Emergency Liver Retransplantation With Marginal Donors.

BACKGROUND: The goal of the present study is to determine if using marginal donors negatively impacts the outcomes of emergency liver retransplantation. METHODS: A retrospective case-control study was performed, including all emergency liver retransplantations done in our center between 1990 and 2021. Recipients from the control group received the second grafts from "ideal donors", and patients from the case group received them from marginal donors. Analyzed variables included demographics of recipients and donors, complications, and survival rates. RESULTS: 38 emergency retransplantations were performed. 23 recipients were included in the control group, and the remaining 15 were in the case group. The second donors from the case group were significantly older (mean age 58 vs 71 years old, P < 0.0001). On the contrary, there were no differences between groups regarding the mean age of recipients, comorbidities, Model for End-Stage Liver Disease scores, or causes of retransplantation (the most common was hepatic artery thrombosis). No differences were found in early perioperative death rates (control group 26.1% vs case group 20%, P =1) and, although the case group seemed to have slightly poorer outcomes in long-term survival (control group 70%, 61%, and 55% vs case group 73%, 59%, and 39%, respectively, at 1, 5, and 10 years), the differences were not statistically significant (log-rank = 0.808). CONCLUSIONS: The use of marginal donors for emergency liver retransplantation was proved safe in our study, as there were no differences in complications or in short- or mid-term survival rates.

Development of a liver graft assessment expert machine-learning system: when the artificial intelligence helps liver transplant surgeons.

Background: The complex process of liver graft assessment is one point for improvement in liver transplantation. The main objective of this study is to develop a tool that supports the surgeon who is responsible for liver donation in the decision-making process whether to accept a graft or not using the initial variables available to it. Material and method: Liver graft samples candidate for liver transplantation after donor brain death were studied. All of them were evaluated "in situ" for transplantation, and those discarded after the "in situ" evaluation were considered as no transplantable liver grafts, while those grafts transplanted after "in situ" evaluation were considered as transplantable liver grafts. First, a single-center, retrospective and cohort study identifying the risk factors associated with the no transplantable group was performed. Then, a prediction model decision support system based on machine learning, and using a tree ensemble boosting classifier that is capable of helping to decide whether to accept or decline a donor liver graft, was developed. Results: A total of 350 liver grafts that were evaluated for liver transplantation were studied. Steatosis was the most frequent reason for classifying grafts as no transplantable, and the main risk factors identified in the univariant study were age, dyslipidemia, personal medical history, personal surgical history, bilirubinemia, and the result of previous liver ultrasound (p < 0.05). When studying the developed model, we observe that the best performance reordering in terms of accuracy corresponds to 76.29% with an area under the curve of 0.79. Furthermore, the model provides a classification together with a confidence index of reliability, for most cases in our data, with the probability of success in the prediction being above 0.85. Conclusion: The tool presented in this study obtains a high accuracy in predicting whether a liver graft will be transplanted or deemed non-transplantable based on the initial variables assigned to it. The inherent capacity for improvement in the system causes the rate of correct predictions to increase as new data are entered. Therefore, we believe it is a tool that can help optimize the graft pool for liver transplantation.

Effects of fresh and field-aged holm-oak biochar on As, Cd and Pb bioaccumulation in different rice growing environments.

Arsenic, Cd, and Pb environmental fate is influenced when the traditional permanent flooding rice production systems are replaced by water-saving and soil conservation practices, urging for additional strategies that avoid their bioaccumulation in rice grain. The aim of this two-years field study was to evaluate the effects of fresh and field-aged biochar on As, Cd, and Pb bioaccumulation, and on As speciation, in rice grain produced in different growing environments (flooding versus sprinkler and conventional tillage versus direct seeding). Biochar produced from holm-oak pruning residues (pyrolysis at 550 °C, 48 h), in a single application (28 Mg ha-1), reduced As bioaccumulation in rice grain in the permanent flooding system to non-quantifiable concentrations (e.g., from 0.178 mg kg-1 to <0.04 mg kg-1, for inorganic-As, respectively), an effect which remained under field-aging conditions, increasing rice commercial value. When adopting sprinkler irrigation, the undesirable increase in Cd bioaccumulation in rice, relatively to the anaerobic system, was counteracted by biochar application, reducing its bioaccumulation in kernels between 32 and 80 %, allowing a simultaneous control of metals and metalloids bioaccumulation in rice. The bioaccumulation of Pb was also prevented with biochar application, with a reduction in its concentration four- to 13-times, in all the management systems, relatively to the non-amended plots, under fresh biochar effects. However, Pb immobilization decreased with biochar field-aging, indicating that the biochar application may have to be repeated to maintain the same beneficial effect. Therefore, the present study shows that the implementation of sprinkler irrigation with holm-oak biochar could reduce the risk of heavy metals(loids) bioaccumulation in rice grains and, thereby, ensuring food safety aspects, particularly under fresh biochar effects.

