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BACKGROUND: The need to expand the pool of available organs for transplantation has meant that the use of marginal organs is increasingly widespread. The advent of antiviral therapy for hepatitis C virus (HCV) has made it possible to consider the donation of organs from HCV-positive donors and even from viremic donors. METHODS: In HCV-positive to HCV-negative antibody donor transplantation, the development of antibodies to HCV is uneven, depending on the organ transplanted and with differences in the time of appearance. Whether the subsequent disappearance is attributed to the development of antibodies or the transmission of immunity between donor and recipient remains unclear. In transplantation from an HCV-infected donor to a HCV-seronegative recipient, the administration of antiviral therapy to the recipient before transplantation or a few days after transplantation achieves sustained response in almost all cases. We wanted to deepen the argument by studying the data in the literature, focusing on kidney transplantation, considering that this could be of interest, particularly for possible long-term renal damage. RESULTS: HCV infection both ongoing and previous, as well as the presence of HCV antibodies alone, can be responsible for kidney damage. CONCLUSIONS: Direct-acting anti-HCV therapy has revolutionized the treatment of HCV disease and the therapeutic possibilities of transplantation. However, we believe it is useful to keep in mind the pathophysiology of HCV-related damage especially in patients with a long life expectancy, using all emerging strategies to minimize the risk of transmission of infection or development of viremia.
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INTRODUCTION AND OBJECTIVES: Epigenetic changes represent a mechanism connecting external stresses with long-term modifications of gene expression programs. In solid organ transplantation, ischemia-reperfusion injury (IRI) appears to induce epigenomic changes in the graft, although the currently available data are extremely limited. The present study aimed to characterize variations in DNA methylation and their effects on the transcriptome in liver transplantation from brain-dead donors. PATIENTS AND METHODS: 12 liver grafts were evaluated through serial biopsies at different timings in the procurement-transplantation process: T0 (warm procurement, in donor), T1 (bench surgery), and T2 (after reperfusion, in recipient). DNA methylation (DNAm) and transcriptome profiles of biopsies were analyzed using microarrays and RNAseq. RESULTS: Significant variations in DNAm were identified, particularly between T2 and T0. Functional enrichment of the best 1000 ranked differentially methylated promoters demonstrated that 387 hypermethylated and 613 hypomethylated promoters were involved in spliceosomal assembly and response to biotic stimuli, and inflammatory immune responses, respectively. At the transcriptome level, T2 vs. T0 showed an upregulation of 337 and downregulation of 61 genes, collectively involved in TNF-α, NFKB, and interleukin signaling. Cell enrichment analysis individuates macrophages, monocytes, and neutrophils as the most significant tissue-cell type in the response. CONCLUSIONS: In the process of liver graft procurement-transplantation, IRI induces significant epigenetic changes that primarily act on the signaling pathways of inflammatory responses dependent on TNF-α, NFKB, and interleukins. Our DNAm datasets are the early IRI methylome literature and will serve as a launch point for studying the impact of epigenetic modification in IRI.
