Síndrome coronario agudo y enfermedad de Erdheim-Chester. Patogénesis e implicaciones terapéuticas

ResumenLa enfermedad de Erdheim-Chester es una histiocitosis celular diferente a la histiocitosis de Langerhans, de origen incierto. Se caracteriza por una implicación multi-orgánica debida a la infiltración de los histiocitos CD68+/CD1a-, en forma de xantogranulomas, que afectan principal y comúnmente a la metáfisis y diáfisis de huesos largos. El diagnóstico se realiza mediante biopsia, donde se revelan histiocitos CD68+/CD1a-, carencia de proteína S, y presencia de gránulos de Birbeck. Se ha subestimado la implicación cardiovascular. Reportamos un caso de un varón de 67 años con la enfermedad de Erdheim-Chester e infarto de miocardio agudo, debido a implicación coronaria, además de enfermedad ósea, vascular, pituitaria y retroperitoneal. Revisamos la literatura relevante y describimos el tratamiento clínico de estos pacientes.AbstractErdheim-Chester disease is a non-Langerhans cell histiocytosis of uncertain origin. It is characterized by multiorgan involvement due to infiltration of CD68+/CD1a- histiocytes, in the form of xantogranulomas, most commonly affecting the metaphysis and diaphysis of long bones. The diagnosis is made by biopsy showing CD68+/CD1ahistiocytes, lack of S protein and Birbeck granules. Cardiovascular involvement is underestimated. We report a case of a 67 year-old man with Erdheim-Chester disease and acute myocardial infarction due to coronary involvement, in addition to bone, vascular, pituitary and retroperitoneal disease. We review relevant literature and describe the clinical management of these patients

P2X7 receptor induces mitochondrial failure in monocytes and compromises NLRP3 inflammasome activation during sepsis

International audienceSepsis is characterized by a systemic inflammatory response followed by immunosuppres-sion of the host. Metabolic defects and mitochondrial failure are common in immunocom-promised patients with sepsis. The NLRP3 inflammasome is important for establishing an inflammatory response after activation by the purinergic P2X7 receptor. Here, we study a cohort of individuals with intra-abdominal origin sepsis and show that patient monocytes have impaired NLRP3 activation by the P2X7 receptor. Furthermore, most sepsis-related deaths are among patients whose NLRP3 activation is profoundly altered. In monocytes from sepsis patients, the P2X7 receptor is associated with mitochondrial dysfunction. Furthermore, activation of the P2X7 receptor results in mitochondrial damage, which in turn inhibits NLRP3 activation by HIF-1α. We show that mortality increases in a mouse model of sepsis when the P2X7 receptor is activated in vivo. These data reveal a molecular mechanism initiated by the P2X7 receptor that contributes to NLRP3 impairment during infection

Purinergic P2X7 receptor expression increases in leukocytes from intra-abdominal septic patients

Inflammation is a tightly coordinated response of the host immune system to bacterial and viral infections, triggered by the production of inflammatory cytokines. Sepsis is defined as a systemic inflammatory response followed by immunosuppression of the host and organ dysfunction. This imbalance of the immune response increases the risk of mortality of patients with sepsis, making it a major problem for critical care units worldwide. The P2X7 receptor plays a crucial role in activating the immune system by inducing the activation of peripheral blood mononuclear cells. In this study, we analyzed a cohort of abdominal origin septic patients and found that the expression of the P2X7 receptor in the plasma membrane is elevated in the different subsets of lymphocytes. We observed a direct relationship between the percentage of P2X7-expressing lymphocytes and the early inflammatory response in sepsis. Additionally, in patients whose lymphocytes presented a higher percentage of P2X7 surface expression, the total lymphocytes populations proportionally decreased. Furthermore, we found a correlation between elevated soluble P2X7 receptors in plasma and inflammasome-dependent cytokine IL-18. In summary, our work demonstrates that P2X7 expression is highly induced in lymphocytes during sepsis, and this correlates with IL-18, along with other inflammatory mediators such as IL-6, IL-8, and procalcitonin

Eficàcia i seguretat d’un tractament oral a base de mucopolisacàrids, col·lagen tipus I i vitamina C en pacients amb tendinopaties

