Incidence and risk factors of de novo hepatitis E virus infection after receiving liver transplantation.

Organ transplant recipients with hepatitis E virus (HEV) infection bears high risk to develop chronic hepatitis, which is generally associated with immunosuppressive therapies. This study aimed to identify the incidence and predictors of de novo HEV infection in patients after receiving transplantation. We performed a large retrospective study to investigate the prevalence of anti-HEV at baseline, incidence of de novo HEV infection after transplantation, and the risk factors of HEV infection among patients with liver transplant in China. A total of 407 liver transplant recipients were examined for the presence of anti-HEV immunoglobulin G, IgM antibodies, and HEV RNA in serum. Basal indexes in individuals with evidence of post-transplant HEV infection were compared with those without evidence of that, and risk factors associated with HEV infection were assessed. The prevalence of anti-HEV at pretransplant in liver transplant recipients was 25.8% (105/407). Serum-negative conversion occurred in 34 (32.38%) of 105 liver transplant patients. Sixty-five out of 302 patients had de novo HEV infection after transplantation, with a cumulative incidence of 42.74% during follow-up. After transplantation, HEV infection was associated with liver failure (p = 0.012), hypoproteinemia (p = 0.030) and higher level of r-glutamyl transferase (GGT) (p = 0.022) before transplantation. Graft rejection (OR = 0.075; p = 0.045) was negatively associated with serum-negative conversion in patients who had positive anti-HEV antibody before transplantation. The incidence of de novo HEV infection after transplantation were higher in China. Liver failure, hypoproteinemia, and GGT elevation may be associated with HEV infection after liver transplantation. This study suggests that prevention and control of HEV infection after liver transplantation should be paid attention in patients bearing these risk factors.

Delphi Panel Consensus Statement Generation: COVID-19 Vaccination Recommendations for Immunocompromised Populations in the European Union.

INTRODUCTION: The coronavirus disease 2019 (COVID-19) pandemic has caused unprecedented pressure on healthcare systems globally. The lack of quality guidelines on the management of COVID-19 in rheumatologic disease, renal disease, hematological malignancy, and solid organ transplant recipients has resulted in a wide variation in clinical practice. METHODS: Using a Delphi process, a panel of 16 key opinion leaders developed clinical practice statements regarding vaccine recommendations in areas where standards are absent or limited. Agreement among practicing physicians with consensus statements was also assessed via an online physician survey. The strength of the consensus was determined by the following rating system: a strong rating was defined as all four key opinion leaders (KOLs) rating the statement ≥ 8, a moderate rating was defined as three out of four KOLs rating the statement ≥ 8, and no consensus was defined as less than three out of four KOLs provided a rating of ≤ 8. Specialists voted on agreement with each consensus statement for their disease area using the same ten-point scoring system. RESULTS: Key opinion leaders in rheumatology, nephrology, and hematology achieved consensuses for all nine statements pertaining to the primary and booster series with transplant physicians reaching consensus on eight of nine statements. Experts agreed that COVID-19 vaccines are safe, effective, and well tolerated by patients with rheumatological conditions, renal disease, hematologic malignancy, and recipients of solid organ transplants. The Delphi process yielded strong to moderate suggestions for the use of COVID-19 messenger ribonucleic acid (mRNA) vaccines and the necessity of the COVID-19 booster for the immunocompromised population. The expert panel had mixed feelings concerning the measurement of antibody titers, higher-dose mRNA vaccines, and the development of disease-specific COVID-19 guidance. CONCLUSIONS: These results confirmed the necessity of COVID-19 vaccines and boosters in immunocompromised patients with rheumatologic disease, renal disease, hematological malignancy, and solid organ transplant recipients. Statements where consensus was not achieved were due to absent or limited evidence.

Meningeal cryptococcosis in a pancreas transplant recipient requiring grafectomy: A case report.

