Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 42
Filtrar
1.
Int J Mol Sci ; 24(17)2023 Aug 22.
Artículo en Inglés | MEDLINE | ID: mdl-37685869

RESUMEN

ITGAM-ITGAX (rs11150612, rs11574637), VAV3 rs17019602, CARD9 rs4077515, DEFA (rs2738048, rs10086568), and HORMAD2 rs2412971 are mucosal immune defence polymorphisms, that have an impact on IgA production, described as risk loci for IgA nephropathy (IgAN). Since IgAN and Immunoglobulin-A vasculitis (IgAV) share molecular mechanisms, with the aberrant deposit of IgA1 being the main pathophysiologic feature of both entities, we assessed the potential influence of the seven abovementioned polymorphisms on IgAV pathogenesis. These seven variants were genotyped in 381 Caucasian IgAV patients and 997 matched healthy controls. No statistically significant differences were observed in the genotype and allele frequencies of these seven polymorphisms when the whole cohort of IgAV patients and those with nephritis were compared to controls. Similar genotype and allele frequencies of all polymorphisms were disclosed when IgAV patients were stratified according to the age at disease onset or the presence/absence of gastrointestinal or renal manifestations. Likewise, no ITGAM-ITGAX and DEFA haplotype differences were observed when the whole cohort of IgAV patients, along with those with nephritis and controls, as well as IgAV patients, stratified according to the abovementioned clinical characteristics, were compared. Our results suggest that mucosal immune defence polymorphisms do not represent novel genetic risk factors for IgAV pathogenesis.


Asunto(s)
Glomerulonefritis por IGA , Vasculitis por IgA , Inmunidad Mucosa , Nefritis , Humanos , Antígeno CD11c , Frecuencia de los Genes , Genotipo , Glomerulonefritis por IGA/genética , Vasculitis por IgA/genética , Polimorfismo Genético , Inmunidad Mucosa/genética
2.
Minerva Obstet Gynecol ; 75(5): 412-423, 2023 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-35758095

RESUMEN

BACKGROUND: Preeclampsia (PE) is a hypertensive disorder of pregnancy and one of the leading causes of maternal and fetal morbidity and mortality worldwide. While the underlying cause of remains unknown, abnormal placentation in early stages of pregnancy is thought to be a main triggering event for the more severe and early-onset forms. A consequence of placental insufficiency is an imbalance of angiogenic factors in the maternal circulation. The objective was to assess the utility of the angiogenic biomarker sFlt-1/PlGF for the diagnosis, follow-up and prognosis of preeclampsia. METHODS: This was a retrospective cohort study based including 65 consecutive singleton pregnancies with suspected preeclampsia referred to our hospital between January 2018 and February 2019. PE was defined as early-onset (20-33+6 weeks) and late-onset (≥34 weeks). The main independent variable was sFlt-1/PlGF classified in women with early or late onset PE, respectively, as low when <38 or <38, intermediate when 38-84 or 38-109, and high when ≥85 or ≥110. RESULTS: PE was confirmed in 14 (4 early-onset, 10 late-onset) of the participants. 122 sFlt-1/PIGF ratio determinations were requested. The optimal sFlt-1/PlGF to predict PE was ≥86 with a sensitivity of 93% and a specificity of 96% (AUC 0.95; CI 95% 0.90-1.0; P<0.001). A multilevel logistic model for the diagnosis of PE was adjusted for age, Body Mass Index, diabetes, proteinuria and mean arterial pressure. Women were 16.5 times (P=0.013) more likely to develop PE if they had intermediate sFlt-1/PlGF levels and 451 times (P<0.001) more likely if they had high biomarker levels compared to those with levels below 38. The probability of PE was 3.73 times (P=0.046) greater in those with maternal and/or fetal complications. CONCLUSIONS: The biomarker proved useful to diagnose PE and assess its prognosis. Patients diagnosed with PE had a higher frequency of complications and their newborns were of lower birth weight.


