Regulation of the Intestinal Extra-Adrenal Steroidogenic Pathway Component LRH-1 by Glucocorticoids in Ulcerative Colitis

Ulcerative colitis (UC) is an inflammatory bowel disease (IBD) and can be treated with glucocorticoids (GC), although some patients are unresponsive to this therapy. The transcription factor LRH-1/NR5A2 is critical to intestinal cortisol production (intestinal steroidogenesis), being reduced in UC patients. However, the relationship between LRH-1 expression and distribution with altered corticosteroid responses is unknown. To address this, we categorized UC patients by their steroid response. Here, we found that steroid-dependent and refractory patients presented reduced glucocorticoid receptor (GR)-mediated intestinal steroidogenesis compared to healthy individuals and responder patients, possibly related to increased colonic mucosa GR isoform beta (GR beta) content and cytoplasmic LRH-1 levels in epithelial and lamina propria cells. Interestingly, an intestinal epithelium-specific GR-induced knockout (GR(iKO)) dextran sodium sulfate (DSS)-colitis mice model presented decreased epithelial LRH-1 expression, whilst it increased in the lamina propria compared to DSS-treated control mice. Mechanistically, GR directly induced NR5A2 gene expression in CCD841CoN cells and human colonic organoids. Furthermore, GR bound to two glucocorticoid-response elements within the NR5A2 promoter in dexamethasone-stimulated CCD841CoN cells. We conclude that GR contributes to intestinal steroidogenesis by inducing LRH-1 in epithelial cells, suggesting LRH-1 as a potential marker for glucocorticoid-impaired response in UC. However, further studies with a larger patient cohort will be necessary to confirm role of LRH-1 as a therapeutic biomarker

Canagliflozin and renal outcomes in type 2 diabetes and nephropathy

BACKGROUND Type 2 diabetes mellitus is the leading cause of kidney failure worldwide, but few effective long-term treatments are available. In cardiovascular trials of inhibitors of sodium–glucose cotransporter 2 (SGLT2), exploratory results have suggested that such drugs may improve renal outcomes in patients with type 2 diabetes. METHODS In this double-blind, randomized trial, we assigned patients with type 2 diabetes and albuminuric chronic kidney disease to receive canagliflozin, an oral SGLT2 inhibitor, at a dose of 100 mg daily or placebo. All the patients had an estimated glomerular filtration rate (GFR) of 30 to <90 ml per minute per 1.73 m2 of body-surface area and albuminuria (ratio of albumin [mg] to creatinine [g], >300 to 5000) and were treated with renin–angiotensin system blockade. The primary outcome was a composite of end-stage kidney disease (dialysis, transplantation, or a sustained estimated GFR of <15 ml per minute per 1.73 m2), a doubling of the serum creatinine level, or death from renal or cardiovascular causes. Prespecified secondary outcomes were tested hierarchically. RESULTS The trial was stopped early after a planned interim analysis on the recommendation of the data and safety monitoring committee. At that time, 4401 patients had undergone randomization, with a median follow-up of 2.62 years. The relative risk of the primary outcome was 30% lower in the canagliflozin group than in the placebo group, with event rates of 43.2 and 61.2 per 1000 patient-years, respectively (hazard ratio, 0.70; 95% confidence interval [CI], 0.59 to 0.82; P=0.00001). The relative risk of the renal-specific composite of end-stage kidney disease, a doubling of the creatinine level, or death from renal causes was lower by 34% (hazard ratio, 0.66; 95% CI, 0.53 to 0.81; P<0.001), and the relative risk of end-stage kidney disease was lower by 32% (hazard ratio, 0.68; 95% CI, 0.54 to 0.86; P=0.002). The canagliflozin group also had a lower risk of cardiovascular death, myocardial infarction, or stroke (hazard ratio, 0.80; 95% CI, 0.67 to 0.95; P=0.01) and hospitalization for heart failure (hazard ratio, 0.61; 95% CI, 0.47 to 0.80; P<0.001). There were no significant differences in rates of amputation or fracture. CONCLUSIONS In patients with type 2 diabetes and kidney disease, the risk of kidney failure and cardiovascular events was lower in the canagliflozin group than in the placebo group at a median follow-up of 2.62 years

Why Are Outcomes Different for Registry Patients Enrolled Prospectively and Retrospectively? Insights from the Global Anticoagulant Registry in the FIELD-Atrial Fibrillation (GARFIELD-AF).

