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1.
Rheumatology (Oxford) ; 60(6): 2878-2883, 2021 06 18.
Artigo em Inglês | MEDLINE | ID: mdl-34144604

RESUMO

OBJECTIVE: FMF is an autoinflammatory disease of genetic origin. Colchicine is the mainstay of treatment for the prevention of attacks and long-term complications but 5-10% of FMF patients are resistant to colchicine therapy. The aim of our study was to investigate the real-life safety and efficacy of anakinra in a cohort of patients with colchicine-resistant FMF. METHODS: In this retrospective study, patients treated with anakinra for colchicine-resistant FMF between 2010 and 2018 were identified using the computerized database of Sheba Medical Center and enrolled in the study. Data from structured clinical files were analysed to evaluate the efficacy and safety outcomes. To assess efficacy, we used the Global Assessment Score (GAS), a measure comprised of three different domains: number of attacks per month, duration of attacks and number of sites involved in the attacks. Reported adverse events were compiled. RESULTS: A total of 44 patients (24 female) were treated with anakinra. Of these patients, 75% were homozygous for the M649V mutation. The mean duration of treatment was 18 months. The GAS decreased significantly from 6.6 (IQR 5.3-7.8) before treatment to 2 (IQR 0-4.2) while on treatment (P < 0.001). During anakinra treatment, six hospitalizations were reported (three due to related adverse effects). In addition, 11 patients suffered from injection site reactions (5 ceased treatment). Twelve patients reported mild side effects. CONCLUSION: Treatment with anakinra is beneficial for the majority of colchicine-resistant FMF patients and is relatively safe.


Assuntos
Febre Familiar do Mediterrâneo/tratamento farmacológico , Proteína Antagonista do Receptor de Interleucina 1/uso terapêutico , Adulto , Antirreumáticos/uso terapêutico , Estudos de Coortes , Colchicina , Resistência a Medicamentos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos
2.
Pediatr Diabetes ; 19(8): 1351-1356, 2018 12.
Artigo em Inglês | MEDLINE | ID: mdl-30225917

RESUMO

BACKGROUND/OBJECTIVE: Lifestyle modification is the therapy of choice for childhood obesity, yet the response rate is variable and may be affected by genetic factors. We aimed to investigate predictors of poor response to lifestyle modification obesity treatment in children. METHODS: A prospective cohort study of 434 youths (64.5% females) between 4 and 20 years of age undergoing a standard care of lifestyle modification obesity management for 35.9 ± 20.8 months at Yale Childhood Obesity Clinic, USA. The primary outcome was a "poor response," defined as the quintile with the largest increase in BMI Z-score over time. The secondary outcome was the endpoint BMI Z-score. Covariates investigated were sex, baseline pubertal status and degree of obesity, race, biochemical profile, and family history of overweight. A subsample (n = 214) had FTO genotyping (SNP rs8050136) tested. RESULTS: Males (hazard ratio [HR] = 5.35, 95% confidence interval [CI] [3.32-8.61], P < 0.0001) and pubertal adolescents (HR = 2.78, [1.40-5.50], P = 0.003) compared to prepubertal children were more prone to respond poorly. Baseline degree of obesity was associated with relative protection from responding poorly (HR per BMI Z-score unit = 0.32, [0.17-0.61], P = 0.0006). Carriers of the FTO obesity-predisposing allele (AA genotype) were protected from responding poorly compared to non-carriers (CC genotype) (HR = 0.33, [0.12-0.88], P = 0.028). CONCLUSIONS: Boys and pubertal adolescents are more prone to respond poorly to standard obesity care while those with greater baseline degree of obesity and carriers of the FTO obesity-predisposing allele are not.


