ABSTRACT
Introducción Los tumores renales son un desafío para los profesionales de la salud debido a su creciente prevalencia y complejidad de manejo. El estudio investiga la utilidad de los sistemas de nefrometría renal R.E.N.A.L. score y Padua en la predicción de complicaciones de la crioablación percutánea (CA). Material y métodos El estudio analiza de forma prospectiva a 90 pacientes con carcinoma de células renales (CCR) estadio T1a tratados con crioablación, totalizando 101 tumores. Resultados Se estudiaron 90 pacientes con 101 tumores renales de pequeño tamaño que recibieron terapia crioablativa. Los pacientes tenían una edad media de 68 años y mayoría eran hombres (74,4%). La mayoría de los tumores eran menores a 4 cm (89,1%) y la puntuación media del Padua y R.E.N.A.L. scores fue de 8,65 y 7,35, respectivamente. Se observaron complicaciones en 12 casos. El PADUA y R.E.N.A.L. scores demostraron un poder predictivo moderado (área bajo la curva [AUC] = 0,58 y AUC = 0,63, respectivamente) para las complicaciones poscrioablación. Conclusiones La CA es un tratamiento seguro y efectivo para los tumores renales de pequeño tamaño. Los sistemas de nefrometría renal R.E.N.A.L. y Padua scores tienen un poder predictivo moderado para las complicaciones asociadas a la CA de tumores renales. (AU)
Introduction Due to their increasing prevalence and complex management, renal tumors are challenging for health professionals. The study aims to evaluate the usefulness of R.E.N.A.L. and PADUA nephrometry scores in the prediction of complications after percutaneous cryoablation. Material and methods The study prospectively analyzed 90 patients with 101 stage T1a renal cell carcinoma (RCC) tumors treated with cryoablation. Results Ninety patients with 101 small renal tumors who received cryoablative therapy were investigated. The mean age of the patients was 68 years and 74.4% were male. Most tumors were smaller than 4 cm (89.1%) and the mean PADUA and R.E.N.A.L. scores were 8.65 and 7.35, respectively. Complications were observed in 12 cases. PADUA and R.E.N.A.L. scores demonstrated moderate predictive power (AUC = 0.58 and AUC = 0.63, respectively) for post-cryoablation complications. Conclusions Percutaneous cryoablation is a safe and effective treatment for small renal tumors. The R.E.N.A.L. and PADUA renal nephrometry scores have moderate predictive power for complications associated with percutaneous cryoablation of renal tumors. (AU)
Subject(s)
Humans , Cryosurgery , Kidney Neoplasms/diagnostic imaging , Forecasting , Postoperative Complications , Prospective Studies , Retrospective StudiesABSTRACT
INTRODUCTION: Due to their increasing prevalence and complex management, renal tumors are challenging for health professionals. The study aims to evaluate the usefulness of R.E.N.A.L. and PADUA nephrometry scores in the prediction of complications after percutaneous cryoablation. MATERIAL AND METHODS: The study prospectively analyzed 90 patients with 101 stage T1a renal cell carcinoma (RCC) tumors treated with cryoablation. RESULTS: Ninety patients with 101 small renal tumors who received cryoablative therapy were investigated. The mean age of the patients was 68 years and 74.4% were male. Most tumors were smaller than 4â¯cm (89.1%) and the mean PADUA and R.E.N.A.L. scores were 8.65 and 7.35, respectively. Complications were observed in 12 cases. PADUA and R.E.N.A.L. scores demonstrated moderate predictive power (AUCâ¯=â¯0.58 and AUCâ¯=â¯0.63, respectively) for post-cryoablation complications. CONCLUSIONS: Percutaneous cryoablation is a safe and effective treatment for small renal tumors. The R.E.N.A.L. and PADUA renal nephrometry scores have moderate predictive power for complications associated with percutaneous cryoablation of renal tumors.
