Antifungal Prophylaxis with Voriconazole or Itraconazole in Lung Transplant Recipients: Hepatotoxicity and Effectiveness

Invasive fungal infections (IFI) are common after lung transplantation and there are limited data for the use of antifungal prophylaxis in these patients. Our aim was to compare the safety and describe the effectiveness of universal prophylaxis with two azole regimens in lung transplant recipients.
This is a retrospective study in lung transplant recipients from July 2003 to July 2006 who received antifungal prophylaxis with itraconazole or voriconazole plus inhaled amphotericin B to compare the incidence of hepatotoxicity. Secondary outcomes include describing the incidence of IFI, clinical outcomes after IFI and mortality.
Sixty-seven consecutive lung transplants received antifungal prophylaxis, 32 itraconazole and 35 voriconazole and inhaled amphotericin B. There were no significant differences between groups in the acute physiology and chronic health evaluation (APACHE) score at the time of transplantation, demographic characteristics, comorbidities and concomitant use of hepatotoxic medications. Hepatotoxicity occurred in 12 patients receiving voriconazole and inhaled amphotericin B and in no patients receiving itraconazole (p < 0.001). There was no significant difference between groups with regard to the percentage of transplants with IFI, but one case of zygomycosis occurred in a transplant treated with voriconazole. Voriconazole prophylaxis after lung transplantation was associated with a higher incidence of hepatotoxicity and similar clinical effectiveness when compared to itraconazole.     

Various Aspects of Bacterial Infections in the Early Postoperative Stage Among Lung Transplant Recipients on Broad-Spectrum Antibiotics: A Single Center Study

BackgroundLife-long immunosuppression after lung transplantation increases the risk of bacterial infections, hence broad-spectrum antibiotics can be implemented after transplant. The aim of this study is to assess various aspects of bacterial infections in the early postoperative stage among lung transplant recipients on broad-spectrum antibiotics at a single center.MethodsThis retrospective study consists of 134 primary lung transplant recipients transplanted between 2014 and 2021 at a single center. Study analyzed the occurrence of de novo bacterium in bronchoalveolar lavage sampled 2 to3 weeks after lung transplantation, as well as survival and the occurrence of bacterial sepsis. Studied antibiotics include linezolid, meropenem, tobramycin, and cloxacillin.ResultsNone of the patients from the broad-spectrum antibiotics developed bacterial sepsis within the first 30 postoperative days. In-hospital mortality due to bacterial sepsis among patients in the broad-spectrum group was 1.89%. The most common new pathogen in first couple of days after lung transplantation was Burkholderia multivorans (42%). After its occurrence, Ceftazidime was administered. It significantly reduced the occurrence of hospital-acquired B multivorans after 2 to 3 weeks post-transplant (χ² = 8.01, P = .005).ConclusionBroad-spectrum antibiotics seem to be an efficient approach against bacterial infections for lung transplant recipients in the early post-transplant period, as patients treated this way very rarely develop fatal bacterial infections in the studied period. Ceftazidime proved efficient for treatment for B multivorans among the studied group. Patients, who acquired new pathogen during post-transplant hospital stay presented comparable lung function at discharge in comparison to those who were not.     

Evaluation of Donor Lungs for Transplantation: The Efficacy of Screening Bronchoscopy for Detecting Donor Aspiration and Its Relationship to the Resulting Allograft Function in Corresponding Recipients

BackgroundPotential organ donors often have suffered anoxic and/or traumatic brain injury during which they may have experienced aspiration of gastric material (AGM). Evaluation of such donors typically includes a screening bronchoscopic examination during which determinations of aspiration are made. The efficacy of this visual screening and its relationship to post-transplant allograft function are unknown.MethodsBefore procurement, bronchoscopy was performed on donors in which both bronchoalveolar lavage fluid (BALF) was collected and a visual inspection made. As a marker of AGM, BALF specimens were analyzed for the presence of bile salts. Data collected on the corresponding recipients included primary graft dysfunction (PGD) score, post-transplant spirometry, acute rejection scores (ARS), and overall survival.ResultsOf 31 donors evaluated, bronchoscopies revealed only 2 with visual evidence of AGM, whereas BALF analysis for bile salts indicated AGM in 14. As such, screening bronchoscopy had a sensitivity of only 7.1%. Visual detection of AGM via bronchoscopy was not associated with any resulting grade of PGD (χ² = 2.96, P = .23); however, AGM defined by detection of bile salts was associated (χ² = 7.56, P = .02). Over the first post-transplant year, the corresponding recipients experienced a similar improvement in allograft function (χ² = 1.63, P = .69), ARS (P = .69), and survival (P = .24).ConclusionVisual inspection during a single bronchoscopic examination of lung donors underestimates the prevalence of AGM. The detection of bile salts in donor BALF is associated with early allograft dysfunction in the corresponding recipients but not with later allograft proficiency, acute rejection responses, or 1-year post-transplant survival.     