BACKGROUND: Through continuous improvement in transplantation medicine, a wider range of solid organ transplant (SOT) recipients is considered suitable for complex procedures. Despite advances in modern transplantation practice, transpiring invasive fungal infections pose a substantial threat for SOT recipients. To our knowledge, cryptococcal infection confined amidst sole pancreas SOT recipients has not been described to date. Enforcement of a multidisciplinary transplant team approach in the management of pancreas SOT recipients presenting with complex cryptococcal complications is fundamental in improving patient outcomes. CASE SUMMARY: We present the case of a female pancreas transplant recipient, with confirmed meningeal cryptococcosis, referred to our institution for further evaluation and treatment from the Regional Center for Infectious Diseases. On admission, the patient was weaned from the protocolized immunosuppression therapy for two consecutive weeks, in addition to tapering systemic corticosteroid remedial treatment. Our novel multidisciplinary transplant team approach embodied exhaustive discussions of possible complex and diverse multiple organ system physiologic and pathologic challenges associated with distinct management strategies in pancreas transplant recipients. Owing to the potentially devastating impact of invasive cryptococcosis in terms of morbidity and mortality, a definitive surgical intervention of pancreas transplant grafectomy was reinforced, as a pathway towards secure access to early meaningful expertise care. The patient was discharged to the Regional Center for Infectious Diseases 2 mo after the admittance further advancing to a clinical improvement. CONCLUSION: The precision transplantation approach by tailoring complex medical interventions to individual needs proved indispensable in improving our patient's outcomes.

Prostate cancer and solid organ transplantation: patient management and outcomes.

OBJECTIVE: To analyse the management and outcomes of individuals diagnosed with prostate cancer either before or after organ transplantation, as the impact of organ transplantation and associated immunosuppression on the incidence, progression, and mortality of prostate cancer remains an area of substantial clinical interest and uncertainty. PATIENTS AND METHODS: We conducted a retrospective analysis of patients from two tertiary care centres who had solid organ transplantation and were diagnosed with prostate cancer before or after organ transplantation. Data collected included demographics and clinical information. RESULTS: The cohort consisted of 110 patients with a median (interquartile range [IQR]) age at prostate cancer diagnosis of 62 (56.6-67.2) years and a median (IQR) age at transplantation of 58.6 (52.7-65.3) years. Renal transplantation was the most common (54%). The median (IQR) prostate-specific antigen concentration at prostate cancer diagnosis was 6.2 (4.5-10) ng/mL, and the distribution of American Urological Association risk groups was: low risk, 36%; intermediate risk, 50%; and high risk, 14%. In all, 45 (41%) patients were diagnosed with prostate cancer prior to transplantation. Management included radical prostatectomy (RP; 62%), prostate radiotherapy (RT; 13%), and active surveillance (AS; 18%). During a median (IQR) follow-up of 5.8 (2.5-10) years from prostate cancer diagnosis, one (2%) patient developed metastatic disease. In all, 65 (59%) patients were diagnosed with prostate cancer subsequent to organ transplantation. Management included AS (29%), RT (45%), and RP (15%). During a median (IQR) follow-up of 5.3 (1-8.4) years, three patients (5%) developed metastatic disease. There were no deaths from prostate cancer. CONCLUSION: A diagnosis of localised prostate cancer should not preclude solid organ transplantation, and the presence of a transplant does not appear to substantially impact risk of prostate cancer progression.

Reducing Blood Draws in Pediatric Patients With Solid Organ Injury Through Protocolized Transcutaneous Hemoglobin Monitoring.

BACKGROUND: Management of pediatric solid organ injuries continues to evolve, decreasing the need for serial hemoglobin measurements, repeat imaging, and operative intervention. Transcutaneous continuous hemoglobin monitoring (TCHM) has been shown to effectively monitor hemoglobin levels in children with solid organ trauma. METHODS: A 6-year, single-center, retrospective chart review was conducted of pediatric solid organ injury patients aged 30 days to <18 years admitted to a quaternary children's hospital following implementation of a highly protocolized TCHM system. A laboratory hemoglobin measurement was obtained at the time of diagnosis and additional measurements were determined based on injury grading. Adverse events were tracked and included: central or arterial line placement, blood product(s) administration, percutaneous embolization procedures, transfer to the pediatric ICU and operative intervention. RESULTS: A total of 97 patients met the inclusion criteria. Blood draws were significantly reduced following TCHM protocol implementation (3.0 [IQR 2.0-5.5] vs 2.0 [IQR 1.0-4.5], p 0.01) without a significant increase in blood product administration (p = 0.30), central or arterial line placement (p = 1), or operative intervention (p = 0.29). Length of stay was not impacted (p = 0.36). The rate of unplanned ICU transfers and percutaneous embolization procedures were too low for statistical evaluation. CONCLUSION: TCHM safely reduces the need for serial blood draws in pediatric trauma patients when utilized within a well-defined protocol for solid organ injury. Further studies are needed to evaluate the role of TCHM in shortening or eliminating hospital admission for low-grade solid organ injuries in children. LEVEL OF EVIDENCE: Level III. TYPE OF STUDY: Single-center, retrospective chart review cohort study.

