Assessment of the nutritional status of patients before, one, and three months after liver transplantation: A multi-center longitudinal study.

BACKGROUND: Nutrition management is an important pre-operative and post-operative challenge in liver transplantation. Preoperative malnutrition is associated with increased length of intensive care unit (ICU) stay, mortality, and length of hospital stay in liver transplant patients. This study aimed to evaluate the nutritional status of patients before and after liver transplantation and post-transplant complications. METHOD: This longitudinal study was conducted on liver transplant patients in Montaserieh Hospital, Mashhad and Firoozgar Hospital, Tehran from May 2021 to January 2022. Demographic characteristics, Subjective Global Assessment (SGA) standard questionnaire, anthropometric indices, laboratory analyses, and 3-day food records were collected before, one, and three months after transplantation. RESULTS: Thirty-nine patients with a mean age of 48.4 ± 14.2 were evaluated. Prevalence of severe malnutrition was 43.6% (56.3% women and 34.8% men) before transplantation. Body mass index (BMI), body weight, lean mass, total body water, and total serum protein significantly decreased after transplantation compared to before transplantation (P < 0.001). One month after transplantation, 54% of the patients lost more than 10% of their weight. Energy intake increased significantly after transplantation (P < 0.001). A significant relationship was observed between BMI (P = 0.005) and metabolic complications and between Arm Muscle Circumference and renal complications (P = 0.003) after transplantation. A cut-off point of 4.6 was determined for the phase angle in terms of SGA three months after transplantation. CONCLUSION: Malnutrition, weight loss, and nutritional problems were common in liver transplantation patients. Screening for nutritional status is necessary in these patients to treat or prevent malnutrition-related complications.

Expression profile analysis of two antisense lncRNAs to improve prognosis prediction of colorectal adenocarcinoma.

BACKGROUND: Long noncoding RNAs (lncRNAs) are involved in different pathogenesis pathways including cancer pathogenesis. The adenoma-carcinoma pathway in colorectal cancer may involve the aberrant and variable gene expression of regulatory RNAs. This study was conducted to analyse the expression and prognosis prediction ability of two natural antisense transcripts, protein kinase C theta antisense RNA 1 (PRKCQ-AS1), and special AT-rich sequence binding protein 1 antisense RNA 1 (SATB1-AS1) in colorectal low-grade adenoma, advanced adenoma, and adenocarcinomas. METHODS: In this study, from two RNA-seq analyses of CCAT1-ko cells and colorectal carcinoma biopsies having diminished and increased levels of CCAT1 transcription, respectively, we nominated two antisense lncRNAs of PRKCQ-AS1 and SATB1-AS1. Samples from colorectal low-grade adenomas, advanced adenomas, adenocarcinomas, and adjacent tissue were subjected to RT-qPCR to determine the expression of PRKCQ-AS1, SATB1-AS1 along with colon cancer-associated transcript 1 (CCAT1) and cMYC. In addition, we used different bioinformatics analyses and webservers (including GEPIA 2, TCGA, and CancerMine) to elucidate the prognosis prediction value, the expression correlation of sense-antisense pair of genes, and the expression profile of these antisense transcripts at the presence or absence of mutations in the driver genes, or the corresponding sense genes. RESULTS: PRKCQ-AS1 showed a wide range of expression levels in colorectal adenoma, advanced adenoma, and adenocarcinoma. Upregulation of PRKCQ-AS1 was related to a significant decrease in survival of colorectal cancer (CRC) patients. The expression levels of PRKCQ-AS1 and PRKCQ were strong and significantly concordant in normal and cancerous colorectal tissues. While SATB1-AS1 showed a wide range of expression in colorectal adenoma, advanced adenoma, and adenocarcinoma as well, its expression was not related to a decrease in survival of CRC patients. The expression levels of SATB1-AS1 and SATB1 (the sense gene) were not strong in normal colorectal tissues. In addition, where SATB1 gene was mutated, the expression of SATB1-AS1 was significantly downregulated. CONCLUSIONS: We found the expression of PRKCQ-AS1 and SATB1-AS1 at a given stage of CRC very variable, and not all biopsy samples showed the increased expression of these antisense transcripts. PRKCQ-AS1 in contrast to SATB1-AS1 showed a significant prognostic value. Since a significantly concordant expression was observed for SATB1-AS1 and SATB1 in only cancerous, and for PRKCQ-AS1 and PRKCQ in both normal and cancerous colorectal tissues, it can be concluded that common mechanisms may regulate the expression of these sense and antisense genes.

