Romiplostim in chronic liver disease with severe thrombocytopenia undergoing an elective invasive procedure

Letters to the EditorDear Editor, Thrombocytopenia is a common complication seen in patients with chronic liver disease, precluding or interfering invasive diagnostic and therapeutic procedures. Etiology is multifactorial, including hypersplenism, bone marrow suppression by HCV and a possible reduction in the level or activity of the hematopoietic growth factor thrombopoietin (TPO)(1). In addition to thrombocytopenia, functional platelet defects has been suggested. Romiplostim (Nplate®, Amgen Inc, Thousands Oaks, Calif) is a new thrombopoietin receptor agonist indicated for the treatment of thrombocytopenia in patients with chronic immune thrombocytopenic purpura who have had an insufficient response to corticosteroids, immunoglobulin or splenectomy (2). It has been not tested in chronic liver disease until now. Another thrombopoietin receptor agonist, eltrombopag (3), has been tested in chronic liver disease undergoing an elective invasive procedure. Although results were satisfactory in terms of platetelet count and avoidance of platelet transfusions, the trial was early stopped due to the observed incidence of portal vein thrombosis in the study group (4). We report a case of a Jehovah’s Witness that could successfully managed with romiplostim use..

Histochemistry evaluation of the oxidative stress and the antioxidant status in Cu-supplemented cattle

The aim of this paper is to evaluate at a histopathological level the effect of the most commonly used copper (Cu) supplementation (15 mg/kg dry matter (DM)) in the liver of intensively reared beef cattle. This was done by a histochemistry evaluation of (i) the antioxidant capacity in the liver – by the determination of metallothioneins (MT) and superoxide dismutase (SOD) expression – as well as (ii) the possible induction of oxidative damage – by the determination of inducible nitric oxide synthase (iNOS), nitrotyrosine (NITT), malondialdehyde (MDA) and 8-oxoguanine (8-oxo) – that (iii) could increase apoptotic cell death – determined by cytochrome-c (cyto-c), caspase 1 (casp1) and terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL). Liver samples from Cu-supplemented (15 mg Cu sulphate/kg DM, n = 5) and non-supplemented calves (n = 5) that form part of other experiments to evaluate Cu status were collected at slaughter and processed for immunohistochemistry and TUNEL. MT expression was diffuse and SOD showed slight changes although without statistical significance. iNOS and NITT positive (+) cells significantly increased, mainly around the central veins in the animals from the Cu-supplemented group, whereas no differences were appreciated for the rest of the oxidative stress and apoptosis markers. Under the conditions of this study, which are the conditions of the cattle raised in intensive systems in NW Spain and also many European countries, routinely Cu supplementation increased the risk of the animals to undergo subclinical Cu toxicity, with no significant changes in the Cu storage capacity and the antioxidant defensive system evaluated by MT and SOD expression, but with a significant and important increase of oxidative damage measured by iNOS and NITT. The results of this study indicated that iNOS and NITT could be used as early markers of initial pathological changes in the liver caused by Cu supplementation in cattle, although more studies in cattle under different levels of Cu supplementation are neededThis work was supported by the Xunta de Galicia (Spain) through contract 07MRU030261PR and by a research grant María Barbeito awarded to M. García-Vaquero by the Dirección Xeral de Investigación, Desenvolvemento e Innovación from Xunta de Galicia and to FSE (Fondo Social Europeo) funds through Programa de Recursos Humanos, do Plan Galego de Investigación, Desenvolvemento e Innovación Tecnolóxica de GaliciaS

Immunodiagnostic tests' predictive values for progression to tuberculosis in transplant recipients. A prospective cohort study

Background: Little is known about the predictive value for progression to tuberculosis (TB) of interferon-γ release assays and how they compare with the tuberculin skin test (TST) in assessing the risk of TB infection in transplant recipients. Methods: We screened 50 liver transplant (LT) and 26 hematopoietic stem cell transplant (HSCT) recipients with both QuantiFERON-TB Gold In-tube (QFT-GT) and TST and prospectively followed them for a median of 47 months without preventive chemoprophylaxis. Results: In the LT cohort, 1 in 22 (4.5%) QFT-GT-positive patients developed posttransplant TB, compared with none of the QFT-GT-negative patients. In the HSCT cohort, none of the 7 QFT-GT-positive patients developed TB, whereas 1 case (5.3%) progressed to active TB among the 19 QFT-GT-negative patients. Comparable results were obtained with the TST: in the LT group, 1 of 23 TST-positive and none of the 27 TST-negative patients developed TB; and in the HSCT group, none of the 8 TST-positive and one of the 18 TST-negative patients progressed to active TB. Conclusions: In this cohort of transplant recipients, the positive predictive value of QFT-GT for progression to active TB was low and comparable to that of TST. Although the risk of developing TB in patients with negative results at baseline is very low, some cases may still occur

