Showing papers in "Clinical Transplantation in 2018"

The impact of kidney donor profile index on delayed graft function and transplant outcomes: A single-center analysis.

Abstract: Introduction Renal transplant outcomes result from a combination of factors. Traditionally, donor factors were summarized by classifying kidneys as extended criteria or standard criteria. In 2014, the nomenclature changed to describe donor factors with the kidney donor profile index (KDPI). We aim to evaluate the relationship between KDPI and delayed graft function (DGF), and the impact KDPI on transplant outcomes for both donor after cardiac death (DCD) and donor after brain death (DBD). Methods An IRB-approved single-center retrospective chart review was performed from January 1999 to July 2013. The patients were divided into six groups: DBD KDPI ≤60, DBD KPDI 61-84, DBD KDPI ≥85, DCD KDPI ≤60, DCD KPDI 61-84, and DCD KDPI ≥85. Rates of DGF, patient survival, and graft survival were examined among groups. Results A total of 2161 kidney transplants were included. DGF rates increased, and graft and patient survival decreased with increasing KDPI (P .302). There was no significant difference in graft or patient survival in all-comers when comparing DCD and DBD kidneys with equivalent KDPIs (P > .317). Patients with DGF across all categories demonstrated worse graft half-lives. Conclusion The KDPI system is an accurate predictor of donor contributions to transplant outcomes. Recipients of DBD kidneys experience an increase in the rate of DGF as their KDPI increases. DCD kidneys have higher DGF rates than their DBD counterparts with similar KDPIs. Patients with documented post-transplant DGF had between 3- and 5-year shorter graft half-lives when compared to recipients that did not experience DGF. Initiatives to reduce the rate of DGF could provide a significant impact on graft survival and result in a reduction in the number of patients requiring retransplant.

Mycobacterium tuberculosis after solid organ transplantation: A review of more than 2000 cases.

Abstract: Background Mycobacterium tuberculosis (TB) is a common pathogen worldwide, and it may cause significant infection after solid organ transplantation (SOT). We reviewed all reported TB cases to provide an update on its epidemiology, clinical presentation, management, and outcome after SOT. Methods MEDLINE, EMBASE, and OVID were reviewed from January 1, 1998, to December 31, 2016, using keywords tuberculosis and solid organ transplant or transplantation. Results There were 187 publications reporting 2082 cases of TB among kidney (n = 1719), liver (n = 253), heart (n = 77), lung (n = 25), and kidney-pancreas (n = 8) recipients. Among cohort studies, the median incidence was 2.37% (range, 0.05%-13.27%) overall. Most TB disease was considered reactivation of latent infection, occurring beyond the first year after SOT. Early-onset cases were seen among donor-derived TB cases. Fever was the most common symptom. Radiologic findings were highly variable. Extrapulmonary and disseminated TB occurred 29.84% and 15.96%, respectively. Multidrug-resistant TB was rare. Treatment using 4 or 5 drugs was commonly associated with hepatotoxicity and graft dysfunction. All-cause mortality was 18.84%. Conclusions This large review highlights the complexity of TB after SOT. Reactivation TB, donor-transmitted infection, extrapulmonary involvement, and disseminated disease are common occurrences. Treatment of TB is commonly associated with hepatotoxicity and graft dysfunction.

The sarcopenia index: A novel measure of muscle mass in lung transplant candidates

Abstract: Background Frailty, including low muscle mass, is an emerging risk factor for poor outcomes after lung transplant. The sarcopenia index (SI)-(serum creatinine value/cystatin C value) × 100-is a novel blood test to approximate muscle mass. We sought to validate SI among lung transplant patients. Methods We retrospectively identified adult lung transplant recipients from 2000 through 2012 at our institution who underwent computed tomography within 1 year before transplant and had preserved blood samples. Creatinine and cystatin C values were measured using the samples and used to calculate SI. Muscle mass was estimated by computed tomographic measurement of skeletal muscle cross-sectional surface area (SA) at the L1 to L3 vertebral levels. Correlation between SI and SA was evaluated. Results Of 28 patients meeting eligibility criteria, most were white (96%) and men (54%). Median (interquartile range) body mass index, SI, and SA were 25.9 (22-30) kg/m2 , 106 (91-119), and 157 (113-195) cm2, respectively. The Pearson correlation coefficient between SI and SA was significant at L2 (0.43; P = .02) and L3 (0.41; P = .03). Conclusion Sarcopenia index is a potentially objective measure for estimating muscle mass that is noninvasive and less expensive. Sarcopenia index could be considered in lung transplant candidate selection following prospective validation in larger cohorts.

