Infectious disease transmission through organ and tissue transplantation has been associated with severe complications in recipients. Determination of donor-derived infectious risk associated with ...organ and tissue transplantation is challenging and limited by availability and performance characteristics of current donor epidemiologic screening (e.g., questionnaire) and laboratory testing tools. Common methods and standards for evaluating potential donors of organs and tissues are needed to facilitate effective data collection for assessing the risk for infectious disease transmission. Research programs can use advanced microbiological technologies to define infectious risks posed by pathogens that are known to be transplant transmissible and provide insights into transmission potential of emerging infectious diseases for which transmission characteristics are unknown. Key research needs are explored. Stakeholder collaboration for surveillance and research infrastructure is required to enhance transplant safety.
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DOBA, IZUM, KILJ, NUK, ODKLJ, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
OBJECTIVESThe inadequate supply of transplantable organs necessitates new approaches to donor screening while avoiding transmission of infections. Donor-derived infections are well described. ...Multiple changes have occurred in donor management and organ utilization, including increased recognition of and therapies for viral infections, the emergence of multidrug antimicrobial-resistant organisms, and identification of some uncommon viral infections transmitted with allografts to clusters of recipients. Donor evaluation has been impacted by substance use-associated deaths and routine use of serologies and nucleic acid testing for hepatitis C virus, hepatitis B virus, and human immunodeficiency virus. Improved assays are needed to prevent infectious transmissions. MATERIALS AND METHODSThe MGH Transplant Center reviewed experience with recipients of organs from donors meeting donor risk criteria and tracked all recipients for possible exposures to hepatitis C virus, hepatitis B virus, and human immunodeficiency virus. This required development of an electronic database to document microbiologic testing data. RESULTSDatabase enhancements allowed tracking of serologic testing. Among our organ recipients, no transmissions of the studied viruses were identified by nucleic acid testing or clinically. Multiple patients had positive serologic assays for tested viruses; all recipients were retested, and appropriate interventions were introduced if the test was confirmed. Some false-positive serologies resulted from recent hepatitis B virus vaccination, receipt of blood products, or transmission of donor B cells with tissues. CONCLUSIONSOrgan transplant from donors meeting donor risk criteria for disease transmission can be performed safely with appropriate informed consent and rigorous pre- and posttransplant microbiological testing. Enhanced compliance with vaccination for hepatitis B virus should be tracked. New sequencing technologies developed for investigation of undiagnosed infections and in xenotransplantation may inform future directions for donor screening. Such tools may increase the safe utilization of organs from donors who have potential risk for transmission of infection to recipients.
Background
COVID‐19 infection varies in severity from minimal symptoms to critical illness associated with a hyperinflammatory response. Data on disease progression in immunosuppressed solid organ ...transplant (SOT) recipients are limited.
Methods
We examined the electronic medical records of all SOT recipients with COVID‐19 from 12 Massachusetts hospitals between February 1, and May 6, 2020. We analyzed the demographics, clinical parameters, course, and outcomes of illness in these patients.
Results
Of 52 COVID‐19‐positive SOT patients, 77% were hospitalized and 35% required ICU admission. Sixty‐nine percent of hospitalized patients had immunosuppression reduced, 6% developed suspected rejection. Co‐infections occurred in 45% in ICU vs 5% in non‐ICU patients (P = .037). A biphasic pattern of evolution of laboratory tests was observed. In the first 5 days of illness, inflammatory markers were moderately increased. Subsequently, WBC, CRP, ferritin, and D Dimer increased with increasing stay in the ICU, and lymphocyte counts were similar. Five patients (16%) died.
Conclusions
Our data indicate that SOT is associated with high rate of hospitalization, ICU admission, and death from COVID‐19 compared to data in the general population of patients with COVID‐19. Despite reduction in immunosuppression, suspected rejection was rare. The clinical course and trend of laboratory biomarkers is biphasic with a later, pronounced peak in inflammatory markers seen in those admitted to an ICU. CRP is a useful marker to monitor disease progression in SOT.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
Various durations of survival have been observed in the xenotransplantation of life-supporting α-1,3-galactosyltransferase knockout (GalT-KO) porcine kidneys into nonhuman primates. Although others ...have demonstrated loss of GalT-KO-transplanted kidneys within 2 weeks, we have reported an average survival of 51 days with the cotransplantation of the kidney and vascularized thymus and an average of 29 days with the kidney alone. To determine the factors responsible for this difference in survival time, we performed xenogeneic kidney transplantations into cynomolgus monkeys with an anti-CD40L-based regimen using two different strains of GalT-KO swine, one derived from MGH miniature swine and the other obtained from Meji University.
Eight cynomolgus moneys received GalT-KO kidneys. Three kidney grafts were from Massachusetts General Hospital (MGH)-Nippon Institute for Biological Science (NIBS) GalT-KO pigs and five GalT-KO grafts were from MEIJI GalT-KO swine. All cynomolgus recipients were treated identically.