Invasive Fungal Disease Among Pediatric and Adolescent Patients Undergoing Itraconazole Prophylaxis After Hematopoietic Stem Cell Transplantation

BackgroundInvasive fungal disease (IFD) is a major cause of morbidity and mortality in patients after hematopoietic stem cell transplantation (HSCT). Itraconazole has been used for prevention of IFD, but data related to incidence and associated factors of IFD in pediatric and adolescent patients on itraconazole prophylaxis remain scarce.ObjectivesTo identify incidence and risk factors associated with IFD among pediatric and adolescent patients receiving itraconazole prophylaxis after HSCT.MethodsPatients younger than 21 years who received itraconazole prophylaxis after HSCT from January 2007 to December 2016 were retrospectively enrolled. Incidence of IFD within 1 year and associated factors were analyzed.ResultsAll patients received itraconazole during the pre-engraftment period. Of 170 patients, 29 had IFD, with an incidence of 17.1% at 1 year. IFD at 1 year was significantly associated with increased mortality. Of 29 patients with IFD, only 9 developed IFD while on itraconazole prophylaxis (5.3%), all of whom had invasive pulmonary aspergillosis. No invasive candidiasis occurred during itraconazole prophylaxis. Prolonged neutropenia (hazard ratio [HR] = 1.08; 95% confidence interval [CI], 1.02-1.13), graft-versus-host disease within 100 days after transplantation (HR = 3.17; 95% CI, 1.17-8.57), and using etoposide in preconditioning regimens (HR = 21.60; 95% CI, 2.44-190.95) were significantly associated with IFD at 1 year. No patients had to discontinue itraconazole because of its adverse effects.ConclusionsItraconazole proffered good efficacy for prevention of candidiasis during the pre-engraftment period. Most IFD episodes occurred after the engraftment period when itraconazole had been discontinued. During this period, patients with risk factors require appropriate fungal prophylaxis.     

Utilidad de la diferencia venoarterial de PCO2 como predictor de complicaciones en el postoperatorio inmediato del trasplante hepático

ObjectiveTest whether the development of abnormal venous-to arterial CO₂ difference (ΔPCO₂) during the early phases of postoperative care after a liver transplantation is related to multi-organ dysfunction and outcomes.Materials and methodsProspective cohort study accomplished in a mixed intensive care unit at a university hospital. We included 150 eligible patients after a liver transplantation between 2015 and 2018.Patients were classified in 4 predefined groups according to the ΔPCO₂ evolution during the first 6 h of resuscitation: 1) persistently normal ΔPCO₂ (normal at T0 and T6); 2) decreasing ΔPCO₂ (high at T0, normal at T6); 3) increasing ΔPCO₂ (normal at T0, high at T6); and 4) persistently high ΔPCO₂ (high at T0 and T6). Multiorgan dysfunction at day-3 was compared for predefined groups and a Kaplan Meier curve was constructed to show the survival probabilities using a log-rank test to evaluate differences between groups. A Spearman-rho was used to test the agreement between cardiac output and ΔPCO₂.ResultsThere were no significant differences between the study groups regarding higher SOFA scores at day-3 (P = 0.86), Δ-SOFA (P = 0.088), as well as global mortality rates (χ² = 5.72; P = 0.126) and mortality rates at day-30 (χ² = 2.23; P = 0.5252).A significantly poor inverse agreement between cardiac output and ΔPCO₂ was observed (rho de Spearman ?0,17; P = 0,002) at different points of resuscitation.ConclusionsAfter a liver transplantation, central venous-to-arterial CO₂ difference was not associated with survival or postoperative adverse outcomes in a critical care patients population.     

