Expansion of Human Limbal Epithelial Stem/Progenitor Cells Using Different Human Sera: A Multivariate Statistical Analysis

Transplantation of human cultured limbal epithelial stem/progenitor cells (LESCs) has demonstrated to restore the integrity and functionality of the corneal surface in about 76% of patients with limbal stem cell deficiency. However, there are different protocols for the expansion of LESCs, and many of them use xenogeneic products, being a risk for the patients’ health. We compared the culture of limbal explants on the denuded amniotic membrane in the culture medium—supplemental hormone epithelial medium (SHEM)—supplemented with FBS or two differently produced human sera. Cell morphology, cell size, cell growth rate, and the expression level of differentiation and putative stem cell markers were examined. Several bioactive molecules were quantified in the human sera. In a novel approach, we performed a multivariate statistical analysis of data to investigate the culture factors, such as differently expressed molecules of human sera that specifically influence the cell phenotype. Our results showed that limbal cells cultured with human sera grew faster and contained similar amounts of small-sized cells, higher expression of the protein p63α, and lower of cytokeratin K12 than FBS cultures, thus, maintaining the stem/progenitor phenotype of LESCs. Furthermore, the multivariate analysis provided much data to better understand the obtaining of different cell phenotypes as a consequence of the use of different culture methodologies or different culture components.Research study supported by grants from Mutua Madrileña Foundation (FMM11/02), Basque Foundation for Health Research and Innovation BIOEF (BIO14/TP/002), National Eye Institute (R01EY021797), California Institute for Regenerative Medicine (TR-TR2-01768 and CLIN1-08686) and an unrestricted grant from Research to Prevent Blindness to the Department of Ophthalmology, University of California, Los Angeles. R.H.-M. was supported by fellowships from the University of the Basque Country UPV/EHU and the Jesus de Gangoiti Barrera foundation

Prevalence study of intermittent hormonal therapy of Prostate Cancer patients in Spain

Background: Although intermittent androgen deprivation therapy was introduced many years ago to improve patients’ quality of life with the same carcinologic efficiency as continuous hormonal therapy, recent data suggest that intermittency could be underutilised. This study aims to estimate the prevalence of prostate cancer patients receiving intermittent androgen deprivation therapy in Spain. Methods: A retrospective, longitudinal study was conducted using electronic drug dispensation data from four Spanish autonomous communities, which encompass 17.23 million inhabitants (36.22% of the total population in Spain). We estimated intermittent androgen therapy use (%IAD) and the prevalence of patients under intermittent androgen therapy in reference to the total number of PC patients using hormonal therapy (P (IAD)) and stratified by region. Other outcome variables included the pharmaceutical forms dispensed and the total direct annual expenditure on androgen deprivation therapy‐associated medications. Results: A total of 863,005 dispensations corresponding to a total of 65,752 men were identified, treated with either luteinizing hormone-releasing hormone (LHRH) analogues (353,162) administered alone or in combination with anti‐androgens (509,843). Overall, the mean (±SD) age of the patients was 76.9 (±10.4) years. Results revealed that the mean annual P (IAD) along the study was 6.6% in the total population studied, and the overall %IAD during the five‐year study period was 5.6%. The mean cost of hormonal therapy per year was 25 million euros for LHRH analogues and 6.3 million euros for anti-androgens. Conclusions:  Few prostate cancer patients in Spain use the intermittent androgen deprivation therapy suggesting underutilization of a perfectly valid option for a significant proportion of patients, missing the opportunity to improve their quality of life and to reduce costs for the National Health Service with comparable overall survival rates than continuous therapy

A new tool to screen patients with severe obstructive sleep apnea in the primary care setting : a prospective multicenter study

Altres ajuts: Sociedad Española de Neumología y Cirugía Torácica (SEPAR), Societat Catalana de Pneumologia (SOCAP).The coordination between different levels of care is essential for the management of obstructive sleep apnea (OSA). The objective of this multicenter project was to develop a screening model for OSA in the primary care setting. Anthropometric data, clinical history, and symptoms of OSA were recorded in randomly selected primary care patients, who also underwent a home sleep apnea test (HSAT). Respiratory polygraphy or polysomnography were performed at the sleep unit to establish definite indication for continuous positive airway pressure (CPAP). By means of cross-validation, a logistic regression model (CPAP yes/no) was designed, and with the clinical variables included in the model, a scoring system was established using the β coefficients (PASHOS Test). In a second stage, results of HSAT were added, and the final accuracy of the model was assessed. 194 patients completed the study. The clinical test included the body mass index, neck circumference and observed apneas during sleep (AUC 0.824, 95% CI 0.763-0.886, P < 0.001). In a second stage, the oxygen desaturation index (ODI) of 3% (ODI3% ≥ 15%) from the HSAT was added (AUC 0.911, 95% CI 0.863-0.960, P < 0.001), with a sensitivity of 85.5% (95% CI 74.7-92.1) and specificity of 67.8% (95% CI 55.1-78.3). The use of this model would prevent referral to the sleep unit for 55.1% of the patients. The two-stage PASHOS model is a useful and practical screening tool for OSA in primary care for detecting candidates for CPAP treatment. Clinical Trial Registration Registry: ClinicalTrials.gov; Name: PASHOS Project: Advanced Platform for Sleep Apnea Syndrome Assessment; URL: ; Identifier: NCT02591979. Date of registration: October 30, 2015. The online version contains supplementary material available at 10.1186/s12890-022-01827-0

