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Objectives Acute and chronic allograft rejection have been continuously an important obstacle in the follow-up of renal transplant recipients. During clinical management, several factors acting simultaneously result in acute rejection and chronic allograft nephropathy. Matrix metalloproteinases and tissue inhibitors of metalloproteinases are responsible for the organization of the extracellular matrix and play roles in cell proliferation and cellular invasion. Changes in matrix metalloproteinase expression levels have been reported to be associated with renal allograft rejection and interstitial fibrosis. In this study, we aimed to investigate functional polymorphisms of MMP2, MMP9, and TIMP2 genes in pediatric renal transplant recipients. Materials and methods Our study included 68 kidney transplant recipients and 58 control patients. The kidney transplant recipient group was further divided into 2 subgroups: no graft rejection (n = 47) and graft rejection (n =21). MMP2 -735C >T (rs2285053), MMP2 -1306C >T (rs243865), MMP2 -1575G >A (rs243866), MMP9 c.-1562C >T (rs3918242), TIMP2 -418G >C (rs8179090), and TIMP2 303C > T (rs2277698) polymorphisms were analyzed with the use of polymerase chain reaction and restriction fragment-length polymorphism methods. Allele prevalence was compared with reference values of the control group, and Hardy-Weinberg equilibrium was tested. Results Mean ages were 16.7 ± 3.9 years for the study group and 14.8 ± 5.6 years for the control group. The mean follow-up time after transplant was 37.7 ± 7.9 months. We compared allele frequencies in the 2 groups and calculated a statistically significant difference in rs2285053, rs243865, rs243866, rs3918242, rs8179090, and rs2277698 polymorphism frequencies between the transplant recipients and control patients. When the transplant recipient group was compared in itself with regard to allograft rejection, all investigated polymorphisms except TIMP2 -418G >C (rs8179090) revealed a statistically significant difference between those with and without rejection (P Conclusions Matrix metalloproteinases and their tissue inhibitors could be important predictive biological markers for the follow-up of kidney transplant recipients.

Ex vivo normothermic perfusion (EVNP) is increasingly recognised as a viability tool to increase organ utilisation in deceased donor transplantation. We report the use of EVNP to assess graft perfusion quality following indication nephrectomy and back-bench arterial reconstruction in a case of renal artery stenosis, unamenable to endovascular treatment. Once explanted, it was not possible to effectively cold perfuse the graft through the main renal artery or collaterals. An arterial reconstruction was performed with patch angioplasty using the largest collateral creating a single common stem. EVNP was used to assess organ perfusion and, therefore, viability. Excellent global perfusion was evident alongside urine production, demonstrating that the arterial reconstruction was satisfactory. A patient with end-stage renal disease was consented with particular attention to the uncertainty of the underlying donor disease process and long-term outcome of the reconstruction. Primary function was achieved and recipient estimated glomerular filtration rate (eGFR) remains stable at 58 mL/min/1.73 m² at 6 months.

Objectives This study aimed to compare the effects of N-acetylcysteine and benfotiamine in protection of ovarian tissue from ischemia caused by slow neovascularization injury due to intraperitoneal ovarian autotransplant in rats. Materials and methods Twenty-eight female rats were divided into 4 groups, each containing 7 rats. Group 1 only had the abdomen opened and closed, group 2 was the transplant-only group, group 3 received benfotiamine for 3 weeks starting 1 day before the transplant procedure, and group 4 received N-acetylcysteine for 3 weeks starting 1 day before the transplant procedure. At the end of the experimental period, malondialdehyde levels in ovarian tissues together with the apoptosis and fibrosis, proliferating cell nuclear antigen and vascular endothelial growth factor immunoreactivity, and ovarian reserves were investigated. Results Apoptosis was significantly increased in group 2 animals. Primordial follicle count was higher in groups 3 and 4 than in group 2. Vascular endothelial growth factor immunoreactivity was decreased in groups 3 and 4 compared with group 2. Proliferating cell nuclear antigen immunoreactivity was reduced in the secondary follicles in all transplant groups. Conclusions In autologous intraperitoneal ovarian transplant, both benfotiamine and N-acetylcysteine are equal and effective agents in protection of ovarian tissue against ischemic injury.

Objectives Infection-associated emergency department use in renal transplant recipients has been increasing as solid-organ transplant has become a more common treatment method for chronic kidney failure. Platelet-to-lymphocyte ratio has been demonstrated to be significantly elevated in nosocomial infections in patients treated at intensive care units and is positively correlated with duration of hospital stay. In this study, we aimed to determine whether the platelet-to-lymphocyte ratio could be used as an indicator of infection in renal transplant patients presenting to emergency departments. Materials and methods This case-control retrospective study included data from between May 2015 and February 2018. We used the patient information management system to review patient medical records and laboratory test results of study participants. Results Our study included 156 adults in the patient group (recipients with infection) and 170 adults in the control group (recipients without infection). We observed significant differences between patient and control groups in terms of the number of days of hospital stay; leukocyte, neutrophil, and lymphocyte counts; the platelet-to-lymphocyte ratio; and C-reactive protein levels. We plotted receiver operating characteristic curves to determine the sensitivity and specificity of the platelet-to-lymphocyte ratio along with C-reactive protein. The areas under the curve were 0.892 for C-reactive protein and 0.707 for the platelet-to-lymphocyte ratio. Conclusions For systemic inflammation, platelet-to-lymphocyte ratio can be used in conjunction with other biomarkers as an indicator of inflammation in renal transplant recipients who present with infection-associated causes to emergency departments.

Objective Genetically engineered pigs are thought to be an alternative organ source for patients in end-stage heart failure unable to receive a timely allograft. However, cardiac xenografts exhibit growth and diastolic heart failure within 1 month after transplantation. Grafts function for up to 6 months, but only after administration of temsirolimus and afterload-reducing agents to reduce this growth. In this study we investigated the growth and hemodynamics of growth hormone receptor (GHR) knockout xenografts, without the use of adjuncts to prevent intrinsic graft growth after transplantation. Methods Genetically engineered pig hearts were transplanted orthotopically into weight-matched baboons between 15 and 30 kg, using continuous perfusion preservation before implantation (n = 5). Xenografts included knockout of carbohydrate antigens and knockin of human transgenes for thromboregulation, complement regulation, and inflammation reduction (grafts with intact growth hormone, n = 2). Three grafts contained the additional knockout of GHR (GHR knockout grafts; n = 3). Transthoracic echocardiograms were obtained twice monthly and comprehensively analyzed by a blinded cardiologist. Hemodynamics were measured longitudinally after transplantation. Results All xenografts demonstrated life-supporting function after transplantation. There was no difference in intrinsic growth, measured using septal and posterior wall thickness and left ventricular mass, on transthoracic echocardiogram out to 1 month in either GHR knockout or GHR intact grafts. However, hypertrophy of the septal and posterior wall was markedly elevated by 2 months post transplantation. There was minimal hypertrophy out to 6 months in GHR knockout grafts. Physiologic mismatch was present in all grafts after transplantation, which is largely independent of growth. Conclusions Xenografts with GHR knockout show reduced post-transplantation xenograft growth using echocardiography >6 months after transplantation, without the need for other adjuncts.

