Newborn Screening for Sickle Cell Disease in Catalonia between 2015 and 2022-Epidemiology and Impact on Clinical Events

Hemoglobinopathies; Newborn screening; Sickle cell diseaseHemoglobinopatías; Cribado neonatal; DrepanocitosisHemoglobinopaties; Cribratge neonatal; DrepanocitosiAbstract In 2015, Catalonia introduced sickle cell disease (SCD) screening in its newborn screening (NBS) program along with standard-of-care treatments like penicillin, hydroxyurea, and anti-pneumococcal vaccination. Few studies have assessed the clinical impact of introducing NBS programs on SCD patients. We analyzed the incidence of SCD and related hemoglobinopathies in Catalonia and the change in clinical events occurring after introducing NBS. Screening 506,996 newborns from 2015 to 2022, we conducted a retrospective multicenter study including 100 screened (SG) and 95 unscreened (UG) SCD patients and analyzed SCD-related clinical events over the first six years of life. We diagnosed 160 cases of SCD, with an incidence of 1 in 3169 newborns. The SG had a significantly lower median age at diagnosis (0.1 y vs. 1.68 y, p < 0.0001), and initiated penicillin prophylaxis (0.12 y vs. 1.86 y, p < 0.0001) and hydroxyurea treatment earlier (1.42 y vs. 4.5 y, p < 0.0001). The SG experienced fewer median SCD-related clinical events (vaso-occlusive crisis, acute chest syndrome, infections of probable bacterial origin, acute anemia requiring transfusion, acute splenic sequestration, and pathological transcranial Doppler echography) per year of follow-up (0.19 vs. 0.77, p < 0.0001), a reduced number of annual emergency department visits (0.37 vs. 0.76, p < 0.0001), and fewer hospitalizations (0.33 vs. 0.72, p < 0.0001). SCD screening in Catalonia’s NBS program has effectively reduced morbidity and improved affected children’s quality of life.L'any 2015, Catalunya va introduir el cribratge de la malaltia de cèl·lules falciformes (SCD) al seu programa de cribratge de nounats (NBS) juntament amb tractaments d'atenció estàndard com la penicil·lina, la hidroxiurea i la vacunació antipneumocòcica. Pocs estudis han avaluat l'impacte clínic de la introducció de programes NBS en pacients amb MSC. S'ha analitzat la incidència de la MSC i les hemoglobinopaties relacionades a Catalunya i el canvi en els esdeveniments clínics que es produeixen després de la introducció de l'ENB. Vam examinar 506.996 nadons del 2015 al 2022, vam realitzar un estudi multicèntric retrospectiu que incloïa 100 pacients amb SCD examinats (SG) i 95 sense cribratge (UG) i vam analitzar els esdeveniments clínics relacionats amb SCD durant els primers sis anys de vida. Es van diagnosticar 160 casos de MSC, amb una incidència d'1 de cada 3.169 nounats. El SG tenia una edat mitjana significativament més baixa en el moment del diagnòstic (0,1 anys vs. 1,68 anys, p <0,0001) i va iniciar la profilaxi amb penicil·lina (0,12 anys vs. 1,86 anys, p <0,0001) i el tractament amb hidroxiurea abans (1,42 anys vs. 4,5 anys). , p <0,0001). El SG va experimentar menys esdeveniments clínics mitjans relacionats amb SCD (crisi vaso-oclusiva, síndrome toràcica aguda, infeccions d'origen bacterià probable, anèmia aguda que va requerir transfusió, segrest esplènic agut i ecografia Doppler transcranial patològica) per any de seguiment (0,19 vs. 0,77, p <0,0001), un nombre reduït de visites anuals al servei d'urgències (0,37 vs. 0,76, p <0,0001) i menys hospitalitzacions (0,33 vs. 0,72, p <0,0001). El cribratge de SCD al programa NBS de Catalunya ha reduït de manera efectiva la morbiditat i ha millorat la qualitat de vida dels nens afectats

Compartir ideas, la universidad va al instituto. Análisis de la primera edición de un proyecto de aprendizaje servicio transversal a la Universidad de Barcelona