Autologous Bone Marrow Stem Cell Transplantation in Liver Cirrhosis after Correcting Nutritional Anomalies, A Controlled Clinical Study.

OBJECTIVE: Liver transplantation is the gold standard approach for decompensated liver cirrhosis. In recent years, stem cell therapy has raised hopes that adjusting some clinical and laboratory parameters could lead to successful treatments for this disease. Cirrhotic patients may have multiple systemic abnormalities in peripheral blood and irregular cell populations in bone marrow (BM). Correcting these abnormalities before BM aspiration may improve the effectiveness of cell-based therapy of liver cirrhosis. MATERIALS AND METHODS: In this controlled clinical trial study, 20 patients with decompensated liver cirrhosis were enrolled. Patients were randomly assigned to control and experimental groups. Blood samples were obtained to measure vitamin B12, folate, serum iron, total iron bonding capacity (TIBC) and ferritin before any intervention. Furthermore, the iron storage and fibrosis level in BM biopsies, as well as the percentage of different cell populations, were evaluated. Prior to cell isolation for transplantation, we performed palliative supplement therapy followed by a correction of nutritional deficiencies. Mononuclear cells (MNCs) were then isolated from BM aspirates and transfused through peripheral vein in patients in the experimental group. The model of end-stage liver disease (MELD) score, The international normalized ratio (INR), serum albumin and bilirubin levels were assessed at 0 (baseline), 3 and 6 months after cell transplantation. RESULTS: The MELD score (P=0.0001), INR (P=0.012), bilirubin (P<0.0001) and total albumin (P<0.0001) levels improved significantly in the experimental group after cell transplantation compared to the baseline and control groups. Moreover, the increase in serum albumin levels of patients in the experimental group was statistically significant 6 months after transplantation. CONCLUSION: We have successfully improved the conditions of preparing -BM-derived stem cells for transplantation. Although these cells are relatively safe and have been shown to improve some clinical signs and symptoms temporarily, there need to be more basic studies regarding the preparation steps for effective clinical use (Registration number: IRCT2014091919217N1).

A randomized clinical trial on the antitumoral effects of low molecular weight heparin in the treatment of esophageal cancer.

The current treatment approaches for esophageal cancer are associated with poor survival, and there are ongoing efforts to find new and more effective therapeutic strategies. There are several reports on the antitumoral effects of low-molecular-weight heparins (LMWHs). We have assessed the possible survival benefit of LMWHs in esophageal malignancies. This was a randomized, single-blind, multicenter, Phase II clinical trial on nonmetastatic esophageal cancer candidate for neoadjuvant chemoradiotherapy. Patients were randomly assigned to the chemoradiotherapy-only arm or chemoradiotherapy plus enoxaparin arm using 1:1 allocation. Radiotherapy was delivered in 1.8-Gy daily fractions to a dose of 50.4 Gy in both groups. Paclitaxel 50 mg/m2 and carboplatin (AUC 2) were administered weekly, concurrent with radiotherapy. In the intervention group, patients received enoxaparin (40 mg) and chemoradiation daily. 4-6 weeks after treatment, all patients underwent esophagectomy. After a median follow up of 7 months, estimated 1 year disease-free survival (DFS) in the intervention group was 78.9% and was 70% in the control groups ( p = 0.5). Toxicity from the experimental treatment was minimal, and there were no treatment-related deaths. A pathologically complete response in intervention and control group was 64.8% and 62.5%, respectively ( p = 0.9). There was a nonsignificant trend toward improved survival by the addition of enoxaparin to the concurrent chemoradiotherapy regimen. However, 1 y DFS of both groups were high as expected. A longer follow-up and a larger sample size are required.

Pistacia atlantica Desf. A review of its traditional uses, phytochemicals and pharmacology.

