Solid Organ Transplant Procedures Research Articles

The value of extracorporeal photopheresis as an immunosuppression-modifying approach in solid organ transplantation: a potential solution to an unmet medical need

Allograft rejection is a critical issue following solid organ transplantation (SOT). Immunosuppressive therapies are crucial in reducing risk of rejection yet are accompanied by several significant side effects, including infection, malignancy, cardiovascular diseases, and nephrotoxicity. There is a current unmet medical need with a lack of effective minimization strategies for these side effects. Extracorporeal photopheresis (ECP) has shown potential as an immunosuppression (IS)-modifying technique in several SOT types, with improvements seen in acute and recurrent rejection, allograft survival, and associated side effects, and could fulfil this unmet need. Through a review of the available literature detailing key areas in which ECP may benefit patients, this review highlights the IS-modifying potential of ECP in the four most common SOT procedures (heart, lung, kidney, and liver transplantation) and highlights existing gaps in data. Current evidence supports the use of ECP for IS modification following SOT, however there is a need for further high-quality research, in particular randomized control trials, in this area.

Descriptive study on risk of increased morbidity of schistosomiasis and graft loss after liver transplantation.

Solid-organ transplantation procedures have witnessed a surge in frequency. Consequently, increased attention to associated infections and their impact on graft success is warranted. The liver is the principal target for infection by the flatworm Schistosoma mansoni. Hence, rigorous screening protocols for this parasite should be implemented for liver transplantation donors and recipients. This study investigated the risks posed by schistosomiasis-infected liver tissues for successful liver transplantation (LT), considering donors and recipients, by analyzing reported cases. Among the 43 patients undergoing LT (donors = 19; recipients = 24), 32 were infected with S. mansoni, five were infected with other Schistosoma species, and no identification was made in four patients. Reported follow-up periods ranged from 1 to 132 months, and all patients achieved successful recovery. As these helminths do not replicate in their vertebrate hosts, immunosuppressive treatment is not expected to promote increased morbidity or reactivation. Moreover, suspected or confirmed schistosomiasis infections often have a benign course, and generally, should not prevent LT. The available literature was reviewed and a provisional screening protocol has been proposed.

Impact of fast tacrolimus metabolizer status on outcome after heart transplantation

Abstract Objective Optimal immunosuppression is an essential component of the best possible long-term survival after heart transplantation (HTX). Optimally patient-tailored immunosuppression is standard in Tx follow-up, balancing harmful side effects and preventing rejection episodes. Hereby, stable blood levels, as well as a stable and calculable absorption rate, is essential. Tacrolimus additionally has a narrow therapeutic range and is particularly difficult to dose stably. It has been shown that interindividual differences in absorption exist among various immunosuppressants, making adequate minimum levels and the avoidance of rejection events more difficult. For other solid organ transplantation procedures there are already studies on the proportion of patients (so-called "fast metabolizers") who experience different kinetics due to very rapid resorption. We here therefore aim to investigate the potential impact of the tacrolimus metabolizer status on outcome in a HTx cohort. Methods We defined fast metabolizers by a low concentration to dose ratio (C/D ratio) of <1.05. The C/D ratio was determined according to the following formula: C/D ratio (ng/ml x 1/mg) = Tacrolimus through level (ng/ml) / daily Tacrolimus dose (mg). We included as a first step here 57 patients undergoing HTx in our center between 09/2010 and 10/2016 and calculated the C/D ratio retrospectivley from routine follow-ups. In both groups baseline characteristics, perioperative parameters and survival after 1 and 5 years after Tx were collected. Results We identified 24 patients (42%) as fast metabolizers and 33 patients as standard metabolizers (58%). The metabolizer status did not significantly correlate with reduced survival of the recipient up to 5 years in Kaplan-Meier-Analysis (Figure 1,A, Log Rank p=0.68). Additionally, regression analysis could not detect an association of 1-year-survival and C/D ratio or the fast metabolizer status definition (HR 1.1, 95% CI 0.17-7.2, p=0.92). Moreover, using ROC-analysis, no clear other cut-off for C/D ratio other than the used published definition (<1.05) could be derived (Figure 1,B, AUC 5-year survival 0.53, p = 0.72). Additionally, these parameters did not change significantly also when focusing on speficic substances with different pharmacodynamics such as Prograf (two doses per day) or Advagraf (delayed release, one dose per day). We could also not detect associations between C/D ratio or metabolizer status and unfavorable outcomes such as cellular or clinical relevant rejection episodes. Conclusion In this retrospective analysis, neither the metabolizer status or the raw tacrolimus concentration to dose ratio was associated with altered survival or outcome after heart transplantation. As we present here a yet small number of investigated patients (pilot study) with a potential era bias by currently not including advances in medication optimization over the last years, future studies are needed to elucidate this phenomen further.

