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1.
J Clin Immunol ; 2020 Feb 10.
Artigo em Inglês | MEDLINE | ID: mdl-32040803

RESUMO

PURPOSE: Chronic granulomatous disease (CGD) is a primary immunodeficiency characterized by an inability of phagocytes to produce reactive oxygen species, impairing their killing of various bacteria and fungi. We summarize here the 93 cases of CGD diagnosed in Mexico from 2011 to 2019. METHODS: Thirteen Mexican hospitals participated in this study. We describe the genetic, immunological, and clinical features of the 93 CGD patients from 78 unrelated kindreds. RESULTS: Eighty-two of the patients (88%) were male. All patients developed bacterial infections and 30% suffered from some kind of fungal infection. Fifty-four BCG-vaccinated patients (58%) presented infectious complications of BCG vaccine. Tuberculosis occurred in 29%. Granulomas were found in 56% of the patients. Autoimmune and inflammatory diseases were present in 15% of patients. A biological diagnosis of CGD was made in 89/93 patients, on the basis of NBT assay (n = 6), DHR (n = 27), and NBT plus DHR (n = 56). The deficiency was complete in all patients. The median age of biological diagnosis was 17 months (range, 0-186 months). A genetic diagnosis was made in 83/93 patients (when material was available), corresponding to CYBB (n = 64), NCF1 (n = 7), NCF2 (n = 7), and CYBA (n = 5) mutations. CONCLUSIONS: The clinical manifestations in these Mexican CGD patients were similar to those in patients elsewhere. This cohort is the largest in Latin America. Mycobacterial infections are an important cause of morbidity in Mexico, as in other countries in which tuberculosis is endemic and infants are vaccinated with BCG. X-linked CGD accounted for most of the cases in Mexico, as in other Latin American countries. However, a significant number of CYBA and NCF2 mutations were identified, expanding the spectrum of known causal mutations.

2.
Gut Microbes ; : 1-18, 2020 Jan 23.
Artigo em Inglês | MEDLINE | ID: mdl-31973685

RESUMO

Background: Gut microbiota, by influencing multiple metabolic processes in the host, is an important determinant of human health and disease. However, gut dysbiosis associated with metabolic complications shows inconsistent patterns. This is likely driven by factors shaping gut microbial composition that have largely been under-evaluated, at a population level, in school-age children, especially from developing countries.Results: Through characterization, by 16S sequencing, of the largest gut microbial population-based school-aged children cohort in Latin America (ORSMEC, N = 926, aged 6-12 y), we identified associations of 14 clinical and environmental covariates (PFDR<0.1), collectively explaining 15.7% of the inter-individual gut microbial variation. Extrinsic factors such as markers of socioeconomic status showed a major influence in the most abundant taxa and in the enterotypes' distribution. Age was positively correlated with higher diversity, but only in normal-weight children (rho = 0.138, P =2 × 10-3). In contrast, this correlation although not significant, was negative in overweight and obese children (rho = -0.125, P = 0.104 and rho = -0.058, P = 0.409, respectively). Finally, co-abundance groups (CAGs) were associated with the presence of metabolic complications.Conclusions: Our study offers evidence that the presence of overweight and obesity could impair the microbial diversity maturation associated with age. Furthermore, it provides novel results toward a better understanding of gut microbiota in the pediatric population that will ultimately help to develop therapeutic approaches to improve metabolic status.

3.
Ann Hematol ; 2020 Jan 28.
Artigo em Inglês | MEDLINE | ID: mdl-31989250

RESUMO

Azacitidine (AZA) is a DNA hypomethylation agent administered in myeloid neoplasms; however, there is still a lack of established predictors of response. We studied 113 patients with myelodysplastic syndromes (n = 85) or acute myeloid leukemia (n = 28) who received AZA to assess the predictive value on response of clinical features, cytogenetics, and molecular markers. Overall, 46 patients (41%) responded to AZA. Platelet doubling after the first AZA cycle was associated with a better response (68% vs. 32% responders, P = 0.041). Co-occurrence of chromosome 7 abnormalities and 17p deletion was associated with a worse response (P = 0.039). Pre-treatment genetic mutations were detected in 98 patients (87%) and methylation of CDKN2B and DLC-1 promoters were detected in 50 (44%) and 37 patients (33%), respectively. Patients with SF3B1 mutations showed a better response to AZA (68% vs. 35% responders, P = 0.008). In contrast, subjects with mutations in transcription factors (RUNX1, SETBP1, NPM1) showed a worse response (20% vs. 47% responders, P = 0.014). DLC-1 methylation pre-treatment was associated with poor clinical features and its reduction post-treatment resulted in a better response to AZA in MDS patients (P = 0.037). In conclusion, we have identified several predictors of response to AZA that could help select the best candidates for this treatment.