Pistacia atlantica is the main herbal medicine that has been widely used in the Middle Eastern and Mediterranean areas since ancient time. Pistacia atlantica has been used for multiple purposes like stomach diseases, renal disorders, wounds and coughs. The aim of this study is to review its botanical characterization, traditional applications, photochemistry effects and pharmacological activities. Data in this review article was gathered from credible pharmacopeias, electronic databases such as Web of Science, Science Direct, PubMed, EMBASE, Scopus, EBSCO, Google Scholar, SID and Iran Medex and textbooks of Persian medicine such as Canon of medicine (Ibn-e Sina, 980-1037 AD) and Makhzan-al-Advia (Aghili, 18th century). The keywords were searched in Persian and English books on medicinal plants and traditional medicine. The results showed that P. atlantica has many medicinal properties such as antioxidant, antidiabetic, antihyperlipidemic, along with others. It can also be effective in gastrointestinal diseases. Thus, different new drugs can be formulated based on P. atlantica for the management of various diseases.

Association between smoking and non-alcoholic fatty liver disease: A systematic review and meta-analysis.

BACKGROUND/AIMS: Non-alcoholic fatty liver disease is one of the most common chronic liver diseases. Some risk factors are known to influence the development of non-alcoholic fatty liver disease, but the effect of tobacco smoking on the progression of non-alcoholic fatty liver disease is controversial. The main goal of this systematic review and meta-analysis is to investigate the association between smoking and non-alcoholic fatty liver disease. METHOD: Electronic databases (PubMed, Scopus, and ISI Web of Science) were searched to find published articles on non-alcoholic fatty liver disease and smoking until December 2016. All relevant studies were screened by inclusion and exclusion criteria and compatible studies were chosen. The Newcastle-Ottawa Scale was used to assess the methodological quality of eligible articles. Subsequently, information was gathered based on the following: author, publication year, keywords, country, inclusion and exclusion criteria, main results, study design, conclusion, and confounder variables (age, body mass index, gender, ethnicity, and diabetes). Finally, analyses were performed using Comprehensive Meta-Analysis Software. RESULTS: Data were extracted from 20 observational studies (9 cross-sectional, 6 case-control, 4 cohort studies, and 1 retrospective cohort study). A significant association was observed between smoking and non-alcoholic fatty liver disease with a pooled odds ratio of 1.110 (95% confidence interval, 1.028-1.199), p-value = 0.008. The statistical heterogeneity was medium with an I2 of 40.012%, p-heterogeneity = 0.074. Also there was a significant relation between non-alcoholic fatty liver disease and passive smoking with a pooled odds ratio of 1.380 (95% confidence interval, 1.199-1.588; p-value = 0.001; I2 = 59.41; p-heterogeneity = 0.117). CONCLUSION: Our meta-analysis demonstrated that smoking is significantly associated with non-alcoholic fatty liver disease. Further prospective studies exploring the underlying mechanisms of this association should be pursued. Also passive smoking increases the risk of non-alcoholic fatty liver disease about 1.38-fold. The effects of smoking cigarettes on active smokers (current smoker, former smoker, and total smoker) are less than passive smokers. Further studies are needed to compare the of effects of passive and active smoking on non-alcoholic fatty liver disease.

Liver transplantation for hepatic alveolar echinococcosis: literature review and three new cases.

BACKGROUND: Echinococcosis is a helminthic infection caused by ingestion of the eggs of the parasitic metacestode of one of four members of the Echinococcus genus. Among them, hepatic alveolar echinococcosis (HAE) mimics slow growing liver tumour with subsequent invasion to liver tissues and metastatic dissemination. Liver transplantation (LT) remains as the only treatment option when the lesions exceed the resectability limits. We described the first three cases of HAE who underwent orthotopic LT in Iran. A literature review was also conducted to summarize experiences of different transplant centres around the world. METHODS: PubMed, Scopus and Web of Science databases were searched up to April 2017 using keywords related to echinococcosis, liver and transplantation. RESULTS: Including this case report, a total of 150 patients underwent LT due to echinococcosis from 1994 to 2017. The mean age at LT was 38 years (range: 12-71) and 51% were male. About 95% of the transplantations were performed due to HAE. Pre- and post-transplant benzimidazole therapy was considered in 69% and 73% of patients, respectively. Recurrence rate varied between 0% and 60%. The overall 1-, 5- and 10-year survival rates were 60-100%, 67-85% and 49-75%, respectively. CONCLUSIONS: LT combined with pre- and post-transplant benzimidazole therapy appears to be feasible and effective for patients with fatal HAE.