Esta comunicación presenta las principales claves de análisis y evaluación de la 1a edición del proyecto Compartir Ideas. La Universidad va al instituto. Este es un proyecto de aprendizaje servicio transversal que consiste en un ciclo de conferencias-taller impartidas por estudiantes de la UB sobre temes de interés general relacionados con sus estudios. El objetivo es compartir conocimientos y conversar sobre un tema que la universidad trabaja y que será relevante para la formación del alumnado de secundaria.El proyecto cuenta con el apoyo del Vicerectorado de Política Docente y Lingüística de la Universitat de Barcelona

Spread of a SARS-CoV-2 variant through Europe in the summer of 2020

[EN] Following its emergence in late 2019, the spread of SARS-CoV-21,2 has been tracked by phylogenetic analysis of viral genome sequences in unprecedented detail3,4,5. Although the virus spread globally in early 2020 before borders closed, intercontinental travel has since been greatly reduced. However, travel within Europe resumed in the summer of 2020. Here we report on a SARS-CoV-2 variant, 20E (EU1), that was identified in Spain in early summer 2020 and subsequently spread across Europe. We find no evidence that this variant has increased transmissibility, but instead demonstrate how rising incidence in Spain, resumption of travel, and lack of effective screening and containment may explain the variant’s success. Despite travel restrictions, we estimate that 20E (EU1) was introduced hundreds of times to European countries by summertime travellers, which is likely to have undermined local efforts to minimize infection with SARS-CoV-2. Our results illustrate how a variant can rapidly become dominant even in the absence of a substantial transmission advantage in favourable epidemiological settings. Genomic surveillance is critical for understanding how travel can affect transmission of SARS-CoV-2, and thus for informing future containment strategies as travel resumes.S

Estudio observacional sobre los criterios de dosificación de carboplatino en pacientes obesos : evaluación de la efectividad y la toxicidad en función del criterio utilizado

Objetivos: Los objetivos principales del estudio fueron: 1) Describir los criterios de dosificación de carboplatino en pacientes obesos en la práctica clínica habitual en el Hospital Clínico Universitario Virgen de la Arrixaca. 2) Evaluación de la toxicidad en función del criterio empleado. 3) Evaluación de la efectividad en los diagnósticos mayoritarios en función del criterio empleado. Metodología: Estudio observacional, retrospectivo, descriptivo, incluyendo todos los pacientes obesos (IMC>30 kg/m2) que comenzaron tratamiento con carboplatino entre el 1 de enero de 2012 y el 31 de enero de 2015. Se recogieron variables de caracterización del paciente, enfermedad y tratamiento. Como variables resultado se recogieron: el método de cálculo de la dosis de carboplatino, criterio de dosificación, otras aproximaciones en la dosificación de carboplatino, retrasos en el tratamiento, reducciones de dosis, intensidad de dosis relativa, reacciones adversas y gravedad (CTCAE v. 4.0) así como la supervivencia global y supervivencia libre de progresión en los diagnósticos mayoritarios. Conclusiones: 1) El empleo de la fórmula de Calvert, para un AUC objetivo y utilización de la fórmula de Cockcroft Gault para la estimación de la tasa de filtración glomerular ha sido el método de dosificación de carboplatino en la práctica clínica habitual en el Hospital Clínico Universitario Virgen de la Arrixaca. 2) Los descriptores de peso utilizados en la fórmula de Cockcroft Gault fueron el peso real y el peso ideal ajustado en proporciones similares. 3) Las estrategias de dosificación mediante la utilización de dosis máximas o dosis fija han sido minoritarias. 4) Se observó una mayor utilización del peso ideal ajustado en pacientes con mayor obesidad, así como en pacientes con diabetes. 5) En la población general, la tendencia al desarrollo de toxicidad durante el tratamiento fue mayor en el grupo dosificado por peso real. 6) En el análisis de toxicidad por ciclos administrados, el grupo dosificado por peso real desarrolló mayor toxicidad, alcanzando diferencias significativas en trombopenia, neutropenia, elevación de la GOT e hiporexia. 7) Los diagnósticos mayoritarios en el presente estudio fueron el cáncer de ovario y el cáncer de pulmón no microcítico. La efectividad en términos de supervivencia global y supervivencia libre de progresión, al comparar los grupos dosificados por peso real y peso ideal ajustado dentro de cada patología, no mostraron diferencias estadísticamente significativas. Objectives: The main aims of the study were: 1) To describe the carboplatin dosing criteria in obese patients in routine clinical practice at the Hospital Clínico Universitario Virgen de la Arrixaca. 2) Evaluation of the toxicity according to the criterion used. 3) Evaluation of the effectiveness in the majority diagnoses according to the criterion used. Methodology: An observational, retrospective, descriptive study, including all obese patients (BMI>30 kg/m2) who started treatment with carboplatin between 1st January 2012 and 31st January 2015. Characterization variables from the patient, disease and treatment were collected. As a result variables were collected: the method of calculating the dose of carboplatin, dosage criteria, others approximations in the dosage of carboplatin, treatment delays, dose reductions, relative dose intensity, adverse reactions and severity (CTCAE v. 4.0) as well as global survival and progressive free survival in the majority of the diagnoses. Conclusions: 1) The use of Calvert´s formula for an objective AUC and the use of Cockcroft Gault´s formula for the estimation of the glomerular filtration rate has been the method of dosing carboplatin in routine clinical practice at the Hospital Clínico Universitario Virgen de la Arrixaca. 2) The weight descriptors used in the Cockcroft Gault´s formula were the actual body weight and the ideal adjusted body weight in similar proportions. 3) Dosing strategies using maximum doses or fixed doses have been used in fewer cases. 4) Greater use of ideal adjusted body weight was observed in patients with greater obesity, as well as in patients with diabetes. 5) In the general population, the developmental trend of toxicity during treatment was greater in the group dosed by actual body weight. 6) In the toxicity analysis by administered cycles, the dosed group by real body weight developed greater toxicity, reaching significant differences in thrombopenia, neutropenia, SGOT elevation and hyporexia. 7) Major diagnoses in the present study were ovarian cancer and non-small cell lung cancer. The effectiveness in terms of overall survival and progression-free survival, comparing the groups dosed by actual body weight and ideal adjusted body weight within each pathology did not show statistically significant differences

