Dolor muscular en una mujer de 46 años

A 46-year-old woman presented with weakness, muscular pain and persistent elevations of creatinine kinase. The analysis (including hormones, autoimmunity and serology), magnetic resonance and an electromyogram did not provide a conclusive diagnosis. However, after performing a muscle biopsy, we diagnosed a glycogen storage disease type V (McArdle disease). Glycogenosis occurs in a group of metabolic and genetic diseases characterized by a disorder in the catabolism of glycogen. The McArdle disease is defined by an absence of glycogen phosphorylase, an enzyme that catalyzes the conversion of glycogen to glucose-1-phosphate in muscle tissue.Se presenta el caso de una paciente que consulta por debilidad y dolor muscular de años de evolución junto con elevación persistente de la creatinina cinasa. Los análisis realizados (que incluyeron hormonas, autoinmunidad y serologías), la resonancia magnética y el electromiograma no mostraron resultados concluyentes. Tras la práctica de una biopsia muscular se diagnostica de glucogenosis tipo V (enfermedad de McArdle). Las glucogenosis son un conjunto de enfermedades metabólicas de base genética caracterizadas por un trastorno en el catabolismo del glucógeno. La enfermedad de McArdle se define por la ausencia de la miofosforilasa, una enzima que cataliza la transformación de glucógeno en glucosa-1-fosfato en las fibras musculares esqueléticas, representando una forma de miopatía pura

CIBERER : Spanish national network for research on rare diseases: A highly productive collaborative initiative

Altres ajuts: Instituto de Salud Carlos III (ISCIII); Ministerio de Ciencia e Innovación.CIBER (Center for Biomedical Network Research; Centro de Investigación Biomédica En Red) is a public national consortium created in 2006 under the umbrella of the Spanish National Institute of Health Carlos III (ISCIII). This innovative research structure comprises 11 different specific areas dedicated to the main public health priorities in the National Health System. CIBERER, the thematic area of CIBER focused on rare diseases (RDs) currently consists of 75 research groups belonging to universities, research centers, and hospitals of the entire country. CIBERER's mission is to be a center prioritizing and favoring collaboration and cooperation between biomedical and clinical research groups, with special emphasis on the aspects of genetic, molecular, biochemical, and cellular research of RDs. This research is the basis for providing new tools for the diagnosis and therapy of low-prevalence diseases, in line with the International Rare Diseases Research Consortium (IRDiRC) objectives, thus favoring translational research between the scientific environment of the laboratory and the clinical setting of health centers. In this article, we intend to review CIBERER's 15-year journey and summarize the main results obtained in terms of internationalization, scientific production, contributions toward the discovery of new therapies and novel genes associated to diseases, cooperation with patients' associations and many other topics related to RD research

EducaFarma 9.0

Memoria ID-020 Ayudas de la Universidad de Salamanca para la innovación docente, curso 2020-2021

EducaFarma 11.0

Memoria ID2022-036. Ayudas de la Universidad de Salamanca para la innovación docente, curso 2022-2023

Educafarma 10.0

Memoria ID-030. Ayudas de la Universidad de Salamanca para la innovación docente, curso 2021-2022

Mortality from gastrointestinal congenital anomalies at 264 hospitals in 74 low-income, middle-income, and high-income countries: a multicentre, international, prospective cohort study

