Mortality In Transplantation Research Articles

Rediscovering CPET: the prognostic value of hemodynamic gain index in heart failure

Abstract Introduction Cardiopulmonary exercise testing (CPET) is recommended in patients with heart failure (HF) to optimize exercise prescription and as part of the evaluation for heart transplantation. Hemodynamic gain index (HGI) derived from CPET has been proposed as a new marker of risk stratification in general population cohorts. Purpose We aimed to evaluate the prognostic value of HGI in patients with HF. Methods We conducted a single-centre study assessing consecutive patients with HF who underwent CPET from 2013 to 2017. HGI was calculated based on heart rate (HR) and systolic blood pressure (SBP): HGI = [(HRpeak × SBPpeak) − (HRrest × SBPrest)] / (HRrest × SBPrest). Classic and recently proposed variables were collected, including peak O2 uptake (pVO2), minute ventilation–CO2 production (VE/VCO2 slope), circulatory power (CP = pVO2 × peak SBP), and ventilatory power (VP = peak SBP/(VE/VCO2) slope). The primary outcome was a composite of HF hospitalization, heart transplant, and all-cause mortality. Results A total of 212 patients (mean age 55.4±10.9, 76.9% male) were included. Most patients had dilated cardiomyopathy (43.9%) followed by ischaemic aetiology (38.7%), with a mean left ventricle ejection fraction of 29±13%. The most used exercise protocol was the modified Naughton (76.6%), followed by the original Naughton (18.7%), and Bruce (4.8%). Mean pVO2 was 16.7±5.9mL O2 kg–1 min–1 and median VE/VCO2 slope was 37.5 [32.7–44.3]. Mean VP was 3.46±1.31mmHg while median CP was 1927 [1427–2697]mmHg min/mL/kg. Mean HGI was 0.90±0.5 bpm/mmHg. Despite weak, there were significant positive correlations between HGI and mean pVO2 (rs=0.55, p<0.01), VP (r=0.60, p<0.01), and CP (rs=0.68, p<0.01), but negative correlation between HGI and VE/VCO2 slope (rs=−0.45, p<0.01). HGI was grouped by terciles: T1 (<0.59), T2 (0.59–1.02), and T3 (>1.02). After a median follow-up of 71 [49–81] months, the primary outcome occurred in 66.0% of patients (rehospitalization, heart transplant, and all-cause death occurred in 56.1%, 25.9%, and 32.5%, respectively). In the T1 group, the multivariable-adjusted odds ratio (OR) for the primary outcome was 3.73 (95% CI 1.97–7.06, p<0.01) compared to the T3. In the T2 group, the multivariable-adjusted OR for the primary outcome was 0.47 (95% CI 0.27–0.81, p<0.01) compared to T1. There were no significant differences between T2 and T3 groups. Kaplan-Meier estimates of primary outcome during follow-up according to HGI tercile are shown in Figure 1. Conclusion HGI is inversely associated with the composite of HF hospitalization, heart transplant, and all-cause mortality in patients with heart failure, enhancing the role of CPET in risk stratification. Funding Acknowledgement Type of funding sources: None.

The Impact of New Treatments on Short- and MID-Term Outcomes in Bilateral Lung Transplant: A Propensity Score Study.

Background: Despite many efforts to improve organ preservation and recipient survival, overall lung transplant (LT) mortality is still high. We aimed to investigate the impact of ‘prophylactic’ veno-arterial extracorporeal membrane oxygenation (VA ECMO) and tacrolimus on 72-h primary graft dysfunction (PGD) and 30-day acute cellular rejection, respectively. Methods: All consecutive LT patients admitted to the Intensive Care Unit of the Padua University Hospital (February, 2016–2022) were screened. Only adult patients undergoing first bilateral LT and not requiring cardio-pulmonary bypass, invasive mechanical ventilation, and/or ECMO before LT, were included. A propensity score weighting analysis was employed to account for the non-random allocation of the subjects to different treatments. Results: A total of 128 LT recipients were enrolled. Compared to the ‘off-pump’-group (n.47, 37%), ‘prophylactic’ VA ECMO (n.51,40%) recorded similar 72-h PGD values, perioperative blood products and lower acute kidney dysfunction. Compared with cyclosporine (n.86, 67%), tacrolimus (n.42, 33%) recorded a lower risk of 30-day cellular rejection, kidney dysfunction, and bacteria isolation. Conclusions: ‘Prophylactic’ VA ECMO recorded 72-h PGD values comparable to the ‘off-pump’-group; while tacrolimus showed a lower incidence of 30-day acute cellular rejection.

Impact of sarcopenia on post-liver transplant morbidity and mortality in cirrhotic patients.