MZT1 regulates microtubule nucleation by linking γTuRC assembly to adapter-mediated targeting and activation

Regulation of the γ-tubulin ring complex (γTuRC) through targeting and activation restricts nucleation of microtubules to microtubule-organizing centers (MTOCs), aiding in the assembly of ordered microtubule arrays. However, the mechanistic basis of this important regulation remains poorly understood. Here, we show that, in human cells, γTuRC integrity, determined by the presence of γ-tubulin complex proteins (GCPs; also known as TUBGCPs) 2–6, is a prerequisite for interaction with the targeting factor NEDD1, impacting on essentially all γ-tubulin-dependent functions. Recognition of γTuRC integrity is mediated by MZT1, which binds not only to the GCP3 subunit as previously shown, but cooperatively also to other GCPs through a conserved hydrophobic motif present in the N-termini of GCP2, GCP3, GCP5 and GCP6. MZT1 knockdown causes severe cellular defects under conditions that leave γTuRC intact, suggesting that the essential function of MZT1 is not in γTuRC assembly. Instead, MZT1 specifically binds fully assembled γTuRC to enable interaction with NEDD1 for targeting, and with the CM1 domain of CDK5RAP2 for stimulating nucleation activity. Thus, MZT1 is a ‘priming factor’ for γTuRC that allows spatial regulation of nucleation.This study was supported by grants from the Ministerio de Economıa y ́ Competitividad (MINECO) (BFU2009-08522, BFU2012-33960 and BFU2015- 69275-P to J.L. and BFU2014-58422-P to J.R.), and IRB Barcelona intramural funds. J.L. acknowledges additional support from the Ramón y Cajal Programme (RYC-2010-07108 MINECO, Spain). R.R.C. was supported by a PhD fellowship from the Consejo Nacional de Ciencia y Tecnologıa (Mexican National Council for ́ Science and Technology; CONACYT) (CVU 269229).Peer reviewe

Treatment adherence in patients older than 65 years who suffer early readmissions