A mobile health technology enabled home-based intervention to treat frailty in adult lung transplant candidates: a pilot study

Abstract: Background Frailty is prevalent in lung transplant candidates (LTC) and is associated with waitlist delisting or death. We performed a pilot study to assess the safety and feasibility of a home-based, mobile health technology-facilitated intervention to treat frailty in LTC. Methods We performed an 8-week, nonrandomized, home-based exercise and nutrition intervention in LTC with Short Physical Performance Battery (SPPB) frailty scores of ≤11. The intervention utilized a customized, mobile device application ("app") enabling monitoring and progression of the intervention in real time. We aimed to evaluate key process measures. Secondarily, we tested whether the intervention could improve frailty scores quantified by the SPPB and Fried Frailty Phenotype (FFP). Results A total of 15 subjects enrolled were 63 ± 5.7 years old; oxygen requirements ranged from 3 to 15LPM. Thirteen subjects completed the intervention. Over 108 subject-weeks, there were no adverse events. Subjects found the app engaging and easy to work with. SPPB frailty improved in 7 (54%) and FFP improved in 8 (62%). There was a strong trend toward improved frailty scores (SPPB change 1.0 ± 1.9; P = .08; FFP change -0.6 ± 1.0; P = .07). Conclusion In this pilot study, we found that a home-based prehabilitation program that leverages mobile health technology to target frailty in LTC is well received, safe, and capable of improving physical frailty scores.

Racial disparities in preemptive referral for kidney transplantation in Georgia.

Abstract: Background Racial disparities persist in access to kidney transplantation. Racial differences in preemptive referral, or referral prior to dialysis start, may explain this discrepancy. Methods Patient-level data on kidney transplant referrals (2005-2012) from all Georgia transplant centers were linked to the United States Renal Data System to examine racial disparities in preemptive referral, waitlisting, and living donor transplant. Adjusted logistic regression and Cox proportional hazard models determined the associations between race (African American vs white) and preemptive referral, and placement on the waitlist and receipt of a living donor kidney, respectively. Results Among 7752 adults referred for transplant evaluation, 20.38% (n = 1580) were preemptively referred. The odds of African Americans being preemptively referred for transplant evaluation were 37% (OR = 0.63; [95% CI: 0.55 0.71]) lower than white patients. Among preemptively referred patients, there was no racial difference (African Americans compared to white patients. HR = 0.96; [95% CI: 0.88, 1.04]) in waitlisting. However, African Americans were 70% less likely than white patients to receive a living donor transplant (HR = 0.30; [95% CI: 0.21, 0.42]). Conclusion Racial disparities in transplant receipt may be partially explained by disparities in preemptive referral. Interventions to reduce racial disparities in kidney transplant access may need to be targeted earlier in the disease process.

Transplant-associated thrombotic microangiopathy: Incidence, prognostic factors, morbidity, and mortality in allogeneic hematopoietic cell transplantation.

Abstract: Renewed interest has emerged in transplant-associated thrombotic microangiopathy (TA-TMA) with novel prognostic, diagnostic, and treatment algorithms. We aimed to investigate the incidence, prognostic factors, morbidity, and mortality of TA-TMA in allogeneic hematopoietic cell transplantation (HCT) recipients. We enrolled consecutive HCT recipients (1990-2017). Among 758 patients, 116 (15.5%) were diagnosed with TA-TMA. In the multivariate analysis, TBI-based conditioning, viral infections, acute and chronic GVHD remained independent predictors of TA-TMA. With a median follow-up of 23 (range 0.1-329) months, TA-TMA resulted in significantly lower overall survival (OS). In the multivariate analysis, TA-TMA remained an independent predictor of OS, along with relapse, acute, and chronic GVHD. Among 116 TA-TMA patients, 70 developed renal (56) and/or neurologic (26) dysfunction that would be necessary for TA-TMA diagnosis according to the Bone Marrow Transplant Clinical Trials Network criteria. TA-TMA patients with renal dysfunction showed increased rates of acute GVHD, but no difference in OS compared to patients without renal dysfunction. However, neurologic dysfunction resulted in significantly lower OS. In conclusion, TA-TMA is associated with increased morbidity and mortality in allogeneic transplant recipients. Successful prevention and treatment strategies of infections and GVHD need to be timely employed to improve survival in this complex setting.

Heart and heart-liver transplantation in adults with failing Fontan physiology.

Abstract: Background As the population of patients with a Fontan palliation grows so does, the number of patients with cardiac failure necessitating orthotopic heart transplant (OHT) and combined heart-liver transplant (CHLT). There is recent evidence that current era cardiac transplant in Fontan patients has improved outcomes, but most studies have a preponderance of pediatrics patients in their cohorts. We examine our institutional experience with adult OHT and CHLT transplantation for failed Fontan physiology. Methods and results Retrospective analysis of patients at the Ahmanson/UCLA Adult Congenital Heart Disease Center who underwent OHT or CHLT for failing Fontan physiology from January 1, 2002 to May 31, 2017. We identified 20 patients with single-ventricle physiology and Fontan palliation who underwent OHT or CHLT. The median age was 29.5 years (range 19-44). Five patients underwent CHLT because of biopsy proven hepatic cirrhosis. The median length of hospital stay was 23 days (range 8-76) post-OHT and 51 days (range 26-77) post-CHLT. During a median follow-up of 56 months (range 2-178), there was one mortality occurring at 34 months post-OHT due to coronary vasculopathy. Most frequent early postoperative complications included bleeding and infection (55% and 20%, respectively) and surgical reintervention for bleeding complications (n = 8, 40%). One CHLT patient experienced clinically significant hepatic rejection requiring admission and steroid treatment. Conclusions Despite inherent risks and complexities of OHT or CHLT in patients with a failed Fontan, transplant is a reasonable therapy. Peri- and postoperative complications are common and may require surgical reintervention. Continued observation of practices and unifying themes may help improve patient selection, pre- and postoperative treatment and ultimately outcomes.

