Alzheimer's disease: Clinical practice guideline

El Grupo de Trabajo de Neurología de la Conducta y Neurociencias Cognitivas de la Sociedad Neurológica Argentina publicó en 2006 la primera Guía de práctica clínica sobre la enfermedad de Alzheimer para su aplicación en nuestro medio y, eventualmente, en el resto de los países hispanoparlantes del Cono Sur. La Guía que hoy publicamos, mediante la revisión y actualización del estado actual del conocimiento sobre la enfermedad de Alzheimer y su manejo clínico y neurológico, provee a los profesionales los estándares surgidos de la medicina basada en la evidencia para una adecuada implementación de las conductas diagnósticas y terapéuticas a su alcance en nuestro medio.In 2006, the Argentine Neurological Society Research Group on Behavioral Neurology and Cognitive Neurosciences published the first Clinical Practice Guideline on Alzheimer's Disease to be consulted in Argentina and eventually in other countries in Latin America. The present Guideline is a review of the state of the art concerning the 2010 knowledge on the management of this disease. It provides physicians with the usual standards provided by evidence based medicine in order to reach the most adequate diagnostic and therapeutic measures at hand in our countries.Fil: Allegri, Ricardo Francisco. Sociedad Neurológica Argentina; Argentina. Fundación para la Lucha contra las Enfermedades Neurológicas de la Infancia. Instituto de Neurociencias - Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Neurociencias; ArgentinaFil: Arizaga, Raúl Luciano. Sociedad Neurológica Argentina; ArgentinaFil: Bavec, Claudia V.. Sociedad Neurológica Argentina; ArgentinaFil: Colli, Liliana P.. Sociedad Neurológica Argentina; ArgentinaFil: Demey, Ignacio. Sociedad Neurológica Argentina; ArgentinaFil: Fernández, María C.. Sociedad Neurológica Argentina; ArgentinaFil: Frontera, Silvina A.. Sociedad Neurológica Argentina; ArgentinaFil: Garau, María L.. Sociedad Neurológica Argentina; ArgentinaFil: Jiménez, Julio J.. Sociedad Neurológica Argentina; ArgentinaFil: Golimstok, Angel. Sociedad Neurológica Argentina; ArgentinaFil: Kremer, Janus. Sociedad Neurológica Argentina; ArgentinaFil: Labos, Edith. Sociedad Neurológica Argentina; ArgentinaFil: Mangone, Carlos Antonio. Sociedad Neurológica Argentina; ArgentinaFil: Ollari, Juan A.. Sociedad Neurológica Argentina; ArgentinaFil: Rojas, Zenón Galeno. Centro de Educación Médica e Investigaciones Clínicas "Norberto Quirno"; Argentina. Sociedad Neurológica Argentina; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Salmini, Omar. Sociedad Neurológica Argentina; ArgentinaFil: Ure, Jorge A.. Sociedad Neurológica Argentina; ArgentinaFil: Zuin, Daniel R.. Sociedad Neurológica Argentina; Argentin

International genome-wide meta-analysis identifies new primary biliary cirrhosis risk loci and targetable pathogenic pathways.

Primary biliary cirrhosis (PBC) is a classical autoimmune liver disease for which effective immunomodulatory therapy is lacking. Here we perform meta-analyses of discovery data sets from genome-wide association studies of European subjects (n=2,764 cases and 10,475 controls) followed by validation genotyping in an independent cohort (n=3,716 cases and 4,261 controls). We discover and validate six previously unknown risk loci for PBC (Pcombined<5 × 10(-8)) and used pathway analysis to identify JAK-STAT/IL12/IL27 signalling and cytokine-cytokine pathways, for which relevant therapies exist

Infected pancreatic necrosis: outcomes and clinical predictors of mortality. A post hoc analysis of the MANCTRA-1 international study

: The identification of high-risk patients in the early stages of infected pancreatic necrosis (IPN) is critical, because it could help the clinicians to adopt more effective management strategies. We conducted a post hoc analysis of the MANCTRA-1 international study to assess the association between clinical risk factors and mortality among adult patients with IPN. Univariable and multivariable logistic regression models were used to identify prognostic factors of mortality. We identified 247 consecutive patients with IPN hospitalised between January 2019 and December 2020. History of uncontrolled arterial hypertension (p = 0.032; 95% CI 1.135-15.882; aOR 4.245), qSOFA (p = 0.005; 95% CI 1.359-5.879; aOR 2.828), renal failure (p = 0.022; 95% CI 1.138-5.442; aOR 2.489), and haemodynamic failure (p = 0.018; 95% CI 1.184-5.978; aOR 2.661), were identified as independent predictors of mortality in IPN patients. Cholangitis (p = 0.003; 95% CI 1.598-9.930; aOR 3.983), abdominal compartment syndrome (p = 0.032; 95% CI 1.090-6.967; aOR 2.735), and gastrointestinal/intra-abdominal bleeding (p = 0.009; 95% CI 1.286-5.712; aOR 2.710) were independently associated with the risk of mortality. Upfront open surgical necrosectomy was strongly associated with the risk of mortality (p &lt; 0.001; 95% CI 1.912-7.442; aOR 3.772), whereas endoscopic drainage of pancreatic necrosis (p = 0.018; 95% CI 0.138-0.834; aOR 0.339) and enteral nutrition (p = 0.003; 95% CI 0.143-0.716; aOR 0.320) were found as protective factors. Organ failure, acute cholangitis, and upfront open surgical necrosectomy were the most significant predictors of mortality. Our study confirmed that, even in a subgroup of particularly ill patients such as those with IPN, upfront open surgery should be avoided as much as possible. Study protocol registered in ClinicalTrials.Gov (I.D. Number NCT04747990)

