Recipient donor sex combinations in solid organ transplantation and impact on clinical outcome: A scoping review.

INTRODUCTION: Solid organ transplantation (SOT) is a lifesaving treatment for end-stage organ failure. Although many factors affect the success of organ transplantation, recipient and donor sex are important biological factors influencing transplant outcome. However, the impact of the four possible recipient and donor sex combinations (RDSC) on transplant outcome remains largely unclear. METHODS: A scoping review was carried out focusing on studies examining the association between RDSC and outcomes (mortality, graft rejection, and infection) after heart, lung, liver, and kidney transplantation. All studies up to February 2023 were included. RESULTS: Multiple studies published between 1998 and 2022 show that RDSC is an important factor affecting the outcome after organ transplantation. Male recipients of SOT have a higher risk of mortality and graft failure than female recipients. Differences regarding the causes of death are observed. Female recipients on the other hand are more susceptible to infections after SOT. CONCLUSION: Differences in underlying illnesses as well as age, immunosuppressive therapy and underlying biological mechanisms among male and female SOT recipients affect the post-transplant outcome. However, the precise mechanisms influencing the interaction between RDSC and post-transplant outcome remain largely unclear. A better understanding of how to identify and modulate these factors may improve outcome, which is particularly important in light of the worldwide organ shortage. An analysis for differences of etiology and causes of graft loss or mortality, respectively, is warranted across the RDSC groups. PRACTITIONER POINTS: Recipient and donor sex combinations affect outcome after solid organ transplantation. While female recipients are more susceptible to infections after solid organ transplantation, they have higher overall survival following SOT, with causes of death differing from male recipients. Sex-differences should be taken into account in the post-transplant management.

Clinically latent and autopsy-verified inflammatory disorders and malignant tumours in transplant patients.

AIMS: The number of clinical autopsies decreases while the rate of missed relevant diagnoses is known to be 2%-20%. In this study, we focused on postmortem examinations of patients after transplantation of solid organs. METHODS: A total of 122 cases were assessed for this study. Transplant organs included liver (LiTx; n=42/122, 34%), heart (n=8/122, 7%), lungs (n=32/122, 26%), kidney (KTx; n=38/122, 31%) and KTx+LiTx (n=2/122, 2%). RESULTS: The most frequent autopsy-verified causes of death were cardiac or respiratory failure (together n=85/122, 70%). The frequency of malignant tumours that were identified at autopsy was 5% (n=6/122). In 3% (n=4/122) of cases, Goldman class I discrepancies between clinical diagnosis and autopsy findings were identified. CONCLUSIONS: The rate of missed relevant diagnoses might be relatively low, but these cases nevertheless refute the contention that modern diagnostic techniques negate the need for autopsies in patients who died after transplantation.

Predicted Cure and Survival Among Transplant Recipients With a Previous Cancer Diagnosis.

PURPOSE: A previous cancer diagnosis is a negative consideration in evaluating patients for possible solid organ transplantation. Statistical models may improve selection of patients with cancer evaluated for transplantation. METHODS: We fitted statistical cure models for patients with cancer in the US general population using data from 13 cancer registries. Patients subsequently undergoing solid organ transplantation were identified through the Scientific Registry of Transplant Recipients. We estimated cure probabilities at diagnosis (for all patients with cancer) and transplantation (transplanted patients). We used Cox regression to assess associations of cure probability at transplantation with subsequent cancer-specific mortality. RESULTS: Among 10,524,326 patients with 17 cancer types in the general population, the median cure probability at diagnosis was 62%. Of these patients, 5,425 (0.05%) subsequently underwent solid organ transplantation and their median cure probability at transplantation was 94% (interquartile range, 86%-98%). Compared with the tertile of transplanted patients with highest cure probability, those in the lowest tertile more frequently had lung or breast cancers and less frequently colorectal, testicular, or thyroid cancers; more frequently had advanced-stage cancer; were older (median 57 v 51 years); and were transplanted sooner after cancer diagnosis (median 3.6 v 8.6 years). Patients in the low-cure probability tertile had increased cancer-specific mortality after transplantation (adjusted hazard ratio, 2.08; 95% CI, 1.48 to 2.93; v the high tertile), whereas those in the middle tertile did not differ. CONCLUSION: Patients with cancer who underwent solid organ transplantation exhibited high cure probabilities, reflecting selection on the basis of existing guidelines and clinical judgment. Nonetheless, there was a range of cure probabilities among transplanted patients and low probability predicted increased cancer-specific mortality after transplantation. Cure probabilities may facilitate guideline development and evaluating individual patients for transplantation.