Introduction Multiple myeloma (MM) patients with renal impairment (RI), especially dialysis-dependent (DD) RI, have poorer outcomes than MM patients with normal renal function. Autologous stem cell transplantation (ASCT) is a treatment option, but there is concern at a perceived higher risk of complications which may be limiting consideration of the use of ASCT in this population. The evidence is inconsistent among studies and interpretation is complicated by heterogeneous datasets, some dating to before the availability of novel agents. Finally, the reversibility of RI following ASCT is an important prognostic factor for both survival and quality of life. Aim To evaluate the safety and efficacy of ASCT in MM patients with DD RI transplanted in EBMT centres between 1997 and 2017. Methods Baseline characteristics at diagnosis, patient treatment regimens and clinical outcomes were collected using standardised report forms. OS was defined as the period between the date of ASCT and the date of death or the date of last observation. PFS was defined as the period between the date of ASCT and date of progression/relapse or death of any causes or the date of the last observation. Cox proportional hazard regression analysis was applied to assess risk factors for progression and death. Survival curves were plotted by the Kaplan-Meier method and compared using log-rank test. P Results A total of 109,959 adult MM patients are registered in the EBMT database as having undergone ASCT between 1997 and 2017. We further analysed 118 DD MM patients who had a first ASCT during this period. The median (range) age was 57 (27-71) years. Seventy (59%) patients were males. Forty nine patients (49/94 patients, 52%) had Karnofsky score ≥90. One hundred and ten patients were treated with hemodialysis and eight with peritoneal dialysis. A total of 68 (58%) patients had Light Chain MM, 43 kappa and 25 Lambda. In first-line induction therapy, 47/76 (62%) patients received bortezomib-based regimens. Forty-four (37%) patients achieved at least VGPR pre-ASCT. The median time from diagnosis to ASCT was 0.7 years (0.3-4.9). Melphalan doses were as follows: 140 mg/m2 (n=55, 67%), 70-100 mg/m2 (n=15, 18%), and >140 mg/m2 (n=12, 15%). The times to Neutrophil (>0.5) and Platelet (>20) engraftment were 12 (10-37) and 14 (4-128) days, respectively. The 30-day and 100-day transplant-related mortality (TRM) rates were 0.0% and 0.9%, respectively. ASCT was associated with a significant deepening of response (at least VGPR pre- vs post-ASCT: 36/93 (39%) vs 48/93 (52%), p < 0.001). The median PFS was 37 months (95% CI: 24-43) and 5-year PFS was 31% (95% CI: 20-41). The median OS was 102 months (95% CI: 67-129). Five-year OS post-ASCT was 62% (52-72) and 10-year OS 36% (17-55). Thirty-one (26%) DD MM patients achieved dialysis independence. There were no differences in PFS or OS when comparing the 1997-2007 and 2008-2017 cohorts: 5-year PFS - 28% (6-49) vs 31% (19-43) (p=0.7) and 5-year OS - 61% (38-84) vs 63% (51-74) (p=0.9), respectively. On univariate analysis of factors affecting PFS, achievement of an Overall Response Rate (ORR) (CR+VGPR+PR vs. Other) pre-ASCT was associated with a lower risk (HR 0.467, p=0.032) and older age (>55 years) with a higher risk (HR 1.786, p=0.035) of post-ASCT progression. Age higher than 55 (HR 2.033, 95%CI: 0.992 - 4.166, p=0.053) increased and achievement of at least VGPR pre-transplant (HR 0.494, 95%CI: 0.224 - 1.091, p=0.081, on the verge of statistical significance) decreased the risk of death. Conclusion To the best of our knowledge, the DIADEM study is the largest analysis of ASCT in DD MM pts to date. This cohort of 118 unselected patients had an OS comparable to patients without RI. This may reflect patient selection based on younger age, Karnofsky scores and pre-ASCT response. The low TRM and excellent outcomes support consideration of the use of ASCT in pts with DD RI. Notably, more than a quarter of patients became dialysis independent, an outcome likely to confer an improved Quality-of-Life.. These results can also inform the debate around the role of renal transplantation in younger DD MM patients who do not achieve dialysis independence. Disclosures Snowden: IDMC: Honoraria; Kiadis: Membership on an entity's Board of Directors or advisory committees; Janssen: Honoraria; Mallinckrodt: Honoraria; Jazz: Honoraria; Gilead: Honoraria. Dreger:MSD: Membership on an entity's Board of Directors or advisory committees, Other: Sponsoring of Symposia; AbbVie, AstraZeneca, Gilead, Janssen, Novartis, Riemser, Roche: Consultancy; AbbVie, Gilead, Novartis, Riemser, Roche: Speakers Bureau; Neovii, Riemser: Research Funding. Illés:Takeda, Seattle: Research Funding; Janssen, Celgene, Novartis, Takeda, Roche, Pfizer: Honoraria, Membership on an entity's Board of Directors or advisory committees. Basak:Teva: Honoraria; Celgene: Honoraria. Gyan:Pfizer: Honoraria. Hayden:Alnylam: Honoraria; Amgen: Honoraria. Beksac:Amgen: Consultancy; Celgene: Consultancy; Janssen&Janssen: Consultancy; Takeda: Consultancy. Schönland:Janssen: Membership on an entity's Board of Directors or advisory committees, Research Funding; Medac: Other: Travel Grant; Takeda: Membership on an entity's Board of Directors or advisory committees, Research Funding; Prothena: Membership on an entity's Board of Directors or advisory committees, Research Funding.

AimsTo identify risk factors for rebubbling, and early graft failure after Descemet membrane endothelial keratoplasty (DMEK).MethodsIn this prospective registry study, all consecutive DMEK procedures registered in the Netherlands Organ Transplant Registry were assessed (n=752). Univariable and multivariable analysis was performed using logistic regression. The effect of rebubbling on endothelial cell density was analysed using a linear mixed model.Results144 of 752 (19%) eyes underwent rebubbling. Rebubbling was successful in 101 eyes (70%). In eyes that underwent rebubbling, the graft failure rate was significantly higher than eyes that did not undergo rebubbling (30% vs 9%, respectively; OR: 4.28, 95% CI 2.72 to 6.73, pConclusionsThis Dutch registry study identified independent risk factors for DMEK graft detachment leading to rebubbling, namely recipient age and surgical complication, and early graft failure, namely transplantation before 2016 and surgical complication. Rebubbling was associated with significantly higher endothelial cell loss in the first year after surgery.

End-stage renal disease in the human immunodeficiency virus-positive population is increasing. Kidney transplant is the optimal therapy for this population rather than dialysis modalities if some criteria are met. These include undetectable plasma human immunodeficiency virus RNA, CD4 cell count over 200 cells/μL, and the absence of any AIDS-defining illness. Here, we describe the first living-donor kidney transplant in a human immunodeficiency virus-positive recipient in Turkey. The patient, a 52-year-old male diagnosed as human immunodeficiency virus positive, was on antiretroviral therapy, which consisted of 400 mg twice daily darunavir, 100 mg/day ritonavir, and 50 mg/day dolutegravir. He had been negative for human immunodeficiency virus RNA for the past 3 years. The patient developed renal insufficiency without any known cause and started hemodialysis. A living donor transplant from his son was performed, and the patient received ATG Fresenius-S (Neovii Biotech, Rapperswil, Switzerland) induction and a maintenance immunosuppression therapy consisting of methyl-prednisolone, mycophenolate mofetil, and tacrolimus. There were no incidences of delayed graft function or acute rejection. Because of tacrolimus and ritonavir interaction, tacrolimus trough levels were too high. With tacrolimus withdrawn, tacrolimus trough level decreased to detectable levels 2 weeks later. Antiretroviral therapy was continued on the same dosage. At month 4 posttransplant, the patient's creatinine level was 1.01 mg/dL. At present, the patient has had no complications and no episodes of rejection. Kidney transplant is the most favorable replacement therapy for HIV-positive patients who are under controlled AIDS care with highly active antiretroviral therapy. However, drug interactions should be carefully evaluated.

Background: The peri-hilar branching pattern of renal arteries and variations such as accessory renal artery and early branching of the renal artery are important factors to be evaluated preoperatively to minimize potential complications during renal transplantation and renal surgeries. The present was done to study the perihilar branching pattern of the renal artery and variations of the renal artery in kidney donors. Materials and methods: 198 kidneys from 99 donors were analyzed using pre-operative CT renal angiograms prospectively, over 1 year 2 months. Results : Based on the branching pattern of primary and secondary branches of renal arteries, we identified 8 cardinal and 10 minor peri-hilar branching patterns. Type I (duplicated fork) peri- hilar branching pattern was the most found (70.2%) among 198 kidneys, followed by type II (triplicated fork) (19.2%) and type III (ladder) (10.6%). Duplicated fork pattern was common in both the right renal artery (75.7%) and left renal artery (64.6%) respectively. The prevalence of accessory renal artery was 39.4% with hilar artery at 21.2% and polar artery at 18.2%, and the prevalence of early division of renal artery was 20.2%. No statistical significance was associated between gender and laterality in the prevalence of both early division and accessory renal arteries (P > 0.05). Early division of renal artery was more frequent in females (28%) whilst accessory renal arteries were more common in males (40.7%). Conclusions: The present study showed a consistent peri-hilar branching pattern with high individual variability among Indian renal donors. The knowledge about the peri-hilar branching pattern as well as renal artery variations conferred by this study would greatly compliment urological surgeons during renal transplant surgeries.

