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The aim of this study was to examine the distribution of nerve endings in the mucosa, submucosa, and cartilage of the epiglottis and the vallecula area and to quantify them. The findings could inform the choice of laryngoscope blades for intubation procedures. Fourteen neck slices from seven unembalmed, cryopreserved human cadavers were analyzed. The slices were stained, and cross and longitudinal sections were obtained from each. The nerve endings and cartilage were identified. The primary metrics recorded were the number, area, and circumference of nerve endings located in the mucosa and submucosa of the pharyngeal and laryngeal sides of the epiglottis, epiglottis cartilage, and epiglottic vallecula zone. The length and thickness of the epiglottis and cartilage were also measured. The elastic cartilage of the epiglottis was primarily continuous; however, it contained several fragments. It was covered with dense collagen fibers and surrounded by adipose cells from the pharyngeal and laryngeal submucosa. Nerve endings were found within the submucosa of pharyngeal and laryngeal epiglottis and epiglottic vallecula. There were significantly more nerve endings on the posterior surface of the epiglottis than on the anterior surface. The epiglottic cartilage was twice the length of the epiglottis. The study demonstrated that the distribution of nerve endings in the epiglottis differed significantly between the posterior and anterior sides; there were considerably more in the former. The findings have implications for tracheal intubation and laryngoscope blade selection and design.
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Epiglote , Terminações Nervosas , Humanos , Mucosa , Intubação IntratraquealRESUMO
Although the general functionality and structures of acupoints have been studied, there has been little insight into their underlying morphology and physical characteristics. We describe the microanatomical structures surrounding acupoints, the electron microscopic appearance of the needles, and the physical effects of acupuncture needling on the fascia. We injected heparinized blood solution through thin needles at seven known and commonly used "sweat acupoints" in eight fresh, unembalmed, cryopreserved human cadavers to mark the needle positions, and later, during histological examination, to identify them. After the solution was injected, samples were dissected and prepared for histological examination. We examined 350 cross-sections of five different paraffin wax sections from each acupoint microscopically. Acupuncture needles were photographed and superimposed on the cross-sectioned tissues at similar magnifications. Needles were also examined under a scanning electron microscope to judge the roughness or smoothness of their surfaces. A greater conglomeration of nerve endings surrounded the acupoints than in tissues more than 1-3 cm distant from them. Nerve endings and blood vessels were in close contact with a complex network of membranes formed by interlacing collagen fibers, and were always enclosed within those collagen membranes. Nerve endings were found within hypodermis, muscles, or both. Scanning electron microscopy demonstrated the three-dimensional shapes and sizes of the needles, and the degree of roughness or smoothness of their polished external surfaces. We demonstrate a delicate arrangement of nerve endings and blood vessels enclosed within complex collagen membrane networks at acupoints within the hypodermis and muscle. This arrangement could explain why needling is an essential step in the acupuncture process that provides favorable outcomes in clinical practice.
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Pontos de Acupuntura , Terapia por Acupuntura , Terapia por Acupuntura/métodos , Elétrons , Humanos , Microscopia Eletrônica , AgulhasRESUMO
PURPOSE: To establish the prevalence and risk factors for intravitreal dexamethasone implant migration into the anterior chamber in eyes with macular edema. METHODS: This was a multicenter, retrospective, observational chart review of data that included patients with macular edema who had been treated with at least one intravitreal dexamethasone injection. Patients with incomplete chart information during the follow-up period were excluded. RESULTS: The prevalence of implant migration in 468 patients, considering the number of injections, was 1.6%, with significant associations between implant migration and cataract surgery (P = 0.043) and intraocular lens status (P = 0.005) and a trend toward statistical significance (P = 0.057) with vitrectomy. A higher rate of implant migration into the anterior chamber was observed in vitrectomized eyes (4.8%) when compared with patients who did not undergo a vitrectomy (1.6%). The implants that migrated were removed with forceps with/without viscoelastic expression or with 20-gauge cannulas connected to the vitreous cutter machine. CONCLUSION: The risk of implant migration into the anterior chamber was 1.6%. Risk factors were a history of cataract surgery or vitrectomy and aphakia. When anterior migration occurs, rapid removal is advised, especially if corneal edema is present.