Modalities available for severity assessment and prediction of complications after liver transplant (LT) in cirrhotic patients are model for end-stage liver disease-sodium (MELD-Na) and Child-Turcotte-Pugh (CTP) scores. The limitation of these scores is the lack of assessment of nutritional and functional status. Sarcopenia is a newer modality, which is developed for objective assessment of nutritional status. The aim of this study is to analyze the significance of sarcopenia in predicting 1-year mortality and morbidity in post-LT patients. In this retrospective study, patients who underwent LT for cirrhosis between January 2013 and December 2018 were included. A computerized tomography (CT) image was used to analyze the psoas muscle index at the L3 vertebra (L3-PMI), and sarcopenia was defined as the values belonging to the lowest quartile of L3-PMI. The effect of sarcopenia on mortality and morbidity in terms of requirement for mechanical ventilation, duration of hospital stay, and occurrence of infections was studied. Among the study population (n = 74), 71 were men and the mean age was 51 years. Sarcopenia was observed in 27% (n = 20). Fifteen recipients had mortality within 1 year after transplant. In our analysis, sarcopenia was significantly associated with 1-year mortality (sensitivity 60%, specificity 81%; positive predictive value [PPV] 45%; negative predictive value [NPV] 88%; and p-value 0.001). Duration of mechanical ventilation, total hospital stay, and occurrence of infection were not significantly associated with sarcopenia. Sarcopenia was found as an independent predictor of mortality on binary logistic regression. The preoperative sarcopenia index in cirrhotic patients can predict the risk of mortality in post-liver transplant patients.

S1359 Post-Liver Transplant Metabolic Changes After One Year

Introduction: Elevations in HbA1c and BMI preoperatively and postoperatively are associated with post-transplant complications that impact long-term morbidity and mortality. The aim of this study is to evaluate the impact of transplant indications and demographic background on postoperative changes in HbA1c and BMI. Understanding factors associated with elevations in HbA1c and BMI can help determine at-risk patient groups. Methods: We performed an IRB-approved retrospective study. We obtained records of patients who underwent liver transplantation at Thomas Jefferson University Hospital from January 2002 to December 2020. We analyzed changes in BMI/HbA1c at transplant and one year post-transplant by age, race, gender, and indication for transplant using STATA statistical software 14.2. Results: Of the 100 liver transplant patients included in our study, 57 (63.3%) were male, and 33 (36.7%) were female. The average age was 63.26 years (61.13- 65.38, 95% CI), and the mean BMI and HbA1c at the time of transplant were 31.01 kg/m2(29.90-32.13, 95% CI) and 6.26 (5.89-6.62, 95% CI), respectively. There was no statistically significant (P >0.05) change in preoperative and one year postoperative BMI in transplant patients who had the following indications: NASH, Alcohol Cirrhosis, HCV, HBV, PSC, HCC, and cryptogenic cirrhosis. There was also no significant change in preoperative and one year postoperative BMI when stratifying patients by gender, race, and age or in preoperative and one year postoperative HbA1c when stratifying by indication for liver transplant, gender, and race. Patients < 50 years had a significantly greater one year postoperative HbA1c compared to their preoperative HbA1c (5.10 vs 6.09, p =0.048). There was no significant difference in preoperative and one year postoperative HbA1c in patients ≥50 years. (Table) Conclusion: Significant elevations in HbA1c post-transplant may predispose patients to post-transplant diabetes, which is associated with transplant dysfunction and mortality, and may cause post-transplant metabolic syndrome, which increases the risk of and complications from cardiovascular events. Our data showed that patients under the age of 50 need careful monitoring to minimize modifiable metabolic abnormalities. Determining high-risk populations for post-transplant complications is crucial to reduce long-term post-transplant morbidity and mortality. Further research is needed to elucidate additional risk factors for post-transplant complications. Table 1. - Metabolic Changes After 1 Year Liver Transplant Total Patients (%) Mean BMI (95% CI) At Transplant At 1 year after Transplant p-value Overall 90 (100) 31.01 (29.90-32.13) 30.88 (29.59-32.17) 0.16 Indication for Transplant NASH/NAFLD 27 (30.7) 33.08 (31.12-35.03) 32.30 (31.55-33.06) 0.21 Alcohol 11 (12.5) 26.19 (23.22-29.16) 25.96 (24.12-27.80) 0.45 HCV 9 (10.2) 30.81 (27.35-34.27) 31.23 (28.83-33.62) 0.36 HBV 2 (2.3) 37.2 (49.12-25.28) 34.40 (57.76-11.04) 0.13 PSC 1 (1.1) 25.8 (n/a) 26.3 (n/a) n/a HCC 3 (3.4) 29.00 (25.88-32.12) 28.53 (24.20-32.86) 0.30 Cirrhosis NOS/Cryptogenic 13 (14.8) 28.57 (25.65-31.49) 29.54 (27.89-31.19) 0.21 HCV + HCC 18 (20.5) 32.09 (29.65-34.53) 31.63 (30.47-32.79) 0.19 NASH + HCC 2 (2.3) 31.40 (19.48-43.32) 33.72 (10.36-57.08) 0.13 Alcohol + HCC 2 (2.3) 30.00 (20.45-39.55) 28.51 (9.80-47.23) 0.37 HCC=hepatocellular carcinoma, NASH= nonalcoholic steatohepatitis, HBV= Hepatitis B, HCV= Hepatitis C, PSC=primary sclerosing cholangitis.