4.
Med Hypotheses ; 134: 109527, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31877441

RESUMO

Obesity is a serious public health problem worldwide and has been associated in epidemiological studies with a unique type of non-atopic asthma, although the causal association of asthma and obesity has certain criteria, such as the strength of association, consistency, specificity, temporality, biological gradient, coherence, analogy and experimentation; nevertheless, the biological plausibility of this association remains uncertain. Various mechanisms have been postulated, such as immunological, hormonal, mechanical, environmental, genetic and epigenetic mechanisms. Our hypothesis favours immunological mechanisms because some cytokines, such as tumour necrosis factor alpha (TNF-α) and interleukin (IL)-17A, are responsible for orchestrating low-grade systemic inflammation associated with obesity; however, these cytokines are regulated by epigenetic mechanisms, such as gene promoter methylation.

5.
Anticancer Res ; 39(9): 4757-4766, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31519576

RESUMO

BACKGROUND/AIM: Azacitidine (AZA) is a hypomethylating agent used in myeloid neoplasms, however, approximately half of patients show treatment failure or relapse. This in vitro study investigated the effect of the combination of AZA with the natural compound curcumin (CUR) in increasing its efficacy. MATERIALS AND METHODS: We analyzed the effects of AZA plus CUR on proliferation, apoptosis, cell cycle and differentiation in myeloid leukemic cell lines (U-937, HL-60, K-562, and OCI-AML3) and bone marrow samples of patients. RESULTS: The results showed a synergy between AZA and CUR in all leukemic lines and in most leukemic samples, with a decrease in proliferation and an increase in apoptosis compared to the activity of each drug separately. In addition, AZA plus CUR showed low cytotoxicity in healthy samples. CONCLUSION: A remarkable antioncogenic effect of the combination of AZA plus CUR was shown, providing a basis for future studies analyzing the clinical efficacy of these drugs.


Assuntos
Antineoplásicos/farmacologia , Azacitidina/farmacologia , Curcumina/farmacologia , Idoso , Idoso de 80 Anos ou mais , Apoptose/efeitos dos fármacos , Ciclo Celular/efeitos dos fármacos , Diferenciação Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Sinergismo Farmacológico , Feminino , Humanos , Leucemia Mieloide/genética , Masculino , Síndromes Mielodisplásicas/genética
6.
Int Orthop ; 43(12): 2825-2829, 2019 12.
Artigo em Inglês | MEDLINE | ID: mdl-31256198

RESUMO

PURPOSE: To analyse a wide set of routine laboratory parameters at admission to predict mortality within 30 post-operative days in elderly patients with hip fracture, as well as calculate the critical values of those biomarkers. METHOD: Data of 994 patients older than 65 years with hip fracture were analysed of which 89 (8.2%) died within 30 post-operative days. Variables described in the literature with potential influence on early mortality were collected, including demographics, fracture type, American Society of Anesthesiologists score, Charlson's comorbidity index and pre-operative Hodkinson's mental test and the Katz index for activities of daily living. In addition, an exhaustive collection of biomarkers from routine blood testing at admission was performed. Critical levels of biomarkers were calculated by the method of area under ROC curve. RESULTS: At admission, early mortality group had significantly higher Charlson's index (p = 0.001) and lower the Katz index (p = 0.001). The surgical delay also was significantly longer in that group (p = 0.001). In univariate analyses, serum concentration at admission of total protein (p = 0.004), albumin (p = 0.001), sodium (p = 0.001), and parathyroid hormone (PTH) (p = 0.001) were significantly different between both groups. In multivariate analysis, serum albumin < 2.9 g/dL (p = 0.013), sodium < 127 mEq/L (p = 0.035) and PTH > 65 pg/mL (p = 0.005) were predictors of early mortality. The three biomarkers together accounted for 67% of the variability in early mortality. CONCLUSION: The association of altered levels at admission of serum concentration of albumin, sodium and PTH was predictor of early mortality following hip fracture surgery in elderly patients.

