Solid Organ Transplant Recipients Research Articles

Bacteremia in Pediatric Solid Organ Transplant Recipients within 1 Year of Transplant.

Bacteremia is a major cause of morbidity and mortality in immunocompromised children, yet there are limited data in children who have undergone solid organ transplantation (SOT). We retrospectively reviewed bloodstream infections (BSI) in 581 recipients of heart, liver, or kidney transplants over a 14-year period. Overall 1-year incidence in this population was 8.4%, and was highest in recipients of liver transplants compared to heart or kidney. Younger age, transplantation earlier in the time period studied, need for repeat surgery within 30 days of transplant, and prior diagnosis of diabetes or tumor were associated with an increased risk of BSI. Most BSI occurred within 90 days of transplant, and most were associated with central venous lines. Coagulase-negative staphylococci and enteric commensals were commonly isolated. Multiple BSI within the year after transplant were uncommon. Although overall mortality was not increased in patients with BSI compared to those without, patients with BSI had more total hospitalizations and more days spent in the hospital in the year following SOT. In a large pediatric SOT population, overall BSI rates were significant but decreased over time. Identifying factors which contribute to BSI after SOT may direct interventions that can impact inpatient care requirements for these patients.

Selective expression of Pneumocystis antigens in different patients during a suspected outbreak of Pneumocystis pneumonia.

The fungus Pneumocystis jirovecii causes severe pneumonia in immunocompromised individuals. It harbors a system of surface antigenic variation involving six families of major surface glycoproteins (Msg). We determined the repertoires of P. jirovecii msg genes of the most abundant family-I present in 15 Swiss patients with Pneumocystis pneumonia (PCP) enrolled randomly. The highly repetitive msg-I genes were sequenced using generic PCRs followed by circular consensus sequencing with long reads. In contrast to the other 12 patients, three renal transplant recipients (RTRs) harbored the same repertoire of msg-I genes. Multilocus genotyping showed that these RTRs were infected by the same P. jirovecii genotype that differed from those present in the other 12 patients. These observations suggested that these RTRs were involved in an outbreak of PCP due to interhuman transmission or a common source of the fungus. Although they harbored the same repertoire of msg-I genes, the sets of msg-I genes that were expressed differed between the three patients. This suggested that selective expression of P. jirovecii surface antigens might have played a role in the pathogenesis of PCP by allowing escape from the immune response specific to each patient. Although expected for a family of genes, this is the first time that selective expression of antigens is observed in Pneumocystis. The previously described adaptation of P. jirovecii to infect solid organ transplant (SOT) recipients through resistance to the immunosuppressant mycophenolate probably also favored the suspected outbreak. Moreover, our study supports the idea that various P. jirovecii genotypes can adapt to infect SOT recipients.IMPORTANCEThe fungus Pneumocystis causes severe pneumonia in patients with weakened immune systems. It possesses a genetic system to vary the antigens at the surface of its cells that are presented to the immune system of the patient. We report for the first time that this system may have been implicated in the infections of renal transplant recipients involved in a suspected outbreak. Our observations suggest that the antigens presented might be selected to avoid the elimination of the fungus by the immune response specific to each patient. The resistance of the fungus to the immunosuppressant mycophenolate administered to these patients to prevent organ rejection probably also played a role in the infections during the suspected outbreak.

Reactivation of cutaneous leishmaniasis in the context of non-HIV immunosuppression: a literature analysis.

Reactivation of cutaneous leishmaniasis in the context of non-HIV immunosuppression: a literature analysis.

Combination of LED illumination and daylight photodynamic therapy for the treatment of actinic keratosis in solid organ transplant recipients: a prospective, randomized, comparative, intra-patient study.

