Occurrence of Severe SARS-CoV-2 Infection in Fully Vaccinated Solid Organ Transplant Recipients

The present study presents the clinical outcome of SARS-CoV-2 disease in relation to the humoral response in fully vaccinated solid organ transplant (SOT) recipients. Our patient cohort consists of 455 SOT recipients, vaccinated with one of the 2 approved mRNA vaccines. The antibody response was measured 1 month after the second dose, and previously infected patients have been excluded. Of the 449 remaining patients, 15 (3.34%) tested positive, using SARS-CoV-2 polymerase chain reaction. Their mean age was 43.7 ±14.4 years, and median time from transplantation was 7.8 years (1.2-30.2). Eleven patients (73.3%) had been vaccinated with BNT162b2 and 4 (26.7%) with the mRNA1273 vaccine. At the time of infection 9 (60%) patients had a negative (<50 AU/mL) antibody titer, and 6 (40%) had a positive one (>50 AU/mL). Median antibody titer, 27.4± 14.0 days after the second dose, measured at 13 AU/mL (0-7480 AU/mL). Renal function did not appear to be affected by the disease. Τhe mean estimated glomerular filtration rate at diagnosis was 48 ± 15 mL/min, and when in a 29-day (1-101) median follow-up was 53.9± 20.9 mL/min. Of the 15 patients, 7 had mild symptoms and were not hospitalized, and of the remaining 8 (53.3%) who needed hospitalization 7 had severe disease and 2 of them expired. The study confirms the variable and often severe course of coronavirus 2019 infection in SOT recipients, even after their full vaccination, highlighting the need to vaccinate their close relatives and to accelerate the implementation of the booster dose of vaccine.     

A Review of Cutaneous Diseases Observed in Solid Organ Transplant Recipients

Solid organ transplant recipients are at increased risk for numerous cutaneous conditions that fall within four categories: pre-neoplastic, neoplastic, infectious, or idiopathic. Many of these diseases can be attributed to immunosuppressive medications, including mycophenolate mofetil, cyclosporine, azathioprine, tacrolimus, or glucocorticoids. Iatrogenic lessening of the immune system places the patient at risk of malignancies, opportunistic infections, immune-mediated dermatoses, and adverse effects of medications. As the life expectancy of patients with solid organ transplants continues to increase, dermatologists and transplant physicians must stay abreast of this spectrum of dermatologic conditions, their respective prognoses, prevention, mitigation, and treatment.     

Chikungunya Infection in Solid Organ Transplant Recipients

Background

Chikungunya virus (CHIKV) is an emerging mosquito-borne disease that causes acute febrile polyarthralgia and arthritis. CHIKV has spread rapidly to the Americas and, in Brazil, autochthonous cases are increasingly been reported. Solid organ transplant (SOT) recipients who travel to or live in CHIKV endemic areas are under high risk of acquiring the disease. Few data exist regarding the clinical characteristics of CHIKV infections in this population. We report the first case series of CHIKV infection in SOT recipients.

Diagnostic Value of Serum Procalcitonin in Solid Organ Transplant Recipients: A Systematic Review and Meta-analysis

Purpose

To perform a systematic review and meta-analysis to define the role of procalcitonin (PCT) in identifying infectious complication in organ transplant recipients.

Methods

We searched EMBASE, MEDLINE, the Cochrane database, and reference lists of relevant articles, with no language restrictions, published from inception through May 2013. We selected original research that reported the diagnostic performance of PCT alone or when compared with other biomarkers to diagnose infectious complication among organ transplant recipients. We summarized test performance characteristics with the use of forest plots, hierarchical summary receiver operating characteristic curves, and bivariate random-effects models.