Background: Retrospective and prospective observational studies are designed to reflect real-world evidence on clinical practice, but can yield conflicting results. The GARFIELD-AF Registry includes both methods of enrolment and allows analysis of differences in patient characteristics and outcomes that may result. Methods and Results: Patients with atrial fibrillation (AF) and ≥1 risk factor for stroke at diagnosis of AF were recruited either retrospectively (n = 5069) or prospectively (n = 5501) from 19 countries and then followed prospectively. The retrospectively enrolled cohort comprised patients with established AF (for a least 6, and up to 24 months before enrolment), who were identified retrospectively (and baseline and partial follow-up data were collected from the emedical records) and then followed prospectively between 0-18 months (such that the total time of follow-up was 24 months; data collection Dec-2009 and Oct-2010). In the prospectively enrolled cohort, patients with newly diagnosed AF (≤6 weeks after diagnosis) were recruited between Mar-2010 and Oct-2011 and were followed for 24 months after enrolment. Differences between the cohorts were observed in clinical characteristics, including type of AF, stroke prevention strategies, and event rates. More patients in the retrospectively identified cohort received vitamin K antagonists (62.1% vs. 53.2%) and fewer received non-vitamin K oral anticoagulants (1.8% vs . 4.2%). All-cause mortality rates per 100 person-years during the prospective follow-up (starting the first study visit up to 1 year) were significantly lower in the retrospective than prospectively identified cohort (3.04 [95% CI 2.51 to 3.67] vs . 4.05 [95% CI 3.53 to 4.63]; p = 0.016). Conclusions: Interpretations of data from registries that aim to evaluate the characteristics and outcomes of patients with AF must take account of differences in registry design and the impact of recall bias and survivorship bias that is incurred with retrospective enrolment. Clinical Trial Registration: - URL: http://www.clinicaltrials.gov . Unique identifier for GARFIELD-AF (NCT01090362)

Risk profiles and one-year outcomes of patients with newly diagnosed atrial fibrillation in India: Insights from the GARFIELD-AF Registry.

BACKGROUND: The Global Anticoagulant Registry in the FIELD-Atrial Fibrillation (GARFIELD-AF) is an ongoing prospective noninterventional registry, which is providing important information on the baseline characteristics, treatment patterns, and 1-year outcomes in patients with newly diagnosed non-valvular atrial fibrillation (NVAF). This report describes data from Indian patients recruited in this registry. METHODS AND RESULTS: A total of 52,014 patients with newly diagnosed AF were enrolled globally; of these, 1388 patients were recruited from 26 sites within India (2012-2016). In India, the mean age was 65.8 years at diagnosis of NVAF. Hypertension was the most prevalent risk factor for AF, present in 68.5% of patients from India and in 76.3% of patients globally (P < 0.001). Diabetes and coronary artery disease (CAD) were prevalent in 36.2% and 28.1% of patients as compared with global prevalence of 22.2% and 21.6%, respectively (P < 0.001 for both). Antiplatelet therapy was the most common antithrombotic treatment in India. With increasing stroke risk, however, patients were more likely to receive oral anticoagulant therapy [mainly vitamin K antagonist (VKA)], but average international normalized ratio (INR) was lower among Indian patients [median INR value 1.6 (interquartile range {IQR}: 1.3-2.3) versus 2.3 (IQR 1.8-2.8) (P < 0.001)]. Compared with other countries, patients from India had markedly higher rates of all-cause mortality [7.68 per 100 person-years (95% confidence interval 6.32-9.35) vs 4.34 (4.16-4.53), P < 0.0001], while rates of stroke/systemic embolism and major bleeding were lower after 1 year of follow-up. CONCLUSION: Compared to previously published registries from India, the GARFIELD-AF registry describes clinical profiles and outcomes in Indian patients with AF of a different etiology. The registry data show that compared to the rest of the world, Indian AF patients are younger in age and have more diabetes and CAD. Patients with a higher stroke risk are more likely to receive anticoagulation therapy with VKA but are underdosed compared with the global average in the GARFIELD-AF. CLINICAL TRIAL REGISTRATION-URL: http://www.clinicaltrials.gov. Unique identifier: NCT01090362

Hyponatremia in neurological patients: Cerebral salt wasting versus inappropriate antidiuretic hormone secretion