Engagement With Sports After Solid Organ Transplant.

Introduction Transplant Games lend a unique opportunity not only by providing a platform for donors and recipients to engage in sports but also to counter the negativity surrounding organ donation and showcase to the world that transplant recipients can lead active lives. When the Transplant Games were held in Kochi, Kerala, India, for the first time, it provided a venue to engage with transplant recipients, donors, and the families of deceased donors. We aimed to understand the impact that engagement in sports brings on the lives of donors and recipients. Methods After obtaining permission from the organizers, we explained the objectives of the survey to the participants and encouraged them to participate. A survey, covering basic demographic information, transplantation details, and questions related to sports engagement was formulated. Participants could complete the survey electronically via a quick response code or in hard copy. They were fully informed about the objectives of the survey and had the right to withdraw at any stage without consequences. The survey was available for five hours during the games. The study received institutional ethics committee approval (ECASM-AIMS-2024-059). Results Among the approximate 150 participants, we received 78 respondents (52%). After the nine who withdrew consent were removed, we had a full response from 69 participants. Of these, 59 were males (85.5%), and 10 (14.5%) were females. The average age of the participants was 45 ± 13 years. Self-motivation was the most common factor in taking up sports for 30.4% of the responders, followed by family and friends in 23.2% and transplant doctors in 5.8%. Liver Foundation of Kerala (LIFOK), a self-help group of transplant recipients, played a major role in 4.3% of the responders. Bowling was the most popular sport with 23 mentions, followed by carroms and badminton with 27 and 20 mentions, respectively. Donors started to take an active role in sports earlier than recipients, 3.1 ± 1.89 vs. 5.7 ± 5.5 months. The most common reason cited for taking up sports was to become part of the transplant community, followed by a desire to embrace a healthier lifestyle and improve fitness levels. Although none had a personalized coach, most intensified their training and improved nutrition as part of their preparation for the games. Conclusion Our survey is limited by its small and self-selected sample size. Our study highlights the significant role of self-motivation, family support, and self-help groups in encouraging solid organ transplant recipients and donors to engage in sports after surgery. It also highlights the need for more proactive encouragement from doctors and better availability of sports facilities and support staff to help transplant recipients and donors engage in physical activities, which are crucial for their physical and emotional well-being.

Recurrent Clostridioides difficile infections in solid organ transplant recipients: the international CALIPSO study.

OBJECTIVE: To evaluate the risk of recurrent Clostridioides difficile infection (CDI) in solid-organ transplant (SOT) recipients. METHODS: Retrospective multicenter study including SOT recipients with a first CDI episode in the year after transplantation (Jan 2017-June 2020). The primary outcome measure was recurrence, defined as a new CDI≤56 days from the first episode. A competing risk analysis was performed using the sub-distribution hazard model multivariable analysis. RESULTS: 191 SOT recipients were included: 101 (52.9%) were kidney, 66 (34.6%) liver, 11 (5.8%) lung, 8 (4.2%) simultaneous pancreas-kidney, 4 (2.1%) heart and 1 (0.5%) pancreas alone recipients. Treatment for the first CDI were: vancomycin (n=114,59.7%), vancomycin+metronidazole (n=39,20.4%), metronidazole (n=26,13.6%), fidaxomicin (n=9,4.7%), 3 patients did not receive any therapy. After the first CDI, 17/191 (8.9%) patients died within 56-day mortality without having a recurrence, while 23/191 (12%) patients had a recurrence. Among patients with recurrent CDI, 56-day mortality rate was 30.4% (7/23 patients). On multivariable analysis, severe CDI (sHR4.01, 95% CI 1.77-9.08, p<.001) and metronidazole monotherapy (sHR 3.65, 95% CI 1.64-8.14, p=.001) were factors independently associated with recurrence. CONCLUSIONS: Metronidazole monotherapy is associated with increased risk of recurrent CDI in SOT recipients. Therapeutic strategies aimed to reduce the risk of recurrence should be implemented in this setting.