Subject(s)
DNA Methylation , Epigenesis, Genetic , Gene Expression Profiling , Liver Transplantation , Liver , Reperfusion Injury , Liver Transplantation/adverse effects , Reperfusion Injury/genetics , Reperfusion Injury/metabolism , Humans , Liver/metabolism , Liver/pathology , Male , Middle Aged , Female , Gene Expression Profiling/methods , Transcriptome , Adult , AgedABSTRACT
To date, caval sparing (CS) and total caval replacement (TCR) for recipient hepatectomy in liver transplantation (LT) have been compared only in terms of surgical morbidity. Nonetheless, the CS technique is inherently associated with an increased manipulation of the native liver and later exclusion of the venous outflow, which may increase the risk of intraoperative shedding of tumor cells when LT is performed for HCC. A multicenter, retrospective study was performed to assess the impact of recipient hepatectomy (CS vs. TCR) on the risk of posttransplant HCC recurrence among 16 European transplant centers that used either TCR or CS recipient hepatectomy as an elective protocol technique. Exclusion criteria comprised cases of non-center-protocol recipient hepatectomy technique, living-donor LT, HCC diagnosis suspected on preoperative imaging but not confirmed at the pathological examination of the explanted liver, HCC in close contact with the IVC, and previous liver resection for HCC. In 2420 patients, CS and TCR approaches were used in 1452 (60%) and 968 (40%) cases, respectively. Group adjustment with inverse probability weighting was performed for high-volume center, recipient age, alcohol abuse, viral hepatitis, Child-Pugh class C, Model for End-Stage Liver Disease score, cold ischemia time, clinical HCC stage within Milan criteria, pre-LT downstaging/bridging therapies, pre-LT alphafetoprotein serum levels, number and size of tumor nodules, microvascular invasion, and complete necrosis of all tumor nodules (matched cohort, TCR, n = 938; CS, n = 935). In a multivariate cause-specific hazard model, CS was associated with a higher risk of HCC recurrence (HR: 1.536, p = 0.007). In conclusion, TCR recipient hepatectomy, compared to the CS approach, may be associated with some protective effect against post-LT tumor recurrence.
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BACKGROUND AND AIMS: Besides the increased risk of perioperative morbidity, graft failure, and mortality, the majority of PVT are diagnosed at liver transplantation (LT). Improving preoperative management and patient selection may lead to better short-term and long-term outcomes and reduce the risk of a futile LT. The authors aimed to identify predictors of adverse outcomes after LT in patients with nonmalignant portal vein thrombosis (PVT) and improve donor to recipient matching by analyzing the results of the Italian cohort of LT recipients. METHODS: Adult patients who underwent LT in Italy between January 2000 and February 2020 diagnosed with PVT pre-LT or at time of LT were considered eligible for inclusion. Based on a survey encompassing all 26 surgeons participating in the study, a binary composite outcome was defined. Patients were classified as having the composite event if at least one of these conditions occurred: operative time more than 600 min, estimated blood loss greater than 5000 ml, more than 20 ICU days, 90 days mortality, 90 days retransplant. RESULTS: Seven hundred fourteen patients were screened and 698 met the inclusion criteria. The analysis reports the results of 568 patients that fulfilled the criteria to enter the composite outcome analysis.Overall, 156 patients (27.5%) developed the composite outcome. PVT stage 3/4 at transplant and need for any surgical correction of PVT are independent predictors of the composite outcome occurrence. When stratified by PVT grade, overall survival at 1-year ranges from 89.0% with PVT grade 0/1 to 67.4% in patients with PVT grade 3/4 at LT ( P <0.001). Nevertheless, patients with severe PVT can improve their survival when identified risk factors are not present. CONCLUSIONS: Potential LT candidates affected by PVT have a benefit from LT that should be adequately balanced on liver function and type of inflow reconstruction needed to mitigate the incidence of adverse events. Nonetheless, the absence of specific risk factors may improve the outcomes even in patients with PVT grades 3-4.
Subject(s)
Liver Transplantation , Portal Vein , Venous Thrombosis , Humans , Liver Transplantation/adverse effects , Portal Vein/surgery , Male , Female , Retrospective Studies , Middle Aged , Venous Thrombosis/surgery , Adult , Italy/epidemiology , Postoperative Complications/epidemiology , Aged , Patient Selection , Treatment OutcomeABSTRACT
Here we present the generation and characterization of patient-derived organoids (PDOs) from colorectal cancer patients. PDOs derived from two patients with TP53 mutations were tested with two different HDAC inhibitors (SAHA and NKL54). Cell death induction, transcriptome, and chromatin accessibility changes were analyzed. HDACIs promote the upregulation of low expressed genes and the downregulation of highly expressed genes. A similar differential effect is observed at the level of chromatin accessibility. Only SAHA is a potent inducer of cell death, which is characterized by the upregulation of BH3-only genes BIK and BMF. Up-regulation of BIK is associated with increased accessibility in an intronic region that has enhancer properties. SAHA, but not NKL54, also causes downregulation of BCL2L1 and decreases chromatin accessibility in three distinct regions of the BCL2L1 locus. Both inhibitors upregulate the expression of innate immunity genes and members of the MHC family. In summary, our exploratory study indicates a mechanism of action for SAHA and demonstrate the low efficacy of NKL54 as a single agent for apoptosis induction, using two PDOs. These observations need to be validated in a larger cohort of PDOs.