Results

We found 7 qualifying studies (studying 1226 episodes of suspected infection with 186 confirmed infectious episodes) from 4 countries. The patients were lung, kidney, liver, and heart transplant recipients. Bivariate pooled sensitivity, specificity, positive likelihood ratios, and negative likelihood ratios for identification of bacterial infections in patients after transplantation were 85% (95% confidence interval [CI], 75%–92%), 81% (95% CI, 72%–88%), 4.41 (95% CI, 2.86–6.81), and 0.18 (95% CI, 0.10–0.33), respectively. Of the 4 studies that reported the experience of liver transplant patients, the pooled sensitivity, specificity, positive likelihood ratios, and negative likelihood ratios were 90% (95% CI, 75%–97%), 85% (95% CI, 77%–91%), 6.12 (95% CI, 3.79–9.88), and 0.11 (95% CI, 0.04–0.32), respectively. There was no evidence of significant heterogeneity.

Conclusion

The existing literature suggests reasonable sensitivity and specificity for the PCT test in identifying infection complications among patients undergoing solid organ transplantation. Given the imperfect sensitivity and specificity of the PCT test, medical decisions should be based on both PCT test results and clinical findings.     

Zygomycosis in Solid Organ Transplant Recipients in a Tertiary Transplant Center and Review of the Literature

Zygomycetes are ubiquitous fungi that can cause invasive disease associated with high mortality. We report 10 solid organ transplant recipients with zygomycosis (incidence 2 per 1000) and reviewed 106 cases in the English-language literature. These included renal (n = 73), heart (n = 16), lung (n = 4), heart/lung (n = 2), liver (n = 19) and kidney/pancreas (n = 2) transplant recipients. All patients were receiving immunosuppression and the vast majority steroids. The clinical presentation included rhino-sino-orbital (n = 20), rhinocerebral (n = 16), pulmonary (n = 28), gastrointestinal (n = 13), cutaneous (n = 18), renal (n = 6) and disseminated disease (n = 15). Most frequently isolated genera were Rhizopus (73%) followed by Mucor (13%). The overall mortality was 49%. While rhino-sino-orbital disease had the best prognosis, rhinocerebral disease had high mortality (93%) comparable to disseminated disease. A favorable outcome was associated with limited, surgically accessible disease and early surgical intervention along with amphotericin B administration.     

Cancer Screening Recommendations for Solid Organ Transplant Recipients: A Systematic Review of Clinical Practice Guidelines

Solid organ transplant recipients (SOTRs) are at increased risk of developing and dying from cancer. However, controversies exist around cancer screening in this population owing to reduced life expectancy and competing causes of death. This systematic review assesses the availability, quality and consistency of cancer screening recommendations in clinical practice guidelines (CPGs). We systematically searched bibliographic databases and gray literature to identify CPGs and assessed their quality using AGREE II. Recommendations were extracted along with their supporting evidence. Thirteen guidelines were included in the review. CPGs for kidney recipients were the most frequent source of screening recommendations, and recommendations for skin cancer screening were most frequently presented. Some screening recommendations differed from those for the general population, based on literature demonstrating higher cancer incidence among SOTRs versus direct evidence of screening effectiveness. Relevant stakeholders such as oncology specialists, primary care providers and public health experts were not involved in the formulation of the screening recommendations. In conclusion, although several guidelines make recommendations for cancer screening in SOTRs, the availability of cancer screening recommendations varied considerably by transplanted organ. More studies are required to inform cancer screening recommendations in SOTRs, and guideline development should involve transplant patients, oncologists and cancer screening specialists.     