Impact of intraoperative cytokine adsorption on outcome of patients undergoing orthotopic heart transplantation-an observational study.

Abstract: AIM The aim of this study was to assess the influence of intraoperative cytokine adsorption on the perioperative vasoplegia, inflammatory response and outcome during orthotopic heart transplantation (OHT). METHODS Eighty-four OHT patients were separated into the cytokine adsorption (CA)-treated group or controls. Vasopressor demand, inflammatory response described by procalcitonin and C-reactive protein, and postoperative outcome were assessed performing propensity score matching. RESULTS In the 16 matched pairs, the median noradrenaline requirement was significantly less in the CA-treated patients than in the controls on the first and second postoperative days (0.14 vs 0.3 μg*kg-1 *min-1 , P = .039 and 0.06 vs 0.32 μg*kg-1 *min-1 , P = .047). The inflammatory responses were similar in the two groups. There was a trend toward shorter length of mechanical ventilation and intensive care unit (ICU) stay in the CA-treated group compared to the controls. No difference in adverse events was observed between the two groups. The frequency of renal replacement therapy was less in the CA‐treated patients than in the controls. CONCLUSIONS Intraoperative CA treatment was associated with reduced vasopressor demand with a favorable tendency in length of mechanical ventilation, ICU stay and renal replacement therapy. CA treatment was not linked to higher rates of adverse events.

Both sarcopenia and frailty determine suitability of patients for liver transplantation—A systematic review and meta‐analysis of the literature

Abstract: Liver grafts are allocated based on both urgency and utility. Due to a tremendous shortage of suitable organs for liver transplantation (LT), a careful selection of suitable recipients is of utmost importance. While the sickest first principle for organ allocation based on MELD score goes along with poor utility, other parameters reflecting the general health condition like frailty and sarcopenia might be essential to detect suitable patients for the waiting list. Thus, this study was designed to evaluate both frailty and sarcopenia in LT. A systematic review of the literature on sarcopenia and frailty measurements in liver transplant recipients was performed. Thirteen of 238 studies were selected for full paper review. Six of the studies investigating the impact of frailty on waitlist mortality were subjected to a meta-analysis. Despite the different methodologies to assess sarcopenia, reports showed that sarcopenia was highly related to waitlist mortality with a sum of all that highly favored negative outcome in case of sarcopenia. The existing literature clearly underlines that frailty and sarcopenia are important to determine in LT candidates. One unique index for transplant candidates reflecting frailty should be developed and be used as a standard in all transplant centers to facilitate comparability.

Depressive symptoms, frailty, and adverse outcomes among kidney transplant recipients.

Abstract: Depressive symptoms and frailty are each independently associated with morbidity and mortality in kidney transplant (KT) recipients We hypothesized that having both depressive symptoms and frailty would be synergistic and worse than the independent effect of each In a multicenter cohort study of 773 KT recipients, we measured the Fried frailty phenotype and the modified 18-question Center for Epidemiologic Studies-Depression Scale (CES-D) Using adjusted Poisson regression and survival analysis, we tested whether depressive symptoms (CES-D score > 14) and frailty were associated with KT length of stay (LOS), death-censored graft failure (DCGF), and mortality At KT admission, 100% of patients exhibited depressive symptoms, 163% were frail, and 36% had both Recipients with depressive symptoms were more likely to be frail (aOR = 397, 95% CI: 228-691, P < 0001) Recipients with both depressive symptoms and frailty had a 188 times (95% CI: 170-208, P < 0001) longer LOS, 620-fold (95% CI:167-2295, P < 001) increased risk of DCGF, and 262-fold (95% CI:103-670, P = 004) increased risk of mortality, compared to those who were nonfrail and without depressive symptoms There was only evidence of synergistic effect of frailty and depressive symptoms on length of stay (P for interaction < 0001) Interventions aimed at reducing pre-KT depressive symptoms and frailty should be explored for their impact on post-KT outcomes

De novo donor-specific antibody following BK nephropathy: The incidence and association with antibody-mediated rejection.

Abstract: Background and objectives The risk of de novo donor-specific antibody (dnDSA) development following BK viremia (BKV) or nephropathy (BKN) after kidney transplant remains unclear. We aimed to evaluate the relationships among dnDSA, BKV (BK blood PCR > 15 000 copies), BKN, antibody-mediated rejection (AMR), and allograft loss. Patients and methods We performed a retrospective cohort study of 904 solitary kidney transplant recipients transplanted between 10/2007 and 5/2014. Cox proportional hazards regression with time-dependent covariates were used to assess the relationships among BKN, isolated BKV, dnDSA, and the subsequent risk of AMR and allograft loss. Results In multivariate analysis, we observed that BKN, but not BKV was a risk factor for dnDSA (HR, 3.18, P = .008). Of the patients with BK nephropathy, 14.0% (6/43) developed dnDSA, which occurred within 14 months of BK diagnosis. DnDSA in this setting remains a risk factor for subsequent AMR (HR 4.75, P = .0001) and allograft loss (HR 2.63, P = .018). Conclusions BKN is an independent risk factor for development of dnDSA. Improved understanding of the characteristics of patients with BKN who are at highest risk for development of dnDSA would be valuable to customize immunosuppression reduction in this population.

