The PPARα agonist fenofibrate reduces the cytokine imbalance in a maternal immune activation model of schizophrenia.

Maternal infections during pregnancy may increase the risk of psychiatric disorders in offspring. We recently demonstrated that activation of peroxisome proliferator-activate receptor-α (PPARα), with the clinically available agonist fenofibrate (FEN), attenuates the neurodevelopmental disturbances induced by maternal immune activation (MIA) in rat offspring. We hypothesized that fenofibrate might reduce MIA-induced cytokine imbalance using a MIA model based on the viral mimetic polyriboinosinic-polyribocytidilic acid [poly (I:C)]. By using the Bio-Plex Multiplex-Immunoassay-System, we measured cytokine/chemokine/growth factor levels in maternal serum and in the fetal brain of rats treated with fenofibrate, at 6 and 24 h after poly (I:C). We found that MIA induced time-dependent changes in the levels of several cytokines/chemokines/colony-stimulating factors (CSFs). Specifically, the maternal serum of the poly (I:C)/control (CTRL) group showed increased levels of (i) proinflammatory chemokine macrophage inflammatory protein 1-alpha (MIP-1α), (ii) tumor necrosis factor-alpha (TNF-α), the monocyte chemoattractant protein-1 (MCP-1), the macrophage (M-CSF) and granulocyte-macrophage colony-stimulating factor (GM-CSF). Conversely, in the fetal brain of the poly (I:C)/CTRL group, interleukin 12p70 and MIP-1α levels were lower than in vehicle (veh)/CTRL group. Notably, MIP-1α, TNF-α, keratinocyte derived chemokine (GRO/KC), GM-CSF, and M-CSF levels were lower in the poly (I:C)/FEN than in poly (I:C)/CTRL rats, suggesting the protective role of the PPARα agonist. PPARα might represent a therapeutic target to attenuate MIA-induced inflammation.

Partial Replacement of Synthetic Vitamin E by Polyphenols in Post-Weaning Piglets.

Vitamin E is an essential nutrient usually recommended in post-weaning piglets, when a decline in the serum vitamin E concentration is observed. Selected polyphenols have the potential to partially replace vitamin E in animal feed. The aim of this study was to investigate the effect of the dietary inclusion of some commercial polyphenol products (PPs) on the growth performance, antioxidant status and immunity of post-weaning piglets. A total of 300 piglets (BW 7.18 kg ± 1.18) were randomly assigned to six dietary groups: CON- (40 mg/kg vitamin E); CON+(175.8 mg/kg vitamin E); and PP1, PP2, PP3 and PP4, in which 50% vitamin E of CON+ was replaced with PP with equivalent vitamin E activity. The PP1 group exhibited lower performance (p < 0.05) than the other dietary groups, but a similar performance to that commonly registered in pig farms. Dietary polyphenols did not influence the IgG concentration or the IL-6, IL-10, IFN-γ and TNF-α cytokine concentrations. A lower IL-8 level was found in the PP4 group than in the other groups. The diets that affected the vitamin A content showed the highest value (p < 0.05) in the PP1 group, and a trend was noted for vitamin E with a higher content in PP4 and CON+. The polyphenols-enriched diets, especially the PP3 diet, maintained an antioxidant capacity (whole blood KRL) similar to the CON+ diet. In conclusion, the replacement of vitamin E with all PPs enables partial vitamin E substitution in post-weaning piglets.

Chemical Characterization and In Vitro Gas Production Kinetics of Alternative Feed Resources for Small Ruminants in the Maltese Islands.