Disparities in the Effects of Acuity Circle-based Liver Allocation on Waitlist and Transplant Practice Between Centers.

Background.Liver allocation in the United States was updated on February 4, 2020, by introducing the acuity circle (AC)–based model. This study evaluated the early effects of the AC-based allocation on waitlist outcomes.Methods.Adult liver transplant (LT) candidates listed between January 1, 2019, and September 30, 2021, were assessed. Two periods were defined according to listing date (pre- and post-AC), and 90-d waitlist outcomes were compared. Median transplant Model for End-stage Liver Disease (MELD) score of each transplant center was calculated, with centers categorized as low- (<25 percentile), mid- (25–75 percentile), and high-MELD (>75 percentile) centers.Results.A total of 12 421 and 17 078 LT candidates in the pre- and post-AC eras were identified. Overall, the post-AC era was associated with higher cause-specific 90-d hazards of transplant (csHR, 1.32; 95% confidence interval [CI], 1.27-1.38; P < 0.001) and waitlist mortality (cause-specific hazard ratio [csHR], 1.20; 95% CI, 1.09-1.32; P < 0.001). The latter effect was primarily driven by high-MELD centers. Low-MELD centers had a higher proportion of donations after circulatory death (DCDs) used. Compared with low-MELD centers, mid-MELD and high-MELD centers had significantly lower cause-specific hazards of DCD-LT in both eras (mid-MELD: csHR, 0.47; 95% CI, 0.38-0.59 in pre-AC and csHR, 0.56; 95% CI, 0.46-0.67 in post-AC and high-MELD: csHR, 0.11; 95% CI, 0.07-0.17 in pre-AC and csHR, 0.14; 95% CI, 0.10-0.20 in post-AC; all P < 0.001). Using a structural Bayesian time-series model, the AC policy was associated with an increase in the actual monthly DCD-LTs in low-, mid-, and high-MELD centers (actual/predicted: low-MELD: 19/16; mid-MELD: 21/14; high-MELD: 4/3), whereas the increase in monthly donation after brain death–LTs were only present in mid- and high-MELD centers.Conclusions.Although AC-based allocation may improve waitlist outcomes, regional variation exists in the drivers of such outcomes between centers.

Role of extracorporeal photopheresis in the management of children with graft-vs-host disease.

Graft-vs-host disease (GVHD) is a frequent cause of morbidity and mortality in allogeneic stem cell transplants. Extracorporeal photopheresis (ECP) is one of the most accepted second-line treatments, but technical issues of ECP in children might be prohibitive. Patients under 18 y of age with corticodependant or corticorefractory GVHD receiving ECP at our hospital were included in this retrospective study. ECP was performed with an in-line system (CellExTherakos) in 2013-2014 and with an off-line system (Spectra Optia) from 2015 onwards. Cumulative incidence curves were obtained to compare ECP efficacy among patients grouped by different baseline, apheresis, and disease characteristics. Significant variables on univariate analysis (Gray's test) were pooled into a multivariate analysis (Fine-Gray proportional hazard regression for competing events). A total of 701 ECP sessions were performed on 33 patients between October 2013 and December 2021. In total, 97% of the sessions could be executed. In 8% of the sessions an incident was detected, most of them mild and related to catheter dysfunction. With a median follow-up for alive patients of 33.6mo (range, 8-95), the composite partial and complete response cumulative incidence was 70% (95% confidence interval, 51%-82%) and the median time to maximal response was 2.8mo (range, 0.25-9.8). Significantly lower response ratios were found in patients with hepatic, gastrointestinal, acute, or severe GVHD. The only variable that influenced response on multivariate analysis was GVHD severity. ECP is feasible, safe, and effective for pediatric patients with corticorefractory or corticodependant GVHD, offering a less toxic and nonimmunosuppressive treatment option.

P483 Invasive fungal infection in hematopoietic stem cell transplant recipient from an Indian oncology setting

