Evaluation of Induction Immunosuppression and Risk of Incisional Hernia After Liver Transplantation.

INTRODUCTION: Liver transplantation (LT) is a technically complex operation and usually performed on ill patients. A major postoperative morbidity is incisional hernia, occurring in 9.5%-32.4% of cases. There are mixed results in transplant studies regarding potential risk factors. Additionally, the literature is lacking in the relationship between specific immunosuppressive induction agents administered during LT and postoperative incisional hernia. METHODS: A single center, retrospective cohort study of patients who underwent primary LT between 4/2011-1/2018 was conducted. Clinical variables including demographics and comorbidities were reviewed. The primary end point was the development of an incisional hernia following LT. Sub analysis was performed for secondary end points to determine potential risk factors, including immunosuppressive induction agent. RESULTS: Overall, 418 patients met inclusion criteria. At 5 y post-LT, there were 66/271 (24.4%) and 53/147 (36.1%) patients diagnosed with an incisional hernia in the methylprednisolone and basiliximab groups, respectively. After propensity score matching, there was no difference in incisional hernia development between induction agents, P = 0.19. For patients with body mass index ≥30 and postoperative seroma of the abdominal wall, the hazard ratios were 2.67 (95% CI = 1.7, 4.3) and 2.03 (95% CI = 1.1, 3.9), respectively. CONCLUSIONS: Incisional hernia rate after LT was 28.5% at 5 y. Our analysis found that immunosuppressive induction agent at LT was not associated with the development of postoperative incisional hernia. However, preoperative obesity (body mass index ≥30) and postoperative seroma of the abdominal wall were potential risk factors. Further studies are needed to delineate if these risk factors remain across institutions and in alternative settings.

Outcomes of kidney transplantation in patients with IgA nephropathy based on induction: A UNOS data analysis.

INTRODUCTION: IgA nephropathy (IgAN) can cause end-stage kidney disease (ESKD). This study assesses the impact of induction and maintenance immunosuppression on IgAN recurrence, graft survival, and mortality in living and deceased donor kidney transplants (LDKT and DDKT). METHODS: Retrospective analysis of the UNOS database in adults with ESKD secondary to IgAN who received kidney transplants between January 2000 and June 30, 2022. Patients with thymoglobulin (ATG), alemtuzumab, or basiliximab/daclizumab induction with calcineurin inhibitor (CNI) and mycophenolate mofetil (MMF) with or without prednisone maintenance were analyzed. Multivariate logistic regression was performed to identify factors correlated with IgA recurrence. Multivariable Cox regression analyses were performed for clinically suspected risk factors. Kaplan Meir Analysis was utilized for overall graft survival. RESULTS: Compared to ATG with steroid maintenance, alemtuzumab with steroid increased the odds of IgAN recurrence in DDKTs (OR 1.90, p < .010, 95% CI [1.169-3.101]). Alemtuzumab with and without steroid increased the odds of recurrence by 52% (p = .036) and 56% (p = .005), respectively, in LDKTs. ATG without steroids was associated with less risk of IgAN recurrence (HR .665, p = .044, 95% CI [.447-.989]), graft failure (HR .758, p = .002, 95% CI [.633-.907]), and death (HR .619, p < .001, 95% CI [.490-.783]) in DDKTs. Recurrence was strongly associated with risks of graft failure in DDKTs and LDKTs and death in LDKTs. CONCLUSION: In patients with IgAN requiring a kidney transplant, Alemtuzumab induction correlates with increased IgAN recurrence. Relapse significantly affects graft survival and mortality. ATG without steroids is associated with the least graft loss and mortality.

Assessment of immunosuppression induction with basiliximab compared to antithymocyte-globulin in adult heart transplant patients.