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Câmara Anterior , Dexametasona/administração & dosagem , Implantes de Medicamento/efeitos adversos , Migração de Corpo Estranho/diagnóstico , Acuidade Visual , Idoso , Feminino , Migração de Corpo Estranho/epidemiologia , Glucocorticoides/administração & dosagem , Humanos , Incidência , Injeções Intravítreas , Edema Macular/diagnóstico , Edema Macular/tratamento farmacológico , Masculino , Estudos Retrospectivos , Estados Unidos/epidemiologiaRESUMO
In a traditional large electricity grid without storage, there is a limit to the maximum photovoltaic energy that can be consumed as the demand and generation may not match, either in magnitude or in time. This paper aims to provide a new method to estimate the limit of the coverage of electricity demand by photovoltaics in large electricity grids. This new method eliminates the random and the periodic variability over time as it is based either on the load duration curve for demand and the output duration curve for PV generation. We will assume there is no energy storage or inter-network exchanges. Moreover, conditions for the best scenario for photovoltaics are provided in order to estimate the upper limit: photovoltaic overgeneration is not considered and a complete system flexibility is assumed. The knowledge of this limit will manage to provide not only a reference for the planning of the energy sector but also to analyze the viability of the integration of future photovoltaic projects in the electrical system. In order to illustrate the method, several large electricity grids have been analysed in order to determine the aforementioned limit. Values between 19.3% and 29.9% have been obtained.
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Various challenges should be considered when measuring photovoltaic array power and energy in pulse width modulation (PWM) charge controllers. These controllers are frequently used not only in stand-alone photovoltaic (SAPV) systems, but may also be found in photovoltaic (PV) self-consumption systems with battery storage connected to the electricity grid. An acceptable solution may be reached using expensive data acquisition systems (DASs), although this could be generally disproportionate to the relatively low cost of SAPV systems. Therefore, the aim of this paper is to develop new and effective monitoring techniques which will provide the PV array direct current (DC), output power (PA,dc), and PV array DC output energy (EA), thus avoiding the use of sophisticated DASs and providing high accuracy for the calculated parameters. Only transducers and electronic circuits that provide the average and true rms values of the PWM signals are needed. The estimation of these parameters through the aforementioned techniques showed high accuracy for both series and shunt PWM battery charge controllers. Normalized root mean square error (NRMSE) was lower than 2.4%, normalized mean bias error (NMBE) was between -1.5% and 1.1%, and mean absolute percentage error (MAPE) was within 1.6%.
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PURPOSE: Hirschsprung disease (OMIM 142623) is a neurocristopathy attributed to a failure of cell proliferation or migration and/or failure of the enteric precursors along the gut to differentiate during embryonic development. Although some genes involved in this pathology are well characterized, many aspects remain poorly understood. In this study, we aimed to identify novel genes implicated in the pathogenesis of Hirschsprung disease. METHODS: We compared the expression patterns of genes involved in human stem cell pluripotency between enteric precursors from controls and Hirschsprung disease patients. We further evaluated the role of DNMT3B in the context of Hirschsprung disease by inmunocytochemistry, global DNA methylation assays, and mutational screening. RESULTS: Seven differentially expressed genes were identified. We focused on DNMT3B, which encodes a DNA methyltransferase that performs de novo DNA methylation during embryonic development. DNMT3B mutational analysis in our Hirschsprung disease series revealed the presence of potentially pathogenic mutations (p.Gly25Arg, p.Arg190Cys, and p.Gly198Trp). CONCLUSION: DNMT3B may be regulating enteric nervous system development through DNA methylation in the neural crest cells, suggesting that aberrant methylation patterns could have a relevant role in Hirschsprung disease. Moreover, the synergistic effect of mutations in both DNMT3B and other Hirschsprung disease-related genes may be contributing to a more severe phenotype in our Hirschsprung disease patients.
