bluuebunny/crossref_metadata_2025_split huggingface dataset:
Defective ATM‐Kap‐1‐mediated chromatin remodeling impairs DNA repair and accelerates senescence in progeria mouse model
Authors: Liu Baohua , Wang Zimei , Ghosh Shrestha , Zhou Zhongjun 
Published: November 2012

SummaryATM‐mediated phosphorylation of KAP‐1 triggers chromatin remodeling and facilitates the loading and retention of repair proteins at DNA lesions. Mouse embryonic fibroblasts (MEFs) derived from Zmpste24−/− mice undergo early senescence, attributable to delayed recruitment of DNA repair proteins. Here, we show that ATM‐Kap‐1 signaling is compromised in Zmpste24−/− MEFs, leading to defective DNA damage‐induced chromatin remodeling. Knocking down Kap‐1 rescues impaired chromatin remodeling, defective DNA repair and early senescence in Zmpste24−/− MEFs. Thus, ATM‐Kap‐1‐mediated chromatin remodeling plays a critical role in premature aging, carrying significant implications for progeria therapy.
Electrocardiographic Predictors of Sudden Cardiac Death in Patients with Left Ventricular Hypertrophy
Authors: Panikkath Ragesh , Reinier Kyndaron , Uy‐Evanado Audrey , Teodorescu Carmen , Gunson Karen , Jui Jonathan , Chugh Sumeet S. 
Published: November 2012

BackgroundLeft ventricular hypertrophy (LVH) has been associated with increased risk of sudden cardiac death (SCD), and improvements in risk stratification methodology are warranted.MethodsWe evaluated electrocardiographic intervals as potential markers of SCD risk in LVH. Corrected QT, QRS, and JT intervals were evaluated in consecutive cases with SCD and LVH from the ongoing Oregon Sudden Unexpected Death study who underwent a 12‐lead electrocardiogram (EKG) and echocardiogram prior to and unrelated to the SCD event. Comparisons of age, gender, body mass index, LV ejection fraction, and EKG intervals together with clinical conditions (hypertension and diabetes) were conducted with geographically matched controls that had coronary artery disease but no history of ventricular arrhythmias or cardiac arrest. LVH was determined using the modified American Society of Echocardiography equation for LV mass. Independent samples t‐test, Pearson's chi‐square test, and multiple logistic regression were used for statistical comparisons.ResultsOf the 109 cases and 49 controls who met study criteria, age, gender, and comorbidities were similar among cases and controls. The mean LV mass index was not significantly different in cases compared to controls. However mean QTc (470.6 ± 53.6 ms vs 440.7 ± 38.7 ms; P < 0.0001) and QRS duration (113.6 ± 30.0 ms vs 104.9 ± 18.7 ms; P = 0.03) were significantly higher in cases than controls. In logistic regression analysis, prolonged QTc was the only EKG interval significantly associated with SCD (OR 1.72 [1.23–2.40]).ConclusionProlonged QTc was independently associated with SCD among subjects with LVH and merits further evaluation as a predictor of SCD in LVH.
Prevention of Post–Coronary Artery Bypass Grafting (CABG) Atrial Fibrillation: Efficacy of Prophylactic Beta‐Blockers in the Modern Era
Authors: Khan Muhammad Fahad , Wendel Christopher S. , Movahed Mohammad Reza 
Published: November 2012

BackgroundAtrial fibrillation/flutter (AF) is a common complication of open heart surgery and ACC/AHA guidelines strongly recommend the use of prophylactic beta‐blockers (BB) for its prevention. Several recent studies, however, have failed to show the desired protective effects of BB against post–coronary artery bypass grafting (CABG) AF. As the protocols of CABG, medical management of CAD (coronary artery disease) and demographic features of the patients undergoing open heart surgery have evolved significantly over the last two decades, we decided to perform a review of evidence from latest randomized controlled trials (RCTs) to confirm the efficacy of prophylactic BB.MethodsWe searched for RCTs comparing the efficacy of prophylactic BB versus placebo/control against post‐CABG AF. We limited our search to 1995 till present to reflect ongoing advancements in the protocols of CABG and the medical management of CAD. Initially, 34 trials were selected; however after certain exclusions only 10 RCTs were included in the final analysis.ResultsProphylactic BB decreased the incidence of post‐CABG AF from 32.8% in the control group to 20% in the prophylactic group with risk ratio (RR) of 0.50 with 95% CI of 0.36–0.69, P value < 0.001. In a subgroup analysis, carvedilol appears to be superior to metoprolol for the prevention of postoperative AF.ConclusionsDespite several limitations, this analysis confirms the efficacy of prophylactic BB against post‐CABG AF in this era. We recommend continuing perioperative BB in the open heart surgery patients in the absence of contraindications.
Indexes of Temporal Myocardial Repolarization Dispersion and Sudden Cardiac Death in Heart Failure: Any Difference?
Authors: Piccirillo Gianfranco , Rossi Pietro , Mitra Marilena , Quaglione Raffaele , Dell'Armi Annalaura , Di Barba Daniele , Maisto Damiana , Lizio Andrea , Barillà Francesco , Magrì Damiano 
Published: November 2012