Peripheral T-cell lymphomas (PTCLs) represent a heterogeneous disease group accounting for 10% of non-Hodgkin lymphomas. PTCL patients have typically poorer outcomes compared to aggressive B-cell lymphomas. However, such outcomes are heavily dependent upon subtype. Although anthracycline-based regimens such as cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) remain the standard first-line treatment for most aggressive PTCLs, there are important variations including incorporation of novel agents, use of radiotherapy and judicious consideration of stem cell transplantation. Relapsed or refractory disease represents a significant area of unmet need where chemotherapy intensification has limited efficacy and novel agents such as brentuximab vedotin and pralatrexate provide additional opportunities for attainment of remission and potential stem cell transplant. In the future, pre-therapy prognostic biomarkers including genomic characterisation, may aid in risk stratification and help guide initial patient management to improve survival. There is an urgent need to better understand the pathogenesis of PTCLs to facilitate novel drug combinatorial approaches to improve survival. This position statement represents an evidence-based synthesis of the literature for application in Australian and New Zealand practice. This article is protected by copyright. All rights reserved.

INTRODUCTION: Organs procured following brain stem death (BSD) are the main source of organ grafts for transplantation. However, BSD is associated with inflammatory responses that may damage the organ and affect both the quantity and quality of organs available for transplant. Therefore, we aimed to investigate plasma and bronchoalveolar lavage (BAL) pro-inflammatory cytokine profiles and cardiovascular physiology in a clinically relevant 6-hour ovine model of BSD. METHODS: Twelve healthy female sheep (37‒42 Kg) were anaesthetized and mechanically ventilated prior to undergoing BSD induction and then monitored for 6 hours. Plasma and BAL endothelin-1 and cytokines (IL-1β, 6, 8 and tumour necrosis factor alpha (TNF-α)) were assessed by ELISA. Differential white blood cell counts were performed. Cardiac function during BSD was also examined using echocardiography, and cardiac biomarkers (A-type natriuretic peptide and troponin I were measured in plasma. RESULTS: Plasma concentrations big ET-1, IL-6, IL-8, TNF-α and BAL IL-8 were significantly (p < 0.01) increased over baseline at 6 hours post-BSD. Increased numbers of neutrophils were observed in the whole blood (3.1×109 cells/L [95% confidence interval (CI) 2.06 - 4.14] vs. 6×109 cells/L [95%CI 3.92 - 7.97]; p < 0.01) and BAL (4.5×109 cells/L [95%CI 0.41 - 9.41] vs. 26 [95%CI 12.29 - 39.80]; p=0.03) after 6 hours of BSD induction vs baseline. A significant increase in ANP production (20.28 pM [95%CI 16.18 - 24.37] vs. 78.68 pM [95%CI 53.16 - 104.21];p < 0.0001) and cTnI release (0.039 ng/mL vs. 4.26 [95%CI 2.69 - 5.83] ng/mL; p < 0.0001), associated with a significant reduction in heart contractile function, were observed between baseline and 6 hours. CONCLUSIONS: BSD induced systemic pro-inflammatory responses, characterized by increased neutrophil infiltration and cytokine production in the circulation and BAL fluid, and associated with reduced heart contractile function in ovine model of BSD.

OBJECTIVES End-stage kidney disease has dramatic health effects and life consequences in children. Presently, kidney transplant has been globally accepted as a treatment of choice for end-stage kidney disease in both children and adults, leading to better quality of life and longer patient survival. Because of lack of comprehensive information on the outcome of kidney transplant among children in Iran, we aimed to present a proper vision of pediatric kidney transplant in Iran by systematically reviewing the current literature. MATERIALS AND METHODS Major databases were searched, including Medline, Web of Knowledge, Google Scholar, Scopus, Cochrane, and the Iranian Scientific Information Database for all eligible studies in accordance with specific keywords. The inclusion criteria for the retrieved studies were determination of graft survival, patient survival, and reasons for graft failure. The exclusion criteria were as follows: (1) a lack of clear results; (2) non-English or non-Persian language format; (3) lack of access to the full-text manuscripts; and (4) case reports, case series, and review papers. A total of 115 studies were initially assessed based on the keywords; of these, 8 met inclusion criteria and were considered for final analysis; these were published between 2005 and 2017. RESULTS According to our results, 1-year graft survival rates were overall 89.7%, and 5-year graft survival rates were 65.4%. The 1-year patient survival rates were estimated to be 97.1%, and 5-year patient survival rates were estimated to be 89.8%. Acute rejection, dialysis status before transplant, and inappropriate immunosuppression were the main risk factors. CONCLUSIONS Our systematic review and meta-analysis indicated a high success rate of childhood kidney transplant in Iran according to long-term graft and patient survival rates.

Ureteral obstruction is one of the most common urological complications after kidney transplant. The definitive treatment of ureteral obstruction has been surgical revision. Because of the increased morbidity of surgery, minimally invasive percutaneous procedures have gained more acceptance in recent years. Presently, interventional radiological procedures are recommended as the first step in treatment of ureteral obstructions. Ureteral occlusions or near-occlusion high-grade stenoses require greater catheter backup force. Antegrade interventions generally prefer upper-to-middle calyx puncture. Cranial/superior proximal ureter stenoses cause severe angulations. Steep angulations of proximal ureter and ureteropelvic tight stenoses may require direct puncture of the renal pelvis or another calyx to achieve a less difficult angle. The double-puncture technique may help to manage severe angulations of proximal ureter and near-occlusion tight stenosis of the ureteropelvic junction.

Chyle leak after living donor nephrectomy is a rare complication and is associated with a significant postoperative burden. To the best of our knowledge, only 1 case of chyle leak after robotic living donor nephrectomy has been reported in the literature. In this study, we present our experience with 2 cases of chyle leak: 1 after and 1 during robotic donor nephrectomy. We discuss previously published studies and man - agement options of chyle leak in kidney donors.

Background Upper extremity (UE) transplantation is a complex undertaking that may require emergent or elective secondary surgery (SS) days to years following transplant. Various patient and transplantation may help determine what SS is needed. In this study, we characterize the SS needed by our UE transplant patients. Methods We retrospectively reviewed 6 patients who underwent hand and UE transplantation by one of the authors. Transplantation and SS details were obtained from medical records. Hand and arm function was quantified both subjectively (patient-reports) and objectively (Disabilities of the Arm, Shoulder, and Hand Score; Carroll test; Action Research Arm Tests; Box and Block test). Results Six patients underwent transplantation for a total of 10 transplanted limbs. Five transplants were performed below and 5 above the elbow. Mean time post-transplantation at last follow-up was 5 years (range: 1-9 years). In all, 66.7% of the patients required SS: total 7 surgeries comprising 13 procedures. The most common procedures were to improve hand function—nerve decompressions and tendon transfer, both in above-elbow transplant. Both patients showed a mean improvement of 15 points on Carroll scores. One above-elbow transplant had a brachioplasty for excess skin and another had a hematoma evacuation immediately after transplantation. Procedures in the below-elbow transplants included multiple incision and drainages for a septic wrist and an open reduction and internal fixation for a forearm fracture. Conclusion Patients receiving UE transplantation often require one or more secondary procedures which may vary with level of transplantation. Secondary surgery should be an important aspect of pretransplant planning and cost-effectiveness determinations. Level of Evidence Level IV

Central nervous system lymphoproliferative disorder (CNS-PTLD) after organ transplant is a unique clinicopathological entity and is associated with poor survival rates. When the CNS is involved, intravenous rituximab might not be the treatment of choice, due to its poor CNS penetration. However, intrathecal (IT) administration of rituximab has shown to be safe and efficient in small studies and in case series. We report here the case of a patient with late development of CNS-PTLD after kidney-pancreas transplantation who achieved complete remission after surgical resection and four cycles of IT rituximab and we provide a review of the literature for this treatment option.