The utility of machine learning for predicting donor discard in abdominal transplantation.

Increasing access and better allocation of organs in the field of transplantation is a critical problem in clinical care. Limitations exist in accurately predicting allograft discard. Potential exists for machine learning to provide a balanced assessment of the potential for an organ to be used in a transplantation procedure. We accessed and utilized all available deceased donor United Network for Organ Sharing data from 1987 to 2020. With these data, we evaluated the performance of multiple machine learning methods for predicting organ use. The machine learning methods trialed included XGBoost, random forest, Naïve Bayes (NB), logistic regression, and fully connected feedforward neural network classifier methods. The top two methods, XGBoost and random forest, were fully developed using 10-fold cross-validation and Bayesian optimization of hyperparameters. The top performing model at predicting liver organ use was an XGBoost model which achieved an AUC-ROC of .925, an AUC-PR of .868, and an F1 statistic of .756. The top performing model for predicting kidney organ use classification was an XGBoost model which achieved an AUC-ROC of .952, and AUC-PR of .883, and an F1 statistic of .786. The XGBoost method demonstrated a significant improvement in predicting donor allograft discard for both kidney and livers in solid organ transplantation procedures. Machine learning methods are well suited to be incorporated into the clinical workflow; they can provide robust quantitative predictions and meaningful data insights for clinician consideration and transplantation decision-making.

Immune checkpoint inhibitors for solid organ transplant recipients: clinical updates.

Transplant care continues to advance with increasing clinical experience and improvements in immunosuppressive therapy. As the population ages and long-term survival improves, transplant patient care has become more complex due to comorbidities, frailty, and the increased prevalence of cancer posttransplantation. Immune checkpoint inhibitors (ICIs) have become a standard treatment option for many cancers in non-transplant patients, but the use of ICIs in transplant patients is challenging due to the possibility of disrupting immune tolerance. However, over the past few years, ICIs have gradually started to be used in transplant patients as well. In this study, we review the current use of ICIs after all solid organ transplantation procedures (kidney, liver, heart, and lung). Increasing data suggest that the type and number of immunosuppressants may affect the risk of rejection after immunotherapy. Immunotherapy for cancer in transplant patients may be a feasible option for selected patients; however, prospective trials in specific organ transplant recipients are needed.

Exercise Progression Protocol for Lung Transplant GO: A Multicomponent Telerehab Exercise Intervention for Patients After Lung Transplantation.

Lung transplantation is one of the fastest growing solid organ transplant procedures in the United States. After transplantation, lung function typically returns to near normal levels; however, reduced physical function and an inactive lifestyle compromise this benefit. To promote rehabilitation goals, lung transplant recipients (LTRs) are advised to participate in pulmonary rehab, but participation is low due to barriers related to scheduling, travel requirements, lack of insurance coverage, and the concern about exposure to infection. Telerehabilitation offers a flexible alternative with the potential to promote self-management of exercise in LTRs. The purpose of this report was to describe the exercise progression protocol for the Lung Transplant GO multicomponent telerehab exercise intervention for patients after lung transplantation. The progression protocol is an evidence-informed exercise protocol designed to improve physical function and physical activity in LTRs safely and effectively in a remote environment. The protocol standardizes the prescription of exercise while permitting adaptation of the program to meet the needs of the individual. Using this model, the decisions about program progression are systematic, transparent, and replicable to other LTRs.