The ever-increasing human population, the problem associated with climate change and recent crises-COVID-19 disease and trade conflicts-all impacted on the availability and cost of animal feed raw materials. This is clearly visible in realities which heavily rely on importation such as islands and small states, where producers involved in the agricultural sector were strongly affected by the sharp increase in prices. To deal with these global issues, alternative resources are perceived to replace conventional ingredients. This work aimed at assessing the nutritive value of different resources (sheep feed, mature carob, Maltese bread, wild asparagus, prickly lettuce, and loquat) for small ruminants present in the Maltese Islands, analyzing their chemical composition, gas production kinetics and antioxidant properties. In general, the variation in chemical composition resulted in different rumen fermentation kinetics (p < 0.007). The ratio between GP-24 h and GP-48 h was higher in Maltese bread than other substrates; loquat, prickly lettuce and wild asparagus showed lower fermentation kinetics in accordance with their high NDF and ADF contents. The antioxidant activity may be partially related to the polyphenolic content that was higher in wild asparagus, prickly lettuce and loquat. All feed characteristic confirmed their potential to be included as ingredients in ruminant diets and as a source of fiber.

Antioxidant Activity of Different Tissues from Rabbits Fed Dietary Bovine Colostrum Supplementation.

Recent advances in animal nutrition have indicated that bovine colostrum (BC), due to its content of macronutrients, micronutrients and bioactive compounds, is an excellent health supplement. To the best of our knowledge, no studies on the effect of BC on antioxidant status have been performed in rabbits. This study aimed to investigate the effect of two BC concentrations on antioxidant status and gene expression of antioxidant enzymes in some tissues of rabbits. Thirty New Zealand White male rabbits were randomly divided into three experimental diets, containing 0% (CON), 2.5%, and 5% of BC (BC-2.5 and BC-5, respectively). The activity of antioxidant enzymes in plasma (catalase: CAT; glutathione peroxidase: GPx; superoxide dismutase: SOD), and the enzymes' gene expression in the liver and longissimus dorsi muscle, were determined. Results showed no significant differences, neither in plasma nor in tissues. A significant tissue-related effect has been observed regarding the mRNA levels of SOD and GPx, which were higher in the LD (p = 0.022) and liver (p = 0.001), respectively. Further studies, considering modifications of the length and dosage of dietary BC supplementation, are required to update the current state of knowledge in rabbits, as well as to fully understand the potential value of BC for possible application in farming use.

Evaluation of Nutraceutical Properties of Eleven Microalgal Strains Isolated from Different Freshwater Aquatic Environments: Perspectives for Their Application as Nutraceuticals.

The increasing global population and the simultaneous growing attention to natural, sustainable, and healthier products are driving the food industry towards research on alternative food sources. In this scenario, microalgae are gaining worldwide attention as "functional feedstocks" for foods, feeds, supplements, and nutraceutical formulations, being a source of high-value metabolites including polyphenols and other antioxidant compounds. In this work, eleven microalgal strains from freshwater environments were evaluated for their nutraceutical properties, focusing on photosynthetic pigments, total polyphenols, and flavonoid content, as well as in vitro antioxidant activities. Data helped to select those strains showing the most promising features for simultaneous massive growth and bioactive compound production. Results highlighted that the microalgae have variable values for both biochemical parameters and antioxidant activities, mainly depending on the solvents and applied treatment rather than on the isolation sources or the phylogenetic attribution. According to our results, the putative best candidates for massive cultivation under laboratory conditions for the simultaneous extraction of different molecules with nutraceutical potential are strains F1 (Scenedesmaceae), F3 (Chlamydomonas debariana), R1 (Chlorella sorokiniana), and C2 (Chlorella-like).

Predictors of solid extra-hepatic non-skin cancer in liver transplant recipients and analysis of survival: A long-term follow-up study.

INTRODUCTION AND OBJECTIVES: De novo malignancies represent an important cause of death for liver transplant recipients. Our aim was to analyze predictors of extra-hepatic non-skin cancer (ESNSC) and the impact of ESNSC on the long-term outcome. PATIENTS: We examined data from patients transplanted between 2000 and 2005 and followed-up in five Italian transplant clinics with a retrospective observational cohort study. Cox Regression was performed to identify predictors of ESNSC. A 1:2 cohort sub-study was developed to analyze the impact of ESNSC on 10-year survival. RESULTS: We analyzed data from 367 subjects (median follow-up: 15 years). Patients with ESNSC (n = 47) more often developed post-LT diabetes mellitus (DM) (57.4% versus 35,9%, p = 0.004). At multivariate analysis, post-LT DM independently predicted ESNSC (HR 1.929, CI 1.029-3.616, p = 0.040). Recipients with ESNSC showed a lower 10-year survival than matched controls (46,8% versus 68,1%, p = 0.023). CONCLUSIONS: Post-LT DM seems to be a relevant risk factor for post-LT ESNSC. ESNSC could have a noteworthy impact on the long-term survival of LT recipients.

