Validation of a novel and accurate ApoE4 assay for automated chemistry analyzers

The allele ε4 of the apolipoprotein E gene (APOE ε4) is the major genetic risk factor for non-dominantly inherited Alzheimer's Disease (AD). Current techniques for APOE ε4 carriers identification show good accuracy but have several disadvantages that limit its implementation in a clinical laboratory. These include the need for sample preprocessing, poor automation, low throughput, requirement of additional equipment, and high cost. We followed ISO 13485 guidelines to validate the e4Risk test, a new latex-enhanced immunoturbidimetric blood assay for apolipoprotein E4 (ApoE4) determination in human plasma samples. The test showed high performance in terms of lot to lot variability, precision, interferences, reagents stability, prozone, and detectability. Furthermore, diagnostic accuracy is almost equal (99%) to the gold standard, APOE ε4 genotyping by polymerase chain reaction (PCR). Furthermore, we demonstrated that the e4Risk test can be adapted to any clinical chemistry analyzer, including the high throughput analyzers present in most hospitals and clinical laboratories. The e4Risk test versatility, low cost, and easiness provides an excellent solution for APOE ε4 carriers identification using the same blood sample drawn for biochemical diagnostic work-up of AD patients, which can have important advantages for patient stratification in clinical trials, preventative strategies for AD, and clinical assessment of risk for brain amyloidosis.This research was fully funded by Biocross and did not receive any other specific grant from funding agencies in the public, commercial, or not-for-profit sectors for this research.S

CONUT: A Useful Alarm of Malnutrition in the Centralized Laboratory of a Spanish Hospital

Background: Hospital malnutrition, usually secondary to various diseases and their treatments, is an important problem in our clinical practice. For its proper assessment, it is crucial to use a nutritional alert system, such as the CONUT (COntrol NUTrition) program; this tool uses 3 analytical parameters: serum albumin, total cholesterol, and total lymphocyte count. Objective: The current study assessed the results of the implementation of this program in the University Hospital Ramón y Cajal. Methods: The CONUT program has been used in the University Hospital Ramón y Cajal since 2013. This retrospective study, throughout 2016, was conducted in the Central Laboratory of Chemical Biochemistry at the University Hospital Ramón y Cajal. All blood tests with serum albumin, total cholesterol, and total lymphocyte count were studied. The degree of malnutrition was assessed using the scale of normal (=0), mild (=4), moderate (=8), and severe (=12). Results: In 2016, there were 405406 analytics performed in the laboratory of University Hospital Ramón y Cajal. The CONUT tool was applied to 3.64% of them (14741 analytics). In the outpatient setting, the highest malnutrition index comprised patients from the liver transplant consultation department, followed by the cardiology, rheumatology, and oncology departments. With inpatients, the hematology, cardiology, and endocrinology departments showed the most severe malnutrition index. Conclusion: The CONUT system seemed to provide useful information about the cohort of the studied hospital. The results showed that 94% of the patients were not classified with malnutrition, there was no gender predilection, and they were younger than the rest. Patients with more severe malnutrition were usually older and male

Correction : Chaparro et al. Incidence, Clinical Characteristics and Management of Inflammatory Bowel Disease in Spain: Large-Scale Epidemiological Study. J. Clin. Med. 2021, 10, 2885

The authors wish to make the following corrections to this paper [...]

Incidence, Clinical Characteristics and Management of Inflammatory Bowel Disease in Spain : Large-Scale Epidemiological Study

(1) Aims: To assess the incidence of inflammatory bowel disease (IBD) in Spain, to describe the main epidemiological and clinical characteristics at diagnosis and the evolution of the disease, and to explore the use of drug treatments. (2) Methods: Prospective, population-based nationwide registry. Adult patients diagnosed with IBD-Crohn's disease (CD), ulcerative colitis (UC) or IBD unclassified (IBD-U)-during 2017 in Spain were included and were followed-up for 1 year. (3) Results: We identified 3611 incident cases of IBD diagnosed during 2017 in 108 hospitals covering over 22 million inhabitants. The overall incidence (cases/100,000 person-years) was 16 for IBD, 7.5 for CD, 8 for UC, and 0.5 for IBD-U; 53% of patients were male and median age was 43 years (interquartile range = 31-56 years). During a median 12-month follow-up, 34% of patients were treated with systemic steroids, 25% with immunomodulators, 15% with biologics and 5.6% underwent surgery. The percentage of patients under these treatments was significantly higher in CD than UC and IBD-U. Use of systemic steroids and biologics was significantly higher in hospitals with high resources. In total, 28% of patients were hospitalized (35% CD and 22% UC patients, p < 0.01). (4) Conclusion: The incidence of IBD in Spain is rather high and similar to that reported in Northern Europe. IBD patients require substantial therapeutic resources, which are greater in CD and in hospitals with high resources, and much higher than previously reported. One third of patients are hospitalized in the first year after diagnosis and a relevant proportion undergo surgery

