Successful development and clinical translation of a novel anterior lamellar artificial cornea

We thank the Andalusian Public Foundation Progress and Health, through the Andalusian Initiative for Advanced Therapies, for assuming the roles and responsibilities of sponsoring this clinical trial. We thank Dr. Manuel de la Rosa and Dr. Salvador Arias Santiago for providing insight and expertise that assisted the research.The datasets generated and/or analyzed during the current study are available in the Gene Expression Omnibus (GEO) public repository, ref. GSE86584 https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE86584Blindness due to corneal diseases is a common pathology affecting up to 23 million individuals worldwide. The tissue‐engineered anterior human cornea, which is currently being tested in a Phase I/II clinical trial to treat severe corneal trophic ulcers with preliminary good feasibility and safety results. This bioartificial cornea is based on a nanostructured fibrin–agarose biomaterial containing human allogeneic stromal keratocytes and cornea epithelial cells, mimicking the human native anterior cornea in terms of optical, mechanical, and biological behavior. This product is manufactured as a clinical‐grade tissue engineering product, fulfilling European requirements and regulations. The clinical translation process included several phases: an initial in vitro and in vivo preclinical research plan, including preclinical advice from the Spanish Medicines Agency followed by additional preclinical development, the adaptation of the biofabrication protocols to a good manufacturing practice manufacturing process, including all quality controls required, and the design of an advanced therapy clinical trial. The experimental development and successful translation of advanced therapy medicinal products for clinical application has to overcome many obstacles, especially when undertaken by academia or SMEs. We expect that our experience and research strategy may help future researchers to efficiently transfer their preclinical results into the clinical settings.This study was supported by the Spanish National Plan for Scientific and Technical Research and Innovation (I + D + I) from the Spanish Ministry of Economy and Competitiveness (Carlos III Institute of Health), grants FIS PI14/0955 and FIS PI17/0391 (both cofinanced by ERDF‐FEDER, European Union); by the Spanish Ministry of Health, Social Policy and Equity, grant EC10‐285; and by preclinical research funds from the Regional Ministry of Health through the Andalusian Initiative for Advanced Therapies

Safety and efficacy of ribociclib plus letrozole in patients with HR+, HER2– advanced breast cancer: Results from the Spanish sub-population of the phase 3b CompLEEment-1 trial

Background: Breast cancer is the most common malignancy and the second leading cause of cancer-related mortality in Spanish women. Ribociclib in combination with endocrine therapy (ET) has shown superiority in prolonging survival in patients with hormone receptor-positive (HR+), human epidermal growth factor receptor 2-negative (HER2-) advanced breast cancer (ABC) vs. ET alone.Methods: CompLEEment-1 is a single-arm, open-label phase 3b trial evaluating ribociclib plus letrozole in a broad population of patients with HR+, HER2- ABC. The primary endpoints were safety and tolerability. Here we report data for Spanish patients enrolled in CompLEEment-1.Results: A total of 526 patients were evaluated (median follow-up: 26.97 months). Baseline characteristics showed a diverse population with a median age of 54 years. At study entry, 56.5% of patients had visceral metastases and 8.7% had received prior chemotherapy for advanced disease. Rates of all-grade and Grade >= 3 adverse events (AEs) were 99.0% and 76.2%, respectively; 21.3% of patients experienced a serious AE, and 15.8% of AEs led to treatment discontinuation. AEs of special interest of neutropenia, increased alanine aminotransferase, increased aspartate aminotransferase and QTcF prolongation occurred in 77.8%, 14.8%, 11.4% and 4.0% of patients, respectively. Patients aged >70 years experienced increased rates of all-grade and Grade >= 3 neutropenia and anemia. Efficacy results were consistent with the global study.Conclusions: Results from Spanish patients enrolled in CompLEEment-1 are consistent with global data showing efficacy and a manageable safety profile for ribociclib plus letrozole treatment in patients with HR+, HER2-ABC, including populations of interest (NCT02941926).Trial registration: ClinicalTrials.gov NCT0294192

Diseño de un módulo de prácticas interdisciplinares en paleontología aplicada

El proyecto de redes ha visto el desarrollo y el diseño de prácticas de carácter interdisciplinar (esquema de trabajo colaborativo entre alumnos y profesores) en el ámbito de la paleontología aplicada en estudios de Grado y de Máster, involucrando tanto el área de conocimiento de paleontología como a la de estratigrafía del Departamento de Ciencias de la Tierra y del Medio Ambiente de la Universidad de Alicante. En la acción educativa propuesta se ha planteado una coordinación entre las áreas de paleontología y estratigrafía para diseñar y llevar a cabo de forma conjunta actividades de campo y de laboratorio. Por ello, se elaboraron actividades de carácter interdisciplinar que los alumnos han ido desarrollando durante las salidas de campo y las sesiones de laboratorio y se realizó un muestreo para el desarrollo de las actividades de laboratorio compartidas entre las asignaturas. Al finalizar cada una de las asignaturas involucradas, se propuso a los alumnos una entrevista sobre la experiencia llevada a cabo, destacando aspectos positivos, elementos a mejorar y dificultades encontradas. Los resultados de las entrevistas y de la puesta en común en grupos de debate se utilizarán para la puesta en marcha de la acción educativa en los siguientes cursos académicos