Genetic variant within CDK6 regulates immune response to palbociclib treatment.

Everyone carries a set of genetic variants that contribute to regulation of the levels of blood cells, with unknown clinical impact. One of them, rs445 within the cell-cycle checkpoint gene CDK6, reduces the levels of myeloid cell types including granulocytes. We treated CD3+ T cells and whole blood with palbociclib in 41 individuals, who were stratified by genotype for analyses. In T cells we assessed cell cycle and apoptosis, whereas in whole blood, apoptosis in activated (CD11b+), unactivated (CD11b-) granulocytes, cytotoxic (CD8 + CD4-), and helper (CD8-CD4+) T cells. We find that rs445 modulates the immune response of CD8+ T cells. It also increases the level of apoptotic CD11b + activated granulocytes after palbociclib treatment, which, in synergy with neutropenia, may affect drug related adverse events. These results suggest that the effect of palbociclib treatment may depend on underlying genetically encoded individual immune response as well as the direct response to the drug.

Molecular and Immunohistochemical Expression of LTA4H and FXR1 in Canine Oral Melanoma.

Oral melanoma is a common canine tumor whose prognosis is considered ominous, but poorly predicted by histology alone. In the present study the gene and protein expression of Leukotriene A4 hydrolase (LTA4H) and Fragile-X-mental retardation-related protein1 (FXR1), both reported as related to metastatic potential in different tumors, were investigated in canine oral melanoma. The main aim of the study was to confirm and quantify the presence of LTA4H and FXR1 genes and protein in oral melanomas. A secondary aim was to investigate their association with histologic prognostic criteria (mitotic count, Ki-67 index). Formalin-fixed-paraffin-embedded canine oral melanomas (36) were collected and histopathological evaluation carried out. Immunolabelling for LTA4H and FXR1 and Ki-67 were performed. RT-PCR evaluated LTA4H and FXR1 gene expressions. Histologically, most tumors were epithelioid cell melanomas (19/36) and were amelanotic, mildly or moderately pigmented (5, 12 and 13/36 respectively), only 6 were highly pigmented. Mitotic count ranged 1-106, Ki-67 index ranged 4.5-52.3. Thirty-two (32/32) melanomas immunolabelled for LTA4H and 33/34 for FXR1. RT-PCR values ranged 0.76-5.11 ΔCt for LTA4H and 0.22-6.24 ΔCt for FXR1. Molecular and immunohistochemical expression of both LTA4H and FXR1 did not statically correlate with mitotic count or Ki-67 index. The present study demonstrates LTA4H and FXR1 gene and protein in canine oral melanoma, however their expression is apparently unrelated to histopathologic prognostic criteria. Although LTA4H and FXR1 seem unrelated to tumor behavior, their extensive expression in the present cohort of cases suggest that they may play a role in canine oral melanoma oncogenesis.

Pilot Study: Does Contamination with Enniatin B and Beauvericin Affect the Antioxidant Capacity of Cereals Commonly Used in Animal Feeding?

Increasing consumption of cereals has been associated with reduced risk of several chronic diseases, as they contain phytochemicals that combat oxidative stress. Cereal contamination by the "emerging mycotoxins" beauvericin (BEA) and enniatins (ENs) is a worldwide health problem that has not yet received adequate scientific attention. Their presence in feeds represents a risk for animals and a potential risk for humans because of their carry-over to animal-derived products. This preliminary study aimed to investigate if the total antioxidant capacity (TAC) of corn, barley, and wheat flours could be influenced by contamination with increasing levels of BEA and ENN B. The highest TAC value was observed in barley compared with wheat and corn (p < 0.001) before and after contamination. No effect of mycotoxin or mycotoxin level was found, whereas cereal x mycotoxin exhibited a significant effect (p < 0.001), showing a lower TAC value in wheat contaminated by ENN B and in barley contaminated by BEA. In conclusion, barley is confirmed as a source of natural antioxidants with antiradical potentials. Additional studies with a larger sample size are necessary to confirm the obtained results, and investigations of the toxic effects of these emergent mycotoxins on animals and humans should be deepened.