Association of positive pre-transplant angiotensin II type 1 receptor antibodies with clinical outcomes in lung transplant recipients

IntroductionAutoantibodies against the angiotensin II type 1 receptor (AT1R-Ab) have been previously associated with de novo donor-specific antibody (DSA) formation in lung transplantation. However, data regarding the clinical significance of AT1R-Ab in long-term graft function after lung transplantation are lacking.MethodsSeventy-one patients who underwent lung transplantation between July 2016 and January 2020 were enrolled in this study. We examined the relationship between pre-transplant AT1R-Ab levels and graft function, clinical outcomes, and human leukocyte antigen (HLA) DSA levels during the first 3 years post-transplantation.ResultsSeventeen (23.9%) patients were AT1R-Ab-positive, and 54 (76.1%) were AT1R-Ab-negative. The median antibody value of the AT1R-Ab-positive group was 18 [18–22.5] U/mL, while that of the AT1R-Ab-negative group was 5.1 [3.5–8.0] U/mL (p < 0.001). There was no significant difference in the median acute cellular rejection (ACR) scores between the two groups (median [interquartile range] 1 [0.8–3] vs. 0.7 [0–1]; p = 0.145). However, there was a significant difference in the distribution of the ACR scores between the two groups (p = 0.015). Most (41.2%) patients in the pre-transplant AT1R-positive group scored above 1. The incidence of de novo DSA was also higher in AT1R-Ab-positive than in AT1R-Ab-negative patients (52.9% vs. 20.4%, p = 0.009). The incidence of chronic lung allograft dysfunction (CLAD) within 3 years was significantly higher in AT1R-Ab-positive than in AT1R-Ab-negative patients (58.3% vs. 11.8%; p < 0.001). In the multivariate Cox regression analysis, AT1R-Ab positivity (hazard ratio, 9.46; 95% confidence interval, 2.89–30.94; p < 0.001) was significantly associated with early CLAD. Furthermore, Kaplan-Meier analysis showed that AT1R-Ab-positive patients had a shorter survival time (χ² = 39.62, p < 0.001).ConclusionHigh AT1R-Ab levels in the pre-transplant serum of lung recipients were associated with the development of de novo HLA-DSA, ACR, early CLAD, and short survival.     

Voriconazole Prophylaxis in Lung Transplant Recipients

Lung transplant recipients have one of the highest rates of invasive aspergillosis (IA) in solid organ transplantation. We used a single center, nonrandomized, retrospective, sequential study design to evaluate fungal infection rates in lung transplant recipients who were managed with either universal prophylaxis with voriconazole (n = 65) or targeted prophylaxis (n = 30) with itraconazole ± inhaled amphotericin in patients at high risk (pre- or posttransplant Aspergillus colonization [except Aspergillus niger ]). The rate of IA at 1 year was better in lung transplant recipients receiving voriconazole prophylaxis as compared to the cohort managed with targeted prophylaxis (1.5% vs. 23%; p = 0.001). Twenty-nine percent of cases in the targeted prophylaxis group were in patients colonized with A. niger who did not receive itraconazole. A threefold or higher increase in liver enzymes was noted in 37–60% of patients receiving voriconazole prophylaxis as compared to 15–41% of patients in the targeted prophylaxis cohort. Fourteen percent in the voriconazole group as compared to 8% in the targeted prophylaxis group had to discontinue antifungal medications due to side effects. Voriconazole prophylaxis can be used in preventing IA in lung transplant recipients. Regular monitoring of liver enzymes and serum concentrations of calcineurin inhibitors are required to avoid hepatotoxicity and nephrotoxicity.     

Pre-existing non-human leukocyte antigen antibodies are associated with allograft rejection after thoracic transplantation

BackgroundThere is growing evidence on the important role of non-human leukocyte antigen (HLA) antibodies in lung and heart transplant rejection. Since data on the prevalence and clinical significance of non-HLA antibodies in the Asian population are scarce, we analyzed non-HLA antibodies in heart and lung transplant patients.MethodsWe used the Luminex method to measure non-HLA antibodies in patients who underwent heart transplantation (N = 28) or lung transplantation (N = 36) between 2016 and 2019. We evaluated the association between pre-existing non-HLA antibodies and acute rejection-free days in these recipients.ResultsOf 64 patients, 27 (42.2%) patients underwent rejection, with 26 (40.6%) acute cellular rejection and one (1.6%) acute antibody-mediated rejection. Among 33 identified different non-HLA antibodies, only the anti-glutathione S-transferase theta-1 (GSTT1) antibody positive rate was significantly higher in patients with acute rejection compared to those without rejection (14.8% vs. 0%, p = 0.016). The angiotensin II type I receptor positive rate was not significantly different between the two groups (40% vs. 18.5%, p = 0.129). In the multivariate Cox regression analysis, anti-GSTT1 antibody-positive patients had a higher risk of acute allograft rejection (hazard ratio, 4.19; 95% confidence interval [CI], 1.41–12.49; p = 0.010). The Kaplan-Meier curve showed that anti-GSTT1 antibody-positive patients had fewer acute rejection-free days (χ² = 7.892; p = 0.005). Additionally, patients who underwent platelet transfusion (odds ratio, 1.49; 95% CI, 1.16–1.91; p = 0.002) before transplantation were more likely to be positive for anti-GSTT1 antibody.ConclusionPatients with antibodies against GSTT1 before heart or lung transplantation have anincreased risk of acute rejection.     

