The Protective Effect of Nutraceuticals on Hepatic Ischemia-Reperfusion Injury in Wistar Rats.

Nutraceuticals are bioactive compounds present in foods, utilized to ameliorate health, prevent diseases, and support the proper functioning of the human body. They have gained attention due to their ability to hit multiple targets and act as antioxidants, anti-inflammatory agents, and modulators of immune response and cell death. Therefore, nutraceuticals are being studied to prevent and treat liver ischemia-reperfusion injury (IRI). This study evaluated the effect of a nutraceutical solution formed by resveratrol, quercetin, omega-3 fatty acid, selenium, ginger, avocado, leucine, and niacin on liver IRI. IRI was performed with 60 min of ischemia and 4 h of reperfusion in male Wistar rats. Afterward, the animals were euthanized to study hepatocellular injury, cytokines, oxidative stress, gene expression of apoptosis-related genes, TNF-α and caspase-3 proteins, and histology. Our results show that the nutraceutical solution was able to decrease apoptosis and histologic injury. The suggested mechanisms of action are a reduction in gene expression and the caspase-3 protein and a reduction in the TNF-α protein in liver tissue. The nutraceutical solution was unable to decrease transaminases and cytokines. These findings suggest that the nutraceuticals used favored the protection of hepatocytes, and their combination represents a promising therapeutic proposal against liver IRI.

Molecular Profile of Intrahepatic Cholangiocarcinoma.

Intrahepatic cholangiocarcinoma (ICC) is a relatively uncommon but highly aggressive primary liver cancer that originates within the liver. The aim of this study is to review the molecular profile of intrahepatic cholangiocarcinoma and its implications for prognostication and decision-making. This comprehensive characterization of ICC tumors sheds light on the disease's underlying biology and offers a foundation for more personalized treatment strategies. This is a narrative review of the prognostic and therapeutic role of the molecular profile of ICC. Knowing the molecular profile of tumors helps determine prognosis and support certain target therapies. The molecular panel in ICC helps to select patients for specific therapies, predict treatment responses, and monitor treatment responses. Precision medicine in ICC can promote improvement in prognosis and reduce unnecessary toxicity and might have a significant role in the management of ICC in the following years. The main mutations in ICC are in tumor protein p53 (TP53), Kirsten rat sarcoma virus (KRAS), isocitrate dehydrogenase 1 (IDH1), and AT-rich interactive domain-containing protein 1A (ARID1A). The rate of mutations varies significantly for each population. Targeting TP53 and KRAS is challenging due to the natural characteristics of these genes. Different stages of clinical studies have shown encouraging results with inhibitors of mutated IDH1 and target therapy for ARID1A downstream effectors. Fibroblast growth factor receptor 2 (FGFR2) fusions are an important target in patients with ICC. Immune checkpoint blockade can be applied to a small percentage of ICC patients. Molecular profiling in ICC represents a groundbreaking approach to understanding and managing this complex liver cancer. As our comprehension of ICC's molecular intricacies continues to expand, so does the potential for offering patients more precise and effective treatments. The integration of molecular profiling into clinical practice signifies the dawn of a new era in ICC care, emphasizing personalized medicine in the ongoing battle against this malignancy.

Liver transplant recipients infected with SARS-CoV-2 in the early postoperative period: Lessons from a single center in the epicenter of the pandemic.

The impact of coronavirus disease-19 (COVID-19) in liver recipients remains largely unknown. Most data derive from small retrospective series of patients transplanted years ago. We aimed to report a single-center case series of five consecutive patients in the early postoperative period of deceased-donor liver transplantation who developed nosocomial COVID-19. Two patients presented important respiratory discomfort and eventually died. One was 69 years old and had severe coronary disease. She rapidly worsened after COVID-19 diagnosis on 9th postoperative day. The other was 67 years old with non-alcoholic steatohepatitis, who experienced prolonged postoperative course, complicated with cytomegalovirus infection and kidney failure. He was diagnosed on 36th postoperative day and remained on mechanical ventilation for 20 days, ultimately succumbing of secondary bacterial infection. The third, fourth, and fifth patients were diagnosed on 10th, 11th, and 18th postoperative day, respectively, and presented satisfactory clinical evolution. These last two patients were severely immunosuppressed, since one underwent steroid bolus for acute cellular rejection and another also used anti-thymocyte globulin for treating steroid-resistant rejection. Our novel experience highlights that COVID-19 may negatively impact the postoperative course, especially in elder and obese patients with comorbidities, and draws attention to COVID-19 nosocomial spread in the early postoperative period.