Subject(s)
Carcinoma, Renal Cell , Kidney Neoplasms , Humans , Male , Aged , Female , Nephrectomy/adverse effects , Retrospective Studies , Kidney Neoplasms/pathology , Kidney/pathology , Carcinoma, Renal Cell/pathologyABSTRACT
Introducción: La distrofia muscular de Duchenne (DMD) es una enfermedad neuromuscular grave que afecta a uno de cada 3.500 varones nacidos y sigue un patrón de herencia ligada al cromosoma X. En esta enfermedad se observa una ausencia total de la distrofina, generalmente debida a mutaciones en el gen DMD, que altera la pauta de lectura y en torno al 80% de los casos son debidos a deleciones y duplicaciones de uno o más exones. Métodos: Se han revisado 284 casos de varones diagnosticados genéticamente de DMD entre los años 2007 y 2014. Estos pacientes provienen de 8 hospitales españoles de referencia que cubren la mayor parte del territorio español. Para la identificación de las mutaciones se realizaron las técnicas de reacción en cadena de la polimerasa multiplex, MLPA y secuenciación. Resultados: Los pacientes con DMD presentan en su mayoría grandes deleciones (46,1%) o grandes duplicaciones (19,7%) en el gen de la distrofina. El restante 34,2% corresponde al conjunto de mutaciones puntuales, destacando las sustituciones nucleotídicas tipo nonsense que aparecen en la mitad de los casos. Este estudio permitió identificar 23 nuevas mutaciones en DMD: 7 grandes deleciones y 16 mutaciones puntuales. Conclusiones: El algoritmo de diagnóstico genético aplicado por los centros participantes es el más adecuado para genotipificar a los pacientes con DMD. La especificidad genética de las distintas terapias en desarrollo pone de manifiesto la importancia de conocer la mutación de cada paciente, siendo un 38,7% de ellos susceptibles de participar en los ensayos clínicos actuales (AU)
Introduction: Duchenne muscular dystrophy (DMD) is a severe X-linked recessive neuromuscular disease that affects one in 3500 live-born males. The total absence of dystrophin observed in DMD patients is generally caused by mutations that disrupt the reading frame of the DMD gene, and about 80% of cases harbour deletions or duplications of one or more exons. Methods: We reviewed 284 cases of males with a genetic diagnosis of DMD between 2007 and 2014. These patients were selected from 8 Spanish reference hospitals representing most areas of Spain. Multiplex PCR, MLPA, and sequencing were performed to identify mutations. Results: Most of these DMD patients present large deletions (46.1%) or large duplications (19.7%) in the dystrophin gene. The remaining 34.2% correspond to point mutations, and half of these correspond to nonsense mutations. In this study we identified 23 new mutations in DMD: 7 large deletions and 16 point mutations. Conclusions: The algorithm for genetic diagnosis applied by the participating centres is the most appropriate for genotyping patients with DMD. The genetic specificity of different therapies currently being developed emphasises the importance of identifying the mutation appearing in each patient; 38.7% of the cases in this series are eligible to participate in current clinical trials (AU)
Subject(s)
Humans , Muscular Dystrophy, Duchenne/genetics , DNA Mutational Analysis/methods , Nucleic Acid Amplification Techniques/methods , Sequence Analysis, DNA/methods , Genetic Techniques , Dystrophin/geneticsABSTRACT
INTRODUCTION: Duchenne muscular dystrophy (DMD) is a severe X-linked recessive neuromuscular disease that affects one in 3500 live-born males. The total absence of dystrophin observed in DMD patients is generally caused by mutations that disrupt the reading frame of the DMD gene, and about 80% of cases harbour deletions or duplications of one or more exons. METHODS: We reviewed 284 cases of males with a genetic diagnosis of DMD between 2007 and 2014. These patients were selected from 8 Spanish reference hospitals representing most areas of Spain. Multiplex PCR, MLPA, and sequencing were performed to identify mutations. RESULTS: Most of these DMD patients present large deletions (46.1%) or large duplications (19.7%) in the dystrophin gene. The remaining 34.2% correspond to point mutations, and half of these correspond to nonsense mutations. In this study we identified 23 new mutations in DMD: 7 large deletions and 16 point mutations. CONCLUSIONS: The algorithm for genetic diagnosis applied by the participating centres is the most appropriate for genotyping patients with DMD. The genetic specificity of different therapies currently being developed emphasises the importance of identifying the mutation appearing in each patient; 38.7% of the cases in this series are eligible to participate in current clinical trials.