Subject(s)
Colonic Neoplasms , Histone Deacetylase Inhibitors , Humans , Histone Deacetylase Inhibitors/pharmacology , Chromatin/genetics , Hydroxamic Acids/pharmacology , Apoptosis/genetics , Colonic Neoplasms/drug therapy , Colonic Neoplasms/genetics , Cell Line, Tumor , Tumor Suppressor Protein p53/geneticsABSTRACT
Abundant ribonucleoside-triphosphate (rNTP) incorporation into DNA by DNA polymerases in the form of ribonucleoside monophosphates (rNMPs) is a widespread phenomenon in nature, resulting in DNA-structural change and genome instability. The rNMP distribution, characteristics, hotspots and association with DNA metabolic processes in human mitochondrial DNA (hmtDNA) remain mostly unknown. Here, we utilize the ribose-seq technique to capture embedded rNMPs in hmtDNA of six different cell types. In most cell types, the rNMPs are preferentially embedded on the light strand of hmtDNA with a strong bias towards rCMPs; while in the liver-tissue cells, the rNMPs are predominately found on the heavy strand. We uncover common rNMP hotspots and conserved rNMP-enriched zones across the entire hmtDNA, including in the control region, which links the rNMP presence to the frequent hmtDNA replication-failure events. We show a strong correlation between coding-sequence size and rNMP-embedment frequency per nucleotide on the non-template, light strand in all cell types, supporting the presence of transient RNA-DNA hybrids preceding light-strand replication. Moreover, we detect rNMP-embedment patterns that are only partly conserved across the different cell types and are distinct from those found in yeast mtDNA. The study opens new research directions to understand the biology of hmtDNA and genomic rNMPs.
Subject(s)
DNA Replication , Genome, Mitochondrial , Ribonucleosides , Humans , DNA, Mitochondrial/genetics , DNA, Mitochondrial/metabolism , Ribonucleosides/metabolism , Ribonucleotides/genetics , Ribonucleotides/metabolismABSTRACT
Introduction: The study of immune response to SARSCoV-2 infection in different solid organ transplant settings represents an opportunity for clarifying the interplay between SARS-CoV-2 and the immune system. In our nationwide registry study from Italy, we specifically evaluated, during the first wave pandemic, i.e., in non-vaccinated patients, COVID-19 prevalence of infection, mortality, and lethality in liver transplant recipients (LTRs), using non-liver solid transplant recipients (NL-SOTRs) and the Italian general population (GP) as comparators. Methods: Case collection started from February 21 to June 22, 2020, using the data from the National Institute of Health and National Transplant Center, whereas the data analysis was performed on September 30, 2020.To compare the sex- and age-adjusted distribution of infection, mortality, and lethality in LTRs, NL-SOTRs, and Italian GP we applied an indirect standardization method to determine the standardized rate. Results: Among the 43,983 Italian SOTRs with a functioning graft, LTRs accounted for 14,168 patients, of whom 89 were SARS-CoV-2 infected. In the 29,815 NL-SOTRs, 361 cases of SARS-CoV-2 infection were observed. The geographical distribution of the disease was highly variable across the different Italian regions. The standardized rate of infection, mortality, and lethality rates in LTRs resulted lower compared to NL-SOTRs [1.02 (95%CI 0.81-1.23) vs. 2.01 (95%CI 1.8-2.2); 1.0 (95%CI 0.5-1.5) vs. 4.5 (95%CI 3.6-5.3); 1.6 (95%CI 0.7-2.4) vs. 2.8 (95%CI 2.2-3.3), respectively] and comparable to the Italian GP. Discussion: According to the most recent studies on SOTRs and SARS-CoV-2 infection, our data strongly suggest that, in contrast to what was observed in NL-SOTRs receiving a similar immunosuppressive therapy, LTRs have the same risk of SARS-CoV-2 infection, mortality, and lethality observed in the general population. These results suggest an immune response to SARS-CoV-2 infection in LTRS that is different from NL-SOTRs, probably related to the ability of the grafted liver to induce immunotolerance.
