Cohort Of Solid Organ Transplant Recipients Research Articles

The performance of bronchoalveolar lavage Aspergillus PCR testing in solid organ transplant recipients with invasive pulmonary aspergillosis.

Invasive aspergillosis affects solid organ transplant (SOT) recipients, carrying a high risk of mortality and morbidity in this population. Rapid and accurate diagnosis is essential to ensure the initiation of correct antifungal therapy. We aimed to evaluate the performance of the bronchoalveolar lavage (BAL) Eurofins Viracor Aspergillus PCR (AspPCR) in diagnosing invasive pulmonary aspergillosis (IPA) in SOT recipients. We conducted a multicenter retrospective study of SOT recipients in Arizona from February 2019 to December 2022 who had AspPCR done at the time of the clinical encounter. Probable IPA was defined as a positive BAL culture with Aspergillus spp. with clinical and imaging findings of IPA per EORTC/MSGERC criteria. Ninety-nine SOT recipients with 131 encounters with BAL AspPCR testing were included. The median age was 66, the majority were White, non-Hispanics (60%), and males (66%). Among the participants, 93 lung transplant recipients with 87 of the encounters received antifungal prophylaxis active against Aspergillus spp. Sixty-four encounters had BAL galactomannan (GM), all of which had BAL GM <1 OD, and one case had a serum GM of 10 OD. Nine cases met the definition of IPA. The sensitivity of the BAL AspPCR was 67% (95% CI 30%-93%), and the specificity was 98% (95% CI 93%-99%). BAL AspPCR had moderate sensitivity and high specificity in identifying IPA in our cohort of SOT recipients. Further studies in populations with a higher prevalence of IPA are needed to evaluate the performance of this test.

Assessing the quality of antimicrobial prescribing in solid organ transplant recipients: a new frontier in antimicrobial stewardship.

Post-transplant infections remain a leading cause of morbidity and mortality in solid organ transplant recipients (SOTRs) and local standardized antimicrobial treatment guidelines may contribute to improved clinical outcomes. Our study assessed the rate of therapeutic compliance with local standard guidelines in the treatment of common infections in SOTR, and their associated outcomes. Consecutive adult SOTRs admitted to the transplant floor from January-September 2020 and were treated for an infectious syndrome were followed until discharge or for 30 days following the date of diagnosis, whichever was shorter. Data was extracted from electronic medical records. Guideline compliance was characterized as either appropriate, effective but unnecessary, undertreatment, or inappropriate. Nine hundred and thirty-six SOTR were admitted to the transplant ward, of which 328 patients (35%) received treatment for infectious syndromes. Guidelines were applicable to 252 patients, constituting 275 syndromes: 86 pneumonias; 82 urinary tract infections; 40 intra-abdominal infections; 38 bloodstream infections; and 29 C. difficile infections. 200/246 (81%) of infectious syndromes received appropriate or effective but unnecessary empiric treatment. In addition, appropriate tailoring of antimicrobials resulted in a significant difference in 30-day all-cause mortality (adjusted OR of 0.07, 95% CI 0.01-0.38; P = .002). Lastly, we found that guideline-compliant empiric therapy was found to prevent the development of multi-drug resistance in a time-dependent analysis (adjusted HR of 0.21, 95% CI 0.08-0.52; P = .001). Our data show that adherence to locally developed guidelines was associated with reduced mortality and resistant-organism development in our cohort of SOTR.

Short-course early outpatient remdesivir prevents severe disease due to COVID-19 in organ transplant recipients during the omicron BA.2 wave

Solid organ transplant recipients (SOTr) remain at risk of severe COVID‐19. Several previous early therapies are no longer effective against new circulating variants. We performed a prospective cohort study in outpatient adult SOTr during the Omicron BA.2 wave (April‐May 2022), to determine the effectiveness of 3 doses of remdesivir given within 7 days of symptoms onset. Patients were followed for at least 30 days. The primary outcome was hospitalization. Of 210 SOTr that had COVID‐19, we included 192. The median age was 54.5 years and 61.5% were men. The most common transplants were kidney (41.7%), lung (19.3%), liver (18.8%), and heart (6.3%). Most patients (90.1%) had previously received ≥3 COVID‐19 vaccine doses. Fifteen(7.8%) were hospitalized, 5(2.6%) required supplemental oxygen, 3(1.6%) ICU admission, and 2(1%) mechanical ventilation with 2(1%) deaths. Age and multiple comorbidities were risk factors for hospitalization. Early remdesivir significantly decreased the hospitalization rate: adjusted hazard ratio 0.12 (95%CI: 0.03 to 0.057). The adjusted number needed to treat to prevent one hospitalization was 15.2 (95%CI: 13.6 to 31.4). No patient that received early remdesivir needed ICU admission or died. In a cohort of SOTr with COVID‐19 infection, administration of 3‐dose early remdesivir independently reduced the disease severity.