Influenza Virus Infection in Adult Solid Organ Transplant Recipients

BACKGROUND: Solid organ transplant (SOT) recipients have been reported to be more susceptible to influenza virus. However, little is known about the clinical epidemiology and the implications of influenza viral infection among SOT recipients. METHODS: Cohort study of influenza viral infection in SOT recipients at the University of Pittsburgh Medical Center. RESULTS: Between November 1990 and April 2000, 30 cases of influenza were diagnosed in SOT recipients at our center, including influenza A (n = 22) and influenza B (n = 8). These included recipients of lung (n = 19), liver (n = 5) and kidney (n = 6) transplants. The incidence of influenza viral infection was 41.8 cases/1,000 person years (PYs), 2.8 cases/1000 PYs and 4.3 cases/ 1,000 PYs among lung, liver and renal transplant patients, respectively (p <0.0001). Symptoms were reported in all patients and included malaise, myalgia/ arthralgia, fever, cough, and shortness of breath. Secondary bacterial pneumonia occurred in five patients (17%). Other complications were seen in three SOT recipients (2 liver and 1 kidney) and included: myocarditis, myositis, and bronchiolitis obliterans. Biopsy of the transplanted organ was performed in 21 SOT recipients (18 lung, 1 liver and 2 kidney) at the time of influenza viral infection. Overall, 62% (13/21) showed variable degrees of acute allograft rejection, and included 61% (11/18) of lung, and 100% (2/2) of kidney transplant recipients. CONCLUSIONS: Influenza infection is associated with significant morbidity in different groups of SOT recipients. Studies are needed to determine if yearly chemoprophylaxis with antiviral drugs might benefit this patient population.     

Plasma Cell Neoplasms in US Solid Organ Transplant Recipients

Transplant recipients have elevated risk for plasma cell neoplasms (PCNs, comprising multiple myeloma and plasmacytoma), but little is known about risk factors in the transplant setting. Through linkage of the US solid organ transplant registry with 15 state/regional cancer registries, we identified 140 PCNs in 202 600 recipients (1987–2009). PCN risk was 1.8‐fold increased relative to the general population (standardized incidence ratio [SIR] 1.80, 95%CI 1.51–2.12). Among cases, 102 were multiple myeloma (SIR 1.41) and 38 were plasmacytoma (SIR 7.06). PCN incidence increased with age, but due to the rarity of PCNs in younger people in the general population, SIRs were highest in younger transplant recipients (p = 0.03). PCN risk was especially high in recipients who were Epstein‐Barr virus (EBV) seronegative at transplantation (SIR 3.93). EBV status was known for 18 tumors, of which 7 (39%) were EBV positive. Following liver transplantation, PCN risk was higher in recipients with cholestatic liver disease (SIR 2.78); five of these cases had primary biliary cirrhosis (PBC). A role for primary EBV infection after transplantation is supported by the increased PCN risk in young EBV seronegative recipients and the presence of EBV in tumors. PBC may be another risk factor, perhaps by causing chronic immune activation.     

Risk of Thyroid Cancer Among Solid Organ Transplant Recipients

Solid organ transplant recipients have an elevated incidence of thyroid cancer. We evaluated a wide range of potential risk factors in a cohort of 229 300 U.S. solid organ transplant recipients linked with 15 stage/regional cancer registries (1987–2012). Incidence rate ratios (IRRs) were adjusted for age, sex, race/ethnicity, transplanted organ, year of transplantation, and time since transplantation. Hazard ratios (HRs) for death and/or graft failure were adjusted for age, sex, race/ethnicity, transplanted organ, and year of transplantation. After transplantation, 356 thyroid cancers were diagnosed. Thyroid cancer incidence was 2.50‐fold higher in transplant recipients than the general population (95% confidence interval [CI] 2.25–2.77). Among recipients of different organs, kidney recipients had the highest incidence of thyroid cancer (IRR = 1.26, 95% CI 1.03–1.53). Elevated thyroid cancer incidence was associated with cholestatic liver disease/cirrhosis as an indication for liver transplantation (IRR = 1.69, 95% CI 1.09–2.63), hypertensive nephrosclerosis as an indication for kidney transplantation (IRR = 1.41, 95% CI 1.03–1.94), and longer prior dialysis among kidney recipients (5+ vs. <1 year, IRR = 1.92, 95% CI 1.32–2.80; p‐trend <0.01). Posttransplantation diagnosis of thyroid cancer was associated with modestly increased risk of death (HR = 1.33, 95% CI 1.02–1.73). Overall, our results suggest that end‐stage organ disease and longer duration of dialysis may contribute to higher thyroid cancer incidence in transplant recipients.     

