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Background: ROHHAD syndrome (Rapid-onset Obesity with Hypothalamic dysfunction, Hypoventilation and Autonomic Dysregulation) is rare. Rapid-onset morbid obesity is usually the first recognizable sign of this syndrome, however a subset of patients develop ROHHAD syndrome without obesity. The prevalence of this entity is currently unknown. Alteration of respiratory control as well as dysautonomic disorders often have a fatal outcome, thus early recognition of this syndrome is essential. Material and methods: A retrospective, observational, multicenter study including all cases of ROHHAD without rapid-onset obesity diagnosed in France from 2000 to 2020. Results: Four patients were identified. Median age at diagnosis was 8 years 10 months. Median body mass index was 17.4 kg/m2. Signs of autonomic dysfunction presented first, followed by hypothalamic disorders. All four patients had sleep apnea syndrome. Hypoventilation led to the diagnosis. Three of the four children received ventilatory support, all four received hormone replacement therapy, and two received psychotropic treatment. One child in our cohort died at 2 years 10 months old. For the three surviving patients, median duration of follow-up was 7.4 years. Conclusion: ROHHAD syndrome without rapid-onset obesity is a particular entity, appearing later than ROHHAD with obesity. This entity should be considered in the presence of dysautonomia disorders without brain damage. Likewise, the occurrence of a hypothalamic syndrome with no identified etiology requires a sleep study to search for apnea and hypoventilation. The identification of ROHHAD syndrome without rapid-onset obesity is a clinical challenge, with major implications for patient prognosis.
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Rationale: The characterization of new theranostic biomarkers is crucial to improving the clinical outcome of patients with advanced lung cancer. Here, we aimed at characterizing the P2RX7 receptor, a positive modulator of the anti-tumor immune response, in patients with lung adenocarcinoma. Methods: The expression of P2RX7 and its splice variants was analyzed by RT-qPCR using areas of tumor and non-tumor lung adenocarcinoma (LUAD) tissues on both immune and non-immune cells. The biological activity of P2RX7 was studied by flow cytometry using fluorescent dyes. Bi-molecular fluorescence complementation and confocal microscopy were used to assess the oligomerization of P2RX7. Tumor immune infiltrates were characterized by immunohistochemistry. Results: Fifty-three patients with LUAD were evaluated. P2RX7A, and 3 alternative splice variants were expressed in LUAD tissues and expression was down regulated in tumor versus adjacent non-tumor tissues. The protein retained biological activity only in immune cells. The P2RX7B splice variant was differentially upregulated in immune cells (P < 0.001) of the tumor and strong evidence of oligomerization of P2RX7A and B was observed in the HEK expression model, which correlated with a default in the activity of P2RX7. Finally, LUAD patients with a high level of P2RX7B had non-inflamed tumors (P = 0.001). Conclusion: Our findings identified P2RX7B as a new theranostic tool to restore functional P2RX7 activity and open alternative therapeutic opportunities to improve LUAD patient outcome.
Asunto(s)
Adenocarcinoma del Pulmón/genética , Biomarcadores de Tumor/genética , Neoplasias Pulmonares/genética , Recurrencia Local de Neoplasia/etnología , Receptores Purinérgicos P2X7/genética , Adenocarcinoma del Pulmón/inmunología , Adenocarcinoma del Pulmón/patología , Adenocarcinoma del Pulmón/terapia , Adulto , Anciano , Anciano de 80 o más Años , Empalme Alternativo , Biomarcadores de Tumor/metabolismo , Quimioterapia Adyuvante , Femenino , Regulación Neoplásica de la Expresión Génica/inmunología , Células HEK293 , Humanos , Pulmón/inmunología , Pulmón/patología , Pulmón/cirugía , Neoplasias Pulmonares/inmunología , Neoplasias Pulmonares/patología , Neoplasias Pulmonares/terapia , Linfocitos Infiltrantes de Tumor/inmunología , Linfocitos Infiltrantes de Tumor/metabolismo , Masculino , Persona de Mediana Edad , Recurrencia Local de Neoplasia/genética , Recurrencia Local de Neoplasia/inmunología , Neumonectomía , Estudios Prospectivos , Isoformas de Proteínas/genética , Isoformas de Proteínas/metabolismo , Multimerización de Proteína/genética , Multimerización de Proteína/inmunología , Receptores Purinérgicos P2X7/metabolismo , Estudios Retrospectivos , Transducción de Señal/genética , Transducción de Señal/inmunología , Linfocitos T/inmunología , Linfocitos T/metabolismo , Regulación hacia ArribaRESUMEN
We reported the first pediatric case of auto-immune hepatitis with positive anti-P antibodies. On the basis of our findings, adding auto anti-P screening in pediatric seronegative HAI may be recommended.
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OBJECTIVES: Plummer-Vinson syndrome (PVS), also called Kelly-Paterson syndrome, is a rare cause of dysphagia in children. This syndrome associates single or multiple webs in the upper esophagus with frequent iron deficiency. METHODS: We reported 3 pediatric cases of PVS before analyzing all of the cases of PVS in children reported in the PubMed and EMBASE databases. RESULTS: Among 17 reported PVS cases in children, all of the patients experienced iron-deficiency anemia, and no immunological disease was reported. The male/female ratio was 1/1.9, and most cases were observed in adolescents. Conversely to adults, endoscopic dilation was often necessary because dysphagia resisted iron supplementation. A single dilation was usually sufficient. One case of pediatric PVS experienced esophageal cancer in adulthood. CONCLUSIONS: In the case of dysphagia in children, a swallow barium exploration with lateral incidence should look for PVS. Conversely to adults, an endoscopic dilation is frequently necessary to control dysphagia in children.