Racial differences in completion of the living kidney donor evaluation process.

Abstract: Racial disparities in living donor kidney transplantation (LDKT) persist but the most effective target to eliminate these disparities remains unknown. One potential target could be delays during completion of the live donor evaluation process. We studied racial differences in progression through the evaluation process for 247 African American (AA) and 664 non-AA living donor candidates at our center between January 2011 and March 2015. AA candidates were more likely to be obese (38% vs 22%: P < .001), biologically related (66% vs 44%: P < .001), and live ≤50 miles from the center (64% vs 37%: P < .001) than non-AAs. Even after adjusting for these differences, AAs were less likely to progress from referral to donation (aHR for AA vs non-AA: 0.26 0.47 0.83; P = .01). We then assessed racial differences in completion of each step of the evaluation process and found disparities in progression from medical screening to in-person evaluation (aHR: 0.41 0.620.94; P = .02) and from clearance to donation (aHR: 0.28 0.510.91; P = .02), compared with from referral to medical screening (aHR: 0.78 1.021.33; P = .95) and from in-person evaluation to clearance (aHR: 0.59 0.931.44; P = .54). Delays may be a manifestation of the transplant candidate's social network, thus, targeted efforts to optimize networks for identification of donor candidates may help address LDKT disparities.

Immediate post-operative broncho-alveolar lavage IL-6 and IL-8 are associated with early outcomes after lung transplantation.

Abstract: INTRODUCTION Previous studies demonstrated that increased cytokine and chemokine levels, either shortly before or after lung transplantation, were associated with post-transplant outcome. However, small patient cohorts were mostly used, focusing on 1 molecule and 1 outcome. In a large single-center cohort, we investigated the predictive value of immediate post-operative broncho-alveolar lavage (BAL) expression of IL-6 and IL-8 on multiple key outcomes, including PGD, CLAD, graft survival, as well as several secondary outcomes. MATERIAL AND METHODS All patients undergoing a first lung transplant in whom routine bronchoscopy with BAL was performed during the first 48 hours post-transplantation were included. IL-6 and IL-8 protein levels were measured in BAL via ELISA. RESULTS A total of 336 patients were included. High IL-6 levels measured within 24 hours of transplantation were associated with longer time on ICU and time to hospital discharge; and increased prevalence of PGD grade 3. Increased IL-8 levels, measured within 24 hours, were associated with PGD3, more ECMO use, higher donor paO2 , younger donor age, but not with other short-or long-term outcome. IL-6 and IL-8 measured between 24 and 48 hours of transplantation were not associated with any outcome parameters. CONCLUSION Recipient BAL IL-6 and IL-8 within 24 hours post-transplant were associated with an increased incidence of PGD3.

Sofosbuvir plus daclatasvir with or without ribavirin is safe and effective for post‐transplant hepatitis C recurrence and severe fibrosis and cirrhosis: A prospective study

Abstract: BACKGROUND In 2012, an Italian Named Patient Program began for hepatitis C virus (HCV)-infected liver transplant (LT) recipients with advanced fibrosis, before approval of direct antiviral agents (DAA), to benefit severely ill patients. The aim of this "real-life" study was to assess treatment efficacy and safety with an extended course of daclatasvir (DCV) plus sofosbuvir (SOF) with or without ribavirin (RBV). METHODS All HCV LT recipients with severe fibrosis in 15 Italian transplant centers were treated with DCV+SOF±RBV for 24 weeks; sustained virological response was assessed at 12 weeks post-treatment (SVR12). RESULTS Eighty-seven patients were enrolled (75.9% males, mean age 58.4 ± 7.2 years, 83.9% genotype 1, 81.6% cirrhosis); 52 (59.8%) received RBV. Overall, 79 obtained SVR12 (90.8%): 100% in F3 and 88.7% in cirrhotics (91.5% in Child-Pugh A, 83.3% in Child-Pugh B and C). According to the treatment group, SVR was 80% in DCV + SOF group and 98.1% in SOF + DCV + RBV. Two virological relapses occurred during follow-up in cirrhotic patients who received DCV + SOF. Four cirrhotic patients in DCV + SOF group and 1 in DCV + SOF + RBV group died on treatment. CONCLUSION An extended course of SOF plus DCV for 24 weeks, with or without RBV, is effective and well tolerated for the treatment of post-LT HCV recurrence with severe fibrosis.

Laparoscopic left lateral section procurement in living liver donors: A single center propensity score‐matched study

Abstract: BACKGROUND Laparoscopic living donor liver procurement for transplantation has increased in popularity over the past decade. The purpose of this study was to compare the laparoscopic and open approaches in living donor left lateral sectionectomy (LLS) and to assess the safety and feasibility of this laparoscopic approach. METHODS A total of 103 living donor LLSs were performed at our center from May 2016 to December 2017. Of these, 35 were completely laparoscopic procedures, which represented the subject of this study. An additional 68 open living donor LLSs performed during the same period were studied as a comparison group. To overcome selection bias, LLS donors were balanced on a 1:1 ratio (laparoscopic [n = 35]: open [n = 35]) according to covariates with similar values. The PSM was based on the operation date, recipient age, diagnosis, recipient weight, and donor age. RESULTS There were significant differences between the laparoscopic and open LLS groups (P < 0.001) in terms of blood loss (96.8 ± 16.5 vs 155.8 ± 17.8 mL) as well as the duration of hospital stay (4 ± 0.4 vs 6.9 ± 0.5 days). CONCLUSION Laparoscopic LLS is a feasible and efficacious in the setting of a developed program with advanced laparoscopic expertise.