Utilization of the Boston Children's Hospital SRTR Cohort Visualization Tool to increase team understanding of reporting cohorts.

BACKGROUND: While reviewing outcomes metrics and data from the SRTR, it became apparent that prospective assessment of the SRTR reporting cohorts would be an important proactive strategy for internal quality control. It was particularly important to identify the number of patient deaths and graft failures within 1 year of transplant that would result in being flagged by the UNOS and the MPSC. METHODS: A simple Microsoft Excel line graph was created to visually display retrospective, current, and future SRTR cohorts. Data provided by the SRTR CUSUM (https://securesrtr.transplant.hrsa.gov/srtr-reports/cusum-charts/) Reports and the SRTR 1 Year Expected Survival Excel Worksheet (https://securesrtr.transplant.hrsa.gov/srtr-reports/current-release/) were leveraged to identify whether programs were in jeopardy of being flagged by UNOS/MPSC for outcomes. RESULTS & CONCLUSIONS: The creation of this visual tool has greatly improved team understanding of SRTR report cohorts, as well as the risk of being flagged by regulatory agencies, for adverse outcomes.

Infective endocarditis and solid organ transplantation: Only worse outcomes during initial transplantation hospitalization.

BACKGROUND: The epidemiology, and outcome of infective endocarditis (IE) among solid organ transplant (SOT) recipients is unknown. METHODS: We used data from the 2013-2018 Nationwide Readmissions Database (NRD). IE- and SOT-associated hospitalizations were identified using diagnosis and procedure codes. Outcomes included inpatient mortality, length of stay, and inpatient costs. Adjusted analyses were performed using weighted regression models. RESULTS: A total of 99,052 IE-associated hospitalizations, corresponding to a weighted national estimate of 193,164, were included for analysis. Of these, 794 (weighted n = 1,574) were associated with transplant history (SOT-IE). Mortality was not significantly different between SOT-IE and non-SOT-IE (17.2% vs. 15.8%, adjusted relative risk [aRR]: 0.86, 95% confidence interval [CI] [0.71, 1.03]), and fewer SOT-IE patients underwent valve repair or replacement than non-SOT-IE (12.5% vs. 16.2%, aRR 0.82, 95% CI [0.71, 0.95]). We then compared outcomes of patients diagnosed with IE during their index transplant hospitalization (index-SOT-IE) to patients without IE during their transplant hospitalization (index-SOT). Index-SOT-IE occurred most frequently among heart transplant recipients (45.1%), and was associated with greater mortality (27.1% vs. 2.3%, aRR 6.07, 95% CI [3.32, 11.11]). CONCLUSION: Dual diagnosis of SOT and IE was associated with worse outcomes among SOT recipients during index hospitalization, but not overall among patients with IE.

The association between severe or death COVID-19 and solid organ transplantation: A systematic review and meta-analysis.

