RESUMO
Background: Meningiomas are the most common primary tumor of the central nervous system. The relationship between meningioma and progestins is frequently mentioned but has not been elucidated. Patients and methods: We identified 40 female patients operated for a meningioma after long-term progestin therapy and performed targeted next generation sequencing to decipher the mutational landscape of hormone-related meningiomas. A published cohort of 530 meningiomas in women was used as a reference population. Results: Compared with the control population of meningiomas in women, progestin-associated meningiomas were more frequently multiple meningiomas [19/40 (48%) versus 25/530 (5%), P < 10-12] and located at the skull base [46/72 (64%) versus 241/481 (50%), P = 0.03]. We found a higher frequency of PIK3CA mutations [14/40 (35%) versus 18/530 (3%), P < 10-8] and TRAF7 mutations [16/40 (40%) versus 140/530 (26%), P < 0.001] and a lower frequency of NF2-related tumors compared with the control population of meningiomas [3/40 (7.5%) versus 169/530 (32%), P < 0.001]. Conclusion: This shift in mutational landscape indicates the vulnerability of certain meningeal cells and mutations to hormone-induced tumorigenesis. While the relationship between PIK3CA mutation frequency and hormone-related cancers such as breast and endometrial cancer is well-known, this hormonally induced mutational shift is a unique feature in molecular oncology.
Assuntos
Neoplasias Meníngeas/genética , Meningioma/genética , Congêneres da Progesterona/efeitos adversos , Adulto , Idoso , Idoso de 80 Anos ou mais , Acetato de Clormadinona/efeitos adversos , Classe I de Fosfatidilinositol 3-Quinases/genética , Acetato de Ciproterona/efeitos adversos , Análise Mutacional de DNA , Feminino , Humanos , Acetato de Megestrol/efeitos adversos , Neoplasias Meníngeas/patologia , Meningioma/patologia , Pessoa de Meia-Idade , Mutação , Estudos Retrospectivos , Adulto JovemRESUMO
BACKGROUND: Lemierre syndrome is typically associated with ear, nose, and throat (ENT) infections caused by Fusobacterium necrophorum. Since 2002, cases of atypical Lemierre-like syndrome secondary to Staphylococcus aureus have been reported. CASES: We report two pediatric cases of atypical Lemierre syndrome with a similar presentation: exophthalmia, absence of pharyngitis, metastatic lung infection, and intracranial venous sinus thrombosis. Both patients had a favorable outcome following treatment with antibiotics, anticoagulation, and corticosteroids. CONCLUSION: Regular therapeutic monitoring of antibiotic levels helped to optimize antimicrobial treatment in both cases.
Assuntos
Síndrome de Lemierre , Faringite , Infecções Estafilocócicas , Humanos , Criança , Meticilina/uso terapêutico , Staphylococcus aureus , Síndrome de Lemierre/diagnóstico , Síndrome de Lemierre/tratamento farmacológico , Síndrome de Lemierre/complicações , Antibacterianos/uso terapêutico , Infecções Estafilocócicas/complicações , Infecções Estafilocócicas/diagnóstico , Infecções Estafilocócicas/tratamento farmacológico , Faringite/etiologiaRESUMO
OBJECTIVES: The aim of this study was to describe severe forms of novel coronavirus disease 2019 in children, including patient characteristics, clinical, laboratory, and imaging findings, as well as the disease management and outcomes. METHODS: This was a retrospective, single-center, observational study conducted in a pediatric intensive and high-dependency care unit (PICU, HDU) in an urban hospital in Paris. All patients, aged from 1 month to 18 years, admitted for confirmed or highly suspected SARS-CoV-2 were included. RESULTS: We analyzed the data of 27 children. Comorbidities (n=19, 70%) were mainly neurological (n=7), respiratory, (n=4), or sickle cell disease (n=4). SARS-CoV-2 PCR results were positive in 24 children (nasopharyngeal swabs). The three remaining children had a chest CT scan consistent with COVID-19. Respiratory involvement was observed in 24 patients (89%). Supportive treatments were invasive mechanical ventilation (n=9), catecholamine (n=4), erythropheresis (n=4), renal replacement therapy (n=1), and extracorporeal membrane oxygenation (n=1). Five children died, of whom three were without past medical history. CONCLUSION: This study highlighted the large spectrum of clinical presentation and time course of disease progression as well as the non-negligible occurrence of pediatric life-threatening and fatal cases of COVID-19 mostly in patients with comorbidities. Additional laboratory investigations are needed to further analyze the mechanism underlying the variability of SARS-Cov-2 pathogenicity in children.