Proficiency testing within Eurotransplant.

Eurotransplant is responsible for the international allocation of organs between eight countries in Europe. All HLA laboratories affiliated to Eurotransplant must be EFI or ASHI-accredited and must participate in the Eurotransplant external proficiency testing (EPT) program, organized by the Eurotransplant Reference Laboratory (ETRL). EPT within Eurotransplant has a long tradition, starting in 1978. The current EPT program consists of the following schemes: HLA typing including serology, CDC crossmatching, HLA-specific antibody detection, and identification. Participants enter the results of laboratory tests using a web-based application. Assessed results are visible on the website. An additional component called "patient-based cases" runs since 2016. Results are summarized and published on the EPT website. Furthermore, these results are discussed during the annual extramural tissue typers meeting, which is organized by the ETRL. Thanks to this EPT program, the performance of all HLA laboratories affiliated to Eurotransplant can be monitored and corrected, if necessary. Because all affiliated laboratories are assessed in the same EPT program, where these laboratories show to be consistent in most of their results, Eurotransplant EPT has proven to be an efficient tool to create a more uniform level of quality of histocompatibility testing within Eurotransplant.

Fatal Hyperacute Liver Failure due to Varicella Zoster Virus Immediately After Living-Donor Liver Transplantation: A Case Report and Review of the Literature.

BACKGROUND: Although acute hepatitis caused by varicella zoster virus mostly develops in immunocompromised patients, hyperacute liver failure is very rare. To our knowledge, there are no previous reports on liver transplant patients. METHODS: We report the first case of fatal hyperacute liver failure due to varicella zoster virus immediately after living-donor liver transplantation without cutaneous lesions and review the literature. RESULT: The present case exhibited rapid development and progression of acute liver failure from postoperative days 11-13, despite being seropositive for varicella zoster virus but unvaccinated and on immunosuppression before transplantation. Especially in solid organ transplantation, only six cases of severe acute liver failure that included hepatic encephalopathy and/or impaired consciousness and sudden extremely high (> 4000 U/L) serum aspartate aminotransferase levels have been reported in heart, lung, and kidney transplant patients. CONCLUSIONS: Early diagnosis of hyperacute liver failure due to varicella zoster virus is challenging because the disease progresses rapidly and skin lesions are absent.

Management of resistant and refractory cytomegalovirus infections after transplantation.

INTRODUCTION: Cytomegalovirus (CMV) is a classic opportunistic infection in transplant recipients. Treatment-refractory CMV infections are of concern, with growing identification of strains that have developed genetic mutations which confer resistance to standard antiviral therapy. Resistant and refractory CMV infections are associated with worse patient outcomes, prolonged hospitalization, and increased healthcare costs. AREAS COVERED: This article provides a comprehensive practical overview of resistant and refractory CMV infections in transplant recipients. We review the updated definitions for these infections, antiviral pharmacology, mechanisms of drug resistance, diagnostic workup, management strategies, and host-related factors including immune optimization. EXPERT OPINION: Resistant and refractory CMV infections are a significant contributor to post-transplant morbidity and mortality. This is likely the result of a combination of prolonged antiviral exposure and active viral replication in the setting of intensive pharmacologic immunosuppression. Successful control of resistant and refractory infections in transplant recipients requires a combination of immunomodulatory optimization and appropriate antiviral drug choice with sufficient treatment duration.

Antibody-Mediated Rejection in Liver Transplantation: Immuno-Pathological Characteristics and Long-Term Follow-Up.

