Building a successful transplant research center: Blueprints and barriers.

A successful multidisciplinary research center depends on the quality of the science being conducted and the quality of the center's design, culture, infrastructure, and institutional support. In this perspective, we describe our experience building and maintaining a multidisciplinary transplant research center with a large focus on transplant infectious diseases. We identify principles that we believe contributed to our success including: taking inventory, defining culture, creating a multidisciplinary shared leadership model, establishing expertise in a multiple method approach, investing in operations and management, building and sharing resources, and securing institutional support.

Invasive Fungal Infections in Inpatient Solid Organ Transplant Recipients With COVID-19: A Multicenter Retrospective Cohort.

Background: The prevalence and outcomes of COVID-19-associated invasive fungal infections (CAIFIs) in solid organ transplant recipients (SOTRs) remain poorly understood.

Methods: A retrospective cohort study of SOTRs with COVID-19 admitted to 5 hospitals within Johns Hopkins Medicine was performed between March 2020 and March 2022. Cox regression multilevel mixed-effects ordinal logistic regression was used.

Progressive disseminated histoplasmosis: The experience in one non-endemic medical center.

Histoplasmosis, the most common endemic mycosis in North America, presents in a myriad of ways, spanning the spectrum from self-limiting pneumonia to progressive disseminated histoplasmosis (PDH). Toward better describing contemporary histoplasmosis syndromes, risks, and outcomes, this single-center retrospective cohort study was performed (2009-2019). The population who developed PDH was similar to that with other forms of histoplasmosis (OFH) except for higher rates of preexisting immunocompromising conditions (91.

HIV-Positive Liver Transplant Does not Alter the Latent Viral Reservoir in Recipients With Antiretroviral Therapy-Suppressed HIV.

The latent viral reservoir (LVR) remains a major barrier to HIV-1 curative strategies. It is unknown whether receiving a liver transplant from a donor with HIV might lead to an increase in the LVR because the liver is a large lymphoid organ. We found no differences in intact provirus, defective provirus, or the ratio of intact to defective provirus between recipients with ART-suppressed HIV who received a liver from a donor with (n = 19) or without HIV (n = 10).

Coronavirus Disease 2019-Associated Pulmonary Aspergillosis: A Noninvasive Screening Model for Additional Diagnostics.

Background: Coronavirus disease 2019 (COVID-19)-associated pulmonary aspergillosis (CAPA) is likely underdiagnosed, and current diagnostic tools are either invasive or insensitive.

Methods: A retrospective study of mechanically ventilated patients with COVID-19 admitted to 5 Johns Hopkins hospitals between March 2020 and June 2021 was performed. Multivariable logistic regression was used for the CAPA prediction model building.

Invasive fungal infections after respiratory viral infections in lung transplant recipients are associated with lung allograft failure and chronic lung allograft dysfunction within 1 year.

Background: Respiratory viral infections (RVI) are associated with chronic lung allograft dysfunction (CLAD) and mortality in lung transplant recipients (LTRs). However, the prevalence and impact of secondary invasive fungal infections (IFIs) post RVIs in LTRs have not been investigated.

Methods: We performed a single center retrospective study including LTRs diagnosed with 5 different respiratory viral pathogens between January 2010 to May 2021 and evaluated their clinical outcomes in 1 year.

The effect of induction immunosuppression for kidney transplant on the latent HIV reservoir.

The HIV latent viral reservoir (LVR) remains a major challenge in the effort to find a cure for HIV. There is interest in lymphocyte-depleting agents, used in solid organ and bone marrow transplantation to reduce the LVR. This study evaluated the LVR and T cell receptor repertoire in HIV-infected kidney transplant recipients using intact proviral DNA assay and T cell receptor sequencing in patients receiving lymphocyte-depleting or lymphocyte-nondepleting immunosuppression induction therapy.

HOPE in action: A prospective multicenter pilot study of liver transplantation from donors with HIV to recipients with HIV.

Liver transplantation (LT) from donors-with-HIV to recipients-with-HIV (HIV D+/R+) is permitted under the HOPE Act. There are only three international single-case reports of HIV D+/R+ LT, each with limited follow-up. We performed a prospective multicenter pilot study comparing HIV D+/R+ to donors-without-HIV to recipients-with-HIV (HIV D-/R+) LT.

Letermovir treatment of cytomegalovirus infection or disease in solid organ and hematopoietic cell transplant recipients.

Background: Few options are available for cytomegalovirus (CMV) treatment in transplant recipients resistant, refractory, or intolerant to approved agents. Letermovir (LET) is approved for prophylaxis in hematopoietic cell transplant (HCT) recipients, but little is known about efficacy in CMV infection. We conducted an observational study to determine the patterns of use and outcome of LET treatment of CMV infection in transplant recipients.

Coronavirus Disease 2019-Associated Pulmonary Aspergillosis in Mechanically Ventilated Patients.

Background: Coronavirus disease 2019 (COVID-19)-associated pulmonary aspergillosis (CAPA) occurs in critically ill patients with COVID-19. Risks and outcomes remain poorly understood.