Gastrointestinal Bleeding in Patients with Hereditary Hemorrhagic Telangiectasia: Risk Factors and Endoscopic Findings

Background: We aimed to describe risk factors for gastrointestinal (GI) bleeding and endoscopic findings in patients with hereditary hemorrhagic telangiectasia (HHT). Methods: This is a prospective study from a referral HHT unit. Endoscopic tests were performed when there was suspicion of GI bleeding, and patients were divided as follows: with, without, and with unsuspected GI involvement. Results: 67 (27.9%) patients with, 28 (11.7%) patients without, and 145 (60.4%) with unsuspected GI involvement were included. Age, tobacco use, endoglin (ENG) mutation, and hemoglobin were associated with GI involvement. Telangiectases were mostly in the stomach and duodenum, but 18.5% of patients with normal esophagogastroduodenoscopy (EGD) had GI involvement in video capsule endoscopy (VCE). Telangiectases ≤ 3 mm and ≤10 per location were most common. Among patients with GI disease, those with hemoglobin 3 mm). After a mean follow-up of 34.2 months, patients with GI involvement required more transfusions and more emergency department and hospital admissions, with no differences in mortality. Conclusions: Risk factors for GI involvement have been identified. Patients with GI involvement and severe anemia had larger telangiectases and higher ESS. VCE should be considered in patients with suspicion of GI bleeding, even if EGD is normal

Gender differences in Hereditary Hemorrhagic Telangiectasia severity

Background: Gender differences in organ involvement and clinical severity have been poorly described in hereditary hemorrhagic telangiectasia (HHT). The aim of this study was to describe differences in the severity of HHT manifestations according to gender. Methods: Severity was measured according to Epistaxis Severity Score (ESS), Simple Clinical Scoring Index for hepatic involvement, a general HHT-score, needing for invasive treatment (pulmonary or brain arteriovenous malformations -AVMs- embolization, liver transplantation or Young's surgery) or the presence of adverse outcomes (severe anemia, emergency department -ED- or hospital admissions and mortality). Results: One hundred forty-two (58.7%) women and 100 (41.3%) men were included with a mean age of 48.9 ± 16.6 and 49 ± 16.5 years, respectively. Women presented hepatic manifestations (7.1% vs 0%) and hepatic involvement (59.8% vs 47%), hepatic AVMs (28.2% vs 13%) and bile duct dilatation (4.9% vs 0%) at abdominal CT, and pulmonary AVMs at thoracic CT (35.2% vs 23%) more often than men. The Simple Clinical Scoring Index was higher in women (3.38 ± 1.2 vs 2.03 ± 1.2), and more men were considered at low risk of harboring clinically significant liver disease than women (61% vs 25.3%). These differences were mantained when considering HHT1 and HHT2 patients separetely. Duodenal telangiectasia were more frequent in men than women (21% vs 9.8%). Invasive treatments were more frequently needed in women (28.2% vs 16%) but men needed attention at the ED more often than women (48% vs 28.2%), with no differences in ESS, HHT-score, anemia hospital admissions or mortality. Conclusions: HHT women showed more severe hepatic involvement than men, also among HHT1 and HHT2 patients. Women had higher prevalence of pulmonary AVMs and needed invasive procedures more frequently, while men needed attention at the ED more often. These data might help physicians to individualize HHT patients follow-up

Evaluation of organic, conventional and intensive beef farm systems: health, management and animal production

The overall aim of the present study was to analyse and compare organic beef cattle farming in Spain with intensive and conventional systems. An on-farm study comparing farm management practices and animal health was carried out. The study also focussed on a slaughterhouse analysis by comparing impacts on the safety and quality of the cattle products. Twenty-four organic and 26 conventional farms were inspected, and farmers responded to a questionnaire that covered all basic data on their husbandry practices, farm management, veterinary treatments and reproductive performance during 2007. Furthermore, data on the hygiene and quality of 244, 2596 and 3021 carcasses of calves from organic, intensive and conventional farms, respectively, were retrieved from the official yearbook (2007) of a slaughterhouse. Differences found between organic and conventional farms across the farm analysis did not substantially reflect differences between both farm types in the predominant diseases that usually occur on beef cattle farms. However, calves reared organically presented fewer condemnations at slaughter compared with intensive and to a lesser extent with conventionally reared calves. Carcass performance also reflected differences between farm type and breed and was not necessarily better in organic farmsThis study was supported by the Xunta de Galicia (Spain;PGIDT02RA6261001PR) and I.B.P. received a research fellow-ship (AP2003-3835) from the Ministry of Science of SpainS