Objective: Analyze the frequency of therapeutic noncompliance in patients who suffer early readmissions, and identify the factors associated with it. Method: Observational, descriptive study of three months duration (March - May 2014). All patients older than 65 years who readmitted in the 3-30 days following the last hospital discharge were included. We excluded programmed re-admissions and readmissions in the Intensive Care Unit. The variables collected were: age, sex, medical service, major diagnostic category, polypharmacy, number of days since the last hospital discharge, presence of hypertension and/or diabetes. The therapeutic compliance and the difficulty in the administration of medication were evaluated by means of the Morisky-Green test and the Haynes-Sackett test respectively. A descriptive analysis of the variables was carried out and they were related to the therapeutic adherence. The variables with statistical significance were included in a multivariate logistic regression model. Results: Fifty seven percent of the patients presented lack of adherence to pharmacological treatment. Twenty three percent had difficulty administering the medication. Eighty six percent had comorbidities (hypertension and/or diabetes) and 79% had a caregiver. Eighty six percent of patients were polymedicated (≥ 5 drugs). There is a relationship between lack of adherence and difficulty in the administration of medications (p=0.021), polypharmacy (p=0.002), and the presence of diabetes mellitus (p=0.018). Conclusions: Polymedication, the presence of diabetes mellitus and the existence of difficulty in the administration of medication are evidenced as prognostic factors of the lack of adherence to treatment in patients older than 65 years

The Usefulness of Intraepithelial Lymphocyte Immunophenotype Testing for the Diagnosis of Coeliac Disease in Clinical Practice

Background: The diagnosis of coeliac disease (CD) in adults is based on clinical, serological and histological criteria. The inappropriate performance of intestinal biopsies, non-specificity of mild histological lesions and initiation of a gluten-free diet (GFD) before biopsy may hamper the diagnosis. In these situations, determining the intraepithelial lymphogram of the duodenum by flow cytometry (IEL-FC) can be helpful. Objectives: To describe the clinical scenarios in which the IEL-FC is used and its impact on the diagnosis of CD. Methods: All adult patients with suspected CD at three tertiary centres for whom the duodenal histology and IEL-FC were available were identified. Catassi and Fasano’s diagnostic criteria and changes to a CD diagnosis after the IEL-FCs were collected. Results: A total of 348 patients were included. The following indications for an IEL-FC formed part of the initial study for CD (38%): negative conventional work-up (32%), already on a GFD before duodenal biopsies (29%) and refractoriness to a GFD (2%). The IEL-FC facilitated a definitive diagnosis in 93% of patients with an uncertain diagnosis who had had a conventional work-up for CD or who were on a GFD before histology. Conclusions: The IEL-FC facilitates the confirmation or rejection of a diagnosis of CD in clinical scenarios in which a conventional work-up may be insufficient

Gene expression profiling of intestinal regeneration in the sea cucumber

Abstract Background Among deuterostomes, the regenerative potential is maximally expressed in echinoderms, animals that can quickly replace most injured organs. In particular, sea cucumbers are excellent models for studying organ regeneration since they regenerate their digestive tract after evisceration. However, echinoderms have been sidelined in modern regeneration studies partially because of the lack of genome-wide profiling approaches afforded by modern genomic tools. For the last decade, our laboratory has been using the sea cucumber Holothuria glaberrima to dissect the cellular and molecular events that allow for such amazing regenerative processes. We have already established an EST database obtained from cDNA libraries of normal and regenerating intestine at two different regeneration stages. This database now has over 7000 sequences. Results In the present work we used a custom-made microchip from Agilent with 60-mer probes for these ESTs, to determine the gene expression profile during intestinal regeneration. Here we compared the expression profile of animals at three different intestinal regeneration stages (3-, 7- and 14-days post evisceration) against the profile from normal (uneviscerated) intestines. The number of differentially expressed probes ranged from 70% at p actins, and developmental genes, such as Wnt and Hox genes, show interesting expression profiles during regeneration. Conclusion Our findings set the base for future studies into the molecular basis of intestinal regeneration. Moreover, it advances the use of echinoderms in regenerative biology, animals that because of their amazing properties and their key evolutionary position, might provide important clues to the genetic basis of regenerative processes.</p