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DNA (Citosina-5-)-Metiltransferases/genética , Sistema Nervoso Entérico , Doença de Hirschsprung/genética , Neurogênese/genética , Biomarcadores , Estudos de Casos e Controles , Pré-Escolar , Análise por Conglomerados , DNA (Citosina-5-)-Metiltransferases/metabolismo , Metilação de DNA , Feminino , Perfilação da Expressão Gênica , Regulação da Expressão Gênica , Ordem dos Genes , Loci Gênicos , Doença de Hirschsprung/metabolismo , Humanos , Lactente , Masculino , Mutação , Células-Tronco Neurais/metabolismo , Células-Tronco Pluripotentes/metabolismo , DNA Metiltransferase 3BRESUMO
Shah-Waardenburg syndrome or Waardenburg syndrome type 4 (WS4) is a neurocristopathy characterized by the association of deafness, depigmentation and Hirschsprung disease. Three disease-causing genes have been identified so far for WS4: EDNRB, EDN3, and SOX10. SOX10 mutations, found in 45-55% of WS4 patients, are inherited in autosomal dominant way. In addition, mutations in SOX10 are also responsible for an extended syndrome involving peripheral and central neurological phenotypes, referred to as PCWH (peripheral demyelinating neuropathy, central dysmyelinating leucodystrophy, Waardenburg syndrome, Hirschsprung disease). Such mutations are mostly private, and a high intra- and inter-familial variability exists. In this report, we present a patient with WS4 and a second with PCWH due to SOX10 mutations supporting again the genetic and phenotypic heterogeneity of these syndromes. Interestingly, the WS4 family carries an insertion of 19 nucleotides in exon 5 of SOX10, which results in distinct phenotypes along three different generations: hypopigmentation in the maternal grandmother, hearing loss in the mother, and WS4 in the proband. Since mosaicism cannot explain the three different related-WS features observed in this family, we propose as the most plausible explanation the existence of additional molecular events, acting in an additive or multiplicative fashion, in genes or regulatory regions unidentified so far. On the other hand, the PCWH case was due to a de novo deletion in exon 5 of the gene. Efforts should be devoted to unravel the mechanisms underlying the intrafamilial phenotypic variability observed in the families affected, and to identify new genes responsible for the still unsolved WS4 cases.
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Mutação , Fatores de Transcrição SOXE/genética , Síndrome de Waardenburg/diagnóstico , Síndrome de Waardenburg/genética , Sequência de Aminoácidos , Substituição de Aminoácidos , Pré-Escolar , Análise Mutacional de DNA , Éxons , Ordem dos Genes , Doença de Hirschsprung , Humanos , Masculino , Dados de Sequência Molecular , Fenótipo , EspanhaRESUMO
Hematopoietic stem cell gene therapy (HSCGT) is a promising therapeutic strategy for the treatment of neurodegenerative, metabolic disorders. The approach involves the ex vivo introduction of a missing gene into patients' own stem cells via lentiviral-mediated transduction (TD). Once transplanted back into a fully conditioned patient, these genetically modified HSCs can repopulate the blood system and produce the functional protein, previously absent or non-functional in the patient, which can then cross-correct other affected cells in somatic organs and the central nervous system. We previously developed an HSCGT approach for the treatment of Mucopolysaccharidosis type II (MPSII) (Hunter syndrome), a debilitating pediatric lysosomal disorder caused by mutations in the iduronate-2-sulphatase (IDS) gene, leading to the accumulation of heparan and dermatan sulfate, which causes severe neurodegeneration, skeletal abnormalities, and cardiorespiratory disease. In HSCGT proof-of-concept studies using lentiviral IDS fused to a brain-targeting peptide ApoEII (IDS.ApoEII), we were able to normalize brain pathology and behavior of MPSII mice. Here we present an optimized and validated good manufacturing practice hematopoietic stem cell TD protocol for MPSII in preparation for first-in-man studies. Inclusion of TEs LentiBOOST and protamine sulfate significantly improved TD efficiency by at least 3-fold without causing adverse toxicity, thereby reducing vector quantity required.
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West syndrome is a severe epilepsy syndrome characterised by the appearance of drug-resistant epileptic disorders associated with hypsarrhythmia and intellectual disability. Among non-pharmacological treatments, the ketogenic diet, which consists of low carbohydrate intake and a rich lipid intake, stands out. This treatment induces a state of ketosis, which has been related to a decrease in the number of seizures. It is essential to control the carbohydrate intake within drug treatment for these patients since many pharmaceutical forms, specifically liquid oral medication, may contain carbohydrates in the form of mono/polysaccharides or polyols. We describe the case report of an infant with drug-resistant West syndrome, treated with a ketogenic diet, whose antiseizure liquid medication impeded a proper response to the diet. After the substitution of these medications, the patient showed a remarkable decrease in the number of seizures.