Solid organ transplant recipients have an increased risk of developing actinic keratosis. Recent studies show greater effectiveness when combining daylight photodynamic therapy with a posterior LED illumination for their treatment in immunocompetent patients. The aim of this study was to compare the effectiveness of combining daylight photodynamic therapy and LED illumination versus daylight photodynamic therapy alone for the treatment of actinic keratosis in solid organ transplant recipients. This randomized intra-patient study was conducted at University of Navarra Clinic. Solid organ transplant recipients with two 25cm2 areas on the face or scalp with at least four actinic keratosis, were included. After receiving daylight photodynamic therapy in both areas, one of them was randomized to receive complementary LED illumination. The primary endpoint was the reduction of the baseline actinic keratosis at 3months post-treatment. Thirteen patients with a total of 169 AKs were recruited. At 12 weeks post-treatment, the area treated with daylight and conventional photodynamic therapy showed a greater reduction in actinic keratoses (79.55% vs. 65.43%, p<0.05). Our results suggest greater effectiveness of combining daylight photodynamic therapy with LED illumination compared to daylight photodynamic therapy alone for the treatment of actinic keratosis in solid organ transplant recipients.

Perioperative complications and mid-term outcomes in total hip and knee joint arthroplasty among solid organ transplant recipients: lowest reoperation-free survival and patient survivorship in lung transplant recipients

IntroductionPerforming total joint replacements (TJR) in patients with solid organ transplantations (SOT) is associated with an increased risk of complications and reoperation. The aim of this study is to report on implant survivorship, patient survivorship, and complication rates for total knee arthroplasty (TKA) and total hip arthroplasty (THA) performed in heart, lung, liver and kidney transplant recipients.Materials and methodsForty patients with heart, lung, liver, or kidney transplants who underwent primary THA or TKA between January 1, 2013, and July 31, 2023, were included. Implant survivorship, reoperation-free survivorship, patient survivorship, and complication rates were compared between the subgroups.ResultsAt a mean follow-up of 5.18 years, Implant survivorship and reoperation-free survival for the entire cohort at the last follow-up were 97.5% and 85%, respectively. Kaplan–Meier survival estimates demonstrated 5- and 10-year reoperation-free survival rates of 86.5% (95% CI: 76%–98.4%) and 57.6% (95% CI: 25.6%–100%), respectively. The lung transplant group had the shortest reoperation-free survival, although not statistically significant (p = 0.07), a significantly higher risk of reoperation, with a hazard ratio (HR) of 6.9 (95% CI: 1.1–41.2, p = 0.04) and both the lowest 5-year patient survivorship at 68.6% (p = 0.04) and the highest risk of death after TJR with a HR of 7 (95% CI: 1.2–45.5, p = 0.03).ConclusionPatients with SOT exhibit excellent mid-term implant survivorship, with a rate of 97.5%. Lung transplant recipients show the lowest rates of both reoperation-free survival and overall patient survivorship compared to heart, kidney, and liver transplant recipients. Despite this, the 90-day complication rates are similar across all organ groups.

Neutralizing Antibody Response to the AreXvy Respiratory Syncytial Virus Vaccine in Lung Transplant Recipients: Assessment Against Reference and Seasonal Strains

Background: Respiratory Syncytial Virus (RSV) is a significant cause of morbidity and mortality among lung transplant (LTx) recipients. Therapeutic options are limited, emphasizing the importance of prevention. The Arexvy® vaccine (RSVPreF3) showed promising efficacy among immunocompetent adults; however, data on its immunogenicity in solid organ transplant recipients remain unclear. Methods: A single-center retrospective cohort study, including all LTx recipients who were vaccinated with Arexvy in February 2024. Baseline and follow-up serum samples (1, 3, and 6 months post-vaccination) were analyzed for antibody responses using a commercial RSV ELISA kit and micro-neutralization assays against historical reference RSV A/B ATCC strains and seasonal RSV strains. Adverse events were documented. Results: A total of 28 recipients received the vaccine. Twenty-one (75%) were male, and the median age was 62 years (interquartile range [IQR], 53–67). The median time from transplant was 486 days (IQR, 243–966). Vaccination elicited strong immunogenic responses, demonstrating a twofold increase in ELISA-determined antibody levels at one month post-vaccination, which were sustained for six months. At one month, 67% of recipients had antibody levels exceeding the cutoff threshold. Micro-neutralization assays showed a significant increase in neutralizing antibodies against all tested variants (RSV A/B ATCC and seasonal RSV A/B), with titers remaining at least twofold higher than pre-vaccination levels. No serious adverse events were observed. Conclusions: Our findings demonstrate a sustained antibody response to the Arexvy® vaccine in a cohort of LTx recipients, with antibody titers sustained over six months. Further research is needed to assess the long-term durability of the immune response and the potential immunogenicity of this vaccine in LTx populations.

