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1.
Pharmacol Res ; 131: 211-217, 2018 05.
Artigo em Inglês | MEDLINE | ID: mdl-29452290

RESUMO

Severely obese patients undergoing bariatric surgery (BS) are at increased risk for venous thromboembolism (VTE). How standard low molecular weight heparin (LMWH) regimen should be adapted to provide both sufficient efficacy and safety in this setting is unclear. We aimed to compare the influence of four body size descriptors (BSD) on peak anti-Xa levels in BS obese patients receiving LMWH fixed doses to identify which one had the greatest impact. One hundred and thirteen BS obese patients [median body mass index (BMI), 43.3 kg/m2 (IQR, 40.6-48.7 kg/m2)] receiving subcutaneous dalteparin 5000 IU twice daily were included in this prospective monocenter study. Peak steady-state anti-Xa levels were measured peri-operatively following thromboprophylaxis initiation. Only 48% of patients achieved target anti-Xa levels (0.2-0.5 IU/ml). In univariate analysis, age, gender, total body-weight (TBW), lean body-weight (LBW), ideal body-weight (IBW), BMI and estimated glomerural filtration rate (eGFR) were associated with anti-Xa levels. The strongest negative association was observed with LBW (r = -0.56, p < .0001). Receiver operating characteristic curves indicated that among BSD, LBW (cut-off >55.8 kg) had the highest sensitivity (73%) and specificity (69%) to predict sub-prophylactic anti-Xa levels. In multivariate analysis, LBW and eGFR remained associated with anti-Xa levels (ß = -0.47 ±â€¯0.08, p < .0001 and ß = -0.19 ±â€¯0.08; p = .02, respectively). In BS morbidly obese patients receiving LMWH for thromboprophylaxis after BS, LBW and eGFR are the main determinants of anti-Xa level, and could be proposed in LMWH-based thromboprophylaxis dosing algorithms. The efficacy of a LBW-scale based dosing algorithm for optimal VTE prevention deserves further prospective randomized trials.


Assuntos
Anticoagulantes/uso terapêutico , Dalteparina/uso terapêutico , Obesidade Mórbida/complicações , Obesidade Mórbida/cirurgia , Tromboembolia Venosa/etiologia , Tromboembolia Venosa/prevenção & controle , Adulto , Cirurgia Bariátrica , Índice de Massa Corporal , Peso Corporal , Feminino , Humanos , Peso Corporal Ideal , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Redução de Peso
2.
J Assist Reprod Genet ; 35(7): 1317-1324, 2018 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-29754264

RESUMO

INTRODUCTION: Although bariatric surgery seems to increase spontaneous fertility by improving ovulatory function in young women, its impact on ovarian reserve remains largely unknown. OBJECTIVE: To evaluate changes in serum anti-Mullerian hormone (AMH) levels in reproductive-age severely obese women after bariatric surgery (BS). METHODS: AMH levels were measured retrospectively in 39 women (mean age 34.6 ± 1.1 years, range 18-45) that underwent a sleeve gastrectomy or Roux-en-Y gastric bypass (RYGB) at baseline, and 6 and 12 months after BS. Metabolic and micronutrient status, including fasting plasma insulin and glucose, HOMA-IR, leptin, adiponectin, calcium, albumin, transthyretin, ferritin, vitamins (B9, B12, B1, A, E, D), zinc, and selenium, were assessed in all patients before and 1 year after BS. RESULTS: Of the patients, 79% had class-3 obesity. At 6 and 12 months, mean total weight losses (TWL) were 26 and 30%; mean excess weight losses (EWL) were 61.7 and 70.2%. Compared to baseline, AMH levels significantly decreased by 18% at 6 months, and 32% at 12 months post-operatively (p = 0.010 and p = 0.001, respectively). There was no correlation between AMH variation and changes in metabolic parameters or micronutrient levels. Remarkably, changes in AMH levels did not differ between sleeve and RYGB patients and were not correlated with EWL. CONCLUSION: This pilot study shows a drastic reduction in AMH levels at 1 year after BS in reproductive-age severely obese women, which was not related to weight loss: this suggests a negative impact of BS on ovarian reserve, at least in the short term.


Assuntos
Hormônio Antimülleriano/sangue , Cirurgia Bariátrica , Obesidade Mórbida/cirurgia , Reserva Ovariana/genética , Adolescente , Adulto , Índice de Massa Corporal , Pré-Escolar , Feminino , Gastrectomia , Derivação Gástrica , Humanos , Lactente , Pessoa de Meia-Idade , Obesidade Mórbida/sangue , Obesidade Mórbida/fisiopatologia , Reserva Ovariana/fisiologia , Redução de Peso , Adulto Jovem
3.
J Clin Endocrinol Metab ; 105(4)2020 04 01.
Artigo em Inglês | MEDLINE | ID: mdl-31589290

RESUMO

AIMS: Recent trials provide conflicting results on the association between glucagon-like peptide 1 receptor agonists (GLP-1RA) and diabetic retinopathy (DR). The aim of the AngioSafe type 2 diabetes (T2D) study was to determine the role of GLP-1RA in angiogenesis using clinical and preclinical models. METHODS: We performed two studies in humans. In study 1, we investigated the effect of GLP-1RA exposure from T2D diagnosis on the severity of DR, as diagnosed with retinal imaging (fundus photography). In study 2, a randomized 4-week trial, we assessed the effect of liraglutide on circulating hematopoietic progenitor cells (HPCs), and angio-miRNAs.We then studied the experimental effect of Exendin-4, on key steps of angiogenesis: in vitro on human endothelial cell proliferation, survival and three-dimensional vascular morphogenesis; and in vivo on ischemia-induced neovascularization of the retina in mice. RESULTS: In the cohort of 3154 T2D patients, 10% displayed severe DR. In multivariate analysis, sex, disease duration, glycated hemoglobin (HbA1c), micro- and macroangiopathy, insulin therapy and hypertension remained strongly associated with severe DR, while no association was found with GLP-1RA exposure (o 1.139 [0.800-1.622], P = .47). We further showed no effect of liraglutide on HPCs, and angio-miRNAs. In vitro, we demonstrated that exendin-4 had no effect on proliferation and survival of human endothelial cells, no effect on total length and number of capillaries. Finally, in vivo, we showed that exendin-4 did not exert any negative effect on retinal neovascularization. CONCLUSIONS: The AngioSafe T2D studies provide experimental and clinical data confirming no effect of GLP-1RA on angiogenesis and no association between GLP-1 exposure and severe DR.


Assuntos
Diabetes Mellitus Tipo 2/complicações , Retinopatia Diabética/patologia , Células Endoteliais/efeitos dos fármacos , Exenatida/farmacologia , Receptor do Peptídeo Semelhante ao Glucagon 1/agonistas , Neovascularização Patológica/patologia , Idoso , Animais , Biomarcadores/análise , Glicemia/análise , Diabetes Mellitus Tipo 2/tratamento farmacológico , Retinopatia Diabética/tratamento farmacológico , Retinopatia Diabética/etiologia , Feminino , Seguimentos , Humanos , Hipoglicemiantes/farmacologia , Masculino , Camundongos , Pessoa de Meia-Idade , Morfogênese , Neovascularização Patológica/tratamento farmacológico , Neovascularização Patológica/etiologia , Prognóstico , Retina/efeitos dos fármacos , Retina/metabolismo , Retina/patologia
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