Reactive oxygen species (ROS) production in hepatic ischemia-reperfusion injury (IRI) is a complex process where multiple cellular and molecular pathways are involved. Few of those molecular pathways are under the direct influence of SIRT3 and its downstream mediators. SIRT3 plays a major role in the mechanism of IRI, and its activation has been shown to attenuate the deleterious effect of ROS during IRI via SOD2-, CYP-D-, and HIF-1α-mediated pathways. The objective of this review is to analyze the current knowledge on SIRT3 and its downstream mediators: SOD2, CYP-D, and HIF-1α, and their role in IRI. For the references of this review article, we have searched the bibliographic databases of PubMed, Web of Science databases, MEDLINE, and EMBASE with the headings “SIRT3,” “SOD2,” “CYP-D,” “HIF-1α,” and “liver IRI.” Priority was given to recent experimental articles that provide information on ROS modulation by these proteins. All the recent advancement demonstrates that activation of SIRT3 can suppress ROS production during IRI through various pathways and few of those are via SOD2, CYP-D, and HIF-1α. This effect can improve the quality of the remnant liver following resection as well as a transplanted liver. More research is warranted to disclose its role in IRI attenuation via this pathway.

Ischemia-reperfusion (IR) injury to the renal epithelia is associated with endoplasmic reticulum stress (ERS) and mitochondria dysfunction, which lead to oxidative stress-induced acute kidney injury (AKI). X-box binding protein 1 (XBP1), an ERS response protein, could play a prominent role in IR-induced AKI. In this study, we revealed that XBP1 and its downstream target HRD1 participated in the crosstalk between ERS and mitochondrial dysfunction via regulation of NRF2/HO-1-mediated reactive oxidative stress (ROS) signaling. Mice with reduced expression of XBP1 (heterozygous Xbp1±) were resistant to IR-induced AKI due to the enhanced expression of NRF2/HO-1 and diminished ROS in the kidney. Downregulation of XBP1 in renal epithelial cells resulted in reduced HRD1 expression and increased NRF2/HO-1 function, accompanied with enhanced antioxidant response. Furthermore, HRD1 served as an E3-ligase to facilitate the downregulation of NRF2 through ubiquitination-degradation pathway, and the QSLVPDI motif on NRF2 constituted an active site for its interaction with HRD1. Thus, our findings unveil an important physiological role for XBP1/HRD1 in modulating the antioxidant function of NRF2/HO-1 in the kidney under stress conditions. Molecular therapeutic approaches that target XBP1-HRD1-NRF2 pathway may represent potential effective means to treat renal IR injury.

BackgroundMalnutrition is a major risk factor for morbidity and mortality following gastrointestinal (GI) surgery. Nutritional Risk Index (NRI) and Body Mass Index (BMI) are the two well-validated tools that are readily available and do not add financial burden to the patients. The study aimed to analyze NRI and BMI as a preoperative nutritional indicator of postoperative complications following GI surgeries.MethodsIt is an observational study, where preoperative nutritional status and early postoperative complications <30 days (infectious or noninfectious) were studied. The patients admitted between July 2015 to May 2017, who underwent major GI surgeries were included in the study. The correlation between NRI and BMI of these patients were evaluated.ResultsThe rate of wound infection was 4 (30.7%) out of 13 in severe malnutrition subgroup defined by NRI <83.5 which was found to be statistically significant (p = 0.003). However, it was not significant in a subgroup of patients with undernutrition defined by BMI <18.49%. In a subgroup analysis, abnormal NRI was found to be statistically significant (p = 0.004) in patients with malignant disease and malnutrition 64 (47.76%) out of 97 (72.3%). The mean NRI (94.49 ± 9.164) better correlated with advancing age (p < 0.05) and the correlation coefficient of 0.3100 showed a significant negative correlation. With 10 fold increase in age (r2 = 0.096) the likelihood of malnutrition was 9.6% and subsequently increased postoperative complications.ConclusionIn cases of malignancy and advanced age, NRI is a better predictor of immediate postoperative outcome than BMI.

