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2.
Radiologia (Engl Ed) ; 66(2): 196-204, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38614536

RESUMO

After the implementation of the European Space for Higher Education, the contents of the Radiology and Physical Medicine Area that were taught in the Medicine Degree have also been incorporated into the new degrees of Dentistry, Nursing, Physiotherapy, Podiatry, and, to a lesser extent, Pharmacy, Occupational Therapy, Logopedia, and Biomedical Engineering As a whole, the basic concepts of radiology and radiological protection are taught in Murcia in 5 different degrees with a total of 52.5 ECTS credits, participating in the training of 1219 students each academic year. This incorporation in the new degrees has tripled the number of subjects in which undergraduate teaching is taught, and doubled both the number of ECTS credits and the number of undergraduate students to whom it directs its training work. Thus, given the possible creation of new university degrees in the near future (Diagnostic Imaging and Radiotherapy Technicians), it would be necessary to involve a greater number of accredited professionals, from different specialties, and to optimize teaching resources (bibliography, material teacher, clinical cases, etc.,) for its usefulness in the different subjects that share similar contents.


Assuntos
Proteção Radiológica , Radiologia , Humanos , Universidades , Radiografia
3.
Artigo em Inglês | MEDLINE | ID: mdl-38428676

RESUMO

The aim of this study is to describe the anaesthesia management of two patients undergoing carinal resection under veno-venous extracorporeal membrane oxygenation (VV ECMO). In both cases, anaesthesia was induced and then maintained with inhalational agents during pneumonectomy and mediastinoscopy (respectively). Then the jugular and femoral veins were cannulated and VV ECMO was started after heparinization. One of the patients presented bleeding during surgery, which was treated with low-dose vasopressors (norepinephrine) and transfusion of platelets, fresh frozen plasma, and concentrated red blood cells. During VV ECMO, anaesthesia was maintained with target-controlled infusion of propofol. VV ECMO can be expected to improve surgical conditions in tracheal surgery; however, it is still a novel technique in this context. In selected patients, it would guarantee ventilatory support during carinal resection, but it is essential to carefully plan anaesthesia maintenance and prepare for VV ECMO-related complications. This technique should only be used in tertiary centres with experience in VV ECMO management.

4.
Rev Neurol ; 78(7): 179-183, 2024 Apr 01.
Artigo em Espanhol | MEDLINE | ID: mdl-38502166

RESUMO

INTRODUCTION: Ryanodine receptor type 1-related myopathies (RYR1-RM) represent the most prevalent category of congenital myopathies. The introduction of genetic techniques has shifted the diagnostic paradigm, suggesting the prioritization of molecular studies over biopsies. This study aims to explore the clinical and epidemiological characteristics of patients with RYR1 gene variants in a tertiary pediatric hospital, intending to enhance the understanding of the genotype-phenotype correlation in RYR1-RM. PATIENTS AND METHODS: An observational, descriptive, and cross-sectional study was conducted on patients under 14 years old with myopathic symptoms and potentially pathogenic RYR1 gene variants from January 2013 to December 2023. Variables such as gender, age, motor development, genetic variants, inheritance pattern, and other manifestations were considered. All variables were tabulated against the genetic variant. RESULTS: Of the nine included patients, the estimated incidence was approximately 1 in 10,000 live births. The median age at diagnosis was six years, with significant phenotypic variability. Common symptoms such as weakness and delayed motor development were observed. Genetic variants affected the RYR1 gene diversely, including five previously undescribed variants. Muscle biopsy was performed in five patients, revealing central core myopathy in two, multiminicore in one, congenital fiber-type disproportion in one, and a nonspecific pattern in another. CONCLUSIONS: RYR1-RM in our series exhibited phenotypic and involvement variability, with an incidence in our area of around 1 in 10,000 live births. Most cases were male, with dominant missense variants. We contribute five previously undescribed genetic variants.