This is the unformatted version of the accepted review paper manuscript "Extended criteria grafts and emerging therapeutics strategy in liver transplantation. The unstable balance between damage and repair" published on Transplant Rev (Orlando)2021 Dec;35(4):100639. doi: 10.1016/j.trre.2021.100639., by Ghinolfi D, Melandro F, Torri F, Martinelli C, Cappello V, Babboni S, Silvestrini B, De Simone P, Basta G,Del Turco S. Due to increasing demand for donor organs, "extended criteria" donors are increasingly considered for liver transplantation, including elderly donors and donors after cardiac death. The grafts of this subgroup of donors share a major risk to develop significant features of ischemia reperfusion injury, that may eventually lead to graft failure. Ex-situ machine perfusion technology has gained much interest in liver transplantation, because represents both a useful tool for improving graft quality before transplantation and a platform for the delivery of therapeutics directly to the organ. In this review, we survey ongoing clinical evidences supporting the use of elderly and DCD donors in liver transplantation, and the underlying mechanistic aspects of liver aging and ischemia reperfusion injury that influence graft quality and transplant outcome. Finally, we highlight evidences in the field of new therapeutics to test in MP in the context of recent findings of basic and translational research.

Pulmonary rehabilitation is a cornerstone of management for patients after lung transplantation (LT), but the benefits of inspiratory muscle training (IMT) after LT in children are unclear. Therefore, we examined whether IMT can improve respiratory function and dyspnoea in a paediatric patient after LT.The patient was a 13-year-old boy who underwent double LT. However, mild physical activity such as walking triggered dyspnoea for the patient. The patient underwent IMT with the intensity of approximately 30% of his maximal inspiratory pressure (MIP) for 2 months.The patient’s MIP was increased by approximately 60% after 2 months, and his forced vital capacity as a percent of the predicted normal value increased from 74.6% to 83.4%, with improvement of dyspnoea.IMT may help improve dyspnoea after LT in children with respiratory muscle weakness and a decline in respiratory function.

The purpose of this study was to determine if an expertnetwork, a form of artificial intelligence, could effectivelystratify cardiac risk in candidates for renal transplant.Input into the expert network consisted of clinical riskfactors and thallium-201 stress test data. Clinical riskfactor screening alone identified 95 of 189 patients ashigh risk. These 95 patients underwent thallium-201stress testing, and 53 had either reversible or fixed defects.The other 42 patients were classified as low risk.This algorithm made up the ‘‘expert system,’’ and duringthe 4-year follow-up period had a sensitivity of 82%,specificity of 77%, and accuracy of 78%. An artificial neural network was added to the expert system, creatingan expert network. Input into the neural networkconsisted of both clinical variables and thallium-201stress test data. There were 5 hidden nodes and the output(end point) was cardiac death. The expert networkincreased the specificity of the expert system alone from77% to 90% (p

Background Employment is important for the quality of life and financial security of patients of working age receiving kidney replacement therapy (KRT). We aimed to examine self-reported work status and general, physical and mental work ability and to determine associations between demographic, disease-related, work-related and macroeconomic factors and employment. Methods Europeans from 37 countries, ages 19–65 years, treated with dialysis or kidney transplantation, filled out the web-based or paper-based cross-sectional EDITH kidney patient survey between November 2017 and January 2019. We performed descriptive analyses and multivariable generalized logistic mixed models. Results Of the 3544 patients, 36.5% were employed and working [25.8% of dialysis patients, 53.9% of kidney transplant recipients (KTRs)]. The mean general work ability was 5.5 out of 10 (dialysis: 4.8, KTRs: 6.5). Non-working patients (all: 4.1, dialysis: 3.9, KTRs: 4.7) scored lower than working patients (all: 7.7, dialysis 7.3, KTRs: 8.0). Working dialysis patients scored lower on physical and mental work ability (7.1 and 8.1) than working KTRs (8.0 and 8.4; P Conclusions Low employment rates and impaired work ability were prevalent among European patients receiving KRT. Demographic, disease-related, work-related and macro-economic factors were associated with employment.

Background This report describes 9 high-risk neonates and infants with hypoplastic left heart syndrome (HLHS) who were stabilized with a combined hybrid approach and ventricular assist device (VAD) insertion (HYBRID+VAD) in preparation for heart transplantation. Methods A total of 9 patients with HLHS (7 neonates, 2 infants) presented with anatomic or physiologic features associated with an increased risk for conventional univentricular palliation with the Norwood operation (large coronary sinusoids or fistulas, severe tricuspid regurgitation, cardiogenic shock, restrictive atrial septum). These patients underwent combined VAD insertion (Berlin EXCOR, Berlin Heart, Inc, Berlin, Germany) and Stage 1 hybrid palliation (application of bilateral pulmonary bands, stent placement in the patent arterial duct, and atrial septectomy if needed). During this same era, at the Congenital Heart Center, University of Florida, Gainesville, Florida, 46 neonates underwent a Norwood operation, 4 neonates underwent a hybrid approach “Stage 1” without VAD, and 3 patients with HLHS were supported with prostaglandin while awaiting heart transplantation. Results At HYBRID+VAD insertion, the median age was 20 days (range, 13 to 143 days), and median weight was 3.25 kg (range, 2.43 to 4.2 kg). Six patients survive (67%), and 3 patients died (33%). Five survivors are at home doing well after successful heart transplantation, and 1 survivor is doing well in the intensive care unit on VAD support while awaiting transplantation. Only 1 of 6 survivors (16.7%) required intubation more than 10 days after HYBRID+VAD insertion. In 8 patients no longer undergoing VAD support, the median length of VAD support was 119.5 days (range, 56 to 196 days). Conclusions High-risk patients with HLHS who are suboptimal candidates for Norwood palliation can be successfully stabilized with pulsatile VAD insertion along with hybrid palliation while awaiting cardiac transplantation. These patients may be extubated and optimized for transplantation while undergoing VAD support.

Meniscal allograft transplantation may be indicated in a subset of patients with high-grade meniscectomy or irreparable meniscal injury and persistent knee pain that is resistant to conservative management. Meniscal allograft transplantation has demonstrated good to excellent results in short-term to midterm follow-up studies and satisfactory outcomes in long-term studies. The goals of the article are to review the indications, preoperative imaging assessment, surgical techniques, and postoperative assessment of uncomplicated and complicated meniscal allograft transplants.

Better diagnostic and treatment modalities for malignancies occurring in childhood and young age have increased the overall survival of the affected young girls and boys, but this has come at a cost of developing premature ovarian failure in girls and azoospermia in boys because of the gonadotoxicity of chemotherapy and radiotherapy. Thus, young girls and women of reproductive age who are at risk of ovarian failure due to cancer treatment must be mandatorily offered fertility preservation in any form such as cryopreservation of mature metaphase II oocytes after ovarian stimulation with gonadotropins and oocyte recovery and cryopreservation of embryos if the young female has a partner. However, these modalities may require the postponement of chemotherapy. Thus, in such instances, cryopreservation of ovarian tissue remains the only option. Herein, we report a case of a nulligravid young female patient who had stage IV Hodgkin’s lymphoma and had to be taken up for immediate fertility preservation owing to the advanced stage of the disease. Therefore, cryopreservation of ovarian tissue was performed. The uniqueness of the case is that after remission of the disease was achieved with chemotherapy, transplantation of the ovarian tissue was carried out which was not successful, but the desire for motherhood prompted to carry out an ovulation induction in the remnant native ovary with a severely compromised ovarian reserve, and she conceived.

