Development and Validation of a Clinical-Genetic Risk Score to Predict Hepatic Encephalopathy in Patients With Liver Cirrhosis.

INTRODUCTION: We aimed to define the impact of the genetic background on overt hepatic encephalopathy (HE) in patients with liver cirrhosis by developing a combined clinical-genetic risk score. METHODS: Patients suffering from liver cirrhosis from the outpatient clinics of 4 hospitals (n = 600) were included and followed up for at least 5 years until HE bouts, liver transplant, or death. Patients were genotyped for 60 candidate single nucleotide polymorphisms together with the microsatellite in the promoter region of the gene GLS. RESULTS: Single nucleotide polymorphisms rs601338 (FUT2), rs5743836 (TRL9), rs2562582 (SLC1A3), rs313853 (SLC1A5), and GLS microsatellite did predict independently the incidence and severity of overt HE and were included as genetic score. Competing risk analysis revealed that bilirubin (subhazard ratio [sHR] 1.30 [1.15-1.48], P < 0.001), albumin (sHR 0.90 [0.86-0.93], P < 0.001), genetic score (sHR 1.90 [1.57-2.30], P < 0.001), and previous episodes of overt HE (sHR 2.60 [1.57-4.29], P < 0.001) were independently associated to HE bouts during the follow-up with an internal (C-index 0.83) and external validation (C-index 0.74). Patients in the low-risk group had 5% and 12% risk of HE at 1 (log-rank 92.1; P < 0.001) and 5 (log-rank 124.1; P < 0.001) years, respectively, whereas 36% and 48% in the high-risk group. DISCUSSION: The genetic background influenced overt HE risk and severity. The clinical-genetic HE Risk score, which combined genetic background together with albumin, bilirubin, and previous episodes of overt HE, could be a useful tool to predict overt HE in patients with cirrhosis.

Hereditary angioedema with F12 mutation: Clinical features and enzyme polymorphisms in 9 Southwestern Spanish families.

BACKGROUND: Information on F12 mutation hereditary angioedema (HAE) is still limited, but Spain is now recognized as having one of the highest concentrations of cases in Western Europe. OBJECTIVE: To describe unique features of HAE in Spanish carriers of the F12 mutation and investigate a potential role for angiotensin-converting enzyme (ACE) and aminopeptidase-P polymorphisms in disease expression. METHODS: This was a prospective observational cohort study of 35 individuals (80% females) from 9 unrelated families carrying the p.Thr309Lys mutation. We analyzed detailed medical records and complement activity (C4, C1q, C1 inhibitor) and screened for mutations in exon 9 of the F12 gene and 2 polymorphisms: XPNPEP2 c-2399A and the ACE insertion/deletion polymorphism. RESULTS: The p.Thr309Lys mutation was found in all individuals. Three of the 9 index patients had a clinically negative family history, and 72% of males and 29% of females were asymptomatic. Sixteen females (44% estrogen dependent, 56% estrogen sensitive) were clearly symptomatic. The most common locations of attacks were the abdomen (63%), face (25%), and peripheral structures (6%). Triggers other than hyperestrogenic states included stress and minor trauma or pressure. Short-term treatment with C1-inhibitor concentrate and icatibant and long-term prophylaxis with tranexamic acid were useful. The combination of the I allele and A allele was detected in 17% of patients. CONCLUSION: The polymorphisms analyzed were not a major determinant of disease expression in our population. We recommend searching for F12 mutations in women with edema attacks without associated wheals and with normal C1-inhibitor levels, particularly when they develop symptoms during hyperestrogenic states or are of Western European or African origin.

Emerging BCR/ABL1 Mutations Under Treatment with Tyrosine Kinase Inhibitors in Paediatric Acute Lymphoblastic Leukaemia.

We report on the emergence and clinical relevance of an unusual BCR-ABL1 kinase domain mutational status in a 2-year-old female with p210-BCR-ABL Philadelphia chromosome-positive acute lymphoblastic leukaemia. We detected three BCR-ABL1 clones determined by the presence of the E255V, D276G and F317L mutations. We point out the usefulness of searching for mutated populations that survive tyrosine-kinase inhibitor therapy and the role of their clonal selection over time in relation to therapeutic intervention.

Eco-innovation of a wooden childhood furniture set: an example of environmental solutions in the wood sector.

The environmental profile of a set of wood furniture was carried out to define the best design criteria for its eco-design. A baby cot convertible into a bed, a study desk and a bedside table were the objects of study. Two quantitative and qualitative environmental approaches were combined in order to propose improvement alternatives: Life Cycle Assessment (LCA) and Design for Environment (DfE). In the first case Life Cycle Assessment (LCA) was applied to identify the hot spots in the product system. As a next step, LCA information was used in eco-briefing to determine several improvement alternatives. A wood products company located in Catalonia (NE Spain) was assessed in detail, dividing the process into three stages: assembly, finishing and packaging. Ten impact categories were considered in the LCA study: abiotic depletion, acidification, eutrophication, global warming, ozone layer depletion, human toxicity, fresh water aquatic ecotoxicity, marine aquatic ecotoxicity, terrestrial ecotoxicity and photochemical oxidant formation. Two processes can be considered the key environmental factors: the production of the wooden boards and electricity, with contributions of 45-68% and 14-33% respectively depending on the impact categories. Subsequently, several improvement alternatives were proposed in the eco-design process (DfE) to achieve reductions in a short-medium period of time in the environmental impact. These eco-design strategies could reduce the environmental profile of the setup by 14%. The correct methodological adaptation of the concept of eco-briefing, as a tool for communication among environmental technicians and designers, the simplification of the analytical tool used and the LCA, could facilitate the environmental analysis of a product. The results obtained provide information that can help the furniture sector to improve their environmental performance.

Gastroduodenal involvement in patients with familial adenomatous polyposis. Prospective study of the nature and evolution of polyps: evaluation of the treatment and surveillance methods applied.

OBJECTIVES: Analysis of the incidence rate and the evolution of duodenal and stomach polyps in our familial adenomatous polyposis (FAP) patients, the suitability of the surveillance method and the cancer-preventing treatment applied and the analysis of the complications arising from each procedure employed. MATERIALS AND METHODS: Twenty-nine patients diagnosed with FAP underwent study and endoscopic surveillance of the upper digestive tract. Front-view and side-view endoscopies were used. Papillary biopsies were performed even when the papilla were macroscopically normal. The Spigelman classification was used to determine the seriousness of the condition and to establish the surveillance and treatment intervals. RESULTS: Duodenal and/or papillary polyps were presented by 79.3% of the patients. Endoscopic polypectomy was performed in 13 patients with duodenal polyps. Endoscopic polypectomies for the papilla were performed in all patients. One patient required a cephalic duodenopancreatectomy and another endoscopic ampullectomy. The condition did not become cancerous in any of the patients who underwent surveillance. We report two complications arising from treatment: one postpolypectomy haemorrhage and one stenosis of the biliary-enteric anastomosis after cephalic duodenopancreatectomy. CONCLUSION: Our study shows a high incidence rate of duodenal polyps in FAP patients. A minute examination of the duodenum and papilla is necessary, using side-view endoscopes and duodenal papilla biopsies even when papilla appears to be normal. None of the patients having completed the surveillance and the prescribed treatment developed cancer and all have a low Spigelman score. This method, therefore, seems to be adequate for the treatment and surveillance of duodenal polyps.