BACKGROUND: Patients undergoing heart transplants are at risk of rejection which can have significant morbidity and mortality. Induction immunosuppression at the time of transplant reduces the early risk and has additional benefits. The induction agent of choice within our program was changed from rabbit antithymocyte-globulin (rATG) to basiliximab, so it was necessary to evaluate whether this had any impact on patient outcomes. OBJECTIVES: Our primary objective was to describe rejection, infection, and other outcomes in adult heart transplant patients at the University of Alberta Hospital in Edmonton, Canada. METHODS: This study was a nonrandomized, retrospective cohort study. RESULTS: Sixty-three patients were included with median ages 50 years versus 54 years. More female patients received rATG (20% vs. 42.4%). The most common indication for transplant in both cohorts was ICM (63.3% vs. 57.6%). Patients who received rATG had significantly higher PRA (0% vs. 43%, p < .001). Acute rejection episodes were similar between basiliximab and rATG at 3 months (16.7% vs. 15.1%; p = 1.0) and 6-months (30.0% vs. 18.1%; p = .376). Infections were not statistically different with basiliximab compared to rATG at 3-months, 43.3% vs. 63.6% and at 6-months 60.0% vs. 66.7%). There were no fatalities in either group. CONCLUSIONS: Our study did not demonstrate differences in rejection with basiliximab compared to rATG. Mortality did not differ, but basiliximab-treated patients had fewer infections and infection-related hospitalizations than those treated with rATG. Larger studies with longer durations are needed to more completely describe the differences in rejection and infectious outcomes.

A heart transplant center experience with basiliximab induction strategies: A double edged sword?

BACKGROUND: The use of induction immunosuppression for heart transplantation (HT) is debated given the uncertain benefit and potential risks of infection and malignancy. METHODS: This is a retrospective single-center analysis of 475 consecutive HT recipients from 2003 to 2020 grouped by use of induction with basiliximab group (BG) and the no basiliximab group (NBG). Subgroup analysis by era compared pre-2016 standard-basiliximab (BX) induction and 2016-2020 with selective-BX use as part of a calcineurin-inhibitor-sparing regimen. RESULTS: When adjusted for confounders (sex, age, PRA, eGFR), the BG was less likely to have acute cellular rejection (ACR) (OR.42, p < .001), but had more antibody mediated rejection (AMR) (OR 11.7, p < .001) and more cardiac allograft vasculopathy (CAV) (OR 3.8, p = .04). There was no difference between BG and NBG in the incidence of malignancies or infections. When stratified by era (pre-2016 vs. 2016-2020), ACR remained less common in the BG than the NBG (36% vs. 50%, p = .045) groups, while AMR remained more common (9.7 vs. 0% p = .005). There was no significant difference in conditional survival comparing pre-and post-2016 NBG (HR 2.20 (95% CI.75-6.43); however, both pre-2016 BG and post-2016 BG have significantly higher mortality (HR 2.37 [95% CI 1.02-5.50) and HR 2.69 (95% CI 1.08-6.71), p = .045 and.03, respectively]. CONCLUSION: Basiliximab reduces the incidence of ACR but increases the risk of AMR, CAV, and may be associated with increased mortality. Mechanistic studies are needed to describe a potential T-cell-escape mechanism with enhanced humoral immunity.

Induction therapy in heart transplantation: A systematic review and network meta-analysis for developing evidence-based recommendations.

INTRODUCTION: Induction therapy (IT) utility in heart transplantation (HT) remains contested. Commissioned by a clinical-practice guidelines panel to evaluate the effectiveness and safety of IT in adult HT patients, we conducted this systematic review and network meta-analysis (NMA). METHODS: We searched for studies from January 2000 to October 2022, reporting on the use of any IT agent in adult HT patients. Based on patient-important outcomes, we performed frequentist NMAs separately for RCTs and observational studies with adjusted analyses, and assessed the certainty of evidence using the GRADE framework. RESULTS: From 5156 publications identified, we included 7 RCTs and 12 observational studies, and report on two contemporarily-used IT agents-basiliximab and rATG. The RCTs provide only very low certainty evidence and was uninformative of the effect of the two agents versus no IT or one another. With low certainty in the evidence from observational studies, basiliximab may increase 30-day (OR 1.13; 95% CI 1.06-1.20) and 1-year (OR 1.11; 95% CI 1.02-1.22) mortality compared to no IT. With low certainty from observational studies, rATG may decrease 5-year cardiac allograft vasculopathy (OR .82; 95% CI .74-.90) compared to no IT, as well as 30-day (OR .85; 95% CI .80-.92), 1-year (OR .87; 95% CI .79-.96), and overall (HR .84; 95% CI .76-.93) mortality compared to basiliximab. CONCLUSION: With low and very low certainty in the synthetized evidence, these NMAs suggest possible superiority of rATG compared to basiliximab, but do not provide compelling evidence for the routine use of these agents in HT recipients.