The diagnosis of liver antibody-mediated rejection (AMR) is challenging and likely under-recognized. The association of AMR with donor-specific antibodies (DSA), and its clinical course in relation to pathologic findings and treatment are ill defined. We identified cases of liver AMR by following the criteria outlined by the 2016 Banff Working Group. Patient demographics, native liver disease, histopathologic findings, treatment type, clinical outcome, and transaminase levels during AMR diagnosis, treatment, and resolution were determined. Patients (n = 8) with AMR average age was 55.2 years (range: 19-68). Seven of eight cases met the Banff criteria for AMR. Personalized treatment regimens consisted of optimization of immunosuppression, intravenous pulse steroids, plasmapheresis, IVIG, rituximab, and bortezomib. Five patients experienced complete resolution of AMR, return of transaminases to baseline, and decreased DSA at long-term follow-up. One patient developed chronic AMR and two patients required re-transplantation. Follow-up after AMR diagnosis ranged from one to 11 years. Because AMR can present at any time, crossmatch, early biopsy, and routine monitoring of DSA levels should be implemented following transaminase elevation to recognize AMR. Furthermore, treatment should be immediately implemented to reverse AMR and prevent graft failure, chronic damage, re-transplantation, and possibly mortality.

Description, clinical impact and early outcome of S. maltophilia respiratory tract infections after lung transplantation, A retrospective observational study.

BACKGROUND AND RESEARCH QUESTION: S. maltophilia infections are associated with significant morbidity and mortality. Little is known regarding its presentation, management, and outcome in lung transplant recipients. STUDY DESIGN AND METHODS: This retrospective case control study reviewed S. maltophilia respiratory tract infection in lung transplant recipients (01/01/2011-31/01/2020) and described the clinical, microbiological and outcome characteristics matched with lung transplant recipients without respiratory tract infection. RESULTS AND INTERPRETATION: We identified 63 S. maltophilia infections in lung transplant recipients. Among them none were colonized before transplantation. Infections occurred a median of 177 (IQR: 45- 681) days post transplantation. Fifty-four (85.7 %) patients received trimethoprim-sulfamethoxazole (400/80 mg three times a week) to prevent Pneumocystis jirovecii pneumonia (PJP). S. maltophilia strains were susceptible to trimethoprim-sulfamethoxazole, levofloxacin, minocycline and ceftazidime in respectively 85.7 %, 82.5 %, 96.8 % and 34.9 % of cases. Median duration of treatment was 9 days (IQR 7-11.5). Clinical and microbiological recurrence were observed in respectively 25.3 % and 39.7 % of cases. Combination therapy was not associated with a decrease in the risk of recurrence and did not prevent the emergence of resistance. S. maltophilia respiratory tract infection was associated with a decline in FEV-1 at one year. CONCLUSION: S. maltophilia is an important cause of lower respiratory tract infection in lung transplant recipients. Trimethoprim-sulfamethoxazole use as prophylaxis for PJP doesn't prevent S. maltophilia infection among lung transplant recipients. Levofloxacin and trimethoprim-sulfamethoxazole appear to be the two molecules of choice for the treatment of these infections and new antibiotic strategies (cefiderocol, aztreonam/avibactam) are currently being evaluated for multi-resistant S. maltophilia infections.

A case controlled study of risk factors for metastatic squamous cell carcinoma in organ transplant recipients: single academic medical center.

Solid organ transplant recipients (SOTRs) are at high risk of cutaneous squamous cell carcinoma (cSCC) metastasis. Despite prior studies identifying risk factors, mortality remains high. Understanding additional risk factors may aid in reducing mortality in this population. This study aimed to investigate risk factors and predictive variables for metastatic cSCC in SOTRs. The primary goal was to accurately identify transplant patients at increased risk of metastatic cSCC. A retrospective case-control study in a single institution of 3576 cases of organ transplants were identified from January 1991 to July 2022. A cohort of metastatic cancer patients and two randomly generated age and organ matched control cohorts were identified. 16 SOTR patients developed metastatic cSCC. The majority were male, with high-risk tumor sites. Tumor depth varied and half exhibited perineural invasion. Cylex® (p = 0.05) and white blood cell counts (p = 0.04) were significantly lower in these patients compared to control. Lung transplants were at highest risk relative to other solid organ transplants. Voriconazole exposure was also associated with increased metastatic risk (p = 0.04). Small sample size at a single institution. Close monitoring of SOTR, especially those with lung transplants given their increased risk, reducing immunosuppression, and limiting exposure to voriconazole can improve outcomes in SOTRs with metastatic cSCC.

