Thrombotic gene polymorphisms and postoperative outcome after coronary artery bypass graft surgery

<p>Abstract</p> <p>Background</p> <p>Emerging perioperative genomics may influence the direction of risk assessment and surgical strategies in cardiac surgery. The aim of this study was to investigate whether single nucleotide polymorphisms (SNP) affect the clinical presentation and predispose to increased risk for postoperative adverse events in patients undergoing coronary artery bypass grafting surgery (CABG).</p> <p>Methods</p> <p>A total of 220 patients undergoing first-time CABG between January 2005 and May 2008 were screened for factor V gene G1691A (FVL), prothrombin/factor II G20210A (PT G20210A), angiotensin I-converting enzyme insertion/deletion (ACE-ins/del) polymorphisms by PCR and Real Time PCR. End points were defined as death, myocardial infarction, stroke, postoperative bleeding, respiratory and renal insufficiency and event-free survival. Patients were compared to assess for any independent association between genotypes for thrombosis and postoperative phenotypes.</p> <p>Results</p> <p>Among 220 patients, the prevalence of the heterozygous FVL mutation was 10.9% (n = 24), and 3.6% (n = 8) were heterozygous carriers of the PT G20210A mutation. Genotype distribution of ACE-ins/del was 16.6%, 51.9%, and 31.5% in genotypes I/I, I/D, and D/D, respectively. FVL and PT G20210A mutations were associated with higher prevalence of totally occluded coronary arteries (p < 0.001). Furthermore the risk of left ventricular aneurysm formation was significantly higher in FVL heterozygote group compared to FVL G1691G (<it>p </it>= 0.002). ACE D/D genotype was associated with hypertension (<it>p </it>= 0.004), peripheral vascular disease (p = 0.006), and previous myocardial infarction (<it>p </it>= 0.007).</p> <p>Conclusions</p> <p>FVL and PT G20210A genotypes had a higher prevalence of totally occluded vessels potentially as a result of atherothrombotic events. However, none of the genotypes investigated were independently associated with mortality.</p

Five-Year Outcomes after Off-Pump or On-Pump Coronary-Artery Bypass Grafting.

BACKGROUND: We previously reported that there was no significant difference at 30 days or at 1 year in the rate of the composite outcome of death, stroke, myocardial infarction, or renal failure between patients who underwent coronary-artery bypass grafting (CABG) performed with a beating-heart technique (off-pump) and those who underwent CABG performed with cardiopulmonary bypass (on-pump). We now report the results at 5 years (the end of the trial). METHODS: A total of 4752 patients (from 19 countries) who had coronary artery disease were randomly assigned to undergo off-pump or on-pump CABG. For this report, we analyzed a composite outcome of death, stroke, myocardial infarction, renal failure, or repeat coronary revascularization (either CABG or percutaneous coronary intervention). The mean follow-up period was 4.8 years. RESULTS: There were no significant differences between the off-pump group and the on-pump group in the rate of the composite outcome (23.1% and 23.6%, respectively; hazard ratio with off-pump CABG, 0.98; 95% confidence interval [CI], 0.87 to 1.10; P=0.72) or in the rates of the components of the outcome, including repeat coronary revascularization, which was performed in 2.8% of the patients in the off-pump group and in 2.3% of the patients in the on-pump group (hazard ratio, 1.21; 95% CI, 0.85 to 1.73; P=0.29). The secondary outcome for the overall period of the trial - the mean cost in U.S. dollars per patient - also did not differ significantly between the off-pump group and the on-pump group ($15,107 and$14,992, respectively; between-group difference, $115; 95$697 to $927). There were no significant between-group differences in quality-of-life measures. CONCLUSIONS: In our trial, the rate of the composite outcome of death, stroke, myocardial infarction, renal failure, or repeat revascularization at 5 years of follow-up was similar among patients who underwent off-pump CABG and those who underwent on-pump CABG. (Funded by the Canadian Institutes of Health Research; CORONARY ClinicalTrials.gov number, NCT00463294 .)

Analysis of the common genetic component of large-vessel vasculitides through a meta- Immunochip strategy

Giant cell arteritis (GCA) and Takayasu's arteritis (TAK) are major forms of large-vessel vasculitis (LVV) that share clinical features. To evaluate their genetic similarities, we analysed Immunochip genotyping data from 1,434 LVV patients and 3,814 unaffected controls. Genetic pleiotropy was also estimated. The HLA region harboured the main disease-specific associations. GCA was mostly associated with class II genes (HLA-DRB1/HLA-DQA1) whereas TAK was mostly associated with class I genes (HLA-B/MICA). Both the statistical significance and effect size of the HLA signals were considerably reduced in the cross-disease meta-analysis in comparison with the analysis of GCA and TAK separately. Consequently, no significant genetic correlation between these two diseases was observed when HLA variants were tested. Outside the HLA region, only one polymorphism located nearby the IL12B gene surpassed the study-wide significance threshold in the meta-analysis of the discovery datasets (rs755374, P?=?7.54E-07; ORGCA?=?1.19, ORTAK?=?1.50). This marker was confirmed as novel GCA risk factor using four additional cohorts (PGCA?=?5.52E-04, ORGCA?=?1.16). Taken together, our results provide evidence of strong genetic differences between GCA and TAK in the HLA. Outside this region, common susceptibility factors were suggested, especially within the IL12B locus

ChemInform Abstract: Bromination of 5-Methoxyindane: Synthesis of New Benzoindenone Derivatives and Ready Access to 7H-Benzo[c]fluoren-7-one Skeleton.

