Fifteen years experience: Egyptian metabolic lab

Background: Inborn errors of metabolism (IEM) are single gene disorders responsible for abnormalities in the synthesis or catabolism of proteins, carbohydrates and fats by means of defective enzymes or transport proteins which results in a block of the metabolic pathway and accumulation of metabolites in different tissues. This study shows the most common diagnosed inherited inborn errors of metabolism among the Egyptian population. Prior to 1995, the diagnosis of inherited metabolic disorders in Egypt was very limited and diagnosed mainly on clinical suspicion. In 1995, The Biochemical Genetics Unit at The National Research Centre has been established as a part of The Human Genetics Department and later on in 2003 it was developed into The Biochemical Genetics Department by applying advanced techniques and equipments and providing early diagnosis for the metabolic disorders which led to better outcome in our patients. Material and methods: We have retrospectively reviewed a total of 12,148 cases suspected to have inborn errors of metabolism (IEM) with different age groups. They had been referred from several diagnostic centers and hospitals in Egypt to The Department of Biochemical Genetics at The National Research Centre. The diagnosis of these disorders was confirmed by qualitative determination of amino acid profile, quantitative determination of phenylalanine and galactose levels using dried blood spots (DBSs), quantitative determination of urinary glycosaminoglycans (GAGs), twodimensional electrophoretic separation of GAGs in urine and the assay for lysosomal enzymes activities in plasma and leukocytes. Results: Out of the total number of cases; 1041 (8.6%) patients were proved to have metabolic disorders. Those patients were classified as: 722 patients (69.4%) with lysosomal storage disorders, 302 patients (29%) with amino acid disorders and 17 patients (1.6%) with galactosemia. Conclusion: This study illustrates the experience of the reference metabolic lab in Egypt over 15 years. The lab began metabolic disorder screening by using simple diagnostic techniques like thin layer chromatography and colored tests in urine which by time updated and upgraded the methods to diagnose a wide range of disorders. This study shows the most common diagnosed inherited inborn errors of metabolism among the Egyptian population.Keywords: IEM; Consanguineous marriages; Aminoacidopathies; Lysosomal storage disorder

Validation of the AASLD recommendations for Classification of Oesophageal Varices in Clinical Practice

Background & Aims The American Association for the Study of Liver Diseases recommends the use of a 2‐grade classification system (small and large) to describe the size of oesophageal varices (OV). Data on observer agreement (OA) on this system are currently lacking. We aimed to evaluate this classification and compare it to the widely used 3‐grade classification (grade 1 ‘small’, grade 2 ‘medium’, grade 3 ‘large’) among operators of variable experience. Methods High‐definition video recordings of 100 patients with cirrhosis were prospectively collected using standardised criteria. Nine observers of variable experience performed independent evaluations of the videos in random order. OV were scored using both systems. All assessments were repeated a year later by the same observers to assess intra‐observer agreement. Results Interobserver agreement (all observers) using the 2‐grade and the 3‐grade system was k = 0.71 (95% CI: 0.64‐0.78) and k = 0.73 (95% CI: 0.66‐0.79) respectively. When using the 2‐grade system, intra‐observer agreement between hepatologists (n = 3), luminal gastroenterologists (n = 3) and trainee gastroenterologists (n = 3) was k = 0.89 (95% CI: 0.86‐0.91), k = 0.72 (95% CI: 0.67‐0.77), and k = 0.74 (95% CI: 0.67‐0.8) respectively. With the 3‐grade system; intra‐observer agreement between the same three subgroups were k = 0.9 (95% CI: 0.87‐0.92), k = 0.73 (95% CI: 0.68‐0.78), k = 0.77 (95% CI: 0.71‐0.82) respectively. Conclusions There was no difference in OA between the 2‐grade and 3‐grade classification systems. Hepatologists had significantly higher levels of consistency in grading OV. This may have implications to create alternative training models for residents and fellows in the recognition and grading of OV

Novel Sequence Variants in the NPC1 Gene in Egyptian Patients with Niemann-Pick Type C

BACKGROUND: Niemann-Pick disease type C (NPC) is a rare, autosomal recessive, progressive neuro-visceraldisease caused by biallelic mutations in either NPC1gene (95% of cases) or NPC2 gene. AIM: This caseseries study aimed at the molecular analysis of certain hot spots of NPC1 genein NPC Egyptian patients. METHODS: The study included 15 unrelated NPC patients and selected parents,as well as20 healthy controls of matched sex and age. Clinical investigations were performed according to well established clinical criteria. Assessment of the chitotriosidase level, as an initial screening tool for NPC, was done in all cases. Polymerase chain reaction amplification of NPC1 exons (17–25) encountering the hotspot residues (855–1098 and1038–1253) was carried out followed by direct sequencingfor mutational analysis. RESULTS: All includedpatients with mainly neurovisceral involvement were characterized. The onset of the disease varied from early-infantile (58.3%) to late-infantile (26.7%) and juvenile-onset (6.7%). Ahigh chitotriosidase level wasobservedin all patients. Molecular analysis of NPC1 (exons 17–25) confirmed 15 mutant alleles out of 30 studied ones. They included two novel homozygous missense variants (p.Ser1169Arg and p.Ser1197Phe) and previously reportedfour mutations (p.Arg958*, p.Gly910Ser, p.Ala927Glyfs*38, and andp.Cys1011*). CONCLUSION: The two studied amino acid residues (855–1098 and 1038–1253) could beconsidered aspotential hotspot regions in NPC1 Egyptian patients

Intraductal fully covered self-expanding metal stents in the management of post-liver transplant anastomotic strictures: a UK wide experience.