Diseño de un módulo de prácticas interdisciplinares en paleontología aplicada

El proyecto de redes ha visto el desarrollo y el diseño de prácticas de carácter interdisciplinar (esquema de trabajo colaborativo entre alumnos y profesores) en el ámbito de la paleontología aplicada en estudios de Grado y de Máster, involucrando tanto el área de conocimiento de paleontología como a la de estratigrafía del Departamento de Ciencias de la Tierra y del Medio Ambiente de la Universidad de Alicante. En la acción educativa propuesta se ha planteado una coordinación entre las áreas de paleontología y estratigrafía para diseñar y llevar a cabo de forma conjunta actividades de campo y de laboratorio. Por ello, se elaboraron actividades de carácter interdisciplinar que los alumnos han ido desarrollando durante las salidas de campo y las sesiones de laboratorio y se realizó un muestreo para el desarrollo de las actividades de laboratorio compartidas entre las asignaturas. Al finalizar cada una de las asignaturas involucradas, se propuso a los alumnos una entrevista sobre la experiencia llevada a cabo, destacando aspectos positivos, elementos a mejorar y dificultades encontradas. Los resultados de las entrevistas y de la puesta en común en grupos de debate se utilizarán para la puesta en marcha de la acción educativa en los siguientes cursos académicos

Comparison of six commercial systems for the detection of non-O157 STEC in meat and vegetables

Shiga toxin-producing Escherichia coli (STEC) are important pathogens transmitted by food that may cause severe illness in human beings. Thus, systems for STEC detection in food should have increasingly higher sensitivity and specificity. Here we compared six commercial systems for non-O157 STEC detection in meat and vegetables and determined their sensitivity, specificity and repeatability. A total of 46 samples (meat n = 23; chard n = 23) were experimentally contaminated with strains O26:H11, O45:H-, O103:H2, O111:NM, O121:H19 and O145:NM isolated in Argentina. Strain detection was confirmed by isolation according to ISO 13136:2012. Detection of the stx and eae genes in meat samples was highly satisfactory with all commercial kits, but only five had 100% sensitivity and specificity in chard. Of four kits evaluated for serogroup detection, three had 100% sensitivity and specificity, and one had 93.7% sensitivity and 100% specificity. All kits were adequate to analyze meat but not vegetable samples, and were not therefore validated for the latter matrix. The challenge for microbiology laboratories is to identify the advantages and disadvantages of the available kits for STEC detection in food based on a clear knowledge of the particular needs of each laboratory.EEA RafaelaFil: Costa, Magdalena. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico CONICET- La Plata. Instituto de Genética Veterinaria "Ing. Fernando Noel Dulout". Universidad Nacional de La Plata. Facultad de Ciencias Veterinarias. Instituto de Genética Veterinaria; ArgentinaFil: Sucari, Adriana. Centro Estudios Infectológicos “Dr. Daniel Stamboulian”. División Higiene y Seguridad Alimentaria y Ambiental; ArgentinaFil: Epszteyn, Sergio. Buenos Aires. Dirección General de Higiene y Seguridad Alimentaria. Laboratorio de Investigación y Monitoreo; ArgentinaFil: Oteiza, Juan Martín. Centro de Investigación y Asistencia Técnica a la Industria. Laboratorio de Microbiología de los Alimentos (Neuquén); ArgentinaFil: Gentiluomo, Jimena. Centro Estudios Infectológicos “Dr. Daniel Stamboulian”. División Higiene y Seguridad Alimentaria y Ambiental; ArgentinaFil: Melamed, Celia. Buenos Aires. Dirección General de Higiene y Seguridad Alimentaria. Laboratorio de Investigación y Monitoreo; ArgentinaFil: Figueroa, Yamila. Centro Estudios Infectológicos “Dr. Daniel Stamboulian”. División Higiene y Seguridad Alimentaria y Ambiental; ArgentinaFil: Mingorance, Santiago Emmanuel. Buenos Aires. Dirección General de Higiene y Seguridad Alimentaria. Laboratorio de Investigación y Monitoreo; ArgentinaFil: Grisaro, Agustina. Centro Estudios Infectológicos “Dr. Daniel Stamboulian”. División Higiene y Seguridad Alimentaria y Ambiental; ArgentinaFil: Spioussas, Silvia. Buenos Aires. Dirección General de Higiene y Seguridad Alimentaria. Laboratorio de Investigación y Monitoreo; ArgentinaFil: Buffoni Almeida, Mariana. Centro Estudios Infectológicos “Dr. Daniel Stamboulian”. División Higiene y Seguridad Alimentaria y Ambiental; ArgentinaFil: Caruso, Mailen. Buenos Aires. Dirección General de Higiene y Seguridad Alimentaria. Laboratorio de Investigación y Monitoreo; ArgentinaFil: Pontoni, Andrés. Buenos Aires. Dirección General de Higiene y Seguridad Alimentaria. Laboratorio de Investigación y Monitoreo; ArgentinaFil: Signorini, Marcelo. Instituto Nacional de Tecnología Agropecuaria (INTA). Estación Experimental Agropecuaria Rafaela; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Leotta, Gerardo Anibal. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico CONICET- La Plata. Instituto de Genética Veterinaria "Ing. Fernando Noel Dulout". Universidad Nacional de La Plata. Facultad de Ciencias Veterinarias. Instituto de Genética Veterinaria; Argentin