BackgroundThe QT variability index, calculated between Q‐ and the T‐wave end (QTendVI), is an index of temporal myocardial repolarization lability associated with sudden cardiac death (SCD) in chronic heart failure (CHF). Little is known about temporal variability in the other two temporal myocardial repolarization descriptors obtained from Q–Tpeak and Tpeak–Tend intervals. We therefore investigated differences between these indexes in patients with CHF who died suddenly and in those who survived with a left ventricular ejection fraction (LVEF) ≤35% or >35%.Methods and ResultsWe selected 127 ECG and systolic blood pressure (SPB) recordings from outpatients with CHF all of whom had been followed up for 30 months. We calculated RR and SPB variability by power spectral analysis and QTendVI, QTpeakVI, TpeakTendVI. We then subdivided data patients into three groups SCD, LVEF ≤ 35%, and LVEF > 35%. The LVEF was higher in the SCD than in the LVEF ≤ 35% group, whereas no difference was found between the SCD and LVEF > 35% groups. QTendVI, QTpeakVI, and TpeakTendVI were higher in the SCD and LVEF ≤ 35% groups than in the LVEF > 35% group. Multivariate analysis detected a negative relationship between all repolarization variability indexes, low frequency obtained from RR intervals and LVEF.ConclusionsOur data show that variability in the first (QTpeakVI) and second halves of the QT interval (Tpeak–TendVI) significantly contributes to the QTendVI in patients with CHF. Further studies should investigate whether these indexes might help stratify the risk of SCD in patients with a moderately depressed LVEF.
Effectiveness of Cardiac Resynchronization Therapy with Defibrillator in At‐Risk Black and White Cardiac Patients
Authors: Elanchenny Meena , Moss Arthur J. , McNitt Scott , Aktas Mehmet , Polonsky Slava , Zareba Wojciech , Goldenberg Ilan 
Published: November 2012

BackgroundThere are limited data regarding racial differences in response to cardiac resynchronization therapy with defibrillator (CRT‐D).MethodsWe assessed the effectiveness of CRT‐D, as compared to implantable cardioverter defibrillator (ICD) therapy alone, in reducing the risk of heart failure (HF) or death and changes in cardiac volumes among 1638 (90%) white patients and 143 (8%) black patients enrolled in the Multicenter Automatic Defibrillator Implantation Trial with Cardiac Resynchronization Therapy (MADIT‐CRT).ResultsEnrolled black patients displayed a higher frequency of diabetes mellitus, treated hypertension, higher creatinine levels, and a lower distance walked in the baseline 6‐minute walk test. Kaplan‐Meier survival analysis showed that at 3 years of follow‐up the cumulative probability of HF or death was higher among blacks (29%) as compared with whites (22%; P = 0.05). Both black and white patients experienced similar and pronounced reductions in cardiac volumes with CRT‐D therapy (all P values for comparison between the two groups >0.10). Risk reduction conferred by CRT‐D therapy as not significantly different between blacks and whites (hazard ratio = 0.78 and 0.60, respectively; P for the difference = 0.44). However, possibly due to sample size limitations the CRT‐D versus ICD only adjusted risk for HF/death in blacks was not statistically significant.ConclusionsBlack patients in MADIT‐CRT experienced increased risk of HF or death as compared with whites, but displayed a similar magnitude echocardiographic response to CRT‐D. These findings suggest that cardiac resynchronization therapy may be an effective therapeutic modality in black patients. However, further studies are needed to assess the clinical response to CRT‐D in this high‐risk population.
The Prognostic Value of Electrocardiographic Estimation of Left Ventricular Hypertrophy in Dialysis Patients
Authors: Covic Adrian C. , Buimistriuc Laura‐Dumitriţa , Green Darren , Stefan Alina , Badarau Silvia , Kalra Philip A. 
Published: November 2012