Impact of early immunosuppression on pediatric liver transplant outcomes within 1 year.

OBJECTIVES: The Starzl Network for Excellence in Pediatric Transplantation identified optimizing immunosuppression (IS) as a priority practice improvement area for patients, families, and providers. We aimed to evaluate associations between clinical characteristics, early IS, and outcomes. METHODS: We analyzed pediatric liver transplant (LT) data from 2013 to 2018 in the United Network for Organ Sharing (UNOS) and the Society of Pediatric Liver Transplantation (SPLIT) registries. RESULTS: We included 2542 LT recipients in UNOS and 1590 in SPLIT. IS choice varied between centers with steroid induction and mycophenolate mofetil (MMF) use each ranging from 0% to 100% across centers. Clinical characteristics associated with early IS choice were inconsistent between the two data sets. T-cell depleting antibody use was associated with improved 1-year graft (hazard ratio [HR] 0.50, 95% confidence interval [CI] 0.34-0.76) and patient (HR 0.40, 95% CI 0.20-0.79) survival in UNOS but decreased 1-year patient survival (HR 4.12, 95% CI 1.31-12.93) and increased acute rejection (HR 1.58, 95% CI 1.07-2.34) in SPLIT. Non-T-cell depleting antibody use was not associated with differential risk of survival nor rejection. MMF use was associated with improved 1-year graft survival (HR 0.73, 95% CI 0.54-0.99) in UNOS only. CONCLUSIONS: Variation exists in center choice of early IS regimen. UNOS and SPLIT data provide conflicting associations between IS and outcomes in multivariable analysis. These results highlight the need for future multicenter collaborative work to identify evidence-based IS best practices.

Efficacy and safety of single-dose anti-thymocyte globulin versus basiliximab induction therapy in pediatric kidney transplant recipients: A retrospective comparative cohort study.

BACKGROUND: This study aimed to compare the efficacy and safety of basiliximab (BAS) versus a single dose of anti-thymocyte globulin (r-ATG) induction therapy in pediatric kidney transplant recipients (KTRs). METHODS: This single-center retrospective comparative cohort study included all pediatric KTRs from May 2013 to April 2018 and followed up to 12 months. In the first period, all recipients received BAS, while from May 2016, a single 3 mg/kg dose of r-ATG was instituted. Maintenance therapy consisted of a calcineurin inhibitor plus prednisone plus azathioprine or mycophenolate. RESULTS: A total of 227 patients were included (BAS, n = 113; r-ATG, n = 114). The main combination of immunosuppressive drugs was tacrolimus, prednisone, and azathioprine in both groups (87% vs. 88%, p = .718). Patients receiving r-ATG showed superior survival-free of the composite endpoint (acute rejection, graft loss, or death; 76% vs. 61%, p = .003; HR 2.08, 1.29-3.34, p = .003) and lower incidence of biopsy-proven acute rejection (10% vs. 21%, p = .015). There was no difference in the overall incidence of CMV infection (33% vs. 37%, p = .457), PTLD (1% vs. 3%, p = .309), 30-day hospital readmissions (24% vs. 23%, p = .847), and kidney function at 12 months (86 ± 29 vs. 84 ± 30 mL/min/1.73m2, p = .614). CONCLUSIONS: These data suggest that induction therapy with a single 3 mg/kg dose of r-ATG is associated with higher efficacy for preventing acute rejection and similar safety profile compared to BAS.

Ruxolitinib versus basiliximab for steroid-refractory acute graft-versus-host disease: a retrospective study.