Knowledge, attitudes, and planned practice of HIV-positive to HIV-positive transplantation in US transplant centers.

Abstract: BACKGROUND HIV+ donor organs can now be transplanted into HIV+ recipients (HIV D+/R+) following the HIV Organ Policy Equity (HOPE) Act. Implementation of the HOPE Act requires transplant center awareness and support of HIV D+/R+ transplants. METHODS To assess center-level barriers to implementation, we surveyed 209 transplant centers on knowledge, attitudes, and planned HIV D+/R+ protocols. RESULTS Responding centers (n = 114; 56%) represented all UNOS regions. Fifty centers (93 organ programs) planned HIV D+/R+ protocols (kidney n = 48, liver n = 34, pancreas n = 8, heart n = 2, lung = 1), primarily in the eastern United States (28/50). Most (91.2%) were aware that HIV D+/R+ transplantation is legal; 21.4% were unaware of research restrictions. Respondents generally agreed with HOPE research criteria except the required experience with ≥5 HIV+ transplants by organ type. Centers planning HIV D+/R+ protocols had higher transplant volume, HIV+ recipient volume, increased infectious risk donor utilization, and local HIV prevalence (P < 0.01). Centers not planning HIV D+/R+ protocols were more likely to believe their HIV+ candidates would not accept HIV+ donor organs (P < 0.001). Most centers (83.2%) supported HIV+ living donation. CONCLUSIONS Although many programs plan HIV D+/R+ transplantation, center-level barriers remain including geographic clustering of kidney/liver programs and concerns about HIV+ candidate willingness to accept HIV+ donor organs.

Systolic heart failure after liver transplantation: Incidence, predictors, and outcome

Abstract: Although most patients presenting for liver transplantation have normal left ventricular function, some develop left ventricular failure after transplantation. The primary objective of our study was to determine the predictors of systolic heart failure (HF) occurring immediately after liver transplantation. Its etiology, prospects of recovery, and factors associated with nonrecovery were also studied. Liver transplantations performed at our institution from January 2006 to February 2015 were evaluated using prospectively collected institutional registries. Patients with echocardiographically documented decline in ejection fraction to <45% within 6 months after liver transplantation were identified. Four controls were chosen per case: matched for age, gender, transplant year, and model for end-stage liver disease score. Conditional multivariable logistic regression was used for primary analysis and nonparametric tests for comparison between groups. In a cohort of 1284 adult patients, 45 cases and 180 controls were identified. Diastolic dysfunction (DD) was an independent predictor (OR 5.26, 95% CI 1.03-28.57, P = .04) of systolic HF in multivariable analysis. Stress-induced cardiomyopathy was the most common etiology. Left ventricular function recovered in 21 patients. Pretransplant DD decreased the chances of recovery (P = .05). In conclusion, patients with pretransplant DD need close post-transplant follow-up for timely identification of HF.

Tacrolimus trough and dose intra‐patient variability and CYP3A5 genotype: Effects on acute rejection and graft failure in European American and African American kidney transplant recipients

Abstract: BACKGROUND Suboptimal immunosuppression after kidney transplantation contributes to toxicity and loss of efficacy. Little is known regarding the impact of intra-patient variability of tacrolimus (TAC) doses and troughs in the early post-transplant period or the influence of genetic variants on variability. METHODS Coefficients of variation (CV) of TAC troughs and doses of 1226 European American (EA) and 246 African American (AA) adult recipients enrolled in DeKAF Genomics were compared for association with acute rejection and graft failure. Additionally, the influence of recipients' number of CYP3A5 loss-of-function alleles was assessed. RESULTS Acute rejection was associated with greater CV of dose in AA (P < 0.001) and EA recipients (P = 0.012). Graft failure was associated with a greater CV of dose (P = 0.022) and trough (P < 0.001) in AA, and higher CV of trough (P = 0.024) in EA recipients. In EA, CYP3A5 loss-of-function alleles were associated with decreased CV of trough (P = 0.0042) and increased CV of dose (P < 0.0001). CONCLUSION CYP3A5 loss-of-function alleles influence intra-patient TAC trough and dose variability. High variability of TAC dose increases risk of acute rejection. High variability of TAC trough increases risk of graft failure. Early clinical recognition of TAC dose and trough variability may improve patient management and outcomes.

Medical crowdfunding for organ transplantation.

Abstract: An increasing number of patients and families are utilizing online crowdfunding to support their medical expenses related to organ transplantation. The factors influencing the success of crowdfunding campaigns are poorly understood. Crowdfunding campaigns were abstracted from a popular crowdfunding web site. Campaigns were included if they were actively accepting donations to fund medical expenses related to transplantation of selected organs. The primary outcome measure was total amount raised among successful campaigns receiving at least one donation. Bivariate and multivariate analyses were performed on various campaign characteristics. A total of 850 campaigns were analyzed. Kidney transplant campaigns were most common (40.5%), followed by liver (33.3%), lung (12.2%), heart (11.3%), and multiorgan (2.7%). 69.1% of campaigns received any donation, and among these, the mean amount raised was $3664 (median $1175). The following factors were significantly associated with amount raised: more positive emotional sentiment in the campaign description (+2.6% per AFINN unit, P < .001), longer campaign description length (+2.4% per 100 characters, P = .001), higher goal amount (+0.6% per $1000 of goal amount, P = .004), and third-person description perspective (+131% vs first person, P < .001). Physicians will likely encounter medical crowdfunding with increasing frequency as it continues to grow in popularity among their patients.