The photobromination of 5-methoxyindane and 5-methoxyindanone was studied at both high and low temperatures. 1,2,3-Tribromo-6-methoxyindene was easily synthesized by photolytic bromination of 5-methoxyindane at low temperature. 1,1,2,3-Tetrabromo-6-methoxyindene was obtained from the photobromination of 5-methoxyindan at 77 degrees C, which could then be easily converted to the 2,3-dibromo-6-methoxyindene by silver-supported hydrolysis. Photochemical bromination of 5-methoxy-1-indanone with N-bromosuccinimide (NBS) gave 3-bromo-6-methoxyindene, which upon thermolysis gave a benzo[c]fluorenone derivative

Bromination of 5-methoxyindane: Synthesis of new benzoindenone derivatives and ready access to 7H-Benzo[c]fluoren-7-one skeleton

The photobromination of 5-methoxyindane and 5-methoxyindanone was studied at both high and low temperatures. 1,2,3-Tribromo-6-methoxyindene was easily synthesized by photolytic bromination of 5-methoxyindane at low temperature. 1,1,2,3-Tetrabromo-6-methoxyindene was obtained from the photobromination of 5-methoxyindan at 77 degrees C, which could then be easily converted to the 2,3-dibromo-6-methoxyindene by silver-supported hydrolysis. Photochemical bromination of 5-methoxy-1-indanone with N-bromosuccinimide (NBS) gave 3-bromo-6-methoxyindene, which upon thermolysis gave a benzo[c]fluorenone derivative

İleri evre kalp yetersizliği ve mekanik destek cihazlarının geleceği: Kardiyoloji ve Kalp Damar Cerrahisi Uzlaşı Raporu

Heart failure is a progressive disease. A considerable portion of patients reach an advanced or terminal phase later or sooner, despite all of the developments in diagnosis, management, and follow-up and alternatives which can slow the disease process. As well as the palliative care of the patient in the terminal phase, definite recognition of the patient with advanced disease is vital for the consideration of therapeutic options in this patient population. Overall management and care of patients with heart failure obligates a collaboration of multiple disciplines. In addition, patients with advanced heart failure should be managed by a ;quot;heart team;quot;, as indicated by the guideline recommendations, since it requires a close communication and collaboration among cardiologists, cardiovascular surgeons, and other medical staff who are responsible for taking care of these patients. In Turkey, we have experienced physicians for managing patients with advanced heart failure. However, we are unlikely to be sufficient in the distribution of the centers and equal accessibility for all patients to therapeutic options. Hence, we still have more to do for the referral of eligible patients and patient circulation issues. This consensus report is developed to strengthen the connection between experienced and certified centers and the centers which take care of heart failure patients independent of the disease phase and other healthcare staff to increase awareness and to provide updated information for the current conditions of Turkey.Kalp yetersizliği ilerleyici bir hastalıktır. Tanı, tedavi ve takibindeki tüm gelişmelere ve hastalık sürecini yavaşlatabilen alternatiflere rağmen, hastaların önemli bir kısmı er ya da geç ileri evre ya da terminal evreye ulaşır. Terminal evredeki hastanın palyatif bakımının yanı sıra ileri evre hastanın dikkatli tanınması, bu hastalara yönelik tedavi seçeneklerinin göz önüne alınması bakımından hayati derecede önemlidir. Kalp yetersizliği hastalarının tedavi ve bakımı, genel açıdan pek çok disiplinin bir arada çalışmasını zorunlu kılmaktadır. Bununla birlikte, ileri evre kalp yetersizliği hastaları; kardiyoloji uzmanları, kalp damar cerrahisi uzmanları ve bu hastaların bakımından sorumlu diğer tıbbi personel arasında çok yakın iletişim ve iş birliğini gerektirmesi nedeniyle, kılavuz önerileri doğrultusunda, "kalp ekibi" tarafından ele alınmalıdır. Ülkemiz, ileri evre kalp yetersizliğinin yönetimi konusunda deneyim sahibi hekimlere sahiptir. Ancak, merkezlerin dağılımı, hastaların tedavi seçeneğine eşit derecede ulaşımı konularında yeterli olduğumuz söylenemez. Bu nedenle, uygun aday hastanın sevki ve hasta dolaşımı konularında daha kat edecek yolumuz bulunmaktadır. Bu uzlaşı raporu; ileri evre kalp yetersizliği yönetiminde deneyimli ve sertifikasyona sahip merkezler ile evresinden bağımsız olarak kalp yetersizliği hastalarının takip ve tedavisinin düzenlendiği merkezler ve diğer sağlık personeli arasındaki bağı güçlendirmek, farkındalığı artırmak ve ülkemiz koşullarına ilişkin güncel bilgi sağlamak amacıyla hazırlanmıştır