Liver Transplantation for HCC in HIV-Infected Patients: Long-Term Single-Center Experience.

BACKGROUND: HIV-infected patients now have long life expectation since the introduction of the highly active antiretroviral therapy (HAART). Liver diseases, especially cirrhosis and hepatocellular carcinoma (HCC), currently represent a leading cause of death in this setting of patients. AIM: To address the results of liver transplantation (LT) for HCC in HIV-infected patients. METHODS: All patients with and without HIV infection who underwent LT for HCC (n = 420) between 2001 and 2021 in our center were analyzed with the intent of comparing graft and patient survival. Cox regression analysis was used to determine prognostic survival factors and logistic regression to determine the predictor factors of post-LT recurrence. RESULTS: Among 1010 LT, 32 were HIV-infected recipients. With an average follow-up of 62 ± 51 months, 5-year overall survival in LT recipients with and without HIV-infection was 71.6% and 69.9%, respectively (p = ns), whereas 5-year graft survival in HIV-infected and HIV-non infected was 68.3% and 68.2%, respectively (p = ns). The independent predictive factor of survival in the study group was: HCV infection (HR 1.83, p = 0.024). There were no significant differences in the pathological characteristics of HCC between the two groups. The logistic regression analysis of the study population demonstrated that microvascular invasion (HR 5.18, p< 0.001), HCC diameter (HR 1.16, p = 0.028), and number of HCC nodules (HR 1.26, p = 0.003) were predictors of recurrence post-LT. CONCLUSION: Our study shows that HIV patients undergoing LT for HCC have comparable results in terms of post-LT survival. Excellent results can be achieved for HIV-infected patients with HCC, as long as a strategy of close surveillance and precise treatment of the tumor is adopted while on the waiting list.

Dietary Polyphenol Supplementation in Food Producing Animals: Effects on the Quality of Derived Products.

The growing interest in producing healthier animal products with a higher ratio of polyunsaturated to saturated fatty acids, is associated with an increase in lipoperoxidation. For this reason, it is essential to attenuate oxidative deterioration in the derived products. Natural antioxidants such as polyphenols represent a good candidate in this respect. The first part of the review highlights the occurrence, bioavailability, and the role of polyphenols in food-producing animals that, especially in intensive systems, are exposed to stressful situations in which oxidation plays a crucial role. The second part offers an overview of the effects of polyphenols either supplemented to the diet of monogastric and ruminants or added directly to meat and dairy products on the physicochemical and sensorial properties of the product. From this review emerges that polyphenols play an important, though not always clear, role in the quality of meat and meat products, milk and dairy products. It cannot be ruled out that different compounds or amounts of polyphenols may lead to different results. However, the inclusion of agro-industrial by-products rich in polyphenols, in animal feed, represents an innovative and alternative source of antioxidants as well as being useful in reducing environmental and economic impact.

Intraoperative thromboelastography as a tool to predict postoperative thrombosis during liver transplantation.