Calidad en las empresas del sector agentes de carga para el comercio internacional en el Perú

El presente estudio de investigación permitió conocer a profundidad el nivel de cumplimiento de los nueves factores del TQM en las empresas del sector agentes de carga para el comercio internacional en el Perú. A su vez se utilizaron herramientas para medir el efecto y la correlación que existen entre las empresas que cuentan con un SGC y las que no lo tienen, todo ello a través de las diferencias significativas encontradas en cada pregunta del cuestionario de calidad. Este modelo implementado por Benzaquen (2018) en relación a los nueve factores del TQM aplicados en las empresas, fue utilizado como base para realizar mediciones de la administración de la calidad total a través de un cuestionario de evaluación de la calidad en el sector. Para esta técnica se utilizó la escala de Likert, la cual está dirigida a los mandos medios y altos de las 144 empresas encuestadas. El estudio se realizó bajo un enfoque y diseño transaccional y no experimental. Los resultados obtenidos a través de las herramientas utilizadas en el presente estudio de investigación permitieron comprobar y validar que existen diferencias significativas en los nueve factores del TQM entre empresas que tenían un SGC frente a aquellas que no la tenían, lo cual significa que existe un impacto altamente positivo en los sistemas de gestión de la calidad en relación al nivel de calidad en las empresas del sector agentes de carga para el comercio internacional en el Perú.This research study allowed to know in depth the level of compliance with the nine factors of the TQM in the companies of the sector of freight forwarders of international trade that operate in Peru. In turn, tools were used to measure the effect and correlation that exist between companies that have a QMS and those that do not, all through the significant differences found in each question of the quality questionnaire. This model implemented by Benzaquen (2018) in relation to the nine TQM factors applied in companies, was used as a basis to measure total quality management through a quality evaluation questionnaire in the sector. For this technique, the Likert scale was used, which is aimed at the middle and senior managers of the 144 surveyed companies. The study was carried out under a non-experimental and non-experimental approach and design. The results obtained through the tools used in this research study allowed us to verify and validate that there are significant differences in the nine TQM factors between companies that had a QMS versus those that did not, which means that there is an impact highly positive in quality management systems in relation to the level of quality in companies in the international trade freight forwarders sector operating in Peru

Prevalencia del déficit de vitamina D y su relación con la hormona paratiroidea

Evaluamos la prevalencia del déficit de la 25-hidroxivitamina D (25-(OH)D) en nuestro entorno, en función de la estación del año, el sexo y la edad de los sujetos. Así mismo, analizamos su relación con los niveles de la hormona paratiroidea (PTH)

Prevalence of vitamin D deficiency and association with parathyroid hormone

We evaluated the prevalence of 25-hydroxyvitamin D (25-(OH)D) deficiency in our setting according to season, sex, and age. We also studied the association with parathyroid hormone (PTH) levels

Serum microRNAs are key predictors of long‐term heart failure and cardiovascular death after myocardial infarction

Abstract Background Patients with acute myocardial infarction (MI) are at high risk of upcoming events, in particular heart failure (HF), but reliable stratification methods are lacking. Our goal was to evaluate the potential role of circulating miRNAs as prognostic biomarkers in patients presenting with MI. Methods and results We conducted a prospective study among 311 consecutive patients hospitalized with MI (65% ST‐segment elevation MI & median age of 55 years) with long‐term follow‐up. An initial screening was conducted to select candidate miRNAs, with subsequent study of 14 candidate miRNAs. The primary outcome was the composite of hospital admission for HF or cardiovascular death. During a mean follow‐up of 2.1 years miR‐21‐5p, miR‐23a‐3p, miR27b‐3p, miR‐122‐5p, miR210‐3p, and miR‐221‐3p reliably predicted the primary outcome. Multivariate Cox regression analyses highlighted that miR‐210‐3p [hazard ratio (HR) 2.65 per 1 SD increase, P < 0.001], miR‐23a‐3p (HR 2.11 per 1 SD increase, P < 0.001), and miR‐221‐3p (HR 2.03 per 1 SD increase, P < 0.001) were able to accurately predict the primary outcome, as well as cardiovascular death, HF hospitalizations, and long‐term New York Heart Association (NYHA) functional class. These three miRNAs clearly improved the performance of multivariate clinical models: ΔC‐statistic = 0.10 [95% confidence interval (CI), 0.03–0.17], continuous net reclassification index = 34.8% (95%CI, 5.8–57.4%), and integrated discrimination improvement (P < 0.001). Conclusions This is the largest study evaluating the prognostic value of circulating miRNAs for HF‐related events among patients with MI. We show that several miRNAs predict HF hospitalizations, cardiovascular mortality, and poor long‐term NYHA status and improve current risk prediction methods

