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ObjectiveTo analyze the long-term survival of subcutaneous biosimilar tumor necrosis factor inhibitors compared to the originator molecules in patients with rheumatic diseases, as well as the factors associated with drug discontinuation.MethodsRetrospective analysis of BIOBADASER, the Spanish multicenter prospective registry of patients with rheumatic disease receiving biologic and targeted disease-modifying antirheumatic drugs. Patients who started etanercept (ETN) or adalimumab (ADA) from January 2016 to October 2023 were included. The survival probabilities of biosimilars and originators were compared using Kaplan-Meier estimating curves. To identify factors associated with differences in the retention rates, hazard ratios (HR) were estimated using Cox regression models for all and specific causes (inefficacy or adverse events [AEs]) of discontinuation.ResultsA total of 4162 patients received 4723 treatment courses (2991 courses of ADA and 1732 courses of ETN), of which 722 (15.29%) were with originator molecules and 4001 (84.71%) were with biosimilars. The originators were more frequently discontinued than biosimilars (53.32% vs 33.37%, respectively). The main reason for discontinuation was inefficacy (60.35% of the treatments). The risk of overall discontinuation was lower for biosimilars (adjusted HR 0.84, 95% CI 0.75-0.95). Female sex, obesity, and second or later treatment lines increased the risk of discontinuation, whereas disease duration and the use of concomitant methotrexate were associated with a greater survival. When assessing cause-specific reasons of discontinuation, excluding nonmedical switching, the results from the crude and adjusted analyses showed no significant differences in the retention rate between biosimilars and originators.ConclusionNo significant differences were found between treatments in long-term survival due to inefficacy or AEs.

Introduction:The pure interstitial trisomy 11q11q23.2 is an uncommon genomic disorder associated with nonrecurrent intrachromosomal duplications. The phenotype is characterized by intellectual disability and craniofacial abnormalities. Given their uncommonness, a comprehensive genotype-phenotype correlation has not fully been defined. Case Presentation:We report the clinical and cytogenomic characterization of a 5-year-old boy with intellectual disability, psychomotor retardation, craniofacial dysmorphism, genital anomalies, and pure interstitial trisomy 11q arising from a nonrecurrent 11q13.1q22.3 intrachromosomal duplication in a high-mosaic state (>80%). The duplicated chromosome was characterized by cytogenetics, multicolor banding FISH, and SNP array. We demonstrated the wide mosaic distribution of the 11q duplication by interphase FISH in tissues from different embryonic germ layers. The duplication involves a copy number gain of 45.3 Mb containing 22 dosage-sensitive genes. We confirmed the overexpression of dosage-sensitive genes along the duplicated region using RT-qPCR. Discussion:Only 8 patients have been described. Our patient shares clinical features with previous reports but differs from them by the presence of genital anomalies. We provide a detailed clinical review and an accurate genotype-phenotype correlation and propose PC, NDUFV1, FGF3, FGF4, and DHCR7as dosage-sensitive genes with a possible role in the clinical spectrum of our patient; however, expression changes of FGF3/4were not detected since they must be regulated in a spatiotemporal way. This patient contributes to the accurate description of the pure interstitial trisomy 11q. Future reports could continue to delineate the description, considering the relationship between the chromosome segment and the genes involved.

Acute exacerbations of chronic obstructive pulmonary disease (AECOPD) are associated with changes in the sputum microbiome, including an increased prevalence of pathogenic bacteria. Vaccination against the most frequent bacteria identified in AECOPD might reduce exacerbation frequency. We assessed the efficacy, safety, and immunogenicity of a candidate vaccine containing surface proteins from non-typeable Haemophilus influenzae(NTHi) and Moraxella catarrhalis(Mcat) in patients with COPD.