Livebirth after uterus transplantation from a deceased donor in a recipient with uterine infertility.

BACKGROUND: Uterus transplantation from live donors became a reality to treat infertility following a successful Swedish 2014 series, inspiring uterus transplantation centres and programmes worldwide. However, no case of livebirth via deceased donor uterus has, to our knowledge, been successfully achieved, raising doubts about its feasibility and viability, including whether the womb remains viable after prolonged ischaemia. METHODS: In September, 2016, a 32-year-old woman with congenital uterine absence (Mayer-Rokitansky-Küster-Hauser [MRKH] syndrome) underwent uterine transplantation in Hospital das Clínicas, University of São Paulo, Brazil, from a donor who died of subarachnoid haemorrhage. The donor was 45 years old and had three previous vaginal deliveries. The recipient had one in-vitro fertilisation cycle 4 months before transplant, which yielded eight cryopreserved blastocysts. FINDINGS: The recipient showed satisfactory postoperative recovery and was discharged after 8 days' observation in hospital. Immunosuppression was induced with prednisolone and thymoglobulin and continued via tacrolimus and mycophenalate mofetil (MMF), until 5 months post-transplantation, at which time azathioprine replaced MMF. First menstruation occurred 37 days post-transplantation, and regularly (every 26-32 days) thereafter. Pregnancy occurred after the first single embryo transfer 7 months post-transplantation. No blood flow velocity waveform abnormalities were detected by Doppler ultrasound of uterine arteries, fetal umbilical, or middle cerebral arteries, nor any fetal growth impairments during pregnancy. No rejection episodes occurred after transplantation or during gestation. Caesarean delivery occurred on Dec 15, 2017, near gestational week 36. The female baby weighed 2550 g at birth, appropriate for gestational age, with Apgar scores of 9 at 1 min, 10 at 5 min, and 10 at 10 min, and along with the mother remains healthy and developing normally 7 months post partum. The uterus was removed in the same surgical procedure as the livebirth and immunosuppressive therapy was suspended. INTERPRETATION: We describe, to our knowledge, the first case worldwide of livebirth following uterine transplantation from a deceased donor in a patient with MRKH syndrome. The results establish proof-of-concept for treating uterine infertility by transplantation from a deceased donor, opening a path to healthy pregnancy for all women with uterine factor infertility, without need of living donors or live donor surgery. FUNDING: Fundação de Amparo à Pesquisa do Estado de São Paulo and Hospital das Clínicas, University of São Paulo, Brazil.

Preservation of platelet function in patients with cirrhosis and thrombocytopenia undergoing esophageal variceal ligation.

BACKGROUND: Thrombocytopenia is a possible risk factor for bleeding after band ligation of esophageal varices. However, elevated von Willebrand factor (VWF) in cirrhosis improves platelet function and could decrease this risk. Our objective was to assess platelet function in patients with cirrhosis undergoing esophageal variceal ligation (EVL). METHODS: The assessment consisted of platelet count, antigen and activity of VWF and VWF-cleaving protease ADAMTS-13 activity, and a platelet adhesion and aggregation test simulating vascular flow in vivo (Impact-RⓇ) prior to EVL. RESULTS: Totally 111 patients were divided into three groups according to platelet count: (1) < 50 × 109/L (n = 38, 34.2%); (2) 50 × 109/L to 100 × 109/L (n = 47, 42.3%); and (3) > 100 × 109/L (n = 26, 23.4%). No statistically significant difference was found in the aggregate size of platelets [group 1: 41.0 (31.8-67.3) µm2; group 2: 47.0 (33.8-71.3) µm2; and group 3: 47.0 (34.0-66.0) µm2; P = 0.60] and no significant correlation was found between aggregate size and platelet count (Spearman r = 0.07; P = 0.47). Surface coverage was 4.1% (2.8%-6.7%), 8.5% (4.0%-10.0%), and 9.0% (7.1%-12.0%) (P < 0.001) in groups 1, 2 and 3, respectively and correlated with platelet count (Spearman r = 0.39; P < 0.0001). There was no significant difference between groups in VWF or ADAMTS-13. Post-EVL bleeding occurred in six (5.4%) patients (n = 2 in group 1, n = 1 in group 2, and n = 3 in group 3; P = 0.32). Patients with bleeding had higher MELD scores [15.0 (11.3-20.3) versus 12.0 (10.0-15.0); P = 0.025], but no difference was demonstrated for platelet function parameters. CONCLUSION: Platelet function is preserved even in the presence of thrombocytopenia, including in the patients with post-EVL bleeding.