TITLE: Miopatías RYR1 en la infancia: correlación fenotipo-genotipo e incidencia.Introducción. Las miopatías relacionadas con el receptor de rianodina de tipo 1 (RYR1-RM) constituyen la categoría más frecuente de miopatías congénitas. La introducción de técnicas genéticas ha cambiado el paradigma diagnóstico y sugiere la prioridad de estudios moleculares sobre biopsias. Este estudio busca explorar las características clinicoepidemiológicas de pacientes con variantes del gen RYR1 en un hospital pediátrico de tercer nivel con el objetivo de ampliar la comprensión de la correlación genotipo-fenotipo en las RYR1-RM. Pacientes y métodos. Estudio observacional, descriptivo y transversal, de pacientes menores de 14 años con síntomas miopáticos y variantes potencialmente patógenas del gen RYR1 entre enero de 2013 y diciembre de 2023, considerando variables como sexo, edad, desarrollo motor, variantes genéticas, patrón de herencia y otras manifestaciones. Todas las variables fueron tabuladas frente a la variante genética. Resultados. De los nueve pacientes incluidos, la incidencia estimada fue de aproximadamente 1/10.000 nacidos vivos. La mediana en el momento del diagnóstico fue de 6 años, con una variabilidad fenotípica significativa. Se observaron síntomas comunes, como debilidad y retraso del desarrollo motor. Las variantes genéticas afectaron al gen RYR1 de manera diversa, y hubo cinco variantes previamente no descritas. La biopsia muscular se realizó en cinco pacientes, en dos de ellos de tipo miopatía central core; en uno, multiminicore; en uno, desproporción congénita de fibras; y en otro, de patrón inespecífico. Conclusiones. Las RYR1-MR de nuestra serie ofrecieron variabilidad fenotípica y de afectación, con una incidencia en nuestra área de en torno a 1/10.000 recién nacidos. La mayoría de los casos fueron varones, de variantes missense dominantes. Aportamos cinco variantes genéticas no descritas con anterioridad.


Assuntos
Doenças Musculares , Canal de Liberação de Cálcio do Receptor de Rianodina , Humanos , Masculino , Criança , Adolescente , Feminino , Canal de Liberação de Cálcio do Receptor de Rianodina/genética , Estudos Transversais , Incidência , Doenças Musculares/epidemiologia , Doenças Musculares/genética , Estudos de Associação Genética , Fenótipo , Genótipo
5.
Arch Soc Esp Oftalmol (Engl Ed) ; 99(7): 288-295, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38309656

RESUMO

The limited accessibility to ophthalmological services in remote regions of developing countries poses a significant challenge in visual healthcare. Cataracts and refractive errors are prominent causes of visual impairment, and surgery, despite being an efficient option, faces barriers in developing countries due to financial and geographical constraints. Humanitarian missions play a vital role in addressing this issue. The improvement in the accuracy of calculating IOL power through techniques such as keratometry and biometry is a fundamental step towards optimizing surgical outcomes and the quality of life for patients in these underserved regions. In this context, the consideration of keratometry and immersion ultrasound biometry as preoperative assessment standards in cataract surgeries in developing countries is presented as a pertinent and advisable strategy.


Assuntos
Extração de Catarata , Missões Médicas , Humanos , Acuidade Visual , Países em Desenvolvimento , Altruísmo , Catarata/complicações , Resultado do Tratamento , Acessibilidade aos Serviços de Saúde , Biometria
6.
Eye (Lond) ; 38(8): 1418-1424, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38347178

RESUMO

Economic evaluations are tools for assessing emerging technologies and a complement for decision-making in healthcare systems. However, this topic may not be familiar for doctors and academics, who may be confused when interpreting the results of studies using these tools. Cataract is a disease which has received special attention in healthcare systems due to its high incidence, the great impact that it could have on patients' quality of life, and the fact that it can be definitively solved in almost all cases through cataract surgery. Historically, economic evaluations in cataract surgery have been conducted for many purposes by simply assessing whether the surgery is cost-effective for specific questions related to the implantation of multifocal intraocular lenses, surgical techniques, optimizing assessments, preventing diseases or complications, etc. Moreover, although there are systematic reviews about cataract surgery and narrative reviews introducing the concept of economic evaluations, as far as we know, no previous study has been conducted that synthesizes and integrates evidence coming from both fields. Thus, the purpose of this narrative review is to introduce doctors and academics to economic evaluation tools, to describe how these have been historically applied to cataract surgery, and to provide special considerations for the correct interpretation of economic studies.