1094. Infective Endocarditis During Index Hospitalization for Solid Organ Transplantation in the United States

BackgroundThe prevalence and impact of infective endocarditis (IE) on organ transplant recipients is unknown. We used a large cohort of transplant recipients to assess the impact of IE on outcomes during index transplant hospitalization.MethodsWe used data from the 2013-2017 Nationwide Readmissions Database (NRD). Hospitalizations associated with solid organ transplantation procedures (heart, liver, kidney, lung, intestines, pancreas) were included. Outcomes included 60-day rates of mortality, ECMO deployment, thromboembolic events, length of stay, and inpatient costs. For data obtained October 2015 and later, rates of graft rejection and graft failure were also measured. Regression models, weighted to account for the NRD sample design, were used to model associations between outcomes and transplant procedure, adjusting for patient age, sex, facility characteristics, comorbid conditions, and organs transplanted.ResultsA total of 75,069 hospitalizations for organ transplantation, corresponding to a national estimate of 160,368, were included. A diagnosis of IE was associated with 416 (weighted estimate = 898). IE cases were less likely to be female (22.2% vs. 37.9%, p< 0.001), and had higher rates of underlying pulmonary disease. The most common organ transplanted in the hospitalization during which IE was diagnosed (allowing for multiple organs) was heart (84.5%) followed by kidney (8.9%) and liver (7.9%), (p< 0.001). IE was associated with higher mortality [adjusted relative risk (aRR): 1.70, 95% confidence interval (CI) (1.09, 2.66)], prolonged ventilation (aRR 1.32 [1.06, 1.65], 4.6 additional inpatient days (CI: 1.5, 7.6) and $28,300 more inpatient cost (CI: $12,000, $44,700) (Table).60-Day Outcomes, Stratified by IE During Index Transplant Hospitalization ConclusionIE complicating hospitalization for organ transplantation is associated with higher rates of morbidity and mortality. IE during index transplant hospitalization occurs most frequently in heart transplant recipients. Understanding the high rate of IE in heart recipients in the early post-transplant period requires further study.Disclosures Vance G. Fowler, Jr., MD, MHS, Achaogen (Consultant)Actavis (Grant/Research Support)Advanced Liquid Logics (Grant/Research Support)Affinergy (Consultant, Research Grant or Support)Affinium (Consultant)Allergan (Grant/Research Support)Ampliphi Biosciences (Consultant)Basilea (Consultant, Research Grant or Support)Bayer (Consultant)C3J (Consultant)Cerexa (Consultant, Research Grant or Support)Contrafect (Consultant, Research Grant or Support)Cubist (Grant/Research Support)Debiopharm (Consultant)Destiny (Consultant)Durata (Consultant)Forest (Grant/Research Support)Genentech (Consultant, Research Grant or Support)Integrated Biotherapeutics (Consultant)Janssen (Consultant, Research Grant or Support)Karius (Grant/Research Support)Locus (Grant/Research Support)Medical Biosurfaces (Grant/Research Support)Medicines Co. (Consultant)Medimmune (Consultant, Research Grant or Support)Merck (Consultant, Research Grant or Support)NIH (Grant/Research Support)Novadigm (Consultant)Novartis (Consultant, Research Grant or Support)Pfizer (Grant/Research Support)Regeneron (Consultant, Research Grant or Support)Tetraphase (Consultant)Theravance (Consultant, Research Grant or Support)Trius (Consultant)xBiotech (Consultant)