BACKGROUND: The effect of solid organ transplantation (SOT) on the severity and mortality of coronavirus disease 2019 (COVID-19) remained controversial. There is still no consensus on whether solid organ transplantation (SOT) recipients with COVID-19 are at greater risk of developing severe or fatal COVID-19. Therefore, we conducted a systematic review and meta-analysis to investigate the association between SOT, severe COVID-19 illness, and mortality. METHODS: A systemically comprehensive search in Pubmed, Embase, the Cochrane Library, Web of Science, and China National Knowledge Infrastructure was performed for relevant studies and articles. Consequently, we pooled the odds ratio (OR) from individual studies and performed heterogeneity, quality assessment and subgroup/sensitivity analysis. RESULTS: A total number of 15 articles with 265,839 participants were included in this study. Among the total number of participants, 1485 were SOT recipients. The meta-analysis results showed that transplant patients with COVID-19 were remarkably associated with a higher risk of intensive care unit admission than non-transplant patients (OR = 1.57, 95%CI: 1.07 to 2.31, P = 0.02). On the other hand, there were no statistically significant differences between SOT recipients and non-SOT recipients in mechanical ventilation need (OR = 1.55, 95%CI: 0.98 to 2.44, P = 0.06). In addition, we found that SOT recipients with COVID-19 had 1.40-fold increased odds of mortality than non-SOT recipients (OR = 1.40, 95%CI: 1.10 to 1.79, P = 0.007). Moreover, pooled analysis of adjusted results revealed that SOT recipients had a greater risk of mortality compared with non-SOT patients (HR = 1.54, 95%CI: 1.03 to 2.32, P = 0.037). LIMITATIONS: The main limitations in our study are attributed to the relatively small sample size, short follow-up period, and the fact that most of the studies included were retrospective in design. CONCLUSIONS: The results of this study indicate that SOT recipients with COVID-19 had a more significant risk of COVID-19 severity and mortality than the general population.

Evidence of Epstein-Barr virus heterogeneous gene expression in adult lung transplant recipients with posttransplant lymphoproliferative disorder.

Epstein-Barr virus (EBV)-driven posttransplant lymphoproliferative disorder (PTLD) is a serious complication following lung transplant. The extent to which the presence of EBV in PTLD tissue is associated with survival is uncertain. Moreover, whether the heterogeneity in expression of EBV latency programs is related to the timing of PTLD onset remains unexplored. We retrospectively performed a comprehensive histological evaluation of EBV markers at the tissue level in 34 adult lung transplant recipients with early- and late-onset PTLD. Early-onset PTLD, occurring within the first 12 months posttransplant, had higher odds to express EBV markers. The presence of EBV in PTLD was not associated with a difference in survival relative to EBV-negative tumors. However, we found evidence of heterogeneous expression of EBV latency programs, including type III, IIb, IIa, and 0/I. Our study suggests that the heterogeneous expression of EBV latency programs may represent a mechanism for immune evasion in patients with PLTD after lung transplants. The recognition of multiple EBV latency programs can be used in personalized medicine in patients who are nonresponsive to traditional types of chemotherapy and can be potentially evaluated in other types of solid organ transplants.

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.

Short-Term Graft Failure of Organs Procured from Drug-Related Deaths Compared with Other Causes of Death.

BACKGROUND: A gap exists between the number of patients on the national organ transplant waiting list and the number of transplants performed. Victims of drug and overdose-related death are increasingly utilized as organ donors. We sought to evaluate the suitability of organs from drug and overdose-related death for organ transplantation. This study compares the proportion of short-term allograft failure of organs procured from patients with drug-related deaths with those without drug-related deaths. METHODS: Organ donations after drug-related deaths (DDD) were compared with organ donations from non-drug-related donations after brain deaths (DBD) and donations after circulatory deaths (DCD) utilizing the Gift of Hope Organ & Tissue Donor Network for a total of 15 months. RESULTS: Eighty-one donors were identified from each of the DDD, DBD, and DCD groups with 264, 234, and 181 organs transplanted, respectively. The proportions of short-term graft failures were 1.15% in the DDD group compared with 2.14% in the DBD group (p = NS) and 5.52% in the DCD group (p = 0.01). The US Public Health Service increased-risk features for transmission of infectious diseases were present in 70.3% of the DDD cases. Donors from the DDD group were younger on average than those in other groups (33 to 42 years). CONCLUSIONS: The proportion of graft failures in the drug-related deaths (DDD) group was equal to or less than those from other causes of death on short-term follow-up. Drug-related death does not appear to be a contraindication for organ procurement despite increased risk features for infectious disease transmission.

Influenza Virus Infection and Transplantation.