To present immunocytochemical characterization of a surgically excised central posterior lens capsule (PLC) that was transplanted to close a secondary refractory full-thickness macular hole (FTMH) as an epiretinal flap. For comparison, tissue of both an unaffected internal limiting membrane and unexposed PLC was processed.Clinical-pathological case report.We report of a 38-year-old patient who underwent pars plana vitrectomy (PPV) with PLC tissue for patching secondary FTMH and silicone oil tamponade after tractional retinal detachment. The PLC was peeled off during a vitrectomy 1 year after positioning. For immunocytochemistry, the removed PLC was prepared as flat mount and showed a positive immunofluorescence of the Müller cells marker glutamine synthetase and for vimentin. The microglia marker IBA and the neuroprotective neurotrophic marker glia cell-derived neurotrophic factor were tested positive too. There was no immunoreactivity of cellular retinaldehyde-binding protein and glial fibrillary acidic protein. In comparison, tissue of a control internal limiting membrane that was obtained during standard FTMH surgery showed few single cells that were likewise positive for glutamine synthetase, glia cell-derived neurotrophic factor, and IBA. The control specimen of unexposed PLC showed rarely cells that were without positive immunostaining for the tested markers.Our analysis revealed positive immunoreactivity of macroglia and microglia cells of the PLC tissue that was used to patch a refractory FTMH. Similar immunostaining of PLC material and internal limiting membrane suggests the PLC transplantation as an alternative treatment option for refractory FTMH.

The recent COVID-19 outbreak has quickly become a worldwide pandemic emergency. The course of this pandemic is still unknown, with more than 6 million cases identified and over 370 000 deaths globally as of June 1, 2020. The uncertainty and anxiety during this period will have a detrimental effect on the global health system. The organ transplantation field has been negatively affected by the COVID-19 pandemic, especially in regions where the intensity of cases exceeds the available capacity of the health care resources. Recently, scattered data have been published in the English literature, mainly in case reports and letters to the editor, that describe the effect of COVID-19 on donors and recipients of abdominal solid organs. Our objective is to review and draw conclusions from these data.

Background Verinurad is a human uric acid (UA) transporter (URAT1) inhibitor known to decrease serum UA (sUA) levels and that may reduce albuminuria. In a Phase 2a study (NCT03118739), treatment with verinurad + febuxostat lowered urine albumin-to-creatinine ratio (UACR) at 12 weeks by 39% (90% confidence interval 4–62%) among patients with Type 2 diabetes mellitus, hyperuricaemia and albuminuria. The Phase 2b, randomized, placebo-controlled Study of verinurAd and alloPurinol in Patients with cHronic kIdney disease and hyperuRicaEmia (SAPPHIRE; NCT03990363) will examine the effect of verinurad + allopurinol on albuminuria and estimated glomerular filtration rate (eGFR) slope among patients with chronic kidney disease (CKD) and hyperuricaemia. Methods Adults (≥18 years of age) with CKD, eGFR ≥25 mL/min/1.73 m2, UACR 30–5000 mg/g and sUA ≥6.0 mg/dL will be enrolled. Approximately 725 patients will be randomized 1:1:1:1:1 to 12, 7.5 or 3 mg verinurad + allopurinol, allopurinol or placebo. An 8-week dose-titration period will precede a 12-month treatment period; verinurad dose will be increased to 24 mg at Month 9 in a subset of patients in the 3 mg verinurad + allopurinol arm. The primary efficacy endpoint the is change from baseline in UACR at 6 months. Secondary efficacy endpoints include changes in UACR, eGFR and sUA from baseline at 6 and 12 months. Conclusions This study will assess the combined clinical effect of verinurad + allopurinol on kidney function in patients with CKD, hyperuricaemia and albuminuria, and whether this combination confers renoprotection beyond standard-of-care.

Background Mortality for infants on the heart transplant wait list remains unacceptably high, and available mechanical circulatory support is suboptimal. Our goal is to demonstrate the feasibility of utilizing genetically engineered pig (GEP) heart as a bridge to allotransplantation by transplantation of a GEP heart in a baboon. Methods Four baboons underwent orthotopic cardiac transplantation from GEP donors. All donor pigs had galactosyl-1,3-galactose knocked out. Two donor pigs had human complement regulatory CD55 transgene and the other 2 had human complement regulatory CD46 and thrombomodulin. Induction immunosuppression included thymoglobulin, and Anti-CD20. Maintenance immunosuppression was Rapamycin, AntiCD-40 and methylprednisolone. One donor heart was preserved with University of Wisconsin (UW) solution and the other three with del Nido solution. Results All baboons weaned from cardiopulmonary bypass. B217 received a donor heart preserved with UW. Ventricular arrhythmias and depressed cardiac function resulted in early death. All recipients of del Nido preserved hearts easily weaned from cardiopulmonary bypass with minimal inotropic support. B15416 and B1917 survived for 90 days and 241 days respectively. Histopathology in B15416 revealed no significant myocardial rejection but cellular infiltrate around Purkinje fibers. Histopathology in B1917 was consistent with severe rejection. B37367 had uneventful transplant but developed significant respiratory distress with a cardiac arrest. Conclusions Survival of B15416 and B1917 demonstrates the feasibility of pursuing additional research to document the ability to bridge an infant to cardiac allotransplant with a GEP heart.

Objectives Postoperative cardiac troponin I concentration is predictive of worsened outcome in cardiac surgery. Lung transplantation (LT) surgery shares common features with cardiac surgery, but postoperative troponin has yet to be investigated. We aimed to evaluate the association between early postoperative troponin concentration and the 1-year mortality after transplantation. Design Retrospective, observational, single-centre study. Setting Tertiary care, university hospital. Participants Patients who underwent lung transplantation from January 2011 to December 2017 Interventions For each patient, preoperative, intraoperative, and postoperative data were collected, as well as the troponin I measurement at the moment of postoperative ICU admission. Measurements and Main Results Two hundred and twenty LT procedures were analysed. Troponin I was elevated in all LT patients with a median of 3.82 ng.ml−1 [2 - 6.42] ng.ml−1, being significantly higher in non-survivors than in survivors, 5.39 [2.88-7.44] versus 3.50 ng.ml−1 [1.74 - 5.76], p=0.005. In the multivariable analysis, we found that only the Simplified Acute Physiology Score II (SAPS 2) score (hazard ratio 1.03; 95% confidence interval [1.001; 1.05]; P=0.007) and the need to maintain extracorporeal life support (ECLS) at the end of surgery (hazard ratio 2.54; 95% confidence interval [1.36; 4.73]; p=0.003) were independently associated with the 1-year mortality. The multiple linear regression model found that troponin levels were associated with the need for ECLS (p=0.014), the amount of transfused packed red blood cells (PRBC) (p=0.008), and to the bilateral LT (p Conclusion Early postoperative troponin serum levels were not independently associated with 1-year mortality. Early postoperative troponin I levels were correlated to bilateral LT, need for ECLS, and intraoperative blood transfusion.

We describe a complex case of liver transplant in a 70-year-old male patient with no known history of coronary artery disease, normal preoperative left ventricular function, and negative preoperative cardiac workup who developed progressive intra-operative left ventricular myocardial dysfunction secondary to class I acute myocardial infarction, ultimately requiring intraoperative intra-aortic balloon pump insertion to optimize myocardial perfusion. Management of myocardial ischemia was complicated by bleeding in the setting of coagulopathy necessitating correction. Once hemostasis was achieved, the patient immediately underwent coronary angiography and bare metal stent placement in the mid-left anterior descending coronary artery for an acute plaque rupture.