A Surveillance Study of Adenovirus Infection in Adult Solid Organ Transplant Recipients

Little is known about adenovirus infections in adult organ transplant recipients. We prospectively assessed adenovirus infection in 263 transplant recipients using polymerase chain reaction (PCR) on plasma samples at regular intervals post-transplant. Adenovirus DNA was detected in 19 of 263 patients (7.2%). Viremia by transplant type was: liver (n = 10 of 121 [8.3%]), kidney (n = 6 of 92 [6.5%]) and heart (n = 3 of 45 [6.7%]). Time to viremia onset was within 10 days post-transplant (n = 4), on day 28 (n = 1), on day 100 (n = 7) and between months 6 and 12 (n = 7). At the time of viremia, 11 of 19 (58%) patients had no symptoms, 2 of 19 (10.5%) had gastrointestinal (GI) symptoms, 2 of 19 (10.5%) had respiratory symptoms and 4 patients (21%) had vague/non-specific symptoms. All patients recovered spontaneously. Only 1 of 19 (5%) patients had subsequent acute rejection. Adenovirus viremia is relatively common in adult liver, kidney and heart transplant recipients and most infections are asymptomatic, transient and self-limited. No serious clinical sequelae or effects on subsequent acute rejection were observed.     

Outcomes of Colorectal Cancer Arising in Solid Organ Transplant Recipients

Introduction

The incidence of colorectal cancer posttransplantation is unclear. Limited reports exist and have conflicting conclusions. We aimed to review the clinical features and oncologic outcomes of colorectal cancer in transplant recipients at our institution.

Methods

A retrospective review of all patients diagnosed with colorectal cancer after solid organ transplantation between 2000 and 2011 was conducted. Clinical features and outcomes were reviewed.

Results

Twenty of 3,946 patients were identified. The most common single organ transplanted was the kidney (n?=?8). Six patients had multiorgan transplantation. Median age of diagnosis of cancer was 64.3 years, and median time from transplant to diagnosis of cancer was 8.7 years. Ten patients were symptomatic at presentation. Cancer was identified on routine colonoscopy in seven patients. Tumors were most commonly found in the right colon (n?=?14, 70 %). Six patients had stage IV disease at presentation. Short-term morbidity was identified in 11 patients. Postoperative mortality occurred in one patient. Median follow-up was 2.47 years. Overall survival at 5 years was 69 %, and disease-free survival was 68 %. Distant recurrence was seen in 3 (15 %) patients.

Conclusion

Colorectal cancer in these patients is rare, and surgery can be done safely. Vigilant screening must be maintained in this patient population.     

Cytomegaloviral Infection in Solid Organ Transplant Recipients: Preliminary Report of One Transplant Center Experience

Background

Despite advances in immunosuppressive therapy and post-transplantation care, antiviral prevention, and therapy, cytomegalovirus (CMV) infection remains the most common viral infection after solid organ transplantation (SOT).

Methods

This study included 2,375 patients under the care of our transplant center during the 1-year period from June 2012 to June 2013. There were 351 patients (14.78%) suspected and tested for CMV infection with the use of viral DNA amplification test.

Results

Symptoms that triggered diagnostics were graft dysfunction in 24 (55.8%), diarrhea in 18 (41.9%), fever in 15 (34.9%), leukopenia in 14 (32.6%), abdominal pain in 13 (30.2%), nausea in 7 (16.3%), cough in 6 (14%), and shivers in 2 (4.7%). Positive test results were obtained in 43 patients (12.3% of patients tested and 1.8% of the entire cohort). The group consisted of 17 women (39.5%) and 26 men (60.5%), 26 kidney (60.5%) and 17 liver (39.5%) transplant recipients, aged 49.3 years (SD 14.9). The initial viral load was median 8,093 (range: 4,232–219,180) copies/mL. The mean ganciclovir (GCV) treatment duration was 19.05 (SD 8.1) days. GCV doses ranged from 100 to 1,000 mg/d, mean 370.6 (SD 254.2) mg/d. Clinical resistance to treatment was diagnosed in 5 patients (11.6%). We found a positive correlation of GCV treatment duration with natural logarithm of initial CMV viremia (r = 0.56; P = .0002) and of time in months to CMV infection with mean cyclosporine level (r = −0.74; P = .04) and GCV dose (r = −0.34; P = .03). The duration of GCV therapy was positively influenced by CMV load and tacrolimus administration and negatively by patient's age and male sex.