Assuntos
Extração de Catarata , Análise Custo-Benefício , Humanos , Extração de Catarata/economia , Qualidade de Vida , Custos de Cuidados de Saúde , Catarata/economia , Anos de Vida Ajustados por Qualidade de Vida
8.
Rev Esp Anestesiol Reanim (Engl Ed) ; 71(3): 171-206, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38340791

RESUMO

The Airway Management section of the Spanish Society of Anesthesiology, Resuscitation, and Pain Therapy (SEDAR), the Spanish Society of Emergency Medicine (SEMES), and the Spanish Society of Otorhinolaryngology and Head and Neck Surgery (SEORL-CCC) present the Guide for the comprehensive management of difficult airway in adult patients. Its principles are focused on the human factors, cognitive processes for decision-making in critical situations, and optimization in the progression of strategies application to preserve adequate alveolar oxygenation in order to enhance safety and the quality of care. The document provides evidence-based recommendations, theoretical-educational tools, and implementation tools, mainly cognitive aids, applicable to airway management in the fields of anesthesiology, critical care, emergencies, and prehospital medicine. For this purpose, an extensive literature search was conducted following PRISMA-R guidelines and was analyzed using the GRADE methodology. Recommendations were formulated according to the GRADE methodology. Recommendations for sections with low-quality evidence were based on expert opinion through consensus reached via a Delphi questionnaire.


Assuntos
Manuseio das Vias Aéreas , Humanos , Manuseio das Vias Aéreas/normas , Manuseio das Vias Aéreas/métodos , Medicina de Emergência/normas , Adulto , Intubação Intratraqueal
9.
Rev Esp Anestesiol Reanim (Engl Ed) ; 71(3): 207-247, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38340790

RESUMO

The Airway Management section of the Spanish Society of Anesthesiology, Resuscitation, and Pain Therapy (SEDAR), the Spanish Society of Emergency Medicine (SEMES), and the Spanish Society of Otorhinolaryngology and Head and Neck Surgery (SEORL-CCC) present the Guide for the comprehensive management of difficult airway in adult patients. Its principles are focused on the human factors, cognitive processes for decision-making in critical situations, and optimization in the progression of strategies application to preserve adequate alveolar oxygenation in order to enhance safety and the quality of care. The document provides evidence-based recommendations, theoretical-educational tools, and implementation tools, mainly cognitive aids, applicable to airway management in the fields of anesthesiology, critical care, emergencies, and prehospital medicine. For this purpose, an extensive literature search was conducted following PRISMA-R guidelines and was analyzed using the GRADE methodology. Recommendations were formulated according to the GRADE methodology. Recommendations for sections with low-quality evidence were based on expert opinion through consensus reached via a Delphi questionnaire.


Assuntos
Manuseio das Vias Aéreas , Humanos , Manuseio das Vias Aéreas/normas , Manuseio das Vias Aéreas/métodos , Medicina de Emergência/normas , Adulto , Intubação Intratraqueal
10.
Environ Sci Technol ; 58(5): 2271-2281, 2024 Feb 06.
Artigo em Inglês | MEDLINE | ID: mdl-38270974

RESUMO

To mitigate methane emission from urban natural gas distribution systems, it is crucial to understand local leak rates and occurrence rates. To explore urban methane emissions in cities outside the U.S., where significant emissions were found previously, mobile measurements were performed in 12 cities across eight countries. The surveyed cities range from medium size, like Groningen, NL, to large size, like Toronto, CA, and London, UK. Furthermore, this survey spanned across European regions from Barcelona, ES, to Bucharest, RO. The joint analysis of all data allows us to focus on general emission behavior for cities with different infrastructure and environmental conditions. We find that all cities have a spectrum of small, medium, and large methane sources in their domain. The emission rates found follow a heavy-tailed distribution, and the top 10% of emitters account for 60-80% of total emissions, which implies that strategic repair planning could help reduce emissions quickly. Furthermore, we compare our findings with inventory estimates for urban natural gas-related methane emissions from this sector in Europe. While cities with larger reported emissions were found to generally also have larger observed emissions, we find clear discrepancies between observation-based and inventory-based emission estimates for our 12 cities.