Sofosbuvir inhibits yellow fever virus in vitro and in patients with acute liver failure.

INTRODUCTION AND OBJECTIVES: Direct antiviral agents (DAAs) are very efficient in inhibiting hepatitis C virus and might be used to treat infections caused by other flaviviruses whose worldwide detection has recently increased. The aim of this study was to verify the efficacy of DAAs in inhibiting yellow fever virus (YFV) by using drug repositioning (a methodology applied in the pharmaceutical industry to identify new uses for approved drugs). MATERIALS AND METHODS: Three DAAs were evaluated: daclatasvir, sofosbuvir and ledipasvir or their combinations. For in vitro assays, the drugs were diluted in 100% dimethyl sulfoxide. Vaccine strain 17D and a 17D strain expressing the reporter fluorescent protein were used in the assays. A fast and reliable cell-based screening assay using Vero cells or Huh-7 cells (a hepatocyte-derived carcinoma ell line) was carried out. Two patients who acquired yellow fever virus with acute liver failure were treated with sofosbuvir for one week as a compassionate use. RESULTS: Using a high-content screening assay, we verified that sofosbuvir presented the best antiviral activity against YFV. Moreover, after an off-label treatment with sofosbuvir, the two female patients diagnosed with yellow fever infection displayed a reduction in blood viremia and an improvement in the course of the disease, which was observed in the laboratory medical parameters related to disease evolution. CONCLUSIONS: Sofosbuvir may be used as an option for treatment against YFV until other drugs are identified and approved for human use. These results offer insights into the role of nonstructural protein 5 (NS5) in YFV inhibition and suggest that nonstructural proteins may be explored as drug targets for YFV treatment.

CRISPR/Cas and recombinase-based human-to-pig orthotopic gene exchange for xenotransplantation.

BACKGROUND: Tools for genome editing in pigs are improving rapidly so that making precise cuts in DNA for the purposes of deleting genes is straightforward. Development of means to replace pig genes with human genes with precision is very desirable for the future development of donor pigs for xenotransplantation. MATERIALS AND METHODS: We used Cas9 to cut pig thrombomodulin (pTHBD) and replace it with a plasmid containing a promoterless antibiotic selection marker and the exon for human thrombomodulin. PhiC31 recombinase was used to remove the antibiotic selection marker to create porcine aortic endothelial cells expressing human instead of pTHBD, driven by the endogenous pig promoter. RESULTS: The promoterless selection cassette permitted efficient enrichment of cells containing correctly inserted transgene. Recombinase treatment of selected cells excised the resistance marker permitting expression of the human transgene by the endogenous pTHBD promoter. Gene regulation was maintained after gene replacement because pig endogenous promoter was kept intact in the correct position. CONCLUSIONS: Cas9 and recombinase technology make orthotopic human for pig gene exchange feasible and pave the way for creation of pigs with human genes that can be expressed in the appropriate tissues preserving gene regulation.

Role of EUS evaluation after endoscopic eradication of esophageal varices with band ligation.