Asunto(s)
Preeclampsia , Embarazo , Femenino , Humanos , Recién Nacido , Preeclampsia/diagnóstico , Factor de Crecimiento Placentario , Estudios Retrospectivos , Estudios de Seguimiento , Placenta , Biomarcadores , Receptor 1 de Factores de Crecimiento Endotelial Vascular
3.
J Clin Med ; 11(19)2022 Sep 22.
Artículo en Inglés | MEDLINE | ID: mdl-36233442

RESUMEN

CD40, BLK and BANK1 genes involved in the development and signaling of B-cells are identified as susceptibility loci for numerous inflammatory diseases. Accordingly, we assessed the potential influence of CD40, BLK and BANK1 on the pathogenesis of immunoglobulin-A vasculitis (IgAV), predominantly a B-lymphocyte inflammatory condition. Three genetic variants within CD40 (rs1883832, rs1535045, rs4813003) and BLK (rs2254546, rs2736340, rs2618476) as well as two BANK1 polymorphisms (rs10516487, rs3733197), previously associated with inflammatory diseases, were genotyped in 382 Caucasian patients with IgAV and 955 sex- and ethnically matched healthy controls. No statistically significant differences were observed in the genotype and allele frequencies of CD40, BLK and BANK1 when IgAV patients and healthy controls were compared. Similar results were found when CD40, BLK and BANK1 genotypes or alleles frequencies were compared between patients with IgAV stratified according to the age at disease onset or to the presence/absence of gastrointestinal or renal manifestations. Moreover, no CD40, BLK and BANK1 haplotype differences were disclosed between patients with IgAV and healthy controls and between patients with IgAV stratified according to the clinical characteristics mentioned above. Our findings indicate that CD40, BLK and BANK1 do not contribute to the genetic background of IgAV.

5.
Acta Dermatovenerol Croat ; 291(1): 54-55, 2021 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-34477066

RESUMEN

Dear Editor, Nivolumab is a fully human monoclonal antibody that targets the programmed cell death 1 (PD-1) immune checkpoint. It has been approved for its use in several types of advanced solid tumors, including melanoma, lung cancer, and renal cell carcinoma (RCC). The inhibition of PD-1 leads to an enhanced adaptive immune response against tumor cells through the activation of T-cells. Vitiligo-like depigmentation (VLD) is a well-known side-effect in patients with melanoma that are being treated with anti PD-1 therapies (1). However, its development in patients undergoing treatment with nivolumab for cancers other than melanomas has been described very rarely. To our knowledge, herein we report the second case of nivolumab-induced VLD in a patient with metastatic RCC (2). The patient was a 63-year-old man who had a medical history of advanced RCC. He had initially undergone nephrectomy, and three months later he presented with local relapse and lung metastases. He had then received different treatment regimes, presenting with progression each time, until he finally started treatment with nivolumab. Five months after its introduction, the patient developed a disseminated hypochromic eruption. No other drugs were started over that period. He had no personal or family history of vitiligo or other autoimmune disorders. Dermatological examination revealed multiple, symmetrical, well-demarcated, depigmented macules involving his face, neck, torso, hands, and forearms. (Figure 1, a). Preservation of pigment in hair follicles could be seen on the dorsal aspect of his hands (Figure 1, b). Two 4-mm punch biopsies were taken, one from one from a depigmented patch and another from normally pigmented skin. In the first one, immunohistochemical analysis with Melan-A immunostaining demonstrated the absence of melanocytes, whereas melanocytes were present in the second one. A CD-8+ positive infiltrate was present in both biopsies, especially in the first one (Figure 2). The patient was diagnosed with VLD associated with nivolumab therapy. Since the patient was asymptomatic, no treatment was prescribed. He was advised to protect the achromic areas from sun exposure. In our patient, a causal association between the onset of VLD and the treatment with nivolumab cannot be completely ruled out. However, the clinical presentation with flecked macules in sun-exposed areas was consistent with what has been described in other patients presenting with VLD after starting treatment with this chemotherapeutic agent. The time to onset in our case was also within the limits which have been previously reported for this side-effect (16-52 weeks) (3). Therefore, we believe that a causal association is very probable. In patients with advanced melanoma who are treated with PD-1 inhibitors, the development of vitiligo-like lesions has been proved to be associated with improved progression-free and overall survival rates (4,5). This mechanism is not fully understood, but it has been suggested that inhibition of PD-1 could cause a loss of tolerance to melanocytic antigens, thus leading to a CD-8 T-cell dependent destruction of melanocytes present in the melanoma as well as in healthy skin (3,5). The presence of CD8 T-lymphocytes in our patient's biopsies supports this theory. However, the development of this condition in patients suffering from non-melanoma cancers suggests that different mechanisms, independent from melanoma, could also be involved. Larger studies are needed in order to determine if VLD also correlates with better survival rates in patients treated with nivolumab for non-melanoma malignancies. In conclusion, new checkpoint inhibitors can cause VLD not only in patients suffering from melanoma but also in those affected by other tumors. We believe dermatologists should play a key role in the management of this side-effect. Therefore, we ought to be familiar with it in order to be able to identify and treat it appropriately without discontinuation of anticancer treatment.