7.
J Pediatr Endocrinol Metab ; 32(8): 811-819, 2019 Aug 27.
Artigo em Inglês | MEDLINE | ID: mdl-31271554

RESUMO

Background The beneficial effects of treating hypertriglyceridemic adults with omega-3 fatty acids have been reported. However, information regarding omega-3 treatment of pediatric patients is limited. To evaluate the efficacy and safety of administering omega-3 fatty acids (3 g/day for 12 weeks) to children/adolescents with obesity and hypertriglyceridemia. Methods A randomized, double-blind, placebo-controlled, parallel study involving pediatric patients (10-16 years old) with obesity and hypertriglyceridemia was conducted. The National Center for Health Statistics (CDC) defines obesity as a body mass index (BMI) ≥95th percentile. Subjects with triglyceride concentrations ranging from 150 to 1000 mg/dL were randomized into two groups: those receiving omega-3 fatty acids (eicosapentaenoic and docosahexaenoic acids) (n = 65) and those receiving a placebo (n = 65) for 12 weeks. Serum triglyceride concentrations were always measured from 8 to 9 am after a 12-h fast. Results By the end of treatment, triglyceride concentrations had decreased by 39.1% in the omega-3 group and 14.6% in the placebo group (p < 0.01). The incidence of adverse gastrointestinal events (e.g. flatulence, belching) was 41.2% and 6.2% in the omega-3 and placebo groups, respectively (p < 0.01). There were no serious drug-related adverse events. Conclusions Supplementation with 3 g/day of omega-3 fatty acids is a safe and effective option for treating hypertriglyceridemia in children and adolescents with obesity.


Assuntos
Biomarcadores/sangue , Suplementos Nutricionais , Ácidos Graxos Ômega-3/administração & dosagem , Hipertrigliceridemia/tratamento farmacológico , Obesidade Pediátrica/tratamento farmacológico , Adolescente , Criança , Método Duplo-Cego , Feminino , Seguimentos , Humanos , Hipertrigliceridemia/sangue , Hipertrigliceridemia/etiologia , Masculino , Obesidade Pediátrica/complicações , Resultado do Tratamento , Triglicerídeos/sangue
8.
Rev Alerg Mex ; 66(2): 263-268, 2019.
Artigo em Espanhol | MEDLINE | ID: mdl-31200425

RESUMO

Although there are high quality clinical guidelines about allergic rhinitis, many patients receive deficient treatment, partly due to the high level of self-medication. MASK (Mobile Airways Sentinel Network) is an integral part of a project against chronic diseases which it is focused on active and healthy aging and is supported by the European Union. It forms the third phase of ARIA (Allergic Rhinitis and its Impact on Asthma) in which, through a mobile app on a smart device, the purpose is to guide patients in the control of their multimorbidity, allergic rhinitis or conjunctivitis, or asthma. The "Allergy Diary" app by MACVIA-ARIA is free and it is available for Android and iOS; on it, patients indicate how unpleasant the symptoms are on a daily basis through five screens with an analogous visual scale; two more screens were recently added (sleep affectation). With the app, it is also possible to download the information of the "Allergy Diary" on the physician's computer through a QR code at the moment of the medical consultation. In this article, we review the first year of experience in Spain, Mexico and Argentina, where the Spanish version is used.