Nocardiosis in solid organ transplant recipients: Clinical challenges

Nocardiosis is an infection caused by Nocardia spp., presenting as pulmonary, cutaneous, or disseminated disease. It predominantly affects immunocompromised individuals, with organ transplant recipients being particularly vulnerable. The rarity of this infection, combined with diverse clinical presentations and challenging growth in culture, complicates diagnosis. Treatment is prolonged and frequently involves combination therapy. We report a case of disseminated nocardiosis in a renal transplant patient and examine the clinical and microbiological features of three additional cases diagnosed at CHUV among organ transplant recipients, highlighting the complexity of clinical management.

Standardizing Care and Management of Cytomegalovirus Infections in Solid Organ Transplant Recipients: Highlights From the Fourth Consensus Guidelines.

Standardizing Care and Management of Cytomegalovirus Infections in Solid Organ Transplant Recipients: Highlights From the Fourth Consensus Guidelines.

Case Report: Maribavir for refractory cytomegalovirus viremia after renal transplantation in a child with Schimke’s immune-osseous dysplasia

Cytomegalovirus (CMV) is a major opportunistic pathogen in recipients of solid organ transplantation. Maribavir, a pUL97 protein kinase inhibitor, was approved for the treatment of refractory post-transplant CMV infection in the US in 2021. However, it is rarely used in pediatric patients worldwide. Here, we report the case of a Chinese boy with Schimke’s immune-osseous dysplasia (SIOD) who developed refractory CMV infection after a renal transplantation. An 11-year-old boy was hospitalized with recurrent abdominal and testicular pain 50 days after renal transplantation. Diagnoses included urinary tract infection, epididymitis, CMV viremia, stage 2 chronic kidney disease, and SIOD. After five days of treatment, his pain improved, but he developed persistent fever and shortness of breath. Blood CMV levels rose to 1.64 × 105 copies/ml after one month of ganciclovir treatment. Significant bone marrow suppression was observed after combined treatment with foscarnet. Anti-rejection treatment was discontinued due to compromised immune function. On day 40, maribavir was initiated with parental consent, resulting in undetectable CMV copies within four days. The patient’s clinical status and bone marrow suppression had improved. Continuing maribavir for two weeks led to the disappearance of CMV viremia, no bone marrow suppression, and normal liver and kidney functions. This case demonstrates the successful short-term use of maribavir in the treatment of refractory CMV infection in an immune-deficient child after renal transplantation. Further studies are required to explore the efficacy and safety of maribavir in pediatric patients.

Physiotherapy Approach to Improve Neuroplasticity in Cryptococcal Meningitis in Post Renal Transplant Recipient: A Case Report

Background: Cryptococcal Meningitis is an opportunistic infection caused by Cryptococcus neoformans. It has been reported to be an important cause of morbidity and mortality in solid organ transplant recipients. Common manifestations of the disease are of pulmonary and central nervous systems (CNS). Case description: We report a case of 21-year-old female, who is known case of cryptococcal meningitis post renal transplant. Clinically, she had symptoms of reduced muscle strength of bilateral lower limbs, paresis of left leg, impaired balance, generalised weakness, headache and blurred vision. On examination lower limb muscle strength, hand grip strength and balance were reduced. Functional independence score was 37 on FIM (Functional Independence Measure) scale, which suggests that patient is fairly dependent for daily activities. We programmed tailor-made rehabilitation to improve neuroplasticity and thus the functional independence. Purpose: To study the effect of physiotherapy rehabilitation in a rare case of cryptococcal meningitis. Methods: Physiotherapy was started in the ICU empirically to increase mobility and prevent secondary complications in the form of positioning, passive exercises and breathing exercises and continued in wards more aggressively with protocols to improve balance and muscular strength for 8 weeks. Result: 8 weeks of physiotherapy rehabilitation showed significant improvement in muscle strength, balance, and functional independence. We saw significant improvement in hand grip strength, lower limb manual muscle testing, balance and FIM score (90). Conclusion: Structured physiotherapy treatment along with medications can improve symptoms of cryptococcal meningitis in solid organ transplant patients. Keywords: Physiotherapy, Neuroplasticity, Cryptococcal meningitis, Solid organ transplant, Physiotherapy in Renal Transplant, Functional independence.