COVID-19 Early After a Deceased Donor Kidney Transplant Surgery

Many transplant centers reduced their solid organ transplant procedures in response to the coronavirus disease 2019 pandemic.1,2 We describe the course of a kidney transplant recipient who presented with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection 10 days after transplant surgery. The patient is a 41-year-old Hispanic woman with end-stage kidney disease secondary to lupus nephritis on maintenance hydroxychloroquine 200 mg daily who presented for a zero HLA A, B, DR mismatched deceased donor kidney transplant. The donor was involved in a motor vehicle accident and sustained multiple injuries resulting in his death. He had a negative SARS-CoV-2 nasopharyngeal swab. The patient denied symptoms of SARS-CoV-2 infection or exposure to SARS-CoV-2-positive individuals and stayed at home before transplant except for going to her dialysis unit. Her preoperative nasopharyngeal swab for SARS-CoV-2 was negative and her chest X-ray was normal. She received induction immunosuppression with intravenous high-dose steroids and reduced-dose rabbit anti-thymocyte globulin, 3 mg/kg per our center’s protocol for zero antigen-mismatched transplants, and maintenance tacrolimus, mycophenolate 500 mg twice daily and prednisone taper in addition to hydroxychloroquine. She had immediate allograft function and was discharged 5 days following her transplant with serum creatinine of 1.7 mg/dL. Her absolute lymphocyte count at the time of discharge was 550 cells/mm3. Ten days posttransplant, she developed a fever of 100°F, dry cough, sore throat, and 2 episodes of diarrhea. A nasopharyngeal swab was obtained and was positive for SARS-CoV-2. It is thought that she acquired SARS-CoV-2 infection from contact with a family member who worked in a grocery store. Her oxygen saturation was 97% on room air and she had normal vital signs. Chest X-ray showed a new discoid opacity within the right lower lung (Figure 1). Mycophenolate was held, prednisone dose was immediately reduced from 20 mg to 10 mg and then to 5 mg maintenance, tacrolimus was dosed to maintain trough levels of 7–10 ng/mL, and hydroxychloroquine was increased to 200 mg twice daily, based on earlier reports in the pandemic about its presumed effectiveness. C-reactive protein was 0.4 mg/dL, absolute lymphocyte count was 1200 cells/mm3, and serum creatinine was 1.1 mg/dL. She received 1 unit of convalescent plasma transfusion through Food and Drug Administration expanded access pathway under a protocol that was approved by our Institutional Review Board; however, after completion, she developed urticaria, which was treated with antihistamines. She had a positive direct antiglobulin test confirming the transfusion reaction. She remained clinically stable and was discharged after 1 day of hospitalization with a pulse oximeter to monitor her oxygen saturation at home. More than 60 days have passed since discharge, and she continues to do well.FIGURE 1.: Left, Preoperative chest X-ray. Right, Chest X-ray at the day of presentation with COVID-19 symptoms.This report demonstrates that despite acquiring SARS-CoV-2 at the “peak” of immunosuppression, which included lymphocyte depletion, our patient had only mild symptoms and did not develop serious complications. The utility of convalescent plasma in renal transplant recipients with SARS-CoV-2 is not well defined. A recent report described successful recovery in a kidney transplant recipient who had severe infection with SARS-CoV-2 and was treated with 2 units of convalescent plasma.3 In view of the very recent and “heavy” immunosuppression in our patient, we decided to utilize convalescent plasma, despite her mild illness. More data are needed to better describe SARS-CoV-2 infection and treatment in peritransplant period. Finally, it is crucial to highlight the importance of taking meticulous measures and precautions in this patient population, especially in the presence of household contacts working at potentially “high risk” jobs for acquiring and transmitting SARS-CoV-2. Self-quarantine, physical distancing, and frequent hand hygiene should be undertaken at the highest potential levels.

Depletion of CD4 and CD8 Positive T Cells Impairs Venous Thrombus Resolution in Mice.

Resolution of deep venous thrombosis involves coordinated inflammatory processes. T cells regulate inflammation in vivo and modulate vascular remodeling in other settings, but their role in venous thrombus resolution remains undefined. To determine the role of T cells in venous thrombus resolution in vivo, stasis induced thrombi were created by vena cava ligation in outbred CD-1 mice. CD4 and CD8 positive T cells, as determined by flow cytometry, were present in thrombi both during thrombus formation and resolution. Depletion of the CD4 and CD8 positive T cells by antibody treatment selectively impaired thrombus resolution compared to animals treated with isotype control antibodies, without an effect on venous thrombus formation. Quantitation of intra-thrombus macrophage numbers, fibrinolytic marker expression, and gelatinolytic activity by zymography revealed that T cell depletion decreased the number of macrophages, reduced the expression of fibrinolytic marker urokinase plasminogen activator (uPA), and decreased the activity of matrix metalloprotinease-9 (MMP-9). These data implicate CD4 and CD8 positive T cells in functionally contributing to venous thrombus resolution, thus representing a potential therapeutic target, but also underscoring potential risks involved in T cell depletion used clinically for solid organ and hematopoietic transplantation procedures.