BACKGROUND AND AIMS: Variceal recurrence after endoscopic band ligation (EBL) for secondary prophylaxis is a frequent event. Some studies have reported a correlation between variceal recurrence and variceal rebleeding with the EUS features of paraesophageal vessels. A prospective observational study was conducted to correlate EUS evaluation of paraesophageal varices, azygos vein, and thoracic duct with variceal recurrence after EBL variceal eradication in patients with cirrhosis. METHODS: EUS was performed before and 1 month after EBL variceal eradication. Paraesophageal varices, azygos vein, and thoracic duct maximum diameters were evaluated in predetermined anatomic stations. After EBL variceal eradication, patients were submitted to endoscopic examinations every 3 months for 1 year. We looked for EUS features that could predict variceal recurrence. RESULTS: Thirty patients completed a 1-year endoscopic follow-up. Seventeen patients (57%) presented variceal recurrence. There was no correlation between azygos vein and thoracic duct diameter with variceal recurrence. Larger paraesophageal varices predicted variceal recurrence in both evaluation periods. Paraesophageal varices diameters that best correlated with variceal recurrence were 6.3 mm before EBL (52.9% sensitivity, 92.3% specificity, and .749 area under the receiver operating characteristic curve [AUROC]) and 4 mm after EBL (70.6% sensitivity, 84.6% specificity, and .801 AUROC). CONCLUSIONS: We conclude that paraesophageal varices diameter measured by EUS predicts variceal recurrence within 1 year after EBL variceal eradication. Paraesophageal diameter after variceal eradication is a better recurrence predictor, because it has a lower cut-off parameter, higher sensitivity, and higher AUROC.

Life-Threatening Ruptured Hepatic Artery Pseudoaneurysm Post-Liver Transplant: A Case Report.

BACKGROUND: Hepatic artery pseudoaneurysm after liver transplantation is a rare condition that can lead to spontaneous bleeding, depending on its extent and location. Treatment involves endovascular and surgical approaches in addition to liver retransplantation in cases of graft failure. CASE REPORT: A 42-year-old female underwent deceased donor liver transplantation due to cryptogenic cirrhosis and schistosomiasis with an uneventful postoperative course. However, 18 days after the operation, she presented to the emergency department with abdominal pain, hypotension, and lipothymia. A computed tomography scan revealed a hepatic artery anastomotic pseudoaneurysm, and due to hemodynamic instability, emergency laparotomy was indicated. During the operation, the pseudoaneurysm was found to be ruptured, and the recipient's hepatic artery was ligated due to life-threatening bleeding. She later developed ischemic cholangiopathy and biliary complications, eventually undergoing retransplantation 7 months after the emergency operation. The patient remains well 11 months after the retransplantation. CONCLUSION: We report a rare case of life-threatening rupture of hepatic artery pseudoaneurysm, which required emergency ligation of the recipient's hepatic artery and subsequent liver retransplantation due to biliary complications.

Liver Transplantation for Adenomatosis: A Single-Center Experience.

BACKGROUND: Liver adenomatosis is characterized by multiple adenomas diffusely distributed throughout the liver parenchyma. Studies addressing liver transplantation for those cases are scarce, and the criteria used to indicate transplantation are still debatable. OBJECTIVE: To report a single-center experience of liver transplantation for diffuse adenomatosis. METHODS: Single-center retrospective study involving all adult patients who underwent liver transplantation due to adenomatosis from January/2010 to June/2023. RESULTS: A total of 13 patients were identified, corresponding to 0.89% of liver transplants performed during the study period. The mean age was 33 ± 6.55 years, and most of them were female (n = 9, 69.23%). There were 12 transplants with deceased donors and 1 with a right lobe from a living donor. The most frequent reason to preclude liver resection was multiple and large unresectable adenomas in patients without previous liver disease (n = 8, 61.58%), followed by underlying liver disease (Abernethy Malformation, n = 3, 23.07%) and recurrence after liver resection (n = 2, 15.38%). The indications for liver transplantation were high risk of malignant transformation (n = 7, 53.84%), increasing size and number of nodules (n = 3, 23.07%), confirmed malignant transformation (n = 2, 15.38%), and hemorrhage (n = 2, 15.38%). There was 1 perioperative death due to primary non-function. Another patient died during follow-up because of COVID-19. CONCLUSION: Liver adenomatosis is a rare indication for liver transplantation, with acceptable post-transplant outcomes. Unresectable adenomas with high-risk or confirmed malignant transformation are the main indications for transplant. Reasons for unresectability involve underlying liver disease, multiple and large high-risk nodules, and recurrence after previous resection.

Surgery is associated with better long-term outcomes than pharmacological treatment for obesity: a systematic review and meta-analysis.