Background: Fully covered intraductal self-expanding metal stents (IDSEMS) have been well described in the management of post-liver transplant (LT) anastomotic strictures (ASs). Their antimigration waists and intraductal nature make them suited for deployment across the biliary anastomosis. Objectives: We conducted a multicentre study to analyse their use and efficacy in the management of AS. Design: This was a retrospective, multicentre observational study across nine tertiary centres in the United Kingdom. Methods: Consecutive patients who underwent endoscopic retrograde cholangiopancreatography with IDSEMS insertion were analysed retrospectively. Recorded variables included patient demographics, procedural characteristics, response to therapy and follow-up data. Results: In all, 162 patients (100 males, 62%) underwent 176 episodes of IDSEMS insertion for AS. Aetiology of liver disease in this cohort included hepatocellular carcinoma (n = 35, 22%), followed by alcohol-related liver disease (n = 29, 18%), non-alcoholic steatohepatitis (n = 20, 12%), primary biliary cholangitis (n = 15, 9%), acute liver failure (n = 13, 8%), viral hepatitis (n = 13, 8%) and autoimmune hepatitis (n = 12, 7%). Early AS occurred in 25 (15%) cases, delayed in 32 (20%) cases and late in 95 (59%) cases. Age at transplant was 54 years (range, 12-74), and stent duration was 15 weeks (range, 3 days-78 weeks). In total, 131 (81%) had complete resolution of stricture at endoscopic re-evaluation. Stricture recurrence was observed in 13 (10%) cases, with a median of 19 weeks (range, 4-88 weeks) after stent removal. At removal, there were 21 (12%) adverse events, 5 (3%) episodes of cholangitis and 2 (1%) of pancreatitis. In 11 (6%) cases, the removal wires unravelled, and 3 (2%) stents migrated. All were removed endoscopically. Conclusion: IDSEMS appears to be safe and highly efficacious in the management of post-LT AS, with low rates of AS recurrence

Prediction of survival among patients receiving transarterial chemoembolization for hepatocellular carcinoma: A response-based approach

Background and aims: The heterogeneity of intermediate-stage hepatocellular carcinoma (HCC) and the widespread use of transarterial chemoembolization (TACE) outside recommended guidelines have encouraged the development of scoring systems that predict patient survival. The aim of this study was to build and validate statistical models that offer individualized patient survival prediction using response to TACE as a variable. Approach and results: Clinically relevant baseline parameters were collected for 4,621 patients with HCC treated with TACE at 19 centers in 11 countries. In some of the centers, radiological responses (as assessed by modified Response Evaluation Criteria in Solid Tumors [mRECIST]) were also accrued. The data set was divided into a training set, an internal validation set, and two external validation sets. A pre-TACE model ("Pre-TACE-Predict") and a post-TACE model ("Post-TACE-Predict") that included response were built. The performance of the models in predicting overall survival (OS) was compared with existing ones. The median OS was 19.9 months. The factors influencing survival were tumor number and size, alpha-fetoprotein, albumin, bilirubin, vascular invasion, cause, and response as assessed by mRECIST. The proposed models showed superior predictive accuracy compared with existing models (the hepatoma arterial embolization prognostic score and its various modifications) and allowed for patient stratification into four distinct risk categories whose median OS ranged from 7 months to more than 4 years. Conclusions: A TACE-specific and extensively validated model based on routinely available clinical features and response after first TACE permitted patient-level prognosticatio

Genetic variation in HSD17B13 reduces the risk of developing cirrhosis and hepatocellular carcinoma in alcohol misusers