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Dieta Cetogênica , Espasmos Infantis , Lactente , Humanos , Convulsões/tratamento farmacológico , Carboidratos/uso terapêutico , Preparações FarmacêuticasRESUMO
Academic achievement, measured with the grade point average (GPA), is a stable characteristic that has been associated with many sociodemographic and psychological variables; however, the relation of these variables with GPA has not been totally elucidated. The objective of this study was to perform an association of health, psychological and personal variables with GPA and non-verbal intelligence in low-academic performance population according to sex. We invited health sciences university students who had failed the same subject twice to complete a set of sociodemographic and psychological variables and a non-verbal intelligence test. The GPA, admission exam test and preparatory GPA were obtained. We included 124 students, and found that GPA was associated with non-verbal intelligence in women but not in men; in whom, having a job and having a romantic partner, were more correlated. In women, positive relations with others, emotion perception and weekly physical activity hours were marginally correlated with GPA; while in men, emotion regulation and self-motivation had a tendency of correlation with GPA. In addition, we found that non-verbal intelligence was associated somatization and the number of diseases in women. Academic achievement is regulated by different variables in each sex; therefore, intervention programs addressed by sex are needed to increase it.
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Sucesso Acadêmico , Avaliação Educacional , Escolaridade , Feminino , Humanos , Inteligência , Masculino , Estudantes/psicologia , UniversidadesRESUMO
PROPOSE: To report two cases of severe acute multi-systemic failure with bilateral ocular toxoplasmosis in immunocompetent patients from urban settings in Colombia. OBSERVATIONS: We report two immunocompetent male patients aged 44- and 67-years-old who, despite not having visited the Amazonian region in Colombia, had severe bilateral posterior uveitis and extensive-bilateral macular lesions and multiple organ failure that required admission to an intensive care unit. Toxoplasma gondii was positive by PCR assay in vitreous humor samples. Patients were treated with intravitreal clindamycin and dexamethasone in addition to systemic treatment with trimethoprim-sulfamethoxazole. In both patients, infection by atypical strains was confirmed; in one case by serotyping and in another one by genotyping (ROP 18 virulent allele). After 2 and 4 months of treatment respectively, the patients showed improvement of the posterior uveitis and its systemic manifestations. However, there was no significant visual acuity improvement due to bilateral extensive macular involvement. CONCLUSIONS AND IMPORTANCE: Clinicians should be aware that toxoplasmosis originating from South America could be associated with severe acute multisystemic and intraocular bilateral involvement, even in patients with no history of exposure to jungle environments.
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BACKGROUND/PURPOSE: Age-related macular degeneration (AMD) is the leading cause of visual impairment in patients over 55 years. Currently, the most common therapies for neovascular AMD (nAMD) are intravitreal antiangiogenics. Studies suggest that genetic factors influence on antiangiogenics therapy outcomes. The purpose of this work was to establish the association between complement factor H (CFH) (Y402H), age-related maculopathy susceptibility 2 (ARMS2) (A69S), and high-temperature requirement factor A1 (HTRA1) (rs11200638) polymorphisms and the response to treatment with ranibizumab in patients with nAMD. METHODS: A cross-sectional study with 61 eyes with nAMD treated with ranibizumab was performed. Association between polymorphisms from CFH, ARMS2, and HTRA1 with the response to treatment was established. RESULTS: The mean age of patients was 76.6 (51-91) years. Only 37.7% of patients had a functional response and 26.2% had an anatomic response. TT polymorphism Y402H from CFH gene was associated with an increased likelihood of functional response to treatment. Otherwise, there was not a statistically significant association between anatomic and functional response to gene polymorphisms rs11200638 from HTRA1 and rs10490924 from ARMS 2. CONCLUSIONS: This study suggests that the response to intravitreal antiangiogenic therapy with ranibizumab was not associated to main polymorphisms from genes HTRA1 and ARMS2. However, it was found that the response to treatment differed according to CFH genotype, suggesting that further investigations are needed to establish if patients with the CC and TC genotype may need to be monitored more closely for disease recurrence than the TT genotype.