Asunto(s)
Carcinoma de Células Renales , Neoplasias Renales , Vitíligo , Carcinoma de Células Renales/tratamiento farmacológico , Humanos , Neoplasias Renales/tratamiento farmacológico , Masculino , Persona de Mediana Edad , Recurrencia Local de Neoplasia , Nivolumab/efectos adversos , Vitíligo/inducido químicamente
6.
Arch Gynecol Obstet ; 304(5): 1205-1212, 2021 11.
Artículo en Inglés | MEDLINE | ID: mdl-33830346

RESUMEN

PURPOSE: compare incidences of maternal-fetal complications during pregnancy, labor, and early puerperium according to baseline BMI in a consecutive cohort of pregnant women. METHODS: This retrospective cohort study compares pregnancy outcome indicators by body mass index (BMI) in 1236 pregnant women managed over the period January 2017 to May 2018. Data were collected regarding the personal history (smoking, diabetes and hypertension), obstetrics and BMI (kg/m2) (normoweight 18.5-24.9, overweight 25-29.9, obese ≥ 30). RESULTS: Of the 1236 women, 354 (28.6%) were overweight and 206 (16.7%) were obese at the start of pregnancy follow-up. Mean age at this time was 33 years (SD 6). Risk factors for a cesarean-section delivery assessed through logistic regression were maternal age (OR 1.05 95% CI 2.06-6.15; p < 0.001) and previous C-section (OR 4.21 95% CI 2.89-6.14; p < 0.001) regardless of BMI. In a propensity score analysis, pregnancy weight gain was found lower in obese vs normoweight (- 2.73 kg 95% CI - 3.74 to - 1.72 p < 0.001), and newborn weight higher in obese vs normoweight women (161.21 g 95% CI 57.94-264.48 p = 0.002). Labor duration and weight gain were reduced in overweight vs normoweight subjects (- 0.72 h 95% CI - 1.27 to - 0.17 p = 0.010 and 0.81 kg 95% CI - 1.50 to - 0.12 p = 0.021, respectively). CONCLUSIONS: In this cohort, obese women showed higher rates of prenatal complications yet obesity and overweight were not related to worse puerperium outcomes.


Asunto(s)
Índice de Masa Corporal , Obesidad Materna/epidemiología , Complicaciones del Embarazo/epidemiología , Resultado del Embarazo/epidemiología , Adulto , Estudios de Cohortes , Diabetes Gestacional/epidemiología , Femenino , Humanos , Hipertensión Inducida en el Embarazo/epidemiología , Hipertensión Inducida en el Embarazo/etiología , Recién Nacido , Obesidad Materna/complicaciones , Sobrepeso/complicaciones , Sobrepeso/epidemiología , Periodo Posparto , Preeclampsia/epidemiología , Preeclampsia/etiología , Embarazo , Complicaciones del Embarazo/etiología , Mujeres Embarazadas , Nacimiento Prematuro/epidemiología , Nacimiento Prematuro/etiología , Estudios Retrospectivos
7.
Australas J Dermatol ; 62(2): 213-216, 2021 May.
Artículo en Inglés | MEDLINE | ID: mdl-33421095