Assuntos
Asma , Aplicativos Móveis , Rinite Alérgica , Argentina , Asma/diagnóstico , Asma/terapia , Humanos , Linguagem , México , Rinite Alérgica/diagnóstico , Rinite Alérgica/terapia , Espanha
9.
Rev Alerg Mex ; 66 Suppl 1: 1-105, 2019.
Artigo em Espanhol | MEDLINE | ID: mdl-31200597

RESUMO

BACKGROUND: In Mexico, allergen immunotherapy (AIT) and immunotherapy with hymenoptera venom (VIT) is traditionally practiced combining aspects of the European and American school. In addition, both types of extracts (European and American) are commercially available in Mexico. Moreover, for an adequate AIT/VIT a timely diagnosis is crucial. Therefore, there is a need for a widely accepted, up-to-date national immunotherapy guideline that covers diagnostic issues, indications, dosage, mechanisms, adverse effects and future expectations of AIT (GUIMIT 2019). METHOD: With nationwide groups of allergists participating, including delegates from postgraduate training-programs in Allergy/Immunology-forming, the guideline document was developed according to the ADAPTE methodology: the immunotherapy guidelines from European Academy of Allergy and Clinical Immunology, German Society for Allergology and Clinical Immunology, The American Academy of Allergy, Asthma and Immunology and American College of Allergy, Asthma, and Immunology were selected as mother guidelines, as they received the highest AGREE-II score among international guidelines available; their evidence conforms the scientific basis for this document. RESULTS: GUIMIT emanates strong or weak (suggestions) recommendations about practical issues directly related to in vivo or in vitro diagnosis of IgE mediated allergic diseases and the preparation and application of AIT/VIT and its adverse effects. GUIMIT finishes with a perspective on AIT modalities for the future. All the statements were discussed and voted on until > 80 % consensus was reached. CONCLUSIONS: A wide and diverse group of AIT/VIT experts issued transculturized, evidence-based recommendations and reached consensus that might improve and standardize AIT practice in Mexico.


Assuntos
Hipersensibilidade/diagnóstico , Hipersensibilidade/terapia , Imunoglobulina E , Imunoterapia/normas , Humanos , Hipersensibilidade/imunologia , Imunoglobulina E/imunologia
10.
Health Econ Rev ; 9(1): 12, 2019 May 07.
Artigo em Inglês | MEDLINE | ID: mdl-31065886

RESUMO

BACKGROUND: Children that attend day-care centers frequently contract acute respiratory tract infections (ARTIs). ARTIs represent a burden for both children and parents. Systematic reviews on the use of immunostimulants for the prevention of juvenile recurrent ARTIs have provided moderate evidence of efficacy and safety. The aim of the study was to establish whether the immunostimulant, OM-85, was cost-effective in preventing ARTIs in children 2-6 years old that attended day-care centers or preschools in Mexico. We performed a systematic review to evaluate the efficacy of OM-85. For costs, we assumed an institutional perspective, which included the costs of care and supplies over a study period of six months, during the autumn-winter seasons. We created decision trees and constructed a model to identify pharmacoeconomic parameters. We generated 1000 estimations with the bootstrap method to calculate descriptive statistics of pharmacoeconomic parameters. We evaluated cost-effectiveness compared to treatment without immunostimulants. RESULTS: The mean (SD) incidences of ARTIs were 5.59 ± 0.29 without immunostimulants and 2.97 ± 0.32 with OM-85, during the study period. The mean (25th, 75th percentile) direct costs of ARTIs were 57.04 (37.11, 76.39) US$ (US dollars) without immunostimulants and 48.53 (37.35, 58.93) US$ with OM-85, with a mean increment of - 8.51(- 17.08, 0.75) US$, and a mean cost-effectiveness of - 17.94 (- 36.48, 1.66) US$. The direct costs plus the cost of one parent missing work to care for the child with ARTI were 125.76 (102.83, 150.16) US$, without immunostimulant and 85.21 (72.15, 98.81) US$, with OM-85. The increment was - 40.55 (- 68.29, - 13.95) US$, and the cost-effectiveness was - 86.89 (- 142.37, - 29.34) US$.Part of the cost reduction was ascribed to the reduced use of medications, particularly antibiotics. CONCLUSIONS: Our results were consistent with previous clinical studies conducted in closed institutions in Mexico. OM-85 reduced the number of ARTIs and the frequency of antibiotics use. We concluded that OM-85 was cost-effective for preventing ARTIs in children that attended day-care centers, particularly when parental absenteeism was covered by the institutions.