Influenza infection poses significant risk for solid organ transplant recipients who often experience more severe infection with increased rates of complications, including those relating to the allograft. Although symptoms of influenza experienced by transplant recipients are similar to that of the general population, fever is not a ubiquitous symptom and lymphopenia is common. Annual inactivated influenza vaccine is recommended for all transplant recipients. Newer strategies such as using a higher dose vaccine or multiple doses in the same season appear to provide greater immunogenicity. Neuraminidase inhibitors are the mainstay of treatment and chemoprophylaxis although resistance may occur in the transplant setting. Influenza therapeutics are advancing, including the recent licensure of baloxavir; however, many remain to be evaluated in transplant recipients and are not yet in routine clinical use. Further population-based studies spanning multiple influenza seasons are needed to enhance our understanding of influenza epidemiology in solid organ transplant recipients. Specific assessment of newer influenza therapeutics in transplant recipients and refinement of prevention strategies are vital to reducing morbidity and mortality.

COVID-19 in Solid Organ Transplantation: A Matched Retrospective Cohort Study and Evaluation of Immunosuppression Management.

BACKGROUND: The epidemiological and clinical characteristics of solid organ transplant (SOT) patients during the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) epidemic remains unclear. We conducted a matched retrospective cohort study to compare clinical outcomes among SOT recipients with the general population and to assess immunosuppression management. METHODS: Adult SOT recipients with laboratory polymerase chain reaction-confirmed SARS-CoV-2 infection admitted to a tertiary-care hospital in Barcelona, Spain, from March 11 to April 25, 2020, were matched to controls (1:4) on the basis of sex, age, and age-adjusted Charlson's Index. Patients were followed for up to 28 days from admission or until censored. Primary endpoint was mortality at 28 days. Secondary endpoints included admission to the intensive care unit and secondary complications. Drug-drug interactions (DDI) between immunosuppressants and coronavirus disease 2019 (COVID-19) management medication were collected. RESULTS: Forty-six transplant recipients and 166 control patients were included. Mean (SD) age of transplant recipients and controls was 62.7 (12.6) and 66.0 (12.7) years, 33 (71.7%) and 122 (73.5%) were male, and median (interquartile range) Charlson's Index was 5 (3-7) and 4 (2-7), respectively. Mortality was 37.0% in SOT recipients and 22.9% in controls (P = 0.51). Thirty-three (71.7%) patients underwent transitory discontinuation of immunosuppressants due to potential or confirmed DDI. CONCLUSIONS: In conclusion, hospitalized SOT recipients with COVID-19 had a trend toward higher mortality compared with controls, although it was not statistically significant, and a notable propensity for DDI.

A Report of 85 Cases of COVID-19 and Abdominal Transplantation From a Single Center: What Are the Associated Factors With Death Among Organ Transplantation Patients.

BACKGROUND: In this study, we report the epidemiology of COVID-19 among recipients of organ transplantation and evaluate associated factors with death. METHODS: We screened 6969 patients who had organ transplantations in our center for COVID-19. Specific data on presentation, clinical course, treatment, and prognosis were acquired. RESULTS: We found 85 patients (66 liver, 16 kidney, 2 kidney-pancreas, and 1 liver-kidney recipient) who acquired COVID-19. Most common symptoms included fever (48.2%), cough (41.2%), myalgia (41.2%), and fatigue (40%). Dyspnea developed in 33% of patients. Overall, one-third of patients had an oxygen saturation of below 90% on admission. Patients were hospitalized for a median (interquartile range) of 9 (5, 13.7) days and had a 33.9% intensive care unit admission rate. Overall, 17 patients (20%) died, which included 31.3% of patients with kidney transplantations and 18.2% of patients with liver transplantations. All 4 pediatric patients in our series died. In our univariate analysis among adults, rates of leukopenia (38.4% versus 13.2%; P = 0.04), low albumin levels (53.8% versus 10.2%; P = 0.001), and shorter duration between transplantation and COVID-19 (P = 0.02), were higher among patients who died. In our least absolute shrinkage and selection operator regression model, low albumin levels (OR, 4.48; 95% confidence interval, 1.16-17.27) were associated with higher risk of death. CONCLUSIONS: This is the largest single-center report on abdominal transplantations and COVID-19. Liver and kidney transplant recipients have an increased risk of mortality compared with the general population due to COVID-19. More specifically, pediatric patients and those with low albumin levels are at higher risks of death due COVID-19.

