Cardiothoracic Surgery Unit

London, United Kingdom

Cardiothoracic Surgery Unit

London, United Kingdom

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Mannila M.N.,Cardiovascular Genetics and Genomics Group | Mahdessian H.,Cardiovascular Genetics and Genomics Group | Franco-Cereceda A.,Cardiothoracic Surgery Unit | De Faire U.,Karolinska Institutet | And 4 more authors.
Arteriosclerosis, Thrombosis, and Vascular Biology | Year: 2013

OBJECTIVE - : There is compelling evidence that the plasma apolipoprotein E (APOE) concentration, in addition to the APOE ε2/ε3/ε4 genotype, influences plasma lipoprotein levels, but the functional genetic variants influencing the plasma APOE concentration have not been identified. APPROACH AND RESULTS - : Genome-wide association studies in 2 cohorts of healthy, middle-aged subjects identified the APOE locus as the only genetic locus showing robust associations with the plasma APOE concentration. Fine-mapping of the APOE locus confirmed that the rs7412 ε2-allele is the primary genetic variant responsible for the relationship with plasma APOE concentration. Further mapping of the APOE locus uncovered that rs769446 (-427T/C) in the APOE promoter is independently associated with the plasma APOE concentration. Expression studies in 199 human liver samples demonstrated that the rs769446 C-allele is associated with increased APOE mRNA levels (P=0.015). Transient transfection studies and electrophoretic mobility shift assays in human hepatoma HepG2 cells corroborated the role of rs769446 in transcriptional regulation of APOE. However, no relationships were found between rs769446 genotype and plasma lipoprotein levels in 2 cohorts (n=1648 and n=1039) of healthy middle-aged carriers of the APOE ε3/ε3 genotype. CONCLUSIONS - : rs769446 is a functional polymorphism involved in the regulation of the plasma APOE concentration. © 2013 American Heart Association, Inc.


Stella G.M.,University of Pavia | Valizia C.,University of Pavia | Zorzetto M.,University of Pavia | Inghilleri S.,University of Pavia | And 6 more authors.
Respiratory Medicine Case Reports | Year: 2015

The presence of activating mutations of the epidermal growth factor receptor (. EGFR)-gene identifies a distinct and clinically relevant molecular subset of non-small-cell lung cancer. It is now well demonstrated that EGFR tyrosine kinase inhibitors (TKIs) gefitinib and erlotinib are superior to standard chemotherapy in this subset of tumors. Nevertheless, in many cases, responses are not durable and last for 6-12 months due to the occurrence of secondary or acquired resistance. Here we present three cases of EGFR-mutant lung adenocarcinomas (ADC), that showed an unexpected response to anti-EGFR small molecules. The first patient presented a continued 89 month-long response to erlotinib in a tumor recurred after surgery and conventional chemotherapy. In the other cases, subclinically persistent tumor in the lung tissue was documented histologically in lung resections performed after partial response to TKI treatment. The persistence of interstitial and endolymphatic tumor cells after TKI treatment might explain the common observation of tumor relapse after TKI discontinuation, and sustain the decision to continue treatment in responsive patients as in our first case. © 2015 Published by Elsevier Ltd.


Tennyson C.,King's College | Young C.P.,Cardiothoracic Surgery Unit | Scarci M.,Cardiothoracic Surgery Unit
Interactive Cardiovascular and Thoracic Surgery | Year: 2010

A best evidence topic in cardiac surgery was written according to a structured protocol. The question addressed was: in [patients undergoing coronary revascularisation] is [endoscopic vein harvest] superior to wopen harvestx in improving [clinical outcome and cost effectiveness]? Altogether >166 papers were found using the reported search, of which eight represented the best evidence to answer the clinical question. All papers agree that endoscopic vein harvesting (EVH) reduces the level of postoperative pain (pain score for EVH=0.52±0.95; open technique=1.02±1.51; P=0.03) and wound complications (range from 3 to 7.4% for EVH and 13 to 19.4% for conventional technique). These clinical benefits were associated with a high level of patient satisfaction. On average, four papers found that the length of hospital stay was reduced in the EVH group [weighted mean difference (WMD) -1.04 to -0.85; confidence interval (CI) -1.92 to -0.16; P=0.02]. The overall occlusion rates of venous grafts after six months were 21.7% for EVH and 17.6% for open technique. There were no differences in the six months occlusion and disease rates between EVH and conventional vein harvest (CVH), as determined by means of univariate analysis (P=0.584). However, some papers (PREVENT-IV sub-analysis and Yun et al.) called into question EVH by reporting high vein occlusion rates. At six months, this was 21.7% for EVH and 17.6% for open technique rising to 46.7% vs. 38.0% (P<0.001) at 12-18 months. At three years, endoscopic harvesting was also associated with higher rates of death, myocardial infarction, or repeat revascularisation (20.2% vs. 17.4%; P=0.04), death or myocardial infarction (9.3% vs. 7.6%; P=0.01), and death (7.4% vs. 5.8%; P=0.005). We conclude that EVH reduces the level of postoperative pain and wound complication, with a high-level of patient satisfaction but a sub-analysis of a large RCT has recently called into question the medium- to long-term patency of grafts endoscopically harvested. © 2010 Published by European Association for Cardio-Thoracic Surgery.


Hadas-Halpern I.,Shaare Zedek Medical Center | Deeb M.,Cardiothoracic Surgery Unit | Abrahamov A.,Shaare Zedek Medical Center | Zimran A.,Shaare Zedek Medical Center | Elstein D.,Shaare Zedek Medical Center
Journal of Ultrasound in Medicine | Year: 2010

Objective. Our large tertiary clinic for patients with Gaucher disease has used sonography as the preferred modality to monitor hepatosplenomegaly in hundreds of patients for more than 18 years. With the advent of specific enzyme replacement therapy (ERT), sonographic monitoring of changes in both hepatomegaly and the echogenicity of the hepatic tissue may highlight features that are amenable to ERT. Methods. All patients (500) seen at presentation and at annual or semiannual routine visits have undergone sonographic examinations by a single senior radiologist (I.H.-H.). Results. Thirty-nine patients (7.8%) had sonographic evidence of hepatic disease (21 male and 18 female; age range, 18-90 years); 26 (66.7%) of these received ERT, and 10 (25.6%) were splenectomized. Conclusions. Liver findings are relatively rare. Among 500 patients, there was no instance of computed tomographic findings that had not been previously shown by sonography. Radiologists should be acquainted with the variable sonographic spectrum of the Gaucher liver. If hepatic lesions are small, hyperechoic, and slowly evolving, one may surmise that they are due to Gaucher cell accumulation. However, special attention should be paid to progressive deterioration and irregularities in liver texture because other metabolic processes and cancers must be ruled out. © 2010 by the American Institute of Ultrasound in Medicine.

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