Subject(s)
Muscular Dystrophy, Duchenne/genetics , Adult , DNA Mutational Analysis , Dystrophin/genetics , Gene Deletion , Genotype , Humans , Male , Muscular Dystrophy, Duchenne/epidemiology , Spain/epidemiologyABSTRACT
En este capítulo describimos brevemente la práctica diaria en las Unidades de Desarrollo Infantil, Neuropediatría, Genética clínica, y Dismorfología. Enumeramos las situaciones de riesgo y patologías más frecuentemente atendidas, y hacemos especial hincapié en la creación de equipos multidisciplinares. Estos equipos son imprescindibles para el diagnóstico preconcepcional y prenatal. Un aspecto clave de nuestra actividad es la detección precoz y prevención de las discapacidades en la infancia. Se requiere para ello una atención coordinada entre los servicios y recursos para una intervención temprana, lo que ofrecemos a través de un proceso de atención integrada centrado en las necesidades de los niños y sus familias. Este proceso incluye en este momento también niños y niñas y sus familias con enfermedades poco frecuentes (AU)
In this chapter we describe briefly the daily practice in Units of Child Development, Pediatric Neurology, Clinical Genetics and Dysmorphology. We list the situations of risk and pathologies most often served, and we make special emphasis on the creation of multidisciplinary teams. These teams are essential for preconception and prenatal diagnosis. A key aspect of our activity is the early detection and prevention of disabilities in children. Resources and services coordination tasks are required for early intervention, what we offer through a process of integrated care centered on the needs of children and their families. This process also includes children and their families with rare diseases at this time (AU)
Subject(s)
Humans , Male , Female , Child , Neurology/organization & administration , Child Development , Genetics, Medical/organization & administration , Body Dysmorphic Disorders , Rare Diseases , Hospitals, University/organization & administration , Comprehensive Health Care/organization & administration , Delivery of Health Care, Integrated/organization & administrationABSTRACT
Mutations in the SPG7 gene were initially reported in patients with autosomal recessive hereditary spastic paraplegia (HSP). Recent works suggested a dominant effect for some SPG7 mutations. To characterize the SPG7 mutational spectrum in a large cohort of Spanish HSP patients, we sequenced the whole SPG7 gene in a total of 285 Spastic Paraplegia patients. Large gene rearrangements were also ascertained in some patients. We found a total of 14 SPG7 mutations (12 new) in 14 patients; 2 were large deletions. All the mutation carriers had an adult onset age but only five (35%) had a complicated phenotype. We identified a single mutation in 13 patients. Familial analysis suggested a dominant inheritance for one (p.Leu78*) of these mutations. Carriers of the rare p.A510V variant were significantly more frequent in patients vs healthy controls (3% vs 1%), suggesting a pathogenic role for this SPG7 variant. We reported a high frequency of patients with only one SPG7 mutation, and a putative pathogenic role for the p.A510V variant.
Subject(s)
Amino Acid Substitution , Metalloendopeptidases/genetics , Mutation , Spastic Paraplegia, Hereditary/genetics , ATPases Associated with Diverse Cellular Activities , Adolescent , Adult , Aged , Aged, 80 and over , Child , Child, Preschool , Cohort Studies , DNA Mutational Analysis , Gene Frequency , Genes, Dominant , Genetic Predisposition to Disease , Genetic Testing , Genotype , Humans , Infant , Middle Aged , Phenotype , Spain , Spastic Paraplegia, Hereditary/diagnosis , Young AdultABSTRACT
Multiple sclerosis (MS) is a chronic inflammatory disease of the central nervous system with presumed autoimmune origin, triggered by genetic and environmental risk factors. A recent genome-wide association study conducted on MS identified new biallelic markers outside the HLA (human leucocyte antigen) region involved in disease susceptibility: rs1109670 (DDEF2); rs1458175 (PDZRN4); rs1529316 and rs2049306 (CSMD1); rs16914086 (TBC1D2); rs1755289 (SH3GL2); rs1841770 (ZIC1); rs651477 (EN1); rs7607490 (TRIB2); rs397020 (C20orf46); rs908821 (SLC25A36); rs7672826 (MGC45800) and rs9523762 (GPC5). We aimed at replicating these top association signals in a Spanish cohort of 2863 MS patients and 2930 sex- and age-matched controls. Only rs9523762 mapping in the GPC5 gene was significantly associated (G allele, P=1.6 × 10(-5); odds ratio (95% confidence interval)=1.23 (1.12-1.36)), supporting a role for this proteoglycan in MS predisposition. The independent replication of association signals to validate data generated by genome-wide association scans is a first step in the effort to improve patient care.
