreg in organ transplantation.
Topics: Humans; Organ Transplantation; Kidney Transplantation; Transplantation, Homologous; T-Lymphocytes; Dendritic Cells; T-Lymphocytes, Regulatory
PubMed: 37991065
DOI: 10.1097/MOT.0000000000001127 -
Journal of Intensive Care Medicine May 2024Intensive care physicians may assume the primary care of patients with transplant-associated thrombotic microangiopathy (TA-TMA), an uncommon but potentially critical... (Review)
Review
Intensive care physicians may assume the primary care of patients with transplant-associated thrombotic microangiopathy (TA-TMA), an uncommon but potentially critical complication of hematopoietic stem cell transplants (HSCTs) and solid organ transplants. TA-TMA can have a dramatic presentation with multiple organ dysfunction syndrome (MODS) associated with high morbidity and mortality. The typical presenting clinical features are hemolytic anemia, thrombocytopenia, refractory hypertension, proteinuria and worsening renal failure. Intestinal involvement, with abdominal pain, nausea and vomiting, gastrointestinal bleeding, and ascites are also common. Cardiopulmonary involvement may develop from various causes including pulmonary arteriolar hypertension, pleural and pericardial effusions, and diffuse alveolar hemorrhage. Due to other often concurrent complications after HSCT, early diagnosis and effective management of TA-TMA may be challenging. Close collaboration between ICU and transplant physicians, along with other relevant specialists, is needed to best manage these patients. There are currently no approved therapies for the treatment of TA-TMA. Plasma exchange and rituximab are not recommended unless circulating factor H (CFH) antibodies or thrombotic thrombocytopenic purpura (TTP; ADAMTS activity < 10%) are diagnosed or highly suspected. The role of the complement pathway activation in the pathophysiology of TA-TMA has led to the successful use of targeted complement inhibitors, such as eculizumab. However, the relatively larger studies using eculizumab have been mostly conducted in the pediatric population with limited data on the adult population. This review is focused on the role of intensive care physicians to emphasize the clinical approach to patients with suspected TA-TMA and to discuss diagnosis and treatment strategies.
Topics: Adult; Humans; Child; Thrombotic Microangiopathies; Hypertension; Multiple Organ Failure; Organ Transplantation; Hematopoietic Stem Cells; Hematopoietic Stem Cell Transplantation
PubMed: 37990516
DOI: 10.1177/08850666231200193 -
Transplant International : Official... 2023Solid organ transplant (SOT) recipients have a higher risk of developing invasive mould diseases (IMD). Isavuconazole is a novel broad-spectrum azole active against... (Review)
Review
Solid organ transplant (SOT) recipients have a higher risk of developing invasive mould diseases (IMD). Isavuconazole is a novel broad-spectrum azole active against spp. and Mucor, well tolerated, with an excellent bioavailability and predictable pharmacokinetics, that penetrates in most tissues rapidly, and has few serious adverse effects, including hepatic toxicity. Contrary to other broad-spectrum azoles, such as voriconazole and posaconazole, isavuconazole appears to show significant smaller drug-drug interactions with anticalcineurin drugs. We have performed an extensive literature review of the experience with the use of isavuconazole in SOT, which included the SOTIS and the ISASOT studies, and published case reports. More than 140 SOT recipients treated with isavuconazole for IMD were included. Most patients were lung and kidney recipients treated for an infection. Isavuconazole was well tolerated (less than 10% of patients required treatment discontinuation). The clinical responses appeared comparable to that found in other high-risk patient populations. Drug-drug interactions with immunosuppressive agents were manageable after the reduction of tacrolimus and the adjustment of mTOR inhibitors at the beginning of treatment. In conclusion, isavuconazole appears to be a reasonable option for the treatment of IMD in SOT. More clinical studies are warranted.
Topics: Humans; Antifungal Agents; Aspergillosis; Nitriles; Organ Transplantation; Transplant Recipients; Voriconazole
PubMed: 38161768
DOI: 10.3389/ti.2023.11845