Screening for Lynch Syndrome in Cases with Colorectal Carcinoma from Mashhad.

INTRODUCTION: Lynch Syndrome (LS) is a genetically inherited autosomal disorder that increases the risk of many types of cancer, especially colorectal cancer (CRC). Identifying these subjects improves morbidity and mortality. We aimed to assess the prevalence of LS with both clinical criteria and universal strategy in Mashhad, Iran. METHODS: In this retrospective study, we screened 322 patients with CRC between 2013 and 2016 in Mashhad, Iran. CRCs were screened based on Amsterdam II criteria, revised Bethesda guideline, and universal strategy. Information regarding the clinical criteria was obtained by interviewing the patients or, their families. Tumors were screened by pathologists with IHC staining of four Mismatch repair (MMR) proteins (MLH1, MSH2, MSH6, and PMS2). Tumors with absent IHC staining of MLH1 were tested for BRAF mutations to exclude sporadic CRCs. RESULTS: Of 322 CRCs, 33 cases were found to be deficient-MMR; 22 of these had concurrent loss of MLH1 and PMS2, followed by concurrent loss of MSH2 and MSH6 in 8 CRCs. Twenty-two cases with a loss of MLH1 underwent testing for the BRAF mutation, 4 of which were recognized as a positive BRAF mutation. Finally, 29 CRCs were found as being positive screen for LS. Poor sensitivity (21.74%) was found for the Amsterdam II criteria and a poor positive predictive value (15.39%) for the revised Bethesda. CONCLUSION: Application of clinical criteria may not be effective enough to identify LS and at least 2-antibody panel (PMS2, MSH6) should be conducted for newly diagnosed CRCs.

Fulminate hepatic failure as an initial presentation of non-hodgkin lymphoma: a case report.

Viral hepatitis and toxins comprise most common causes of fulminate hepatic failure that are often diagnosed with standard laboratory tests. Herein we discuss a rare, difficult to diagnosis etiology of acute liver failure (ALF). A 62-year-old man presented with a two-week history of fever and fatigue. At four days before admission he became lethargic. His past medical and drug histories were unremarkable. Physical examination revealed generalized jaundice, fever and loss of consciousness. Laboratory tests showed elevated liver transaminases with direct hyper-bilirubinemia. Abdominal ultrasonography and CT scan showed hepatosplenomegaly and para-aortic abdominal lymphadenopathy. A further work-up included liver biopsy. The histopathology and imunohistochemistry was compatible with diffuse large B-cell lymphoma. He underwent high dose glucocorticoid therapy but his condition deteriorated rapidly and he died eight days after admission. ALF as an initial manifestation of malignant hepatic infiltration is extremely rare yet should be considered in all patients with unknown hepatic failure that are highly suspicious for malignant neoplasm.

Doppler surrogate endoscopy for screening esophageal varices in patients with cirrhosis.

BACKGROUND: Portal hypertension is a common consequence of hepatic cirrhosis, which causes esophageal varices. Bleeding from varices has a high mortality rate. The present gold standard for diagnosing varices is endoscopy. Considering endoscopy side effects and patients' low acceptance, there have been always efforts for finding alternative diagnostic methods including Doppler ultrasonography (US). OBJECTIVES: The aim of the present study was to evaluate changes of Doppler indices in cirrhotic patients with and without esophageal varices. PATIENTS AND METHODS: Sixty six patients with known cirrhosis entered this cross-sectional study. Gastroscopy was performed for patients, and the first questionnaire was filled based on the Japanese Portal Hypertension Society guidelines. Then patients were referred for Doppler US of splenoportal system, and information was documented in the second questionnaire. RESULTS: Forty-four patients were male and 22 female. Forty six patients had esophageal varices, and 20 did not. There were no significant associations between splenoportal indices found by Doppler US, and presence of esophageal varices in patients. However, we found a negative association between platelet ratio to spleen diameter, and to splenic vein diameter. CONCLUSIONS: Neither of studied variables was perfect to differentiate cirrhotic patients with and without EVs. Endoscopy is still the gold standard diagnostic method for diagnosing esophageal varices in patients with cirrhosis. It seems that some of the splenoportal Doppler indices are promising, but more research and evaluation is necessary.