Effects of Body Mass Index Changes In Pediatric Kidney Transplant Patients

BackgroundThe negative effects of pretransplant obesity and post-transplant body mass index (BMI) increase on graft survival have been reported in recent years. The aim of this study is to evaluate the effects of BMI changes on post-transplant graft function, lipid profile, and blood pressure.MethodsThe study included 133 pediatric patients transplanted between 1994 and 2019 in Ege University. BMI Z-scores (BMIZs) were calculated according to age and sex before and after transplantation using the World Health Organization criteria. Patients with BMIZs >+1 standard deviation (SD) were defined as overweight, and those with BMIZs >+2 SD were defined as obese: Group 1: Obese or overweight before transplantation; Group 2: Thin or normal weight before and 2 years after transplantation; and Group 3: Thin or normal weight before transplantation and obese or overweight 2 years after transplantation.ResultsAt the time of transplantation 8% of the patients were overweight, and 1% were obese. Overweight and obesity statistically significantly increased (31.6%) 2 years after renal transplantation (P = .001). Obese and overweight patients have lower high-density lipoprotein levels and were younger at the time of transplantation. Graft functions, lipid levels, and blood glucose levels of the groups were similar (P > .05). The only significant difference between the groups was that Group 1 patients were younger than Group 2.ConclusionsObesity develops at a significant rate in pediatric patients after renal transplantation. In this study, we could not demonstrate negative effects of obesity and being overweight in terms of post-transplant graft function, lipid profile, blood glucose, and blood pressure.     

Hyperparathyroidism at 1 year after kidney transplantation is associated with graft loss

BackgroundHyperparathyroidism persists in many patients after kidney transplantation. The purpose of this study was to evaluate the association between post-transplant hyperparathyroidism and kidney transplantation outcomes.MethodsWe identified 824 participants from a prospective longitudinal cohort of adult patients who underwent kidney transplantation at a single institution between December 2008 and February 2020. Parathyroid hormone levels before and after kidney transplantation were abstracted from medical records. Post-transplant hyperparathyroidism was defined as parathyroid hormone level ≥70 pg/mL 1 year after kidney transplantation. Cox proportional hazards models were used to estimate the adjusted hazard ratios of mortality and death-censored graft loss by post-transplant hyperparathyroidism. Models were adjusted for age, sex, race/ethnicity, college education, parathyroid hormone level before kidney transplantation, cause of kidney failure, and years on dialysis before kidney transplantation. A Wald test for interactions was used to evaluate the risk of death-censored graft loss by age, sex, and race.ResultsOf 824 recipients, 60.9% had post-transplant hyperparathyroidism. Compared with non-hyperparathyroidism patients, those with post-transplant hyperparathyroidism were more likely to be Black (47.2% vs 32.6%), undergo dialysis before kidney transplantation (86.9% vs 76.6%), and have a parathyroid hormone level ≥300 pg/mL before kidney transplantation (26.8% vs 9.5%) (all P < .001). Patients with post-transplant hyperparathyroidism had a 1.6-fold higher risk of death-censored graft loss (adjusted hazard ratio = 1.60, 95% confidence interval: 1.02–2.49) compared with those without post-transplant hyperparathyroidism. This risk more than doubled in those with parathyroid hormone ≥300 pg/mL 1 year after kidney transplantation (adjusted hazard ratio = 4.19, 95% confidence interval: 1.95–9.03). The risk of death-censored graft loss did not differ by age, sex, or race (all P_interaction > .05). There was no association between post-transplant hyperparathyroidism and mortality.ConclusionThe risk of graft loss was significantly higher among patients with post-transplant hyperparathyroidism when compared with patients without post-transplant hyperparathyroidism.     