COVID-19 in Immunocompromised Children and Adolescents.

COVID-19 in Immunocompromised Children and Adolescents.

Breakthrough COVID-19 after SARS-CoV-2 vaccination in solid organ transplant recipients: An analysis of symptomatic cases and monoclonal antibody therapy.

Solid organ transplant (SOT) recipients are at increased risk for complications from SARS-CoV-2 infection. Little is known regarding clinical course and outcomes of breakthrough COVID-19 in the fully vaccinated SOT population. We sought to describe our cohort of SOT recipients who developed symptomatic breakthrough COVID-19 after full vaccination. We conducted a retrospective review of SOT recipients diagnosed with COVID-19 at least 14 days after completing SARS-CoV-2 vaccination. Patients were analyzed according to those presenting with mild-to-moderate and severe COVID-19, respectively. We described presenting characteristics, COVID-19 therapy, and analyzed outcomes including emergency department (ED) visits, hospitalization, and intensive care unit (ICU) admission. Thirty-five patients met inclusion criteria. These had a mean age of 60.8 years and kidney transplant was the most common SOT type. Five patients presented with severe COVID-19 at diagnosis, all requiring hospitalization without ICU admission. From the 30 patients who presented with mild-to-moderate infection, 28 received casirivimab-imdevimab. Four of these 28 (14.3%) had an ED visit, with one requiring hospital admission (3.4%). No patients required ICU admission. Breakthrough COVID-19 may occur in SOT recipients after full vaccination, though they appear to have acceptable outcomes. Anti-spike monoclonal antibody therapy for eligible SOT patients may have mitigated clinical progression and improved the outcomes. Further study with large cohorts is warranted.

COVID-19 in Solid Organ Transplant Recipient: Exploring Cumulative Incidence, Seroprevalence and Risk Factors for Disease Severity.

Simple SummaryIt is still uncertain whether recipients of solid organ transplant (SOT) are at increased risk of SARS-CoV-2 infection and/or poor outcomes due to COVID-19 in comparison to the general population. In this study, we report the cumulative incidence and outcomes of SARS-CoV-2 infection in a cohort of 291 SOT recipients. The COVID-19 cumulative incidence in SOT recipients resulted slightly higher compared to that of age-matched population during the study period. Moreover, the SARS-CoV-2 antibody frequency was around 2.6-fold higher than the incidence of cases who tested positive for SARS-CoV-2 RT-PCR, suggesting that the number of SOT recipients infected with SARS-CoV-2 is likely higher than described. In symptomatic recipients, kidney transplant was associated with a higher risk of developing moderate/critical disease, while common risk factors, including age and comorbidities, resulted less relevant for COVID-19 severity. Due to the high estimated crude mortality, symptomatic SOT recipients should be considered at high risk in case of SARS-CoV-2 infection.Background: Solid organ transplant (SOT) recipients may be at increased risk for severe disease and mortality from COVID-19 because of immunosuppression and prolonged end-stage organ disease. As a transplant center serving a diverse patient population, we report the cumulative incidence and outcomes of SARS-CoV-2 infection in our cohort of SOT recipients. Methods: We prospectively included in this observational study SOT recipients with a functioning kidney (n = 201), pancreas ± kidney (n = 66) or islet transplant (n = 24), attending outpatient regular follow-up at the San Raffaele Hospital from February 2020 to April 2021. Antibodies to SARS-CoV-2 were tested in all patients by a luciferase immunoprecipitation system assay. Results: Of the 291 SOT recipients, 30 (10.3%) tested positive for SARS-CoV-2 during the study period and prevalence was not different among different transplants. The SARS-CoV-2 antibody frequency was around 2.6-fold higher than the incidence of cases who tested positive for SARS-CoV-2 RT-PCR. As for the WHO COVID-19 severity classification, 19 (63.3%) SOT recipients were mild, nine (30%) were moderate, and two were critical and died yielding a crude mortality rate in our patient population of 6.7%. Kidney transplant (OR 12.9 (1.1–150) p = 0.041) was associated with an increased risk for moderate/critical disease, while statin therapy (OR 0.116 (0.015–0.926) p = 0.042) and pancreas/islet transplant (OR 0.077 (0.007–0.906) p = 0.041) were protective. Conclusions: The incidence of SARS-CoV-2 infection in SOT recipients may be higher than previously described. Due to the relative high crude mortality, symptomatic SOT recipients must be considered at high risk in case of SARS-CoV-2 infection.

