Biomarkers of Chronic Inflammatory State in Uremia and Cardiovascular Disease

Cardiovascular disease is the leading cause of death in the general population; traditional risk factors seem inadequate to explain completely the remarkable prevalence of cardiovascular mortality and morbidity observed in the uremic population. A role for chronic inflammation has been well established in the development of atherosclerotic disease, and, on the basis of these observations, atherosclerosis might be considered an inflammatory disease. Inflammation has been implicated in the etiology of coronary artery disease in the general population, and traditional inflammatory biomarkers such as C-reactive protein (CRP) and interleukin-6 (IL-6) have been shown to predict cardiovascular events in both symptomatic and asymptomatic individuals as well as those in the uremic population. Later on, new nontraditional markers were related to the risk of cardiovascular morbidity and mortality in general and in uremic population. As a consequence of the expanding research base and availability of assays, the number of inflammatory marker tests ordered by clinicians for cardiovascular disease (CVD) risk prediction has grown rapidly and several commercial assays have become available. So, up to now we can consider that several new nontraditional markers as CD40-CD40 ligand system and pentraxin-3 seem to be significant features of cardiovascular disease in general and in ESRD population

Adherence to riluzole therapy in patients with amyotrophic lateral sclerosis in three Italian regions-The CAESAR study

Introduction: Amyotrophic lateral sclerosis (ALS) is a rare neurodegenerative disease. Riluzole may increase survival and delay the need for mechanical ventilation. The CAESAR project ('Comparative evaluation of the efficacy and safety of drugs used in rare neuromuscular and neurodegenerative diseases', FV AIFA project 2012-2013-2014) involves evaluating prescribing patterns, and analysing effectiveness and comparative safety of drugs, in patients with neurodegenerative diseases. The aim of this study is to evaluate adherence to riluzole in patients with ALS during the first year of use, identifying adherence clusters. Methods: A retrospective cohort study was conducted using administrative data from Latium, Tuscany, and Umbria. We identified subjects with a new diagnosis of ALS between 2014 and 2019, with the first dispensation of riluzole within 180 days of diagnosis. We considered a two-year look-back period for the characterization of patients, and we followed them from the date of first dispensing of riluzole for 1 year. We calculated 12 monthly adherence measures, through a modified version of the Medication Possession Ratio, estimating drug coverage with Defined Daily Dose. Adherence trajectories were identified using a three-step method: (1) calculation of statistical measures; (2) principal component analysis; (3) cluster analysis. Patient characteristics at baseline and during follow-up were described and compared between adherence groups identified. Results: We included 264 ALS patients as new users of riluzole in Latium, 344 in Tuscany, and 63 in Umbria. We observed a higher frequency of males (56.2%) and a mean age of 67.4 (standard deviation, SD, 10.4) in the overall population. We identified two clusters in all regions: one more numerous, including adherent patients (60%, 74%, 88%, respectively), and another one including patients who discontinued therapy (40%, 26%, 12%, respectively). In Tuscany patients discontinuing riluzole more frequently died (28.6% vs. 15.4%, p-value <0.01). Additionally, low-adherers had a higher frequency of central nervous system disorders (69.0% vs. 52.5%, p-value 0.01), and a greater use of non-pharmacological treatments (p-values ≤0.01 for invasive ventilation and tracheostomy). We did not observe any differences in Lazio, whereas in Umbria we observed a higher use of drugs for dementia-related psychiatric problems among low-adherers (57.1% vs. 7.8%, respectively, p-value <0.01), although with small numbers. Conclusion: Most ALS patients who start riluzole adhere to therapy during the first year. Patients who discontinue therapy early show greater fragility and mortality

Non-invasive sensors for wound monitoring and therapy

Chronic wounds such as diabetic foot ulcers and venous leg ulcers affect in Europe more than 10 million people, a number that is expected to grow due to the aging of the population. Sensors can be a valid tool to improve the quality of healthcare for wound monitoring and management. The integration of sensor data within health information and decision support systems may allow the delivery of personalized treatments at decreased cost. The EU FP7 SWAN-iCare project is developing a negative-pressure device associated with non-invasive sensors capable to monitor some physiological parameters related to the wound status, such as pH, temperature and transepidermal water loss. These sensors will help to provide personalized therapies to patients and check the effectiveness of treatments remotely

Intervenciones colaborativas durante la pandemia en la Tecnicatura Universitaria en Asistencia Odontológica