Endobronchial Topical Amphotericin B Instillation for Pulmonary Chromomycosis After Lung Transplantation: A Case Report

We report a very rare case of pulmonary chromomycosis caused by Scedosporium prolificans that developed after lung transplantation and was successfully treated with endobronchial topical amphotericin B instillation. The subject was a woman in her 50s with a history of bilateral lobar lung transplantation from living donors for idiopathic pulmonary hypertension. Eight years after the lung transplantation, chest radiography X-ray and computed tomography showed an abnormal shadow in the right lung. Bronchoscopic findings showed obstruction by a fungal component at the laterobasal bronchus B9. She was diagnosed with pulmonary chromomycosis after S. prolificans was detected in the bronchial aspirate. Systemic antifungal treatment with itraconazole was ineffective. Therefore, we administered topical amphotericin B weekly via endobronchial instillation and replaced oral itraconazole with voriconazole. The endobronchial procedure was safe and tolerable. Bronchial obstruction improved after three 3 instillations. We continued topical amphotericin B instillation once every 3 months for 2 years, and the abnormal shadow nearly disappeared. This case report describes infection by S. prolificans, which rarely becomes an etiologic agent in lung transplant patients, and shows that endobronchial topical amphotericin B instillation is a therapeutic option when systemic antifungal treatment is ineffective.     

Impact of Tacrolimus Trough Variability on Acute Rejection Following Lung Transplantation

BackgroundAcute rejection is a risk factor for the development of chronic lung allograft dysfunction, the leading cause of morbidity and mortality in lung transplant recipients. Calcineurin inhibitors are the cornerstone of immunosuppression regimens after lung transplantation.MethodsWe retrospectively evaluated the association of tacrolimus level variability with total acute rejection score at 12 months post-transplant. Secondary outcomes included the development of chronic lung allograft dysfunction and antibody-mediated rejection at 24months post-transplant. There were 229 lung transplant recipients included.ResultsThe mean (standard deviation) total rejection score of the cohort was 1.6 (1.7). Patients with high tacrolimus variability at 0 to 3, 3 to 6, and 6 to 12 months on average scored 0.18 (mean 1.6 vs 1.5; 95% CI): -0.3 to 0.66, P =.46), 0.14 (mean 1.7 vs 1.5; 95% CI: -0.32 to 0.6, P = .55), and 0.12 (mean 1.6 vs 1.5; 95% CI: -0.34 to 0.58, P = .62) point higher in 12-month total acute rejection scores, respectively; however, these differences were not statistically significant. The incidences of chronic lung allograft dysfunction and antibody-mediated rejection were numerically greater in the high variability group throughout certain periods; however, this was not consistent throughout all study timeframes and statistical significance was not evaluated.ConclusionsHigh tacrolimus variability was not associated with increased 12-month total acute rejection score. Further studies are needed to assess long-term outcomes with tacrolimus level variability.     

Immune reconstitution syndrome-like entity in lung transplant recipients with invasive aspergillosis

BackgroundIncidence, characteristics, and risk-factors for invasive aspergillosis (IA)-associated immune reconstitution syndrome (IRS) in lung transplant recipients are not known.MethodsPatients comprised 68 lung transplant recipients with proven/probable IA followed for 12 months. IRS was defined based on previously proposed criteria.ResultsIn all, 7.3% (5/68) of the patients developed IRS based on aforementioned criteria, a median of 56 days after initiation of antifungal therapy. This entity was associated with heart–lung transplantation (p = 0.006), anti T-cell agent use (p = 0.003), discontinuation of calcineurin inhibitor agent (p = 0.002), and disseminated IA (p = 0.069). In a risk assessment model, IRS developed in 0% (0/55) of the patients with none of the aforementioned factors, 28.6% (2/7) with one, 33.3% (1/3) with two, and in 1/1 patient with 3 factors (X² for trend p = 0.0001). Three out of 5 patients with IRS died and 2 of 3 deaths in this group were due to chronic rejection.ConclusionsOverall 7% of the lung transplant recipients with IA appear to develop an IRS-like entity. Clinically assessable factors can identify patients at risk for post-transplant IA-associated IRS. Deaths due to chronic rejection were significantly higher in patients with IRS than those without IRS.     

Sex- and age-based comparison of serum immunoglobulins following liver transplantation

BackgroundOver a quarter of organ transplant recipients have low immunoglobulin levels in their early post-transplant course, which is associated with increased risk of infection and mortality. Although immunoglobulin level varies by sex among healthy individuals, it is unknown how such differences are affected by transplant-related immunosuppression. This study compared post-liver transplant immunoglobulin G (IgG) between sexes at varying ages.MethodsSerum specimens from a prospective cohort of 130 liver transplant recipients were analyzed. IgG was measured at time of transplant and from one-month post-transplant samples. Post-transplant IgG was compared between sexes using multivariable linear regression. Four age and sex categories were created (women<50, women≥50, men<50, men≥50) and the model repeated with this as the explanatory variable. The relationship between sex hormone concentrations and post-transplant IgG was also explored. Infection type and incidence were examined within groups.ResultsThe cohort included 99 men, 31 women (mean age 53). In adjusted linear regression, post-transplant IgG was not significantly different by sex (p = 0.92). However, when broken into four categories by age and sex, the contrast in IgG levels between younger versus older patients was strikingly greater among women than among men. An interaction term including age and sex was statistically significant (p = 0.03). The combined age-sex categorical variable was also significantly associated with post-transplant IgG (p = 0.01). Finally, an association was identified between baseline estradiol level and post-transplant change in IgG (p = 0.04).ConclusionsSex and age have an important relationship with post-transplant IgG with older women demonstrating lowest concentrations. Immunoglobulin levels have previously demonstrated association with post-transplant outcomes.     