Introducció i objectius La tendinopatia és una lesió freqüent durant la pràctica esportiva que es manifesta amb una alteració estructural del tendó. L’objectiu d’aquest estudi fou avaluar l’eficàcia i la seguretat d’un complement alimentari a base de mucopolisacàrids, col·lagen tipus i i vitamina C (Tendoactive®) sobre l’evolució clínica i estructural de les tendinopaties del tendó d’Aquil·les, del rotular i de l’epicòndil lateral del colze. Material i mètodes Es realitzà un estudi multicèntric prospectiu, de tipus exploratori en fase iv, obert i no comparatiu. S’inclogueren un total de 98 pacients amb tendinopaties (32 d’Aquil·les, 32 de rotular i 34 de l’epicòndil lateral) que reberen una dosi diària de 435 mg de mucopolisacàrids, 75 mg de col·lagen tipus i i 60 mg de vitamina C (equivalent a 3 càpsules al dia de Tendoactive®) durant 90 dies consecutius. Mensualment s’avaluà el dolor en repòs i en activitat mitjançant una escala visual analògica (EVA), la funció articular mitjançant els qüestionaris VISA-A, VISA-P i PRTEE, i el tendó afectat es caracteritzà ecogràficament. Resultats En els 3 tipus de tendinopatia es registrà una reducció significativa del dolor, tant en repòs com en activitat, des de la primera visita de control (dia 30) fins al final de l’estudi (dia 90). Així mateix, el dia 90 es detectà una millora del 38% en VISA-A, del 46% en VISA-P i del 77% en PRTEE (p < 0,001). Simultàniament es registrà una reducció del 12% en el gruix del tendó d’Aquil·les, del 10% en el rotular i del 20% en el tendó de l’epicòndil lateral (p < 0,05). Conclusions Els resultats de l’estudi indiquen que l’administració de Tendoactive® és segura i eficaç per millorar els símptomes clínics i l’evolució estructural de les tendinopaties del tendó d’Aquil·les, del tendó rotular i del tendó de l’epicòndil lateral

The efficacy and safety of oral mucopolysaccharide, type I collagen and vitamin C treatment in tendinopathy patients

Introduction and objectives Tendinopathy, which is accompanied by structural changes to the tendon, is a common sporting injury. The aim of this study was to evaluate the efficacy and safety of a nutritional supplement containing mucopolysaccharides, type I collagen and vitamin C (TendoactiveTM) on the clinical and structural evolution of tendinopathies of the Achilles tendon, patellar tendon and lateral epicondyle tendon in the elbow. Materials and methods A multicenter, open-label, non-comparative, prospective, exploratory phase iv study was performed. A total of 98 tendinopathy patients (32 Achilles, 32 patellar and 34 lateral epicondylar), who received a daily dose of 435 mg mucopolysaccharides, 75 mg type i collagen and 60 mg vitamin C (equivalent to three capsules of TendoactiveTM per day) for 90 consecutive days, were included. Every month, pain at rest and when active was assessed using a visual analogue scale (VAS), joint function was assessed using the VISA-A, VISA-P and PRTEE questionnaires, and the tendon affected was characterized by ultrasound. Results A significant reduction in pain both at rest and when active was observed between the first control visit (day 30) and the end of the study (day 90) for all three types of tendinopathy. Thus, a 38% improvement in VISA-A, 46% in VISA-P and 77% in PRTEE was observed on day 90 (P < .001). Similarly, a 12% decrease in the thickness of the Achilles tendon, a 10% decrease in the patellar tendon and a 20% decrease in the lateral epicondyle tendon was observed (P < .05). Conclusions The results of this study show that the administration of TendoactiveTM is safe and effective for improving the clinical symptoms and structural evolution of tendinopathies of the Achilles, patella and lateral epicondyle tendons

Eficacia y seguridad de un tratamiento oral a base de mucopolisacáridos, colágeno tipo i y vitamina C en pacientes con tendinopatías

Introducción y objetivos La tendinopatía es una lesión frecuente durante la práctica deportiva que cursa con una alteración estructural del tendón. El objetivo de este estudio fue evaluar la eficacia y la seguridad de un complemento alimentario a base de mucopolisacáridos, colágeno tipo i y vitamina C (Tendoactive®) sobre la evolución clínica y estructural de las tendinopatías del tendón de Aquiles, rotuliano y del epicóndilo lateral del codo. Material y métodos Se realizó un estudio multicéntrico prospectivo, de tipo exploratorio en fase iv , abierto y no comparativo. Se incluyeron un total de 98 pacientes con tendinopatías (32 de Aquiles, 32 de rotuliano y 34 del epicóndilo lateral) que recibieron una dosis diaria de 435 mg de mucopolisacáridos, 75 mg de colágeno tipo i y 60 mg de vitamina C (equivalente a 3 cápsulas al día de Tendoactive®) durante 90 días consecutivos. Mensualmente se evaluó el dolor en reposo y en actividad mediante una escala visual analógica (EVA), la función articular mediante los cuestionarios VISA-A, VISA-P y PRTEE, y se caracterizó ecográficamente el tendón afectado. Resultados En los 3 tipos de tendinopatía se registró una reducción significativa del dolor tanto en reposo como en actividad desde la primera visita de control (día 30) hasta el final del estudio (día 90). Asimismo el día 90 se detectó una mejora del 38% en VISA-A, del 46% en VISA-P y del 77% en PRTEE (p < 0,001). Simultáneamente se registró una reducción del 12% en el grosor del tendón de Aquiles, del 10% en el rotuliano y del 20% en el tendón del epicóndilo lateral (p < 0,05). Conclusiones Los resultados del estudio indican que la administración de Tendoactive® es segura y eficaz para mejorar los síntomas clínicos y la evolución estructural de las tendinopatías del tendón de Aquiles, tendón rotuliano y tendón del epicóndilo lateral