12.
Rev Alerg Mex ; 66(1): 140-146, 2019.
Artigo em Espanhol | MEDLINE | ID: mdl-31013416

RESUMO

The vast majority of patients with allergic rhinitis (AR) do not receive the proper management which is recommended by the guidelines, but they frequently self-medicate. MASK (Mobile Airways Sentinel Network) is an integral part of a project that is supported by the European Union against chronic diseases and focused on active and healthy aging. MASK represents the third phase of ARIA (Allergic Rhinitis and its Impact on Asthma), in which, by using a mobile application in a smart device, the objective is to guide the patient in the control of his/her multi-morbidity, AR and/or allergic conjunctivitis (AC) and/or asthma. The mobile app Allergy Diary by MACVIA-ARIA is free and it is available for both Android and iOS platforms. After it is downloaded to the patient's cell phone, it first requests some information about the patient's profile, allergic pathologies and medication; afterwards, through a visual analog scale, the patient is invited to determine the degree of affectation in the nose, eyes, and bronchi, and its influence on their productivity at work / school. After analyzing the data generated by filling the Allergy Diary, it became clear there is a new clinical entity: allergic rhinitis+ allergic conjunctivitis +asthma, with greater effect; in addition to a high level of self-medication: in general, the patient takes medication on days when symptoms are present. The app has already been deployed in 23 countries, including several Spanish-speaking countries.


Assuntos
Asma/tratamento farmacológico , Conjuntivite Alérgica/tratamento farmacológico , Aplicativos Móveis , Rinite Alérgica/tratamento farmacológico , Asma/complicações , Conjuntivite Alérgica/complicações , Humanos , Multimorbidade , Rinite Alérgica/complicações , Automedicação
13.
J Neurotrauma ; 36(19): 2785-2802, 2019 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-30963801

RESUMO

Traumatic axonal injury (TAI) is the main cause of cognitive and psychological disfunction after a traumatic brain injury (TBI). Diffusion tensor imaging (DTI) is considered a useful technique for indirect assessment of white matter (WM) integrity after a TBI. Scattered WM alterations and its relationship with patient severity have been discovered in normal appearing conventional magnetic resonance imaging (MRI) studies based on DTI sequences. However, there is a lack of large sample studies on the longitudinal changes of DTI metrics to be used to determine the temporal profile after head injury and its association with patient outcome. We performed a prospective observational study in 118 moderate-to-severe TBI patients. The study included clinical outcome assessment based on the Glasgow Outcome Scale Extended (GOSE) and serial DTI studies in the early subacute setting (< 60 days) and 6 and 12 months after injury. Fractional anisotropy (FA) and axial and radial diffusivities (AD and RD, respectively) were measured in the three portions of corpus callosum (genu, body, splenium) at each time-point and compared with normalized values from an age-matched control group. Longitudinal FA analysis and its correlation with patient improvement also was done by non-parametric testing and ordinal regression analysis. Our main results indicated that between all the time-points, dynamic changes in DTI metrics in all three portions of corpus callosum were detected, but TBI patients continued to show significantly lower FA and AD values and higher RD values compared with controls. We also have discovered differences in the change of DTI metrics among different time-points in patient subgroups according with their outcome improvement. In conclusion, even without normalization of DTI metrics in the long-term, knowledge of the temporal profile of change in DTI metrics can provide important information about patients' clinical recovery after TBI.

14.
Bol. méd. Hosp. Infant. Méx ; 76(1): 5-17, ene.-feb. 2019. tab, graf
Artigo em Espanhol | LILACS-Express | ID: biblio-1038886

RESUMO

Resumen La terapia inhalada se considera la piedra angular del manejo del asma. Sin embargo, a pesar de ser la forma ideal de administración de estos medicamentos, solamente el 70% de los pacientes cumple el tratamiento adecuadamente y sólo del 39 al 67% de los médicos conocen y pueden explicar de forma adecuada las distintas técnicas de inhalación. La terapia inhalada tiene características muy particulares. El depósito pulmonar de un medicamento inhalado a través del tracto respiratorio es más complejo que cuando se administra por vía oral, y varía dependiendo de varios factores, tanto inherentes al medicamento como a la forma de administrarlo. Para que la terapia inhalada sea exitosa, se requiere que se generen partículas del medicamento de un tamaño apropiado que penetren más allá de la orofaringe y la laringe, y que puedan depositarse en los pulmones. Existen múltiples dispositivos para la administración de medicamentos en la vía respiratoria baja. Cada uno ha probado tener una eficacia similar, siempre y cuando se utilicen con la técnica correcta. La decisión para su uso se realiza con base en la edad del paciente, la capacidad de coordinar entre la inhalación y la activación del dispositivo y la presencia de síntomas agudos. La elección del dispositivo a utilizar siempre deberá hacerse de forma conjunta, evaluando pros y contras de cada uno de los dispositivos y siempre de forma individualizada.