PD45-04 OUTCOMES OF GENITOURINARY MALIGNANCY IN SOLID ORGAN TRANSPLANT RECIPIENTS

You have accessJournal of UrologyRenal Transplantation & Vascular Surgery II (PD45)1 Sep 2021PD45-04 OUTCOMES OF GENITOURINARY MALIGNANCY IN SOLID ORGAN TRANSPLANT RECIPIENTS Song Jiang, Brent Cleveland, and Christopher Warlick Song JiangSong Jiang More articles by this author , Brent ClevelandBrent Cleveland More articles by this author , and Christopher WarlickChristopher Warlick More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000002059.04AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: The management of genitourinary (GU) malignancy in transplant recipients is challenging and remains controversial, often based on historical practices that fail to take into account recent progress in both genitourinary cancer diagnosis and management, as well as immunosuppression protocols used by modern transplant teams. Data regarding rates and outcomes of GU malignancy in the solid organ transplant (SOT) population is lacking, and studies that exist have small numbers of patients. The purpose of this study is to examine the incidence, disease characteristics, and clinical course of bladder and kidney cancer diagnosed in a large solid organ transplant cohort. METHODS: The University of Minnesota SOT database, curated based on UNOS data collected from 1984–2019, was queried for SOT recipients who subsequently developed bladder cancer and renal neoplasm. A retrospective chart review of available electronic medical records was performed based on the results of this query to obtain patient characteristics, pathology, treatment, and outcomes. RESULTS: In our cohort of SOT recipients, 42 patients were subsequently diagnosed with bladder cancer. High grade and advanced disease (T2 or greater) were present in 27 (64.3%) and 16 (38.1%) of patients, respectively. Recurrences occurred in 17 patients with 6 (35%) of these being progression in disease. Bladder cancer-related deaths occurred in 8 patients (19.1%). The mean overall survival after initial diagnosis was 2.8 (±3.3) years. 111 SOT patients developed a renal neoplasm in the native kidney, whereas 33 developed a neoplasm in a graft kidney. The large majority of renal masses were localized and treated with radical nephrectomy. 2 patients developed progression of disease after radical surgery with evidence of metastasis, while 3 patients had evidence of metastasis on presentation. CONCLUSIONS: Previously, we have described cumulative incidence of genitourinary malignancy in a large cohort of renal transplant recipients at the University of Minnesota. Herein, we present a study of the broader solid organ transplant population and present disease characteristics and outcomes of bladder and kidney cancer patients, which revealed that those diagnosed with de novo bladder malignancy after their transplant had increased rates of high grade and advanced disease (T2 or greater) at initial diagnosis compared to commonly cited rates for the general population, whereas in the case of renal cell cancer we noted an increased rate of diagnosis, but rates of disease progression and metastasis largely in line with the general population. Source of Funding: None © 2021 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 206Issue Supplement 3September 2021Page: e743-e743 Advertisement Copyright & Permissions© 2021 by American Urological Association Education and Research, Inc.MetricsAuthor Information Song Jiang More articles by this author Brent Cleveland More articles by this author Christopher Warlick More articles by this author Expand All Advertisement Loading ...

A propensity score-matched analysis of mortality in solid organ transplant patients with COVID-19 compared to non-solid organ transplant patients.