Immune Checkpoint Inhibitors in Transplantation-A Case Series and Comprehensive Review of Current Knowledge.

Cancer is a leading cause of morbidity and deaths in solid organ transplant recipients. In immunocompetent patients, cancer prognosis has been dramatically improved with the development of immune checkpoint inhibitors (ICI), as programmed cell death protein 1/programmed death-ligand 1 and cytotoxic T lymphocyte-associated antigen 4 inhibitors, that increase antitumor immune responses. ICI has been developed outside of the scope of transplantation because of the theoretical risk of graft rejection, which has later been confirmed by the publication of several cases and small series. The use of ICI became unavoidable for treating advanced cancers including in organ transplant patients, but their management in this setting remains highly challenging, as to date no strategy to adapt the immunosuppression and to prevent graft rejection has been defined. In this article, we report a monocentric series of 5 solid organ transplant recipients treated with ICI and provide a comprehensive review of current knowledge of ICI management in the setting of solid organ transplantation. Strategies warranted to increase knowledge through collecting more exhaustive data are also discussed.

COVID-19 Outcomes Among Solid Organ Transplant Recipients: A Case-control Study.

BACKGROUND: Solid organ transplant (SOT) recipients are considered to be "vulnerable" to COVID-19 infection due to immunosuppression. To date, there are no studies that compared the disease severity of COVID-19 in SOT recipients with nontransplant patients. METHODS: In this case-control study, we compared the outcomes of COVID-19 between SOT recipients and their matched nontransplant controls. The cases were all adult SOT recipients (N = 41) from our academic health center who were diagnosed with COVID-19 between March 10, 2020 and May 15, 2020 using positive reverse transcriptase polymerase chain reaction for SARS-CoV2. The controls (N = 121) were matched on age (±5 y), race, and admission status (hospital or outpatient). The primary outcome was death and secondary outcomes were severe disease, intubation and renal replacement therapy (RRT). RESULTS: Median age of SOT recipients (9 heart, 3 lung, 16 kidney, 8 liver, and 5 dual organ) was 60 y, 80% were male and 67% were Black. Severe disease adjusted risk of death was similar in both the groups (hazard ratio = 0.84 [0.32-2.20]). Severity of COVID-19 and intubation were similar, but the RRT use was higher in SOT (odds ratio = 5.32 [1.26, 22.42]) compared to non-SOT COVID-19 patients. Among SOT recipients, COVID-19-related treatment with hydroxychloroquine (HCQ) was associated with 10-fold higher hazard of death compared to without HCQ (hazard ratio = 10.62 [1.24-91.09]). CONCLUSIONS: Although African Americans constituted one-tenth of all SOT in our center, they represented two-thirds of COVID-19 cases. Despite high RRT use in SOT recipients, the severe disease and short-term death were similar in both groups. HCQ for the treatment of COVID-19 among SOT recipients was associated with high mortality and therefore, its role as a treatment modality requires further scrutiny.

Coronavirus Disease-19: Disease Severity and Outcomes of Solid Organ Transplant Recipients: Different Spectrums of Disease in Different Populations?