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An extremely affordable virus concentration method based on adsorption-elution to glass wool and subsequent reconcentration through polyethylene glycol 6000 (PEG) precipitation was optimized to recover not only non-enveloped viruses but also enveloped viruses. Hepatitis A virus (HAV) and transmissible gastroenteritis virus (TGEV) were employed as surrogates for naked and enveloped viruses, respectively, to set up the methodology. Initial experimentation in small-volume samples showed that both types of particles readily adsorbed to the positively charged glass wool but were poorly detached from it through standard elution with 0.05 M glycine with 3% of beef extract buffer, pH 9.5, with elution efficiencies of 7.2% and 2.6%, for HAV and TGEV, respectively. To improve the recovery of enveloped viruses, several modifications in the elution were assayed: increasing the elution pH, extending glass wool and eluent contact time, adding a detergent, or performing the elution by recirculation or under agitation. Considering practicability and performance, recircularization of the eluent at pH 11.0 for 20 min was the elution procedure of choice, with efficiencies of 25.7% and 18.8% for HAV and TGEV in 50 L of water. Additionally, employing 20% PEG instead of 10% for virus reconcentration improved recoveries up to 47% and 51%, respectively. The optimized procedure was applied to detect naturally occurring HAV and coronaviruses in surface water of Wadi Hanifa, Riyadh. HAV was detected in 38% of the samples, while one sample was positive for an alphacoronavirus. This cheap virus detection system enables the comprehensive surveillance of viruses present in water samples.
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Água Doce/virologia , Vidro/química , Vírus da Hepatite A/química , Vírus da Gastroenterite Transmissível/química , Virologia/métodos , Adsorção , Vírus da Hepatite A/isolamento & purificação , Vírus da Gastroenterite Transmissível/isolamento & purificação , Virologia/instrumentação , Vírus/química , Vírus/isolamento & purificaçãoRESUMO
Non-homologous end-joining (NHEJ) is the preferred mechanism used by hematopoietic stem cells (HSCs) to repair double-stranded DNA breaks and is particularly increased in cells deficient in the Fanconi anemia (FA) pathway. Here, we show feasible correction of compromised functional phenotypes in hematopoietic cells from multiple FA complementation groups, including FA-A, FA-C, FA-D1, and FA-D2. NHEJ-mediated repair of targeted CRISPR-Cas9-induced DNA breaks generated compensatory insertions and deletions that restore the coding frame of the mutated gene. NHEJ-mediated editing efficacy was initially verified in FA lymphoblastic cell lines and then in primary FA patient-derived CD34+ cells, which showed marked proliferative advantage and phenotypic correction both in vitro and after transplantation. Importantly, and in contrast to homologous directed repair, NHEJ efficiently targeted primitive human HSCs, indicating that NHEJ editing approaches may constitute a sound alternative for editing self-renewing human HSCs and consequently for treatment of FA and other monogenic diseases affecting the hematopoietic system.
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Sistemas CRISPR-Cas/genética , Reparo do DNA por Junção de Extremidades/genética , Proteína do Grupo de Complementação A da Anemia de Fanconi/genética , Anemia de Fanconi/terapia , Edição de Genes/métodos , Terapia Genética/métodos , Transplante de Células-Tronco Hematopoéticas , Alelos , Animais , Antígenos CD34/metabolismo , Linhagem Celular , Proliferação de Células/genética , Quebras de DNA de Cadeia Dupla , Anemia de Fanconi/genética , Anemia de Fanconi/metabolismo , Proteína do Grupo de Complementação A da Anemia de Fanconi/metabolismo , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Transplante de Células-Tronco Hematopoéticas/métodos , Células-Tronco Hematopoéticas/citologia , Células-Tronco Hematopoéticas/metabolismo , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Mutação INDEL , Camundongos , Camundongos Endogâmicos NOD , Camundongos NusRESUMO
Fanconi anemia (FA) is a rare genetic syndrome characterized by progressive marrow failure. Gene therapy by infusion of FA-corrected autologous hematopoietic stem cells (HSCs) may offer a potential cure since it is a monogenetic disease with mutations in the FANC genes, coding for DNA repair enzymes [1]. However, the collection of hCD34+-cells in FA patients implies particular challenges because of the reduced numbers of progenitor cells present in their bone marrow (BM) [2] or mobilized peripheral blood [3-5]. In addition, the FA genetic defect fragilizes the HSCs [6]. These particular features might explain why the first clinical trials using murine leukemia virus derived retroviral vectors conducted for FA failed to show engraftment of corrected cells. The gene therapy field is now moving towards the use of lentiviral vectors (LVs) evidenced by recent succesful clinical trials for the treatment of patients suffering from adrenoleukodystrophy (ALD) [7], ß-thalassemia [8], metachromatic leukodystrophy [9] and Wiskott-Aldrich syndrome [10]. LV trials for X-linked severe combined immunodificiency and Fanconi anemia (FA) defects were recently initiated [11, 12]. Fifteen years of preclinical studies using different FA mouse models and in vitro research allowed us to find the weak points in the in vitro culture and transduction conditions, which most probably led to the initial failure of FA HSC gene therapy. In this review, we will focus on the different obstacles, unique to FA gene therapy, and how they have been overcome through the development of optimized protocols for FA HSC culture and transduction and the engineering of new gene transfer tools for FA HSCs. These combined advances in the field hopefully will allow the correction of the FA hematological defect in the near future.
