Efecto de los polifenoles sobre la microbiota intestinal en el síndrome metabólico

Durante los últimos años, el estudio de la microbiota intestinal ha surgido como un campo de investigación emergente, ya que se ha demostrado que se ve involucrada en una infinidad de procesos metabólicos que repercuten en la salud del huésped. En concreto, se ha visto que las personas que padecen alguna de las patologías asociadas al síndrome metabólico poseen una microbiota intestinal alterada que provoca un estado patológico denominado “disbiosis intestinal”. Este estado, provocado en parte por el consumo actual de dietas altas en grasa y azúcares y pobres en fibra, se caracteriza por una disminución de la diversidad microbiana y una alteración en su composición, y parece estar fuertemente relacionado con la aparición y desarrollo de las patologías del síndrome metabólico. Entre las distintas estrategias descritas para modificar la microbiota intestinal alterada, se ha observado que la suplementación de la dieta con ciertos tipos de polifenoles, como el resveratrol o las antocianinas, pueden revertir la disbiosis intestinal, ayudando a la proliferación de bacterias beneficiosas para nuestro organismo, como Akkermansia muciniphila, a la vez que disminuyen la cantidad de bacterias nocivas, como las pertenecientes al filo Firmicutes y estimulando así una mayor producción de ácidos grasos de cadena corta, como el butirato. En este trabajo se ha llevado a cabo una revisión de la bibliografía disponible sobre la capacidad de diversos polifenoles (no flavonoides, flavonoles y flavanoles) de contrarrestar el efecto de una dieta occidental sobre la microbiota intestinal, revirtiendo los efectos del síndrome metabólico, así como un estudio de los principales mecanismos implicados en este proceso.In recent years, the study of the intestinal microbiota has emerged as a field of research. Since it has been shown that it is involved in an infinite number of metabolic processes that affect the health of the host. Specifically, people suffering from any of the pathologies associated with the metabolic syndrome have an altered intestinal microbiota that causes a medical state called "intestinal dysbiosis". This state is caused partially due to current consumption of diets high in fat and sugars, and poor in fiber. Consequently, decreasing microbial diversity and altering its composition. Strongly correlating with the appearance and development of metabolic syndrome pathologies. Among the different strategies described to modify the altered intestinal microbiota, it has been observed that dietary supplementation with certain types of polyphenols, such as resveratrol or anthocyanins can reverse intestinal dysbiosis. Therefore, promoting the proliferation of beneficial bacteria for our body, like Akkermansia muciniphila, while reducing the number of harmful bacteria such as those belonging to the Firmicutes phylum. As a result, stimulating a greater production of short chain fatty acids as butyrate. This paper reviews the available literature on various polyphenols (non-flavonoids, flavonols and flavanols) and their ability to counteract the effect of a western diet on the intestinal microbiota. Focusing on reversing the effects of the metabolic syndrome, as well as analyzing the main mechanism involved in this process

Inappropriate Hospital Admission According to Patient Intrinsic Risk Factors: an Epidemiological Approach

Background: Inappropriate hospital admissions compromise the efficiency of the health care system. This work analyzes, for the first time, the prevalence of inappropriate admission and its association with clinical and epidemiological patient characteristics. Objectives: To estimate the prevalence, associated risk factors, and economic impact of inappropriate hospital admissions. Design and Participants: This was a cross-sectional observational study of all hospitalized patients in a high complexity hospital of over 901 beds capacity in Spain. The prevalence of inappropriate admission and its causes, the association of inappropriateness with patients’ intrinsic risk factors (IRFs), and associated financial costs were analyzed with the Appropriateness Evaluation Protocol in a multivariate model. Main Measures and Key Results: A total of 593 patients were analyzed, and a prevalence of inappropriate admissions of 11.9% (95% CI: 9.5 to 14.9) was found. The highest number of IRFs for developing health care-related complications was associated with inappropriateness, which was more common among patients with 1 IRF (OR [95% CI]: 9.68 [3.6 to 26.2.] versus absence of IRFs) and among those with surgical admissions (OR [95% CI]: 1.89 [1.1 to 3.3] versus medical admissions). The prognosis of terminal disease reduced the risk (OR [95% CI]: 0.28 [0.1 to 0.9] versus a prognosis of full recovery based on baseline condition). Inappropriate admissions were responsible for 559 days of avoidable hospitalization, equivalent to €17,604.6 daily and €139,076.4 in total, mostly attributable to inappropriate emergency admissions (€96,805.3). Conclusions: The prevalence of inappropriate admissions is similar to the incidence found in previous studies and is a useful indicator in monitoring this kind of overuse. Patients with a moderate number of comorbidities were subject to a higher level of inappropriateness. Inappropriate admission had a substantial and avoidable financial impact