Impact of the kidney allocation system on young pediatric recipients.

Abstract: The kidney allocation system (KAS) altered pediatric candidate prioritization. We determined KAS's impact on pediatric kidney recipients by examining delayed graft function (DGF) rates from 2010 to 2016. A propensity score-matched pediatric recipients pre- and post-KAS. A semiparametric decomposition analysis estimated the contributions of KAS-related changes in donor characteristics and dialysis time on DGF rate. The unadjusted odds of DGF were 69% higher post-KAS for young (<10 years at listing) recipients (N = 1153, P = .02) but were not significantly increased for older pediatric (10-17 years at listing) recipients (N = 2624, P = .48). Post-KAS, young recipients received significantly fewer pediatric (<18 years) donor kidneys (21% vs 32%, P < .01) and had longer median pretransplant dialysis time (603 vs 435 days, P < .01). After propensity score matching, post-KAS status increased the odds of DGF in young recipients 71% (OR 1.71, 95% CI 1.01-2.46). In decomposition analysis, 24% of the higher DGF rate post-KAS was attributable to donor characteristics and 19% to increased recipient dialysis time. In a confirmatory survival analysis, DGF was associated with a 2.2 times higher risk of graft failure (aHR2.28, 95% CI 1.46-3.54). In conclusion, KAS may lead to worse graft survival outcomes in children. Allocation changes should be considered.

Incidence and predictors of sudden cardiac death after heart transplantation: A systematic review and meta-analysis.

Abstract: Purpose Sudden cardiac death (SCD) is an important post-transplant problem being responsible for ~10% of deaths. We conducted a systematic review and meta-analysis to evaluate incidence and predictors of post-heart transplant SCD and the use of implantable cardiac defibrillator (ICD). Methods Citations were identified in electronic databases and references of included studies. Observational studies on adults reporting on incidence and predictors of post-transplant SCD and ICD use were selected. We meta-analyzed SCD in person-years using random effects models. We qualitatively summarized predictors. Results This study includes 55 studies encompassing 47 901 recipients. The pooled incidence rate of SCD was 1.30 per 100 person-years (95% CI: 1.08-1.52). Cardiac allograft vasculopathy (CAV) was associated with higher SCD risk (2.40 per 100 patient-years, 95% CI: 1.46-3.34). Independent predictors of SCD identified by two moderate-quality studies were older donor age, younger recipient age, non-Caucasian race, reduced left ventricular ejection fraction, rejection, infection, and cancer. Authors rarely reported on ICD use. Conclusion This meta-analysis found that post-transplant SCD risk in heart transplant recipients is higher than that in the general population. CAV was associated with increased SCD risk. Observational studies reporting on absolute risk of SCD are needed to better identify populations at a clinically significant increased risk.

Impact of machine perfusion after long static cold storage on delayed graft function incidence and duration and time to hospital discharge.

Abstract: Delayed graft function (DGF) is very high in our center (70-80%), we usually receive a kidney for transplant after more than 22 hours of static cold ischemia time (CIT). Also, there is an inadequate care of the donors contributing to a high rate of delayed graft function (DGF). We decided to test whether machine perfusion (MP) after a cold ischemic time (CIT) improved the outcome of our transplant patients. We analyzed the incidence of DGF, its duration and the length of hospital stay (LOS) in patients who received a kidney preserved with MP after a CIT (Hybrid Perfusion - HP). We included 54 deceased donors kidneys preserved with HP transplanted from Feb/13 to Jul/14, and compared them to 101 kidney transplants preserved by static cold storage (CS) from Nov/08 to May/12. The median pumping time was 11hours. DGF incidence was 61.1% versus 79.2% (p=0.02), median DGF duration was 5 versus 11 days (p<0.001) and median LOS was 13 versus 18 days (p<0.011), for the HP compared to CS group. The observed reduction of DGF with machine perfusion did not occur in donors over 50 years old. In the multivariate analysis, risk factors for DGF, adjusted for CIT, were donor age (OR, 1.04; p=0.005) and absence of use of MP (OR, 1.54; p=0.051). In conclusion, the use of HP contributed to faster recovery of renal function and to a shorter length of hospital stay. This article is protected by copyright. All rights reserved.