Stability of SARS-CoV-2 spike antigens against mutations

Modern health care needs preventive vaccines and therapeutic treatments with stability against pathogen mutations to cope with current and future viral infections. At the beginning of the COVID-19 pandemic, our analytic and predictive tool identified a set of eight short SARS-CoV-2 S-spike protein epitopes that had the potential to persistently avoid mutation. Here a combination of genetic, Systems Biology and protein structure analyses confirm the stability of our identified epitopes against viral mutations. Remarkably, this research spans the whole period of the pandemic, during which 93.9% of the eight peptides remained invariable in the globally predominant 43 circulating variants, including Omicron. Likewise, the selected epitopes are conserved in 97% of all 1,514 known SARS-CoV-2 lineages. Finally, experimental analyses performed with these short peptides showed their specific immunoreactivity. This work opens a new perspective on the design of next-generation vaccines and antibody therapies that will remain reliable against future pathogen mutations.Dr. Lozano-Perez acknowledges the European Commission ERDF/FEDER Operational Program 'Murcia' CCI No. 2007ES161PO001 (Project No. 14-20/20). Miodrag Grbic acknowledges support from the NSERC Discovery grant (Canada). This work also has received funding from the Department of Education of the Basque Government via the Consolidated Research Group MATH MODE (IT1456-22). Besides, Ildefonso Martinez De la Fuente and Iker Malaina were supported by the UPV/EHU and Basque Center of Applied Mathematics, grant US21/27N

Bladder cancer index: cross-cultural adaptation into Spanish and psychometric evaluation

BACKGROUND: The Bladder Cancer Index (BCI) is so far the only instrument applicable across all bladder cancer patients, independent of tumor infiltration or treatment applied. We developed a Spanish version of the BCI, and assessed its acceptability and metric properties. METHODS: For the adaptation into Spanish we used the forward and back-translation method, expert panels, and cognitive debriefing patient interviews. For the assessment of metric properties we used data from 197 bladder cancer patients from a multi-center prospective study. The Spanish BCI and the SF-36 Health Survey were self-administered before and 12 months after treatment. Reliability was estimated by Cronbach's alpha. Construct validity was assessed through the multi-trait multi-method matrix. The magnitude of change was quantified by effect sizes to assess responsiveness. RESULTS: Reliability coefficients ranged 0.75-0.97. The validity analysis confirmed moderate associations between the BCI function and bother subscales for urinary (r = 0.61) and bowel (r = 0.53) domains; conceptual independence among all BCI domains (r ≤ 0.3); and low correlation coefficients with the SF-36 scores, ranging 0.14-0.48. Among patients reporting global improvement at follow-up, pre-post treatment changes were statistically significant for the urinary domain and urinary bother subscale, with effect sizes of 0.38 and 0.53. CONCLUSIONS: The Spanish BCI is well accepted, reliable, valid, responsive, and similar in performance compared to the original instrument. These findings support its use, both in Spanish and international studies, as a valuable and comprehensive tool for assessing quality of life across a wide range of bladder cancer patients

Clinical interval and diagnostic characteristics in a cohort of bladder cancer patients in Spain : a multicenter observational study

We performed a cohort study in seven hospitals in Spain to determine the clinical characteristics of incident patients with bladder cancer, the diagnostic process, and the conditions that might affect health care interval times. 314 patients with bladder cancer were included, 70.3 (Standard Deviation [SD] 11.2) years old and 85.0% male. Clinical stage was T1 in 45.9% of patients. The median interval time between first consultation and diagnosis was of 104.0 days (Inter quartile range [IQR]:112.0; range from 0 to 986), being shorter for those patients who attended a hospital for their first consultation. The median interval time between diagnosis and first treatment was of 0.0 days (IQR: 0.0; range from 0 to 366), being longer when the patient had a pathologic tumor stage ≥ T2a. The online version of this article (10.1186/s13104-017-3024-8) contains supplementary material, which is available to authorized users

DianaHealth.com, an On-Line Database Containing Appraisals of the Clinical Value and Appropriateness of Healthcare Interventions : Database Development and Retrospective Analysis