Subject(s)
Genome-Wide Association Study , Multiple Sclerosis/genetics , Adult , Alleles , Case-Control Studies , Cohort Studies , DNA Replication/genetics , Female , Gene Frequency/genetics , Genetic Markers/genetics , Genetic Predisposition to Disease , HLA Antigens/genetics , Humans , Male , Multiple Sclerosis/immunology , SpainABSTRACT
In recent reports, IRF5 polymorphisms showed significant association with multiple sclerosis (MS) susceptibility in three studied populations and Irf5-deficient mice exhibited an increased susceptibility to viral infection, linked to a significant decrease in the induction of serum type I interferon (IFN). In the present study, we evaluated the association of two IRF5 polymorphisms with MS predisposition and we also addressed whether these polymorphisms were associated with active replication of human herpes virus-6 (HHV-6) observed in a subgroup of MS patients, and/or with response to IFN-ß therapy. A total of 1494 MS patients and 1506 ethnically matched controls were genotyped for rs4728142 and rs3807306 with TaqMan pre-designed assays. One hundred and six patients were classified as responders to IFN-ß therapy (no relapses/increases in EDSS over the 2-year follow-up) and 112 as non-responders (at least two relapses or an increase in expanded disability status scale (EDSS) of at least one point during the same period). The combined analysis of available datasets yielded an effect size on MS with odds ratio (OR)(Mantel-Haenszel)=1.14 (P<0.002) for the IRF5 polymorphisms rs4728142 and rs3807306. Additionally, trends for association were observed between rs3807306T and infection with HHV-6 [p=0.05, OR (95% CI)=1.56 (1.00-2.44)] and response to IFN-ß therapy [P=0.09, OR (95% CI)=1.39 (0.95-2.05)].
Subject(s)
Interferon Regulatory Factors/genetics , Interferon-beta/therapeutic use , Multiple Sclerosis/genetics , Roseolovirus Infections/drug therapy , Case-Control Studies , Herpesvirus 6, Human/physiology , HumansABSTRACT
Genome-wide association studies (GWAS) have revealed that different diseases share susceptibility variants. Twelve single-nucleotide polymorphisms (SNPs) previously associated with different immune-mediated diseases in GWAS were genotyped in a Caucasian Spanish population of 2864 multiple sclerosis (MS) patients and 2930 controls. Three SNPs were found to be associated with MS: rs1678542 in KIF5A (P=0.001, odds ratio (OR)=1.13, 95% confidence interval (CI)=1.05-1.23); rs3184504 in SH2B3 (P=0.00001, OR=1.19, 95% CI=1.10-1.27) and rs763361 in CD226 (P=0.00007, OR=1.16, 95%CI=1.08-1.25). These variants have previously been associated with rheumatoid arthritis and type 1 diabetes. The SH2B3 polymorphism has additionally been associated with systemic lupus erythematosus. Our results, in addition to validating some of these loci as risk factors for MS, are consistent with shared genetic mechanisms underlying different immune-mediated diseases. These data may help to shape the contribution of each pathway to different disorders.
Subject(s)
Antigens, Differentiation, T-Lymphocyte/genetics , Genetic Predisposition to Disease/genetics , Kinesins/genetics , Multiple Sclerosis/genetics , Proteins/genetics , Adaptor Proteins, Signal Transducing , Autoimmune Diseases/genetics , Case-Control Studies , Genome-Wide Association Study , Humans , Intracellular Signaling Peptides and Proteins , Polymorphism, Single Nucleotide/genetics , Spain , White People/geneticsABSTRACT
Hereditary susceptibility to pheochromocytoma (PCC) and paraganglioma (PGL) represents a very complex genetic scenario. It has been reported that the absence of familial antecedents of the disease does not preclude the existence of a mutation affecting any of the five major susceptibility genes. In fact, 11-24% of apparently sporadic cases (without familial or syndromic antecedents) harbor an unexpected germline mutation, but we do not know what is happening in "truly apparently" sporadic patients (i.e., apparently sporadic cases diagnosed with only one tumor). In the present study, we have analyzed 135 apparently sporadic patients developing a single tumor for the five major susceptibility genes: VHL, RET, SDHB, SDHC, and SDHD. Fourteen percent of cases were found to harbor a germline mutation, and only 2.2% of patients were older than 45 years at onset. By taking into account the tumor location and a threshold age at onset of 45 years, we propose a rational scheme for genetic testing. Analyzing VHL and RET genes would be recommended only in young patients developing a single PCC. On the other hand, genetic testing of SDHD should be done in all patients developing an extra-adrenal tumor before the age of 45, and SDHC could be the responsible gene in cases developing a single head and neck tumor, independently of age. Finally, the analysis of SDHB should always be performed because of its association to malignancy and the low penetrance of mutations affecting this gene.