Subject(s)
COVID-19 , Organ Transplantation , Humans , COVID-19/epidemiology , SARS-CoV-2 , Liver , Organ Transplantation/adverse effects , Italy/epidemiologyABSTRACT
BACKGROUND & AIMS: Split liver transplant(ation) (SLT) is still considered a challenging procedure that is by no means widely accepted. We aimed to present data on 25-year trends in SLT in Italy, and to investigate if, and to what extent, outcomes have improved nationwide during this time. METHODS: The study included all consecutive SLTs performed from May 1993 to December 2019, divided into three consecutive periods: 1993-2005, 2006-2014, and 2015-2019, which match changes in national allocation policies. Primary outcomes were patient and graft survival, and the relative impact of each study period. RESULTS: SLT accounted for 8.9% of all liver transplants performed in Italy. A total of 1,715 in situ split liver grafts were included in the analysis: 868 left lateral segments (LLSs) and 847 extended right grafts (ERGs). A significant improvement in patient and graft survival (p <0.001) was observed with ERGs over the three periods. Predictors of graft survival were cold ischaemia time (CIT) <6 h (p = 0.009), UNOS status 2b (p <0.001), UNOS status 3 (p = 0.009), and transplant centre volumes: 25-50 cases vs. <25 cases (p = 0.003). Patient survival was significantly higher with LLS grafts in period 2 vs. period 1 (p = 0.008). No significant improvement in graft survival was seen over the three periods, where predictors of graft survival were CIT <6 h (p = 0.007), CIT <6 h vs. ≥10 h (p = 0.019), UNOS status 2b (p = 0.038), and UNOS status 3 (p = 0.009). Retransplantation was a risk factor in split liver graft recipients, with significantly worse graft and patient survival for both types of graft (p <0.001). CONCLUSIONS: Our analysis showed Italian SLT outcomes to have improved over the last 25 years. These results could help to dispel reservations regarding the use of this procedure. IMPACT AND IMPLICATIONS: Split liver transplant(ation) (SLT) is still considered a challenging procedure and is by no means widely accepted. This study included all consecutive in situ SLTs performed in Italy from May 1993 to December 2019. With more than 1,700 cases, it is one of the largest series, examining long-term national trends in in situ SLT since its introduction. The data presented indicate that the outcomes of SLT improved during this 25-year period. Improvements are probably due to better recipient selection, refinements in surgical technique, conservative graft-to-recipient matching, and the continuous, yet carefully managed, expansion of donor selection criteria under a strict mandatory split liver allocation policy. These results could help to dispel reservations regarding the use of this procedure.
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Liver Transplantation , Humans , Liver Transplantation/methods , Treatment Outcome , Retrospective Studies , Liver , Tissue Donors , Graft Survival , Italy/epidemiologyABSTRACT
BACKGROUND: The role of nutrition in donor after brain deaths (DBDs) has yet to be adequately discussed. The primary aim of this study was to investigate whether the nutritional intake in the 48 h before organ retrieval may play a role on the graft functional recovery assessed with Model for Early Allograft Function (MEAF) Score. METHODS: Single-center retrospective study evaluating all liver transplants performed at the University Hospital of Udine from January 2010 to August 2020. Patients receiving grafts from DBD donors fed with artificial enteral nutrition in the 48 h prior to organ procurement (EN-group) or who did not (No-EN-group). Caloric debt was calculated using the difference between the calculated caloric needs and the effective calories delivered through enteral nutrition. RESULTS: Livers from EN-group presented a lower mean MEAF score compared to the no-EN-group: 3.39 ± 1.46 versus 4.15 ± 1.51, respectively (p = .04). A positive correlation between caloric debt and the MEAF score was found within the overall population (r = .227, p = .043) as well as in EN-group (r = .306, p = .049). CONCLUSIONS: Donor's nutritional intake in the final 48 h before organ procurement correlates with MEAF score, and nutrition probably plays a positive role on the functional recovery of the graft. Large future randomized controlled trials are needed to confirm this preliminary results.