Crohn's Disease Disturbs the Immune Properties of Human Adipose-Derived Stem Cells Related to Inflammasome Activation

Crohn's disease (CD) is characterized by the expansion of mesenteric fat, also known as “creeping fat.” We explored the plasticity and immune properties of adipose-derived stem cells (ASCs) in the context of CD as potential key players in the development of creeping fat. Mesenteric CD-derived ASCs presented a more proliferative, inflammatory, invasive, and phagocytic phenotype than equivalent cells from healthy donors, irrespective of the clinical stage. Remarkably, ASCs from the subcutaneous depot of patients with CD also showed an activated immune response that was associated with a reduction in their immunosuppressive properties. The invasive phenotype of mesenteric CD ASCs was governed by an inflammasome-mediated inflammatory state since blocking inflammasome signaling, mainly the secretion of interleukin-1β, reversed this characteristic. Thus, CD alters the biological functions of ASCs as adipocyte precursors, but also their immune properties. Selection of ASCs with the best immunomodulatory properties is advocated for the success of cell-based therapies

Adipose stem cells from patients with Crohn's disease show a distinctive DNA methylation pattern

Crohn's disease (CD) is characterized by persistent inflammation and ulceration of the small or large bowel, and expansion of mesenteric adipose tissue, termed creeping fat (CF). We previously demonstrated that human adipose-derived stem cells (hASCs) from CF of patients with CD exhibit dysfunctional phenotypes, including a pro-inflammatory profile, high phagocytic capacity, and weak immunosuppressive properties. Importantly, these phenotypes persist in patients in remission and are found in all adipose depots explored including subcutaneous fat. We hypothesized that changes in hASCs are a consequence of epigenetic modifications. We applied epigenome-wide profiling with a methylation array (Illumina EPIC/850k array) and gene expression analysis to explore the impact of CD on the methylation signature of hASCs isolated from the subcutaneous fat of patients with CD and healthy controls (n = 7 and 5, respectively; cohort I). Differentially methylated positions (p value cutoff < 1 × 10 −4 and ten or more DMPs per gene) and regions (inclusion threshold 0.2, p value cutoff < 1 × 10 −2 and more than 2 DMRs per gene) were identified using dmpfinder and Bumphunter (minfi), respectively. Changes in the expression of differentially methylated genes in hASCs were validated in a second cohort (n = 10/10 inactive and active CD and 10 controls; including patients from cohort I) and also in peripheral blood mononuclear cells (PBMCs) of patients with active/inactive CD and of healthy controls (cohort III; n = 30 independent subjects). We found a distinct DNA methylation landscape in hASCs from patients with CD, leading to changes in the expression of differentially methylated genes involved in immune response, metabolic, cell differentiation, and development processes. Notably, the expression of several of these genes in hASCs and PBMCs such as tumor necrosis factor alpha (TNFA) and PR domain zinc finger protein 16 (PRDM16) were not restored to normal (healthy) levels after disease remission. hASCs of patients with CD exhibit a unique DNA methylation and gene expression profile, but the expression of several genes are only partially restored in patients with inactive CD, both in hASCs and PBMCs. Understanding how CD shapes the functionality of hASCs is critical for investigating the complex pathophysiology of this disease, as well as for the success of cell-based therapies. Human adipose-stem cells isolated from subcutaneous fat of patients with Crohn's disease exhibit an altered DNA methylation pattern and gene expression profile compared with those isolated from healthy individuals, with immune system, cell differentiation, metabolic and development processes identified as the main pathways affected. Interestingly, the gene expression of several genes involved in these pathways is only partially restored to control levels in patients with inactive Crohn's disease, both in human adipose-stem cells and peripheral blood mononuclear cells. Understanding how Crohn's disease shapes the functionality of human adipose-stem cells is critical for investigating the complex pathophysiology of this disease, as well as for the success of cell-based therapies