Evaluation of appendicitis risk prediction models in adults with suspected appendicitis

Background Appendicitis is the most common general surgical emergency worldwide, but its diagnosis remains challenging. The aim of this study was to determine whether existing risk prediction models can reliably identify patients presenting to hospital in the UK with acute right iliac fossa (RIF) pain who are at low risk of appendicitis. Methods A systematic search was completed to identify all existing appendicitis risk prediction models. Models were validated using UK data from an international prospective cohort study that captured consecutive patients aged 16–45 years presenting to hospital with acute RIF in March to June 2017. The main outcome was best achievable model specificity (proportion of patients who did not have appendicitis correctly classified as low risk) whilst maintaining a failure rate below 5 per cent (proportion of patients identified as low risk who actually had appendicitis). Results Some 5345 patients across 154 UK hospitals were identified, of which two‐thirds (3613 of 5345, 67·6 per cent) were women. Women were more than twice as likely to undergo surgery with removal of a histologically normal appendix (272 of 964, 28·2 per cent) than men (120 of 993, 12·1 per cent) (relative risk 2·33, 95 per cent c.i. 1·92 to 2·84; P < 0·001). Of 15 validated risk prediction models, the Adult Appendicitis Score performed best (cut‐off score 8 or less, specificity 63·1 per cent, failure rate 3·7 per cent). The Appendicitis Inflammatory Response Score performed best for men (cut‐off score 2 or less, specificity 24·7 per cent, failure rate 2·4 per cent). Conclusion Women in the UK had a disproportionate risk of admission without surgical intervention and had high rates of normal appendicectomy. Risk prediction models to support shared decision‐making by identifying adults in the UK at low risk of appendicitis were identified

The effect of alkaline-earth substitution on the Li K-edge of lithium silicate glasses

International audienceWe present the first Li K-edge XANES study of a varied suite of lithium silicate (LS) and lithium alkaline-earth silicate (LMS) glasses. The LS series contains three glasses with compositions LS4 (20 Li2O-80 SiO2), LS2 (33 Li2O-67 SiO2) and LS1.5 (40 Li2O-60 SiO2) and the LMS series is comprised of four glasses of compositions 20 Li2O-20 M2O-60 SiO2 where M = Mg, Ca, Sr and Ba. The spectra were compared to those of known salts and minerals, particularly to lithium metasilicate (Li2SiO3) and lithium carbonate (Li2CO3). Crystalline lithium metasilicate has a sharp, strong intensity absorption edge whereas the lithium silicate glasses all have a weak intensity edge feature, similar to that of lithium carbonate (Li2CO3). The intensity of the edge is governed by the existence of a 2p electron and can be correlated with the ionicity of the Lisbnd O bond. Therefore, the bonding environment in LS glasses differs considerably from their crystalline counterparts. The area of the absorption edge peak increases with the lithium content of the LS glasses. As for the LMS glasses the edge peak changes drastically depending on the alkaline-earth present. The peak area of the LMS glasses decreases with increasing charge density (Z/r2) from barium to magnesium. The area of the absorption edge peak in the LS glasses is larger than that of the LMS glasses. Thus, the addition of alkaline-earth elements to lithium silicate glasses modifies the glass network differently depending on the specific element, which in turn creates an altered lithium bonding environment as evidenced by their Li K-edge XANES spectra

Genome-wide binding of posterior HOXA/D transcription factors reveals subgrouping and association with CTCF

Homeotic genes code for key transcription factors (HOX-TFs) that pattern the animal body plan. During embryonic development, Hox genes are expressed in overlapping patterns and function in a partially redundant manner. In vitro biochemical screens probing the HOX-TF sequence specificity revealed largely overlapping sequence preferences, indicating that co-factors might modulate the biological function of HOX-TFs. However, due to their overlapping expression pattern, high protein homology, and insufficiently specific antibodies, little is known about their genome-wide binding preferences. In order to overcome this problem, we virally expressed tagged versions of limb-expressed posterior HOX genes (HOXA9-13, and HOXD9-13) in primary chicken mesenchymal limb progenitor cells (micromass). We determined the effect of each HOX-TF on cellular differentiation (chondrogenesis) and gene expression and found that groups of HOX-TFs induce distinct regulatory programs. We used ChIP-seq to determine their individual genome-wide binding profiles and identified between 12,721 and 28,572 binding sites for each of the nine HOX-TFs. Principal Component Analysis (PCA) of binding profiles revealed that the HOX-TFs are clustered in two subgroups (Group 1: HOXA/D9, HOXA/D10, HOXD12, and HOXA13 and Group 2: HOXA/D11 and HOXD13), which are characterized by differences in their sequence specificity and by the presence of cofactor motifs. Specifically, we identified CTCF binding sites in Group 1, indicating that this subgroup of HOX-proteins cooperates with CTCF. We confirmed this interaction by an independent biological assay (Proximity Ligation Assay) and demonstrated that CTCF is a novel HOX cofactor that specifically associates with Group 1 HOX-TFs, pointing towards a possible interplay between HOX-TFs and chromatin architecture