BACKGROUND: Thromboembolic complications are relatively common causes of increased morbidity and mortality in the perioperative period in liver transplant patients. Early postoperative portal vein thrombosis (PVT, incidence 2%-2.6%) and early hepatic artery thrombosis (HAT, incidence 3%-5%) have a poor prognosis in transplant patients, having impacts on graft and patient survival. In the present study, we attempted to identify the predictive factors of these complications for early detection and therefore monitor more closely the patients most at risk of thrombotic complications. AIM: To investigate whether intraoperative thromboelastography (TEG) is useful in detecting the risk of early postoperative HAT and PVT in patients undergoing liver transplantation (LT). METHODS: We retrospectively collected thromboelastographic traces, in addition to known risk factors (cold ischemic time, intraoperative requirement for red blood cells and fresh-frozen plasma transfusion, prolonged operating time), in 27 patients, selected among 530 patients (≥ 18 years old), who underwent their first LT from January 2002 to January 2015 at the Liver University Transplant Center and developed an early PVT or HAT (case group). Analyses of the TEG traces were performed before anesthesia and 120 min after reperfusion. We retrospectively compared these patients with the same number of nonconsecutive control patients who underwent LT in the same study period without developing these complications (1:1 match) (control group). The chosen matching parameters were: Patient graft and donor characteristics [age, sex, body mass index (BMI)], indication for transplantation, procedure details, United Network for Organ Sharing classification, BMI, warm ischemia time (WIT), cold ischemia time (CIT), the volume of blood products transfused, and conventional laboratory coagulation analysis. Normally distributed continuous data are reported as the mean ± SD and compared using one-way Analysis of Variance (ANOVA). Non-normally distributed continuous data are reported as the median (interquartile range) and compared using the Mann-Whitney test. Categorical variables were analyzed with Chi-square tests with Yates correction or Fisher's exact test depending on best applicability. IBM SPSS Statistics version 24 (SPSS Inc., Chicago, IL, United States) was employed for statistical analysis. Statistical significance was set at P < 0.05. RESULTS: Postoperative thrombotic events were identified as early if they occurred within 21 d postoperatively. The incidence of early hepatic artery occlusion was 3.02%, whereas the incidence of PVT was 2.07%. A comparison between the case and control groups showed some differences in the duration of surgery, which was longer in the case group (P = 0.032), whereas transfusion of blood products, red blood cells, fresh frozen plasma, and platelets, was similar between the two study groups. Thromboelastographic parameters did not show any statistically significant difference between the two groups, except for the G value measured at basal and 120' postreperfusion time. It was higher, although within the reference range, in the case group than in the control group (P = 0.001 and P < 0.001, respectively). In addition, clot lysis at 60 min (LY60) measured at 120' postreperfusion time was lower in the case group than in the control group (P = 0.035). This parameter is representative of a fibrinolysis shutdown (LY60 = 0%-0.80%) in 85% of patients who experienced a thrombotic complication, resulting in a statistical correlation with HAT and PVT. CONCLUSION: The end of surgery LY60 and G value may identify those recipients at greater risk of developing early HAT or PVT, suggesting that they may benefit from intense surveillance and eventually anticoagulation prophylaxis in order to prevent these serious complications after LT.

Robotic Liver Resection Versus Percutaneous Ablation for Early HCC: Short- and Long-Term Results.

BACKGROUND: The correct approach for early hepatocellular carcinoma (HCC) is debatable, since multiple options are currently available. Percutaneous ablation (PA) is associated in some series to reduced morbidity compared to liver resection (LR); therefore, minimally invasive surgery may play a significant role in this setting. METHODS: All consecutive patients treated by robotic liver resection (RLR) or PA between January 2014 and October 2019 for a newly diagnosed single HCC, less than 3 cm in size (very early/early stages according to the Barcelona Clinic Liver Cancer (BCLC)) on chronic liver disease or liver cirrhosis, were enrolled in this retrospective study. The aim of this study was to compare short- and long-term outcomes to define the best approach in this specific cohort. RESULTS: 60 patients fulfilled the inclusion criteria: 24 RLR and 36 PA. The two populations were homogeneous in terms of baseline characteristics. There were no statistically significant differences regarding the incidence of postoperative morbidity (RLR 38% vs. PA 19%, p = 0.15). The cumulative incidence of recurrence (CIR) was significantly higher in patients who underwent PA, with the one, two, and three years of CIR being 42%, 69%, and 73% in the PA group and 17%, 27%, and 27% in the RLR group, respectively. CONCLUSIONS: RLR provides a significantly higher potential of cure and tumor-related free survival in cases of newly diagnosed single HCCs smaller than 3 cm. Therefore, it can be considered as a first-line approach for the treatment of patients with those characteristics in high-volume centers with extensive experience in the field of hepatobiliary surgery and minimally invasive approaches.

Robotic versus laparoscopic gastrectomy for gastric cancer: The largest meta-analysis.