Hematopoietic Cell Transplantation (HCT) Followed By Solid Organ Transplantation (SOT) and SOT Followed By HCT: A Descriptive Analysis of Patients Undergoing Sequential Transplantation in the United States

<h3>Background</h3> Survival after solid organ transplantation(SOT) and hematopoietic cell transplantation(HCT) has increased over time. Despite these improvements, recipients of SOT are at increased risk for conditions leading to bone marrow failure, necessitating HCT. Moreover, recipients of HCT are at increased risk of developing organ failure, necessitating SOT. Complications of SOT and HCT have led the SOT and HCT communities to consider so-called, "sequential transplantation"; however, little data exists to inform outcomes and guide management decisions. We utilized data from the Center for International Blood and Marrow Transplant Research(CIBMTR) and the United Network for Organ Sharing(UNOS) to describe the characteristics and outcomes of patients with sequential transplantation in the United States. <h3>Methods</h3> A descriptive analysis of patients with sequential transplantation(SOT followed by HCT, HCT followed by SOT, HCT followed by SOT waitlist[WL]) was conducted. Analyses focused on SOT and HCT characteristics, outcomes including overall survival(OS) from first transplant and complications(graft-versus-host disease[GVHD] and SOT failure). <h3>Results</h3> We identified 258 patients registered with the CIBMTR and UNOS that had undergone sequential transplantation or been placed on the WL. Among patients who received a SOT followed by HCT(n=84), 50% underwent allogeneic HCT. In this group, there were 15 thoracic, 43 kidney, and 26 liver transplants performed prior to HCT, with living donation accounting for 23(54%) kidney and 2(8%) liver transplants. Five-year OS among recipients of SOT followed by HCT was 34%. Among patients who received an HCT followed by SOT(n=87) or HCT followed by WL(n=73), 45% underwent allogeneic HCT. Plasma cell disorder or multiple myeloma was the most common indication for HCT(48%).(Figure 1) There were 26 thoracic, 49 kidney, and 5 liver SOT procedures performed after initial HCT. Living donation accounted for 27(55%) kidney and 2(40%) liver transplants in this group. Five-year OS among recipients of HCT followed by SOT was 82%. Among all patients who underwent HCT, acute GVHD occurred in 47% and chronic GVHD in 53%. SOT graft failure occurred in 81(44%): 26(30%) SOT failures among HCT followed by SOT and 55(56%) SOT failures among SOT followed by HCT. <h3>Conclusion</h3> Sequential transplantation poses an enormous clinical challenge for members of the transplant community. OS among recipients of SOT followed by HCT is considerably less than OS among recipients of HCT followed by SOT. Additional analyses further characterizing outcomes of sequential transplantation and investigating potential factors associated with these outcomes are planned to assist SOT and HCT care providers in the management of these challenging clinical scenarios.

Calcium Score of Iliac Vessels and Relative Sparing of the External Iliac Artery Could Recommend Surgical Arterial Graft Selection

Background: Calcified plaque build-up can increase the risk of subsequent vascular complications in pelvic solid organ transplantation and vascular bypass procedures. Objectives: To assess the atherosclerotic calcification of pelvic vessels by measuring Agatston score and comparing it among abdominal aorta, common iliac artery (CIA), external iliac artery (EIA), and common femoral artery (CFA). Patients and Methods: We retrospectively reviewed the unenhanced computed tomography scans of 197 patients from August 2016 to March 2018. Using calcium-scoring software, we examined the distribution map of calcified plaques, focusing on four different arterial segments -the abdominal aorta, the common iliac artery (CIA), the external iliac artery (EIA), and the common femoral artery (CFA)- to determine which one showed the least mural calcification. Results: A total of 197 patients (118 men, 79 women) with a mean age of 61.19 ± 10.8 years were included in this study. The right EIA segment had the lowest average calcification score (92.1 ± 18.2), including 180 cases (91.4%) of zero calcification, followed by 178 cases (90.4%) of zero calcification in the left EIA. When adjustments were made for age, gender, smoking status, diabetes, hypertension and hyperlipidemia, the odds ratio (OR) of the left EIA for reaching a higher calcium score level was 1.19 (P = 0.44) times greater than the reference group (right EIA). The ratio was markedly higher in the abdominal aorta segment (OR = 146.7.4, P < 0.001), followed by the right CIA (OR = 42.5, P < 0.001), the left CIA (OR = 27.3, P < 0.001), the right CFA (OR = 3.96, P < 0.001), and the left CFA (OR = 3.51, P < 0.001). Conclusion: The study demonstrates a significantly less calcific plaque burden in EIA compared to the adjacent arterial bed.

Solid-organ transplant surgeries in era of COVID-19 pandemic: How to go about it?

Solid-organ transplant surgeries in era of COVID-19 pandemic: How to go about it?