BackgroundLeft ventricular hypertrophy (LVH) is associated with poor cardiovascular outcome in CKD. Electrocardiogram (ECG) is low‐cost but infrequently used to assess presence of LVH in dialysis patients. The aim of this study was to establish which ECG‐determined LVH method is most sensitive in dialysis patients, and also most predictive of death.MethodsThis was a longitudinal observational study in dialysis patients from a single center, undergoing interval ECGs. Fourteen methods of ECG LVH assessment were compared. Survival was also compared between four LVH evolutionary categories: persistent LVH; new LVH; LVH regression; and no LVH.ResultsThe study included 418 dialysis patients (46.3% women, mean age 51 years, mean follow up 67 months, 76 deaths, 37 cardiovascular deaths). LVH prevalence varied according to method (range 13.4–41.9%).No measurement predicted all‐cause mortality. After Cox regression, there was an independent association between LVH and cardiovascular mortality using Novacode (HR = 3.04; 95% [CI] = 1.11–8.28, P < 0.05), but not with other methods. Patients with persistent ECG changes of LVH had increased risk of cardiovascular mortality compared to other LVH evolutionary categories (P < 0.044).ConclusionsECG scoring of LVH can be predictive of cardiovascular mortality. The Novacode method, based on repolarization abnormalities, is a better predictor than standard ECG techniques that are based on voltage criteria. Novacode LVH estimation at dialysis initiation may prove to be a noninvasive and cost‐effective bedside tool for cardiovascular risk stratification in patients receiving dialysis.
The Prognostic Significance of Frequency and Morphology of Premature Ventricular Complexes during Ambulatory Holter Monitoring
Authors: Ephrem Georges , Levine Michael , Friedmann Patricia , Schweitzer Paul 
Published: November 2012

BackgroundMultiform premature ventricular complexes (PVCs) are associated with an adverse prognosis in patients with structural heart disease. Very frequent PVCs are associated with ventricular dysfunction. Our hypothesis is that multiform PVCs confer an adverse prognosis in the general population.MethodsWe performed a retrospective cohort study of patients ≥18 years old referred to our institution for 24‐hour ambulatory Holter monitoring between July 1, 2008 and December 31, 2009. Holters without PVCs or with more frequent ectopy (couplets, triplets, or nonsustained ventricular tachycardia) were excluded. Clinical and adverse event (AE) data (“major adverse cardiovascular event” or new/worsening heart failure) were gathered from chart review. Data was analyzed by PVC frequency (rare, occasional, or frequent) and pattern (uniform or multiform).ResultsA total of 222 patients (43% male, mean age: 55 ± 16 years) were evaluated (median follow‐up 2.3 years [IQR: 2.0–2.6]). Median frequency was 2 PVCs per hour (IQR: 1–13). Multiform PVCs were noted in 48%. Patients with multiform PVCs were older, and had a higher prevalence of comorbidities. Thirty‐nine AE were noted. Patients with an AE were younger, had a higher prevalence of HTN, diabetes, CAD, CHF, and previous MI. The multiform group had a higher incidence of AE (28%) compared to the uniform group (8%) (P < 0.001). Increasing PVC frequency was associated with a higher incidence of AE (8% vs 24% vs 35%, respectively). In Cox regression analyses, the multiform pattern but not frequency predicted AE.ConclusionsMultiform PVCs were associated with a 4‐fold increase in AE in patients referred for ambulatory Holter monitoring.
A Reappraisal on Lidocaine‐Sensitive Repetitive, Uniform Atrial Tachycardia
Authors: Garro Hugo A. , Elizari Marcelo V. , Baranchuk Adrian , Femenía Francisco , Chiale Pablo A. 
Published: November 2012