BACKGROUND: Minimally invasive surgery (MIS) has been increasingly used in the treatment of gastric cancer (GC). Laparoscopic gastrectomy (LG) has shown several advantages over open surgery in dealing with GC, although it is still considered a demanding procedure. Robotic gastrectomy (RG) is now being employed with increased frequency worldwide and has been reported to overcome some limitations of conventional LG. The aim of this updated meta-analysis is to compare surgical and oncological outcomes of RG versus LG for gastric cancer. MATERIALS AND METHODS: A systematic review and meta-analysis was conducted using the PubMed, MEDLINE and Cochrane library database of published studies comparing RG and LG up to March 2020. The evaluated end-points were intra-operative, post-operative and oncological outcomes. Dichotomous data were calculated by odds ratio (OR) and continuous data were calculated by mean difference (MD) with 95% confidence intervals (95% CI), and a random-effect model was always applied. RESULTS: Forty retrospective studies describing 17,712 patients met the inclusion criteria. With respect to surgical outcomes, robotic compared with laparoscopic gastrectomy was associated with higher operating time [MD 44.73, (95%CI 36.01, 53.45) p < 0.00001] and less intraoperative blood loss [MD -18.24, (95%CI -25.21, -11.26) p < 0.00001] and lower rate of surgical complication in terms of Dindo-Clavien ≥ 3 classification [OR 0.66, (95%CI 0.49, 0.88) p = 0.005]. With respect to oncological outcomes, the RG group showed a significantly increased mean number of retrieved lymph nodes [MD 1.84, (95%CI 0.84, 2.84) p = 0.0003], but mean proximal and distal resection margin distance and the recurrence rate were not significantly different between the two approaches. CONCLUSIONS: With respect to safety, technical feasibility and oncological adequacy, robotic and laparoscopic groups were comparable, although the robotic approach seems to achieve better short-term surgical outcomes. Moreover, a higher rate of retrieved lymph nodes was observed in the RG group.

Pre-transplant diabetes predicts atherosclerotic vascular events and cardiovascular mortality in liver transplant recipients: a long-term follow-up study.

Background Early after surgery, liver transplant (LT) recipients often develop weight gain. Metabolic disorders and cardiovascular disease represent main drivers of morbidity and mortality. Our aim was to identify predictors of atherosclerotic vascular events (AVE) and to assess the impact of AVE on the long-term outcome. Methods We retrospectively analyzed data from patients transplanted between 2000 and 2005 and followed-up in five Italian transplant clinics. Cox Regression analysis was performed to identify predictors of AVE, global mortality, and cardiovascular mortality. Survival analysis was performed using the Kaplan-Meier method. Results We analyzed data from 367 subjects during a median follow-up of 14 years. Thirty-seven post-LT AVE were registered. Patients with AVE more frequently showed pre-LT diabetes mellitus (DM) (48.6 vs 13.9%, p=0.000). In the post-LT period, patients with AVE satisfied criteria of metabolic syndrome in 83.8% vs. 36.7% of subjects without AVE (p=0.000). At multivariate analysis, pre-LT DM independently predicted AVE (HR 2.250, CI 4.848-10.440, p=0.038). Moreover, both pre-LT DM and AVE strongly predicted cardiovascular mortality (HR 5.418, CI 1.060-29.183, p=0.049, and HR 86.097, CI 9.510-779.480, p=0.000, respectively). Conclusions Pre-LT DM is the main risk factor for post-LT AVE. Pre-LT DM and post-LT AVE are strong, long-term predictors of cardiovascular mortality. Patients with pre-LT DM should obtain a personalized follow-up for prevention or early diagnosis of AVE.

Laparoscopic versus open liver resection for intrahepatic cholangiocarcinoma: the first meta-analysis.