Pyrethroid insecticides are commonly used worldwide. The chronic effects of these compounds are of concern given that epidemiological studies have suggested an association with hematological cancer, particularly in children. However, the biological evidence at molecular and cellular levels is limited. A review on the molecular and cellular effects of pyrethroids is helpful to guide the study of the biological plausibility of the association of pyrethroids with hematological cancer. We reviewed studies suggesting that pyrethroids are genotoxic, induce genetic rearrangements, alter gene expression and modify DNA. All of these biological modifications could potentially contribute to the carcinogenic process in hematopoietic cells.

Una enfermedad foliar fue detectada en la plantación comercial de Khaya senegalensiscon 3 años de edad, en la localidad de Huimanguillo (Tabasco, México). Mediante la caracterización morfológica y molecular, y por el cumplimiento de los postulados de Koch, se determinó que el agente causal corresponde al hongo Sclerotium coffeicola.Este es el primer reporte de S. coffeicolacausando mancha foliar en caoba africana en México.

La leucemia linfoblástica aguda (LLA) es el tipo de cáncer más frecuente en niños. Aunque se sabe que las alteraciones genéticas constituyen la base de la etiología de la LLA, se ha demostrado que no son suficientes para el desarrollo leucémico; son necesarias alteraciones adicionales, como las modificaciones epigenéticas. En la LLA se han identificado alteraciones de este tipo, como la metilación del DNA, la modificación de histonas y la regulación por RNAs no codificantes. La hipermetilación del DNA en regiones promotoras es una de las alteraciones epigenéticas más frecuentes en LLA: y conlleva al silenciamiento de genes que generalmente son supresores de tumor y, en consecuencia, contribuye a la leucemogénesis. También se han detectado alteraciones en proteínas remodeladoras de histonas, como la sobreexpresión de enzimas desacetilasas de histonas, así como alteraciones en enzimas acetil transferasas y metil transferasas. En la LLA también se altera la expresión de miRNAs, lo cual produce desregulación en la expresión de sus genes blanco. Estas modificaciones epigenéticas son eventos clave en la transformación maligna, e involucran la desregulación de oncogenes como BLK, WNT5By WISP1y de supresores de tumor como FHIT, CDKN2A, CDKN2B y TP73, lo que afecta diversos procesos celulares fundamentales que conllevan al desarrollo de LLA. Las alteraciones epigenéticas y genéticas contribuyen en conjunto al desarrollo y evolución de la LLA.

Los procedimientos de cirugía cardiotorácica mínimamente invasiva (MICS, su sigla en Inglés) buscan reducir las complicaciones de las grandes disecciones. No obstante, ante la falta de contacto directo con el tejido por parte del cirujano, éste recibe una sensación parcial de tacto y fuerza, lo que puede originar errores de procedimiento, inadecuada fuerza aplicada al tejido y fatiga durante el acto quirúrgico. La inclusión de dispositivos robóticos con la técnica MICSha potencializado las habilidades del cirujano para la manipulación de los tejidos, y aunque los desarrollos del mercado no cuentan aún con retroalimentación táctil, se trabaja en prototipos robóticos que incorporan realimentación de fuerza y torque.

Background Data suggest that estrogen-metabolizing genes may be involved in breast cancer carcinogenesis.Objective The aim of this study was to determine the association of CYP1A1 and COMT polymorphisms with this disease. Material and methods: A pilot case-control study was conducted with Mexican women. Ninety-one breast cancer patients and 94 healthy controls were selected. Epidemiological and clinical questionnaires were answered by all participants, and genotyping data were obtained. CYP1A1 3801 T>C (rs4646903), CYP1A1 4889 A>G (rs1048943) and COMT 1947 G>A (rs4680) polymorphisms were analyzed by PCR-RFLP.Results The results showed a high risk of breast cancer in women carrying the CYP1A1 (3801 T>C) m2/m2 genotype (OR=2.52; 95%CI=1.04–6.08). The risk was higher in postmenopausal women (OR=3.38; 95%CI=1.05–10.87). No association between COMT 1947 G>A (rs4680) or CYP1A1 4889 A>G (rs1048943) and breast cancer was found.Conclusions This study suggests that the CYP1A1 (3801 T>C) m2/m2 genotype may contribute to breast cancer susceptibility in Mexican women.