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Anemia de Fanconi/terapia , Terapia Genética/métodos , Vetores Genéticos/genética , Lentivirus/genética , Animais , Anemia de Fanconi/genética , Técnicas de Transferência de Genes , Transplante de Células-Tronco Hematopoéticas/métodos , Células-Tronco Hematopoéticas/metabolismo , HumanosRESUMO
PURPOSE: To describe the clinical features of uveitis in children treated at two ophthalmologic centers in Bogotá, Colombia, in a 13 year-period. METHODS: Retrospective observational clinical record review of pediatric children with diagnosis of uveitis. RESULTS: In total, 310 children were evaluated, 51.9% were female, mean age of 10.1 years. Posterior uveitis was the most common location (58.7%), of insidious onset (87.4%) and chronic course (78.1%). The most common etiology was infection (58.4%) caused by toxoplasmosis (76.8%). There was a statistically significant difference in visual acuity between anterior (20/68) and intermediate uveitis (20/70), compared with posterior uveitis (20/434) (p<0.05). CONCLUSIONS: This is the first study to report the clinical features of pediatric uveitis in Colombia, where infectious etiologies are the leading cause. It will improve awareness and knowledge of pediatric uveitis in developing countries, and contribute to the development of public health policies of pediatric visual health. Received 12 September 2015; revised 23 February 2016; accepted 25 February 2016; published online 18 May 2016.
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Países em Desenvolvimento , Uveíte/epidemiologia , Adolescente , Criança , Pré-Escolar , Colômbia/epidemiologia , Feminino , Humanos , Lactente , Recém-Nascido , Masculino , Estudos Retrospectivos , Uveíte/classificação , Uveíte/diagnóstico , Acuidade VisualRESUMO
In this report, we present an unusual case of jaundice in a patient with advanced colorectal cancer due to intraductal tumour invasion of the intra- and extrahepatic biliary tree. This complication proved to be fatal despite aggressive therapeutic management. A correct diagnosis of this type of involvement was achieved by a combination of diagnostic and therapeutic cholangiography. Despite adequate biliary decompression, the patient died from liver failure and biliary sepsis.
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La fibrilación auricular es muy frecuente en el paciente anciano. Aunque existe una amplia experiencia con los antagonistas de la vitamina K, el empleo de estos fármacos en el paciente anciano presenta numerosas limitaciones, con una mayor susceptibilidad a las hemorragias y un peor control de la anticoagulación que en la población general. Los anticoagulantes orales de acción directa han demostrado ser una mejor alternativa terapéutica para los pacientes ancianos, no solo por su mayor simplicidad de uso, sino por sus mayores eficacia y seguridad en comparación con los antagonistas de la vitamina K, con datos que en general concuerdan con los ensayos clínicos fundamentales. Sin embargo, en el paciente anciano hay una tendencia al uso de dosis inadecuadas, generalmente por infradosificación, sobre todo con algunos de ellos, lo que conlleva una menor protección contra los ictus, sin una clara ventaja antihemorrágica. El rivaroxabán se ha estudiado ampliamente en la población anciana y no solo en ensayos clínicos, sino también en multitud de estudios en la práctica clínica real, con datos muy consistentes. En estos estudios, en comparación con los antagonistas de la vitamina K, se ha demostrado que el rivaroxabán reduce el riesgo de ictus sin un incremento de las hemorragias mortales, con lo que tiene un beneficio clínico neto favorable en la población con fibrilación auricular no valvular con mayor riesgo tromboembólico