Obesity is a highly prevalent disease with numerous complications. Both intensive medical treatment with the use of pharmacological drugs and bariatric surgery are current options. The objective of this meta-analysis was to compare, in the long-term, intensive medical treatment and surgery based on twelve parameters related to weight loss, cardiovascular and endocrine changes. A review of the literature was conducted in accordance with the PRISMA guidelines (PROSPERO: CRD42021265637). The literature screening was done from inception to October 2023 through PubMed, EMBASE and Web of Science databases. We included randomized clinical trials that had separate groups for medical treatment and bariatric surgery as an intervention for obesity. The risk of bias was assessed through RoB2. A meta-analysis was performed with measures of heterogeneity and publication bias. Subgroup analysis for each surgery type was performed. Data is presented as forest-plots. Reviewers independently identified 6719 articles and 6 papers with a total 427 patients were included. All studies were randomized controlled trials, three had a follow up of 5 years and two had a follow up of 10 years. Both groups demonstrated statistical significance for most parameters studied. Surgery was superior for weight loss (- 22.05 kg [- 28.86; - 15.23), total cholesterol (- 0.88 [- 1.59; - 0.17]), triglycerides (- 0.70 [- 0.82; - 0.59]), HDL (0.12 [0.02; 0.23]), systolic pressure (- 4.49 [- 7.65; - 1.33]), diastolic pressure (- 2.28 [- 4.25; - 0.31]), Hb glycated (- 0.97 [- 1.31; - 0.62]), HOMA IR (- 2.94; [- 3.52; - 2.35]) and cardiovascular risk (- 0.08; [- 0.10; - 0.05]). Patient in the surgical treatment group had better long term outcomes when compared to the non-surgical group for most clinical parameters.

Retransplantation for Late Hepatic Artery Thrombosis: Results from a Single Center.

BACKGROUND: Hepatic artery thrombosis is the most common vascular complication of liver transplantation. When occurring late in the postoperative course, it may have no clinical repercussions, and conservative treatment may be implemented. Some patients, however, will develop severe biliary complications due to ischemic cholangiopathy and require retransplantation. The aim of this study is to report the outcomes of retransplantation in this population. METHODS: This is a single-center retrospective study involving all adult patients who underwent liver retransplantation due to late hepatic artery thrombosis from January/2010 to December/2022. RESULTS: During the study period, 1378 liver transplants were performed in our center; 147 were retransplantations, with 13 cases of late hepatic artery thrombosis (0.94%). All had symptomatic ischemic cholangiopathy. Twelve of them had already presented previous cholangitis, bilomas, or liver abscesses and had undergone biliary stenting or percutaneous drainage. The median time between the first liver transplant and late hepatic artery thrombosis diagnosis and between this diagnosis and retransplantation were 73 and 50 days, respectively. Arterial reconstruction using splenic artery, celiac trunk, or arterial conduit from the aorta was performed in 7 cases, whereas biliary reconstruction was mostly done with choledochojejunostomy (n = 8). There were 4 perioperative deaths, 2 due to primary non-function and 2 due to refractory shock after exceedingly complex retransplants. CONCLUSION: Liver retransplantation due to late hepatic artery thrombosis is a rare condition that should be offered to patients who develop severe biliary complications and recurrent infections. It is nonetheless a challenging procedure associated with significant perioperative mortality.

Liver Transplantation for Benign Massive Hepatomegaly: Results From a Single Center and Contribution of the Left-to-Right Piggyback Approach.

INTRODUCTION: Polycystic liver disease and giant hepatic hemangioma may present with severe symptom burden and indicate orthotopic liver transplantation. The left-to-right piggyback approach is a useful technique for performing total hepatectomy of enlarged livers. OBJECTIVE: The purpose of this study is to analyze the results of liver transplantation in patients with benign massive hepatomegaly. METHODS: This is a single-center retrospective study involving all adult patients who underwent liver transplantation due to benign massive hepatomegaly from January 2002 to June 2023. RESULTS: A total of 22 patients underwent liver transplantation (21 cases of polycystic live disease and 1 case of giant hepatic hemangioma). During the same time, there were 2075 transplants; therefore, benign massive hepatomegaly accounted for 1.06% of cases. Most patients (59.09%) were transplanted using the left-to-right piggyback technique. Seven patients had previous attempted treatment of hepatic cysts. Another patient previously underwent bilateral nephrectomy and living-donor kidney transplantation. Among these patients, in 5 cases there were massive abdominal adhesions with increased bleeding. Four of these 8 patients died in the very early perioperative period. In comparison to patients without previous cysts manipulation, massive adhesions and perioperative death were significantly higher in those cases (62.5 vs 0%, P = .002 and 50% vs 0%, P = .004, respectively). CONCLUSION: Liver transplantation due to polycystic liver disease and giant hemangioma is a rare event. Total hepatectomy is challenging due to the enlarged native liver. The left-to-right piggyback technique is useful, because it avoids vena cava twisting and avulsion of its branches. Massive adhesions due to previous cysts manipulation may lead to increased bleeding, being a risk factor for mortality.