BACKGROUND & AIMS: Carriage of rs738409:G in patatin-like phospholipase domain-containing 3 (PNPLA3) is associated with an increased risk for developing alcohol-related cirrhosis and hepatocellular carcinoma (HCC). Recently, rs72613567:TA in hydroxysteroid 17-beta dehydrogenase 13 (HSD17B13) was shown to be associated with a reduced risk for developing alcohol-related liver disease and to attenuate the risk associated with PNPLA3 rs738409:G. This study explores the risk-associations between these two genetic variants and the development of alcohol-related cirrhosis and HCC. APPROACH AND RESULTS: Variants in HSD17B13 and PNPLA3 were genotyped in 6,171 participants, including: 1,031 with alcohol-related cirrhosis and HCC; 1,653 with alcohol-related cirrhosis without HCC; 2,588 alcohol misusers with no liver disease; and 899 healthy controls. Genetic associations with the risks for alcohol-related cirrhosis and HCC were determined using logistic regression analysis. Carriage of HSD17B13 rs72613567:TA was associated with a lower risk for both cirrhosis (OR 0.79 [95% CI 0.72-0.88], p=8.13×10-6) and HCC (OR 0.77 [95% CI 0.68-0.89], p=2.27×10-4), while carriage of PNPLA3 rs738409:G was associated with an increased risk for developing cirrhosis (OR 1.70 [95% CI 1.54-1.88], p=1.52x10-26) and HCC (OR 1.77 [95% CI 1.58-1.98], p=2.31×10-23). These associations remained significant after adjusting for age, sex, body mass index, type II diabetes mellitus and country. Carriage of HSD17B13 rs72613567:TA attenuated the risk for developing cirrhosis associated with PNPLA3 rs738409:G in both men and women but the protective effect against the subsequent development of HCC was only observed in men (p=1.72×10-4; ORallelic, 0.75; 95% CI, 0.64-0.87). CONCLUSIONS: Carriage of variants in PNPLA3 and HSD17B13 differentially affect the risk for developing advanced alcohol-related liver disease. A genotypic/phenotypic risk score might facilitate earlier diagnosis of HCC in this population

Semi-empirical correlation for binary interaction parameters of the Peng–Robinson equation of state with the van der Waals mixing rules for the prediction of high-pressure vapor–liquid equilibrium

Peng–Robinson equation of state is widely used with the classical van der Waals mixing rules to predict vapor liquid equilibria for systems containing hydrocarbons and related compounds. This model requires good values of the binary interaction parameter kij. In this work, we developed a semi-empirical correlation for kij partly based on the Huron–Vidal mixing rules. We obtained values for the adjustable parameters of the developed formula for over 60 binary systems and over 10 categories of components. The predictions of the new equation system were slightly better than the constant-kij model in most cases, except for 10 systems whose predictions were considerably improved with the new correlation

Role of physical function in predicting short-term treatment outcome in Egyptian acute myeloid leukemia patients: a single center experience

Background: Acute myeloid leukemia (AML) is a potentially fatal hematological disease. Along with disease-related factors, patient-related factors, in particular age, are a strong predictor of outcome that influence treatment decisions. Many acute myeloid leukemia risk stratification models have been developed to predict the outcome of intensive chemotherapy. However, these models did not include physical function assessments. Methods: This study investigated the impact of several factors, namely the performance status, physical function and age on the short-term outcomes of intensive chemotherapy in a cohort of 50 Egyptian patients with de novo acute myeloid leukemia. Results: Complete remission after intensive chemotherapy in these myeloid leukemia patients at Day 28 was 56% and the mortality rate was 12% and 34% at Day 28 and Day 60, respectively. The pretreatment Eastern Cooperative Oncology Group score was significantly correlated with outcomes on Day 28 and Day 60 (p-value = 0.041 and p-value = 0.032, respectively). There were significant correlations between the two-minute walk test and outcomes of therapy on Day 28 and 60 (p-value = 0.032 and p-value = 0.047, respectively) and between grip strength test and outcomes of therapy on Day 28 and 60 (p-value = 0.046 and p-value = 0.047 respectively). Furthermore, there was a significant correlation between chair stand test and outcome of therapy on Day 28 (p-value = 0.023). Conclusion: Performance status and physical function assessments were strong predictors of outcome of intensive chemotherapy in acute myeloid leukemia and we recommend the incorporation of these variables in risk stratification models for the personalization of therapy before treating acute myeloid leukemia patients with intensive chemotherapy. Keywords: Acute myeloid leukemia, Physical functions, Performance status, ECO

Gravitational Search, Monkey and Krill Herd Swarm Algorithms for Phase Stability, Phase Equilibrium and Chemical Equilibrium Problems

<div><p>ABSTRACT</p><p>Phase equilibrium calculations (PEC) and phase stability (PS) analysis of reactive and non-reactive systems problems are important for the simulation and design of chemical engineering processes. These problems, which are challenging multi-variable and non-convex, require optimization techniques that are both efficient and effective in finding the solution. Stochastic global optimization algorithms, especially swarm algorithms, are promising tools for such problems. In this study, Monkey Algorithm (MA), Gravitational Search Algorithm (GSA) and Krill Herd Algorithm (KHA) were used to solve phase stability, phase equilibrium and chemical equilibrium problems. We have also studied the effect of adding a local optimizer at the end of the stochastic optimizer run. The results were compared to determine the strengths and weaknesses of each algorithm. When a local optimizer was used, MA was found to be a reliable algorithm in solving the problems. GSA had relatively the least numerical effort for all problems among the three algorithms but with low reliability. KHA was more reliable than other two algorithms without the use of a local optimizer. The performance of GSA, MA, and KHA was compared with Firefly Algorithm (FA) and Cuckoo Search (CS). In summary, this study found that CS algorithm was more reliable than the newly tested algorithms. Nevertheless, MA and GSA algorithms, when combined with a local optimizer, solve the thermodynamic problems as reliably and efficiently as CS.</p></div