Acute graft-versus-host disease (aGVHD) remains a major limitation of allogeneic hematopoietic stem cell transplantation; not all patients respond to standard glucocorticoids treatment. This study retrospectively evaluated the effects of ruxolitinib compared with basiliximab for steroid-refractory aGVHD (SR-aGVHD). One hundred and twenty-nine patients were enrolled, 81 in ruxolitinib and 48 in basiliximab group. The overall response (OR) at day 28 was higher in ruxolitinib group (72.8% vs. 54.2%, P = 0.031), as with complete response (CR) (58.0% vs. 35.4%, P = 0.013). Ruxolitinib led to significantly lower 1-year cumulative incidence of chronic GVHD (cGVHD) (29.6% vs. 43.8%, P = 0.021). Besides, ruxolitinib showed higher 1-year overall survival (OS) and 1-year cumulative incidence of failure-free survival (FFS) (OS: 72.8% vs. 50.0%, P = 0.008; FFS: 58.9% vs. 39.6%, P = 0.014). The 1-year cumulative incidence of non-relapse mortality (NRM) was lower in ruxolitinib group (16.1% vs. 37.5%, P = 0.005), and the 1-year relapse was not different. The 1-year cumulative incidence of cytomegalovirus (CMV) viremia, CMV-associated diseases and Epstein-Barr virus (EBV)-associated diseases was similar between the two groups, but EBV viremia was significantly lower in ruxolitinib group (6.2% vs. 29.2%, P < 0.001). Subgroup analyses revealed that OR and survival were similar in ruxolitinib 5 mg twice daily (bid) and 10 mg bid groups. However, ruxolitinib 10 mg bid treatment markedly reduced 1-year cumulative incidence of cGVHD compared with 5 mg bid (21.1% vs. 50.0%, P = 0.016). Our study demonstrated that ruxolitinib was superior to basiliximab in SR-aGVHD treatment and cGVHD prophylaxis, therefore should be recommended.

Impact of induction therapy on cytomegalovirus infection and post-transplant outcomes in pediatric heart transplant recipients receiving routine antiviral prophylaxis.

OBJECTIVES: Induction therapy has been increasingly used in pediatric heart transplantation. This study evaluated the impact of anti-thymocyte globulin (ATG) versus basiliximab as induction therapy on post-transplant cytomegalovirus (CMV) infection, rejection at 1 year, coronary allograft vasculopathy (CAV), and mortality in pediatric heart transplant recipients receiving antiviral prophylaxis. RESULTS: Of the 96 patients (age < 18 years) analyzed, 46 (47.9%) patients received basiliximab, and 50 (52.1%) received ATG. Median follow-up was 3.0 (IQR, 1.7-4.9) years with 32.3% reporting CMV infection. The ATG group, as compared with the basiliximab group, had similar incidences of CMV infection (36% vs. 28.3%, p = .418), CMV viremia (22% vs. 19.6%, p = .769), and CMV-positive tissue biopsy (30% vs. 22%, p = .486). The ATG group had lower incidences of rejection at 1 year (16% vs. 36.9%, p = .022) and CAV (4% vs. 23.9%, p = .006) with no difference in mortality (8% vs. 15.2%, p = .343), compared with the basiliximab group. Multivariate analysis showed that induction with ATG was associated with a lower risk of rejection at 1 year (OR, .31; 95% CI, .09-.94; p = .039) with no impact on the incidences of CMV infection (HR, 2.06; 95% CI, .54-7.89; p = .292), CAV (HR, .30; 95% CI, .04-2.58; p = .275), and mortality (HR, .39; 95% CI, .09-1.82; p = .233) compared to basiliximab induction. DISCUSSION AND CONCLUSIONS: In conclusion, induction with ATG was associated with reduction in risk of rejection at 1 year with no effects on CMV infection, CAV, and mortality in pediatric heart transplant recipients with universal antiviral prophylaxis compared with basiliximab induction therapy.

Basiliximab induction versus no induction in adult heart transplantation.