Serum follistatin level as a prognostic marker in Haploidentical stem cell transplantation

BackgroundThe treatment of hematological diseases with Haploidentical transplantation has made significant progress. Follistatin is an angiogenic factor that is elevated in the circulation after allogeneic Hematopoietic Cell Transplantation (HCT). Elevated follistatin levels have been linked to poor survival after graft versus host disease (GVHD).ObjectivePre- and post-transplant Follistatin levels were measured in patients subjected to Haploidentical HSCT and correlated with transplant outcomes.Patients and methodsThis study included 45 patients who underwent allogeneic stem cell transplants from Haploidentical donors.ResultsThe mean Follistatin level before stem cells infusion (88.81 ± 49.11 ng/ml) and at day 28 post-transplant (78.61 ± 45.50 ng/ml). The mean follistatin level was higher among the patients who had acute severe GVHD grade 3–4 pre-transplant at day zero and day 28 without statistical significance.The incidence of veno-occlusive disease was higher in patients with elevated serum follistatin levels on day 0 (108.58 ± 64.12 Vs 82.16 ± 46.05 ng/ml. p value = 0.134) and day 28 (112 ± 49.36 vs 66.06 ± 38.96 ng/ml) with statistically significance at day 28 post-transplant (p value = 0.011).After 180 days of follow-up, patients with high serum follistatin (i.e. >60 ng/ml) on day 28 post-transplant had lower OS, (P = 0.381).ConclusionIn the setting of Haploidentical HSCT, higher follistatin levels post-transplant are associated with severe acute GVHD and inferior overall survival.     

Correlation analysis of the peripheral blood lymphocyte count and occurrence of pneumonia after lung transplantation

BackgroundInfections are the most common complication in patients after lung transplantation and the main cause of death at all stages after transplantation; therefore, awareness regarding the occurrence of infectious pneumonia after lung transplantation is vital. This study aimed to explore the correlation between the absolute lymphocyte and T-lymphocyte subpopulation counts in the peripheral blood and the occurrence of pneumonia after lung transplantation and to predict the risk of pneumonia development after lung transplantation.MaterialsPatients who underwent lung transplantation with long-term follow-up between June 2018 and December 2021 were prospectively included. The patients were divided into pneumonia and non-pneumonia groups. Demographic and clinical characteristics, and the levels of leukocytes, neutrophils, platelets, C-reactive protein (CRP), procalcitonin (PCT), serum albumin, peripheral blood T lymphocytes, and CD4+ and CD8+ T cells in the peripheral blood were measured in both groups.ResultsWe included 22 patients with post-lung transplants in the analysis. Of the 104 collected samples, 26 (56.5%) were pathogenically positive, 16 (61.5%) had bacterial infections, 7 samples (26.9%) had fungal infections, and 8 (30.8%) had viral infections. Patients with pneumonia had higher levels of peripheral blood neutrophils (P = 0.01), platelets (P = 0.03), and CRP (P < 0.001) than did those without pneumonia. Logistic regression analysis showed that the levels of peripheral blood neutrophils, total T lymphocytes, CRP, and PCT were associated with the development of pneumonia after transplantation (P < 0.05), as documented by their area under the curve (AUC) values of 0.702, 0.792, 0.899, and 0.789, respectively. The AUC for the combined receiver operating characteristic curve for predicting the development of pneumonia was 0.943, with a sensitivity of 91.3% and specificity of 93.1%. There was no significant difference in T-lymphocyte counts in patients with lung transplants between the pneumonia and non-pneumonia groups who were treated with two anti-rejection agents. In contrast, the absolute lymphocyte, total T-lymphocyte, and CD4+ and CD8+ T-cell counts in patients who developed pneumonia after treatment with three anti-rejection agents were lower than those in patients who did not develop pneumonia (P < 0.05).ConclusionBacterial pneumonia is more common after lung transplantation than after fungal or viral infections. Peripheral blood T-lymphocyte counts combined with neutrophil, CRP, and PCT levels had good predictive value for the development of pneumonia after lung transplantation. Monitoring of patients should be strengthened by implementing peripheral blood T-lymphocyte counts to improve the early identification and prevention of pneumonia after lung transplantation.     