Cutaneous Squamous Cell Carcinoma in Patients with Solid-Organ-Transplant-Associated Immunosuppression.

The management of advanced cutaneous squamous cell carcinoma (CSCC) has been revolutionized by the introduction of immunotherapy. Yet, successful treatment with immunotherapy relies on an adequate antitumor immune response. Patients who are solid-organ transplant recipients (SOTRs) have a higher incidence of CSCC compared to the general population. This review discusses the current knowledge of epidemiology, pathophysiology, and management of patients with CSCC who are immunocompromised because of their chronic exposure to immunosuppressive medications to prevent allograft rejection. First, we discuss the prognostic impact of immunosuppression in patients with CSCC. Next, we review the risk of CSCC development in immunosuppressed patients due to SOT. In addition, we provide an overview of the biological immune disruption present in transplanted immunosuppressed CSCC patients. We discuss the available evidence on the use of immunotherapy and provide a framework for the management approach with SOTRs with CSCC. Finally, we discuss potential novel approaches that are being investigated for the management of immunosuppressed patients with CSCC.

Cutaneous squamous cell carcinoma in solid organ transplant recipients: Current therapeutic and screening strategies.

Solid organ transplant recipients (SOTRs) are particularly prone to developing malignancies, often manifesting multiple tumors and tumors with a heightened susceptibility to metastasis, resulting in much lower survival rates when compared to the general population. Among these, cutaneous squamous cell carcinoma (CSCC) respresent a major challenge in terms of morbidity and mortality following organ transplantation. The management of post-transplant CSCC requires expertise from various disciplines, including dermatology, maxillofacial surgery, transplant medicine, radiation oncology, and medical oncology. Furthermore, the unique behaviors and prevalence of tumors in SOTRs necessitate tailored pathways for screening and treatment, distinct from those designed for immunocompetent patients. Despite the proven efficacy of immune checkpoint inhibitors (ICIs) in several cancers, SOTRs have often been systematically excluded from clinical trials due to concerns about potential allograft rejection and loss. Consequently, most data on the safety and efficacy of ICIs in SOTRs are derived from case series and reports. Given the significant risks involved, alternative therapeutic options should be thoroughly discussed with patients before considering ICI therapy. This literature review aims to provide an overview of CSCC in SOTRs, with a specific emphasis on therapeutic and screening strategies, particularly highlighting immunotherapy.

Vaccinations in Paediatric Solid Organ Transplant Candidates and Recipients.

Solid organ transplant (SOT) candidates and recipients are a fragile population, in which the presence of a pre-transplant disease leading to organ insufficiency and the post-transplant immunosuppressive treatment expose them to an increased risk of infectious diseases. The best intervention to guarantee efficient prevention of infections, with optimal cost-benefit ratio, is represented by vaccination programs; however, the response to vaccines needs that the immune system maintains a good function. This is even more relevant at paediatric age, when specific immunological conditions make transplant candidates and recipients particularly vulnerable. Paediatric patients may be naïve to most infections and may have incomplete immunization status at the time of transplant listing due to their age. Moreover, the unaccomplished development of a mature immune system and the immunosuppressive regimen adopted after transplant might affect the efficacy of post-transplant vaccinations. Therefore, every effort should be made to obtain the widest vaccination coverage before the transplantation, whenever possible. This review reports the most relevant literature, providing information on the current approach to the vaccinations in paediatric SOT candidates and recipients.

Conferring alloantigen specificity to regulatory T cells: A comparative analysis of cell preparations undergoing clinical development in transplantation.