Advanced heart failure and future of mechanical assist devices: a Consensus Report on Cardiology and Cardiovascular Surgery

Kalp yetersizliği ilerleyici bir hastalıktır. Tanı, tedavi ve takibindeki tüm gelişmelere ve hastalık sürecini yavaşlatabilen alternatiflere rağmen, hastaların önemli bir kısmı er ya da geç ileri evre ya da terminal evreye ulaşır. Terminal evredeki hastanın palyatif bakımının yanı sıra ileri evre hastanın dikkatli tanınması, bu hastalara yönelik tedavi seçeneklerinin göz önüne alınması bakımından hayati derecede önemlidir. Kalp yetersizliği hastalarının tedavi ve bakımı, genel açıdan pek çok disiplinin bir arada çalışmasını zorunlu kılmaktadır. Bununla birlikte, ileri evre kalp yetersizliği hastaları; kardiyoloji uzmanları, kalp damar cerrahisi uzmanları ve bu hastaların bakımından sorumlu diğer tıbbi personel arasında çok yakın iletişim ve iş birliğini gerektirmesi nedeniyle, kılavuz önerileri doğrultusunda, "kalp ekibi" tarafından ele alınmalıdır. Ülkemiz, ileri evre kalp yetersizliğinin yönetimi konusunda deneyim sahibi hekimlere sahiptir. Ancak, merkezlerin dağılımı, hastaların tedavi seçeneğine eşit derecede ulaşımı konularında yeterli olduğumuz söylenemez. Bu nedenle, uygun aday hastanın sevki ve hasta dolaşımı konularında daha kat edecek yolumuz bulunmaktadır. Bu uzlaşı raporu; ileri evre kalp yetersizliği yönetiminde deneyimli ve sertifikasyona sahip merkezler ile evresinden bağımsız olarak kalp yetersizliği hastalarının takip ve tedavisinin düzenlendiği merkezler ve diğer sağlık personeli arasındaki bağı güçlendirmek, farkındalığı artırmak ve ülkemiz koşullarına ilişkin güncel bilgi sağlamak amacıyla hazırlanmıştır.Heart failure is a progressive disease. A considerable portion of patients reach an advanced or terminal phase later or sooner, despite all of the developments in diagnosis, management, and follow-up and alternatives which can slow the disease process. As well as the palliative care of the patient in the terminal phase, definite recognition of the patient with advanced disease is vital for the consideration of therapeutic options in this patient population. Overall management and care of patients with heart failure obligates a collaboration of multiple disciplines. In addition, patients with advanced heart failure should be managed by a &quot;heart team&quot;, as indicated by the guideline recommendations, since it requires a close communication and collaboration among cardiologists, cardiovascular surgeons, and other medical staff who are responsible for taking care of these patients. In Turkey, we have experienced physicians for managing patients with advanced heart failure. However, we are unlikely to be sufficient in the distribution of the centers and equal accessibility for all patients to therapeutic options. Hence, we still have more to do for the referral of eligible patients and patient circulation issues. This consensus report is developed to strengthen the connection between experienced and certified centers and the centers which take care of heart failure patients independent of the disease phase and other healthcare staff to increase awareness and to provide updated information for the current conditions of Turkey

Effects of off-pump and on-pump coronary-artery bypass grafting at 1 year

BACKGROUND: Previously, we reported that there was no significant difference at 30 days in the rate of a primary composite outcome of death, myocardial infarction, stroke, or new renal failure requiring dialysis between patients who underwent coronary-artery bypass grafting (CABG) performed with a beating-heart technique (off-pump) and those who underwent CABG performed with cardiopulmonary bypass (on-pump). We now report results on quality of life and cognitive function and on clinical outcomes at 1 year. METHODS: We enrolled 4752 patients with coronary artery disease who were scheduled to undergo CABG and randomly assigned them to undergo the procedure off-pump or on-pump. Patients were enrolled at 79 centers in 19 countries. We assessed quality of life and cognitive function at discharge, at 30 days, and at 1 year and clinical outcomes at 1 year. RESULTS: At 1 year, there was no significant difference in the rate of the primary composite outcome between off-pump and on-pump CABG (12.1% and 13.3%, respectively; hazard ratio with off-pump CABG, 0.91; 95% confidence interval [CI], 0.77 to 1.07; P=0.24). The rate of the primary outcome was also similar in the two groups in the period between 31 days and 1 year (hazard ratio, 0.79; 95% CI, 0.55 to 1.13; P=0.19). The rate of repeat coronary revascularization at 1 year was 1.4% in the off-pump group and 0.8% in the on-pump group (hazard ratio, 1.66; 95% CI, 0.95 to 2.89; P=0.07). There were no significant differences between the two groups at 1 year in measures of quality of life or neurocognitive function. CONCLUSIONS: At 1 year after CABG, there was no significant difference between off-pump and on-pump CABG with respect to the primary composite outcome, the rate of repeat coronary revascularization, quality of life, or neurocognitive function. (Funded by the Canadian Institutes of Health Research; CORONARY ClinicalTrials.gov number, NCT00463294.)