Abstract Inhaled therapy is considered the cornerstone of asthma treatment. However, despite being the ideal form of drug delivery, it is recognized that only 70% of patients have an adequate attachment to their treatment and only 39-67% of physicians can explain the optimal inhaler technique. Inhaled therapy has very specific characteristics. Pulmonary deposit of an inhaled medication through the respiratory tract is more complex than when administered orally and depends on several factors inherent to both the medication and the administration. For successful inhaled therapy, the drug needs to be converted into particles of an appropriate size, which can enter beyond the oropharynx and larynx, and be deposited in the lungs. There are multiple devices for the administration of drugs in the lower respiratory tract, each one with a similar efficacy as long as it is used with the correct technique. The decision of which device should be used is made based on the age of the patient, the ability to coordinate between the inhalation and activation of the device, and the presence of acute symptoms. The choice of the device must be evaluated individually.

15.
Bol Med Hosp Infant Mex ; 76(1): 5-17, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30657469

RESUMO

Inhaled therapy is considered the cornerstone of asthma treatment. However, despite being the ideal form of drug delivery, it is recognized that only 70% of patients have an adequate attachment to their treatment and only 39-67% of physicians can explain the optimal inhaler technique. Inhaled therapy has very specific characteristics. Pulmonary deposit of an inhaled medication through the respiratory tract is more complex than when administered orally and depends on several factors inherent to both the medication and the administration. For successful inhaled therapy, the drug needs to be converted into particles of an appropriate size, which can enter beyond the oropharynx and larynx, and be deposited in the lungs. There are multiple devices for the administration of drugs in the lower respiratory tract, each one with a similar efficacy as long as it is used with the correct technique. The decision of which device should be used is made based on the age of the patient, the ability to coordinate between the inhalation and activation of the device, and the presence of acute symptoms. The choice of the device must be evaluated individually.


Assuntos
Antiasmáticos/administração & dosagem , Asma/tratamento farmacológico , Sistemas de Liberação de Medicamentos , Administração por Inalação , Antiasmáticos/farmacocinética , Humanos , Pulmão/metabolismo , Nebulizadores e Vaporizadores , Distribuição Tecidual
16.
Int Orthop ; 43(2): 441-448, 2019 02.
Artigo em Inglês | MEDLINE | ID: mdl-29744645

RESUMO

PURPOSE: The purposes of this study were to identify the reasons for delayed surgery following hip fractures and analyze the impact of these reasons on 1-year mortality. METHODS: A prospective cohort study of 1234 patients with mean age of 83.1 (range 65-92, SD 8.0) who underwent hip fracture surgery compared three subgroups: (1) surgery within two days from admission (609 patients); (2) delayed surgery for medical reasons (286); and (3) delayed surgery for organizational causes (339). Medical reason was defined as the need of medical optimization of the patient prior to surgery. Pre-operative assessment was performed by the American Society of Anesthesiologists (ASA) score, Charlson Comorbidity Index (CCI), Hodkinson mental status, Katz index for activities of daily living, and Short-Form (SF-12) questionnaire. Univariate analyses were used (chi-square and Fisher exact or Mantel-Haenszel tests for categorical data, and variance analysis, Student t test, or Mann-Whitney U test for continuous data). Logistic regression models were used for influence of variables on complications and one year mortality. RESULTS: There were no significant differences in complications or one year mortality rates between patients with surgery within two days and those with delayed surgery for medical reasons. However, the patients with delayed surgery for organizational causes had significant higher rates of both complications and one year mortality compared to the other two groups (p = 0.001). CONCLUSIONS: This study suggests that waiting time for hip fracture surgery more than two days was not associated with higher complication or mortality rate if waiting was to stabilize patients with active comorbidities at admission, compared to stable patients at admission with early surgery. Although early surgery within two days from admission is desirable for stable patients at admission, in patients with complex comorbidities, the surgery should be performed once they are optimized. However, the patients with delayed surgery for organizational reasons had a significant higher rate of post-operative complications and one year mortality compared to the other two groups.