Serum-Metaboliten-Konzentrationen und Enzymaktivitäten in mit verschiedenen Futtermittelarten mit hohem Getreideanteil gefütterten Mastbullenkälbern

Between the ages of 23 and 35 weeks, various serum metabolites and enzymes were monitored in three 10-animal groups of double-muscled Belgian Blue bull calves maintained in a feedlot in Galicia (NW Spain) on high-grain finishing diets that mainly differed in whether the grain used was predominantly maize (group M), predominantly barley (group B), or a mixture of maize and barley in approximately equal proportions (group MB). The parameters determined were glucose, non-esterified fatty acids (NEFA), total serum protein concentration (TSP), albumin, serum urea nitrogen (SUN), creatinine, aspartate aminotransferase (AST), and gamma-glutamyltransferase (GGT). Throughout the study period, all these parameters remained within the physiological ranges for beef under intensive conditions, and no animal ever showed clinical symptoms of ruminal alterations; indicating that none of these highgrain diets were detrimental to animal health. Although average serum NEFA, creatinine, albumin, AST and GGT levels all differed among groups, only AST can be considered as possible age-independent marker of grain-type-related metabolic alterations, since the other parameters all showed significant time×group interaction. In terms of this parameter, animals fed a MB diet behaved similarly to those fed a B diet. The absence of between-group differences in blood glucose level may reflect a genetic characteristic of this double-muscled breed. Our results, in conjunction with the best productive results obtained in animals fed de B-diet, aim us to suggest that the risk of an acidogenic diet would depend strongly on the nutritional management (in terms of crude protein (CP) and quality of straw in the ration) and not only the type of grain.Zwischen dem Alter von 23 und 35 Wochen wurde ein Monitoring durchgeführt der verschiedenen Serum-Metaboliten und Enzyme mit drei Gruppen zu jeweils 10 Weißblauen Belgier-Bullenkälbern mit starker Muskelfülle, die in einer Mastparzelle in Galizien (NW Spanien) mit Mastfuttermittelarten mit hohem Getreideanteil gehalten wurden, die sich hauptsächlich darin unterschieden, dass das verwendete Getreide überwiegend aus Mais (Gruppe M), überwiegend aus Gerste (Gruppe B) oder aus einem Gemisch von Mais und Gerste zu ungefähr gleichen Teilen (Gruppe MB) bestand. Die nachgewiesenen Parameter waren Glukose, nicht veresterte Fettsäuren (NEFA), Serum-Gesamtproteinkonzentration (TSP), Albumin, Serum-Harnstoffstickstoff (SUN), Creatinin, Aspartataminotransferase (ASTZ) und γ-Glutamyltransferase (GGT). Während des Untersuchungszeitraums blieben diese Parameter durchwegs innerhalb des für Rindfleisch unter intensiven Haltungsbedingungen physiologischen Bereichs, und kein Tier zeigte zu irgendeiner Zeit klinische Symptome einer Rumen-Veränderung, so dass keines dieser Futtermittel mit hohem Getreideanteil der tierischen Gesundheit abträglich war. Obwohl die durchschnittlichen Konzentrationen von NEFA, Creatinin, Albumin, AST und GGT im Serum in den Gruppen alle unterschiedlich waren, kann nur AST als möglicher altersunabhängiger Marker von getreidebedingten Stoffwechselveränderungen betrachtet werden, da die anderen Parameter alle eine signifikante Wechselwirkung zwischen Zeit und Gruppe zeigten. Im Hinblick auf diese Parameter verhielten sich Tiere, an die ein MB-Futtermittel verfüttert wurde, wie diejenigen, an die ein B-Futtermittel verfüttert wurde. Das Fehlen von Intergruppenunterschieden hinsichtlich des Blut-Glukosespiegels könnte ein genetisches Merkmal dieser Rasse mit starker Muskelfülle widerspiegeln. Unsere Ergebnisse, zusammen mit den besten, mit Tieren, denen das B-Futter verfüttert wurde, erhaltenen Nutzergebnissen veranlassen uns zu dem Vorschlag, dass das Risiko einer azidogenen Fütterung stark vom Fütterungsmanagement (hinsichtlich Roheiweiß (CP) und Qualitätsstroh in der Ration) und nicht nur vom Getreidetyp abhängt.This work was supported by the Xunta de Galicia (Spain) through grant XUGA 2002/CG320S