La Tecnicatura Universitaria en Asistencia Odontológica, es una carrera que dicta la FOUNLP. El Plan de estudios posee una estructura curricular organizada en áreas de formación. Las evaluaciones finales de cada asignatura se realizan en forma presencial. El 12 de marzo de 2020, a través del decreto de necesidad y urgencia 260 de 2020 (Presidencia de La Nación), se amplío la emergencia pública en materia sanitaria establecida por la ley 27541, en virtud de la pandemia declarada por la OMS en relación con el Covid-19. En el caso de la FOUNLP, en menos de una semana, las autoridades de la misma comenzaron a evaluar la intensificación de la utilización de las TIC para poder implementar el calendario académico 2020. Para la realización de los exámenes finales en dicha tecnicatura, se implementaron talleres de acompañamiento de forma optativa, cuyo objetivo esencial era acompañar a las estudiantes en la construcción del conocimiento con prácticas de estudio en función a las competencias y contenidos disciplinares de cada asignatura. La experiencia fue llevada a cabo por la asignatura de los días lunes en relación con la implementación de estos talleres y el importante vínculo generado entre alumnos y docentes a pesar de la no presencialidad.Especialización en Docencia Universitari

CA-125 early dynamics to predict overall survival in women with newly diagnosed advanced ovarian cancer based on meta-analysis data

(1) Background: Cancer antigen 125 (CA-125) is a protein produced by ovarian cancer cells that is used for patients’ monitoring. However, the best ways to analyze its decline and prognostic role are poorly quantified. (2) Methods: We leveraged individual patient data from the Gynecologic Cancer Intergroup (GCIG) meta-analysis (N = 5573) to compare different approaches summarizing the early trajectory of CA-125 before the prediction time (called the landmark time) at 3 or 6 months after treatment initiation in order to predict overall survival. These summaries included observed and estimated measures obtained by a linear mixed model (LMM). Their performances were evaluated by 10-fold cross-validation with the Brier score and the area under the ROC (AUC). (3) Results: The estimated value and the last observed value at 3 months were the best measures used to predict overall survival, with an AUC of 0.75 CI 95% [0.70; 0.80] at 24 and 36 months and 0.74 [0.69; 0.80] and 0.75 [0.69; 0.80] at 48 months, respectively, considering that CA-125 over 6 months did not improve the AUC, with 0.74 [0.68; 0.78] at 24 months and 0.71 [0.65; 0.76] at 36 and 48 months. (4) Conclusions: A 3-month surveillance provided reliable individual information on overall survival until 48 months for patients receiving first-line chemotherapy

Assessing disease activity of rheumatoid arthritis patients and drug-utilization patterns of biologic disease-modifying antirheumatic drugs in the Tuscany region, Italy

Introduction: The disease activity associated with the drug-utilization patterns of biologic Disease Modifying Anti-Rheumatic Drugs (DMARDs) is poorly investigated in real-world studies on rheumatoid arthritis (RA) patients. To investigate the relationship between biologic DMARD initiation/discontinuations in RA patients identified in the healthcare administrative databases of Tuscany and the Disease Activity Score 28 (DAS28) reported in the medical charts.Methods: This retrospective population-based study included RA’s first-ever biologic DMARD users of the Pisa University Hospital from 2014 to 2016. Patients were followed up until 31 December 2019. We evaluated the DAS28 recorded before (T0) and after (T1) the biologic DMARD initiation and before (TD0) and after (TD1) discontinuations. Patients were classified as “off-target” (DAS28 > 3.2) or “in-target” (DAS28 ≤ 3.2). We described the disease activity trends at initiation and discontinuation.Results: Ninety-five users were included (73 women, mean age 59.6). Among 70 patients (74%) with at least three DAS28 measures, 28 (40.0%) were off-target at T0 and 38 (54.3%) in-target at T1. Thirty-three (47%) patients had at least one discontinuation, among those with at least three DAS28 assessments. In the disease activity trend, disease stability or improvement was observed in 28 out of 37 (75.7%) patients at initiation and in 24 out of 37 (64.9%) at discontinuation.Discussion: Biologic DMARD discontinuations identified in the healthcare administrative databasese of Tuscany are frequently observed in situations of controlled RA disease. Further studies are warranted to confirm that these events can be used in studies using healthcare administrative databases as proxies of treatment effectiveness

