RESUMEN
BACKGROUND: Fibrodysplasia ossificans progressiva (FOP) is a very rare, severe genetic disorder triggered by a gain-of-function mutation in the ACVR1 gene that codes for the type I bone morphogenetic protein (BMP) receptor ACVR1 (activin A receptor-type 1), also known as ALK2 (activin receptor-like kinase-2). It leads to the onset and progression of heterotopic ossification (HO) in soft and connective tissue. HO is often preceded by episodes of soft tissue swelling or flare-ups. Flare-ups, characteristic of FOP, may be induced by trauma, infection, vaccination, or other medications, as well as surgical procedures or may occur spontaneously. As patients age, they develop severe mobility limitations due to progressive HO formation, including immobility, causing a shortened life expectancy. FOP's first characteristic clinical sign is the congenital malformation of one or both big toes with valgus axis deviation, which is present in almost all patients. To confirm the diagnosis, molecular genetic analysis of the ACVR1 gene is possible. AIM OF THE RECOMMENDATIONS: This white paper aims to provide an overview of the necessary prerequisites and conditions for the care of patients with FOP and positively contribute to patients with FOP by improving the overall availability of knowledge. To achieve this, relevant aspects of the care of the very rare disease FOP are presented, from the initial diagnosis to the care in regular care based on the authors' knowledge (German FOP network) and the international FOP Treatment Guidelines. The recommendations presented here are addressed to all actors and decision-makers in the health care system and are also intended to inform patients and the public.
Asunto(s)
Miositis Osificante , Osificación Heterotópica , Humanos , Miositis Osificante/diagnóstico , Mutación , Osificación Heterotópica/genética , Proteínas Morfogenéticas Óseas/genética , Atención a la SaludRESUMEN
INTRODUCTION: Neuroblastoma (NB) is one of the most common malignant tumors in infancy. The commonly used International Neuroblastoma Staging System is not suitable for determining the surgical risks. To address this, we aimed to evaluate the correlation between so-called image-defined risk factors (IDRFs) and the surgical risks in abdominal neuroblastoma. MATERIAL AND METHODS: We evaluated 60 cases who underwent surgical intervention and examined the pre-surgical radiological imaging to look for IDRFs and surgical complications in children with abdominal neuroblastoma. RESULTS: The MRI- and CT-scans showed a total of 122 IDRFs in 39 cases. Complete resection was carried out in 50%, partial excision in 32%, and biopsy in 18% of cases. Total resection was possible in 100% of cases with no IDRF. Where IDRFs were present, total resection was only possible in 26% of cases (p<0.0001). We found a highly significant, negative correlation between the number of IDRFs and the possibility of performing complete resection of NB (p<0.0001). 7 (11.6%) complications were detected, all in patients who showed at least one IDRF previously. CONCLUSION: Our findings indicate that IDRFs are useful indicators for predicting surgical risk and surgical outcome and thus should be taken into account when planning surgery.
Asunto(s)
Neoplasias Abdominales/cirugía , Neuroblastoma/cirugía , Complicaciones Posoperatorias , Neoplasias Abdominales/complicaciones , Neoplasias Abdominales/patología , Vasos Sanguíneos/lesiones , Preescolar , Femenino , Humanos , Lactante , Riñón/lesiones , Imagen por Resonancia Magnética , Masculino , Estadificación de Neoplasias , Neuroblastoma/complicaciones , Neuroblastoma/patología , Valor Predictivo de las Pruebas , Factores de Riesgo , Tomografía Computarizada por Rayos XRESUMEN
Integral membrane proteins are sorted via the secretory pathway. It was proposed that this pathway is non-selective provided that the cargo protein is properly assembled and lacks an endoplasmic reticulum (ER) retention signal. However, recent experimental evidence suggests that efficient export of proteins from the ER to the Golgi complex is not simply a default pathway. Here we demonstrate a novel sequence motif (FxYENEV) in the cytoplasmic C-terminus of mammalian inward rectifier potassium (Kir) channels which determines ER export. This motif is found to be both necessary and sufficient for efficient export from the ER that eventually leads to efficient surface expression of Kir2.1 channels.