Complex Variant t(9;22) Chromosome Translocations in Five Cases of Chronic Myeloid Leukemia

The Philadelphia (Ph1) chromosome arising from the reciprocal t(9;22) translocation is found in more than 90% of chronic myeloid leukemia (CML) patients and results in the formation of the chimeric fusion gene BCR-ABL. However, a small proportion of patients with CML have simple or complex variants of this translocation, involving various breakpoints in addition to 9q34 and 22q11. We report five CML cases carrying variant Ph translocations involving both chromosomes 9 and 22 as well as chromosomes 3, 5, 7, 8, or 10. G-banding showed a reciprocal three-way translocation involving 3q21, 5q31, 7q32, 8q24, and 10q22 bands. BCR-ABL fusion signal on der(22) was found in all of the cases by FISH

Treatment with tocilizumab or corticosteroids for COVID-19 patients with hyperinflammatory state: a multicentre cohort study (SAM-COVID-19)

Objectives: The objective of this study was to estimate the association between tocilizumab or corticosteroids and the risk of intubation or death in patients with coronavirus disease 19 (COVID-19) with a hyperinflammatory state according to clinical and laboratory parameters. Methods: A cohort study was performed in 60 Spanish hospitals including 778 patients with COVID-19 and clinical and laboratory data indicative of a hyperinflammatory state. Treatment was mainly with tocilizumab, an intermediate-high dose of corticosteroids (IHDC), a pulse dose of corticosteroids (PDC), combination therapy, or no treatment. Primary outcome was intubation or death; follow-up was 21 days. Propensity score-adjusted estimations using Cox regression (logistic regression if needed) were calculated. Propensity scores were used as confounders, matching variables and for the inverse probability of treatment weights (IPTWs). Results: In all, 88, 117, 78 and 151 patients treated with tocilizumab, IHDC, PDC, and combination therapy, respectively, were compared with 344 untreated patients. The primary endpoint occurred in 10 (11.4%), 27 (23.1%), 12 (15.4%), 40 (25.6%) and 69 (21.1%), respectively. The IPTW-based hazard ratios (odds ratio for combination therapy) for the primary endpoint were 0.32 (95%CI 0.22-0.47; p < 0.001) for tocilizumab, 0.82 (0.71-1.30; p 0.82) for IHDC, 0.61 (0.43-0.86; p 0.006) for PDC, and 1.17 (0.86-1.58; p 0.30) for combination therapy. Other applications of the propensity score provided similar results, but were not significant for PDC. Tocilizumab was also associated with lower hazard of death alone in IPTW analysis (0.07; 0.02-0.17; p < 0.001). Conclusions: Tocilizumab might be useful in COVID-19 patients with a hyperinflammatory state and should be prioritized for randomized trials in this situatio

Selection of Reference Genes for Quantitative Real Time PCR (qPCR) Assays in Tissue from Human Ascending Aorta.

Journal Article;Dilatation of the ascending aorta (AAD) is a prevalent aortopathy that occurs frequently associated with bicuspid aortic valve (BAV), the most common human congenital cardiac malformation. The molecular mechanisms leading to AAD associated with BAV are still poorly understood. The search for differentially expressed genes in diseased tissue by quantitative real-time PCR (qPCR) is an invaluable tool to fill this gap. However, studies dedicated to identify reference genes necessary for normalization of mRNA expression in aortic tissue are scarce. In this report, we evaluate the qPCR expression of six candidate reference genes in tissue from the ascending aorta of 52 patients with a variety of clinical and demographic characteristics, normal and dilated aortas, and different morphologies of the aortic valve (normal aorta and normal valve n = 30; dilated aorta and normal valve n = 10; normal aorta and BAV n = 4; dilated aorta and BAV n = 8). The expression stability of the candidate reference genes was determined with three statistical algorithms, GeNorm, NormFinder and Bestkeeper. The expression analyses showed that the most stable genes for the three algorithms employed were CDKN1β, POLR2A and CASC3, independently of the structure of the aorta and the valve morphology. In conclusion, we propose the use of these three genes as reference genes for mRNA expression analysis in human ascending aorta. However, we suggest searching for specific reference genes when conducting qPCR experiments with new cohort of samples.This work was supported in part by grants PI-0689/2010 (Consejería de Salud, Junta de Andalucía, Spain), P10-CTS-06068 (Consejería de Innovación, Ciencia y Empresa, Junta de Andalucía, Spain), and Red de Investigación Cardiovascular (RIC) from Redes Temáticas de Investigación Cooperativa (RETIC)Ye