Assuntos
Poluentes Atmosféricos , Gás Natural , Cidades , Gás Natural/análise , Metano/análise , Poluentes Atmosféricos/análise , Londres
11.
ACS Med Chem Lett ; 14(12): 1800-1806, 2023 Dec 14.
Artigo em Inglês | MEDLINE | ID: mdl-38116409

RESUMO

The androgen receptor (AR) is central to prostate cancer pathogenesis and has been extensively validated as a drug target. However, small-molecule anti-androgen therapies remain limited due to resistance and will eventually fail to suppress tumor growth, resulting in progression to castration-resistant prostate cancer (CRPC). The intrinsically disordered N-terminal domain (NTD) is crucial for AR transactivation and has been investigated as a suitable target in the presence of ligand binding domain mutations. A screening campaign identified biaryl isoxazole compound 7 as a weak inhibitor of the AR NTD. A library of biaryl analogues were synthesized, and their biological activities were assessed in a VCaP cell-based luciferase reporter gene assay. A structure-activity relationship (SAR) study revealed that indazole analogue 16 exhibited increased potency and favorable physicochemical properties with a benchmarked pharmacokinetic profile, providing a suitable starting point for further optimization of 16 as a CRPC therapeutic in the presence of AR mutations.

12.
Rev Esp Anestesiol Reanim (Engl Ed) ; 70(8): 458-466, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-37669701

RESUMO

In an effort to standardize perioperative management and improve postoperative outcomes of adult patients undergoing surgery, the Ministry of Health, through the Spanish Multimodal Rehabilitation Group (GERM), and the Aragonese Institute of Health Sciences, in collaboration with multiple Spanish scientific societies and based on the available evidence, published in 2021 the Spanish Intensified Adult Recovery (RICA) guideline. This document includes 12 perioperative measures related to fluid therapy and hemodynamic monitoring. Fluid administration and hemodynamic monitoring are not straightforward but are directly related to postoperative patient outcomes. The Fluid Therapy and Hemodynamic Monitoring Subcommittee of the Hemostasis, Transfusion Medicine and Fluid Therapy Section (SHTF) of the Spanish Society of Anesthesiology and Critical Care (SEDAR) has reviewed these recommendations and concluded that they should be revised as they do not follow an adequate methodology.

13.
Rev Neurol ; 77(6): 141-145, 2023 09 16.
Artigo em Espanhol | MEDLINE | ID: mdl-37668235

RESUMO

INTRODUCTION: KIF1A-associated-neurological-disorder (KAND) encephalopathy is a group of progressive neurodegenerative pathologies of varying severity caused by mutations in the KIF1A gene (Kinesin family member 1A) located on chromosome 2q37.3. This gene encodes a protein of the kinesin-3 family that participates in the ATP-dependent anterograde transport of presynaptic vesicles through neuronal microtubules. CASE REPORT: Four patients are described, aged 1-13 years, with a median onset of symptoms of 5 months (IQR 0-11 months), which represents an approximate prevalence of 1 per 64,000 children under 14 years of age for our pediatric population. Clinically, intellectual disability (ID), axial hypotonia and spastic paraparesis stood out in 4/4 and cerebellar symptoms in 2/4. Other manifestations were urinary incontinence, sensory-motor polyneuropathy, and behavioral alteration. In case 2, the alteration in the video-EEG stands out, which showed focal epilepsy with secondary generalization and right posterior occipito-parietal paroxysmal focality with contralateral transmission. She also showed instantaneous pluricotidian supraversion oculogyric seizures without EEG correlates. CONCLUSIONS: In our series, KAND encephalopathy had a predominant neurodegenerative disorder phenotype with global developmental delay, gait delay, and progressive spasticity of the lower limbs, cerebellar atrophy, and/or involvement of the visual cortex, which in one case was associated with sensory-motor polyneuropathy. The de novo missense mutation was more frequent and in three cases it is the first known description. One case showed focal epilepsy and nonepileptic oculogyric seizures.