To describe the development of a novel on-line database aimed to serve as a source of information concerning healthcare interventions appraised for their clinical value and appropriateness by several initiatives worldwide, and to present a retrospective analysis of the appraisals already included in the database. Database development and a retrospective analysis. The database DianaHealth.com is already on-line and it is regularly updated, independent, open access and available in English and Spanish. Initiatives are identified in medical news, in article references, and by contacting experts in the field. We include appraisals in the form of clinical recommendations, expert analyses, conclusions from systematic reviews, and original research that label any health care intervention as low-value or inappropriate. We obtain the information necessary to classify the appraisals according to type of intervention, specialties involved, publication year, authoring initiative, and key words. The database is accessible through a search engine which retrieves a list of appraisals and a link to the website where they were published. DianaHealth.com also provides a brief description of the initiatives and a section where users can report new appraisals or suggest new initiatives. From January 2014 to July 2015, the on-line database included 2940 appraisals from 22 initiatives: eleven campaigns gathering clinical recommendations from scientific societies, five sets of conclusions from literature review, three sets of recommendations from guidelines, two collections of articles on low clinical value in medical journals, and an initiative of our own. We have developed an open access on-line database of appraisals about healthcare interventions considered of low clinical value or inappropriate. DianaHealth.com could help physicians and other stakeholders make better decisions concerning patient care and healthcare systems sustainability. Future efforts should be focused on assessing the impact of these appraisals in the clinical practice

Factores de riesgo y mortalidad de los derrames pleurales que precisan de una toracocentesis diagnóstica

Resumen: Introducción: El derrame pleural (DP) maligno se asocia a un mal pronóstico, pero la mortalidad de los pacientes con derrames no malignos no ha sido suficientemente estudiada. Nuestro objetivo fue describir la evolución clínica y explorar los factores asociados con la mortalidad por todas las causas a 1, 5 y 10 años de los pacientes que desarrollan un DP. Métodos: Estudio observacional retrospectivo de los pacientes intervenidos mediante toracocentesis diagnóstica durante el decenio 2008-2017 en un servicio de neumología. Se evaluaron variables demográficas, bioquímicas, anatomopatológicas y evolutivas. La etiología de los derrames se determinó mediante criterios estandarizados. Resultados: Se estudió a 358 pacientes con líquido pleural analizado; el 69,2% de los cuales eran varones con una edad media de 68,9 años (DE 15,1). Predominaron los derrames malignos (29,4%), paraneumónicos (19,8%) y secundarios a insuficiencia cardiaca (18,9%). Los pacientes con derrame maligno y por insuficiencia cardiaca tuvieron tasas de mortalidad a un año del 60,0% y 30,8%, respectivamente y del 85% y 64,7% a 5 años. El sexo masculino (hazard ratio [HR] 1,46; IC 95%: 1,03-2,07), la citología positiva para malignidad (HR 1,66; IC 95%: 1,03-2,68) y la recidiva del derrame (HR 1,61; IC 95%: 1,17-2,21) se asociaron a un peor pronóstico y a mortalidad a 5 años. Conclusiones: Los pacientes intervenidos mediante toracentesis por derrame tienen una alta mortalidad a corto y largo plazo. En nuestros pacientes hospitalizados con DP, los factores asociados con mayor mortalidad a 1 y 5 años fueron la edad, el sexo masculino, la recidiva del DP y la coexistencia de neoplasia maligna. Abstract: Introduction: Occurrence of malignant pleural effusion (PE) is known to be associated with a poor prognosis, but the mortality of patients with non-malignant effusions has not been sufficiently studied. Our objective was to describe the clinical course and explore risk factors associated with all-cause mortality at 1, 5 and 10 years in patients who develop a PE. Methods: Retrospective observational study of patients undergoing diagnostic thoracentesis during the decade 2008-2017 in a pulmonology service. Demographic, biochemical, pathological and evolutionary variables were evaluated. The etiology of the effusions was determined using standardized criteria. Results: Pleural fluid samples from 358 patients with a mean age of 68.9 years (SD 15.1 years), 69.2% males, were analyzed. Malignant (29.4%), parapneumonic (19.8%) and secondary to heart failure (18.9%) effusions predominated. Patients with malignant and heart failure related PE had 1-year mortality rates of 60.0% and 30.8%, respectively, and 85% and 64.7% at 5 years. Male gender (hazard ratio [HR] 1.46; 95% CI: 1.03-2.07), positive cytology for malignancy (HR 1.66; 95% CI: 1.03-2.68) and effusion recurrence (HR 1.61; 95% CI: 1.17-2.21) were associated with a worse prognosis and 5-year mortality. Conclusions: Patients undergoing thoracentesis for effusion have a high short and long-term mortality. In our series of hospitalized patients with PE, the factors associated with higher mortality at 1 and 5 years were age, male sex, recurrence of PE, and coexistence of malignancy