Shedding light on an unknown reality in solid organ transplant patients’ self‐management: A contextual inquiry study

Abstract: Traditional quantitative and qualitative research methods inadequately capture the complexity of patients' daily self-management. Contextual inquiry methodology, using home visits, allows a more in-depth understanding of how patients integrate immunosuppressive medication intake, physical activity, and healthy eating in their daily lives, and which difficulties they experience when doing so. This mixed-method study comprised 2 home visits in 19 purposively selected adult heart, lung, liver, and kidney transplant patients, asking them to demonstrate how they implement the aforementioned health behaviors. Meanwhile, conversations were audio-taped and photographs were taken. Audio-visual materials were coded using directed content analysis. Difficulties and supportive strategies were identified via inductive thematic analysis. We learned that few patients understood what "sufficiently active" means. Physical discomforts and poor motivation created variation across activity levels observed. Health benefits of dietary guidelines were insufficiently understood, and their implementation into everyday life considered difficult. Many underestimated the strictness of immunosuppressive medication intake, and instructions on handling late doses were unclear. Interruptions in routine and busyness contributed to nonadherence. We also learned that professionals often recommend supportive strategies, which patients not always like or need. This contextual inquiry study revealed unique insights, providing a basis for patient-tailored self-management interventions.

Report from the American Society of Transplantation Psychosocial Community of Practice Adherence Task Force: Real-world options for promoting adherence in adult recipients.

Abstract: Starting in 2015, the American Society of Transplantation Psychosocial Community of Practice, with representatives of the Transplant Pharmacy Community of Practice, convened a taskforce to develop a white paper that focused on clinically practical, evidenced-based interventions that transplant centers could implement to increase adherence to medication and behavioral recommendations in adult solid organ transplant recipients. The group focused on what centers could do in their daily routines to implement best practices to increase adherence in adult transplant recipients. We developed a list of strategies using available resources, clinically feasible methods of screening and tracking adherence, and activities that ultimately empower patients to improve their own self-management. We limited the target population to adults because they predominate the research, and because adherence issues differ in pediatric patients, given the necessary involvement of parents/guardians. We also examined broader multilevel areas for intervention including provider and transplant program practices. Ultimately, the task force aims to foster greater recognition, discussion, and solutions required for implementing practical interventions targeted at improving adherence.

First‐line choice for severe aplastic anemia in children: Transplantation from a haploidentical donor vs immunosuppressive therapy

Abstract: We retrospectively compared the outcomes of children with severe aplastic anemia (SAA) who received immunosuppressive therapy (IST) or who underwent hematopoietic stem cell transplantation (HSCT) from a haploidentical donor (HID), between 2007 and 2016. A total of 52 children with SAA under the age of 17 years were initially treated with IST (n = 24) or haploidentical HSCT (n = 28) as first-line treatment. The estimated 10-year overall survival was 73.4 ± 12.6% and 89.3 ± 5.8% in patients treated with IST or HID-HSCT (P = .806). The failure-free survival was significantly inferior in patients receiving IST than in those undergoing transplantation from an HID (52.6 ± 10.5% vs 89.3 ± 5.8, P = .008). In univariate and multivariate analysis, the choice of first-line immunosuppressive therapy was the only adverse predictor for failure-free survival. At the last follow-up, completely normal blood count was observed in 11 of 20 (55.0%) and 24 of 25 (96.0%) live cases in IST and HID-HSCT cohort (P = .003). These suggest that HSCT from a haploidentical donor could be considered as first-line treatment in children who lack a matched related donor, especially in experienced transplantation centers.

The pretreatment neutrophil-lymphocyte ratio may predict prognosis of patients with liver cancer: A systematic review and meta-analysis

Abstract: Background At present, several studies have reported that the pretreatment Neutrophil-Lymphocyte ratio (NLR) may be associated with the prognosis of liver cancer. Nevertheless, their conclusions remain controversial. Thus we performed a meta-analysis of 54 studies to evaluate the prognostic value of NLR. Method Databases including PubMed, Embase, Cochrane Library and Web of Science were searched to July, 2017. Result A total of 54 studies including 12979 patients were included in this meta-analysis. Elevated NLR had a close relationship with the overall survival (OS) (HR 1.52; 95% CI 1.39–1.67), recurrence-free survival (RFS) (HR 1.84; 95% CI 1.48–2.30) and disease-free survival (DFS) (HR 1.71; 95% CI 1.39–2.11) of liver cancer, respectively. In addition, Elevated NLR was associated with the presence of tumor vascular invasion (OR 2.35; 95% CI 1.93–2.86), multiple tumors (OR 1.38; 95% CI 1.15–1.66), alpha-fetoprotein≧400 ng/ml (OR 1.51; 95% CI 1.15–1.98), presence of HbsAg (+) (OR 0.68; 95% CI 0.51–0.90) and cirrhosis (OR: 0.59; 95% CI 0.44–0.80). Conclusion This meta-analysis indicated that elevated NLR may be an effective and noninvasive indicator for prognosis of patients with liver cancer. This article is protected by copyright. All rights reserved.