Quantification and Characterization of CTCs and Clusters in Pancreatic Cancer by Means of the Hough Transform Algorithm.

Circulating Tumor Cells (CTCs) are considered a prognostic marker in pancreatic cancer. In this study we present a new approach for counting CTCs and CTC clusters in patients with pancreatic cancer using the IsofluxTM System with the Hough transform algorithm (Hough-IsofluxTM). The Hough-IsofluxTM approach is based on the counting of an array of pixels with a nucleus and cytokeratin expression excluding the CD45 signal. Total CTCs including free and CTC clusters were evaluated in healthy donor samples mixed with pancreatic cancer cells (PCCs) and in samples from patients with pancreatic ductal adenocarcinoma (PDAC). The IsofluxTM System with manual counting was used in a blinded manner by three technicians who used Manual-IsofluxTM as a reference. The accuracy of the Hough-IsofluxTM approach for detecting PCC based on counted events was 91.00% [84.50, 93.50] with a PCC recovery rate of 80.75 ± 16.41%. A high correlation between the Hough-IsofluxTM and Manual-IsofluxTM was observed for both free CTCs and for clusters in experimental PCC (R2 = 0.993 and R2 = 0.902 respectively). However, the correlation rate was better for free CTCs than for clusters in PDAC patient samples (R2 = 0.974 and R2 = 0.790 respectively). In conclusion, the Hough-IsofluxTM approach showed high accuracy for the detection of circulating pancreatic cancer cells. A better correlation rate was observed between Hough-IsofluxTM approach and with the Manual-IsofluxTM for isolated CTCs than for clusters in PDAC patient samples.

TARTESSUS: A Customized Electrospun Drug Delivery System Loaded with Irinotecan for Local and Sustained Chemotherapy Release in Pancreatic Cancer.

Post-surgical chemotherapy in pancreatic cancer has notorious side effects due to the high dose required. Multiple devices have been designed to tackle this aspect and achieve a delayed drug release. This study aimed to explore the controlled and sustained local delivery of a reduced drug dose from an irinotecan-loaded electrospun nanofiber membrane (named TARTESSUS) that can be placed on the patients' tissue after tumor resection surgery. The drug delivery system formulation was made of polycaprolactone (PCL). The mechanical properties and the release kinetics of the drug were adjusted by the electrospinning parameters and by the polymer ratio between 10 w.t.% and 14 w.t.% of PCL in formic acid:acetic acid:chloroform (47.5:47.5:5). The irinotecan release analysis was performed and three different release periods were obtained, depending on the concentration of the polymer in the dissolution. The TARTESSUS device was tested in 2D and 3D cell cultures and it demonstrated a decrease in cell viability in 2D culture between 72 h and day 7 from the start of treatment. In 3D culture, a decrease in viability was seen between 72 h, day 7 (p < 0.001), day 10 (p < 0.001), 14 (p < 0.001), and day 17 (p = 0.003) as well as a decrease in proliferation between 72 h and day 10 (p = 0.030) and a reduction in spheroid size during days 10 (p = 0.001), 14 (p < 0.001), and 17 (p < 0.001). In conclusion, TARTESSUS showed a successful encapsulation of a chemotherapeutic drug and a sustained and delayed release with an adjustable releasing period to optimize the therapeutic effect in pancreatic cancer treatment.

Combined use of biochar and alternative management systems for imazamox induced pollution control in rice growing environments.