BackgroundLidocaine sensitive, repetitive atrial tachycardia is an unusual arrhythmia whose electrophysiologic substrate remains undefined. We aimed to analyze the electropharmacologic characteristics of this arrhythmia with emphasis on its cellular substrate and response to drug challenges.MethodsWe retrospectively analyzed a series of 18 patients from an electrocardiographic and electrophysiologic perspective and the response to pharmacological challenge.ResultsThere was no evidence of structural heart disease in 12 patients, 4 patients presented with systemic hypertension; one patient had a prior myocardial infarction and one a mitral valve prolapse. The arrhythmia depicted a consistent pattern in nine patients. The first initiating ectopic beat showed a long coupling interval, the cycle length of the second atrial ectopic beat presented the shortest cycle length and a further prolongation was apparent towards the end of the atrial salvos. Conversely, in the other nine cases, the atrial tachycardia cycle length was erratic. The arrhythmia was suppressed by asynchronous atrial pacing at cycle lengths longer than those of the atrial tachycardia. Intravenous lidocaine eliminated the arrhythmia in all patients, but intravenous verapamil suppressed the atrial tachycardia in only two patients while adenosine caused a transient disappearance in 2/8 patients. Only one patient responded to all the three agents. Radiofrequency ablation was successfully performed in 10 patients.ConclusionsRepetitive uniform atrial tachycardia can be sensitive to lidocaine. In few cases, this rare focal arrhythmia may be also suppressed by adenosine and/or verapamil, which suggests a diversity of electrophysiologic substrates that deserve to be accurately identified.
Assessment of Ventricular Repolarization Variability with the DeltaT50 Method Improves Identification of Patients with Congenital Long QT Syndromes
Authors: Abrahamsson Christina , Dota Corina , Skallefell Bo , Carlsson Leif , Frison Lars , Berggren Anders , Edvardsson Nils , Duker Göran 
Published: November 2012

BackgroundWe analyzed ventricular repolarization variability in genotyped long QT syndrome (LQTS) patients and in healthy volunteers (HV).MethodThe deltaT50, that is, the temporal variability of ventricular repolarization at 50% of the T‐wave downslope, was analyzed every 15th minute on 175 and 390 Holter electrocardiogram (ECG) recordings from HV and genotyped LQTS patients, respectively. The average deltaT50 and QTcF were calculated in each subject.ResultsDeltaT50 was 2.26 ± 0.71 ms (mean ± SD) in the HV and 5.74 ± 2.30 ms in the LQTS population (P < 0.0001). The sensitivity and specificity of QTcF (cutoff value 450 ms) to discriminate between the LQTS patients and the HV were 51.5% and 98.9%, and for deltaT50 (cutoff value 3 ms) 93.9% and 88.6%, respectively. The combination of both variables improved the diagnosis of the LQTS patients even further. Subgroups of LQTS patients at higher risk of cardiac events (with LQTS3, JLN, QTc > 500 ms or symptoms) had higher deltaT50 than subgroups at lower risk (with LQTS1, QTc < 450 ms or without symptoms). The variation in deltaT50 between day and night was concordant with the risk of symptoms; patients with LQTS1 had higher deltaT50 in the daytime and patients with LQTS3 had higher deltaT50 during the night.ConclusionDeltaT50 more accurately distinguished between LQTS patients and HV than QTcF and was higher in LQTS patients with a higher risk of cardiac events. DeltaT50 can be used together with QTcF to improve the diagnosis in patients with the LQTS phenotype and tentatively also be of value for risk assessment in such patients.
The Findings of Electrocardiography in Patients with Cardiac Amyloidosis
Authors: Cheng Zhongwei , Zhu Kongbo , Tian Zhuang , Zhao Dachun , Cui Quancai , Fang Quan 
Published: November 2012

ObjectiveThe electrocardiography (ECG) was the simplest and common adjunctive diagnostic tool for cardiac amyloidosis (CA). We sought to clarify the findings of ECG in patients with CA in order to early identification of CA according to the findings of ECG.MethodsA total of 276 patients with diagnosis of systemic amyloidosis admitted to Peking Union Medical College Hospital from January 2000 to December 2011, were enrolled. Two groups were classified according to the cardiac involvement or not, namely CA (n = 189) and control (n = 87) groups. The low voltage on limb leads defined by the amplitude of the QRS complex in each limb leads ≤0.5 mV. The pseudo‐infarct pattern defined by the presence of pathologic Q waves on at least two contiguous leads on ECG without obstructive coronary artery disease.ResultsThe mean age was 55 ± 12 (15–88) years, 168 patients (61%) were male. Atrial arrhythmia (15.9% vs 3.4%, P = 0.003), low voltage on limb leads (54.5% vs 20.7%, P < 0.001), atrioventricular block (14.8% vs 1.1%, P = 0.001) and pseudo‐infarct pattern (40.2% vs 4.6%, P < 0.001) were more prevalent in CA than control groups. The combination of low voltage on limb leads and pseudo‐infarct pattern was more common (28.0% vs 2.3%, P < 0.001) in CA than control groups. The sensitivity, specificity, positive and negative predictive values of the presence of low voltage on limb leads and pseudo‐infarct pattern for the diagnosis of CA were 28%, 98%, 96%, and 39%, respectively.ConclusionIn CA patients, low voltage on limb leads and pseudo‐infarct pattern were the most common ECG findings. Atrial arrhythmia and atrioventricular block were the most common arrhythmias in CA patients. The combination of low voltage on limb leads and pseudo‐infarct pattern had high specificity and positive predictive value for the diagnosis of CA.
Educational strategies in performing cesarean section
Authors: Madsen Kristine , Grønbeck Lene , Rifbjerg Larsen Christian , Østergaard Jeanett , Bergholt Thomas , Langhoff‐Roos Jens , Sørensen Jette Led 
Published: November 2012