Clinical Features of Post-Transplant Lymphoproliferative Disease Are Different between Kidney-Transplant Recipients from a Cadaveric Donor and Those from a Living Donor

Background: The number of solid organ transplantation (SOT) is increasing. While the remarkable improvement in SOT procedures provides recipients with a good chance of long-term survival, the prolonged immunosuppression has led toa variety of malignancies in solid organ transplant (SOT) recipients; post-transplant lymphoproliferative disorder (PTLD) is a life-threating complication among them. However, there remain some controversies regarding its clinical features. Method: We retrospectively surveyed the patients who had visited both departments: hematology and urology, or renal surgery in kidney center at Tokyo Women's Medical University Hospital from 2003 to 2017. We identified 61 patients diagnosed with hematological disorder in kidney-transplant recipients. Among them, PTLD were analyzed. Continuous variables were compared using Student's t-tests. Overall survival rate (OS) was calculated using the Kaplan-Meier method. P values &lt; 0.05 were considered significant. Statistical analyses were performed using JMP Pro 14 (SAS Institute Inc., Cary, NC, USA) and GraphPadPrism version 7.0 (GraphPad Software, San Diego, USA). This study was conducted in accordance with the Declaration of Helsinki and approved by the institutional review boards. Results: During the survey period, 3,133 patients had visited both departments: hematology and urology, or surgery in Kidney Center. Among them, 61 kidney-transplant recipients were diagnosed with hematological disorder; they comprised 27 PTLD, 10 plasmacytic disorder, 6 idiopathic thrombocytopenic purpura, 5 myelodysplastic syndromes, 4 acute leukemia, 3 polycythemia, 6 other diseases. Among the patients with PTLD (n = 27), 18 patients (66.7%) were male.Median patient ages at the diagnosis of PTLD and kidney transplant were 54 (25-79) and 43 (16-75) years, respectively. Eighteen and nine patients had received kidney-transplant from a living donor (15 related and three unrelated donors) and a cadaveric donor, respectively. The median time from kidney transplant to diagnosis of PTLD was 7.8 years; there was a significant difference in the time between the kidney-transplant recipients from a cadaveric donor and those from a living donor (Figure 1A, 11.3 and 5.6 years, P = 0.02). With regard to the histological subtypes of PTLD, they comprised 17 diffuse large B-cell lymphoma (63.0%), 2 Burkitt lymphoma (7.4%), 4 unclassified B-cell lymphoma (14.8%), 2 T-cell lymphoma (7.4%), and 2 unknown cases (7.4%). 24 of 27 patients had extranodal involvement: 9 central nervous system (33.3%), 7 gastrointestinal tract (25.9%) and other sites. First-line treatment procedure which all patients received was the modification of immunosupressants; complete response (CR) rate was 37.0%. After the failure of first-line therapy, 15 of 27 patients received chemotherapy: 4 rituximab monotherapy (30.8%), 6 CHOP-like regimens (46.2%), and other regimens (33.3%). Among them, five patients experienced relapse. They received salvage chemotherapy, and 2 and one patients achieved CR and partial response, respectively. Rest of them died of lymphoma and infection. The estimated five-year OS from the diagnosis of PTLD and the initiation of chemotherapy was 88.7% and 86.7%, respectively. During the survey period, 5 patients died; their causes of death were 3 lymphomas, 1 infection, and 1 heart failure. There were no deaths in kidney-transplant recipients from a cadaveric donor (Figure 1B). Discussion: While our cohort had more extranodal PTLD recipients than those reported previously, the modification of immunosupressants improved them in more than one-third of cases, which showed the usefulness of it as first-line treatment procedure for PTLD. Nearly half of cases were identified in recipients from a cadaveric donor; the results suggest that the incidence o PTLD among them is higher than those from a living donor because the number of kidney-transplant from a living donor was 10 times higher than those from a cadaveric donor. This study has several limitations due to its retrospective nature and small sample size. In addition, the estimated five-year OS might be better than actual because some patients became lost to follow-up. Further large-scale studies are warranted to validate the findings of this study. Disclosures Hagiwara: Bristol Myers Squibb: Membership on an entity's Board of Directors or advisory committees, Research Funding; Celgene: Membership on an entity's Board of Directors or advisory committees. Tanaka:Bristol-Myers Squibb: Research Funding.