Poster session 1, September 21, 2022, 12:30 PM - 1:30 PM ObjectivesInvasive fungal infections (IFI) are one of the major causes of morbidity and mortality in post-hematopoietic stem cell transplant (HSCT) recipients. Data from India are limited. The objective was to analyze the incidence, risk factors, and outcomes associated with IFI in our center.MethodsAdult patients, who underwent marrow/stem cell transplantation between 2014-2018, in an oncology center in India, were included in this retrospective observational study. The revised consensus definition of IFI by the European Organization for Research and Treatment of Cancer/Invasive Fungal Infections Cooperative Group and the National Institute of Allergy and Infectious Diseases Mycoses Study Group (EORTC/MSG) in 2008, was considered to define cases. Incidence, risk factors, and outcomes associated with IFI were analyzed.ResultsOut of the 126 patients who underwent HSCT between 2014-2018, 56 (44.4%) had Allo HSCT, 64 (50.8%) had auto HSCT and 6 (4.8%) had haplo-identical HSCT. A total of 83 (63%) were males and 43 (34%) females, 113 (83.9%) Asians, and 13 (10.3%) Africans. Total 111 (88%) patients received myeloablative conditioning and 24 (19%) received total body irradiation. The hematological conditions were acute myeloid leukemia (AML) n = 23 (18.25%), acute lymphoblastic leukemia (ALL) n = 16 (12.69%), chronic myeloid leukemia (CML) n = 4 (3.17%), Hodgkins lymphoma (HL) n = 17 (13.4%), non-Hodgkins lymphoma (NHL) n = 11 (8.73%), Myeloma n = 35 (27.7%), sickle cell disease n = 13 (10.31%), etc. Most patients received fluconazole 78 (61.9%) followed by micafungin 23 (18.25%), posaconazole 20 (15.87%), voriconazole 4 (3.17%), and liposomal amphoterin B 1 (0.79%) as antifungal prophylaxis. The overall rate of IFI (possible cases included) was auto-HSCT n = 5 (7.81%), and Allo-HSCT n = 5 (8.92%). Among auto-HSCT, the IFI was Proven = 0, Probable n = 1 (1.5%), and Possible n = 4 (6.25%), and among Allo-HSCT Proven = 0, Probable n = 2 (3.57%), and Possible n = 3 (5.35%). These cases had IFI lung based on imaging and serological tests. None of the cases had a lung biopsy. There were no incidents of candidemia. No patients in Haplo-HSCT had IFI. The 1-year survival rate among the IFI cases was 8/10 (80%). As the number of patients with IFI was very low, a meaningful comparison of the risk factors, and the impact of prophylactic regimens were difficult.ConclusionsThe overall rate of IFI in HSCT patients in our setting was low compared to global data.

Patient age and donor HLA matching can stratify allogeneic hematopoietic cell transplantation patients into prognostic groups.

Mixed results surround the accuracy of commonly used prognostic risk scores to predict overall survival (OS) and non-relapse mortality (NRM) in allogeneic hematopoietic stem cell transplant (allo-HCT) recipients. We hypothesize that a simple prognostic score performs better than conventional scoring systems. OS risk factors, HCT-CI, age-HCT-CI, and augmented-HCT-CI were studied in 299 patients who underwent allo-HCT for myeloid and lymphoid malignancies. A scoring system was developed based on results and validated in a different cohort of 455 patients. Two-year OS was 51% (95% confidence interval (CI) 0.45-0.56); 2-year NRM was 34% (95% CI 0.29-0.39). HCT-CI and associated scores were grouped into 0-2 and ≥3. Age and HLA mismatch status were the only risk factors to affect OS in multivariate analysis (p= 0.02 and 0.05, respectively). HCT-CI and associated scores were not informative for OS prediction. The weighted scoring system assigned 0 to 2 points for age < 50, 50-64, or ≥65, respectively, and 0-1 points for no HLA mismatch versus any mismatch (except HLA-DQ). Distinct 2-year OS (62%, 53%, and 38% [p= <0.001]) and NRM (24%, 34%, and 43% [p= 0.02]) groups were characterized. The scoring system was validated in a second independent cohort with similar results on OS and NRM (p< 0.001). A simple scoring system based on recipient's age and mismatch status accurately predict OS and NRM in two distinct cohorts of allo-HCT patients. Its simplicity makes it a helpful tool to aid clinicians and patients in clinical decision-making.

216.14: Validating a Cut-off of IgG Hypogammaglobulinemia as a Risk Factor of Severe Infection in Solid Organ Transplantation

Backgound and aims: Severe infection is a leading cause of morbidity and mortality in solid organ transplantation. IgG hypogammaglobulinemia has been previously investigated in single and multicenter studies in distinct solid organ transplantations as a predictor of infection. We aimed to validate the IgG cut-off of 600 mg/dl as a risk factor of severe infection in solid organ transplantation. The potential utility of this biomarker is that this can be modulated by therapeutic intervention. Materials and Methods: 538 heart, liver or kidney recipients were analysed in a prospective study performed in 2 centers. During a follow-up during the first 6 months after solid organ transplantation 298 (55.4%) patients developed at least one episode of severe infection the majority of which were bacterial infections. As a secondary outcome we retrospectively analysed the impact of IgG hypogammaglobulinemia early after transplantation on the rate of death. Survival analysis was performed by Kaplan-Meier. Risk for development of severe infection was also performed by logistic regression analysis. Results: The rate of decrease of IgG after transplantation was similar in both participating centers. Cumulative survival without severe infection during the first 6 months after transplantation was lower in solid organ transplantation recipients with IgG hypogammaglobulinemia defined as IgG < 600 mg/dl at days 7 or 30 after transplantation (Log Rank 5.22, p=0.022). IgG hypogammaglobulinemia was associated with higher rates of death after solid organ transplantation (Log Rank 5.75, p=0.017). In logistic regression analysis IgG hypogammaglobulinemia was significantly associated with risk of severe infection (OR 1.635, p=0.040, 95%CI 1.022-2.615). IgG hypogammaglobulinemia was a risk factor of death (OR 1.078, p= 0.011, 95%CI 1.180 – 3.668). We performed an immunological score for development of severe infection composed of pre transplant monocytes < 7% (2 points), IgG hypogammaglobulinemia (2 points), CD4 <400 cells/uL at day 30 (2 points), C3 < 60 mg/dl at day 30 (2 points) and CRP > 3 mg/dl at day 30 (2 points). In those patients with 4 or more points, OR for development of infection was 2.89 (95% CI 1.641 – 5.123; p<0.001). Conclusion: IgG hypogammaglobulinemia (defined as IgG < 600 mg/dL early after transplantation) is associated with risk of severe infection in solid organ transplantation. This cut-off should be taken into account in future clinical trials that evaluate the impact of the modification of this risk factor by adding intravenous immunoglobulin to these patients to prevent severe infection. An immunological score combining IgG hypogammaglobulinemia and other innate and acquired immunity parameters could be a better way to identify the risk for development of severe infection in solid organ recipients.