Selection of nature-based solutions to improve comfort in schools during heat waves

Climate change impacts particularly affect vulnerable populations such as children. Therefore, addressing the adaptation of educational buildings is crucial in avoiding these negative effects on school performance. In this paper, three educational buildings, located in Badajoz (Spain), Evora (Portugal) and Porto (Portugal), serve as pilot samples to study the suitability of nature-based solutions (NBS), chosen for each one of three climatic zones. The NBS selected include green roofs, vertical structures with vegetation to shade holes, outdoor trees and free-cooling ventilation. The scenarios of the different NBS implemented in the three models were simulated with the software EnergyPlus, which allows optimising the appropriate decision before renovation operations begin. The results obtained from the simulations suggest energy performance improvements after applying the most adequate NBS selection to each one of the three buildings tested. Particularly, a reduction in radiation on both roofs and facades is required in the case of Evora and Badajoz, where both climate zones have similar features, that is, warm and dry. While in Porto, milder and more humid than the former ones, it is very effective to operate mainly on the roof, complemented by small ventilation operations.The authors gratefully acknowledge the support of this work by the LIFE+ Programme under the responsibility of the Directorate General for the Environment of the European Commission through the agreement LIFE17 CCA/ES/00088, LIFE myBUILDINGisGREEN

Endoscopic biliary drainage in unresectable biliary obstruction: the role of endoscopic ultrasound-guidance in a cohort study

Background and study aims: the use of endoscopic ultrasound-guided biliary drainage (EUS-BD) has increased in cases of failed endoscopic retrograde cholangiopancreatography (ERCP) and there are some concerns. The main aim of the study was to determine the role of EUS-BD in a palliative case cohort. The secondary aim was to compare the efficacy, safety and survival of EUS-BD and ERCP procedures. Patients and methods: this was an observational study at a single tertiary institution, with a consecutive inclusion from January 2015 to December 2016. The inclusion criteria were unresectable tumors of the biliopancreatic region with an indication of BD. Statistical comparison analysis was performed between the ERCP and EUS-BD groups. The incidence between groups was compared using the Chi-square and Fisher exact tests. The log rank test was used to compare the risk of death. Results: fifty-two cases with an indication of palliative BD were included in the study. Transpapillary drainage via ERCP was possible in 44 procedures and EUS-BD was required in eight cases; 15.4% of the cohort and seven using lumen apposing metal stent (LAMS). The technical and clinical success of global endoscopic BD was 100% and 88.5% (ERCP: 84.6% and 78.9%; EUS-BD: 100% and 62.5%, respectively). Pancreatitis was the most frequent adverse event (AE) in the ERCP group (9.62%) and bleeding in the EUS-BD (25%). There were fatal AEs in ERCP (1.9%) and EUS-BD (25%) cases. Patient survival was higher with ERCP transpapillary stents compared to EUS-guided stents, which was statistically significant (p = 0.007). Conclusions: the requirement of EUS-BD in palliative biliopancreatic pathology is not marginal. EUS-BD is associated with a lower survival rate and a higher rate of fatal AE, which argues against its use as a first choice procedure

Adrenomedullin as a potential biomarker involved in patients with hereditary hemorrhagic telangiectasia

Background: Adrenomedullin (AM) is a vasoactive peptide mostly secreted by endothelial cells with an important role in preserving endothelial integrity. The relationship between AM and hereditary hemorrhagic telangiectasia (HHT) is unknown. We aimed to compare the serum levels and tissue expression of AM between HHT patients and controls. Methods: Serum AM levels were measured by radioimmunoassay and compared between control and HHT groups. AM levels were also compared among HHT subgroups according to clinical characteristics. The single nucleotide polymorphism (SNP) rs4910118 was assessed by restriction analysis and sequencing. AM immunohistochemistry was performed on biopsies of cutaneous telangiectasia from eight HHT patients and on the healthy skin from five patients in the control group. Results: Forty-five HHT patients and 50 healthy controls were included, mean age (SD) was 50.7 (14.9) years and 46.4 (9.9) years (p = 0.102), respectively. HHT patients were mostly female (60% vs 38%, p = 0.032). Median [Q1-Q3] serum AM levels were 68.3 [58.1-80.6] pg/mL in the HHT group and 47.7 [43.2-53.8] pg/mL in controls (p<0.001), with an optimal AM cut-off according to Youden's J statistic of 55.32 pg/mL (J:0.729). Serum AM levels were similar in the HHT subgroups. No patient with HHT had the SNP rs4910118. AM immunoreactivity was found with high intensity in the abnormal blood vessels of HHT biopsies