Targeting the undruggable: exploiting neomorphic features of fusion oncoproteins in childhood sarcomas for innovative therapies

While sarcomas account for approximately 1% of malignant tumors of adults, they are particularly more common in children and adolescents affected by cancer. In contrast to malignancies that occur in later stages of life, childhood tumors, including sarcoma, are characterized by a striking paucity of somatic mutations. However, entity-defining fusion oncogenes acting as the main oncogenic driver mutations are frequently found in pediatric bone and soft-tissue sarcomas such as Ewing sarcoma (EWSR1-FLI1), alveolar rhabdomyosarcoma (PAX3/7-FOXO1), and synovial sarcoma (SS18-SSX1/2/4). Since strong oncogene-dependency has been demonstrated in these entities, direct pharmacological targeting of these fusion oncogenes has been excessively attempted, thus far, with limited success. Despite apparent challenges, our increasing understanding of the neomorphic features of these fusion oncogenes in conjunction with rapid technological advances will likely enable the development of new strategies to therapeutically exploit these neomorphic features and to ultimately turn the \textquotedblundruggable\textquotedbl into first-line target structures. In this review, we provide a broad overview of the current literature on targeting neomorphic features of fusion oncogenes found in Ewing sarcoma, alveolar rhabdomyosarcoma, and synovial sarcoma, and give a perspective for future developments. Graphical abstract Scheme depicting the different targeting strategies of fusion oncogenes in pediatric fusion-driven sarcomas. Fusion oncogenes can be targeted on their DNA level (1), RNA level (2), protein level (3), and by targeting downstream functions and interaction partners (4)

Prevalence, characteristics, and impact of adverse events in 34 Madrid hospitals. The ESHMAD study

Introduction: Adverse Events (AE) are one of the main problems in healthcare. Therefore, many policies have been developed worldwide to mitigate their im pact. The Patient Safety Incident Study in Hospitals in the Community of Madrid (ESHMAD) measures the results of them in the region. Methods: Cross-sectional study, conducted in May 2019, in hospitalised patients in 34 public hospitals using the Harvard Medical Practice Study methodology. A logistic regression model was carried out to study the association of the variables with the presence of AE, calibrated and adjusted by patient. Results: A total of 9975 patients were included, estimating a prevalence of AE of 11.9%. A higher risk of AE was observed in patients with surgical procedures (OR[CI95%]: 2.15[1.79 to 2.57], vs. absence), in Intensive Care Units (OR[CI95%]: 1.60[1.17 to 2.17], vs. Medical) and in hospitals of medium complexity (OR[CI95%]: 1.45[1.12 to 1.87], vs. low complexity). A 62.6% of AE increased the length of the stay or it was the cause of admission, and 46.9% of AE were considered prevent able. In 11.5% of patients with AE, they had contributed to their death. Conclusions: The prevalence of AE remains similar to the previously estimated one in studies developed with the same methodology. AE keep leading to longer hospital stays, contributing to patient's death, showing that it is necessary to put focus on patient safety again. A detailed analysis of these events has enabled the detection of specific areas for improvement according to the type of care, centre and patient

Avoidable Adverse Events Related to Ignoring the Do-Not-Do Recommendations: A Retrospective Cohort Study Conducted in the Spanish Primary Care Setting