Atrial fibrillation is common in elderly patients. Although vitamin K antagonists have been widely used for many years, they have a number of limitations in elderly patients, who are particularly susceptible to bleeding and in whom anticoagulation control is poorer than in the general population. Direct oral anticoagulants have been shown to be a better therapeutic option for these patients, not only because they are simpler to use, but also because they are more effective and safer than vitamin K antagonists. Moreover, their performance in practice is generally consistent with that in pivotal clinical trials. Nevertheless, there is a tendency to administer inappropriate doses to elderly patients, generally underdosing, particularly in certain subgroups. This can result in less protection against stroke without any clear reduction in bleeding risk. Rivaroxaban has been widely studied in the elderly population, not only in clinical trials, but also in a range of studies in routine clinical practice - findings have been highly consistent. According to these studies, and compared to vitamin K antagonists, rivaroxaban reduces the risk of stroke without increasing the rate of fatal bleeding, with a net clinical benefit in patients with nonvalvular atrial fibrillation and a high thromboembolic risk
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Humanos , Múltiplas Afecções Crônicas/tratamento farmacológico , Anticoagulantes/administração & dosagem , Rivaroxabana/administração & dosagem , Fibrilação Atrial/tratamento farmacológico , Acidente Vascular Cerebral/prevenção & controle , Fragilidade/complicações , Fragilidade/tratamento farmacológico , Polimedicação , Envelhecimento/efeitos dos fármacos , 50293 , Vitamina K/antagonistas & inibidores , Antifibrinolíticos/administração & dosagem , Varfarina/administração & dosagemRESUMO
La preservación de la fertilidad es la aplicación de estrategias médicas y de laboratorio para preservar la descendencia genética parental en adultos o niños en riesgo de esterilidad. El cáncer es la principal indicación de preservación de fertilidad en pacientes en edad reproductiva. En las últimas décadas ha incrementado la incidencia de cáncer en adolescentes. Los tratamientos oncológicos también han mejorado significativamente, por lo que hoy es posible la curación en un amplio porcentaje de pacientes. La mayoría de los niños y adolescentes con cáncer se convierten en sobrevivientes a largo plazo, lo que aumenta el interés en los efectos del tratamiento del cáncer sobre la fertilidad. Las condiciones sociales, económicas y culturales también son determinantes para decidir el momento que una pareja busque promover su fertilidad. Además, otras patologías o incluso fármacos para prevención del rechazo de órganos trasplantados pueden afectar la fertilidad y, por tanto, tales pacientes son susceptibles de orientación sobre preservación de la fertilidad. El éxito en los programas de reproducción asistida y en los tratamientos oncológicos brindan alternativas para preservar la fertilidad. En esta primera Opinión de Grupo de Expertos Mexicanos en Preservación de la Fertilidad hemos evaluado pacientes oncológicas que son candidatas a preservación de fertilidad: jóvenes con riesgo de compromiso de su fertilidad por el tratamiento oncológico, pero con reserva ovárica suficiente y pronóstico vital aceptable. También se consideraron casos especiales como la preservación social, en casos de conceptualización sexual diferente, así como los aspectos legales y éticos básicos
Fertility preservation is the application of medical and laboratory strategies to preserve parental genetic offspring in adults or children at risk of sterility. Cancer is the main indication of fertility preservation in patients of reproductive age. In recent decades, the incidence of cancer in adolescents has increased. Cancer treatments have also improved significantly, making cure possible today in a large percentage of patients. Most children and adolescents with cancer become long-term survivors, increasing interest in the effects of cancer treatment on fertility. Social, economic and cultural conditions are also decisive in deciding when a couple seeks to promote their fertility. Furthermore, other pathologies or even drugs for the prevention of rejection of transplanted organs can affect fertility and, therefore, such patients are susceptible to guidance on fertility preservation. Success in assisted reproduction programs and cancer treatments provide alternatives to preserve fertility. In this first Opinion of the Group of Mexican Experts on Fertility Preservation, we have evaluated oncological patients who are candidates for fertility preservation: young people at risk of compromising their fertility due to oncological treatment, but with sufficient ovarian reserve and acceptable vital prognosis. Special cases such as social preservation were also considered, in cases of different sexual conceptualization, as well as the basic legal and ethical aspects