Post-acute phase and sequelae management of epidermal necrolysis: an international, multidisciplinary DELPHI-based consensus.

BACKGROUND: Long-term sequelae are frequent and often disabling after epidermal necrolysis (Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN)). However, consensus on the modalities of management of these sequelae is lacking. OBJECTIVES: We conducted an international multicentric DELPHI exercise to establish a multidisciplinary expert consensus to standardize recommendations regarding management of SJS/TEN sequelae. METHODS: Participants were sent a survey via the online tool "Survey Monkey" consisting of 54 statements organized into 8 topics: general recommendations, professionals involved, skin, oral mucosa and teeth, eyes, genital area, mental health, and allergy workup. Participants evaluated the level of appropriateness of each statement on a scale of 1 (extremely inappropriate) to 9 (extremely appropriate). Results were analyzed according to the RAND/UCLA Appropriateness Method. RESULTS: Fifty-two healthcare professionals participated. After the first round, a consensus was obtained for 100% of 54 initially proposed statements (disagreement index < 1). Among them, 50 statements were agreed upon as 'appropriate'; four statements were considered 'uncertain', and ultimately finally discarded. CONCLUSIONS: Our DELPHI-based expert consensus should help guide physicians in conducting a prolonged multidisciplinary follow-up of sequelae in SJS-TEN.

Supportive care in the acute phase of Stevens-Johnson syndrome and toxic epidermal necrolysis: an international, multidisciplinary Delphi-based consensus.

BACKGROUND: Supportive care is the cornerstone of management of adult and paediatric Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN). However, consensus on the modalities of supportive care is lacking. OBJECTIVES: Our aim in this international multicentric Delphi exercise was to establish a multidisciplinary expert consensus to standardize recommendations regarding supportive care in the acute phase of SJS/TEN. METHODS: Participants were sent a survey via the online tool SurveyMonkey, consisting of 103 statements organized into 11 topics: multidisciplinary team composition, suspect drug management, infection prevention, fluid resuscitation and prevention of hypothermia, nutritional support, pain and psychological distress management, management of acute respiratory failure, local skincare, ophthalmological management, management of other mucosa, and additional measures. Participants evaluated the level of appropriateness of each statement on a scale of 1 (extremely inappropriate) to 9 (extremely appropriate). The results were analysed according to the RAND/UCLA Appropriateness Method. RESULTS: Forty-five participants from 13 countries (on three continents) participated. After the first round, a consensus was obtained for 82.5% of the 103 initially proposed statements. After the second round, a final consensus was obtained for 102 statements. CONCLUSIONS: We have reached an international Delphi-based consensus on best supportive care practice for SJS/TEN. Our expert consensus should help guide physicians in treating patients with SJS/TEN and thereby improve short-term prognosis and the risk of sequelae.

Thrombin-promoted release of UDP-glucose from human astrocytoma cells.

BACKGROUND AND PURPOSE: The P2Y14 receptor is activated by UDP-sugars, most potently by UDP-glucose, but not by free nucleotides, suggesting that UDP-glucose is the cognate agonist for this receptor. However, evidence for regulated release of UDP-glucose is scarce. In the present study, the occurrence of receptor-promoted release of UDP-glucose was investigated, using 1321N1 human astrocytoma cells. EXPERIMENTAL APPROACH: UDP-glucose release and hydrolysis were measured using HPLC-based techniques. Phospholipase C activation and actin cytoskeleton reorganization were assessed by measuring inositol phosphate formation and fluorescence confocal microscopy, respectively. KEY RESULTS: Thrombin and the protease-activating receptor-1 (PAR1) peptide TFLLRNPNDK (PAR1-AP) evoked the release of UDP-glucose and ATP, which was accompanied by enhanced inositol phosphate formation. Although carbachol promoted fourfold greater inositol phosphate formation than thrombin, it failed to promote nucleotide release. Thrombin-promoted nucleotide release was inhibited by BAPTA-AM, brefeldin A and cytochalasin D, and was insensitive to Pertussis toxin and PI3-kinase inhibitors. Thrombin, but not carbachol, induced actin cytoskeleton reorganization, a hallmark of Rho activation in 1321N1 cells. However, PAR-promoted UDP-glucose release was not affected by Rho kinase inhibition. CONCLUSIONS AND IMPLICATIONS: PAR1-evoked UDP-glucose release reflected a Ca2+-dependent mechanism, engaging additional signalling independently of G(i) and Rho kinase activation and requiring a functional actin cytoskeleton and Golgi structures. Our study demonstrates the occurrence of Ca2+ -dependent release of UDP-glucose from astrocytoma cells in response to a physiologically relevant stimulus, that is, a G-protein-coupled receptor agonist. Given the presence of P2Y14 receptors in astrocytes, UDP-glucose may have important autocrine/paracrine functions in the brain.

La formación del médico en Perú y en los EE. UU: la carrera del especialista / No disponible

La educación médica es un proceso que se inicia de forma temprana y continúa durante toda la vida, y a lo largo de ella se adquieren no sólo conocimientos y habilidades sino también aptitudes. En este artículo informamos a los jóvenes estudiantes de medicina acerca de las posibilidades de superación profesional en la carrera médica, así como de las dificultades a las que se enfrentarán, ya sea en Perú, en los EE.UU. o en cualquier otro país del mundo. Para ello describimos de manera comparativa el camino que se sigue en Perú y en los. EE.UU. para llegar a ser médico y luego especialista utilizando el ejemplo del dermatólogo. Hacemos hincapié en los problemas que se observan en ciertos países latinoamericanos: la sobreproducción de médicos, la exigencia de másters y doctorados a los médicos docentes, la necesidad de cargos "vitalicios", además de la crisis económica y social que sufren las universidades y los países y de cómo todo esto repercute en la salud del pueblo. Además, mostramos la preparación íntegra, calificada y garantizada por múltiples instituciones que reciben los médicos y especialistas en los EE.UU. para que se tome como modelo que seguir y superar (AU)

Medical education is a process that begins early and continues throughout life. During this process not only knowledge and skills are acquired but also attitudes. In the present article we provide information to young medical students on the possibilities of professional betterment during their careers as well as on the difficulties they will face during this process, whether in Peru, the United States or in any other country. To do this, we compare the route followed in Peru and the United States to qualify as a doctor and later as a specialist using the example of dermatologist. We emphasize the problems observed in some Latin American countries: the training of too many doctors, the need for master's degrees and doctorates for medical teachers, and the need for position held for life, as well as the economic and social crisis in the universities and countries as how all of this affects the health of the populace. Moreover, we demonstrate the integrated training, recognized and guaranteed by multiple Institutlons that receive doctors and specialists in the United States, so that it can be taken as a model to be followed and improved (AU)