BACKGROUND: Laparoscopic liver resection (LLR) has gained increasing acceptance for surgical treatment of malignant and benign liver tumors. LLR for intrahepatic cholangiocarcinoma (ICC) is not commonly performed because of the concern for the frequent need for major hepatectomy, vascular-biliary reconstructions, and lymph node dissection (LND). The aim of this present meta-analysis is to compare surgical and oncological outcomes of laparoscopic (LLR) versus open liver resection (OLR) for ICC. MATERIALS AND METHODS: A systematic review was conducted using the PubMed, MEDLINE, and Cochrane library database of published studies comparing LLR and OLR up to October 2019. Two reviewers independently assessed the eligibility and quality of the studies. Dichotomous data were calculated by odds ratio (OR), and continuous data were calculated by mean difference (MD) with 95% confidence intervals (95% CI). RESULTS: Four retrospective observational studies describing 204 patients met the inclusion criteria. With respect to surgical outcomes, laparoscopic compared with open liver resection was associated with lower blood loss [MD - 173.86, (95% CI - 254.82, -92.91) p < 0.0001], less requirement of blood transfusion [OR 0.34, (95% CI 0.14, 0.82) p = 0.02], less need for Pringle maneuver [OR 0.17, (95% CI 0.07, 0.43) p = 0.0002], shorter hospital stay [MD - 3.77, (95% CI - 5.09, - 2.44; p < 0.0001], and less morbidity [OR 0.44, (95% CI 0.21, 0.94) p = 0.03]. With respect to oncological outcomes, the LLR group was prone to lower rates of lymphadenectomy [OR 0.12, (95% CI 0.06, 0.25) p < 0.0001], but surgical margins R0 and recurrence rate were not significantly different. CONCLUSION: Laparoscopic liver resection for ICC seems to achieve better surgical outcomes, providing short-term benefits without negatively affecting oncologic adequacy in terms of R0 resections and disease recurrence. However, a higher LND rate was observed in the open group. Due to the risk of bias and the statistical heterogeneity between the studies included in this review, further RCTs are needed to reach stronger scientific conclusions.

University of Modena Experience With Liver Grafts From Donation After Circulatory Death: What Really Matters in Organ Selection?

INTRODUCTION: The use of grafts from donation after circulatory death (DCD) is an important additional source to implement within the donor pool. We herein report the outcomes of our early experience with DCD grafts for liver transplantation (LT). METHODS: Ten patients successfully underwent LT with grafts from DCD donors between August 2017 and January 2019 at the Hepato-Pancreato-Biliary Surgery and Liver Transplant Unit of University of Modena and Reggio Emilia. All donors underwent normothermic regional perfusion after death declaration and, after the procurement, all the suitable grafts underwent ex situ hypothermic perfusion prior to transplantation. RESULTS: Mean postoperative hospital stay after transplant was 12.7 days (range, 5-26), and in 5 cases we placed a biliary drainage (Kehr tube) during surgery. Primary graft nonfunction did not occur after LT in this cohort, although, we registered one case of biliary anastomosis stricture that was managed endoscopically by endoscopic retrograde cholangiopancreatography. All patients are alive and none required retransplantation. CONCLUSIONS: In our experience with controlled DCD donors, the demonstration of: (1) a negative trend of lactate during normothermic regional perfusion; (2) an aspartate aminotransferase and alanine aminotransferase level lower than 2000 mU/dL; and (3) less than 1 hour of functional warm ischemia time along with no signs of microscopic or macroscopic ischemia of the grafts, are related to positive outcomes in the first year after transplant. A DCD risk score based on Italian population characteristics and regulations on death observation may improve donor-recipient match and avoid futile transplants.

Vacuum-assisted management of surgical site infections after liver transplantation: 15-year experience in a tertiary hepatobiliary center.

Immune compromised as well as critically ill patients are at higher risk of surgical wound infection and dehiscence. Wound infections critically influence the outcomes after liver transplantation. In particular, it was shown that they significantly reduce the overall survival rate when compared to patients with uneventful wound healing, and their occurrence is associated with death or graft loss within 1-year post-transplantation. From January 2001 through December 2017, 763 patients underwent liver transplantation in our Institution, the Hepato-Pancreato-Biliary Surgery and Liver Transplantation Unit, "Policlinico" University Hospital, University of Modena and Reggio Emilia, Modena, Italy. We retrospectively analyzed data from our prospectively maintained database of patients treated with a negative pressure therapy device due to wound or abdominal infections. 13 patients underwent negative pressure treatments for surgical site infection after liver transplantation in our institution. Ten superficial "supra-fascial" applications (SF group) and three deeper abdominal (Ab group) were reported. Mean in-hospital stay for the SF group was 42.6 days, ranging from 8 to 80, while for the Ab group was 62 days (range 23-133), with an overall survival of 34 and 4.6 months, respectively. A multifactorial multidisciplinary approach is needed in the prevention of surgical site infections instead of mere antimicrobial prophylaxis The application of negative pressure wound therapy may help in controlling the diffusion of the infection and preventing sepsis.