TITLE: Enfermedad neurológica asociada al gen KIF1A: correlación genotipo/fenotipo.Introducción. La encefalopatía KIF1A-associated-neurological-disorder (KAND) es un grupo de patologías neurodegenerativas progresivas de diversa gravedad ocasionadas por mutaciones en el gen KIF1A (kinesin family member 1A) situado en el cromosoma 2q37.3. Dicho gen codifica una proteína de la familia de las cinesinas 3 que participa en el transporte anterógrado de las vesículas presinápticas dependientes del trifosfato de adenosina a través de microtúbulos neuronales. Casos clínicos. Se describen cuatro pacientes, con edades entre 1 y 13 años, con mediana de inicio de los síntomas de cinco meses (rango intercuartílico: 0-11 meses), lo que supone una prevalencia aproximada de 1 de cada 64.000 menores de 14 años para nuestra población pediátrica. Clínicamente, destacaron discapacidad intelectual, hipotonía axial y paraparesia espástica en 4/4, y síntomas cerebelosos en 2/4. Otras manifestaciones fueron incontinencia urinaria, polineuropatía sensitivomotora y alteración conductual. Destaca, en el caso 2, la alteración en el videoelectroencefalograma, que mostraba epilepsia focal con generalización secundaria y focalidad paroxística occipitoparietal posterior derecha con transmisión contralateral. También mostraba crisis oculógiras en supraversión instantáneas pluricotidianas sin correlato electroencefalográfico. Conclusiones. En nuestra serie, la encefalopatía KAND, fenotipo trastorno neurodegenerativo con retraso global del desarrollo, de la marcha y espasticidad progresiva de los miembros inferiores, atrofia cerebelosa y/o afectación de la corteza visual, fue predominante, y en uno de los casos asoció polineuropatía sensitivomotora. La mutación de novo missense fue más frecuente y en tres casos es la primera descripción conocida. Un caso mostraba epilepsia focal y crisis oculógiras no epilépticas.


Assuntos
Encefalopatias , Epilepsias Parciais , Cinesinas , Criança , Feminino , Humanos , Genótipo , Cinesinas/genética , Fenótipo , Convulsões , Lactente , Pré-Escolar , Adolescente
14.
Pharmaceuticals (Basel) ; 16(7)2023 Jul 14.
Artigo em Inglês | MEDLINE | ID: mdl-37513915

RESUMO

Studies have shown high comorbidity of anxiety disorder and chronic pain; generalized anxiety disorder (GAD) and neuropathic pain are among these pathologies. Cannabidiol (CBD) has been considered a promising treatment for these conditions. This study investigated whether chronic systemic treatment with CBD alters pain in high- (CHF) and low-freezing (CLF) Carioca rats (GAD model) and control rats (CTL) submitted to chronic neuropathic pain. The rats were evaluated in the sensory aspects (von Frey, acetone, and hot plate tests) before the chronic constriction injury of the ischiatic nerve (CCI) or not (SHAM) and on days 13 and 23 after surgery. Chronic treatment with CBD (5 mg/kg daily) was used for ten days, starting the 14th day after surgery. The open field test on the 22nd also evaluated locomotion and anxiety-like behavior. CBD treatment had an anti-allodynic effect on the mechanical and thermal threshold in all lineages; however, these effects were lower in the CHF and CLF lineages. Considering emotional evaluation, we observed an anxiolytic effect in CTL+CCI and CHF+CCI after CBD treatment and increased mobility in CLF+SHAM rats. These results suggest that the CBD mechanical anti-allodynic and emotional effects can depend on anxiety level.