Surgical site infections in liver transplant recipients in the model for end-stage liver disease era: an analysis of the epidemiology, risk factors, and outcomes.

In recipients of liver transplantation (LT), surgical site infection (SSIs) are among the most common types of infection occurring in the first 60 days after LT. In 2007, the Model for End-Stage Liver Disease (MELD) scoring system was adopted as the basis for prioritizing organ allocation. Patients with higher MELD scores are at higher risk for developing SSIs as well as other health care-associated infections. However, there have been no studies comparing the incidence of SSIs in the pre-MELD era with the incidence in the period since its adoption. Therefore, the objectives of this study were to evaluate the incidence, etiology, epidemiology, and outcomes of post-LT SSIs in those 2 periods and to identify risk factors for SSIs. We evaluated all patients who underwent LT over a 10-year period (2002-2011). SSI cases were identified through active surveillance. The primary outcome measure was an SSI during the first 60 days after LT. Risk factors were analyzed via logistic regression, and 60-day survival rates were evaluated via Cox regression. We evaluated 543 patients who underwent LT 597 times. The SSI rates in the 2002-2006 and 2007-2011 periods were 30% and 24%, respectively (P = 0.21). We identified the following risk factors for SSIs: retransplantation, the transfusion of more than 2 U of blood during LT, dialysis, cold ischemia for >400 minutes, and a cytomegalovirus infection. The overall 60-day survival rate was 79%. Risk factors for 60-day mortality were retransplantation, dialysis, and a longer surgical time. The use of the MELD score modified the incidence and epidemiology of SSIs only during the first year after its adoption. Risks for SSIs were related more to intraoperative conditions and intercurrences after LT than to a patient's status before LT.

Impact of the severity of end-stage liver disease in cardiac structure and function.

BACKGROUND: The impact of end-stage liver disease (ESLD) in cardiac remodeling of patients with cirrhosis is unknown. Our aim was to correlate the severity of ESLD with morphologic and functional heart changes. MATERIAL AND METHODS: 184 patients underwent a protocol providing data on the severity of ESLD and undergoing echocardiography to assess the diameters of the left atrium and right ventricle; the systolic and diastolic diameters of the left ventricle, interventricular septum, and posterior wall of the left ventricle; systolic pulmonary artery pressure; ejection fraction; and diastolic function. Severity of ESLD was assessed by the Model for End-Stage Liver Disease (MELD) score. RESULTS: Left-atrial diameter (r = 0.323; IC 95% 0.190-0.455; p < 0.001), left-ventricular diastolic diameter (r = 0.177; IC 95% 0.033-0.320; p = 0.01) and systolic pulmonary artery pressure (r = 0.185; IC 95% 0.036-0.335; p = 0.02) significantly correlated with MELD score. Patients with MELD ≥ 16 had significantly higher left-atrial diameter and systolic pulmonary artery pressure, compared with patients with MELD scores < 16 points. CONCLUSIONS: Changes in cardiac structure and function correlate with the severity of ESLD.

Effects of intravenous administration of pentoxifylline in pancreatic ischaemia-reperfusion injury.