BACKGROUND: Coronavirus disease-19 (COVID-19) is associated with significant mortality. The elderly, patients with comorbidities, and solid organ transplant (SOT) recipients are particularly at risk. We observed a low incidence of severe disease in our population and aimed to determine the outcomes of COVID-19 (disease severity/intensive care unit [ICU] admissions/mortality) in SOT recipients. METHODS: All SOT recipients diagnosed with COVID-19 were included. Their demographic and clinical data were recorded from the hospital electronic system. Patients were assigned to 1 of 4 stages of disease severity: stage A = asymptomatic, stage B = mild, stage C = moderate, and stage D = severe. RESULTS: Of the 3052 SOT recipients, 67 were diagnosed with COVID-19. The mean age was 52 years, and 69% were male. There were approximately 25% patients in stage A, 28% in stage B, 34% in stage C, and 12% in stage D. Patients in stages C and D were older than those in stage A (P = 0.04) or stage B (P = 0.03). Lactic dehydrogenase (P < 0.01) and D-dimer (P < 0.01) levels were higher across the stages. Approximately 70% of patients were admitted for a median duration of 9 days and the median follow-up was 35 days. Acute kidney injury occurred in 19% of patients, and 45% required supplementary oxygen. The symptomatic patients were treated with Hydroxychloroquine (83%), Azithromycin (89%), and Tocilizumab (23%). Around 15% of patients were admitted to ICU and 2 patients have died. CONCLUSIONS: Most SOT recipients developed mild to moderate COVID-19 infection; few required ICU admission and 2 patients have died. Remaining patients have recovered and have been discharged from the hospital.

COVID-19 and Solid Organ Transplantation: A Review Article.

The coronavirus pandemic has significantly impacted solid organ transplantation (SOT). Early in the outbreak period, transplant societies recommended suspending living kidney transplant programs in communities with widespread transmission to avoid exposing recipients to increased risk of immunosuppression, while recommendations were made to reserve deceased-donor kidney transplantation for likely life-saving indications. SOT recipients may be at high risk from COVID-19 disease due to chronic immunosuppressive treatment and other medical comorbidities. Mortality rates reported between 13 to over 30% in SOT recipients. In addition to high rates of complications and mortality attributable to COVID-19 infections, the pandemic has also led to additional complexities in transplantation including new questions regarding screening of donors and recipients, decision making to accept a patient for kidney transplant or wait after pandemic. The clinical implications of COVID-19 infection may also differ depending on the type of the transplanted organ and recipient comorbidities which further impacts decisions on continuing transplantation during the pandemic. Transplant activity during a pandemic should be tailored with careful selection of both donors and recipients. Furthermore, while tremendous strides have been made in treatment strategies and vaccinations, the impact of these in transplant recipients may be attenuated in the setting of their immunosuppression. In this review, we aim to summarize several aspects of COVID-19 in transplantation, including the immune response to SARS-CoV-2, SARS-CoV-2 diagnostics, clinical outcomes in SOT recipients, and end-stage kidney disease patients, transplant activity during the pandemic, and treatment options for COVID-19 disease.

Clinicopathologic Features of Tissue Granulomas in Transplant Recipients: A Single Center Study in a Nontuberculosis Endemic Region.

CONTEXT.­: There is a paucity of literature about tissue granulomas in transplant patients. OBJECTIVE.­: To characterize the clinicopathologic features of granulomas in this population and develop a clinically judicious approach to their evaluation. DESIGN.­: We performed chart reviews of solid organ and allogeneic hematopoietic stem cell transplant recipients at Yale New Haven Hospital to identify patients with granulomas on biopsy obtained pathologic specimens. Pretransplant and posttransplant specimens were included. Data points included demographics, clinical presentation, epidemiologic risk factors, biopsy indication, location and timing, immunosuppression, histopathology, microbiology, and associated clinical diagnosis. Granuloma-related readmissions and mortality were recorded at 1, 3, and 12 months. RESULTS.­: Biopsy proven granulomas were identified in 56 of 2139 (2.6%) patients. Of 56, 16 (29%) were infectious. Common infectious etiologies were bartonellosis (n = 3) and cytomegalovirus hepatitis (n = 3). Tuberculosis was not identified. Clinical symptoms prompted tissue biopsy in 27 of 56 (48.2%) cases while biopsies were obtained for evaluation of incidental findings or routine disease surveillance in 29 of 56 (51.8%). Presence of symptoms was significantly associated with infectious etiologies; 11 of 27 (40.7%) symptomatic patients compared with 5 of 29 (17.2%) asymptomatic patients had infectious causes. One death from granulomatous cryptogenic organizing pneumonia occurred. In pretransplant asymptomatic patients, no episodes of symptomatic disease occurred posttransplantation. CONCLUSIONS.­: Granulomas were uncommon in a large transplant population; most were noninfectious but presence of symptoms was associated with infectious etiologies. Granulomas discovered pretransplant without clear infectious etiology likely do not require prolonged surveillance after transplantation. Symptomatology and epidemiologic risks factors should guide extent of microbiologic evaluation.