Multiple Myeloma: Impact of Time to Transplant on the Outcome.

Autologous stem cell transplant (ASCT) is a standard therapy for transplant eligible patients of multiple myeloma (MM). To evaluate impact of time to transplant on subsequent outcomes, we analyzed data on consecutive MM patients who received novel agents-based induction prior to transplant. Between 2006 and 2019, 363 MM patients underwent ASCT. Patients' median age was 52 years, ranging from 20 to 72 years, 233 (64.2%) were males. Median interval from diagnosis to transplant was 11.5 months (range, 4-67.5); 201 (55.4%) patients underwent ASCT within 12 months (early) and 162 (44.6%) beyond 12 months since diagnosis (delayed ASCT). Primary objective was progression-free survival. Secondary objectives were-response rate to transplant, overall survival (OS), and transplant-related mortality (TRM). Post-ASCT complete response (CR) (77.1% vs. 64.8%; P < .025) and CR+ very good partial response rate (89% vs. 81.5%; P < .03) was higher for early ASCT cohort. Engraftment characteristics, regimen-related toxicities, and day +100 TRM (3.5% vs 3.7%; P = .564) were similar in 2 cohorts. Median OS for early versus late cohort from date of diagnosis is 127.0 (95% CI, 98.9-155.1) versus 104.5 months (95% CI, 79.3-129.6; P = .356) and from date of transplant is 119.0 (95% CI, 93.4-144.6) versus 89.5 months (95% CI, 57.4-121.6), P < .02. Median PFS is better for early transplant cohort; 69.5 (95% CI, 56.7-82.3) versus 50.0 months (95% CI, 35.6-64.4), P < .05, respectively. Early transplant for myeloma is associated with higher response rate and better progression-free survival.

The U-shaped association of post-lung transplant mortality with pretransplant eGFR underscores possible limitations of creatinine-based estimation equations for risk stratification.

Pre-existing chronic kidney disease (CKD) may have an impact on post-lung transplant survival and the development of end stage kidney disease (ESKD). We analyzed the US transplant database from 2006 to 2020. Adult patients who received their first lung transplant and were not on dialysis were included. Multivariable Cox regression was used to assess the effect of pretransplant eGFR on mortality and cumulative incidence competing risk was used to explore the effect on ESKD. The adjusted hazard ratio (aHR) for mortality showed a "U" shaped association with eGFR with a rising mortality at <60 and >100 ml/min/1.73m2. The increase in mortality with higher eGFR was only seen in those <30 year and were primarily in whites with a lower body mass index and in patients with cystic fibrosis (CF). The aHR for ESKD increased below an eGFR of 100 rising to 1.74 at an eGFR of 60. Any decrease in eGFR between listing and transplant >10% was associated with higher risk of ESKD. The U-shaped association of pretransplant eGFR with post-transplant mortality correlated with younger age, lower BMI and a diagnosis of CF. The aHR for ESKD following lung transplantation increased exponentially with worsening eGFR pretransplant.

Sarcopenic visceral obesity is associated with increased post-liver transplant mortality in acutely ill patients with cirrhosis

"Sarcopenic obesity" refers to a condition of low muscle mass in the context of obesity, though may be difficult to assess in patients with cirrhosis who are acutely ill. We aimed to define sarcopenic visceral obesity (SVO) using CT-based skeletal muscle index (SMI) and visceral-to-subcutaneous adipose tissue ratio (VSR) to examine its association with post-transplant mortality. We analyzed 116 adult inpatients with cirrhosis who were urgently listed and transplanted between 1/2005 and 12/2017 at 4North American transplant centers. SVO was defined as patients with sarcopenia (SMI <50cm2 /m2 in men and <39cm2 /m2 in women) and visceral obesity (VSR≥1.54 in men and ≥1.37 in women). The percentage who met criteria for sarcopenia, visceral obesity, and SVO were 45%, 42%, and 20%, respectively. Cumulative rates of post-transplant mortality were higher in patients with SVO compared to patients with sarcopenia or visceral obesity alone at 36months (39% vs. 14% vs. 8%) [logrank p=.01]. In univariable regression, SVO was associated with post-transplant mortality (HR 2.92, 95%CI 1.04-8.23) and remained significant after adjusting for age, sex, diabetes, encephalopathy, hepatocellular carcinoma, and MELD-Na (HR 3.50, 95%CI 1.10-11.15). In conclusion, SVO is associated with increased post-transplant mortality in acutely ill patients with cirrhosis.