Efficacy and tolerability of EH301 for amyotrophic lateral sclerosis: a randomized, double-blind, placebo-controlled human pilot study

Amyotrophic lateral sclerosis (ALS) is a devastating neurodegenerative disease, characterized by progressive loss of spinal and cortical motor neurons, leading to muscular atrophy, respiratory failure, and ultimately death. There is no known cure, and the clinical benefit of the two drugs approved to treat ALS remains unclear. Novel disease-modifying therapeutics that are able to modulate the disease course are desperately needed. Our objective was to evaluate the efficacy and tolerability of Elysium Health's candidate drug EH301 in people with ALS (PALS).This was a single-center, prospective, double-blind, randomized, placebo-controlled pilot study. Thirty-two PALS were recruited thanks to the collaboration of the Spanish Foundation for ALS Research (FUNDELA). Study participants were randomized to receive either EH301 or placebo and underwent evaluation for 4 months. Differences between EH301 and placebo-treated participants were evaluated based on standard clinical endpoints, including the revised ALS functional rating scale (ALSFRS-R), forced vital capacity (FVC), and the Medical Research Council (MRC) grading scale.Compared to placebo, participants treated with EH301 demonstrated significant improvements in the ALSFRS-R score, pulmonary function, muscular strength, and in skeletal muscle/fat weight ratio. EH301 was shown to significantly slow the progression of ALS relative to placebo, and even showed improvements in several key outcome measures compared with baseline.This study provides evidence in support of the disease-modifying effects of EH301 for the treatment of ALS.Study Funded by the Catholic University San Vicente Mártir [grant 2017-216-001] and the University of Valencia [grant OTR2017-18255INVES] (Valencia, Spain). Elysium Health, Inc., NY (USA), provided the compounds tested in this study.Medicin

Pre-operative anxiolysis in children through a combined pharmacological therapy with hydroxyzine and a non-pharmacological distraction technique with a clown (SONRISA): study protocol for randomised double-blind clinical trial.

Background Surgery can generate significant stress and anxiety in up to 70% of the paediatric population. There are several pharmacological and non-pharmacological strategies to reduce pre-operative anxiety in children, however, they have several side effects and the available information about them is contradictory. The role of clowns and hydroxyzine in the management of anxiety is controversial, with some studies supporting and others contraindicating both strategies. Methods We propose a randomised double-blind, controlled clinical trial that will evaluate the effectiveness of both interventions (hydroxyzine and clowns), alone or in combination, to reduce pre-operative anxiety (using the modified Yale scale of preoperative anxiety) in children aged 2–16 years undergoing outpatient surgery (n = 188). Subjects will be randomised into two groups – (1) standard procedure (parental accompaniment) combined with placebo or (2) standard procedure combined with preoperative hydroxyzine. After randomisation, they will be divided by chance into two further groups, depending on the presence of clowns on the patient’s surgery day. Control of pre-operative anxiety will be determined in the four groups by a modified Yale scale of preoperative anxiety and cortisol levels. Compliance of children during induction of anaesthesia, time until anaesthesia recovery, presence of postoperative delirium and use of analgesia until discharge will be also assessed. For additional information, the children, parents and healthcare professionals involved in the study will complete a satisfaction survey. Conclusions This study aims to gather evidence on which of these four therapeutic options achieves the highest reduction of pre-operative anxiety with the best safety profile to allow paediatricians and anaesthesiologists to use the most effective and safe option for their patients.post-print781 K

Prevention, Diagnosis and Management of Post-Surgical Mediastinitis in Adults Consensus Guidelines of the Spanish Society of Cardiovascular Infections (SEICAV), the Spanish Society of Thoracic and Cardiovascular Surgery (SECTCV) and the Biomedical Research Centre Network for Respiratory Diseases (CIBERES)

Prevention, Diagnosis and Management of Post-Surgical Mediastinitis in Adults Consensus Guidelines of the Spanish Society of Cardiovascular Infections (SEICAV), the Spanish Society of Thoracic and Cardiovascular Surgery (SECTCV) and the Biomedical Research Centre Network for Respiratory Diseases (CIBERES) doctors and radiologists. Despite the clinical and economic consequences of sternal wound infections, to date, there are no specific guidelines for the prevention, diagnosis and management of mediastinitis based on a multidisciplinary consensus. The purpose of the present document is to provide evidencebased guidance on the most effective diagnosis and management of patients who have experienced or are at risk of developing a post-surgical mediastinitis infection in order to optimise patient outcomes and the process of care. The intended users of the document are health care providers who help patients make decisions regarding their treatment, aiming to optimise the benefits and minimise any harm as well as the workload.Funding: J.M. Miró was a recipient of a personal 80:20 research grant from IDIBAPS during the period 2017–2021