Recipients of kidneys from the MGH GalT-KO kidneys swine, produced by nuclear transfer in Japan, survived an average of 28.7 days, whereas recipients of MEIJI GalT-KO kidneys swine survived an average of 9.2 days. Among the differences between these two groups, one potentially revealing disparity was that the MEIJI swine were positive for porcine cytomegalovirus, whereas the MGH-derived swine were negative.
This is the first study comparing renal xenotransplantation from two different sources of GalT-KO swine into nonhuman primates at a single center. The results demonstrate that porcine cytomegalovirus may be responsible for early loss of GalT-KO swine kidney xenografts.
Increased regulatory oversight, mandated use of electronic medical records, and economic constraints on healthcare and research confront academic medical institutions while the core requirements for ...productivity in research, teaching and excellence and equity in clinical care remain. “Burnout” is an important challenge to healthcare and reflects the alienation, cynicism and decreased productivity of responsibilities in medicine that may detract from individual career engagement. Mentorship is advantageous in the successful navigation of careers in academic medicine, notably for individuals in need of specialized knowledge, skills or psychological support to accelerate their development. A formalized mentorship program provides individuals with the guidance and support needed for career development and may alleviate some of the alienation associated with burnout. The interdisciplinary nature of biomedicine supports the use of multiple mentors to provide diverse perspectives for trainees and junior faculty. Mentorship programs require institutional engagement with clear articulation of institutional goals and values as well as financial and political support. Such programs will identify and train potential leaders throughout an organizational hierarchy, support innovation and flexibility within the organization, increase job satisfaction and retention, and, as a result, enhance the institution's competitive position. Notably, relationships developed within a supportive environment may also mitigate the development of professional burnout.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
BACKGROUNDInvasive aspergillosis carries a high mortality with a rising prevalence in immunocompromised hosts. Diagnosis of invasive aspergillosis is challenging and delays in treatment are ...associated with poor outcomes. The galactomannan assay (GM), a non–culture-based surrogate marker of fungal infection, is widely used in diagnosis. It is unknown whether this assay impacts clinical decision making. We evaluated whether GM testing results in earlier initiation of antifungal therapy and is cost effective.
METHODSWe carried out a retrospective review of the electronic medical records of all patients undergoing GM at a 907-bed tertiary-care general hospital from July 11, 2011, to June 12, 2012. Records of patients with a positive GM were individually reviewed to determine the timing of the assay result, presence and timing of relevant culture data, whether BAL GM was performed, radiology data consistent with invasive aspergillosis, and the timing of initiation of antifungal therapy. For each case, it was determined whether GM results impacted the decision to initiate antifungal therapy.
RESULTSForty-six nonduplicate GM samples were positive (>0.5) of 1419 performed. Results were considered to be false positives in 18 cases by care teams. In 21 cases, antifungal therapy was initiated before the assay result based on clinical suspicion, culture data, and/or radiology. The serum GM was performed 164 times at a cost of $21,789 for a single positive result effecting modification of patient care.
CONCLUSIONSerum GM testing at a tertiary-care institution is commonly used but infrequently impacts clinical decision making with major financial burden.
A 70-year-old man who had recently undergone kidney transplantation was evaluated because of rashes that had developed during an admission for Covid-19, respiratory failure, and bacteremia. A ...diagnosis was made.
Heart of the matter—infection and xenotransplantation Saharia, Kapil K.; Hall, Victoria G.; Chesdachai, Supavit ...
Transplant infectious disease,
February 2024, 2024-Feb, 2024-02-00, 20240201, Volume:
26, Issue:
1
Journal Article
Peer reviewed
In this clinicopathological conference, invited experts discussed a previously published case of a patient with nonischemic cardiomyopathy who underwent heart transplantation from a genetically ...modified pig source animal. His complex course included detection of porcine cytomegalovirus by plasma microbial cell‐free DNA and eventual xenograft failure. The objectives of the session included discussion of selection of immunosuppressive regimens and prophylactic antimicrobials for human xenograft recipients, description of infectious disease risk assessment and mitigation in potential xenograft donors and understanding of screening and therapeutic strategies for potential xenograft‐related infections.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
Tuberculosis (TB) is a possible complication of solid organ and hematopoietic stem cell transplantation. The identification of candidates for preventive chemotherapy is an effective intervention to ...protect transplant recipients with latent infection with Mycobacterium tuberculosis from progressing to active disease. The best available proxy for diagnosing latent infection with M. tuberculosis is the identification of an adaptive immune response by the tuberculin skin test or an interferon-γ based ex vivo assay. Risk assessment in transplant recipients for the development of TB depends on, among other factors, the locally expected underlying prevalence of infection with M. tuberculosis in the target population. In areas of high prevalence, preventive chemotherapy for all transplant recipients may be justified without immunodiagnostic testing while in areas of medium and low prevalence, preventive chemotherapy should only be offered to candidates with positive M. tuberculosis-specific immune responses. The diagnosis of TB in transplant recipients can be challenging. Treatment of TB is often difficult due to substantial interactions between anti-TB drugs and immunosuppressive medications. This management guideline summarises current knowledge on the prevention, diagnosis and treatment of TB related to solid organ and hematopoietic stem cell transplantation and provides an expert consensus on questions where scientific evidence is still lacking.
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