BACKGROUND: Induction immunosuppression in heart transplant recipients varies greatly by center. Basiliximab (BAS) is the most commonly used induction immunosuppressant but has not been shown to reduce rejection or improve survival. The objective of this retrospective study was to compare rejection, infection, and mortality within the first 12 months following heart transplant in patients who received BAS or no induction. METHODS: This was a retrospective cohort study of adult heart transplant recipients given BAS or no induction from January 1, 2017 to May 31, 2021. The primary endpoint was incidence of treated acute cellular rejection (ACR) at 12-months post-transplant. Secondary endpoints included ACR at 90 days post-transplant, incidence of antibody-mediated rejection (AMR) at 90 days and 1 year, incidence of infection, and all-cause mortality at 1 year. RESULTS: A total of 108 patients received BAS, and 26 patients received no induction within the specified timeframe. There was a lower incidence of ACR within the first year in the BAS group compared to the no induction group (27.7 vs. 68.2%, p < .002). BAS was independently associated with a lower probability of having a rejection event during the first 12-months post-transplant (hazard ratio (HR) .285, 95% confidence interval [CI] .142-.571, p < .001). There was no difference in the rate of infection and in mortality after hospital discharge at 1-year post-transplant (6% vs. 0%, p = .20). CONCLUSION: BAS appears to be associated with greater freedom from rejection without an increase in infections. BAS may be a preferred to a no induction strategy in patients undergoing heart transplantation.

Basiliximab as maintenance immunosuppression in heart transplant recipients: A single pediatric center experience.

BACKGROUND: Pediatric heart transplant recipients are at risk for complications from prolonged exposure to immunosuppressive drugs, pharmacokinetic challenges in maintaining consistent immunosuppression, and medication non-adherence. Basiliximab (BAS), an interleukin-2 receptor antagonist, is used for induction therapy across many pediatric heart transplant centers, but use as maintenance immunosuppression has not been well described. METHODS: This was a retrospective, single pediatric center cohort study of heart transplant recipients who received BAS for maintenance immunosuppression (defined as >2 monthly doses) from January 1, 2011, to December 31, 2021. RESULTS: Ten patients met study criteria with a median age of 17.5 (5-22) years and median 9.6 (1.2-18.9) years since transplant at time of BAS initiation. The primary indications for BAS use were recurrent rejection (n = 4), fluctuating immunosuppression levels (n = 3), and renal dysfunction (n = 3). A median of 5.5 (3-32) monthly BAS doses were received. Three patients had a rejection event while on BAS. Calcineurin inhibitor exposure was reduced in 70% of patients. Three of the 10 patients were alive at last follow-up. There was one documented infection during BAS use, and no hypersensitivity reactions. CONCLUSIONS: Monthly BAS infusions were well tolerated and allowed for reduced calcineurin inhibitor exposure in most patients. Mortality commonly occurred despite BAS use, potentially reflecting the acuity of this patient cohort. BAS can be considered for maintenance immunosuppression in pediatric patients with fluctuating immunosuppressive levels and/or renal dysfunction. More studies are needed to determine long-term outcomes and explore expanded use of BAS in the pediatric heart transplant population.

Basiliximab therapy for immune-mediated bowel disease in a pediatric heart transplant patient.

In pediatric patients who undergo heart transplantation, severe immune-mediated bowel disease has been reported. Management is complex, and there are little data discussing the use of basiliximab for immune-mediated bowel disease. This case report discusses a pediatric patient who developed immune-mediated bowel disease following heart transplantation and was successfully managed with basiliximab.

Impact of Induction Immunosuppressants on T Lymphocyte Subsets after Kidney Transplantation: A Prospective Observational Study with Focus on Anti-Thymocyte Globulin and Basiliximab Induction Therapies.