Methods: A retrospective cohort study of mechanically ventilated adult patients with COVID-19 admitted to 5 Johns Hopkins hospitals was conducted between March and August 2020.

Utility of Serial Donor-derived Cell-free DNA Measurements for Detecting Allograft Rejection in a Kidney Transplant Recipient After PD-1 Checkpoint Inhibitor Administration.

Background: Donor-derived cell-free DNA (dd-cfDNA) is a useful biomarker of rejection that originates from allograft cells undergoing injury. Plasma levels <1% in kidney transplant recipients have a high negative predictive value for active allograft rejection. The utility of this biomarker in kidney transplant recipients receiving immune checkpoint inhibitor therapy is unknown.

Inpatient COVID-19 outcomes in solid organ transplant recipients compared to non-solid organ transplant patients: A retrospective cohort.

Immunosuppression and comorbidities might place solid organ transplant (SOT) recipients at higher risk from COVID-19, as suggested by recent case series. We compared 45 SOT vs. 2427 non-SOT patients who were admitted with COVID-19 to our health-care system (March 1, 2020 - August 21, 2020), evaluating hospital length-of-stay and inpatient mortality using competing-risks regression.

A prospective multicenter pilot study of HIV-positive deceased donor to HIV-positive recipient kidney transplantation: HOPE in action.

HIV-positive donor to HIV-positive recipient (HIV D+/R+) transplantation is permitted in the United States under the HIV Organ Policy Equity Act. To explore safety and the risk attributable to an HIV+ donor, we performed a prospective multicenter pilot study comparing HIV D+/R+ vs HIV-negative donor to HIV+ recipient (HIV D-/R+) kidney transplantation (KT). From 3/2016 to 7/2019 at 14 centers, there were 75 HIV+ KTs: 25 D+ and 50 D- (22 recipients from D- with false positive HIV tests).

A Multicenter, Longitudinal Cohort Study of Cryptococcosis in Human Immunodeficiency Virus-negative People in the United States.

Background: Cryptococcosis is increasingly recognized in people without human immunodeficiency virus (HIV).

Methods: A multicenter, prospective cohort study was performed in 25 US centers. Consenting patients were prospectively followed for ≤2 years.

Organs from deceased donors with false-positive HIV screening tests: An unexpected benefit of the HOPE act.

Organs from deceased donors with suspected false-positive HIV screening tests were generally discarded due to the chance that the test was truly positive. However, the HIV Organ Policy Equity (HOPE) Act now facilitates use of such organs for transplantation to HIV-infected (HIV+) individuals. In the HOPE in Action trial, donors without a known HIV infection who unexpectedly tested positive for anti-HIV antibody (Ab) or HIV nucleic acid test (NAT) were classified as suspected false-positive donors.

Urine Antigen Detection as an Aid to Diagnose Invasive Aspergillosis.

Background: Establishing rapid diagnoses of invasive aspergillosis (IA) is a priority tests that detect galactomannan and β-d-glucan are available, but are technically cumbersome and rely on invasive sampling (blood or bronchoalveolar lavage).

Methods: We optimized a lateral flow dipstick assay using the galactofuranose-specific monoclonal antibody (mAb476), which recognizes urine antigens after Aspergillus fumigatus pulmonary infection in animals. Urine samples were obtained from a cohort of 78 subjects undergoing evaluation for suspected invasive fungal infections, and stored frozen until testing.

Direct-Acting Antiviral Prophylaxis in Kidney Transplantation From Hepatitis C Virus-Infected Donors to Noninfected Recipients: An Open-Label Nonrandomized Trial.

Background: Given the high mortality rate for patients with end-stage kidney disease receiving dialysis and the efficacy and safety of hepatitis C virus (HCV) treatments, discarded kidneys from HCV-infected donors may be a neglected public health resource.

Objective: To determine the tolerability and feasibility of using direct-acting antivirals (DAAs) as prophylaxis before and after kidney transplantation from HCV-infected donors to non-HCV-infected recipients (that is, HCV D+/R- transplantation).

Design: Open-label nonrandomized trial.

Unique characteristics of cryptococcosis identified after death in patients with liver cirrhosis: comparison with concurrent cohort diagnosed antemortem.

Characteristics of cirrhosis-associated cryptococcosis first diagnosed after death are not fully known. In a multicenter study, data generated as standard of care was systematically collected in 113 consecutive patients with cirrhosis and cryptococcosis followed for 80 patient-years. The diagnosis of cryptococcosis was first established after death in 15.

Outcomes in Transplant Recipients Treated With Foscarnet for Ganciclovir-Resistant or Refractory Cytomegalovirus Infection.

Background: Antiviral-resistant or refractory cytomegalovirus (CMV) infection is challenging, and salvage therapies, foscarnet, and cidofovir, have significant toxicities. Several investigational anti-CMV agents are under development, but more information is needed on outcomes of current treatments to facilitate clinical trial design for new drugs.

Methods: Records of solid organ transplant (SOT) and hematopoietic cell transplant (HCT) recipients at a single center over a 10-year period were reviewed retrospectively to characterize those who had received foscarnet treatment for ganciclovir-resistant or refractory CMV infection.