Escuchamos a nuestros hijos rechinar los dientes III

La Universidad Nacional de La Plata, a través de sus Unidades Ejecutoras, brinda un abanico muy amplio de posibles trabajos compartidos junto a diferentes comunidades fuera del ámbito institucional. Dicho proceso de articulación da lugar a la disminución de distancias entre el desarrollo de contenidos áulicos y los ambientes que se encuentran más allá de cada casa de estudios. A continuación realizaremos una breve descripción de acciones desarrolladas en el marco del proyecto “Escuchamos a nuestros hijos rechinar los dientes III” que viene desarrollándose desde del año 2017 desde la Secretaría de Planificación y Extensión Universitaria de la Facultad de Odontología de UNLP, con muy buena respuesta de las comunidades que fueron comprometidas hasta el momento. El recorrido por distintas escuelas primarias y jardines de infantes ha sido extenso con excelentes devoluciones por parte de sus responsables. Si bien la temática del bruxismo no es tratada frecuentemente en los programas preventivos, la repercusión y el interés manifestado por los responsables de los niños, nos moviliza a continuar trabajando en esa línea. Especialmente por la gran cantidad de consultas realizadas sobre las particularidades del bruxismo y de experiencias por ellos compartidas, enlazadas a la problemática actual de pandemia por Covid 19.Facultad de Odontologí

Multi-messenger observations of a binary neutron star merger

On 2017 August 17 a binary neutron star coalescence candidate (later designated GW170817) with merger time 12:41:04 UTC was observed through gravitational waves by the Advanced LIGO and Advanced Virgo detectors. The Fermi Gamma-ray Burst Monitor independently detected a gamma-ray burst (GRB 170817A) with a time delay of ~1.7 s with respect to the merger time. From the gravitational-wave signal, the source was initially localized to a sky region of 31 deg2 at a luminosity distance of 40+8-8 Mpc and with component masses consistent with neutron stars. The component masses were later measured to be in the range 0.86 to 2.26 Mo. An extensive observing campaign was launched across the electromagnetic spectrum leading to the discovery of a bright optical transient (SSS17a, now with the IAU identification of AT 2017gfo) in NGC 4993 (at ~40 Mpc) less than 11 hours after the merger by the One- Meter, Two Hemisphere (1M2H) team using the 1 m Swope Telescope. The optical transient was independently detected by multiple teams within an hour. Subsequent observations targeted the object and its environment. Early ultraviolet observations revealed a blue transient that faded within 48 hours. Optical and infrared observations showed a redward evolution over ~10 days. Following early non-detections, X-ray and radio emission were discovered at the transient’s position ~9 and ~16 days, respectively, after the merger. Both the X-ray and radio emission likely arise from a physical process that is distinct from the one that generates the UV/optical/near-infrared emission. No ultra-high-energy gamma-rays and no neutrino candidates consistent with the source were found in follow-up searches. These observations support the hypothesis that GW170817 was produced by the merger of two neutron stars in NGC4993 followed by a short gamma-ray burst (GRB 170817A) and a kilonova/macronova powered by the radioactive decay of r-process nuclei synthesized in the ejecta

<i>GRIN2A</i>-related disorders:genotype and functional consequence predict phenotype

Alterations of the N-methyl-d-aspartate receptor (NMDAR) subunit GluN2A, encoded by GRIN2A, have been associated with a spectrum of neurodevelopmental disorders with prominent speech-related features, and epilepsy. We performed a comprehensive assessment of phenotypes with a standardized questionnaire in 92 previously unreported individuals with GRIN2A-related disorders. Applying the criteria of the American College of Medical Genetics and Genomics to all published variants yielded 156 additional cases with pathogenic or likely pathogenic variants in GRIN2A, resulting in a total of 248 individuals. The phenotypic spectrum ranged from normal or near-normal development with mild epilepsy and speech delay/apraxia to severe developmental and epileptic encephalopathy, often within the epilepsy-aphasia spectrum. We found that pathogenic missense variants in transmembrane and linker domains (misTMD+Linker) were associated with severe developmental phenotypes, whereas missense variants within amino terminal or ligand-binding domains (misATD+LBD) and null variants led to less severe developmental phenotypes, which we confirmed in a discovery (P = 10-6) as well as validation cohort (P = 0.0003). Other phenotypes such as MRI abnormalities and epilepsy types were also significantly different between the two groups. Notably, this was paralleled by electrophysiology data, where misTMD+Linker predominantly led to NMDAR gain-of-function, while misATD+LBD exclusively caused NMDAR loss-of-function. With respect to null variants, we show that Grin2a+/- cortical rat neurons also had reduced NMDAR function and there was no evidence of previously postulated compensatory overexpression of GluN2B. We demonstrate that null variants and misATD+LBD of GRIN2A do not only share the same clinical spectrum (i.e. milder phenotypes), but also result in similar electrophysiological consequences (loss-of-function) opposing those of misTMD+Linker (severe phenotypes; predominantly gain-of-function). This new pathomechanistic model may ultimately help in predicting phenotype severity as well as eligibility for potential precision medicine approaches in GRIN2A-related disorders