15.
Front Nutr ; 10: 1198121, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37521419

RESUMO

Background: Glucosinolates (GSLs) constitute a characteristic group of secondary metabolites present in the Brassica genus. These compounds confer resistance to pests and diseases. Moreover, they show allelopathic and anticarcinogenic effects. All those effects are dependent on the chemical structure of the GSL. The modification of the content of specific GSLs would allow obtaining varieties with enhanced resistance and/or improved health benefits. Moreover, the attainment of varieties with the same genetic background but with divergent GSLs concentration will prompt the undertaking of studies on their biological effects. Objective and Methods: The objective of this study was to evaluate the efficacy of two divergent mass selection programs to modify GSL content in the leaves of two Brassica species: nabicol (Brassica napus L.), selected by glucobrassicanapin (GBN), and nabiza (Brassica rapa L.), selected by gluconapin (GNA) through several selection cycles using cromatographic analysis. Results: The response to selection fitted a linear regression model with no signs of variability depletion for GSL modification in either direction, but with higher efficiency in reducing the selected GSL than in the increasing. The selection was also effective in other parts of the plant, suggesting that there is a GSL translocation in the plant or a modification in their synthesis pathway that is not-organ specific. There was an indirect response of selection in other GSL; thus this information should be considered when designing breeding programs. Finally, populations obtained by selection have the same agronomic performance or even better than the original population. Conclusion: Therefore, mass selection seems to be a good method to modify the content of specific GSL in Brassica crops.

16.
Artigo em Inglês | MEDLINE | ID: mdl-37279834

RESUMO

BACKGROUND: Research in fluid therapy and perioperative hemodynamic monitoring is difficult and expensive. The objectives of this study were to summarize these topics and to prioritize these topics in order of research importance. METHODS: Electronic structured Delphi questionnaire over three rounds among 30 experts in fluid therapy and hemodynamic monitoring identified through the Fluid Therapy and Hemodynamic Monitoring Subcommittee of the Hemostasis, Transfusion Medicine and Fluid Therapy Section of the Spanish Society of Anesthesiology and Critical Care. RESULTS: 77 topics were identified and ranked in order of prioritization. Topics were categorized into themes of crystalloids, colloids, hemodynamic monitoring and others. 31 topics were ranked as essential research priority. To determine whether intraoperative hemodynamic optimization algorithms based on the invasive or noninvasive Hypotension Prediction Index versus other management strategies could decrease the incidence of postoperative complications. As well as whether the use of renal stress biomarkers together with a goal-directed fluid therapy protocol could reduce hospital stay and the incidence of acute kidney injury in adult patients undergoing non-cardiac surgery, reached the highest consensus. CONCLUSIONS: The Fluid Therapy and Hemodynamic Monitoring Subcommittee of the Hemostasis, Transfusion Medicine and Fluid Therapy Section of the Spanish Society of Anesthesiology and Critical Care will use these results to carry out the research.


Assuntos
Anestesiologia , Monitorização Hemodinâmica , Medicina Transfusional , Adulto , Humanos , Consenso , Técnica Delphi , Hidratação , Cuidados Críticos , Hemostasia
17.
Langenbecks Arch Surg ; 408(1): 206, 2023 May 24.
Artigo em Inglês | MEDLINE | ID: mdl-37221304

RESUMO

PURPOSE: Surgery of primary thyroid lymphoma (PTL) has been mostly limited to diagnostic work-up. This study aimed to further study its potential role. METHODS: This was a retrospective study from a multi-institutional registry of PTL patients. Clinical, diagnostic work-up (fine needle aspiration, FNA; core needle biopsy, CoreNB), contribution of surgery (open surgical biopsy, OpenSB; thyroidectomy), histology subtype, and outcome data were evaluated. RESULTS: Some 54 patients were studied. Diagnostic work-up included FNA in 47 patients, CoreNB in 11, and OpenSB in 21. CoreNB yielded the best sensitivity (90.9%). Thyroidectomy was performed in 14 patients with other diagnosis (incidental PTL), in 4 for diagnosis and in 4 for elective treatment of PTL. Incidental PTL was associated with not performed FNA nor CoreNB (OR 52.5; P = 0.008), mucosa-associated lymphoid tissue (MALT) subtype (OR 24.3; P = 0.012), and Hashimoto's thyroiditis (OR 11.1; P = 0.032). Lymphoma-related death (10 cases) mostly occurred within the first year after diagnosis and was associated with diffuse large B-cell (DLBC) subtype (OR 10.3; P = 0.018) and older patients (OR 1.08 for every 1-year increase; P = 0.010). There was a trend towards lower mortality rate in patients receiving thyroidectomy (2/22 versus 8/32, P = 0.172). CONCLUSION: Incidental PTL accounts for most of thyroid surgery cases and are associated with incomplete diagnostic work-up, Hashimoto's thyroiditis and MALT subtype. CoreNB appears to be the best tool for diagnosis. Most of PTL deaths occurred during the first year after diagnosis and mostly related to systemic treatment. Age and DLBC subtype are poor prognostic factors.