Clinical Study Complex Variant t(9;22) Chromosome Translocations in Five Cases of Chronic Myeloid Leukemia

The Philadelphia (Ph 1 ) chromosome arising from the reciprocal t(9;22) translocation is found in more than 90% of chronic myeloid leukemia (CML) patients and results in the formation of the chimeric fusion gene BCR-ABL. However, a small proportion of patients with CML have simple or complex variants of this translocation, involving various breakpoints in addition to 9q34 and 22q11. We report five CML cases carrying variant Ph translocations involving both chromosomes 9 and 22 as well as chromosomes 3, 5, 7, 8, or 10. G-banding showed a reciprocal three-way translocation involving 3q21, 5q31, 7q32, 8q24, and 10q22 bands. BCR-ABL fusion signal on der(22) was found in all of the cases by FISH

Rara complicación con un catéter de Swan-Ganz

Presentamos el caso de una paciente de 44 años, con insuficiencia mitral severa por prolapso de P2. Realizamos una reparación mitral mediante resección cuadrangular y anuloplastia con anillo, a través de auriculotomía izquierda en surco. La paciente se extuba a las 6 h, presentando buena hemodinámica sin aminas. Se realiza ecocardiograma a las 24 h confirmando el buen resultado de la cirugía. Se intenta retirar el catéter de Swan-Ganz sin éxito, por lo que se decide reintervención. En el quirófano se intenta retirar el catéter de manera directa comprobándose que se encuentra firmemente fijado. Se decide entrar en bypass y sin isquemia se realiza una auriculotomía derecha comprobando que se encuentra incluido en la sutura de cierre de la auriculotomía izquierda. Cortamos el catéter a nivel de la sutura y, con la ayuda de un gancho de nervio, se consigue movilizar y retirar el mismo. No fue necesario rehacer la sutura de la auriculotomía, por lo que se consiguió evitar el pinzamiento aórtico. La paciente se volvió a extubar a las 4 h, siguiendo un curso postoperatorio satisfactorio y siendo dada de alta a los 5 días

Fibrillin 2 is upregulated in the ascending aorta of patients with bicuspid aortic valve.

Bicuspid aortic valve (BAV) is the most prevalent congenital cardiac malformation, frequently associated with aortic dilatation (AD). The molecular mechanisms involved in AD and its aetiological link with BAV formation are poorly understood. Altered fibrillin-1 (FBN1) and metalloprotease-2, -9 (MMP2,9) protein activities have been suggested to be involved in BAV aortopathy. In addition, FBN2 participates in embryonic valve formation, but its possible involvement in BAV-associated AD has never been explored. In this report, we evaluate the expression levels of MMP2,9 and FBN1,2 in the ascending aorta of patients with normal or dilated aortas and with tricuspid aortic valve (TAV) or BAV, using appropriate tissue-specific reference genes. Gene expression was quantified by real-time quantitative polymerase chain reaction in 52 patients, using one or three reference genes previously validated in the same patient population. FBN2 expression was significantly increased in the aortas of patients with BAV compared with individuals with TAV (0.178 ± 0.042 vs 0.096 ± 0.021, P = 0.015), whereas differences in FBN1 did not reach statistical significance (1.946 ± 0.228 vs 1.430 ± 0.114, P = 0.090). When four groups of samples were considered, FBN2 expression was significantly higher in patients with BAV and AD compared with patients with TAV and AD (0.164 ± 0.035 vs 0.074 ± 0.027, P = 0.040). No significant differences were found when FBN1/FBN2 ratio, and MMP2 and MMP9 expression levels were analysed. No linear relationship between aortic diameter and gene expression levels were found. BAV patients have an increased FBN (especially FBN2) gene expression level in the ascending aorta, irrespective of dilatation, whereas MMP expression does not change significantly. These results add a new piece of information to the pathophysiology of BAV disease and point to FBN2 as a new molecular player

Amplicon length (A), correlation coefficient (R²), and amplification efficiencies (E%) of reference genes.

<p>Amplicon length (A), correlation coefficient (R²), and amplification efficiencies (E%) of reference genes.</p

Stability values of reference genes and their variation obtained by NormFinder.

<p>A) Stability values considering all the samples in one group. B) Stability values considering the four groups of samples. C) Variation of the stability values in the four groups of samples. In C, the columns represent the inter-group variation and the error bars represent the intra-group variation of the stability value of each reference gene.</p