Conclusions

Appearance of any symptoms occurring after transplantation, even nonspecific, should lead to diagnostics for CMV infection. The duration of treatment depends on the severity of the infection expressed by CMV viremia. Clinical resistance to GCV is not frequent, but it is an important transplantologic problem.     

Alpine Skiing and Anaerobic Performance in Solid Organ Transplant Recipients

Limited information has been published about sporting activities in solid organ transplant recipients. The aim of this study was to assess “in the field” performance capacities of a group of transplant recipients involved in an alpine skiing competition. We studied 16 transplant recipients (13 men and 3 women) who had undergone transplantations (11 kidney, 4 liver, and 1 heart) at 89 ± 68 months prior while participating in an alpine skiing race. The patients performed a countermovement jumping test to measure the explosive power of the lower limbs. In all patients blood lactate concentrations (La) were measured at the end of a giant slalom race. The maximum displacement of the center of mass during the jumping test was 22.4 ± 9.3 cm; the time to complete the giant slalom was 75.5 ± 16.5 seconds and La was 3.5 ± 0.8 mmol/L. We observed significant linear relationships between race time and La (R² = 0.4733; P < .01) and between race time and performance in the jumping test (R² = 0.3655; P < .05). This study indicated that recovery of anaerobic and technical sporting activities is possible in organ transplant recipients. Muscular power and anaerobic performances among a selected group of solid organ transplant recipients were similar to those of the general untrained population.     

A Seroprevalence Study of West Nile Virus Infection in Solid Organ Transplant Recipients

West Nile virus (WNV) causes severe neurological disease in less than 1% of infections. However, meningoencephalitis may be more common in immunosuppressed transplant patients. In 2002, a WNV outbreak occurred in our region. To determine the spectrum of disease of community acquired WNV infection and assess public health behavior patterns in transplant recipients, we carried out a seroprevalence study. Patients were enrolled from outpatient transplant clinics in October 2002 and sera were screened for WNV. Questionnaires about WNV were provided to patients. Eight hundred sixteen organ transplant patients were enrolled. The seroprevalence of WNV IgM was 2/816 (0.25%; 95% CI 0.03-0.88%). By extrapolation to our entire transplant population of 2360 patients, and using data from hospital-based surveillance, the risk of meningoencephalitis in a transplant patient infected with WNV is estimated to be 40% (95% CI 16-80%). With regards to knowledge and behavior, 56% patients knew of and 47% used at least one protective measure against WNV. Only 33% used insect repellent. The risk of meningoencephalitis in transplant recipients is much higher than in the general population. There is incomplete knowledge and poor rates of compliance amongst patients with regards to WNV prevention.     

Pulmonary Zygomycosis in Solid Organ Transplant Recipients in the Current Era

Fifty-eight solid organ transplant recipients with zygomycosis were studied to assess the presentation, radiographic characteristics, risks for extra-pulmonary dissemination and mortality of pulmonary zygomycosis. Pulmonary zygomycosis was documented in 31 patients (53%) and developed a median of 5.5 months (interquartile range, 2–11 months) posttransplantation. In all, 74.2% (23/31) of the patients had zygomycosis limited to the lungs and 25.8% (8/31) had lung disease as part of disseminated zygomycosis; cutaneous/soft tissue (50%, 4/8) was the most common site of dissemination. Pulmonary disease presented most frequently as consolidation/mass lesions (29.0%), nodules (25.8%) and cavities (22.6%). Patients with disseminated disease were more likely to have Mycocladus corymbifer as the causative pathogen. The mortality rate at 90 days after the treatment was 45.2%. In summary, pulmonary zygomycosis is the most common manifestation in solid organ transplant recipients with zygomycosis, and disseminated disease often involves the cutaneous/soft tissue sites but not the brain.     

