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991.
The presence of genomic imbalances is associated with poor outcome in patients with burkitt lymphoma treated with dose‐intensive chemotherapy including rituximab
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Maribel Forero‐Castro Cristina Robledo Eva Lumbreras Rocio Benito Jesús M. Hernández‐Sánchez María Hernández‐Sánchez Juan L. García Luis A. Corchete‐Sánchez Mar Tormo Pere Barba Javier Menárguez Jordi Ribera Carlos Grande Lourdes Escoda Carmen Olivier Estrella Carrillo Alfonso García de Coca Josep‐María Ribera Jesús M. Hernández‐Rivas 《British journal of haematology》2016,172(3):428-438
The introduction of Rituximab has improved the outcome and survival rates of Burkitt lymphoma (BL). However, early relapse and refractoriness are current limitations of BL treatment and new biological factors affecting the outcome of these patients have not been explored. This study aimed to identify the presence of genomic changes that could predict the response to new therapies in BL. Forty adolescent and adult BL patients treated with the Dose‐Intensive Chemotherapy Including Rituximab (Burkimab) protocol (Spanish Programme for the Study and Treatment of Haematological Malignancies; PETHEMA) were analysed using array‐based comparative genomic hybridization (CGH). In addition, the presence of TP53, TCF3 (E2A), ID3 and GNA13 mutations was assessed by next‐generation sequencing (NGS). Ninety‐seven per cent of the patients harboured genomic imbalances. Losses on 11q, 13q, 15q or 17p were associated with a poor response to Burkimab therapy (P = 0·038), shorter progression‐free survival (PFS; P = 0·007) and overall survival (OS; P = 0·009). The integrative analysis of array‐CGH and NGS showed that 26·3% (5/19) and 36·8% (7/19) of patients carried alterations in the TP53 and TCF3 genes, respectively. TP53 alterations were associated with shorter PFS (P = 0·011) while TCF3 alterations were associated with shorter OS (P = 0·032). Genetic studies could be used for risk stratification of BL patients treated with the Burkimab protocol. 相似文献
992.
José Hernández-Rodríguez Giuseppe Murgia Irama Villar Elías Campo Sarah L. Mackie Aruna Chakrabarty Elizabeth M.A. Hensor Ann W. Morgan Carme Font Sergio Prieto-González Georgina Espígol-Frigolé Josep M. Grau Maria C. Cid 《Medicine》2016,95(8)
The extent of inflammatory infiltrates in arteries from patients with giant-cell arteritis (GCA) have been described using different terms and definitions. Studies investigating the relationship between GCA histological features and clinical manifestations have produced controversial results. The aims of this study were to characterize and validate histological patterns in temporal artery biopsies (TABs) from GCA patients, to explore additional histological features, including the coexistence of different patterns, and also to investigate the relationship of the inflammatory patterns with clinical and laboratory features.We performed histological examination of TAB from patients with GCA consecutively diagnosed between 1992 and 2012. Patterns of inflammation were defined according to the extent and distribution of inflammatory infiltrates within the artery. Clinical and laboratory variables were recorded. Two external investigators underwent a focused, one-day training session and then independently scored 77 cases. Quadratic-weighted kappa was calculated.TAB from 285 patients (200 female/85 male) were evaluated. Four histological inflammatory patterns were distinguished: 1 – adventitial (n = 16); 2 – adventitial invasive: adventitial involvement with some extension to the muscular layer (n = 21); 3 – concentric bilayer: adventitial and intimal involvement with media layer preservation (n = 52); and 4 – panarteritic (n = 196). Skip lesions were observed in 10% and coexistence of various patterns in 43%. Raw agreement of each external scorer with the gold-standard was 82% and 77% (55% and 46% agreement expected from chance); kappa = 0.82 (95% confidence interval [CI] 0.70–0.95) and 0.79 (95% CI 0.68–0.91). Although abnormalities on temporal artery palpation and the presence of jaw claudication and scalp tenderness tended to occur more frequently in patients with arteries depicting more extensive inflammation, no statistically significant correlations were found between histological patterns and clinical features or laboratory findings.In conclusion, we have described and validated 4 histological patterns. The presence of different coexisting patterns likely reflects sequential steps in the progression of inflammation and injury. No clear relationship was found between these patterns and clinical or laboratory findings. However, several cranial manifestations tended to occur more often in patients with temporal arteries exhibiting panarteritic inflammation. This validated score system may be useful to standardize stratification of histological severity for immunopathology biomarker studies or correlation with imaging. 相似文献
993.