Cytomegalovirus Management in Solid Organ Transplant Recipients

Cytomegalovirus (CMV) remains a significant cause of morbidity and mortality in solid organ transplant (SOT) recipients. Despite advancements in prophylaxis and antiviral therapy, CMV continues to pose clinical challenges in transplant medicine. This review provides a comprehensive overview of CMV, exploring its pathophysiology, epidemiology, and clinical presentation in SOT patients, in whom CMV infection can lead to direct organ involvement and systemic symptoms. Additionally, CMV has indirect effects, including graft dysfunction and an increased risk of opportunistic infections. We examine the immune responses to CMV, focusing on the roles of both innate and adaptive immunity. The importance of personalized prophylaxis and preemptive therapy is emphasized based on serostatus and individual risk factors. Furthermore, this review discusses resistance mechanisms to standard therapies exploring alternative treatments.

The Prevalence, Risk Factors, and Outcomes of Hepatitis E Virus Infection in Solid Organ Transplant Recipients in a Highly Endemic Area of Italy

Hepatitis E virus (HEV) infection can become chronic in immunocompromised patients, like solid organ transplant recipients (SOTRs). We evaluated HEV prevalence, risk factors, and outcomes among SOTRs in a hyperendemic HEV area. Three hundred SOTRs were enrolled from April to July 2019 and tested for anti-HEV IgM and IgG and HEV RNA. Sixty-three recipients (21%) were positive for any HEV marker. HEV infection was independently associated with older age and pork liver sausage consumption. Three viremic recipients harbored genotype 3e and 3f according to HEV RNA sequencing and phylogenetic analysis. Overall, 10 recipients had markers of active/recent infection (HEV RNA and/or anti-HEV IgM) and were followed up prospectively. Five of them spontaneously resolved their HEV infection. In two recipients, HEV clearance was achieved only through immunosuppression reduction, while three needed ribavirin therapy to achieve virologic resolution. We observed a chronic course in 30% of SOTRs with active/recent HEV infection. No association was found between tacrolimus assumption and chronicization. In conclusion, we found a high prevalence of infection among SOTRs attending a transplant center in a hyperendemic Italian HEV region. Systematic screening for all HEV markers and dietary education for infection control are needed for transplant recipients.

Immune checkpoint inhibitors use in lung transplant recipients: a case series and systematic review of literature.

Immune checkpoint inhibitors use in lung transplant recipients: a case series and systematic review of literature.

Psychiatric Consultations and Treatment Adherence in Pediatric Solid Organ Transplant Recipients: The Role of Adjustment Disorder

Psychiatric Consultations and Treatment Adherence in Pediatric Solid Organ Transplant Recipients: The Role of Adjustment Disorder