Assuntos
Betacoronavirus , Infecções por Coronavirus/diagnóstico , Infecções por Coronavirus/mortalidade , Pneumonia Viral/diagnóstico , Pneumonia Viral/mortalidade , Adolescente , Betacoronavirus/isolamento & purificação , COVID-19 , Teste para COVID-19 , Criança , Pré-Escolar , Técnicas de Laboratório Clínico , Comorbidade , Infecções por Coronavirus/epidemiologia , Infecções por Coronavirus/terapia , Progressão da Doença , Feminino , Humanos , Lactente , Masculino , Pandemias , Paris/epidemiologia , Pneumonia Viral/epidemiologia , Pneumonia Viral/terapia , Prognóstico , Estudos Retrospectivos , Fatores de Risco , SARS-CoV-2 , Índice de Gravidade de DoençaRESUMO
The number of reports on baclofen intoxication has increased in recent years. Here we report the case of a 4-year-old boy in deep coma who was referred to the pediatric intensive care unit. The patient was intubated and mechanically ventilated. A computerized tomography scan without contrast showed a collapsed appearance of the ventricular system suggesting diffuse cerebral edema. A multichannel electroencephalogram registered 6 h after admission showed a very slow and ample continuous pattern, without structure, nonreactive to stimulations, expressing diffuse and severe nonspecific cerebral pain. A targeted analysis to determine the baclofen plasma levels was performed. Test results of plasma samples were highly positive for baclofen (2009 ng/mL). Following 36 h of mechanical ventilation, the patient rapidly regained consciousness and recovered normal neurological behavior. The present case demonstrates the importance of considering baclofen overdosage in cases of deep coma with areflexia, and emphasizes the importance of warning parents about the potential toxicity of baclofen when prescribing the drug to a family member. A review of the literature on pediatric baclofen overdose is included.
Assuntos
Baclofeno/intoxicação , Coma/induzido quimicamente , Overdose de Drogas/complicações , Pré-Escolar , Coma/terapia , Overdose de Drogas/terapia , Humanos , Masculino , Índice de Gravidade de DoençaRESUMO
Prevalence of complement protein deficiency in the general population is rare and its association with an increased risk of meningococcal infection is well established. However, management of these patients with potentially serious infections and indications warranting a search for such a deficiency have not met with consensus. We report the case of a 3-year-old child with no significant medical history who consulted in an emergency department for a fever after a stay in Senegal. Medical explorations concluded in septicemia and meningococcal W meningitis with a favorable outcome. Secondarily, we highlighted a complete deficiency of complement component C6. We diagnosed the same deficit in his twin sister who presented no infection. A long-term prophylactic antibiotic therapy and a meningococcal conjugate vaccine A,C,Y,W were set up for the twins. Recurrent invasive meningococcal infections and highlighting certain meningococcal serogroups are currently indications for complement protein exploration. We suggest expanding the search criteria for a complement protein deficiency after a single event of invasive meningococcal infection. This is an easy, rapid, and cost-effective screening system by dosage of CH50, C3, C4, and AP50. The arrival of the new meningococcal B vaccine will contribute to improving these patients' care. Family screening is necessary for prophylactic therapy.