Objectives Acute kidney injury (AKI) remains a leading source of morbidity and mortality after cardiothoracic surgery. Insulin-like growth factor-binding protein 7 (IGFBP7), and tissue inhibitor of metalloproteinases-2 (TIMP-2), are novel early-phase renal biomarkers that have been validated as sensitive predictors of AKI. Here the authors studied the efficacy of these biomarkers for predicting AKI after left ventricular assist device (LVAD) implantation and cardiac transplantation. Design/Setting/Participants/Interventions This was a prospective study of 73 patients undergoing LVAD implantation (n = 37) or heart transplant (n = 36) from 2016 to 2017 at the authors’ center. TIMP-2 and IGFBP7 were measured with the NephroCheck Test on urine samples before surgery and one-to-six hours after surgery. NephroCheck scores were assessed as predictors of moderate/severe AKI (Kidney Disease International Global Outcomes 2/3 creatinine criteria) within 48 hours of surgery, and the association with survival to one year was investigated. Measurements and Main Results The LVAD and transplant cohorts overall were similar in demographics and baseline creatinine (p > 0.05), with the exception of having more African-American patients in the LVAD arm (p = 0.003). Eleven (30%) LVAD and 16 (44%) transplant patients developed moderate/severe AKI. Overall, AKI was associated with postsurgery NephroCheck (odds ratio [95% confidence interval] for 0.1 mg/dL increase: 1.36 [1.04-1.79]; p = 0.03), but not with baseline NephroCheck (p = 0.92). When analyzed by cohort, this effect remained for LVAD (1.68 [1.05-2.71]; p = 0.03) but not for transplant (p = 0.15). Receiver operating characteristic analysis showed postoperative NephroCheck to be superior to baseline creatinine in LVAD (p = 0.046). Furthermore, an increase of 0.1 mg/dL in postoperative NephroCheck was associated with a 10% increase in the risk of mortality (adjusted hazard ratio: 1.11 [1.01-1.21]; p = 0.04) independent of age and body mass index. Conclusion Assessment of TIMP-2 and IGFBP7 within six hours after surgery appeared effective at predicting AKI in patients with LVADs. Larger studies are warranted to validate these findings.

Background Whether the anti-gp210 antibody can be used as a biomarker in patients with primary biliary cholangitis (PBC) remains controversial. Aims We aimed to investigate the association between anti-gp210 antibodies and prognosis in ursodeoxycholic acid (UDCA)-treated PBC patients. Methods We conducted a retrospective cohort study of 180 UDCA-treated PBC patients to assess the prognostic value of anti-gp210 antibodies using the Kaplan–Meier method and Cox proportional hazard regression analysis. Results Of the patients included in our analysis, 50 (27.8%) were anti-gp210 positive, and 130 (72.2%) were anti-gp210 negative. The incidence of liver-related death or transplantation was more common in the anti-gp210 + group (22.0 vs. 9.2%, P=0.022). The five-year transplant-free survival rates of anti-gp210-positive patients vs. anti-gp210-negative patients were 77.0% and 90.3%, respectively. We found that the probability of transplant-free survival was significantly lower in the anti-gp210-positive patients than in the anti-gp210-negative patients (log-rank P=0.004). After adjusting for potential confounders using multivariable Cox regression model, positivity for anti-gp210 antibody (hazard ratio: 4.619, 95% confidence interval: 1.895–11.261, P=0.001) was found to be independently associated with an increase in liver-related mortality or transplantation. Conclusion In this cohort of UDCA-treated PBC patients, positivity for anti-gp210 antibody was independently associated with a higher risk of liver-related death or transplantation.

Primary nonfunction is a rare but lethal complication that occurs in a small number of liver transplants. When primary nonfunction occurs, the only definite treatment is retransplant; however, another liver might not be readily available at that time. Hence, a surgeon should be aware of the various options available at hand for patient care during the time interval between the primary nonfunction and retransplant. Here, we describe the management strategy that was devised to take care of an unstable anhepatic patient in the intensive care unit, care of the patient during anhepatic phase, and successful outcome with a second liver transplant. Our index patient was a recipient of a liver donated after cardiac death. While in the operating room, after reperfusion of the liver, the patient had right heart dysfunction leading to hemodynamic instability and congestion of the liver, which culminated in primary nonfunction. Graft hepatectomy had to be done on postoperative day 1 because of deteriorating condition of the patient, and the patient was maintained in anhepatic phase in the intensive care unit for 27 hours.

Objective Ex vivo lung perfusion has emerged as a novel technique to safely preserve lungs before transplantation. Recent studies have demonstrated an accumulation of inflammatory molecules in the perfusate during ex vivo lung perfusion. These proinflammatory molecules, including damage-associated molecular patterns and inflammatory cytokines, may contribute to acute and chronic allograft dysfunction. At present, ex vivo lung perfusion is performed clinically at normothermic temperature (37°C). The effect of lowering temperature to the subnormothermic range during ex vivo lung perfusion has not been reported. In this study, we hypothesized that lower ex vivo lung perfusion temperature will lead to a reduction in allograft inflammation and result in improved post-transplant graft function. Methods Lewis rat heart-lung blocs underwent 4 hours of ex vivo lung perfusion in 3 temperature groups: 37°C (MP37), 30°C (MP30), and 25°C (MP25). In the control group, lung grafts were preserved by static cold storage before transplantation. After ex vivo lung perfusion or static cold storage, the left lung was transplanted for 2 hours before the animal was killed. Sera and tissue were collected and analyzed. Results There were no differences in partial pressure of arterial oxygenation to fraction of inspired oxygen ratios during 4 hours of ex vivo lung perfusion between temperature groups. Tumor necrosis factor α significantly increased in the MP37 group during ex vivo lung perfusion, whereas this was not seen at lower temperatures. Extracellular DNA and high-mobility group box 1 perfusate concentrations increased significantly during ex vivo lung perfusion in all groups, but the rate of increase was diminished at lower temperature. Two hours post-transplant, there were no significant differences in partial pressure of arterial oxygenation to fraction of inspired oxygen ratios of the lung graft or serum damage-associated molecular pattern levels among groups. On histologic grading after transplantation, greater injury was observed in the MP30 and MP37 groups, but not MP25, when compared with static cold storage. Conclusions Subnormothermic ex vivo lung perfusion at 25°C reduces the production of inflammatory mediators during ex vivo lung perfusion and is associated with reduced histologic graft injury after transplantation.

The nasal mucosa functions as a frontline biological defense against various foreign substances and pathogens. Maintaining homeostasis of the nasal epithelium is necessary to promote good health. Nasal epithelia are constantly replaced under normal conditions. However, hereditary diseases, including primary ciliary dyskinesia and cystic fibrosis, can result in intractable dysfunction of the nasal mucosa. Since there is no treatment for this underlying condition, extrinsic manipulation is necessary to recover and maintain nasal epithelia in cases of hereditary diseases. In this study, we explored the use of airway epithelial cells (AECs), including multiciliated airway cells, derived from human induced pluripotent stem cells (iPSCs) on porcine atelocollagen vitrigel membranes, as a candidate of a therapeutic method for irreversible nasal epithelial disorders. To confirm the regenerative capacity of iPSC-derived AECs, we transplanted them into nasal cavities of nude rats. Although the transplanted cells were found within cysts isolated from the recipient nasal respiratory epithelia, they survived in some rats. Furthermore, the surviving cells were composed of multiple cell types similar to the human airway epithelia. The results could contribute to the development of novel transplantation-related technologies for the treatment of severe irreversible nasal epithelial disorders. Impact Statement Nasal respiratory epithelia are important for the functions of nasal cavity, including humidifying the air and filtering various toxic substances. However, hereditary diseases, including primary ciliary dyskinesia and cystic fibrosis, can result in intractable dysfunction of the nasal mucosa. Our novel method to transplant airway epithelial cells derived from human induced pluripotent stem cells will be a candidate method to replace malfunctioned nasal respiratory epithelia in such a situation. To secure our method's safety, we used porcine atelocollagen vitrigel membranes, which prevent the immune response and bovine spongiform encephalopathy, as a scaffold.