Imazamox (IMZX) is a persistent herbicide having probable risks for non-target organisms in the environment and water contamination. Alternatives to conventional flooding rice production, including biochar amendment, may induce changes in soil properties which can greatly modify the environmental fate of IMZX. This two-year study is the first to evaluate how tillage and irrigation practices, with or without fresh or aged biochar (Bc), that are alternatives to conventional rice production impact IMZX's environmental fate. The treatments were: conventional tillage and flooding irrigation (CTFI), conventional tillage and sprinkler irrigation (CTSI), no-tillage and sprinkler irrigation (NTSI), and the corresponding Bc-amendment treatments (CTFI-Bc, CTSI-Bc, and NTSI-Bc). Fresh and aged Bc amendment decreased IMZX's sorption onto the soil in tillage treatments, with Kf values decreasing 3.7 and 4.2-fold (fresh case) and 1.5 and 2.6-fold (aged case) for CTSI-Bc and CTFI-Bc, respectively. The transition to sprinkler irrigation reduced IMZX persistence. Overall, Bc amendment also reduced chemical persistence with half-life values decreasing 1.6 and 1.5-fold for CTFI and CTSI (fresh year) and 1.1, 1.1, and 1.3-fold for CTFI, CTSI, and NTSI (aged year), respectively. Sprinkler irrigation reduced IMZX leaching by up to a factor of 2.2. The use of Bc as amendment led to a significant decrease in IMZX leaching only under tillage conditions, but notable in particular for the CTFI case where leaching losses were reduced in the fresh year from 80% to 34% and, in the aged year, from 74% to 50%. Hence the change in irrigation from flooding to sprinkler either alone or in combination with the use of Bc (fresh or aged) amendment could be considered an effective way to sharply mitigate IMZX contamination of water in environments where rice is grown, particularly in those managed with tillage.

Effects of Combined Use of Olive Mill Waste Compost and Sprinkler Irrigation on GHG Emissions and Net Ecosystem Carbon Budget under Different Tillage Systems.

Traditional rice (Oryza sativa L.) production by flooding is a source of greenhouse gases (GHG), especially methane. The high consumption of water, as well as the chemical and physical degradation caused by these traditional practices in rice soils, is promoting a decrease in rice production in the Mediterranean area. The aim of this study was to monitor GHG emissions and the net ecosystem carbon balance (NECB) from rice produced with sprinkler irrigation techniques and also assess the impact of olive mill waste compost (C-OW) application and tillage on GHG emissions and the NECB. A field experiment for irrigated rice production was implemented by considering four different treatments: (1) tillage (T); (2) no tillage-direct seeding techniques (DS); (3) application of C-OW followed by tillage (TC); and (4) application of C-OW followed by direct seeding (DSC). The C-OW was only applied in the first year at a dose of 80 Mg ha-1. GHG emissions were monitored over three years in these four treatments in order to estimate the direct (first year) and residual (third year) effects of such practices. The application of C-OW caused an increase of 1.85 times the emission of CO2-C in the TC-DSC compared to the T-DS in the first year. It is noteworthy that the TC treatment was the only one that maintained an emission of CO2-C that was 42% higher than T in the third year. Regardless of the treatments and year of the study, negative values for the cumulative CH4 were found, suggesting that under sprinkler irrigation, CH4 oxidation was the dominant process. A decrease in N2O emissions was observed under direct seeding relative to the tillage treatments, although without significant differences. Tillage resulted in an increase in the global warming potential (GWP) of up to 31% with respect to direct seeding management in the third year, as a consequence of the greater carbon oxidation caused by intensive tillage. DS presented a positive NECB in the accumulation of C in the soil; therefore, it provided a greater ecological benefit to the environment. Thus, under Mediterranean conditions, rice production through a sprinkler irrigation system in combination with direct seeding techniques may be a sustainable alternative for rice crops, reducing their GWP and resulting in a lower carbon footprint. However, the use of C-OW as an organic amendment could increase the GHG emissions from rice fields irrigated by sprinklers, especially under tillage conditions.

Impact of a Donor Age >75 Years on the Survival of Liver Transplant Recipients.