In the context of COVID-19 pandemic, we aimed to analyze the epidemiology, clinical characteristics, risk factors for mortality and impact of COVID-19 on outcomes of solid organ transplant (SOT) recipients compared to a cohort of non transplant patients, evaluating if transplantation could be considered a risk factor for mortality. From March to May 2020, 261 hospitalized patients with COVID-19 pneumonia were evaluated, including 41 SOT recipients. Of these, thirty-two were kidney recipients, 4 liver, 3 heart and 2 combined kidney-liver transplants. Median time from transplantation to COVID-19 diagnosis was 6 years. Thirteen SOT recipients (32%) required Intensive Care Unit (ICU) admission and 5 patients died (12%). Using a propensity score match analysis, we found no significant differences between SOT recipients and non-transplant patients. Older age (OR 1.142; 95% [CI 1.08-1.197]) higher levels of C-reactive protein (OR 3.068; 95% [CI 1.22-7.71]) and levels of serum creatinine on admission (OR 3.048 95% [CI 1.22-7.57]) were associated with higher mortality. The clinical outcomes of SARS-CoV-2 infection in our cohort of SOT recipients appear to be similar to that observed in the non-transplant population. Older age, higher levels of C-reactive protein and serum creatinine were associated with higher mortality, whereas SOT was not associated with worse outcomes.

Burden, epidemiology, and outcomes of microbiologically confirmed respiratory viral infections in solid organ transplant recipients: a nationwide, multi-season prospective cohort study.

Solid organ transplant (SOT) recipients are exposed to respiratory viral infection (RVI) during seasonal epidemics; however, the associated burden of disease has not been fully characterized. We describe the epidemiology and outcomes of RVI in a cohort enrolling 3294 consecutive patients undergoing SOT from May 2008 to December 2015 in Switzerland. Patient and allograft outcomes, and RVI diagnosed during routine clinical practice were prospectively collected. Median follow-up was 3.4years (interquartile range 1.61-5.56). Six hundred ninety-six RVIs were diagnosed in 151/334 (45%) lung and 265/2960 (9%) non-lung transplant recipients. Cumulative incidence was 60% (95% confidence interval [CI] 53%-69%) in lung and 12% (95% CI 11%-14%) in non-lung transplant recipients. RVI led to 17.9 (95% CI 15.7-20.5) hospital admissions per 1000 patient-years. Intensive care unit admission was required in 4% (27/691) of cases. Thirty-day all-cause case fatality rate was 0.9% (6/696). Using proportional hazard models we found that RVI (adjusted hazard ratio [aHR] 2.45; 95% CI 1.62-3.73), lower respiratory tract RVI (aHR 3.45; 95% CI 2.15-5.52), and influenza (aHR 3.57; 95% CI 1.75-7.26) were associated with graft failure or death. In this cohort of SOT recipients, RVI caused important morbidity and may affect long-term outcomes, underlying the need for improved preventive strategies.

Association of Sirolimus Use With Risk for Skin Cancer in a Mixed-Organ Cohort of Solid-Organ Transplant Recipients With a History of Cancer.

Solid-organ transplant recipients (OTRs) are at an increased risk for skin cancer. Prior studies have demonstrated a reduced incidence of skin cancer in renal OTRs treated with sirolimus. However, little information exists on the use of sirolimus for the prevention of skin cancer in nonrenal OTRs or those already diagnosed as having a posttransplant cancer. To compare subsequent skin cancer formation in a mixed-organ cohort of OTRs who were or were not treated with sirolimus after developing a posttransplant index cancer of any type. A 9-year retrospective cohort study at 2 academic tertiary care centers. Electronic medical records were reviewed for OTRs diagnosed as having a posttransplant cancer of any type to determine the type of organ transplanted, pretransplant and posttransplant cancer, and immunosuppressive medications. Patients underwent transplant from January 1, 2000, to December 31, 2008. Data were collected from July 30, 2011, to December 31, 2012, when follow-up was completed, and analyzed from April 28, 2013, to October 4, 2014. Factors associated with subsequent skin cancer development were evaluated via multivariate Cox regression analysis. Of 329 OTRs with an index posttransplant cancer (100 women and 229 men; mean [SD] age, 56 [19] years), 177 (53.8%) underwent renal transplant; 58 (17.6%), heart transplant; 54 (16.4%), lung transplant; 34 (10.3%), liver transplant; and 6 (1.8%), mixed-organ transplant. Ninety-seven OTRs (29.5%) underwent conversion to sirolimus therapy after diagnosis. One hundred thirty OTRs (39.5%) developed second posttransplant cancers, of which 115 cases (88.5%) were skin cancers. An 11.6% reduction in skin cancer risk was observed in the sirolimus-treated vs non-sirolimus-treated groups overall (26 of 97 [26.8%] vs 89 of 232 [38.4%]; P = .045) and among nonrenal OTRs only (8 of 34 [23.5%] vs 44 of 112 [39.3%], respectively), although the latter difference was not significant (P = .09). Independent predictors of skin cancer formation after the index posttransplant cancer were history of pretransplant skin cancer (subhazard ratio, 2.1; 95% CI, 1.2-3.7), skin cancer as the index posttransplant cancer (subhazard ratio, 5.5; 95% CI, 2.5-6.4), and sirolimus treatment (subhazard ratio, 0.6; 95% CI, 0.4-0.9). These same risk factors were associated with skin cancer formation when the analysis was limited to nonrenal OTRs. No difference was found in allograft rejection or death between sirolimus-treated and non-sirolimus-treated groups. In this mixed-organ cohort of OTRs, patients taking sirolimus after developing posttransplant cancer had a lower risk of developing subsequent skin cancer, with no increased risk for overall mortality. Thus, conversion to sirolimus therapy may be considered in OTRs who develop cancer if the risk for skin cancer is of concern. Larger studies are needed to quantify sirolimus-associated risk reduction for other cancer types.