316.16: Which Patients Over 60 Years Old Are Candidates for a Kidney Transplant? Usefulness of a Mortality Predictive Score

Introduction: The decision to indicate a kidney transplant (KT) to an elderly patient with end-stage chronic kidney disease is not simple due to the high morbidity and mortality associated. The Dusseux et al. score was originally developed in France to predict 3-year post kidney transplant mortality in subjects older than 70 years. The objective of this study was to evaluate the usefulness of this score to predict 1-year post KT mortality in patients older than 60 years and to identify the best cut-off point. Methods: A retrospective cohort study was performed. All patients over 60 years old who received a KT at Hospital Privado Universitario de Córdoba between January 2009 and December 2015 were consecutively included. A one-year post-KT follow-up was carried out and variables associated with mortality were analyzed. The Dusseux et al. score considers as predictive variables: sex, age, etiology of chronic kidney disease, comorbidities, mobility status, body mass index and the presence of a temporary catheter at the time of dialysis initiation. The t test or Mann-Whitney test were used to evaluate differences between continuous variables t, and chi2 or Fisher’s test for categorical variables, as appropriate. To evaluate the predictive capacity, the area under the curve (AUC) was used and the Youdex Index J was applied to identify the best cut-off point, with its sensitivity and specificity. Kaplan Meier survival curves were made and then compared with the logRank test. A value of p<0.05 was considered statistically significant. Results: We included 111 patients aged 66.2 ± 5.2 years, 54.9% were men. As relevant comorbidities, 30.7% were diabetic and 13.5% had ischemic heart disease. 82% received a cadaveric KT. As induction, 100% were given steroids, 60.3% basiliximab, 22.5% thymoglobulin and 9.9% gamma globulin. As maintenance, 93.7% were treated with steroids, tacrolimus and mycophenolate. Mortality during follow-up was 9.9% (n:11; 8 due to infectious etiology and 3 from cardiovascular disease). The patients who died were older (70.3 ± 6.6 vs 65.8 ± 4.9; p=0.05), had a greater history of ischemic heart disease (36.7% vs 11%; p=0.04), and had a higher mortality predictive score (9.4 ± 3 vs 6.8 ± 2.5, p=0.02). There were no differences in the rest of the variables. This score obtained a high AUC to predict mortality (AUC=0.75; p<0.01; figure 1) and the best cut-off point was 8, with a sensitivity of 72.7% and a specificity of 78%. Subjects with a score >8 had higher mortality than those with a score ≤8 (26.7% vs 3.7% respectively; p<0.01). There were significant differences between the survival curves of these groups (p<0.01; figure 2). Conclusion: This clinical score is a good predictor of mortality 1-year after KT in patients over 60 years old. The best cut-off point of the score was 8 points. This could be a useful and simple tool to help in the decision to indicate a KT in this type of patients. Fundación Nefrológica de Córdoba.

Reducing Mortality of Single-Unit Unrelated Cord Blood Transplantation for Relapsed Acute Myeloid Leukemia after a Previous Allogeneic Transplantation: A Real-World Retrospective Study Over the Past 19 Years in Japan

Relapse is the most common cause of treatment failure after allogeneic hematopoietic cell transplantation (HCT) for acute myeloid leukemia (AML). Second or subsequent allogeneic HCT using unrelated cord blood has been performed for adult patients with AML who have relapsed after a previous allogeneic HCT. Although outcomes after unrelated cord blood transplantation (CBT) as the first allogeneic HCT have significantly improved in recent years, it is unclear whether survival and engraftment improve after CBT as the second or subsequent allogeneic HCT for adult AML patients relapsing after a previous allogeneic HCT. The objective of this retrospective study was to evaluate trends of survival and other transplantation outcomes after single-unit unrelated CBT as a second or subsequent allogeneic HCT in adult patients with relapsed AML after a previous allogeneic HCT over the past 19 years in Japan. We retrospectively assessed survival trends and other outcomes of single-unit unrelated CBT as a second or subsequent allogeneic HCT in adult patients with relapsed AML after a previous allogeneic HCT according to the time period of CBT (2001-2007, 2008-2013, or 2014-2019) using a nationwide Japanese database. The median age was 45 years among 1109 CBTs, and 844 (78.6%) patients were not in complete remission at the time of CBT. Over the 3 time periods, there was a progressive increase in higher cryopreserved cord blood total nucleated cell dose and myeloablative conditioning regimens. The 2-year overall survival was 14.0% in 2001-2007, 19.9% in 2008-2013, and 24.4% in 2014-2019 (P <.001 by log-rank trend test). The 2-year relapse-related mortality was 54.0% in 2001-2007, 44.4% in 2008-2013, and 39.1% in 2014-2019 (P < 0.001 by Gray's test), but nonrelapse mortality was not significantly different across the time periods (P=0.557 by Gray's test). The 42-day neutrophil engraftment also significantly improved (62.9% in 2001-2007, 69.7% in 2008-2013, and 79.9% in 2014-2019; P < 0.001 by Gray's test). Our data demonstrate significant improvements in overall and relapse-related mortality, as well as neutrophil engraftment, after single-unit unrelated CBT as a second or subsequent allogeneic HCT for adult patients with AML relapsed after previous allogeneic HCT over the past 19 years.