De-novo nonalcoholic steatohepatitis is associated with long-term increased mortality in liver transplant recipients.

OBJECTIVE: Patients who have undergone transplantation often develop metabolic syndrome (MetS) and de-novo nonalcoholic fatty liver disease (NAFLD). Our aim was to evaluate the impact of metabolic disease on cardiovascular and neoplastic risk and survival. PATIENTS AND METHODS: Data from patients who underwent transplantation between 2000 and 2005 in two Italian transplant centers were analyzed. Cox regression analysis was carried out for predictors of de-novo NAFLD and nonalcoholic steatohepatitis (NASH), cardiovascular events, de-novo extrahepatic cancers, and survival. Survival analysis was completed using the Kaplan-Meier method. A P value less than 0.05 was considered significant for all tests. RESULTS: De-novo NAFLD was found in one-fifth of 194 patients. Patients with de-novo NAFLD fulfilled the criteria of MetS in 74.4% of cases, while patients without de-novo NAFLD in 29.8% (P=0.000). On multivariate analysis, MetS correlated independently with de-novo NAFLD and this emerged as an independent predictor of cardiovascular events and as a relevant risk factor for solid extrahepatic cancer. Data on smoking habits, which represent a consolidated risk factor for cardiovascular events and cancer in both the general population and patients who have undergone transplantation, are not available. In the subset of histologically proven NASH, it was the strongest predictor of long-term survival (hazard ratio=4.133, 95% confidence interval: 1.385-12.331, P=0.011). CONCLUSION: Post-transplant NAFLD represented a strong risk factor for cardiovascular atherosclerotic disease and solid extrahepatic cancer, whereas de novo histologically proven NASH was an independent predictor of long-term mortality.

Overexpression of the Cytokine BAFF and Autoimmunity Risk.

BACKGROUND: Genomewide association studies of autoimmune diseases have mapped hundreds of susceptibility regions in the genome. However, only for a few association signals has the causal gene been identified, and for even fewer have the causal variant and underlying mechanism been defined. Coincident associations of DNA variants affecting both the risk of autoimmune disease and quantitative immune variables provide an informative route to explore disease mechanisms and drug-targetable pathways. METHODS: Using case-control samples from Sardinia, Italy, we performed a genomewide association study in multiple sclerosis followed by TNFSF13B locus-specific association testing in systemic lupus erythematosus (SLE). Extensive phenotyping of quantitative immune variables, sequence-based fine mapping, cross-population and cross-phenotype analyses, and gene-expression studies were used to identify the causal variant and elucidate its mechanism of action. Signatures of positive selection were also investigated. RESULTS: A variant in TNFSF13B, encoding the cytokine and drug target B-cell activating factor (BAFF), was associated with multiple sclerosis as well as SLE. The disease-risk allele was also associated with up-regulated humoral immunity through increased levels of soluble BAFF, B lymphocytes, and immunoglobulins. The causal variant was identified: an insertion-deletion variant, GCTGT→A (in which A is the risk allele), yielded a shorter transcript that escaped microRNA inhibition and increased production of soluble BAFF, which in turn up-regulated humoral immunity. Population genetic signatures indicated that this autoimmunity variant has been evolutionarily advantageous, most likely by augmenting resistance to malaria. CONCLUSIONS: A TNFSF13B variant was associated with multiple sclerosis and SLE, and its effects were clarified at the population, cellular, and molecular levels. (Funded by the Italian Foundation for Multiple Sclerosis and others.).