BACKGROUND: Therapeutic strategies to reduce the occurrence of pancreatic ischaemia-reperfusion (I-R) injury might improve outcomes in human pancreas and kidney transplantation. In addition to its haemorrheologic effects, pentoxifylline has an anti-inflammatory effect by inhibiting NF-κB activation. This group has previously demonstrated that pentoxifylline induces an anti-inflammatory response in acute pancreatitis and liver I-R models. This led to the hypothesis that pentoxifylline might reduce pancreatic and renal lesions and the systemic inflammatory response in pancreatic I-R injury. The aim of this experimental study was to evaluate the effect of pentoxifylline administration in a rat model of pancreatic I-R injury. METHODS: Pancreatic I-R was performed in Wistar rats over 1 h by clamping the splenic vessels. The animals submitted to I-R were divided into two groups: Group 1 (n = 20, control) rats received saline solution administered i.v. at 45 min after ischaemia, and Group 2 (n = 20) rats received pentoxifylline (25 mg/kg) administered i.v. at 45 min after ischaemia. Blood samples were collected to enable the determination of amylase, creatinine, tumour necrosis factor-α (TNF-α), interleukin-6 (IL-6) and IL-10. Pancreatic malondialdehyde (MDA) content, pancreas histology and pulmonary myeloperoxidase (MPO) were also assessed. RESULTS: Significant reductions in serum TNF-α, IL-6 and IL-10 were observed in Group 2 compared with Group 1 (P < 0.05). No differences in pancreatic MDA content or serum amylase levels were observed between the two groups. The histologic score was significantly lower in pentoxifylline-treated animals, denoting less severe pancreatic histologic damage. CONCLUSIONS: Pentoxifylline administration reduced the systemic inflammatory response, the pancreatic histological lesion and renal dysfunction in pancreatic I-R injury and may be a useful tool in pancreas and kidney transplantation.

Risk factors for blood transfusion and its prognostic implications in curative gastrectomy for gastric cancer.

BACKGROUND: Gastric cancer (GC) is still a prevalent neoplasm around the world and its main treatment modality is surgical resection. The need for perioperative blood transfusions is frequent, and there is a long-lasting debate regarding its impact on survival. AIM: To evaluate the factors related to the risk of receiving red blood cell (RBC) transfusion and its influence on surgical and survival outcomes of patients with GC. METHODS: Patients who underwent curative resection for primary gastric adenocarcinoma at our Institute between 2009 and 2021 were retrospectively evaluated. Clinicopathological and surgical characteristics data were collected. The patients were divided into transfusion and non-transfusion groups for analysis. RESULTS: A total of 718 patients were included, and 189 (26.3%) patients received perioperative RBC transfusion (23 intraoperatively, 133 postoperatively, and 33 in both periods). Patients in the RBC transfusions group were older (P < 0.001), and had more comorbidities (P = 0.014), American Society of Anesthesiologists classification III/IV (P < 0.001), and lower preoperative hemoglobin (P < 0.001) and albumin levels (P < 0.001). Larger tumors (P < 0.001) and advanced tumor node metastasis stage (P < 0.001) were also associated with the RBC transfusion group. The rates of postoperative complications (POC) and 30-d and 90-d mortality were significantly higher in the RBC transfusion group than in the non-transfusion group. Lower hemoglobin and albumin levels, total gastrectomy, open surgery, and the occurrence of POC were factors associated with the RBC transfusion. Survival analysis demonstrated that the RBC transfusions group had worse disease-free survival (DFS) and overall survival (OS) compared with patients who did not receive transfusion (P < 0.001 for both). In multivariate analysis, RBC transfusion, major POC, pT3/T4 category, pN+, D1 lymphadenectomy, and total gastrectomy were independent risk factors related to worse DFS and OS. CONCLUSION: Perioperative RBC transfusion is associated with worse clinical conditions and more advanced tumors. Further, it is an independent factor related to worse survival in the curative intent gastrectomy setting.

Current aspects of renal dysfunction after liver transplantation.

The development of chronic kidney disease (CKD) after liver transplantation (LT) exerts a severe effect on the survival of patients. The widespread adoption of the model for end-stage liver disease score strongly impacted CKD incidence after the procedure, as several patients are transplanted with previously deteriorated renal function. Due to its multifactorial nature, encompassing pre-transplantation conditions, perioperative events, and nephrotoxic immunosuppressor therapies, the accurate identification of patients under risk of renal disease, and the implementation of preventive approaches, are extremely important. Methods for the evaluation of renal function in this setting range from formulas that estimate the glomerular filtration rate, to non-invasive markers, although no option has yet proved efficient in early detection of kidney injury. Considering the nephrotoxicity of calcineurin inhibitors (CNI) as a factor of utmost importance after LT, early nephroprotective strategies are highly recommended. They are based mainly on delaying the application of CNI during the immediate postoperative-period, reducing their dosage, and associating them with other less nephrotoxic drugs, such as mycophenolate mofetil and everolimus. This review provides a critical assessment of the causes of renal dysfunction after LT, the methods of its evaluation, and the interventions aimed at preserving renal function early and belatedly after LT.