319 Exploring late effects care for PTLD survivors using the consolidated framework for implementation research

Objectives/Goals: With qualitative interviews we aim to 1-Describe barriers and facilitators for post-transplant lymphoproliferative disease (PTLD) survivors’ access to late effects (LE) care. 2-Investigate clinicians’ perceptions of current and ideal PTLD LE care. Our long-term goal is to develop and pilot implementation strategies to standardize PTLD LE care. Methods/Study Population: Study population: We will recruit 20–25 PTLD survivors or their caregivers and 10–15 health care workers (HCW) from oncology, LE, and solid organ transplant (SOT) teams at St. Louis Children’s Hospital (SLCH). PTLD is a lymphoma-like cancer that occurs in solid organ transplant (SOT) recipients. PTLD survivors experience LE from cancer, yet many do not receive LE care. Research strategy: We will conduct qualitative semi-structured interviews based on the Consolidated Framework for Implementation Research (CFIR). A preliminary codebook will be based on CFIR and refined through transcript review. Team-based coding includes double coding and checking for intercoder reliability. We will generate coding reports to understand themes and identify barriers and facilitators of LE care. Results/Anticipated Results: We hypothesize survivors, caregivers, and HCWs will identify actionable factors to inform future studies to optimize LE care. We will examine the CFIR inner setting (resources, communication, and structural characteristics), outer setting (local attitudes and external pressures), innovation domain (adaptability, evidence base, and relative advantage), individuals domain (need, opportunity, and motivation), and implementation process domain. Our contribution will be novel. 1-This is the first assessment of barriers and facilitators for LE care in pediatric PTLD survivors. 2-We will consider input from HCWs across various disciplines delivering care to PTLD survivors. 3-We anticipate identifying unique contextual factors in PTLD survivors that will influence implementation of evidence-based LE care. Discussion/Significance of Impact: Pediatric cancer survivors experience LE. Coordinated care mitigates LE. PTLD survivors experience a high burden of LE, but less than 10% of PTLD survivors at SLCH follow in LE clinic. No studies have evaluated ideal delivery of LE care for PTLD survivors. Our findings will inform an implementation trial to improve delivery of LE care for PTLD survivors.

Direct-Acting Antiviral Treatment Failure and Retreatment Strategies Following Hepatitis C-Positive Solid Organ Transplantation in Hepatitis C-Negative Recipients: A Multicenter Case Series.

Transplanting solid organs from hepatitis C virus (HCV) nucleic acid testing (NAT+) donors (D+) into HCV-negative recipients (R-) has become more common with the development of curative direct-acting antiviral (DAA) treatment. Limited information exists to guide retreatment strategies for patients not achieving sustained virologic response (SVR) with DAAs. This multisite case series examines retreatment strategies and subsequent SVR rates in HCV-negative solid-organ transplant (SOT) recipients who did not achieve SVR following reactive initial DAA therapy following NAT+ SOT. A retrospective multisite case series was conducted on patients not achieving SVR with initial DAA treatment post-NAT+ HCV SOT between September 2016 and September 2022 across four tertiary medical centers in the United States. Thirteen patients were identified, predominantly receiving HCV NAT+ kidneys (77%) and SOF/VEL for 12 weeks as initial DAA therapy (43%). Baseline resistance testing was not performed. Median time to treatment initiation post-SOT was 35 [IQR 22-41] days, and to retreatment postpositive viral load was 35 days [IQR 17-76]. Most patients (62%) were retreated with sofosbuvir/velpatasvir/voxilaprevir (SOF/VEL/VOX) for 12 weeks. Two patients required retreatment extension with SOF/VEL/VOX and SOF/VEL/VOX + ribavirin (RBV) from 12 to 24 weeks due to persistent viremia. Only one patient did not achieve SVR following retreatment with SOF/VEL/VOX for 12 weeks but did achieve SVR after a third course of treatment with SOF + GLE/PIB + RBV for 24 weeks. Despite initial DAA failures, all HCV-negative SOT recipients achieved SVR following one or more courses of retreatment with DAAs.

Spectrum of cancer risk in Asian American and Pacific Islander solid organ transplant recipients.