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Liver Transplantation , Tissue and Organ Procurement , Humans , Retrospective Studies , Brain Death , Tissue Donors , Allografts , Graft SurvivalABSTRACT
BACKGROUND: Patients with unresectable Colorectal Liver Metastases (CLM) receiving palliative chemotherapy have a 5-year overall survival (OS) of less than 30%. Liver transplantation (LT) can improve OS up to 60%-83% (SECA-I and SECA-II trials). The aim of the study is to assess the efficacy of LT in liver-only metastatic CRC compared with a matched cohort of patients included in a phase III trial on triplet chemotherapy + antiEGFR. PATIENTS AND METHODS: The COLT trial is an investigator-driven, multicenter, non-randomized, open-label, controlled, prospective, parallel trial (ClinicalTrials.gov NCT03803436). Hyperselected patients with liver-limited unresectable CLM, RAS and BRAF wild-type and curatively removed primary colon cancer are included. The observed post-transplant outcomes will be prospectively compared 1:5 with those obtained in a matched cohort from the TRIPLETE trial (NCT03231722). RESULTS: Primary endpoint is to compare the 3 and 5-years OS of patients enrolled in the COLT trial with COLT-eligible population enrolled in the TRIPLETE trial. An expected gain in OS of 40% at 5-years is predicted for the COLT population (the expected OS at 5-years in COLT vs. TRIPLETE is 70% vs. 30%). Secondary endpoints are to compare the 5-years disease-free survival and to assess the safety of LT (Dindo-Clavien Classification and the Comprehensive Complication Index). CONCLUSION: LT offers the longest OS reported in selected patients with CLM. Improving the selection strategies can give patients a 5-year OS similar to other indications for LT and a better outcome than those undergoing chemotherapy alone.
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Colorectal Neoplasms , Liver Neoplasms , Liver Transplantation , Humans , Colorectal Neoplasms/pathology , Prospective Studies , Disease-Free Survival , Liver Neoplasms/drug therapy , Liver Neoplasms/surgery , Antineoplastic Combined Chemotherapy Protocols/therapeutic useABSTRACT
BACKGROUND: Over the last decades relevant epidemiological changes of liver diseases have occurred, together with greatly improved treatment opportunities. AIM: To investigate how the indications for elective adult liver transplantation and the underlying disease etiologies have evolved in Italy. METHODS: We recruited from the National Transplant Registry a cohort comprising 17,317 adults patients waitlisted for primary liver transplantation from January-2004 to December-2020. Patients were divided into three Eras:1(2004-2011),2(2012-2014) and 3(2015-2020). RESULTS: Waitlistings for cirrhosis decreased from 65.9% in Era 1 to 46.1% in Era 3, while those for HCC increased from 28.7% to 48.7%. Comparing Eras 1 and 3, waitlistings for HCV-related cirrhosis decreased from 35.9% to 12.1%, yet those for HCV-related HCC increased from 8.5% to 26.7%. Waitlistings for HBV-related cirrhosis remained almost unchanged (13.2% and 12.4%), while those for HBV-related HCC increased from 4.0% to 11.6%. ALD-related cirrhosis decreased from 16.9% to 12.9% while ALD-related HCC increased from 1.9% to 3.9%. CONCLUSIONS: A sharp increase in liver transplant waitlisting for HCC and a concomitant decrease of waitlisting for cirrhosis have occurred In Italy. Despite HCV infection has noticeably decreased, still remains the primary etiology of waitlisting for HCC, while ALD and HBV represent the main causes for cirrhosis.