SCOPUS: ar.jinfo:eu-repo/semantics/publishe

GIS and user experience in decision support for retail type organizations

In recent years, spatial data analysis has become a transcendental strategy for companies, because these organizations can be more competitive in the market. For this, companies need to be linked in the field of Business Intelligence and be able to create a beneficial environment to obtain a better exploitation and visualization of their information. With the proper management of the information they can generate an appropriate knowledge so that the activities related to the company improve and generate an economic benefit. In the case of companies of the retail type, the analysis of spatial data allows them to discover valuable information, on occasions this information is only detectable by observing and analyzing through maps. Today, there are a lot of tools to perform this type of analysis. However, many tools are focused on technical level users and not employees. This research paper presents an analysis of the Handytec Company and how it manages its information and how a web solution improves the visualization and analysis of spatial data and helps in making decisions for its employees. The application allows the end user to visualize spatial information through maps and graphs, execute analysis tasks without having technical knowledge with the objective of supporting decision making. © 2019 IEEE.In recent years, spatial data analysis has become a transcendental strategy for companies, because these organizations can be more competitive in the market. For this, companies need to be linked in the field of Business Intelligence and be able to create a beneficial environment to obtain a better exploitation and visualization of their information. With the proper management of the information they can generate an appropriate knowledge so that the activities related to the company improve and generate an economic benefit. In the case of companies of the retail type, the analysis of spatial data allows them to discover valuable information, on occasions this information is only detectable by observing and analyzing through maps. Today, there are a lot of tools to perform this type of analysis. However, many tools are focused on technical level users and not employees. This research paper presents an analysis of the Handytec Company and how it manages its information and how a web solution improves the visualization and analysis of spatial data and helps in making decisions for its employees. The application allows the end user to visualize spatial information through maps and graphs, execute analysis tasks without having technical knowledge with the objective of supporting decision making. © 2019 IEEE.QUIT

Lactate / pyruvate ratio in sceptic shock

info:eu-repo/semantics/nonPublishe

Measuring quality of employment: an application for Ecuador in the period from 2007 to 2017

Este trabajo investiga la evolución de la calidad del empleo en Ecuador en el periodo de 2007 a 2017. Debido al carácter multidimensional de la calidad del empleo, se construyen tres tipos de indicadores compuestos. Primero, se elabora un índice compuesto con dos tipos de ponderaciones de las dimensiones: uno que pondera de igual forma cada dimensión y otro que da mayor peso a la dimensión de remuneraciones. Segundo, reconociendo que cada mercado laboral tiene particularidades y que la ponderación de las dimensiones que representan la calidad del empleo no es el mismo para cada país, se aplica un análisis de componentes principales (ACP) policórico. Además, se calcula el indicador de calidad del empleo para diferentes sectores de actividad económica. Los resultados señalan que existe una mejora en el indicador de calidad del empleo en 2017 en relación con el nivel observado en 2007, lo que responde principalmente a los mayores niveles de estabilidad laboral y cobertura de seguridad social que experimentaron los trabajadores durante el periodo de estudio. No obstante, el porcentaje de personas con precariedad laboral sigue siendo bastante significativa, de la misma forma que se señalan marcadas diferencias en el nivel de calidad del empleo entre los diferentes sectores de actividad económica considerados. Los sectores de servicios presentan el mejor indicador, mientras que los sectores de agricultura, ganadería y pesca, y construcción registran el peor indicador.The document investigates the evolution of the quality of employment in Ecuador in the years 2007-2017. Due to the multidimensional nature of job quality, three types of composite indicators are constructed. First, a composite index is constructed with two types of dimension weights; one that weights each dimension in the same way, and another that gives greater weight to the remuneration dimension. Second, recognizing that each labor market has particularities and that the weighting of the dimensions that represent the quality of employment is not the same for each country, a Polychoric Principal Component Analysis (PCA) is applied. Additionally, the employment quality indicator is calculated for different sectors of economic activity. The results indicate that there is an improvement in the employment quality indicator in 2017 in relation to the level observed in 2007, what mainly responds to the higher levels of job stability and social security coverage that workers experienced during the study period. However, the percentage of people with job insecurity is still quite significant, in the same way that there are marked differences in the level of quality of employment between the different sectors of economic activity considered in the study. The services sectors present the best indicator, while the agriculture, livestock and fishing, and construction sectors register the worst indicator

Albumin administration improves organ function in critically ill hypoalbuminemic patients: A prospective, randomized, controlled, pilot study

SCOPUS: ar.jinfo:eu-repo/semantics/publishe

Septic shock of early or late onset: Does it matter?

SCOPUS: ar.jinfo:eu-repo/semantics/publishe