17.
J Nutr Biochem ; 64: 162-169, 2019 02.
Artigo em Inglês | MEDLINE | ID: mdl-30513433

RESUMO

Obesity in adolescents is considered a major public health problem; combined interventional approaches such as omega-3 supplementation with lifestyle intervention (LI) might exert synergistic effects and exceed the impact of each individual strategy. The purpose of the present study was to evaluate if the supplementation of omega-3 with LI could improve metabolic and endothelial abnormality in obese adolescents with hypertriglyceridemia. The study involved sixty-nine adolescents with normal weight and seventy obese adolescents with hypertriglyceridemia. All obese adolescents were applied to LI and randomly assigned to omega-3 supplementation or placebo group for 12 weeks. The obese adolescents with hypertriglyceridemia presented increased levels of leptin, retinol binding protein 4 (RBP4), selectin E (sE) and asymmetric dimethylarginine (ADMA) and decreased levels of adiponectin compared with control subjects. After 12-week intervention, omega-3 supplementation with LI decreased significantly in triglycerides, HOMA, leptin, RBP4, ADMA and sE. Moreover, omega-3 with LI displayed a significant reduction in triglycerides, ADMA and sE in comparison with LI alone. In subjects with omega-3 combined with LI assessed by multivariate regression model, the reduction in triglycerides was the only independent determinant of the decrease in ADMA. The reductions in triglycerides and HOMA were significantly contributed to the changes in sE. Our data indicated that omega-3 combined with LI in short duration significantly improved dyslipidemia, insulin resistance, abnormality of adipokines, endothelial dysfunction in comparison of LI alone, indicating the combined approach is an effective clinical and applicable strategy to control metabolic abnormality and decrease the risks of cardiovascular diseases in obese adolescents.

18.
Int J Cardiol ; 279: 168-173, 2019 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-30305239

RESUMO

BACKGROUND: Serum uric acid (SUA) is a heritable trait associated with cardiovascular risk factors and coronary artery disease (CAD). Genome wide association studies (GWAS) have identified several genes associated with SUA, mainly in European populations. However, to date there are few GWAS in Latino populations, and the role of SUA-associated single nucleotide polymorphisms (SNPs) in cardiovascular disease has not been studied in the Mexican population. METHODS: We performed genome-wide SUA association study in 2153 Mexican children and adults, evaluated whether genetic effects were modified by sex and obesity, and used a Mendelian randomization approach in an independent cohort to study the role of SUA modifying genetic variants in premature CAD. RESULTS: Only two loci were associated with SUA levels: SLC2A9 (ß = -0.47 mg/dl, P = 1.57 × 10-42 for lead SNP rs7678287) and ABCG2 (ß = 0.23 mg/dl, P = 2.42 × 10-10 for lead SNP rs2231142). No significant interaction between SLC2A9 rs7678287 and ABCG2 rs2231142 genotypes and obesity was observed. However, a significant ABCG2 rs2231142 genotype*sex interaction (P = 0.001) was observed in adults but not in children. Although SUA levels were associated with premature CAD, metabolic syndrome and decreased glomerular filtration rate (eGFR), only ABCG2 rs2231142 was associated with decreased eGFR in the premature CAD group. CONCLUSIONS: SUA elevation was independently associated with premature CAD, metabolic syndrome and decreased eGFR in the Mexican population. However, a Mendelian randomization approach using the lead SUA-associated SNPs (SLC2A9 and ABCG2) did not support a causal role of elevated SUA levels for premature CAD.