Assuntos
Linfoma , Neoplasias da Glândula Tireoide , Tireoidite , Humanos , Estudos Retrospectivos
19.
Med Res Rev ; 43(5): 1701-1747, 2023 09.
Artigo em Inglês | MEDLINE | ID: mdl-37062876

RESUMO

The androgen receptor (AR) has been shown to be a key determinant in the pathogenesis of castration-resistant prostate cancer (CRPC). The current standard of care therapies targets the ligand-binding domain of the receptor and can afford improvements to life expectancy often only in the order of months before resistance occurs. Emerging preclinical and clinical compounds that inhibit receptor activity via differentiated mechanisms of action which are orthogonal to current antiandrogens show promise for overcoming treatment resistance. In this review, we present an authoritative summary of molecules that noncompetitively target the AR. Emerging small molecule strategies for targeting alternative domains of the AR represent a promising area of research that shows significant potential for future therapies. The overall quality of lead candidates in the area of noncompetitive AR inhibition is discussed, and it identifies the key chemotypes and associated properties which are likely to be, or are currently, positioned to be first in human applications.


Assuntos
Neoplasias de Próstata Resistentes à Castração , Receptores Androgênicos , Masculino , Humanos , Neoplasias de Próstata Resistentes à Castração/tratamento farmacológico , Neoplasias de Próstata Resistentes à Castração/patologia , Antagonistas de Androgênios/uso terapêutico , Linhagem Celular Tumoral
20.
Neurologia (Engl Ed) ; 38(4): 256-261, 2023 May.
Artigo em Inglês | MEDLINE | ID: mdl-37031801

RESUMO

INTRODUCTION: Advances in the treatment of myasthenia gravis (MG) have improved quality of life and prognosis for the majority of patients. However, 10%-20% of patients present refractory MG, with frequent relapses and significant functional limitations. PATIENTS AND METHODS: Patients with refractory MG were selected from a cohort of patients diagnosed with MG between January 2008 and June 2019. Refractory MG was defined as lack of response to treatment with prednisone and at least 2 immunosuppressants, inability to withdraw treatment without relapse in the last 12 months, or intolerance to treatment with severe adverse reactions. RESULTS: We identified 84 patients with MG, 11 of whom (13%) met criteria for refractory MG. Mean (standard deviation) age was 47 (18) years; 64% of patients with refractory MG had early-onset generalised myasthenia (as compared to 22% in the group of patients with MG; P < .01), with a higher proportion of women in this group (P < .01). Disease severity at diagnosis and at the time of data analysis was higher among patients with refractory MG, who presented more relapses during follow-up. Logistic regression analysis revealed an independent association between refractory MG and the number of severe relapses. CONCLUSIONS: The percentage of patients with refractory MG in our series (13%) is similar to those reported in previous studies; these patients were often women and presented early onset, severe forms of onset, and repeated relapses requiring hospital admission during follow-up.


Assuntos
Miastenia Gravis , Qualidade de Vida , Humanos , Feminino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia , Miastenia Gravis/tratamento farmacológico , Miastenia Gravis/diagnóstico , Prednisona/uso terapêutico , Imunossupressores/uso terapêutico
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