Subject(s)
Adrenal Gland Neoplasms/genetics , Genetic Testing , Paraganglioma/genetics , Pheochromocytoma/genetics , Adolescent , Adrenal Gland Neoplasms/diagnosis , Adult , Aged , Female , Germ-Line Mutation , Humans , Male , Middle Aged , Paraganglioma/diagnosis , Pheochromocytoma/diagnosis , Proto-Oncogene Proteins c-ret/genetics , Succinate Dehydrogenase/genetics , Von Hippel-Lindau Tumor Suppressor Protein/genetics , Young AdultSubject(s)
Adenoma, Liver Cell/pathology , Liver Neoplasms/pathology , Child , Female , Humans , Magnetic Resonance ImagingABSTRACT
We present the case of a patient with tuberous sclerosis and multiple bilateral renal angiomyolipomas (AML) who developed an intralesional pseudoaneurysm in the context of bleeding from an AML. The diagnosis was reached by ultrasonography and computed tomography, and the histological diagnosis of a contained hematoma confirmed the bleeding.
Subject(s)
Aneurysm, False/diagnostic imaging , Angiomyolipoma/diagnostic imaging , Hemorrhage/diagnostic imaging , Kidney Neoplasms/diagnostic imaging , Tuberous Sclerosis/complications , Aneurysm, False/complications , Angiomyolipoma/complications , Female , Hemorrhage/etiology , Humans , Kidney Neoplasms/complications , Middle Aged , Radiography , UltrasonographyABSTRACT
Presentamos el caso de una paciente afecta de esclerosis tuberosa con múltiples angiomiolipomas (AML) renales bilaterales, que en el contexto del sangrado de uno de ellos desarrolla un pseudoaneurisma intralesional, cuyo diagnóstico se realiza mediante ecografía y tomografía computarizada (TC), existiendo confirmación histológica del mismo como hematoma contenido, que traduce sangrado (AU)
We present the case of a patient with tuberous sclerosis and multiple bilateral renal angiomyolipomas (AML) who developed an intralesional pseudoaneurysm in the context of bleeding from an AML. The diagnosis was reached by ultrasonography and computed tomography, and the histological diagnosis of a contained hematoma confirmed the bleeding (AU)
Subject(s)
Humans , Female , Middle Aged , Aneurysm, False/diagnosis , Angiomyolipoma/pathology , Kidney Neoplasms/pathology , Tuberous Sclerosis/pathology , Tomography, X-Ray Computed , UltrasonographySubject(s)
Ethics, Professional , Periodicals as Topic/ethics , Professional Misconduct/ethics , Publishing/ethics , Alcoholic Intoxication/drug therapy , Animals , Chemical and Drug Induced Liver Injury , Liver Diseases/drug therapy , Mice , Parenteral Nutrition, Total/adverse effects , Periodicals as Topic/standards , Publishing/standards , Research Support as Topic , Resveratrol , Stilbenes/therapeutic useABSTRACT
No disponible
Subject(s)
Humans , Periodicals as Topic/ethics , Biomedical Research , Editorial Policies , Peer Review/ethicsABSTRACT
Liver sinusoids, in contrast with the capillaries of other tissues, contain large numbers of sequestered lymphocytes. These blood-borne cells preferentially home in the liver. The mechanism regulating the recruitment of these cells and molecular regulation of the recognition of endothelial cells is as yet unclear. The present study sought to evaluate the cell adhesion molecules on human liver-associated lymphocytes and their ligands on sinusoidal lining cells in 29 patients undergoing partial hepatectomy for liver tumors. Liver-associated lymphocytes and peripheral blood lymphocytes were analyzed by flow cytometry using monoclonal antibodies. Frozen sections of liver tissue were stained according to alkaline phosphatase anti-alkaline phosphatase method. Cytometric analysis showed that virtually all liver-associated lymphocytes expressed on their surface the cell adhesion molecules LFA-1 and VLA-4. This liver-associated lymphocyte population also presented a significantly higher percentage of Mac 1, ICAM-1, and LFA-3 and an increased surface expression of LFA-1, LFA-2, and NCAM in comparison with peripheral blood lymphocytes. It was likewise shown that sinusoidal cells express ICAM-1, ICAM-2, ICAM-3, VCAM-1 and LFA-3 ligands. Liver-associated lymphocytes thus strongly express a number of different adhesion molecules. The corresponding ligands were also detected on sinusoidal lining cells. LFA-1 and VLA-4 would seem to be important pathways of temporary lymphocyte-endothelial adhesion in liver sinusoids.