Coronavirus disease (COVID-19) vaccine and its utility in solid organ transplantation (SOT) needs to be revised timely and updated. These guidelines have been formalized by the experts -the apex technical committee members of the National Organ and Tissue Transplant Organization (NOTTO), and the heads of transplant societies for the guidance of transplant communities. In our general recommendations, we recommend that all personnel involved in organ transplantation should get vaccinated as early as possible and continue COVID-19 appropriate behaviour, despite a full course of vaccination. For specific guidelines of recipients, we suggest completing the full schedule before transplantation whenever the clinical condition permits. We also suggest a single dose, rather than proceeding unvaccinated for transplant, in case a complete course is not feasible. In case, vaccination is planned before surgery, we recommend a gap of at least 2 weeks between the last dose of vaccine and surgery. For those not vaccinated prior to transplant, we suggest waiting for 4-12 weeks after transplant. For the potential living donors, we recommend the complete vaccination schedule before transplant. However, if not feasible, we suggest getting at least a single dose of vaccine, 2 weeks prior to donation. We suggest that suitable transplant patients and those on the waiting list should accept a third dose of the vaccine when one is offered to them. In the context of Vaccine-induced thrombotic thrombocytopenia (VITT), we recommend organs from a deceased donor with suspected/proven VITT should be notified and best avoided and are justified only in case of emergency situations with informed consent and counselling.

In this case report, we present the rare complication of proximal migration of ureteral stent after kidney transplant, and we describe our approach for its diagnosis and treatment. Although endoscopic management is the treatment of choice for retrieval of migrated stents, we reexplored the transplant in response to erroneous reporting of ureteral stent lying in an extravesicular position on a pelvic computed tomography scan. Subsequent exploration disproved the original interpretation of the image. Proximal stent migration may result from retrograde peristalsis and is generally related to suboptimal stent length.

Background Coronavirus disease 2019 (COVID-19) infection may become more severe in those who have undergone kidney transplantation than in the general population. False-negative reverse transcription-polymerase chain reaction (RT-PCR) results have been reported for COVID-19 infection. Patients might carry infection even though RT-PCR results are negative. Case report A 65-year-old man with a 19-year history of ABO-incompatible kidney transplantation presented with fever and arthralgia. Although the RT-PCR result was negative, a focal slit-glass shadow in the left upper lobe on computed tomography (CT) suggested COVID-19 pneumonia. His symptoms did not improve until after 10 days, and CT showed multiple slit-glass shadows in the bilateral lung fields. However, RT-PCR remained negative. The patient was admitted, and mycophenolate mofetil was discontinued. Anticoagulants were administered on the third day of hospitalization. Because of poor oxygenation, the patient was intubated in the intensive care unit on the fifth day, and sivelestat sodium was administered. The patient was extubated on the 12th day after improvement in oxygenation. There was no exacerbation, and CT showed improvements on day 51. Conclusion We report a case of pneumonia with suspected COVID-19 infection 18 years after living donor kidney transplantation. If COVID-19 is suspected, infection control and aggressive therapeutic interventions should be undertaken while considering the possibility of a positive result.

With the rapid and massive vaccination campaign against coronavirus disease 2019 (COVID-19) taking place across the globe, there are increasing reports of thrombotic complications with various COVID-19 vaccines such as the Pfizer-BioNTech mRNA, Moderna mRNA, AstraZeneca Oxford (serum institute), and JohnsonJohnson/Janssen vaccines. We report a case of successful organ donation from an 18-year-old woman who presented with cerebral venous thrombosis caused by vaccine-induced thrombotic thrombocytopenia following the first dose of the COVID-19 vaccine (AstraZeneca, University of Oxford, and Serum Institute of India), which caused brain death. Four recipients received 5 organs, kidneys (2), liver (1), and combined heart and lung (1). All 4 recipients had normal graft function without any thrombotic complications after 16 weeks of transplantation. This is first such case being reported from Asian countries.

Organ transplant recipients exhibit lower rates of immune response to coronavirus disease 2019 (COVID-19) vaccination. Even when they do mount a demonstrable antibody response, it is unclear what degree of protection is conferred against the myriad potential complications of COVID-19 infection. We present here a case of a kidney transplant recipient who was homozygous for APOL1 risk alleles on low-dose immunosuppression who developed an antibody response to COVID-19 vaccination and subsequently acquired COVID-19 infection. Although she experienced relatively minor effects in other organ systems, she developed severe collapsing focal segmental glomerulosclerosis that left her dependent on hemodialysis on hospital discharge. This suggests that COVID-19 vaccination may not provide protection from infection-associated focal segmental glomerulosclerosis in patients with APOL1 risk alleles.

Background Heart transplantation (HTx) surgically denervates the heart. We examined indices of sinoatrial reinnervation, with emphasis on (1) the occurrence and timing of parasympathetic reinnervation, and (2) the consequences of reinnervation for heart rate (HR) responsiveness and arterial baroreceptor sensitivity. Methods Fifty HTx recipients were prospectively followed for 36 months after surgery. Hemodynamic variables and heart rate variability were continuously recorded at supine rest, 60 degrees head-up-tilt, during the Valsalva maneuver and during handgrip isometric exercise. Results Suggesting parasympathetic reinnervation: at baseline rest, root of the mean squared differences of successive RR intervals increased from median 3.9(5.9) to 7.1(5.1) ms (p < 0.001); high-frequency power increased from 4.0(12) to 5.7(18.9) ms2 (p = 0.018); and baroreceptor sensitivity increased from 0.04(0.36) to 1.3(2.4) ms/mmHg (p < 0.001). Suggesting sympathetic reinnervation: at baseline rest low-frequency power increased from 0.49(2.5) to 7.5(18.1) ms2 (p < 0.001); and HR responses to sympathetic stimulation during (1) head-up tilt increased from 1.9(4.2) to 9.1(8.2) bpm (p < 0.001), (2) Valsalva increased from 1.6(1.4) to 8.3(10.8) bpm (p < 0.001) and (3) handgrip increased from 0.3(0.6) to 1.9(5.1) bpm (p < 0.001). Signs of sympathetic reinnervation emerged within 6 months, while signs of parasympathetic reinnervation emerged by 24 months. Conclusions Root of the mean squared differences of successive RR intervals, high-frequency and low-frequency variability, HR responsiveness and arterial baroreflex sensitivity all increased after HTx, suggesting functional parasympathetic and sympathetic sinoatrial reinnervation. Accordingly, the pathological regulatory state present in heart transplant recipients, which is responsible for a host of functional and clinical abnormalities, is being partially offset over time by restored autonomic control of the heart in many heart transplant recipients.

Rationale and Objective Concerns about non-adherent behaviors often prevent dialysis patients from entering waitlists for transplantation, despite an inconsistent association with posttransplant outcomes. We examined the association between plausible metrics of non-adherence related to dialysis treatment and posttransplant outcomes. Study Design Retrospective cohort. We linked national dialysis treatment data with transplant registry data. Setting and Participants Adult patients on maintenance hemodialysis from 1/1/2004-12/31/2014 who received a kidney transplant at US centers. Exposures We examined five nonadherence metrics: serum potassium (≥5.2 mEq/L), serum phosphorus (>5.5 mg/dL), intradialytic weight gain (IDWG, ≥5 L), shortened treatments (≥30 minutes) and missed treatments (≥1); missed treatment data was only available for 2004-2009. These metrics were characterized as the proportion of time under observation. Dialysis observation time was divided into 3-month intervals (quarters) and the number of “non-adherent” measurements in each domain was calculated for each quarter. Outcomes Allograft loss; mortality; and acute rejection in the first posttransplant year. Analytical approach Using Cox proportional hazards and logistic regression, we estimated the hazard ratios (HRs) for graft loss and mortality, and odds ratios (OR) for rejection. Results 9543 patients met inclusion criteria. In our primary model, hyperphosphatemia (aHR 1.27, 05% CI 1.08-1.49), IDWG (aHR 1.39, 95% CI 1.23-1.59) and shortened treatments (aHR 1.54, 95% CI 1.12-2.13) were associated with greater rates of allograft loss but hyperkalemia was not. IDWG (aHR 1.49, 95% CI 1.29-1.73) and shortened treatments (aHR 1.34, 95% CI 1.13-1.58) were associated with mortality while hyperkalemia and hyperphosphatemia were not. Only shortened treatments was associated with an increased risk of acute rejection (aOR 3.88, 95% CI 1.98-7.58). In models limited to the years 2004 to 2009 that included missed treatments, missed treatments were only associated with mortality. Limitations Unmeasured confounding (e.g., dietary data); adherence metrics used may have multiple, complex causes. Conclusions Plausible measures of dialysis nonadherence have long-term associations with allograft and patient survival. Behavioral metrics were more closely associated with outcomes than laboratory markers. The implications of non-adherent behaviors for dialysis patients must be carefully considered before excluding patients from transplantation.