Induction immunosuppressive therapy for kidney transplant recipients (KTRs) primarily includes interleukin-2 receptor antagonists, such as basiliximab (BXM) or lymphocyte-depleting agents, and anti-thymocyte globulin (ATG). This study aimed to investigate their effects on T cell dynamics during the early post-transplantation period. This prospective observational study included 157 KTRs. Peripheral blood samples were collected from each patient within 5 days before and 4 and 12 weeks after transplantation. Flow cytometric analysis was performed to assess various T cell subsets whose changes were then analyzed. In the ATG group, CD4+ T cell expression decreased significantly compared with that in the BXM group. However, CD4+CD161+ and CD4+CD25+CD127low T cell expression levels increased significantly. In the CD8+ T cell subset, a decrease in CD8+CD28nullCD57+ and CD8+CCR7+ T cell expression was observed in the ATG group. However, among patients diagnosed with biopsy-proven acute rejection, T cell subset expression did not significantly differ relative to non-rejection cases. In conclusion, ATG induction therapy resulted in more pronounced changes in T lymphocyte subsets than BXM induction, with increased CD4+CD161+ and CD4+CD25+CD127low T cells and an early decrease in CD8+CD28nullCD57+ and CD8+CCR7+ T cells, some of which are associated with acute rejection.

124I Radiolabeled Basiliximab for CD25-Targeted Immuno-PET Imaging of Activated T Cells.

Activated T cells played critical roles in immunotherapy and adoptive T cell therapy, and a non-invasive imaging strategy can provide us useful information concerning the transportation, accumulation, and homing of T cells in vivo. In this paper, by utilizing the long half-life radionuclide iodine-124 (124I) and CD25 specific monoclonal antibody Basiliximab, we have fabricated a novel probe, namely, 124I-Basiliximab, which was highly promising in the immuno-PET imaging of T cells. In vitro, 124I-Basiliximab had superior affinity to CD25 protein (Kd = 5.31 nM) and exhibited much higher accumulation in CD25 high-expression lymphoma cell line Karpas299 than that in CD25-negative cell line Daudi. In vivo, 124I-Basiliximab was excreted slowly from the body of mice, rendering it a relatively high effective dose (0.393 mSv/MBq) when applied in the immuno-PET imaging. In Karpas299 tumor xenograft, 124I-Basiliximab probe was observed to accumulate in the tumor quickly after tracer administration, with the optimal image acquired at 24 h post-injection. More importantly, PHA-activated hPBMC had much higher uptake of 124I-Basiliximab, indicating the potential utility of 124I-Basiliximab to discriminate activated hPBMC from its non-activated status. In summary, 124I-Basiliximab was fabricated for the first time, which can be applied in CD25-targeted immuno-PET imaging of activated T cells in vivo.

Is CD25 blockade optimal in kidney transplant patients treated with basiliximab? A target-mediated drug disposition model.

AIMS: Basiliximab, an anti-CD25 chimeric monoclonal antibody, is approved in prevention of acute kidney transplant rejection. This study aims at investigating target-mediated pharmacokinetics of basiliximab. METHODS: Data from the IDEALE study, where 16 kidney transplant patients were treated with 2 40- or 80-mg basiliximab injections, were reanalysed. Basiliximab pharmacokinetics was described using a population 2-compartment target-mediated drug disposition model with the quasi-steady-state approximation. RESULTS: Volume of distribution was significantly higher in males (P = .029). Estimated baseline target antigen (CD25) level was lower is patients cotreated with cyclosporine (P = .026). CONCLUSION: This analysis allows the first description of the target-mediated nonlinear elimination of basiliximab. Our results suggest that cyclosporine cotreatment is associated with decreased target level and that an optimized dosing regimen may improve basiliximab effects.

Reduced calcineurin inhibitor exposure with antibody induction and recurrent hepatocellular carcinoma after liver transplantation.