BACKGROUND: An organ shortage is the reason why it is necessary to expand the pool of donors, which can be achieved by using elderly donors. The main goal of this study is to analyze the outcomes of liver transplant (LT) when it is performed with donors older than 75 years. METHODS: We carried out a retrospective case-control study (N = 212) that included LTs with donors older than 75 years (group A, n = 106 cases) that were performed in our center between the years 2010 and 2020. This cohort has been paired off with a similar control group (group B, n = 106) whose donors were significantly younger. A survival analysis using the Kaplan-Meier model was performed. RESULTS: Average (SD) age of donors in group A was statistically greater than group B (A, 79.1 [3.0] years vs B, 54.4 [15.3], P < .001). There were no differences either in the average age of the recipients or in the Model for End-Stage Liver Disease score of both groups. Indications for LT were distributed equally in both groups: the most common was cellular hepatocarcinoma followed by alcohol-related cirrhosis. Survival rates for group A were 81%, 78%, and 67%, in 1, 3, and 5 years, respectively, while in group B they were 85%, 76%, and 71%, respectively, without differences found between the groups (P = .57). CONCLUSIONS: Using elderly liver donors is safe, achieving good outcomes in terms of short- and midterm rates of survival.

Liver Resuscitation With Hypothermic Oxygenated Perfusion After Donation in Asystolic Type Iii With Regional Perfusion in Normothermia: A Case Report About First Experience in Spain.

BACKGROUND: Extended criteria donor livers are increasingly being accepted for transplant in an attempt to bridge the gap between the number of patients on the waiting list and the number of available donor livers. Our objective was to describe our first case of hepatic resuscitation by means of an ex situ perfusion machine in hypothermia with oxygen insufflation of a liver graft extracted from a donor in type 3 asystole after regional perfusion in normothermia. METHODS: A 53-year-old woman with disabling polycystic liver disease was included on the liver transplant waiting list. Donation was offered in type 3 asystole with regional perfusion in normothermia. Given that it was an elderly donor with a low-weight graft, hepatic resuscitation was decided by means of an ex situ perfusion machine in hypothermia with oxygen insufflation. RESULTS: After performing the bench work, the injector is selectively cannulated via the portal to connect it to the hypothermic perfusion machine. The average temperature of the perfusate (3 L modified Belzer) was 10°C for 120 minutes at 250 mL/min. The implant was completed without the need for transfusion of blood products, postreperfusion Sd, or vasoactive support. Peak of GOT/GPT was 803/276 at 24 hours posttransplant.

A scoring system for predicting malignancy in intraductal papillary mucinous neoplasms of the pancreas: a multicenter EUROPEAN validation.

PURPOSE: A preoperative estimate of the risk of malignancy for intraductal papillary mucinous neoplasms (IPMN) is important. The present study carries out an external validation of the Shin score in a European multicenter cohort. METHODS: An observational multicenter European study from 2010 to 2015. All consecutive patients undergoing surgery for IPMN at 35 hospitals with histological-confirmed IPMN were included. RESULTS: A total of 567 patients were included. The score was significantly associated with the presence of malignancy (p < 0.001). In all, 64% of the patients with benign IPMN had a Shin score < 3 and 57% of those with a diagnosis of malignancy had a score ≥ 3. The relative risk (RR) with a Shin score of 3 was 1.37 (95% CI: 1.07-1.77), with a sensitivity of 57.1% and specificity of 64.4%. CONCLUSION: Patients with a Shin score ≤ 1 should undergo surveillance, while patients with a score ≥ 4 should undergo surgery. Treatment of patients with Shin scores of 2 or 3 should be individualized because these scores cannot accurately predict malignancy of IPMNs. This score should not be the only criterion and should be applied in accordance with agreed clinical guidelines.

Environmental fate and efficiency of bispyribac­sodium in rice soils under conventional and alternative production systems affected by fresh and aged biochar amendment.