Dominance of free wall radial motion in global right ventricular function of heart transplant recipients

Abstract: Assessment of right ventricular (RV) function using conventional echocardiography might be inadequate as the radial motion of the RV free wall is often neglected. Our aim was to quantify the longitudinal and the radial components of RV function using three-dimensional (3D) echocardiography in heart transplant (HTX) recipients. Fifty-one HTX patients in stable cardiovascular condition without history of relevant rejection episode or chronic allograft vasculopathy and 30 healthy volunteers were enrolled. RV end-diastolic (EDV) volume and total ejection fraction (TEF) were measured by 3D echocardiography. Furthermore, we quantified longitudinal (LEF) and radial ejection fraction (REF) by decomposing the motion of the RV using the ReVISION method. RV EDV did not differ between groups (HTX vs control; 96 ± 27 vs 97 ± 2 mL). In HTX patients, TEF was lower, however, tricuspid annular plane systolic excursion (TAPSE) decreased to a greater extent (TEF: 47 ± 7 vs 54 ± 4% [-13%], TAPSE: 11 ± 5 vs 21 ± 4 mm [-48%], P < .0001). In HTX patients, REF/TEF ratio was significantly higher compared to LEF/TEF (REF/TEF vs LEF/TEF: 0.58 ± 0.10 vs 0.27 ± 0.08, P < .0001), while in controls the REF/TEF and LEF/TEF ratio was similar (0.45 ± 0.07 vs 0.47 ± 0.07). Current results confirm the superiority of radial motion in determining RV function in HTX patients. Parameters incorporating the radial motion are recommended to assess RV function in HTX recipients.

Metformin use in the first year after kidney transplant, correlates, and associated outcomes in diabetic transplant recipients: A retrospective analysis of integrated registry and pharmacy claims data.

Abstract: While guidelines support metformin as a therapeutic option for diabetic patients with mild-to-moderate renal insufficiency, the frequency and outcomes of metformin use in kidney transplant recipients are not well described. We integrated national U.S. transplant registry data with records from a large pharmaceutical claims clearinghouse (2008-2015). Associations (adjusted hazard ratio, 95% LCL aHR95% UCL ) of diabetes regimens (with and excluding metformin) in the first year post-transplant with patient and graft survival over the subsequent year were quantified by multivariate Cox regression, adjusted for recipient, donor, and transplant factors and propensity for metformin use. Among 14 144 recipients with pretransplant type 2 diabetes mellitus, 4.7% filled metformin in the first year post-transplant; most also received diabetes comedications. Compared to those who received insulin-based regimens without metformin, patients who received metformin were more likely to be female, have higher estimated glomerular filtration rates, and have undergone transplant more recently. Metformin-based regimens were associated with significantly lower adjusted all-cause (aHR 0.18 0.410.91 ), malignancy-related (aHR 0.45 0.450.99 ), and infection-related (aHR 0.12 0.320.85 ) mortality, and nonsignificant trends toward lower cardiovascular mortality, graft failure, and acute rejection. No evidence of increased adverse graft or patient outcomes was noted. Use of metformin-based diabetes treatment regimens may be safe in carefully selected kidney transplant recipients.

Accepting hepatitis C virus-infected donor hearts for transplantation: Multistep consent, unrealized opportunity, and the Stanford experience.

Abstract: The current mismatch between supply and demand of organs has prompted transplant clinicians to consider innovative solutions to broaden the donor pool. Advancements of direct-acting antiviral agent (DAA) therapy for hepatitis C virus (HCV) have allowed entertaining the use of viremic donor organs in nonviremic recipients. In this report, we describe the evolution of HCV treatment, ethics and informed consent, cost-effectiveness of HCV medications in treating acute HCV post-transplantation, and the Stanford experience with two HCV-viremic donor heart transplantations. We describe excellent short-term outcomes post-heart transplantation with HCV NAT-positive organs. The availability of this therapy may expand the donor pool. While we await larger-scale clinical data on the effectiveness and safety of DAA therapy in patients after heart transplantation, many transplant centers have already started accepting organs from HCV-infected donors, balancing the unknown long-term risks versus the benefits of shorter wait times and expansion of the donor pool. Protocols and multidisciplinary teams are needed to effectively communicate risk to potential recipients, to ensure timely DAA access, and to implement appropriate clinical follow-up in order to achieve excellent clinical outcomes and to maximize the donor pool by utilizing HCV-infected organs for heart transplantation.

Risk factors for post-transplant lymphoproliferative disorder after Thymoglobulin-conditioned hematopoietic cell transplantation.

Abstract: Epstein-Barr virus (EBV)-induced post-transplant lymphoproliferative disorder (PTLD) occurs frequently when rabbit antithymocyte globulin (ATG) is used in hematopoietic cell transplant (HCT) conditioning. We retrospectively studied 554 patients undergoing ATG-conditioned myeloablative HCT. Strategies used to minimize mortality due to PTLD were either therapy of biopsy-diagnosed PTLD in the absence of EBV DNAemia monitoring (n=266) or prompt therapy of presumed PTLD (based on clinical/radiologic signs and high EBV DNAemia, in the setting of weekly EBV DNAemia monitoring) (n=199). Both strategies resulted in similar mortality due to PTLD (0.7% vs 1% at 2 years, p = 0.43) and similar overall survival (63% vs 67% at 2 years, p = 0.23) even though there was a trend toward higher PTLD incidence with the prompt therapy. Donor positive with recipient negative EBV (D+R–) serostatus was a risk factor for developing PTLD. Older patient age, HLA mismatched donor and graft-vs-host disease were not associated with increased risk of PTLD. In summary, in ATG-conditioned HCT, D+R– serostatus, but not older age, mismatched donor or GVHD, is a risk factor for developing PTLD. EBV DNAemia monitoring may be a weak risk factor for developing/diagnosing PTLD; the monitoring coupled with prompt therapy does not improve survival. This article is protected by copyright. All rights reserved.