Summary Background Congenital anomalies are the fifth leading cause of mortality in children younger than 5 years globally. Many gastrointestinal congenital anomalies are fatal without timely access to neonatal surgical care, but few studies have been done on these conditions in low-income and middle-income countries (LMICs). We compared outcomes of the seven most common gastrointestinal congenital anomalies in low-income, middle-income, and high-income countries globally, and identified factors associated with mortality. Methods We did a multicentre, international prospective cohort study of patients younger than 16 years, presenting to hospital for the first time with oesophageal atresia, congenital diaphragmatic hernia, intestinal atresia, gastroschisis, exomphalos, anorectal malformation, and Hirschsprung’s disease. Recruitment was of consecutive patients for a minimum of 1 month between October, 2018, and April, 2019. We collected data on patient demographics, clinical status, interventions, and outcomes using the REDCap platform. Patients were followed up for 30 days after primary intervention, or 30 days after admission if they did not receive an intervention. The primary outcome was all-cause, in-hospital mortality for all conditions combined and each condition individually, stratified by country income status. We did a complete case analysis. Findings We included 3849 patients with 3975 study conditions (560 with oesophageal atresia, 448 with congenital diaphragmatic hernia, 681 with intestinal atresia, 453 with gastroschisis, 325 with exomphalos, 991 with anorectal malformation, and 517 with Hirschsprung’s disease) from 264 hospitals (89 in high-income countries, 166 in middleincome countries, and nine in low-income countries) in 74 countries. Of the 3849 patients, 2231 (58·0%) were male. Median gestational age at birth was 38 weeks (IQR 36–39) and median bodyweight at presentation was 2·8 kg (2·3–3·3). Mortality among all patients was 37 (39·8%) of 93 in low-income countries, 583 (20·4%) of 2860 in middle-income countries, and 50 (5·6%) of 896 in high-income countries (p<0·0001 between all country income groups). Gastroschisis had the greatest difference in mortality between country income strata (nine [90·0%] of ten in lowincome countries, 97 [31·9%] of 304 in middle-income countries, and two [1·4%] of 139 in high-income countries; p≤0·0001 between all country income groups). Factors significantly associated with higher mortality for all patients combined included country income status (low-income vs high-income countries, risk ratio 2·78 [95% CI 1·88–4·11], p<0·0001; middle-income vs high-income countries, 2·11 [1·59–2·79], p<0·0001), sepsis at presentation (1·20 [1·04–1·40], p=0·016), higher American Society of Anesthesiologists (ASA) score at primary intervention (ASA 4–5 vs ASA 1–2, 1·82 [1·40–2·35], p<0·0001; ASA 3 vs ASA 1–2, 1·58, [1·30–1·92], p<0·0001]), surgical safety checklist not used (1·39 [1·02–1·90], p=0·035), and ventilation or parenteral nutrition unavailable when needed (ventilation 1·96, [1·41–2·71], p=0·0001; parenteral nutrition 1·35, [1·05–1·74], p=0·018). Administration of parenteral nutrition (0·61, [0·47–0·79], p=0·0002) and use of a peripherally inserted central catheter (0·65 [0·50–0·86], p=0·0024) or percutaneous central line (0·69 [0·48–1·00], p=0·049) were associated with lower mortality. Interpretation Unacceptable differences in mortality exist for gastrointestinal congenital anomalies between lowincome, middle-income, and high-income countries. Improving access to quality neonatal surgical care in LMICs will be vital to achieve Sustainable Development Goal 3.2 of ending preventable deaths in neonates and children younger than 5 years by 2030

β-Cryptoxanthin synergistically enhances the antitumoral activity of oxaliplatin through ΔNP73 negative regulation in colon cancer

[Background]: The acquired resistance to chemotherapy represents the major limitation in the treatment of cancer. New strategies to solve this failure and improve patients' outcomes are necessary. The cancer preventive effect of β-cryptoxanthin has been widely described in population studies. Few reports support its putative use as an antitumoral compound. Here we focus on the therapeutic potential of β-cryptoxanthin individually or in combination with oxaliplatin in colon cancer and try to decipher the molecular basis underlying its effect. [Methods]: Apoptosis, viability and proliferation assays, mouse models, and an intervention study in 20 healthy subjects were performed. A PCR array was carried out to unravel the molecular putative basis of the β-cryptoxanthin effect, and further signaling experiments were conducted. Comet Assay was completed to evaluate the genotoxicity of the treatments. [Results]: β-Cryptoxanthin differentially regulates the expression of the P73 variants in vitro, in vivo, and in a human intervention study. This carotenoid decreases the proliferation of cancer cells and cooperates with oxaliplatin to induce apoptosis through the negative regulation of ΔNP73. The antitumoral concentrations of oxaliplatin decrease in the presence of β-cryptoxanthin to achieve same percentage of growth inhibition. The genotoxicity in peripheral blood mononuclear cells of mice decreased in the combined treatment. [Conclusions]: We propose a putative novel therapeutic strategy for the treatment of colon cancer based on the combination of β-cryptoxanthin and oxaliplatin. The combined regimen produced more benefit than either individual modality without increasing side effects. In addition, the concentration-limiting toxicity of oxaliplatin is reduced in the presence of the carotenoid.This study was supported by FIS-ISCIII grant PI11/00593 (cosupported with FEDER Funds), Fundacion Banco Santander, ISCIII-RTICC-RD12/0036/0041, Fundacón Científica AECC, and Comunidad de Madrid S2010/BMD-2344.Peer Reviewe