Characteristics, outcomes, and predictors of de novo malignancy after heart transplantation.

BackgroundPost-transplant malignancy (PTM) causes long-term morbidity and mortality in heart transplant (HTx) recipients. However, the detailed characteristics or predictors of PTM are not well-known. We evaluated the incidence, characteristics, long-term outcomes, and predictors of de novo PTM using a single center large-volume database.MethodsWe retrospectively analyzed the types and characteristics of de novo PTM in 989 patients who underwent HTx. Univariate and multivariate logistic regression analyses were used for the PTM prediction model.ResultsTwo hundred and six patients (20.8%) had de novo PTMs (241 cancers) during a median follow-up of 11.5 years. PTM patients were older than non-PTM patients, received immunosuppressive therapy for a longer period, and were more likely to be male and white. Skin cancers were the most frequent types of malignancy (60.6%) followed by prostate (9.5%), lung (7.1%), and breast (4.1%) cancers. Although most cancers (88.8%) were surgically resected at initial presentation, about half (47.3%) recurred or progressed. Patients with skin cancer and non-skin cancer had significantly lower overall survival (P < 0.001) than patients without cancer. Older age (P < 0.001), white race (P = 0.001), and longer time receiving immunosuppressive therapy (P < 0.001) were independent predictors for PTM.ConclusionOlder age, white race, and longer administration of immunosuppressive therapies were independent risk factors for PTM, which was associated with increased mortality. Further research is necessary for the prevention and early detection of PTM in HTx recipients.

25 Years of a Standardized Technique for Living Donor Intestinal Transplantation: A Systematic Review

A safe, reproducible and standardized surgical technique for intestinal procurement and transplantation from a living donor (LD) was introduced in 1997 and has been used in the majority of cases since. The key principles are: 1. procurement of 180-200 cm of distal ileum in adults (about 60-150 cm in pediatric recipients depending on age and weight) on a vascular pedicle comprising the LD ileocolic vessels or terminal branches of the superior mesenteric vessels, 2. the terminal ileum (30-40 cm of the most distal ileum), the ileocecal valve and the cecum remain with the donor to not interfere with B12-absorption and bowel transit time, 3. systemic venous drainage with anastomoses between the LD ileocolic vessels and the recipient's infrarenal aorta and vena cava, and 4. restoration of recipient bowel continuity through proximal anastomosis and distal graft ileostomy for biopsy access and graft monitoring. Recipients of a successful LD intestinal transplant become total parenteral nutrition (TPN)-independent within a few weeks posttransplant. LD vs deceased donor (DD) intestinal transplants can be performed in a more timely fashion. Hence, LD (in contrast to DD) intestinal transplants are also pre-emptive procedures in patients with advanced, but still reversible, TPN-induced liver disease and help reduce the wait-list mortality for combined DD intestinal and liver transplants. Life-saving combined LD intestinal and liver transplants, albeit rare, have also been successfully performed either simultaneously or subsequently. There have been no reported deaths or major complications of living intestinal donors. A better metabolic profile has been reported in some donors post-donation. In total, 85 documented LD intestinal transplants have been performed worldwide at over 20 different transplant centers in 12 different countries. In about 70 transplants, the standardized technique was used. There has been no difference in outcome between LD vs DD intestinal transplants. Long-term studies have shown that > 10 year of graft function is not uncommon. Since the introduction of the standardized surgical technique, LD intestinal transplantation has evolved from an experimental to an established and standardized procedure.

Validation of 5 models predicting transfusion, bleeding, and mortality in liver transplantation: an observational cohort study.