Objective This study aimed to measure the frequency and severity of avoidable adverse events (AAEs) related to ignoring do-not-do recommendations (DNDs) in primary care. Methods A retrospective cohort study analyzing the frequency and severity of AAEs related to ignoring DNDs (7 from family medicine and 3 from pediatrics) was conducted in Spain. Data were randomly extracted from computerized electronic medical records by a total of 20 general practitioners and 5 pediatricians acting as reviewers; data between February 2018 and September 2019 were analyzed. Results A total of 2557 records of adult and pediatric patients were reviewed. There were 1859 (72.7%) of 2557 (95% confidence interval [CI], 71.0%-74.4%) DNDs actions in 1307 patients (1507 were performed by general practitioners and 352 by pediatricians). Do-not-do recommendations were ignored more often in female patients (P < 0.0001). Sixty-nine AAEs were linked to ignoring DNDs (69/1307 [5.3%]; 95% CI, 4.1%-6.5%). Of those, 54 (5.1%) of 1062 were in adult patients (95% CI, 3.8%-6.4%) and 15 (6.1%) of 245 in pediatric patients (95% CI, 3.1%-9.1%). In adult patients, the majority of AAEs (51/901 [5.7%]; 95% CI, 4.2%-7.2%) occurred in patients 65 years or older. Most AAEs were characterized by temporary minor harm both in adult patients (28/54 [51.9%]; 95% CI, 38.5%-65.2%) and pediatric patients (15/15 [100%]). Conclusions These findings provide a new perspective about the consequences of low-value practices for the patients and the health care systems. Ignoring DNDs could place patients at risk, and their safety might be unnecessarily compromised

t(12;18)(p13;q12)

Review on t(12;18)(p13;q12), with data on clinics, and the genes involved

Decontamination of filtering facepiece respirators using a low-temperature-steam–2%-formaldehyde sterilization process during a pandemic: a safe alternative for re-use

Background The coronavirus disease 2019 pandemic has caused problems with respirator supplies. Re-use may minimize the impact of the shortage, but requires the availability of an efficient and safe decontamination method. Aim To determine whether low-temperature-steam–2%-formaldehyde (LTSF) sterilization is effective, preserves the properties of filtering facepiece (FFP) respirators and allows safe re-use. Methods Fourteen unused FFP2, FFP3 and N95 respirator models were subjected to two cycles of decontamination cycles. After the second cycle, each model was inspected visually and accumulated residual formaldehyde levels were analysed according to EN 14180. After one and two decontamination cycles, the fit factor (FF) of each model was tested, and penetration tests with sodium chloride aerosols were performed on five models. Findings Decontamination physically altered three of the 14 models. All of the residual formaldehyde values were below the permissible threshold. Irregular decreases and increases in FF were observed after each decontamination cycle. In the sodium chloride aerosol penetration test, three models obtained equivalent or superior results to those of the FFP classification with which they were marketed, both at baseline and after one and two cycles of decontamination, and two models had lower filtering capacity. Conclusion One and two decontamination cycles using LTSF did not alter the structure of most (11/14) respirators tested, and did not degrade the fit or filtration capacity of any of the analysed respirators. The residual formaldehyde levels complied with EN 14180. This reprocessing method could be used in times of shortage of personal protective equipment

Genetic variation at MECOM, TERT, JAK2 and HBS1L-MYB predisposes to myeloproliferative neoplasms

Clonal proliferation in myeloproliferative neoplasms (MPN) is driven by somatic mutations in JAK2, CALR or MPL, but the contribution of inherited factors is poorly characterized. Using a three-stage genome-wide association study of 3,437 MPN cases and 10,083 controls, we identify two SNPs with genome-wide significance in JAK2V617F-negative MPN: rs12339666 (JAK2; meta-analysis P=1.27 × 10−10) and rs2201862 (MECOM; meta-analysis P=1.96 × 10−9). Two additional SNPs, rs2736100 (TERT) and rs9376092 (HBS1L/MYB), achieve genome-wide significance when including JAK2V617F-positive cases. rs9376092 has a stronger effect in JAK2V617F-negative cases with CALR and/or MPL mutations (Breslow–Day P=4.5 × 10−7), whereas in JAK2V617F-positive cases rs9376092 associates with essential thrombocythemia (ET) rather than polycythemia vera (allelic χ2 P=7.3 × 10−7). Reduced MYB expression, previously linked to development of an ET-like disease in model systems, associates with rs9376092 in normal myeloid cells. These findings demonstrate that multiple germline variants predispose to MPN and link constitutional differences in MYB expression to disease phenotype