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Carcinoma, Hepatocellular , Hepatitis C , Liver Neoplasms , Liver Transplantation , Adult , Humans , Carcinoma, Hepatocellular/epidemiology , Carcinoma, Hepatocellular/surgery , Liver Neoplasms/epidemiology , Liver Neoplasms/surgery , Liver Cirrhosis/epidemiology , Liver Cirrhosis/surgery , Registries , Hepatitis C/complications , Hepatitis C/epidemiologyABSTRACT
N/A.
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Indocyanine Green , Liver Failure, Acute , Humans , Liver , Liver Failure, Acute/diagnosisABSTRACT
Background: We investigated the effects of single (SL-ET) and double leg (DL-ET) high-intensity interval training on O2 deficit (O2Def) and mean response time (MRT) during square-wave moderate-intensity exercise (DL-MOD), and on the amplitude of VËO2p slow component (SCamp), during heavy intensity exercise (DL-HVY), on 33 patients (heart transplant = 13, kidney transplanted = 11 and liver transplanted = 9). Methods: Patients performed DL incremental step exercise to exhaustion, two DL-MOD tests, and a DL-HVY trial before and after 24 sessions of SL-ET (n = 17) or DL-ET (n = 16). Results: After SL-ET, O2Def, MRT and SCamp decreased by 16.4% ± 13.7 (p = 0.008), by 15.6% ± 13.7 (p = 0.004) and by 35% ± 31 (p = 0.002), respectively. After DL-ET, they dropped by 24.9% ± 16.2 (p < 0.0001), by 25.9% ± 13.6 (p < 0.0001) and by 38% ± 52 (p = 0.0003), respectively. The magnitude of improvement of O2Def, MRT, and SCamp was not significantly different between SL-ET and DL-ET after training. Conclusions: We conclude that SL-ET is as effective as DL-ET if we aim to improve VËO2p kinetics in transplanted patients and suggest that the slower, VËO2p kinetics is mainly caused by the impairment of peripherals exchanges likely due to the immunosuppressive medications and disuse.
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Endurance Training , Oxygen Consumption , Adenosine Monophosphate , Exercise/physiology , Exercise Test , Humans , Kinetics , Oxygen/physiology , Oxygen Consumption/physiology , Physical EnduranceABSTRACT
BACKGROUND: In deceased donor kidney transplantation (KT), the use of hypothermic machine perfusion (HMP) has been acquiring the status of best practice in the pre-transplant management of kidney grafts. Two types of HMP are currently available, oxygenated HMP and non-oxygenated HMP. However, data on the real clinical impact of oxygenation on KT outcome are still heterogeneous. METHODS: Retrospective study on a cohort of 103 patients transplanted with a single kidney graft that was managed either with end-ischemic oxygenated (O2 group, Waves Machine, n = 51, 49.5%) or non-oxygenated HMP (no-O2 group, Life Port Kidney Transporter Machine, n = 52, 50.5%), during the period January 2016-December 2020. Oxygenation was performed at pO2 21%. RESULTS: The median cold ischemia time was 29 h:40 min [IQR 26 h:55 min-31 h:10 min] and the prevalence of grafts from extended criteria donors (ECD) was 46.7%, with a median kidney donor profile index (KDPI) of 72 [41-94]. The study groups were homogeneous in terms of recipient characteristics, ischemia times and donor characteristics. O2 and no-O2 groups showed comparable outcomes in terms of delayed graft function (O2 vs no-O2, 21.5% vs 25%, p = 0.58), vascular (0.2% vs 0.2%, p > 0.99) and urologic (13.7% vs 11.5%, p = 0.77) complications, and episodes of graft rejection (11.7% vs 7.7%, p = 0.52). At 1 year follow up, even creatinine serum levels were comparable between the groups (1.27 mg/dL [1.09 and 1.67] vs 1.4 mg/dL [1.9-1.78], p = 0.319), with similar post-transplant trend (p = 0.870). No significant benefit was either observed in ECD or KDPI > 60 subgroups, respectively. CONCLUSIONS: Oxygenation at pO2 21% during HMP seems not to significantly enhance the KT outcomes in terms of postoperative complications or graft function.