Characteristics and Motivation of Solid Organ Transplant Recipients Attending the Canadian Transplant Games

BackgroundThe Canadian Transplant games (“Games”) were created to increase awareness of organ donation and highlight the importance of staying active and healthy post-transplant. It is unclear what motivates solid organ transplant (SOT) recipients to participate and whether the games serve as an incentive for SOT recipients to increase their physical activity (PA) levels.Objectives1. To describe the characteristics of participants from past games and their motivation for attending and 2. to determine whether there was an interest in participating in goal-based, pre-games exercise training programs.MethodsA web-based questionnaire was sent to adult SOT recipients who were members of the Canadian Transplant Association. The survey included questions about why participants attended, their PA levels, and their interest in a pre-games training program.ResultsOf the 157 participants, more were male than female; the 35-54-year-old age group was the most common; and 62% of respondents received a liver or kidney transplant. The most common reasons for participating in the games were to showcase health post-transplant, promote awareness of organ donation, sports competition, and social reasons. Sixty-five percent of respondents reported that they would be interested in an exercise program to be more physically prepared for the competition.ConclusionPre-games training programs could be developed to motivate participation and help participants achieve higher training intensities and foster social interaction. Directing resources to individuals who do not attend the games and to those who are not physically active should be considered.     

Clinical Aspects of Intravenous Immunoglobulin Use in Solid Organ Transplant Recipients

Intravenous immunoglobulin products (IVIG) are derived from pooled human plasma from thousands of donors and have been used for the treatment of primary immunodeficiency disorders for nearly 30 years. IVIG products are also effective in the treatment of autoimmune and inflammatory disorders, however the precise mechanism(s) of immune modulation are unknown. Recent data suggests that IVIG has a much broader ability to regulate cellular immunity, including innate and adaptive components. IVIG is also a recently recognized modifier of complement activation and injury. These attributes suggests IVIG would have clinical applications in solid organ transplantation. Analysis of clinical studies examining the use of IVIG in desensitization protocols and for treatment of antibody‐mediated rejection (AMR) are supportive for kidney transplant recipients, although no clinical trials using IVIG in sensitized patients were performed seeking an Federal Drug Administration indication. Data regarding the use of IVIG for desensitization and treatment of AMR in cardiac and lung allograft recipients is not conclusive. IVIG is useful in the treatment and prevention of posttransplant infectious complications including cytomegalovirus, parvovirus B19 and polyoma BK virus. In addition, we address the risk of adverse events associated with IVIG use in sensitized end‐stage renal disease and transplant patients.     

Baseline Quality of Life and Anxiety in Solid Organ Transplant Recipients: A Pilot Study

BACKGROUND: Solid organ transplant recipients on high doses of immunosuppression are at increased risk for the development of nonmelanoma skin cancer (NMSC). OBJECTIVE: The objective was to assess the possible factors impacting quality of life (QOL) in solid organ transplant recipients. METHODS: Patients were seen in a dermatology clinic integrated within the transplant center at a university-based hospital. One anxiety questionnaire and three QOL questionnaires were administered to each patient. A regression model was used to determine possible predictors of anxiety and lower QOL. RESULTS: The baseline scores on the QOL instruments and anxiety questionnaire indicate poor organ-specific and general QOL as well as high levels of anxiety. Time since transplant was predictive of lower QOL as measured by Skindex-16 (p<.01). While not significant, number of NMSCs correlated with higher anxiety as measured by the STAI (p=.055). CONCLUSIONS: While transplant patients enjoy longer survival, the quality of the extended life has room for improvement. Future studies will determine how QOL changes over time as these patients develop more numerous and aggressive skin cancers. Intervention with regular screening may not only lessen morbidity associated with skin cancer but may improve overall QOL in the posttransplant period.