Assuntos
Doença da Artéria Coronariana/sangue , Doença da Artéria Coronariana/genética , Estudo de Associação Genômica Ampla/métodos , Polimorfismo de Nucleotídeo Único/genética , Ácido Úrico/sangue , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores/sangue , Criança , Doença da Artéria Coronariana/epidemiologia , Feminino , Humanos , Masculino , Análise da Randomização Mendeliana/métodos , México/epidemiologia , Pessoa de Meia-Idade , Adulto Jovem
19.
J Allergy Clin Immunol ; 143(3): 957-969, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-30201514

RESUMO

BACKGROUND: Asthma is a common but complex disease with racial/ethnic differences in prevalence, morbidity, and response to therapies. OBJECTIVE: We sought to perform an analysis of genetic ancestry to identify new loci that contribute to asthma susceptibility. METHODS: We leveraged the mixed ancestry of 3902 Latinos and performed an admixture mapping meta-analysis for asthma susceptibility. We replicated associations in an independent study of 3774 Latinos, performed targeted sequencing for fine mapping, and tested for disease correlations with gene expression in the whole blood of more than 500 subjects from 3 racial/ethnic groups. RESULTS: We identified a genome-wide significant admixture mapping peak at 18q21 in Latinos (P = 6.8 × 10-6), where Native American ancestry was associated with increased risk of asthma (odds ratio [OR], 1.20; 95% CI, 1.07-1.34; P = .002) and European ancestry was associated with protection (OR, 0.86; 95% CI, 0.77-0.96; P = .008). Our findings were replicated in an independent childhood asthma study in Latinos (P = 5.3 × 10-3, combined P = 2.6 × 10-7). Fine mapping of 18q21 in 1978 Latinos identified a significant association with multiple variants 5' of SMAD family member 2 (SMAD2) in Mexicans, whereas a single rare variant in the same window was the top association in Puerto Ricans. Low versus high SMAD2 blood expression was correlated with case status (13.4% lower expression; OR, 3.93; 95% CI, 2.12-7.28; P < .001). In addition, lower expression of SMAD2 was associated with more frequent exacerbations among Puerto Ricans with asthma. CONCLUSION: Ancestry at 18q21 was significantly associated with asthma in Latinos and implicated multiple ancestry-informative noncoding variants upstream of SMAD2 with asthma susceptibility. Furthermore, decreased SMAD2 expression in blood was strongly associated with increased asthma risk and increased exacerbations.

20.
Haematologica ; 104(3): 576-586, 2019 03.
Artigo em Inglês | MEDLINE | ID: mdl-30262568

RESUMO

Mutations in genes of the RAS-BRAF-MAPK-ERK pathway have not been fully explored in patients with chronic lymphocytic leukemia. We, therefore, analyzed the clinical and biological characteristics of chronic lymphocytic leukemia patients with mutations in this pathway and investigated the in vitro response of primary cells to BRAF and ERK inhibitors. Putative damaging mutations were found in 25 of 452 patients (5.5%). Among these, BRAF was mutated in nine patients (2.0%), genes upstream of BRAF (KITLG, KIT, PTPN11, GNB1, KRAS and NRAS) were mutated in 12 patients (2.6%), and genes downstream of BRAF (MAPK2K1, MAPK2K2, and MAPK1) were mutated in five patients (1.1%). The most frequent mutations were missense, subclonal and mutually exclusive. Patients with these mutations more frequently had increased lactate dehydrogenase levels, high expression of ZAP-70, CD49d, CD38, trisomy 12 and unmutated immunoglobulin heavy-chain variable region genes and had a worse 5-year time to first treatment (hazard ratio 1.8, P=0.025). Gene expression analysis showed upregulation of genes of the MAPK pathway in the group carrying RAS-BRAF-MAPK-ERK pathway mutations. The BRAF inhibitors vemurafenib and dabrafenib were not able to inhibit phosphorylation of ERK, the downstream effector of the pathway, in primary cells. In contrast, ulixertinib, a pan-ERK inhibitor, decreased phospho-ERK levels. In conclusion, although larger series of patients are needed to corroborate these findings, our results suggest that the RAS-BRAF-MAPK-ERK pathway is one of the core cellular processes affected by novel mutations in chronic lymphocytic leukemia, is associated with adverse clinical features and could be pharmacologically inhibited.

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