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Kidney Transplantation , Cold Ischemia , Graft Survival , Humans , Kidney , Kidney Transplantation/adverse effects , Organ Preservation , Perfusion/adverse effects , Retrospective Studies , Tissue DonorsABSTRACT
The liver-gut axis has been identified as crucial mediator of liver regeneration. Thus, the use of a T-tube in liver transplantation (LT), which interrupts the enterohepatic bile circulation, may potentially have a detrimental effect on the early allograft functional recovery. We retrospectively analyzed a cohort of 261 patients transplanted with a whole liver graft, with a duct-to-duct biliary anastomosis, who did not develop any surgical complication within postoperative day 14. Early allograft dysfunction (EAD) was defined according to the criteria of Olthoff et al. (EAD-O), and graded according to the Model for Early Allograft Function (MEAF) score. EAD-O developed in 24.7% of recipients and the median MEAF score was 4.0 [interquartile range 2.9-5.5]. Both MEAF and EAD predicted 90-day post-LT mortality. A T-tube was used in 49.4% of cases (n = 129). After a propensity score matching for donor age, cold and warm ischemia time, donor risk index, balance of risk score, Child-Pugh class C, and MELD score, the T-tube group showed a significantly higher prevalence of EAD-O and value of MEAF than the no-T-tube group (EAD-O: 29 [34.1%] vs 16 [19.0%], p = 0.027; MEAF 4.5 [3.5-5.7] vs 3.7 [2.9-5.0], p = 0.014). In conclusion, T-tube use in LT may be a risk factor for EAD and higher MEAF, irrespective of graft quality and severity of pre-LT liver disease.
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Liver Transplantation , Delayed Graft Function , Graft Survival , Humans , Retrospective Studies , Risk Factors , Tissue DonorsABSTRACT
Kidneys with multiple renal arteries (MRAs) from different patches, may provide to the surgeon additional technical difficulties that make kidney transplants very challenging. MRAs have been largely debated over the years whether to be anastomosed or not due to the disappointing outcomes when it comes to inappropriate ligation or anastomosis. Some authors empirically reassure that smaller branches can be safely ligated and dissected without intraoperative and postoperative complications or compromising the functional recovery of the graft. Literature is poor about the possible differences in the management of superior and inferior polar arteries. Inferior polar arteries represent a topic of great interest as they may also supply the proximal ureter. The aim of this article is to merge the current knowledge about the management of inferior polar arteries and to highlight if there is any role of the methylene blue dye (MB) in the study of the ureteral vascularization in kidney transplantation. MB can be considered a safe and simple tool of vascular perfusion assessment in kidney transplantation. By injecting the dye-solution into the inferior MRA hidden ureteral branches can be unmasked and guide the surgeon to preserve important vessels. In view of their fundamental role in the vascularization of the ureter, the lower polar arteries of the graft, should be invariably studied by MB. It provides an objective, simple and fast tool for the evaluation of the ureteral vascularization when injected through the inferior MRA of the graft.