Influenza vaccination and humoral alloimmunity in solid organ transplant recipients

Annual influenza vaccination is recommended in solid organ transplant (SOT) recipients. However, concerns have been raised about the impact of vaccination on antigraft alloimmunity. We evaluated the humoral alloimmune responses to influenza vaccination in a cohort of SOT recipients between October 2008 and December 2011. Anti-HLA antibodies were measured before and 4-8weeks after influenza vaccination using a solid-phase assay. Overall, 169 SOT recipients were included (kidney=136, lung=26, liver=3, and combined=4). Five (2.9%) of 169 patients developed de novo anti-HLA antibodies after vaccination, including one patient who developed donor-specific antibodies (DSA) 8months after vaccination. In patients with pre-existing anti-HLA antibodies, median MFI was not significantly different before and after vaccination (P=0.73 for class I and P=0.20 for class II anti-HLA antibodies) and no development of de novo DSA was observed. Five episodes of rejection (2.9%) were observed within 12months after vaccination, and only one patient had de novo anti-HLA antibodies. The incidence of development of anti-HLA antibodies after influenza vaccination in our cohort of SOT recipients was very low. Our findings indicate that influenza vaccination is safe and does not trigger humoral alloimmune responses in SOT recipients.

P633 Whole blood real-time PCR for cytomegalovirus DNA quantification: analysis of PCR data and pp65 antigen test in a cohort of solid-organ transplant recipients

P633 Whole blood real-time PCR for cytomegalovirus DNA quantification: analysis of PCR data and pp65 antigen test in a cohort of solid-organ transplant recipients

Quantitative pp65 antigenemia in the diagnosis of cytomegalovirus disease: prospective assessment in a cohort of solid organ transplant recipients

Objectives To assess the accuracy of quantitative pp65 antigenemia (pp65Ag) in the diagnosis of CMV disease, in a cohort of solid-organ transplant recipients. Methods Prospective observational study during the first 6 months following transplantation, with determination of pp65Ag at weeks 2, 4, 6, 8, 10, 11, 12, 14 and 16. Sensitivity ( S), specificity ( E), positive and negative predictive values (PPV, NPV), and the optimal cut-off point for diagnosing CMV disease, were determined. Results The cohort consisted of 35 liver, 26 renal and 12 heart graft recipients. Thirteen (17.2%) were seronegative and received a seropositive graft. Of 583 blood samples, pp65Ag was positive in 109 (18.7%) from 37 patients (51%). Twenty-two patients developed CMV disease (0.3 episodes/patient); gastrointestinal disease was the most frequent (15 episodes), followed by viral syndrome (3 episodes). Patients with positive pp65Ag had a relative risk for CMV disease of 6.19 [IC95%=1.99–19.04], ( P=.0001). Diagnostic values of pp65Ag were: S=86%, E=65%, PPV=51%, NPV=92%. The cut-off of ≥10 infected cells/10 5, at weeks 2, 4, 6 and 8 obtained the best PPV (0, 67, 91 and 54%), and NPV (47, 52, 67 and 50%). Conclusions In the studied population, the presence of positive pp65Ag was associated with a high risk of developing CMV disease, and the most useful cut-off point for the diagnosis was ≥10 infected cells/10 5.