Hepatocellular carcinoma (HCC) is among the most common and fatal cancers. It is a multistage and multifactorial carcinoma, in which a number of factors serve roles in its initiation and progression. Small nucleolar RNAs (snoRNAs), considered to serve a role in various cancers, have recently been identified to have significant contributions to HCC tumorigenesis. Recent studies suggest that snoRNAs have a critical role in the pathogenesis of HCC. Moreover, detailed studies have demonstrated that various snoRNAs are involved in a range of biological processes associated with HCC, including initiation, proliferation, tumor growth, the cell cycle, apoptosis and metastasis. In the present review, an overview of recent studies to date has been provided, focusing on the association of snoRNAs with HCC. Based on the findings, further studies focusing on the association of snoRNAs with HCC are required to verify the diagnostic and therapeutic capacities of snoRNAs in HCC.

Background: Neutrophil lymphocyte Ratio (NLR) and Platelet lymphocyte Ratio (PLR) are an indicator of the status of inflammation. The objective of this study was to evaluate the relationship between recipient pre-operative Neutrophil lymphocyte Ratio (NLR) and Platelet lymphocyte Ratio (PLR) with delayed graft function in the kidney transplant patient. Methods: The preoperative full blood count, data regarding patient demographics and postoperative graft function was retrospectively evaluated from the database of our institution. All statistical calculations were carried out using SPSS 20.0 version (SPSS Inc., Chicago, IL, USA). A p-value<0.05 was considered statistically significant. Results: 289 patients were included in this study. DGF occurred in 33 cases. Elevated preoperative NLR had a sensitivity of 75.75% and specificity of 76.56% whereas elevated preoperative PLR had a sensitivity of 72.72% and specificity of 58.20% for predicting DGF. The area under the ROC curve was found to be 0.762 and 0.655 for NLR and PLR, respectively. Multivariate analysis showed NLR>3.5 and PLR>120 independently responsible for DGF. Conclusion: Recipient preoperative NLR and PLR can predict the occurrence of DGF following DBD renal transplantation. In addition, NLR is better than PLR in predicting DGF. DGF prolongs the total ICU and in-hospital stay.

Background: Colorectal malignancy is a very common disease of the gastrointestinal tract. Surgery following neoadjuvant chemoradiotherapy has been found to improve the survival of the patients with colorectal carcinoma. Research on bowel, bladder and sexual dysfunction following colorectal surgery remains limited in Nepal. The aim of this study is to evaluate the incidence of the bowel, bladder, and sexual dysfunction after colorectal surgery.Methods: It is a cross-sectional study carried out at National Academy of Medical Science, Bir hospital. Patients who underwent low anterior resection and abdominoperineal resection with curative intention post neoadjuvant chemoradiotherapy were included in the study.Results: A total of 26 patients [20 (76.9%) males and 6 (23.1%) females] who underwent surgery for the colorectal malignant disease were included. 24 (92.30%) underwent low anterior resection and 2(7.6%) patient underwent abdominoperineal resection respectively after neoadjuvant chemo radiotherapy. 19(79.16%) of the patients developed bowel dysfunction with mean low anterior resections score of 22.88±4.394. And 5(20.83%) had normal bowel function. Bladder dysfunction was seen in 3 (11.5%) patients. And rest of the 23 (88.5%) patient had normal bladder function. In males, Sexual Dysfunction was observed in 11 (42.3%)and no sexual dysfunction was observed in 15(57.69%). While in females, 38.46% had no sexual desire and 50% had dyspareunia due to vaginal dryness.Conclusions: This study clearly demonstrated a higher incidence of bowel and sexual dysfunction compared to bladder dysfunction following low anterior resection and abdominoperineal resection for colorectal malignant diseases.Keywords: Bowel; bladder; sexual dysfunction; low anterior resection;abdominoperineal resection.