Assuntos
Dioxigenase FTO Dependente de alfa-Cetoglutarato/genética , Obesidade Infantil/diagnóstico , Obesidade Infantil/genética , Obesidade Infantil/terapia , Adolescente , Adulto , Terapia Comportamental/métodos , Glicemia/análise , Glicemia/genética , Glicemia/metabolismo , Criança , Pré-Escolar , Feminino , Predisposição Genética para Doença , Genótipo , Humanos , Estilo de Vida , Masculino , Ambulatório Hospitalar , Obesidade Infantil/sangue , Polimorfismo de Nucleotídeo Único , Prognóstico , Fatores de Risco , Comportamento de Redução do Risco , Padrão de Cuidado , Resultado do Tratamento , Adulto Jovem
3.
J Clin Endocrinol Metab ; 102(9): 3406-3414, 2017 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-28911135

RESUMO

Context: Homeostatic energy balance is controlled via the hypothalamus, whereas regions controlling reward and cognitive decision-making are critical for hedonic eating. Eating varies across the menstrual cycle peaking at the midluteal phase. Objective: To test responses of females with regular cycles during midfollicular and midluteal phase and of users of monophasic oral contraception pills (OCPs) to visual food cues. Design: Participants performed a functional magnetic resonance imaging while exposed to visual food cues in four time points: fasting and fed conditions in midfollicular and midluteal phases. Patients: Twenty females with regular cycles and 12 on monophasic OCP, aged 18 to 35 years. Main Outcome Measures: Activity in homeostatic (hypothalamus), reward (amygdala, putamen and insula), frontal (anterior cingulate cortex, dorsolateral prefrontal cortex), and visual regions (calcarine and lateral occipital cortex). Setting: Tertiary hospital. Results: In females with regular cycles, brain regions associated with homeostasis but also the reward system, executive frontal areas, and afferent visual areas were activated to a greater degree during the luteal compared with the follicular phase. Within the visual areas, a dual effect of hormonal and prandial state was seen. In females on monophasic OCPs, characterized by a permanently elevated progesterone concentration, activity reminiscent of the luteal phase was found. Androgen, cortisol, testosterone, and insulin levels were significantly correlated with reward and visual region activation. Conclusions: Hormonal mechanisms affect the responses of women's homeostatic, emotional, and attentional brain regions to food cues. The relation of these findings to eating behavior throughout the cycle needs further investigation.


Assuntos
Córtex Cerebral/diagnóstico por imagem , Comportamento Alimentar/fisiologia , Imageamento por Ressonância Magnética/métodos , Ciclo Menstrual/fisiologia , Sistemas Neurossecretores/fisiologia , Estimulação Luminosa , Adolescente , Adulto , Tonsila do Cerebelo/fisiologia , Córtex Cerebral/fisiologia , Sinais (Psicologia) , Comportamento Alimentar/psicologia , Feminino , Fase Folicular/fisiologia , Humanos , Hipotálamo/fisiologia , Fase Luteal/fisiologia , Ciclo Menstrual/psicologia , Estudos de Amostragem , Adulto Jovem
4.
Diabetologia ; 56(9): 1914-8, 2013 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-23765186

RESUMO

AIMS/HYPOTHESIS: Bariatric surgery is gaining acceptance as a 'metabolic surgical intervention' for patients with type 2 diabetes. The optimal form of surgery and the mechanism of action of these procedures are much debated. We compared two bariatric procedures for obese patients with type 2 diabetes and evaluated their effects on HbA1c and glucose tolerance. METHODS: We performed a parallel un-blinded randomised trial of Roux-en-Y gastric bypass (RYGB) vs sleeve gastrectomy (SG) in 41 obese patients with type 2 diabetes, who were bariatric surgery candidates attending the obesity clinic. HbA1c, body composition and glucose tolerance were evaluated at baseline, and at 3 and 12 months. RESULTS: Of the 41 patients, 37 completed the follow-up (19 RYGB, 18 SG). Both groups had similar baseline anthropometric and biochemical measures, and showed comparable weight loss and fat:fat-free mass ratio changes at 12 months. A similar normalisation of HbA1c levels was observed as early as 3 months post-surgery (6.37 ± 0.71% vs 6.23 ± 0.69% for RYGB vs SG respectively, p < 0.001 in both groups for baseline vs follow-up). CONCLUSIONS/INTERPRETATION: In this study, RYGB did not have a superior effect in comparison to SG with regard to HbA1c levels or weight loss during 12 months of follow-up. TRIAL REGISTRATION: ClinicalTrials.gov NCT00667706. FUNDING: This work was supported by grant no. 3-000-8480 from the Israel Ministry of Health Chief Scientist, the Stephen Morse Diabetes Research Foundation and by Johnson & Johnson.


Assuntos
Diabetes Mellitus Tipo 2/cirurgia , Gastrectomia/métodos , Derivação Gástrica/métodos , Obesidade/cirurgia , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade
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