Conferring alloantigen-specificity to ex vivo expanded CD4+CD25+FOXP3+ regulatory T cells (Tregs) increases their capacity to counteract effector alloimmune responses following adoptive transfer into transplant recipients. Three strategies are currently undergoing clinical development, which involve the following: (1) expanding Tregs in the presence of donor B cells (donor alloantigen-reactive [DAR] Tregs); (2) culturing Tregs with donor cells in the presence of costimulation blockade (CSB-Tregs); and (3) transducing Tregs with an human leukocyte antigen A2-specific chimeric antigen receptor (CAR-Tregs). Our goal in this study was to assess the relative potency of each of these manufactured Treg products both in vitro and in vivo. When compared with polyclonal Tregs, all 3 manufacturing strategies increased the precursor frequency of alloreactive Tregs, and this was proportional to the overall in vitro immunosuppressive properties of the cell products. Accordingly, CAR-Tregs, which contained the highest frequency of donor-reactive Tregs, exhibited the strongest suppressive effects on a cell-per-cell basis. Similarly, in an in vivo mouse model of graft-vs-host disease, infusion of CAR-Tregs conferred a significantly longer recipient survival than any other Treg product. Our results highlighting the alloantigen-reactivity and associated immunosuppressive properties of different manufactured Treg products have implications for the mechanistic interpretation of currently ongoing clinical trials in transplantation.

Diagnosis and Prevention of Invasive Fungal Infections in the Immunocompromised Host.

TOPIC IMPORTANCE: The prevalence of invasive fungal infections (IFIs) has risen in the past 3 decades, attributed to advancements in immune-modulatory therapies used in transplantation, rheumatology, and oncology. REVIEW FINDINGS: Organisms that cause IFI evade the host's natural defenses or at opportunities of immunologic weakness. Infections occur from inhalation of potentially pathogenic organisms, translocation of commensal organisms, or reactivation of latent infection. Organisms that cause IFI in immunocompromised populations include Candida species, Cryptococcus species, environmental molds, and endemic fungi. Diagnosis of these infections is challenging due to slow organism growth and fastidious culture requirements. Moreover, fungal biomarkers tend to be nonspecific and can be negatively impacted by prophylactic antifungals. Antibody-based tests are not sensitive in immunocompromised hosts making antigen-based testing necessary. Risk reduction of IFI is guided by pathogen avoidance, removal or minimization of immune-suppressing factors, and pharmacologic prophylaxis in select hosts. SUMMARY: Understanding the complex interplay between the immune system and opportunistic fungal pathogens plays a key role in early diagnosis and prevention.

Pre-transplant Loco-Regional Therapy for Hepatocellular Carcinoma and Post-transplant Outcomes: A National Study.

The ultimate preferred treatment for hepatocellular carcinoma (HCC) complicated with cirrhosis and portal hypertension is an orthotopic liver transplant (OLT). Loco regional therapy (LRT) has emerged to prevent tumor growth and progression of disease beyond the Milan criteria to achieve transplant. There is a paucity of data regarding safety, posttransplant survival benefits, and tumor recurrence rate achieved by these LRT modalities. We aim to assess and compare the five-year survival rate and tumor recurrence rate with or without LRT in patients after OLT with diagnosed HCC utilizing the nation's largest dataset. This is a retrospective observational study approved by Saint Louis University institutional review board. We utilized the largest dataset from the years 2003-2013 where pertaining data were gathered from Organ Procurement Transplant Network (OPTN) standard analysis and research files (STAR) through novel linkages with Medicare bills. Descriptive and comparative statistics were performed. 2412 (51.6%) patients received any form of locoregional therapy (single or combination) out of 4669 total study sample size. The overall five-year survival in the study sample was 76.1%. There was statistically no significant improvement seen in five-year posttransplant survival in the group that received one mode of LRT (adjusted hazard ratio (aHR) 0.97, P<0.64) or a combination of LRT (aHR 0.94, P<0.58) in comparison to those that received none after adjusting donor and recipient clinical characteristics. However, five-year survival trended higher among those treated with combination therapy over those treated with single LRT or none. Overall HCC recurrence was 4.8%, while no significant difference was noted when comparing above-mentioned groups. Five-year posttransplant survival and HCC recurrence rate were also found to have no difference when compared between above-mentioned groups after adjusting explant pathology. This is the largest retrospective study comparing liver transplant patients with HCC who received LRT to none. Although it did not show any statistically significant benefit of single or combination of LRT on survival or tumor recurrence after liver transplant for HCC patients, the outcomes encourage the safe and feasible use of LRT as a bridging therapy. Our study also suggests an observed pattern of improved posttransplant survival and tumor recurrence rate with combination loco-regional therapy. Larger multicenter prospective studies will be required to achieve the effect size to determine the best therapies for maximizing patient survival cost-effectively.