The ideal management of cholecysto-choledocholithiasis is an open cholecystectomy (OC) with the common bile duct (CBD) exploration worldwide. The single setting 2-stage approach- endoscopic retrograde cholangiopancreatography (ERCP), endoscopic sphincterotomy (EST), and CBD clearance followed by laparoscopic cholecystectomy (LC) offers an advantage, mainly by reducing the hospital stay, the cost, and the morbidity. The Objective of the study is to compare the ERCP+LC single setting approach with an OC+CBD exploration for the treatment of cholecysto-choledocholithiasis. This is an interim analysis of 160 patients with 83 (51.9%) patients in ERCP+LC and 77 (48.1%) in an open procedure (OC+CBD exploration) group respectively. We did a prospective study in patients admitted for the management of the cholecysto-choledocholithiasis in the Department of Surgery at the Lumbini Medical College and Teaching Hospital from November 2012–October 2015. They underwent 2-stage ERCP+LC in a single setting and we compared them with 2-stage OC+CBD exploration in a single setting approach. The patients with the open procedure were our control group. All the included cases in the study were elective. The procedure was feasible in our hospital. Similarly, the hospital stay was significantly shorter in the ERCP+LC group; 3.92±0.719 days vs 10.30±1.557 days, p <0.05. There was a significant difference in the total morbidity of ERCP+LC group 7 (8.4%) vs 14 (18.2%), p <0.05. Here, wound infection in the ERCP+LC group was 2 (2.4%) vs 4 (5.2%) and there was one case of abdominal collection 1 (1.2%) which was managed symptomatically. The incidence of retained CBD stone in the ERCP+LC was 3 (1.2%) which was managed successfully with ERCP. In all the cases, post- ERCP amylase value was found to be within the normal limit. The result of our study suggests, single setting ERCP+LC at the peripheral-level hospital is feasible in terms of cost, length of hospital stay, morbidity and stone clearance.

Background The liver is the second most injured organ following blunt abdominal trauma (BAT) after the spleen. Although the computed tomography (CT) scan is considered as the gold standard for diagnosing liver injury in BAT, it may not readily available in all the hospitals. This study was performed to evaluate the role of aspartate transaminase (AST) and alanine transaminase (ALT) in patients with BAT and its significance in predicting the diagnosis and severity of the liver injury. Method The study was conducted in Chitwan Medical College Teaching Hospital (CMCTH) from February 2019 to May 2020. It was a prospective observational study. All the patients with BAT were received by on-duty surgical residents in the emergency department. Based on the imaging and operative finding, patients with liver injury and without liver injury were noted with the associated injury. For comparisons of clinical and grading characteristics between the two groups (liver injury and no liver injury), the chi-squared test was used for categorical variables as appropriate, and the Mann-Whitney U test used for quantitative variables (AST and ALT). The comparisons between more than two groups (grade of injury) were performed using the Kruskal-Wallis test. The receiver operating characteristic (ROC) was used to calculate the optimal cut-off value of AST and ALT. Results Among the 96 patients admitted with BAT, 38 patients had liver injury and 58 patients had no liver injury. The median length of the intensive care unit (ICU) stay of patients with liver injury was higher than without liver injury. There was a significant difference in the median level of AST and ALT (< 0.001) between patients with liver injury and no liver injury. The area under the ROC curve of AST was 0.89 (95% confidence interval 0.86–0.98) and of ALT was 0.92 (95% confidence interval 0.83–0.97). The area under the curve demonstrated that the test was a good predictor for the identification of liver injury and also the severity of liver enzymes. The cut-off values for the liver injury were 106 U/l and 80 U/l for AST and ALT, respectively. Based on these values, AST ≥ 106 U/l had a sensitivity of 71.7%, a specificity of 90%, a positive predictive value of 86.8%, and a negative predictive value of 77.6%. The corresponding values for ALT ≥ 80 U/l were 77.8%, 94.1%, 92.1%, and 82.8%, respectively. Conclusion In conclusion, we report the optimal cut-off value of AST and ALT for liver injury in BAT as ≥ 106 U/l and 80 U/l, respectively. The elevated level of AST and ALT might assist the emergency physicians and surgeons to timely refer the suspected patients with the liver injury to a tertiary center.