RESUMEN

Syringotropic mycosis fungoides is a very rare variant of cutaneous T-cell lymphomas characterised by prominent involvement of the eccrine glands. Hypereosinophilic syndrome refers to a rare group of conditions that are associated with persistent eosinophilia with organ involvement. It is classified into idiopathic, primary and secondary (reactive). We report herein an unusual case of hypereosinophilic syndrome with great impact on morbidity, which developed in a patient with human immunodeficiency virus infection and long-time misdiagnosed syringotropic mycosis fungoides.


Asunto(s)
Infecciones por VIH/complicaciones , Síndrome Hipereosinofílico/patología , Micosis Fungoide/patología , Neoplasias Cutáneas/patología , Humanos , Masculino , Persona de Mediana Edad
11.
Int J Dermatol ; 59(12): 1475-1484, 2020 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-33070314

RESUMEN

BACKGROUND: Many cutaneous manifestations have been described in possible association with the COVID-19 pandemic, including acral lesions resembling chilblains. The underlying pathomechanisms of COVID-19 chilblains are not fully understood. The aim of this study was to describe the clinical, pathological, and laboratory findings of a series of patients who developed chilblains during the COVID-19 outbreak and to investigate the possible factors that could be involved in the pathogenesis of these lesions. METHODS: We conducted a prospective cohort study that included 54 patients who presented with chilblains during the highest peak in the incidence of COVID-19 in Cantabria (northern Spain). Skin biopsies were performed on 10 of these patients who presented with recent lesions. Laboratory investigations, including immunological analysis, serological studies, and the assessment of cryoproteins, were also performed. RESULTS: Most patients presented erythematous plaques located on the toes and/or purpuric macules located on the feet. Histopathological findings were compatible with those of idiopathic chilblains. Immunohistochemical evaluation showed C3d and C4d deposits in the vessel walls in seven cases. The autoimmunity panel was negative in most of our series. Cryoprotein testing showed positive cryofibrinogen in two-thirds (66.7%) of the patients assessed. On follow-up, most patients presented almost complete resolution, although six patients required prednisone and antiaggregant drug treatment. CONCLUSIONS: This study shows, for the first time to our knowledge, a high prevalence of cryofibrinogenemia in patients with chilblains during the COVID-19 pandemic. Cryofibrinogenemia could be implicated in the pathogenesis of chilblains related to COVID-19.


Asunto(s)
Betacoronavirus/aislamiento & purificación , Eritema Pernio/sangre , Infecciones por Coronavirus/complicaciones , Crioglobulinemia/epidemiología , Neumonía Viral/complicaciones , Adolescente , Adulto , Anciano , Biopsia , COVID-19 , Eritema Pernio/diagnóstico , Eritema Pernio/epidemiología , Eritema Pernio/etiología , Niño , Infecciones por Coronavirus/sangre , Infecciones por Coronavirus/diagnóstico , Infecciones por Coronavirus/epidemiología , Crioglobulinemia/sangre , Crioglobulinemia/diagnóstico , Crioglobulinemia/etiología , Crioglobulinas/análisis , Femenino , Fibrinógenos Anormales/análisis , Humanos , Masculino , Persona de Mediana Edad , Pandemias , Neumonía Viral/sangre , Neumonía Viral/diagnóstico , Neumonía Viral/epidemiología , Prevalencia , Estudios Prospectivos , SARS-CoV-2 , Piel/patología , España/epidemiología , Adulto Joven
15.
Brain Connect ; 9(8): 594-603, 2019 10.
Artículo en Inglés | MEDLINE | ID: mdl-31244329