High levels of soluble Major Histocompatibility Complex class I related chain A (MICA) are associated with biliary cast syndrome after liver transplantation

BackgroundThe biliary cast syndrome (BCS) is a frequent problem following liver transplantation. The pathogenesis of this complication is not well understood. Previous research has demonstrated that the soluble form of MICA (sMICA) is significantly higher in patients with chronic liver disease and hepatocellular carcinoma (HCC) than in healthy volunteers. The aim of this study is to investigate the possible involvement of sMICA in the formation of BCS after liver transplantation.MethodsSerum soluble MICA was retrospectively evaluated in pre- and post-transplant sera from 133 consecutive primary liver transplant patients and in sera from 88 healthy volunteers using sandwich ELISA. Normal distribution of serum sMICA was described by the data obtained from healthy population and sMICA concentration that was greater than the upper bound 95% normal range was considered as high levels of sMICA. Patient records were reviewed to identify patients who developed BCS.ResultsThe results demonstrated that 37.6% of patients with end-stage liver diseases had significantly higher pre-transplant serum sMICA than in healthy population. 34.4% of recipients with post-transplant high levels of sMICA developed BCS. In contrast, 17.3% of patients with post-transplant normal levels of sMICA developed BCS. The risk of BCS development is significantly associated with the presence of post-transplant high levels of sMICA (P = 0.0365). Further analysis disclosed that patients with decreased post-transplant sMICA following liver transplantation had a lower incidence rate of BCS than those with remained high levels of sMICA after transplantation (10.5% vs. 38.7%, P = 0.0302). Furthermore, log-rank test showed that BCS occurrence was significantly associated with dynamic changes of sMICA among different groups (P = 0.0188).ConclusionsBiliary cast syndrome is more likely to develop in recipients who have post-transplant high levels of sMICA. The data suggested that sMICA might have some immunologic effect on BCS development following liver transplant. Monitoring of serum sMICA could have a prognostic value in assessment of patients with liver transplantation.     

Circulating “Neutrophils extra-cellular traps” during the early post-renal transplant period and correlation with graft dysfunction and rejection

BackgroundNeutrophil extracellular traps (NETs) have a role in infection, autoimmunity, autoinflammation, thrombosis, ischemia-reperfusion injury (IRI), epithelial-mesenchymal transition, vasculitis, and metabolic diseases. However, its role in early graft injury and graft outcome has not been elucidated till now. We evaluated the circulating NETs during early post-transplant periods and their correlation with graft outcome and IRI.MethodsProspectively, thirty kidney transplants recipient (KTR) were recruited and grouped into non-dysfunction (Group-A) and dysfunction groups (Group-B). Serum levels of circulating NETs were estimated by measuring myeloperoxidase-DNA complex at three-time points: pre-transplant, 8 h post-transplant, and 18 h post-transplant; and correlated with early graft outcome. Malondialdehyde (MDA), a marker of oxidative stress or IRI, was also measured to assess its relation with NETs and early graft outcome.ResultsCirculating NETs were significantly increased in both non-dysfunctional [Median OD: 0.11 (0.01–0.19) to 0.51 (0.22–0.91); p = 0.001] and dysfunctional [Median OD: 0.16 (0.12–0.27) to 0.38 (0.19–0.68); p = 0.047] KTR during first 8 h of transplant followed by fall at 18 h post-transplant [0.25 (0.18–0.72) and 0.35 (0.26–0.36) respectively]; however, no significant difference were observed between two groups at any time points. Isolated biopsy-proven graft rejection KTR also had higher circulating NETs during the early post-transplant period [Median OD: 0.16 (0.13–0.31) to 0.38 (0.28–1.5); p > 0.05] but no significant difference compared to non-dysfunctional KTR. MDA also displayed similar trends with an early significant rise [9.30 (7.74–12.56) μM to 17.37 (9.11–22.25) μM; p = 0.03 in group-A, and 8.7 (6.04–10.30) μM to 14.66 (13.39–21.63) μM; p = 0.01in group-B] followed by fall at 18 h in both groups [10.21 (7.64–13.90) μM and 11.11 (9.15–17.54) μM respectively]. Despite similar trends of both NETs and MDA, there was no significant correlation between these; however, creatinine exhibits a significant inverse correlation with NETs and MDA both.ConclusionCirculating NETs are significantly increased during the early post-transplant period in KTR irrespective of early graft outcome. Similar dynamics of MDA indicate that the early rise of NETs might be a part of IRI. However, molecular studies with large sample sizes and longer follow up are required to reach more defined conclusions.     