Increased Presentation of Diabetic Ketoacidosis and Changes in Age and Month of Type 1 Diabetes at Onset during the COVID-19 Pandemic in Spain

Objective: To assess the impact of the COVID-19 pandemic and lockdown measures on the presenting characteristics (age at diagnosis, severity, monthly distribution) of newly diagnosed type 1 diabetes in Spanish children. Research Design and Methods: An ambispective observational multicenter study was conducted in nine Spanish tertiary-level hospitals between January 2015 and March 2021. Inclusion criteria: new cases of type 1 diabetes in children (0–14 years) recording age, sex, date of diagnosis, presence of diabetic ketoacidosis (DKA) at onset, and severity of DKA. Data were compared before and during the pandemic. Results: We registered 1444 new cases of type 1 diabetes in children: 1085 in the pre-pandemic period (2015–2019) and 359 during the pandemic (2020–March 2021). There was a significant increase in the group aged ≤4 years in the pandemic period (chi-squared = 10.986, df 2, p = 0.0041). In 2020–2021, cases of DKA increased significantly by 12% (95% CI: 7.2–20.4%), with a higher percentage of moderate and severe DKA, although this increase was not significant. In 2020, there was a sharp decrease in the number of cases in March, with a progressive increase from May through November, higher than in the same months of the period 2015–2019, highlighting the increase in the number of cases in June, September, and November. The first three months of 2021 showed a different trend to that observed both in the years 2015–2019 and in 2020, with a marked increase in the number of cases. Conclusions: A change in monthly distribution was described, with an increase in DKA at onset of type 1 diabetes. No differences were found in severity, although there were differences in the age distribution, with an increase in the number of cases in children under 4 years of age

Prospective Multicentre Study on the Epidemiology and Current Therapeutic Management of Severe Bronchiolitis in Spain

Objective. To determine the epidemiology and therapeutic management of patients with severe acute bronchiolitis (AB) admitted to paediatric intensive care units (PICUs) in Spain. Design. Descriptive, prospective, multicentre study. Setting. Sixteen Spanish PICUs. Patients. Patients with severe AB who required admission to any of the participating PICUs over 1 year. Interventions. Both epidemiological variables and medical treatment received were recorded. Results. A total of 262 patients were recruited; 143 were male (54.6%), with median age of 1 month (0–23). Median stay in the PICU was 7 days (1–46). Sixty patients (23%) received no nebuliser treatment, while the rest received a combination of inhalation therapies. One-quarter of patients (24.8%) received corticosteroids and 56.5% antibiotic therapy. High-flow oxygen therapy was used in 14.3% and noninvasive ventilation (NIV) was used in 75.6%. Endotracheal intubation was required in 24.4% of patients. Younger age, antibiotic therapy, and invasive mechanical ventilation (IMV) were risk factors that significantly increased the stay in the PICU. Conclusions. Spanish PICUs continue to routinely use nebulised bronchodilator treatment and corticosteroid therapy. Despite NIV being widely used in this condition, intubation was required in one-quarter of cases. Younger age, antibiotic therapy, and IMV were associated with a longer stay in the PICU

Impact of late presentation of HIV infection on short-, mid- and long-term mortality and causes of death in a multicenter national cohort : 2004-2013

To analyze the impact of late presentation (LP) on overall mortality and causes of death and describe LP trends and risk factors (2004-2013). Cox models and logistic regression were used to analyze data from a nation-wide cohort in Spain. LP is defined as being diagnosed when CD4 < 350 cells/ml or AIDS. Of 7165 new HIV diagnoses, 46.9% (CI:45.7-48.0) were LP, 240 patients died.First-year mortality was the highest (aHR = 10.3[CI:5.5-19.3]); between 1 and 4 years post-diagnosis, aHR = 1.9(1.2-3.0); an