Irrigation and tillage practice alternatives to conventional flooding production, with or without organic amendments, are attracting great interest to adapt rice cultivation to climate change. However, they can alter the behaviour of pesticides and their efficiency against weeds. A two-year field experiment was conducted to investigate how the environmental fate and the weed control efficiency (WCE) of bispyribac­sodium (BS) were influenced by biochar produced from holm oak prunings (BHO) testing both the fresh and the aged effects. The treatments were: flooding irrigation and tillage (FT), sprinkler irrigation and tillage (ST), sprinkler irrigation and no-tillage (SNT), and the corresponding homologues with BHO addition (FT-BHO, ST-BHO, and SNT-BHO, respectively). Fresh BHO amendment decreased the sorption of BS onto the soil in all treatments, while, after aging, it also decreased sorption in FT-BHO (1.3-fold) but increased it in SNT-BHO and ST-BHO (1.1-fold). BHO addition reduced BS persistence under non-flooding and flooding incubation conditions, except for FT under the former condition for which t1/2 increased ≈1.5-fold in both years. The addition of BHO led to a decrease in BS leaching from 58.3 % and 44.6 % and from 70.4 % and 58.1 % in ST and FT to 50.1 % and 38.3 % and 63.6 % and 50.3 % in the homologue amended soils for the fresh and aged years, respectively. While fresh BHO addition decreased the WCE of BS in SNT-BHO, ST-BHO, and FT-BHO on average by a factor of 1.5, with aged BHO there was only such a decrease (by a factor of 1.4) in FT-BHO. The use of BHO could be effective for reducing water contamination by BS in flooding or sprinkler irrigation rice farming as long as conventional tillage is used. But it may also contribute to greatly reducing the herbicide's efficiency, although with time to allow aging, this reduction would only persist under conventional flooding production.

Body mass index interacts with a genetic-risk score for depression increasing the risk of the disease in high-susceptibility individuals.

Depression is strongly associated with obesity among other chronic physical diseases. The latest mega- and meta-analysis of genome-wide association studies have identified multiple risk loci robustly associated with depression. In this study, we aimed to investigate whether a genetic-risk score (GRS) combining multiple depression risk single nucleotide polymorphisms (SNPs) might have utility in the prediction of this disorder in individuals with obesity. A total of 30 depression-associated SNPs were included in a GRS to predict the risk of depression in a large case-control sample from the Spanish PredictD-CCRT study, a national multicentre, randomized controlled trial, which included 104 cases of depression and 1546 controls. An unweighted GRS was calculated as a summation of the number of risk alleles for depression and incorporated into several logistic regression models with depression status as the main outcome. Constructed models were trained and evaluated in the whole recruited sample. Non-genetic-risk factors were combined with the GRS in several ways across the five predictive models in order to improve predictive ability. An enrichment functional analysis was finally conducted with the aim of providing a general understanding of the biological pathways mapped by analyzed SNPs. We found that an unweighted GRS based on 30 risk loci was significantly associated with a higher risk of depression. Although the GRS itself explained a small amount of variance of depression, we found a significant improvement in the prediction of depression after including some non-genetic-risk factors into the models. The highest predictive ability for depression was achieved when the model included an interaction term between the GRS and the body mass index (BMI), apart from the inclusion of classical demographic information as marginal terms (AUC = 0.71, 95% CI = [0.65, 0.76]). Functional analyses on the 30 SNPs composing the GRS revealed an over-representation of the mapped genes in signaling pathways involved in processes such as extracellular remodeling, proinflammatory regulatory mechanisms, and circadian rhythm alterations. Although the GRS on its own explained a small amount of variance of depression, a significant novel feature of this study is that including non-genetic-risk factors such as BMI together with a GRS came close to the conventional threshold for clinical utility used in ROC analysis and improves the prediction of depression. In this study, the highest predictive ability was achieved by the model combining the GRS and the BMI under an interaction term. Particularly, BMI was identified as a trigger-like risk factor for depression acting in a concerted way with the GRS component. This is an interesting finding since it suggests the existence of a risk overlap between both diseases, and the need for individual depression genetics-risk evaluation in subjects with obesity. This research has therefore potential clinical implications and set the basis for future research directions in exploring the link between depression and obesity-associated disorders. While it is likely that future genome-wide studies with large samples will detect novel genetic variants associated with depression, it seems clear that a combination of genetics and non-genetic information (such is the case of obesity status and other depression comorbidities) will still be needed for the optimization prediction of depression in high-susceptibility individuals.