RESUMEN

The prognostic capacity of the diffusion tensor imaging measures fractional anisotropy (FA) and mean diffusivity (MD) to detect mild cognitive impairment (MCI) progression to Alzheimer's disease (AD) was assessed in 135 MCI patients and 72 healthy subjects over a median follow-up of 40 months. Forty-nine MCI patients (36.3%) developed AD. The factors MD left hippocampus, FA left cingulate, and FA left hippocampus emerged as predictors of progression. Age (hazard ratio [HR] 1.21), delayed text recall (HR 0.89), FA left uncinate (HR 1.90), FA left hippocampus (HR 2.21), and carrying at least one ApoE4 allele (HR 2.86) were associated with a high conversion rate. FA measures revealed the greatest discriminative capacity (Harrell's C = 0.73 versus 0.65 without FA; p = 0.034). The inclusion of FA structural connectivity data in our model improved discrimination between subjects with MCI progressing or not to dementia.


Asunto(s)
Enfermedad de Alzheimer/diagnóstico por imagen , Encéfalo/diagnóstico por imagen , Imagen de Difusión Tensora , Anciano , Anciano de 80 o más Años , Apolipoproteínas E/genética , Disfunción Cognitiva/diagnóstico por imagen , Diagnóstico Diferencial , Progresión de la Enfermedad , Diagnóstico Precoz , Femenino , Estudios de Seguimiento , Humanos , Masculino , Recuerdo Mental , Vías Nerviosas/diagnóstico por imagen , Pruebas Neuropsicológicas , Síntomas Prodrómicos , Estudios Prospectivos
19.
Exp Dermatol ; 26(10): 896-903, 2017 10.
Artículo en Inglés | MEDLINE | ID: mdl-28266728

RESUMEN

Sunlight exposure induces signalling pathways leading to the activation of melanin synthesis and tanning response. MicroRNAs (miRNAs) can regulate the expression of genes involved in pigmentation pathways by binding to the complementary sequence in their 3'untranslated regions (3'UTRs). Therefore, 3'UTR SNPs are predicted to modify the ability of miRNAs to target genes, resulting in differential gene expression. In this study, we investigated the role in pigmentation and sun-sensitivity traits, as well as in melanoma susceptibility, of 38 different 3'UTR SNPs from 38 pigmentation-related genes. A total of 869 individuals of Spanish origin (526 melanoma cases and 343 controls) were analysed. The association of genotypic data with pigmentation traits was analysed via logistic regression. Web-based tools for predicting the effect of genetic variants in microRNA-binding sites in 3'UTR gene regions were also used. Seven 3'UTR SNPs showed a potential implication in melanoma risk phenotypes. This association is especially noticeable for two of them, rs2325813 in the MLPH gene and rs752107 in the WNT3A gene. These two SNPs were predicted to disrupt a miRNA-binding site and to impact on miRNA-mRNA interaction. To our knowledge, this is the first time that these two 3'UTR SNPs have been associated with sun-sensitivity traits. We state the potential implication of these SNPs in human pigmentation and sensitivity to sunlight, possibly as a result of changes in the level of gene expression through the disruption of putative miRNA-binding sites.


Asunto(s)
Regiones no Traducidas 3'/genética , Proteínas Adaptadoras Transductoras de Señales/genética , Melanoma/genética , MicroARNs/metabolismo , ARN Mensajero/metabolismo , Neoplasias Cutáneas/genética , Pigmentación de la Piel/genética , Proteína Wnt3A/genética , Sitios de Unión , Estudios de Casos y Controles , Color del Ojo/genética , Frecuencia de los Genes , Predisposición Genética a la Enfermedad , Color del Cabello/genética , Humanos , Lentigo/genética , MicroARNs/genética , Fenotipo , Trastornos por Fotosensibilidad/genética , Polimorfismo de Nucleótido Simple , Factores Protectores , ARN Mensajero/genética , Factores de Riesgo , España , Población Blanca/genética
SELECCIÓN DE REFERENCIAS
DETALLE DE LA BÚSQUEDA
...