Beyond Survival in Solid Organ Transplantation: A Summary of Expert Presentations from the Sandoz 6th Standalone Transplantation Meeting, 2018.

Beyond Survival in Solid Organ Transplantation: A Summary of Expert Presentations from the Sandoz 6th Standalone Transplantation Meeting, 2018.

Epidemiology and successful containment of a carbapenem-resistant Enterobacteriaceae outbreak in a Southern Italian Transplant Institute.

Carbapenem-resistant enterobacteriaceae (CRE) infections are difficult to treat and pose a serious threat to solid organ transplant (SOT) recipients. At our institute we observed an infection burden in 2012. In order to contain the spread of CRE infections, we established a taskforce to implement guidelines suggested by the Centers for Disease Control and Prevention (CDC) for this type of outbreak. Here, we describe the epidemiology of the outbreak in our SOT population, and the effectiveness of such interventions, by comparing levels of CRE hospital-acquired infection (HAI) pre- and post-task force intervention (from January 2009 to December 2012, and from September 2013 to December 2016, respectively) through a linear regression model. In this study, we included 933 patients who underwent a total of 1017 SOT procedures, 286 of whom had a CRE-positive culture (28.8%), of which 65 (22.7% of CRE positive) developed infection. One-year mortality post-SOT was significantly higher in patients with CRE infection. After the taskforce intervention, the CRE HAI rate in SOT showed a significant inverse trend (event rate: -1.28, CI -1.70 to 0.86; P<0.01). In the paucity of treatment options, the application of CDC measures in our SOT institute contributed significantly to containing CRE infections.

Risk Factors for Sepsis Based on Sepsis-3 Criteria after Orthotopic Liver Transplantation.

Sepsis is a common complication of solid organ transplant procedures and, in particular, can affect the prognosis of orthotopic liver transplantation (OLT). This retrospective study determined the pre-, peri-, and postoperative risk factors for sepsis after OLT, using as reference the 2016 Third International Consensus Definitions for Sepsis and Septic Shock (Sepsis-3). Pre-, peri-, and postoperative clinical data of the sepsis-positive (n = 85) and sepsis-negative (n = 41) groups were analyzed for potential risk factors of OLT-related sepsis. The sepsis-positive patients had a significantly higher rate of dialysis (49.4%), longer time under mechanical ventilation (1.5 d), higher hospitalization costs (0.41 million RMB), and worse survival rate (68.5%), compared with the sepsis-negative patients (4.8%, 1 d, 0.30 million RMB, and 73.1%, resp.). The multivariate logistic analysis identified the following as risk factors for OLT-related sepsis: preoperative Child-Pugh grade C (OR 10.43; 95% CI 2.081–52.292; P = 0.004), preoperative hypercalcemia (OR 6.372; 95% CI 1.693–23.98; P = 0.006), and perioperative acidosis (OR 6.364; 95% CI 1.196–33.869; P = 0.030). Patients with preoperative Child-Pugh grade C, preoperative hypercalcemia, or perioperative acidosis are at higher risk for developing sepsis after OLT. When any of these problems occur, timely sepsis management should be planned.

Use of Everolimus After Multivisceral Transplantation: A Report of Two Cases

Inhibitors of mechanistic target of rapamycin are used in solid organ transplant procedures to avoid calcineurin inhibitor complications, including nephrotoxicity and malignancy. We present 2 cases of multivisceral transplantation for neuroendocrine tumor (NET) for which everolimus was implemented for its potential to prevent NET recurrence as well as preserve renal function. The first case was complicated by NET recurrence in the liver before initiation of everolimus. After initiation of everolimus, the patient developed a ventral hernia and elevated aminotransferase levels with nonspecific biopsy findings. The second case was complicated by cytomegalovirus infection with elevated everolimus trough levels as well as acute cellular rejection. Everolimus was reinitiated in both cases in addition to decreasing the dosage of tacrolimus, and there were no further complications. Everolimus was beneficial in stabilizing renal function in both patients and has the theoretical potential to prevent recurrence of NET.