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Kidney Transplantation , Ureter , Humans , Kidney , Methylene Blue , Renal Artery/surgeryABSTRACT
BACKGROUND: After liver transplantation, HCV/HIV co-infected patients present, compared to the HCV mono-infected ones, increased HCV viral load, rapid progression to liver fibrosis and higher mortality. Liver biopsies (LB), obtained routinely 6 months after transplantation, represent a unique model to assess the early events related to graft re-infection. Here, we used miRNA sequencing of LB obtained from both HCV-and HCV/HIV-infected recipients, to identify transcriptional profiles able to explain the more severe outcome of these latter. METHODS: miRNAs of 3 healthy livers, 3 HCV-LB and 3 HCV/HIV-LB were sequenced by Illumina HiSeq2500 platform. The DIANA-miRPath v3.0 webserver and DIANA-microT-CDS algorithm (v5.0) were used to characterize the functions of differentially expressed (DE-) miRNAs, querying the KEGG and Gene Ontology-Biological Process databases. RESULTS: LB obtained from infected patients were characterized, with respect to controls, by a miRNA profile related to viral infection, immune system signaling and DNA damage in HCV-induced carcinogenesis. Instead, HCV-LB and HCV/HIV-LB differed in the expression of miRNAs involved in immunological and apoptotic processes and in extracellular matrix remodeling. CONCLUSIONS: liver reinfection processes are associated with early miRNA changes. Further studies are necessary to establish their prognostic role and possible actionability.
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HIV Infections , Hepatitis C , Liver Transplantation , MicroRNAs , HIV Infections/metabolism , Hepatitis C/complications , Humans , MicroRNAs/genetics , MicroRNAs/metabolism , ReinfectionABSTRACT
OBJECTIVES: To investigate the association between the grade of diastolic dysfunction (DD) and the occurrence of early allograft dysfunction (EAD) in liver transplant patients following the new 2016 American Society of Echocardiography/European Association of Cardiovascular Imaging (ASE/EACVI) guidelines. METHODS: From January 2015 to December 2019, we retrospectively analyzed 83 patients who underwent orthotopic liver transplantation (OLTx) and their susceptibility to develop EAD according to the grade of preoperative DD. EAD was defined according to the criteria proposed by Olfhoff et al.; DD was defined with four parameters: E/A, e/e', Left Atrium volume, and Tricuspid Regurgitation velocity. RESULTS: According to the ASE/EACVI guidelines grade II DD was detected in 20 patients (24.1%) undergoing OLTx. A statistically significant association was found between grade II DD and the occurrence of EAD (p-value < 0.003). The Kaplan-Meier analysis failed to find any significant difference between the survival probability, nevertheless at the end of a 90-day follow-up period, mortality showed a different trend in classes with more severe diastolic dysfunction. CONCLUSION: According to the ASE/EACVI guidelines from 2016, patients with grade II DD seem to have a higher propensity to develop early allograft dysfunction EAD after OLTx. Our study advises a need for an urgent prospective multicenter study to elucidate the long-term outcomes of liver transplants patients with diastolic dysfunction.
Subject(s)
Cardiomyopathies , Liver Transplantation , Ventricular Dysfunction, Left , Allografts , Cardiomyopathies/complications , Humans , Liver Transplantation/adverse effects , Prospective Studies , Retrospective StudiesABSTRACT
BACKGROUND: Assessment of hepatic steatosis (HS) before transplantation requires the pathologist to read a graft biopsy. A simple method based on the evaluation of images from tissue samples with a smartphone could expedite and facilitate the liver selection. This study aims to assess the degree of HS by analysing photographic images from liver needle biopsy samples. METHODS: Thirty-three biopsy-images were acquired with a smartphone. Image processing was carried out using ImageJ: background subtraction, conversion to HSB colour space, segmentation of the biopsy area, and evaluation of statistical features of Hue, Saturation, Brightness, Red, Green, and Blue channels on the biopsy area. After feature extraction, correlations were made with gold standard HS percentage assessed at two levels (frozen-section vs glass-slide). Sensitivity, specificity, and accuracy were calculated for each feature. RESULTS: Correlations were found for H, S, R. The sensitivity, specificity, and accuracy of the final classifier based on the K* algorithm were 94%, 92%, 94%. LIMITATIONS: Accuracy assessment was performed considering macrovesicular steatosis on specimens with mostly < 30% HS. CONCLUSIONS: The steatosis assessment based on needle biopsy images, proved to be an effective and promising method. Deep learning approaches could also be experimented with a larger set of images.