Solid organ transplant recipients (SOTRs) have increased cancer risk, which may differ across racial groups. Cancer risk among Asian American and Pacific Islander SOTRs is ill-defined. We evaluated Asian, Pacific Islander, and White SOTRs from a linkage of the United States SOTR registry with 34 cancer registries (1990-2019). We calculated age-and-sex adjusted incidence rate ratios (aIRRs) to compare cancer risk between races and standardized incidence ratios (SIRs) to measure risk relative to race-matched general populations. Compared with Asian SOTRs, Pacific Islander SOTRs had notably higher incidence of pancreatic cancer (aIRR = 3.7, 95%CI = 1.6-8.6) and melanoma (aIRR = 6.7, 95%CI = 1.2-36). Compared with White SOTRs, Asian and Pacific Islander SOTRs had lower melanoma incidence but higher nasopharyngeal carcinoma incidence. Compared with the general population, Asian SOTRs had increased risk of cancers of the anus (SIR = 7.9, 95%CI = 3.6-15), penis (SIR = 8.9, 95%CI = 2.9-21), non-epithelial skin (SIR = 9.8, 95%CI = 5.4-17), kidney (SIR = 5.3, 95%CI = 4.3-6.5), and renal pelvis (SIR = 7.4, 95%CI = 3.7-13); non-Hodgkin lymphoma including chronic lymphocytic leukemia (NHL/CLL) (SIR = 6.4, 95%CI = 5.6-7.3); Hodgkin lymphoma (SIR = 6.1, 95%CI = 2.8-12); and Kaposi sarcoma (SIR = 15, 95%CI = 6.6-30). Compared with the general population, Pacific Islander SOTRs had increased risk of cancers of the anus (SIR:12, 95%CI = 1.5-45), pancreas (SIR = 3.3, 95%CI = 1.3-6.8), non-epithelial skin (SIR = 9.3, 95%CI = 1.1, 34), and thyroid (SIR = 3.4, 95%CI = 1.2-7.4); NHL/CLL (SIR = 4.5, 95%CI = 2.3-7.9); and Kaposi sarcoma (SIR = 71, 95%CI = 8.6-258). Asian, Pacific Islander and White SOTRs all experienced elevated cancer risk compared with their race-matched general population. Different cancer risks in these racial groups might be explained by differences in risk factors in the general population or unique features of SOTRs in these groups.

Efficacy of antimicrobials in preventing resistance in solid organ transplant recipients: A systematic review of clinical trials.

In the absence of effective antimicrobials, transplant surgery is not viable, and antirejection immunosuppressants cannot be administered, as resistant infections compromise the life-saving goal of organ transplantation. To evaluate the efficacy of antimicrobials in preventing resistance in solid organ transplant recipients. A systematic review was conducted using a search methodology consistent with the preferred reporting items for systematic reviews and meta-analyses. This review included randomized clinical trials that evaluated the efficacy of antimicrobial agents (prophylactic or therapeutic) aimed at preventing antimicrobial resistance. The search strategy involved analyzing multiple databases, including PubMed/MEDLINE, Web of Science, Embase, Scopus, and SciELO, as well as examining gray literature sources on Google Scholar. A comprehensive electronic database search was conducted from the databases' inception until May 2024, with no language restrictions. After the final phase of the eligibility assessment, this systematic review ultimately included 7 articles. A total of 2318 patients were studied. The most studied microorganisms were cytomegalovirus, although vancomycin-resistant enterococci, Clostridioides difficile, and multidrug-resistant Enterobacterales were also analyzed. The antimicrobials used in the interventions were mainly maribavir, valganciclovir, ganciclovir, and colistin-neomycin. Of concern, all clinical trials showed significant proportions of resistant microorganisms after the interventions, with no statistically significant differences between the groups (mean resistance 13.47% vs 14.39%), except for two studies that demonstrated greater efficacy of maribavir and valganciclovir (mean resistance 22.2% vs 41.1% in the control group; P < 0.05). The total reported deaths in three clinical trials were 75, and there were 24 graft rejections in two studies. All clinical trials reported significant proportions of antimicrobial-resistant microorganisms following interventions. More high-quality randomized clinical trials are needed to corroborate these results.

Pregnancy After Solid Organ Transplantation: Review of the Evidence and Recommendations.

Solid organ transplantation (SOT) offers people with end-stage organ disease an increased quality of life, which includes the return of fertility and the potential for pregnancy. Although the number of pregnancies has increased, definitive recommendations have been lacking. To address reproductive health in SOT recipients, the American Society of Transplantation Women's Health Community of Practice held a virtual Controversies Conference with subject matter experts gathered to discuss topics of contraception, immunosuppression, and pregnancy in SOT recipients and pregnancy post-living donation. This publication is a synthesis of expert guidance and available data regarding pregnancy management and outcomes after all types of SOTs.

Diagnosis of donor-derived Malassezia restricta &Aspergillus species invasive fungal infection in renal transplant recipient using next generation sequencing - A report of 2 cases and literature review.

Diagnosis of donor-derived Malassezia restricta &Aspergillus species invasive fungal infection in renal transplant recipient using next generation sequencing - A report of 2 cases and literature review.