Hospital Demand for Blood Components in Ontario Correlates with Selected Diagnostic and Procedural Activities

AbstractAbstract 4272 Introduction:Demand for blood components in Canada is a significant and growing contributor to health care spending, but the drivers of this demand remain poorly characterized. While most institutions do not routinely monitor the transfusion requirements of individual diagnoses and procedures, an institution's overall demand for blood components and the types of clinical activities it provides are both well documented. Development of an institution-level inferential model may allow for more accurate demand forecasting for blood components. Methods:Hospital shipments of all blood components from Canadian Blood Services (red blood cells, platelets, plasma and cryoprecipitate) in the province of Ontario during the period 2006–2009 were merged with institution-level administrative data containing hospital characteristics and selected diagnostic and procedural codes as obtained from inpatient and ambulatory clinical databases maintained by the Canadian Institute for Health Information. Simple linear correlation and several nested multivariable linear regression models were fitted and compared. Results:From 2006–2009, our sample included 137 healthcare facilities, representing approximately 1.4 million units of RBCs, 400 000 units of plasma, 166 000 doses of platelets (defined as either one pool of whole blood-derived platelets or a single apheresis platelet), and 20 000 units of unpooled cryoprecipitate. Institutional demand for these blood components correlated with both hospital-level characteristics and diagnostic and procedural activity data. Institutional demand for red blood cells correlated most strongly with visits for cirrhosis and chemotherapy. Demand for plasma correlated most strongly with visits for cirrhosis and cardiac surgery procedures. Demand for platelets correlated most strongly with bone marrow and solid organ transplant procedures. Demand for cryoprecipitate correlated most strongly with visits for valvular heart disease and cardiac procedures. The strength of these correlations generally remained stable over the four years of analysis, during which time demand for red blood cells and platelets increased, demand for plasma decreased, and demand for cryoprecipitate remained stable. Conclusions:In the largest province of Canada, institutional demand for blood components correlate strongly with disease burden measured by diagnostic and procedural codes contained within administrative data. Disclosures:Pendergrast:Canadian Blood Services: Research Funding. Zagorski:Canadian Blood Services: Research Funding.

Predicted Cost Analysis for Solid Organ Transplantation in Private Practice in Greece

Introduction: Involvement of the private health sector in the field of solid organ transplantation was enabled by law for the first time in Greece in 2011. An analysis of the predicted cost of initiating a transplant program, especially considering the country's current austerity, is of vital importance before launching such an attempt. Methods: A detailed material and transportation cost analysis was performed. The budget units under consideration were pre-transplant patient evaluation, operative procedure (organ procurement & transplantation), and uneventful postoperative course for kidney (6 days) and liver (15 days) transplantation. Surgeons' fees and calculated profit for the providing private healthcare company were not included in the study. Results:Conclusion: To the best of our knowledge, this is the first cost analysis of solid organ transplantation procedures in private practice in Greece. Given the recent failure of introducing diagnosis-related groups (DRGs) within the framework of the country's public health sector, this study currently depicts the only opportunity for ascertainment of expenses in the field of transplantation. Furthermore, it strengthens the argument for Greek patients avoiding expensive treatment abroad and even more, it opens the perspective of foreign patients undergoing cost-effective treatment in Greece.

Single dose Dexamethasone for Postoperative Nausea and Vomiting – a Matched Case-Control Study of Postoperative Infection Risk

Dexamethasone is an effective prophylaxis against postoperative nausea and vomiting but is immunosuppressive and may predispose patients to an increased postoperative infection risk. This matched case-control study examined the association between the administration of a single intraoperative anti-emetic dose of dexamethasone (4 to 8 mg) and postoperative infection in patients undergoing non-emergency surgery in a university trauma centre. Cases were defined as patients who developed infection between one day and one month following an operative procedure under general anaesthesia. Controls who did not develop infection were matched for procedure, age and gender Exclusion criteria included immunosuppressive medications, chronic glucocorticoid therapy, cardiac surgical and solid-organ transplantation procedures. Sixty-three cases and 172 controls were identified. Cases were more likely to have received dexamethasone intraoperatively (25.4 vs. 11%, P = 0.006), and less likely to have received perioperative antibiotic prophylaxis (60.3 vs. 84.3%, P = 0.001). Stepwise, multivariate conditional logistic regression confirmed these associations, with adjusted odds ratios of 3.03 (1.06 to 19.3, P = 0.035) and 0.12 (0.02 to 0.7, P = 0.004) respectively for the associations between dexamethasone and perioperative antibiotic prophylaxis, with postoperative infection. We conclude that intraoperative administration of dexamethasone for anti-emetic purposes may confer an increased risk of postoperative infection.