Conventional cytogenetics (CC) can be used to identify chromosomal abnormalities that are predictors of treatment outcome in acute lymphoblastic leukemia (ALL). The detection of abnormalities in ALL is difficult because low mitotic index and poor-quality metaphases are obtained. Flow cytometry (FC) and fluorescence in situ hybridization (FISH) can be used to detect aneuploidy in any phase of the cell cycle, increasing the number of analyzable cells. The aim of this study was to develop a strategy combining these methods to improve the frequency of chromosome abnormality detection. One hundred children with newly diagnosed ALL were included. CC and DNA content analysis by FC were performed in all patients. The numerical abnormalities identified by both methods were compared and patients were classified as concordant or discordant. FISH was used to support aneuploidy results in discrepant cases using centromeric probes for the chromosomes most frequently involved in aneuploidy. CC and FC showed high concordance (86). Fourteen cases were discrepant nine showed hypodiploidy and low hyperdiploidy by cytogenetics and five showed high hyperdiploidy by FC. FISH confirmed aneuploidy in 12 cases in which it could be performed. High hyperdiploidy was the most common abnormality; the 31 cases showing this aneuploidy were identified by FC. The search for abnormalities must begin by measuring DNA content to detect this aneuploidy, which is useful to evaluate the patient’s risk. However, it is important to screen for structural abnormalities by CC or molecular techniques. This strategy may detect chromosomal abnormalities, optimizing resources in laboratories where not all the screening methods are available.

We report on a Mexican boy with microcephaly, short stature, and a high frequency of chromosome aberrations with rearrangements involving chromosomes 7 and 14, typical of ataxia telangiectasia (AT) patients. He had neither ataxia nor telangiectasia, and his immunological status and serum alpha feto protein (AFP) level were normal. Bleomycin hypersensitivity, which has been demonstrated in AT patients, was tested in the patient using AT and normal subjects for comparison. The frequency of spontaneously occurring chromosome aberrations in lymphocyte cultures was significantly higher in the patient and the AT patient than in the normal subject. Four cells from the patient showed structural rearrangements involving chromosomes 7 or 14, with breakpoints typical for AT. When exposed to 5.0 μg bleomycin, the lymphocytes from the AT patient showed the highest sensitivity to this agent; our patient had an intermediate sensitivity. In both patients several rearrangements involving chromosomes 7 and 14 were scored, while none were observed in the normal subject. A colony survival assay (CSA) [Huo et al., 1994: Cancer Res 54:2544–2547], using a lympho-blastoid cell line (LCL) derived from our patient, showed a survival fraction (SF) of 7%, which is in the same range as in AT patients. The clinical picture, together with the cytogenetic and radiosensitivity results, suggests that our patient fits the variable spectrum of Nijmegen breakage syndrome. Am. J. Med. Genet. 70:24–27, 1997. © 1997 Wiley-Liss, Inc.

We report on a Mexican girl who developed cerebellar ataxia at age 3 years and pancytopenia at age 13 years. Cerebral computed tomography scan and magnetic resonance imaging showed evidence of severe cerebellar atrophy. Telangiectasias were not present; immunoglobulins and alpha-fetoprotein levels were normal. Cytogenetic studies showed no evidence of spontaneous chromosome aberrations, a normal rate of diepoxybutane (DEB) and mitomycin C (MMC)-induced chromosome aberrations, but an increased response to bleomycin. The phenotype support the diagnosis of ataxia-pancytopenia syndrome, although monosomy of chromosome 7 was not found in bone marrow. The cytogenetic studies suggest that this may be a chromosomal instability disorder. Am. J. Med. Genet. 90:252–254, 2000. © 2000 Wiley-Liss, Inc.