Barbara Kronsteiner Josep Bassaganya-Riera Casandra Philipson Monica Viladomiu Adria Carbo Vida Abedi 《Gut microbes》2016,7(1):3-21
Helicobacter pylori is the dominant member of the gastric microbiota in over half of the human population of which 5–15% develop gastritis or gastric malignancies. Immune responses to H. pylori are characterized by mixed T helper cell, cytotoxic T cell and NK cell responses. The presence of Tregs is essential for the control of gastritis and together with regulatory CX3CR1+ mononuclear phagocytes and immune-evasion strategies they enable life-long persistence of H. pylori. This H. pylori-induced regulatory environment might contribute to its cross-protective effect in inflammatory bowel disease and obesity. Here we review host-microbe interactions, the development of pro- and anti-inflammatory immune responses and how the latter contribute to H. pylori's role as beneficial member of the gut microbiota. Furthermore, we present the integration of existing and new data into a computational/mathematical model and its use for the investigation of immunological mechanisms underlying initiation, progression and outcomes of H. pylori infection. 相似文献
994.
Qian Chen Irene Belmonte Maria Buti Leonardo Nieto Damir Garcia-Cehic Josep Gregori Celia Perales Laura Ordeig Meritxell Llorens Maria Eugenia Soria Rafael Esteban Juan Ignacio Esteban Francisco Rodriguez-Frias Josep Quer 《World journal of gastroenterology : WJG》2016,22(43):9604-9612
AIM To develop a fast, low-cost diagnostic strategy to identify single point mutations in highly variable genomes such as hepatitis C virus(HCV).METHODS In patients with HCV infection, resistance-associated amino acid substitutions within the viral quasispecies prior to therapy can confer decreased susceptibility to direct-acting antiviral agents and lead to treatment failure and virological relapse. One such naturally occurring mutation is the Q80 K substitution in the HCV-NS3 protease gene, which confers resistance to PI inhibitors, particularly simeprevir. Low-cost, highly sensitive techniques enabling routine detection of these single point mutations would be useful to identify patients at a risk of treatment failure. Light Cycler methods, based on real-time PCR with sequencespecific probe hybridization, have been implemented in most diagnostic laboratories. However, this technique cannot identify single point mutations in highly variable genetic environments, such as the HCV genome. To circumvent this problem, we developed a new method to homogenize all nucleotides present in a region except the point mutation of interest. RESULTS Using nucleotide-specific probes Q, K, and R substitutions at position 80 were clearly identified at a sensitivity of 10%(mutations present at a frequency of at least 10% were detected). The technique was successfully applied to identify the Q80 K substitution in 240 HCV G1 serum samples, with performance comparable to that of direct Sanger sequencing, the current standard procedure for this purpose. The new method was then validated in a Catalonian population of 202 HCV G1-infected individuals. Q80 K was detected in 14.6% of G1 a patients and 0% of G1 b in our setting. CONCLUSION A fast, low-cost diagnostic strategy based on real-time PCR and fluorescence resonance energy transfer probe melting curve analysis has been successfully developed to identify single point mutations in highly variable genomes such as hepatitis C virus. This technique can be adapted to detect any single point mutation in highly variable genomes. 相似文献
995.
Sabaté JM Gómez A Torrubia S Blancas C Sánchez G Alonso MC Lerma E 《European radiology》2006,16(3):702-706
We describe the clinical, radiological, and pathological findings of the diverse benign and malignant breast neoplasms found
in association with Cowden syndrome. Patients with Cowden syndrome had a substantially increased risk of breast carcinoma.
We find that 33% of the patients in our study population with Cowden disease have developed breast carcinoma to date. An association
between Cowden disease and multiple tubular adenomas or breast hamartomas was found in two patients, suggesting a genetic
origin. PTEN germ-line mutations were found in all four patients presenting with relevant benign or malignant breast pathology.
We also assess the value of specific diagnostic tools used in the surveillance management. Screening mammography was useful
in the diagnosis of small, high-grade carcinomas. 相似文献
996.