Historically, orthotopic liver transplantation (OLT) has been associated with massive blood loss, blood transfusion and morbidity. In order to predict such outcomes five nomograms have been published relating to transfusions and morbidity associated with OLTs. These nomograms, developed on the basis of three cohorts of patients consisting of 406, 750, and 800 having undergone OLTs, aimed to predict a transfusion of ≥1 red blood cell unit (RBC), a transfusion of >2 RBC units, a blood loss of >900ml, as well as one-month and one-year survival rates. The aim of this study was to validate these five nomograms in a contemporary, independent cohort of patients. Five nomograms were previously developed based on 406, 750, and 800 OLTs. In this study we performed a temporal validation of these nomograms on contemporary patients that consisted of three cohorts of 800, 250, and 200 OLTs. Logistic regression coefficients from the historic development cohorts were applied to the three contemporary temporal validation cohorts. The most accurate nomogram was able to predict transfusion of ≥1 RBC units with an area under the curve (AUC) was 0.91. The second-best nomogram was able to predict bleeding of >900ml with an AUC of 0.70. T he AUC of the third nomogram (transfusion of >2 RBC units) was 0.70. However, is temporal validation was suboptimal, due to a low prevalence of OLTs transfused with >2 RBC units. The last 2 nomograms exhibited clearly suboptimal AUC values of 0.54 and 0.61. Two of the five nomograms predict blood transfusion and blood loss with excellent accuracy. Transfusion of ≥1 RBC unit and blood loss of >900ml can be predicted on the basis of these nomograms. However, these nomograms are not accurate to predict one-month and one-year survival rates. These results should be further cross-validated, ideally prospectively, in additional external independent cohorts.

Inflammation in the early phase after kidney transplantation is associated with increased long-term all-cause mortality

In the general population, low-grade inflammation has been established as a risk factor for all-cause mortality. We hypothesized that an inflammatory milieu beyond the time of recovery from the surgical trauma could be associated with increased long-term mortality in kidney transplant recipients (KTRs). This cohort study included 1044 KTRs. Median follow-up time post-engraftment was 10.3 years. Inflammation was assessed 10 weeks after transplantation by different composite inflammation scores based on 21 biomarkers. We constructed an overall inflammation score and five pathway-specific inflammation scores (fibrogenesis, vascular inflammation, metabolic inflammation, growth/angiogenesis, leukocyte activation). Mortality was assessed with Cox regression models adjusted for traditional risk factors. A total of 312 (29.9%) patients died during the follow-up period. The hazard ratio (HR) for death was 4.71 (95% CI: 2.85–7.81, p < .001) for patients in the highest quartile of the overall inflammation score and HRs 2.35–2.54 (95% CI: 1.40–3.96, 1.52–4.22, p = .001) for patients in the intermediate groups. The results were persistent when the score was analyzed as a continuous variable (HR 1.046, 95% CI: 1.033–1.056, p < .001). All pathway-specific analyses showed the same pattern with HRs ranging from 1.19 to 2.70. In conclusion, we found a strong and consistent association between low-grade systemic inflammation 10 weeks after kidney transplantation and long-term mortality.

Systematic review and meta-analysis of the diagnostic accuracy of procalcitonin for post-operative sepsis/infection in liver transplantation

BackgroundPost-operative infection is a major cause of morbidity and mortality in Liver Transplantation (LT). Early diagnosis and antimicrobial treatment improves outcomes and ruling out sepsis aids immunosuppression decisions. Procalcitonin (PCT) has recently become part of such decision making in COVID-19 pneumonia but its role in LT is not established. We assessed the diagnostic accuracy of PCT as a diagnostic biomarker for infection or sepsis following LT. MethodsA systematic search was conducted for studies reporting diagnostic performance of PCT for infection/sepsis following LT. Studies were assessed for reporting of diagnostic accuracy, relevance and quality. ResultsEight studies with 363 participants reported data on the diagnostic accuracy of PCT, with pooled sensitivity, specificity, diagnostic odds ratio and summary receiver operator curve of 70% (95% CI 62–78), 77% (95% CI 73–83), 15.82 (95% CI 5.82–43.12) and 0.871 respectively. There was variability in the timing of sampling (post-operative day 1–8) and range of cut-off values (0.48 to 42.8 ng/mL). Heterogeneity was reduced when only studies with adult LT recipients were considered. ConclusionsPCT performs moderately well as a diagnostic test for postoperative infection/sepsis following LT. This marker is more suited for use in adult LT populations.

Utility of the IMPACT score for predicting heart transplant mortality. Analysis on a contemporary cohort of the Spanish Heart Transplant Registry.

The Index for Mortality Prediction After Cardiac Transplantation (IMPACT) score was derived and validated as a predictor of mortality after heart transplantation (HT). The primary objective of this work is to externally validate the IMPACT score in a contemporary Spanish cohort. Spanish Heart Transplant Registry data were used to identify adult (>16 years) HT patients between January 2000 and December 2015. Retransplantation, multiorgan transplantation and patients in whom at least one of the variables required to calculate the IMPACT score was missing were excluded from the analysis (N=2810). Median value of the IMPACT score was five points (IQR: 3, 8). Overall, 1-year survival rate was 79.1%. Kaplan-Meier 1-year survival rates by IMPACT score categories (0-2, 3-5, 6-9, 10-14, ≥15) were 84.4%, 81.5%, 79.3%, 77.3%, and 58.5%, respectively (Log-Rank test: p<.001). Performance analysis showed a good calibration (Hosmer-Lemeshow chi-square for 1 year was 7.56; p=.47) and poor discrimination ability (AUC-ROC .59) of the IMPACT score as a predictive model. In a contemporary Spanish cohort, the IMPACT score failed to accurately predict the risk of death after HT.