Systematic Review with Meta-Analysis: Fecal Microbiota Transplantation for Severe or Fulminant Clostridioides difficile

Digestive Diseases and Sciences - Severe and fulminant Clostridioides difficile infection (CDI) is associated with significant morbidity and mortality. While fecal microbiota transplantation (FMT)...     

Impaired transforming growth factor-beta signaling in idiopathic pulmonary arterial hypertension

Mutations in transforming growth factor-beta family receptor-II, bone morphogenetic protein receptor-2, and activin-like kinase-1 have been associated with pulmonary hypertension. In the present study, we determined that pulmonary arteries in normal lungs and in lungs of patients with emphysema and idiopathic pulmonary arterial hypertension comparably expressed transforming growth factor-beta receptors I and II, Smad(1, 5, 8), Smad2, Smad3, Smad4, phosphorylated Smad(1, 5, 8), and phosphorylated Smad2 (the latter two both indicative of active in vivo signaling) in endothelial cells, as assessed by immunohistochemistry and quantitative morphometry. Medial or intimal smooth muscle cells had weak or absent expression of these molecules. In clear contrast to endothelial cell expression in pulmonary arteries and in endothelial cells lining incipient vessels within plexiform lesions of hypertensive lungs, endothelial cells present in the core of the lesions lacked expression of all examined members of the signaling molecules. These findings were made irrespective of the mutation status of bone morphogenetic protein receptor-2 in hypertensive patients. Our findings suggest that pulmonary artery endothelial cells in both normal and severely hypertensive lungs have active transforming growth factor-beta family signaling, and that loss of signaling might contribute to the abnormal growth of endothelial cells in plexiform lesions in idiopathic pulmonary arterial hypertension.     

Fibrinogen and Fibrin Clot Structure in Diabetes

Diabetes is associated with an increased risk of developing cardiovascular disease, which is not fully accounted for by the accumulation of classic cardiovascular risk factors in patients. Recent evidence has demonstrated fibrinogen to be a powerful independent risk marker for cardiovascular disease in the general population, and it is also likely to contribute toward the increased atherosclerotic risk in diabetes. The etiology of hyperfibrinogenemia in diabetes is likely to be multifactorial, and at present the mechanisms involved have not been clarified. However, insulin, insulin resistance and inflammation are likely to be involved, especially in type 2 diabetes. The influence of diabetes in determining an individual's atherothrombotic risk is likely to extend beyond that of elevated fibrinogen levels, and may also act via changes in the structure and function of the fibrin clot that forms. Further research is needed to determine the mechanisms underlying these changes, which may lead to development of future interventions to reduce the excessive vascular risk associated with this disease.     

Accuracy of chitotriosidase activity and CCL18 concentration in assessing type I Gaucher disease severity. A systematic review with meta-analysis of individual participant data

Chitotriosidase activity and CCL18 concentration are interchangeably used for monitoring Gaucher disease (GD) activity, together with clinical assessment. However, comparative studies of these two biomarkers are scarce and of limited sample size. The aim of this systematic review with meta-analysis of individual participant data (IPD) was to compare the accuracy of chitotriosidase activity and CCL18 concentration for assessing type I GD severity. We identified cross-sectional and prospective cohort studies by searching Medline, EMBASE, and CENTRAL from January 1995 to June 2017, and by contacting research groups. The primary outcome was a composite of liver volume >1.25 multiple of normal (MN), spleen volume >5 MN, hemoglobin concentration <11 g/dL, and platelet count <100x109/L. Overall, IPD included 1,109 observations from 334 patients enrolled in nine primary studies, after excluding 111 patients with undocumented values and 18 patients with deficient chitotriosidase activity. IPD were unavailable for 14 eligible primary studies. The primary outcome was associated with a 5.3-fold (95% Confidence Interval [CI]: 4.2-6.6) and 3.0-fold (95% CI: 2.6-3.6) increase of the geometric mean for chitotriosidase activity and CCL18 concentration, respectively. The corresponding areas under the receiver operating characteristics curves were 0.82 and 0.84 (summary difference, 0.02, 95% CI: -0.02 to 0.05). The addition of chitotriosidase activity did not improve the accuracy of the CCL18 concentration. Estimates remained robust in the sensitivity analysis and consistent across subgroups. Neither the chitotriosidase activity nor the CCL18 concentration varied significantly according to a recent history of bone events among 97 patients. In conclusion, the CCL18 concentration is as accurate as chitotriosidase activity in assessing hematological and visceral parameters of GD severity and can be measured in all GD patients. This meta-analysis supports the use of CCL18 rather than chitotriosidase activity for monito-ring GD activity in routine practice.     

Therapeutic biliary endoscopy in patients over 90 years of age

Endoscopic retrograde cholangiopancreatography (ERCP) is an established method to treat bile duct obstruction. Besides, ERCP is one of the most stricking parts of interventional endoscopy and takes advantage of its minimal invasive condition to be applied to a wide variety of patients. We present five patients over 90 years of age who underwent successfully and without complications six therapeutic ERCPs. Endoscopic biliary sphincterotomy, common bile duct stone extraction and plastic stent insertion all were performed uneventfully and solving the biliary obstruction. Therapeutic ERCP is a safe and effective modality to treat bile duct obstruction in patients over 90 years of age.     

Moderate early life stress improves adult zebrafish (Danio rerio) working memory but does not affect social and anxiety‐like responses

Early life stress (ELS) is defined as a short or chronic period of trauma, environmental or social deprivation, which can affect different neurochemical and behavioral patterns during adulthood. Zebrafish (Danio rerio) have been widely used as a model system to understand human neurodevelopmental disorders and display translationally relevant behavioral and stress‐regulating systems. In this study, we aimed to investigate the effects of moderate ELS by exposing young animals (6‐weeks postfertilization), for 3 consecutive days, to three stressors, and analyzing the impact of this on adult zebrafish behavior (16‐week postfertilization). The ELS impact in adults was assessed through analysis of performance on tests of unconditioned memory (free movement pattern Y‐maze test), exploratory and anxiety‐related task (novel tank diving test), and social cohesion (shoaling test). Here, we show for the first time that moderate ELS increases the number of alternations in turn‐direction compared to repetitions in the unconditioned Y‐maze task, suggesting increased working memory, but has no effect on shoal cohesion, locomotor profile, or anxiety‐like behavior. Overall, our data suggest that moderate ELS may be linked to adaptive flexibility which contributes to build “resilience” in adult zebrafish by improving working memory performance.     

Distinct Haplotype in Non-Ashkenazi Gaucher Patients with N370S Mutation

ABSTRACT: A new polymorphism, in intron 7 of glucocerebrosidase gene, has been identified in Gaucher Disease patients. It seems to appear only in Pv1.1^-alleles bearing the N370S mutation. This new sub-haplotype was only identified in Portuguese patients, of origins spanning all of the Portuguese continental territory. This finding indicates that, in the Portuguese, mutation N370S has existed in the context of two slightly different haplotypes and thus must be relatively ancient.