Fraile M Gubern JM Rull M Julián FJ Serra C Llatjós M Culell P Puig P Solà M Vallejos V Mariscal A Janer J Deulofeu P Fusté F 《Nuclear medicine communications》2006,27(10):785-789
BACKGROUND: The indication for sentinel node biopsy (SNB) has not been fully established yet for patients with ductal carcinoma in situ (DCIS). AIM: To relate the conversion rate to invasive carcinoma with sentinel node positivity in high risk DCIS, and to refine the clinical presentation analysis in order to better select patients for SNB. For this purpose, a risk score was devised. METHODS: From 1998 to 2005, 151 high-risk DCIS patients from six clinical centres were included in a prospective sentinel node database. The conversion rate to invasive carcinoma was 39%. Ten of 142 (7%) successful SNBs showed a positive sentinel node (eight micrometastatic). The sentinel node was positive in 1% of pure DCIS, in 5.5% of DCIS with micro-invasion, and in 19.5% of invasive carcinoma. RESULTS: Both clinical presentation and corresponding risk score were closely related to conversion to invasive carcinoma. The association of risk score and sentinel node positivity approached but did not reach statistical significance (P=0.06); therefore a subset of further selected higher risk patients could not be defined. CONCLUSION: The relevance of SNB positivity cannot be overlooked in high-risk DCIS patients, however, because SNB is not free from morbidity and cost, more studies are needed to refine its final indication. 相似文献
997.
Prematurity is associated with reduced brain volume, and the thalamus is among the structures most affected. We used a voxel-based morphometry analysis of gray matter to map regional atrophy in the thalamus in a sample of 30 adolescents with antecedents of very preterm birth. The preterm sample was compared with 30 controls matched by age, sex, handedness and sociocultural status. Individuals with very preterm birth differed from controls in several thalamic nuclei, and semantic and phonetic fluency showed different correlation patterns with brain volume. Semantic fluency achieved significant correlations with more thalamic nuclei than phonetic fluency. These results agree with functional magnetic resonance imaging studies showing that semantic fluency involves more cerebral regions than phonetic fluency. 相似文献
998.
A mismatch negativity event-related potential protocol was administered to dyslexic children and their respective controls to test whether a specific auditory deficit concerning phonetic processing or a lower level auditory processing deficit was present in developmental dyslexia. Three different contrast conditions were explored, including nonphonological sounds, contrasted in pitch and duration, and phonemes. Mismatch negativity amplitudes differed significantly between groups in the duration condition, whereas no differences were found in the frequency and phoneme conditions. Moreover, the dyslexic children had delayed mismatch negativity latencies in the three contrast conditions. Our results suggest a deficit in low-level auditory discrimination in dyslexic children, in particular when detecting stimulus duration, and support the rapid auditory processing theory of dyslexia. 相似文献
999.
Haro JM Arbabzadeh-Bouchez S Brugha TS de Girolamo G Guyer ME Jin R Lepine JP Mazzi F Reneses B Vilagut G Sampson NA Kessler RC 《International journal of methods in psychiatric research》2006,15(4):167-180
The DSM-IV diagnoses generated by the fully structured lay-administered Composite International Diagnostic Interview Version 3.0 (CIDI 3.0) in the WHO World Mental Health (WMH) surveys were compared to diagnoses based on follow-up interviews with the clinician-administered non-patient edition of the Structured Clinical Interview for DSM-IV (SCID) in probability subsamples of the WMH surveys in France, Italy, Spain, and the US. CIDI cases were oversampled. The clinical reappraisal samples were weighted to adjust for this oversampling. Separate samples were assessed for lifetime and 12-month prevalence. Moderate to good individual-level CIDI-SCID concordance was found for lifetime prevalence estimates of most disorders. The area under the ROC curve (AUC, a measure of classification accuracy that is not influenced by disorder prevalence) was 0.76 for the dichotomous classification of having any of the lifetime DSM-IV anxiety, mood and substance disorders assessed in the surveys and in the range 0.62-0.93 for individual disorders, with an inter-quartile range (IQR) of 0.71-0.86. Concordance increased when CIDI symptom-level data were added to predict SCID diagnoses in logistic regression equations. AUC for individual disorders in these equations was in the range 0.74-0.99, with an IQR of 0.87-0.96. CIDI lifetime prevalence estimates were generally conservative relative to SCID estimates. CIDI-SCID concordance for 12-month prevalence estimates could be studied powerfully only for two disorder classes, any anxiety disorder (AUC = 0.88) and any mood disorder (AUC = 0.83). As with lifetime prevalence, 12-month concordance improved when CIDI symptom-level data were added to predict SCID diagnoses. CIDI 12-month prevalence estimates were unbiased relative to SCID estimates. The validity of the CIDI is likely to be under-estimated in these comparisons due to the fact that the reliability of the SCID diagnoses, which is presumably less than perfect, sets a ceiling on maximum CIDI-SCID concordance. 相似文献
1000.