Post-transplant eosinophilic gastrointestinal disorders and lymphoproliferative disorder in pediatric liver transplant recipients on tacrolimus

AimTo examine and characterize post-transplant eosinophilic gastrointestinal disorders (PTEGID) and post-transplant lymphoproliferative disorder (PTLD) in pediatric liver transplant recipients.MethodsThis is a single center retrospective study of all liver transplant recipients aged 0–18 years from 1999 to 2019 who received tacrolimus as their primary immunosuppressant. Demographic data and clinical/laboratory data including PTEGID, PTLD, liver transplant types, Epstein-Barr virus status, and blood eosinophil count were reviewed. Analysis was done with logistic regression and Mann-Whitney U test.ResultsNinety-eight pediatric liver transplant recipients were included with median age at transplantation of 3.3 years (IQR: 1.1–9.3). The major indication for transplantation was biliary atresia, 51 (52%) cases. Eight (8%) children had PTLD and 14 (14%) had PTEGID. Receiving liver transplantation at an age of ≤1 year was associated with developing PTEGID (OR = 11.9, 95% CI = 3.5–45.6, p < 0.001). Additionally, eosinophilic count of ≥500/μL was associated with having PTLD (OR = 10.7, 95% CI = 1.8–206.0, p = 0.030) as well as having at least one liver rejection (OR = 2.8, 95% CI = 1.2–7.0, p = 0.024). The frequency of food-induced anaphylaxis significantly increased post-transplantation (p = 0.023).ConclusionsPTEGID and PTLD are common in this cohort and are associated with certain risk factors that help screen children to improve recipient survival. Further studies are needed to evaluate the clinical benefits of these findings.     

Evaluating the Use of CT-Derived Lung Volumes in Donor-Recipient Lung Size Matching for Lung Transplantation in Patients With Interstitial Lung Disease and/or Idiopathic Pulmonary Fibrosis

PurposeThis study aims to assess the efficacy of current measurement strategies for lung sizing and the feasibility of future use of computed tomography (CT)-derived lung volumes to predict a donor-recipient lung size match during bilateral lung transplants.MethodsWe reviewed the data of 62 patients who underwent bilateral lung transplantation for interstitial lung disease and/or idiopathic pulmonary fibrosis from 2018 to 2019. Data for recipients was retrieved from the department's transplant database and medical records, and the donor's data was retrieved from the DonorNet. The data included demographic data, lung heights, measured total lung capacity (TLC) from plethysmography for recipients and estimated TLC for donors, clinical data, and CT-derived lung volumes in both pre- and post-transplant recipients. The post-transplant CT-derived lung volume in recipients was used as a surrogate for donor lung CT volumes due to inadequate or poor donor CT data. Computed tomography–derived lung volumes were calculated using thresholding, region growing, and cutting techniques on Computer-Aided Design and Mimics (Materialise NV, Leuven, Belgium) programs. Preoperative CT-derived lung volumes in recipients were compared with the plethysmography TLC, Frustum Model, and donor-predicted TLC. The ratio of the recipient's pre-and postoperative CT-derived volumes, the ratio of preoperative CT-derived lung volume, and donor-estimated TLC were studied to detect a correlation with 1-year outcomes.ResultsThe recipient preoperative CT-derived volume correlated with the recipient preoperative plethysmography TLC (Pearson correlation coefficient [PCC] of 0.688) and with the recipient Frustum model volume (PCC of 0.593). The recipient postoperative CT-derived volume correlated with the recipient's postoperative plethysmography TLC (PCC of 0.651). There was no statistically significant correlation between recipients' CT-derived pre- or postoperative volume with donor-estimated TLC. The ratio of preoperative CT-derived volume to donor-estimated TLC correlated inversely with the length of ventilation (P value = .0031). The ratio of postoperative CT-derived volume to preoperative CT-derived volume correlated inversely with delayed sternal closure (P = .0039). No statistically significant correlations were found in evaluating outcomes related to lung oversizing in the recipient (defined as a postoperative to preoperative CT-derived lung volume ratio of >1.2).ConclusionsGenerating CT-derived lung volumes is a valid and convenient method for evaluating lung volumes for transplantation in patients with ILD and/or IPF. Donor-estimated TLC should be interpreted carefully. Further studies should derive donor lung volumes from CT scans for a more accurate evaluation of lung size matching.