BACKGROUND: Hepatocellular carcinoma (HCC) is a common indication for liver transplantation (LT), but post-LT tumor recurrence remains a concern. Early post-LT immunosuppression is suggested to affect recurrence risk. We evaluated the impact on HCC recurrence of an immunosuppression protocol introduced in 2010 with interleukin-2 receptor antibody (IL-2RA) induction and delayed-introduction of reduced-dose tacrolimus with mycophenolate. METHODS: We included consecutive HCC patients transplanted 2000-2017 in Gothenburg. The impact on HCC recurrence of IL-2RA induction and mean tacrolimus trough concentration during the first 20 post-LT days was analyzed by multivariable Cox regression and propensity score-adjusted analyses. RESULTS: The study comprised 235 patients (mean age 57 yrs, men 80%, mean MELD 13, within Milan criteria 57%). The cumulative 5-yr HCC recurrence rate among patients transplanted before and after 2010 were 28.6% and 19.7%, respectively. IL-2RA induction had no independent effect on HCC recurrence. High tacrolimus exposure (mean 20-day tacrolimus concentration ≥8ng/mL) was associated with increased HCC recurrence risk on univariable analysis (HR 2.22, 95% CI 1.23-4.01, p = .008), but was non-significant on multivariable analysis (p = .17). Outside Milan criteria, high tacrolimus exposure was significant for HCC recurrence (HR 3.68, 95% CI 1.34-10.11, p = .012) independently of tumor characteristics and AFP level. This was confirmed on multivariable propensity score-adjusted analysis. CONCLUSIONS: Reduced early tacrolimus exposure, facilitated by IL-2RA induction, was associated with reduced risk for HCC recurrence among patients outside Milan criteria. Prospective studies are needed to confirm if early tacrolimus-minimization strategies can help reduce HCC recurrence rates and help extend transplant criteria.

Risk factors of bronchial dehiscence after primary lung transplantation.

BACKGROUND: Although the incidence of bronchial dehiscence following lung transplantation has decreased significantly due to improvements in perioperative managements and surgical techniques, it remains a devastating postoperative complication associated with high morbidity and mortality. METHODS: We retrospectively reviewed 811 lung transplantation performed at our institution between January 2011 and December 2020. Bronchial dehiscence was confirmed with flexible bronchoscopy, computed tomography (CT) scan, or clinical findings grade using International Society for Heart and Lung Transplantation recommendations. RESULTS: Bronchial dehiscence was diagnosed in 38 patients (4.7%). The overall survival rates of the patients with bronchial dehiscence were significantly worse than those of the patients without bronchial dehiscence (p = .003). Multivariate analysis identified use of our basiliximab induction protocol (odds ratio = 3.03, p = .008) as an independent predictive factor of postoperative airway dehiscence in our multivariable model, along with total ventilator duration (odds ratio = 1.02, p = .002). CONCLUSIONS: Based on our analysis, patients that underwent our basiliximab induction protocol for lung transplantation experienced a higher rate of postoperative bronchial dehiscence when compared with patients who receive alemtuzumab induction. We believe this may be associated with a higher steroid exposure in this population. Additional studies are necessary to further characterize the relationship between different induction protocols and bronchial dehiscence following transplantation.

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OBJECTIVES: Liver transplant recipients have a high rate of postoperative infection, and identification of patients at high risk for bacterial and fungal infections will help prevent disease and improve long-term outcomes for them. This study aims to understand the composition, distribution, prognosis of bacterial and fungal infections within 2 months after liver transplantation and to analyze their risk factors. METHODS: The data of pathogen composition, distribution, and prognosis of bacterial and fungal infections among liver transplant recipients in the Third Xiangya Hospital of Central South University from May 2020 to October 2021 were collected, and the risk factors for these infections were analyzed. RESULTS: A total of 106 episodes of bacterial or fungal infections occurred in 71.4% of liver transplant recipients (75/105). Gram-negative bacteria were the dominant pathogenic bacteria (49/106, 46.2%), followed by Gram-positive bacteria (31/106, 29.2%). The most common Gram-negative bacterium was Acinetobacter baumannii (13/106, 12.3%). The most common Gram-positive bacterium was Enterococcus faecium (20/106, 18.9%). The most common infections were pulmonary (38/105, 36.2%) and multiple site infections (30/105, 28.6%). Six (6/105, 5.7%) patients with infections died within 2 months after liver transplantation. Univariate analysis showed that the model for end-stage liver disease (MELD) score ≥25, antibiotic use within half a month before transplantation, infections within 2 months prior to transplantation, intraoperative red blood cell infusion≥8 U, indwelling urinary tract catheter ≥4 days after transplantation, and the dosage of basiliximab use ≥40 mg were associated with infections. Multivariate logistic regression analysis revealed that only infections within 2 months prior to transplantation (OR=5.172, 95% CI 1.905-14.039, P<0.01) was an independent risk factor for bacterial and fungal infections after liver transplantation. Postoperative bacterial and fungal infections were reduced in liver transplant recipients receiving basiliximab ≥40 mg (OR=0.197, 95% CI: 0.051-0.762, P<0.05). CONCLUSIONS: The incidence of bacterial and fungal infections is high in the early stage after liver transplantation, and the mortality after infection is significantly higher than that of non-infected patients. The most common infection is respiratory infection, and the dominant pathogens is Gram-negative bacteria. Patients infected within 2 months prior to liver transplantation are prone to bacterial and fungal infections. Standard use of basiliximab can reduce the incidence of infections after liver transplantation.