Real-world Outcomes With Rituximab-based Therapy for Posttransplant Lymphoproliferative Disease Arising After Solid Organ Transplant.

BACKGROUND: Optimal upfront therapy for posttransplant lymphoproliferative disease (PTLD) arising after solid organ transplant remains contentious. Rituximab monotherapy (R-Mono) in unselected patients has shown a lack of durable remissions. Cyclophosphamide, doxorubicin, vincristine, and prednisolone (CHOP)-based chemotherapy confers improved response rates, although concerns exist about toxicity. METHODS: This multicenter retrospective study reports outcomes for adults with biopsy-proven B-cell PTLD treated initially with R-Mono or Rituximab plus CHOP (R-CHOP). Selection of therapy was made according to physician preference. RESULTS: Among 101 patients, 41 received R-Mono and 60 had R-CHOP. Most (93%) had undergone renal or liver transplantation. R-CHOP showed a trend toward improved complete (53% versus 71%; P = 0.066) and overall (75% versus 90%; P = 0.054) response rates. In the R-Mono group, 13 of 41 (32%) subsequently received chemotherapy, while 25 of 41 (61%) remained progression-free without further therapy. With median follow-up of 47 months, overall survival (OS) was similar for R-Mono and R-CHOP, with 3-year OS of 71% and 63%, respectively (P = 0.722). Non-PTLD mortality was 3 of 41 (7%) and 4 of 60 (7%) within 12 months of R-Mono or R-CHOP, respectively. The International Prognostic Index was statistically significant, with low- (0-2 points) and high-risk (≥3 points) groups exhibiting 3-year OS of 78% and 54%, respectively (P = 0.0003). In low-risk PTLD, outcomes were similar between therapies. However, in high-risk disease R-Mono conferred an inferior complete response rate (21% versus 68%; P = 0.006), albeit with no impact on survival. CONCLUSIONS: Our data support R-Mono as initial therapy for PTLD arising after renal or liver transplantation. However, upfront R-CHOP may benefit selected high-risk cases in whom rapid attainment of response is desirable.

Solid Organ Transplantation in the Coronavirus Disease 2019 Era: "The Great Bet" in the North Italy Transplant Program Area.

INTRODUCTION: Solid organ transplantation is challenging for waitlist patients during the coronavirus disease 2019 (COVID-19) pandemic. AIM: This study investigates COVID-19 incidence and mortality in patients transplanted in the North Italy Transplant program (NITp) during the outbreak. MATERIALS AND METHODS: All consecutive patients transplanted from February 20 to April 3, 2020 (6 weeks), were included in our cohort and were observed for at least 4 weeks. Survival analyses were performed. RESULTS: In this study, 124 patients were transplanted with 12 (9.7%) hearts, 4 (3.2%) lungs, 39 (31.4%) livers, 67 (54%) kidneys, and 2 (1.6%) combined kidney-pancreas. Recipients' mean age was 51 years (standard deviation [SD] ± 16.6), and 76 of 124 (61%) were men. Five (4%) patients developed COVID-19 after a mean of 13 days (SD ± 6.7), with a cumulative incidence of 4.0% (95% confidence interval [CI], 0.5-7.5). During the follow-up period, 5 of 124 (4%) recipients died; overall mortality was 4.3% (95% CI, 0.6-8.0), with only 1 patient dying of COVID-19, for a COVID-19-related mortality of 0.8% (95% CI, 0-6.0). CONCLUSIONS: This study showed a low COVID-19 incidence and COVID-19-related mortality in patients transplanted during the COVID-19 pandemic. Further studies with a longer follow-up period are mandatory to confirm the safety of transplant procedures.