Hepatocellular carcinoma (HCC) is a type of primary liver malignant tumor with a high recurrence rate and poor prognosis even undergoing resection or transplantation. Accurate discrimination of the histologic grades of HCC plays a critical role in the management and therapy of HCC patients. In this paper, we discuss a deep learning-based diagnostic model for HCC histologic grading with multimodal Magnetic Resonance Imaging (MRI) images to overcome the problem of limited well-annotated data and extract the discriminated fusion feature referring to the clinical diagnosis experience of radiologists. Accordingly, we propose a novel Multimodality-Contribution-Aware TripNet (MCAT) based on the metric learning and the attention-aware weighted multimodal fusion. The novelty of the method lies in the multimodality small-shot learning architecture designation and the multimodality adaptive weighted computing scheme. The comprehensive experiments are done on the clinic dataset with the well-annotation of lesion location by the professional radiologist. The experimental results show that our proposed MCAT is not only able to achieve acceptable quantitative measuring of HCC histologic grading based on the MRI sequences with small cases but also outperforms previous models in HCC histologic grading, reaching an accuracy of 84 percent, a sensitivity of 87 percent and precision of 89 percent.

BACKGROUND: Treatment with high-dose chemotherapy and stem cell transplantation has prolonged survival in patients of multiple myeloma (MM). A dose-response relationship between number of CD34+ cells infused and leukocyte and platelet recovery, exists. Patients receiving dose of 5 × 10(6)/kg (category 3), the mean (SD) neutrophil engraftment time was 11.3 (0.5) days, 10.6 (0.9) days, and 10.2 (1.3) days respectively. Platelet engraftment time was 12.4 (2.60) days, 10.6 (1.14) days, and 11.2 (1.64) days for category 1, 2, and 3 patients, respectively. Correlation co-efficient between CD 34+cell dose and days for neutrophil and platelet engraftment was found to be −0.24 and −0.20, respectively. Time for neutrophil engraftment was found to be significantly associated with CD34+ cell dose category. CONCLUSION: CD 34+ cell dose appears as the strongest predictor of leukocyte and platelet engraftment. CD 34+ cell dose of >5.0 × 10(6) cells/kg leads to an accelerated neutrophil and platelet engraftment in patients of MM.

We report our experience with a new case of lymphedema of the upper extremity in a renal transplant recipient under treatment with everolimus immunosuppression, and we emphasize the effects of complete decongestive therapy on this chronic condition.

A 58-year-old woman with a prior radical cystectomy and ileal conduit underwent a living-related donor renal transplant for end-stage renal disease secondary to autoimmune glomerulonephritis. She subsequently developed an ischaemic stricture of the transplant ureter. A successful ureteropyelostomy was performed with the native right ureter anastomosed to the pelvis of the renal transplant. She presented to the emergency department 18 months later feeling unwell and with raised inflammatory markers. Imaging demonstrated a large soft tissue mass over the right psoas muscle and hydronephrosis of the native right kidney. A nephrostomy and nephrostogram of the native right kidney diagnosed a urine leak from the native right kidney and she underwent an open right native nephrectomy. She recovered well postoperatively and continues to have excellent graft function. Renal transplantation in an abnormal urinary tract carries a high risk of complications. A multidisciplinary team approach is essential in offering the most appropriate treatment and ensuring good graft function is preserved.

As the incidence of fatal drug overdose has quadrupled in the U.S. in the past two decades, patients awaiting organ transplants may be unintended beneficiaries. We use Vital Statistics mortality data, merged with data on the universe of transplant candidates and recipients in the U.S. from the Scientific Registry of Transplant Recipients, to study the extent to which the growth in opioid-related deaths affects the supply of deceased organ donors and transplants. Using two separate identification strategies, we find that opioid-related deaths led to more than 22,000 organ transplants in the U.S. between 2008 and 2018. Although we detect little evidence of demand responses to opioid-induced organ supply shocks, we find that transplant centers are increasingly recovering organs from overdose victims for transplant, with the association between opioid-related deaths and organ donors more than doubling between 2008 and 2018. We also present evidence that transplant candidates appear to be more willing to use organs from those who died of opioid-related causes when organ shortages are relatively severe.

Background The most important cause of heart transplant loss is early acute allograft rejection, caused by the infiltration of lymphocytes, development of edema and myocardial necrosis. It has been propagated that [68Ga]DOTA-TATE PET might be suitable to quantify the presence of SSTR over-expressing lymphocytes. With heterotopic allogenic heart transplant models in the rat readily available, we aimed to investigate, if monitoring and quantification of acute allograft rejection after heterotopic allogenic heart transplantation was feasible by non-invasive serial [68Ga]DOTA-TATE PET. Methods 17 Lewis rats (9 for serial PET imaging, 8 for histological correlation) received allogenic heterotopic heart transplants from 17 Brown-Norway rats. On days 4, 6 and 7 a [68Ga]DOTA-TATE PET scan was performed. Results Imaging of acute transplant rejection until 7 days after allogenic heart transplantation in the rat is feasible. Heterotopic allografts showed significantly increased tracer uptake on day 4 until day 7 after transplantation, reflecting the process of histologically detected myocardial lymphocytic infiltration. Both the area of infarction and the amount of necrosis increased over the course of 7 days, with necrosis reaching statistical significance. Conclusions We purport that the detected PET signal is primarily a specific marker of lymphocyte infiltration and only to a lesser extent an unspecific marker of infarction and necrosis. Thus, [68Ga]DOTA-TATE PET might be a suitable tool for serial imaging and quantification of lymphocyte infiltration as a direct mediator of acute allograft rejection at an early stage after heart transplantation.

Air pollution is associated with cardiopulmonary disease and death in the general population. Fine particulate matter (PM2.5) is particularly harmful due to its ability to penetrate into areas of gas exchange within the lungs. Persons with advanced lung disease are believed to be particularly susceptible to PM2.5 exposure, but only a few studies have examined the effect of exposure on this population. Here we investigate the association between PM2.5 exposure and adverse waitlist events among lung transplant (LT) candidates.US registry data were used to identify LT candidates listed between January 1, 2010 and December 31, 2016. Annual PM2.5 concentration at year of listing was estimated for each candidate's ZIP Code using National Aeronautics and Space Administration's (NASA) Socioeconomic Data and Applications Center Global Annual PM2.5 Grids. We estimated crude and adjusted hazard ratios for adverse waitlist events, defined as death or removal, using Cox proportional hazards regression.Of the 15 075 included candidates, median age at listing was 60, 43.8% were female individuals, and 81.7% were non-Hispanic White. Median ZIP Code PM2.5 concentration was 9.06 µg/m3. When compared with those living in ZIP Codes with lower PM2.5 exposure (PM2.510.53 µg/m3), candidates in ZIP Codes in the highest quartile of PM2.5 exposure (≥10.53 µg/m3) had 1.14-fold (95% confidence interval, 1.04-1.25) risk of adverse waitlist events. The result remained significant after adjusting for demographics, education, insurance, smoking, lung allocation score, body mass index, and blood type (hazard ratio, 1.17; 95% confidence interval, 1.07-1.29).Elevated ambient PM2.5 concentration was associated with adverse waitlist events among LT candidates. These findings highlight the impact of air pollution on clinical outcomes in this critically ill population.