Impact of induction strategy change on first-year rejection in pediatric heart transplantation at a single center-From postoperative basiliximab to either postoperative anti-thymocyte globulin or preoperative basiliximab.

BACKGROUND: Our pediatric heart transplant center transitioned from post-bypass basiliximab (BAS) induction to either anti-thymocyte globulin (ATG) or pre-bypass BAS. The purpose of this study was to compare first-year rejection rates before and after this change. METHODS: A single-center retrospective analysis was conducted of pediatric heart transplant recipients from 2010 to 2019. Primary outcome was first-year rejection. Bivariate analysis, Kaplan-Meier curves, and multivariable regression were performed across eras. RESULTS: Forty-three early era patients (55%) received post-bypass BAS, and 35 late era patients (45%) received pre-bypass BAS (n = 17) or ATG (n = 18). First-year rejection decreased in the late era (31% vs 53%, p = .05). This finding was more pronounced after excluding infants (38% vs 73%, p = .006). Late era was associated with a decreased likelihood of rejection (all cohort OR 0.19, 95% CI 0.05-0.66; infants excluded OR 0.17, 95% CI 0.04-0.61). No differences in post-transplant lymphoproliferative disease, donor-specific antibody, or infection were observed. CONCLUSIONS: Fewer late era patients receiving ATG or pre-bypass BAS induction had first-year rejection compared to the early era patients receiving standard post-bypass BAS induction. This programmatic shift in induction strategy was readily achievable and potentially effective in reducing first-year rejection.

Basiliximab as Treatment for Steroid-Refractory Acute Graft-versus-Host Disease in Pediatric Patients after Haploidentical Hematopoietic Stem Cell Transplantation.

Basiliximab has been used successfully as a second-line treatment for steroid-refractory (SR) acute graft-versus-host disease (aGVHD) in adult patients after haploidentical hematopoietic stem cell transplant (haplo-HSCT) but has not been studied separately in the pediatric setting. We retrospectively reviewed 100 pediatric patients after haplo-HSCT receiving basiliximab for grades II (57%), III (27%), and IV (16%) SR aGVHD between January 2015 and December 2017. The median number of basiliximab doses was 4 (range, 2 to 9). The day 28 overall response rate was 85%, with complete response in 74% of patients, partial response in 11% of patients, and no response in 15% of patients. The day 28 overall response rates were 94.6% in skin SR aGVHD, 81.6% in gut SR aGVHD, and 66.7% in liver SR aGVHD. Infectious complications included bacterial infection (11%), presumed or documented fungal infections (7%), cytomegalovirus viremia (53%), Epstein-Barr virus viremia (11%), human herpesvirus-6 viremia (7%), and herpes simplex virus viremia (1%). The 3-year overall survival, disease-free survival, nonrelapse mortality, and relapse rates between responders and nonresponders were 81.3% versus 46.7% (P < .001), 79.0% versus 46.7% (P = .001), 6.1% versus 33.3% (P < .001), and 14.9% versus 20.0% (P = .46), respectively. We conclude that basiliximab is an effective second-line agent for pediatric patients with SR aGVHD after haplo-HSCT, particularly for skin SR aGVHD.