RESUMO
Myelofibrosis (MF) occurs as part of the natural history of polycythemia vera (PV) and essential thrombocythemia (ET), and remarkably shortens survival. Although JAK2V617F and CALR allele burden are the main transformation risk factors, inflammation plays a critical role by driving clonal expansion toward end-stage disease. NF-κB is a key mediator of inflammation-induced carcinogenesis. Here, we explored the involvement of miR-146a, a brake in NF-κB signaling, in MPN susceptibility and progression. rs2910164 and rs2431697, that affect miR-146a expression, were analyzed in 967 MPN (320 PV/333 ET/314 MF) patients and 600 controls. We found that rs2431697 TT genotype was associated with MF, particularly with post-PV/ET MF (HR = 1.5; p < 0.05). Among 232 PV/ET patients (follow-up time=8.5 years), 18 (7.8%) progressed to MF, being MF-free-survival shorter for rs2431697 TT than CC + CT patients (p = 0.01). Multivariate analysis identified TT genotype as independent predictor of MF progression. In addition, TT (vs. CC + CT) patients showed increased plasma inflammatory cytokines. Finally, miR-146a-/- mice showed significantly higher Stat3 activity with aging, parallel to the development of the MF-like phenotype. In conclusion, we demonstrated that rs2431697 TT genotype is an early predictor of MF progression independent of the JAK2V617F allele burden. Low levels of miR-146a contribute to the MF phenotype by increasing Stat3 signaling.
Assuntos
MicroRNAs/genética , Transtornos Mieloproliferativos/genética , Mielofibrose Primária/genética , Idoso , Alelos , Animais , Citocinas/genética , Progressão da Doença , Feminino , Genótipo , Humanos , Inflamação/genética , Inflamação/patologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Pessoa de Meia-Idade , Mutação/genética , Transtornos Mieloproliferativos/patologia , NF-kappa B/genética , Policitemia Vera/genética , Policitemia Vera/patologia , Transdução de Sinais/genética , Trombocitemia Essencial/genética , Trombocitemia Essencial/patologiaRESUMO
Resumen ANTECEDENTES: Los oblitomas, u objetos extraños retenidos en el abdomen posterior a una cirugía, son consecuencia de una iatrogenia que causa morbilidad, dificultad diagnóstica, problemas médico-legales, y complicaciones para las pacientes, el médico y la institución hospitalaria. CASO CLINICO: Paciente de 27 años de edad, con un cuerpo extraño retenido en la cavidad abdominal (bulbo de la cánula de Yankauer), olvidado durante una cesárea de urgencia. El diagnóstico y tratamiento fueron expeditos, con reintervención quirúrgica para extraer el cuerpo extraño, sin complicaciones y con evolución satisfactoria de la paciente. CONCLUSIONES: El estudio actual de los oblitomas u objetos extraños retenidos es un problema creciente, con estadísticas en contra, sobre todo asociadas con elevada frecuencia de cesáreas y alta prevalencia de obesidad materna durante el embarazo, esto debe alertar a los ginecoobstetras a conducirse con más cuidado para evitar este tipo de accidentes.
Abstract BACKGROUND: Oblitomas or retained surgical items (RSI) in the abdominal cavity after surgery are cause of iatrogenic medical problems, that origin high morbidity, difficult diagnosis and medical malpractice claims to may lead complications to patients, physicians included to hospital. CLINICAL CASE: We report an exceptional case, in a 27-year-old women, with a bulb of Yankahuer cannula retained in abdominal cavity, Forgotten during an emergency cesarean section. The diagnosis and management was realized with opportunity, avoiding complications. CONCLUSION: Actually, the study of oblitoma or foreign objects retained that's considered a growing problem, with statistics against it, mainly associated with high frequency of cesarean sections and high prevalence of maternal obesity during pregnancy. In fact, that situation place the gynecologists and obstetricians at a latent risk for this event. It is important to know the predisposing factors for its prevention and to implement institutional programs to reduce complications.
RESUMO
Few data are available on the prevalence and relevance of chlamydiae in wild mammals, and even fewer studies have been conducted to determine the prevalence of Chlamydophila abortus in wildlife hosts, most probably due to the absence of suitable species-specific serological assays for testing sera from wild animals. In light of this, we have developed two in-house blocking-ELISA tests for detection of antibodies against Chlamydiaceae and C. abortus in wild ungulates, and analyzed the relationship between geographical and biological factors and the prevalence of antibodies against Chlamydiaceae and C. abortus in 434 wild ungulates from Spain, including sera from European wild boar, Red deer, Fallow deer, Roe deer, Mouflon, Barbary sheep, Southern chamois, and Iberian ibex. Serology revealed that 41.7+/-4% of the sera were positive for the b-ELISA-LPS (Chlamydiaceae-specific) and 18.9+/-3% for the b-ELISA-rPOMP (C. abortus-specific). Antibodies against Chlamydiaceae lipopolysaccharide (LPS) were detected in sera from all eight ungulate species, the prevalence ranging from 23 to 60%. Iberian ibex was the only wild ungulate not showing seropositivity to the C. abortus specific polymorphic outer membrane protein (POMP). The prevalence of anti-POMP antibodies in the other seven wild ungulate species ranged from 7 to 40%. While significant seroprevalence differences were detected among species and among sampling regions, no effect of age and sex was observed. The high prevalence levels found should be considered with regards to livestock and human health, and warrant further research.