AbstractCesarean section is a common operation and one of the first surgeries performed independently by trainees/residents in obstetrics and gynecology. Determination of trainees' technical skills level is dependent upon subjective faculty assessment. Based on three studies on learning curves in cesarean section, it is recommended that trainees perform between 10–15 and 40 supervised cesarean sections before operating independently. Surgical technical skills of trainees/residents may be assessed by Objective Structured Assessment of Technical Skills (OSATS), which provides a foundation for constructive feedback during surgical training. The Danish, Swedish and British Obstetric and Gynecological Societies' guidelines on cesarean section were reviewed regarding cesarean section surgical technique. Placental removal by traction on the umbilical cord is recommended uniformly; however, the Danish guidelines recommend one‐layer uterine incision closure, whereas the Swedish and British guidelines recommend two‐layer closure. Maternal complications at cesarean section increase when the primary surgeon is a trainee/resident rather than an experienced surgeon. Basic surgical proficiencies regarding instruments, sutures and surgical technique as well as basic anatomy, should be verified before entering a training program for cesarean section. Such a training program for technical and non‐technical skills in cesarean section should include theoretical instruction, video tutorials, practical experience and direct supervision. Development of a specific OSATS for cesarean section is recommended. Training must be individually structured accommodating the differences in trainees' competencies. Before clinical training in the operating room begins, all trainees must attain standardized cognitive and technical skills.
Neonatal and parental predictors of executive function in very preterm children
Authors: Aarnoudse‐Moens Cornelieke Sandrine Hanan , Weisglas‐Kuperus Nynke , Duivenvoorden Hugo Joseph , Oosterlaan Jaap , van Goudoever Johannes Bernard 
Published: November 2012

AbstractAimTo examine neonatal and parental predictors of executive function in very preterm (gestational age ≤30 weeks) children aged 4.0–12.0 years.MethodsTwo‐hundred very preterm (mean age 8.2 ± 2.5 years) children without severe disabilities, born between 1996 and 2004, were assessed with measures of executive function including working memory, verbal fluency, planning and inhibitory control. Neonatal predictors were obtained from clinical records. Parental predictors included parental education, which was derived from questionnaires. Multiple linear regression analyses identified associations between neonatal and parental predictors and executive function in very preterm children.ResultsBetter postnatal growth at 6 weeks of corrected age‐predicted better spatial span (R² = 0.03, β = 0.17, p = 0.02) and planning (R² = 0.03, β = 0.16, p = 0.04). A higher level of parental education predicted better verbal fluency (R² = 0.02, β = 0.12, p = 0.02). Verbal working memory was not predicted by neonatal risk factors or by parental education (βs < 0.09, ps > 0.20).ConclusionsExecutive function in very preterm children is associated with early postnatal growth and level of parental education but not with neonatal complications.
One‐year maintenance outcomes among patients with moderately‐to‐severely active ulcerative colitis who responded to induction therapy with adalimumab: subgroup analyses from ULTRA 2
Authors: Sandborn W. J. , Colombel J.‐F. , D'Haens G. , Van Assche G. , Wolf D. , Kron M. , Lazar A. , Robinson A. M. , Yang M. , Chao J. D. , Thakkar R. 
Published: November 2012

SummaryBackgroundPatients with moderately‐to‐severely active ulcerative colitis (UC) are unlikely to continue anti‐TNF therapy in the absence of early therapeutic response.AimTo assess week 52 efficacy, safety and benefit/risk balance of adalimumab treatment in patients with moderately‐to‐severely active UC failing conventional therapy who achieved clinical response at week 8 in the 52‐week ULTRA 2 trial.MethodsPatients randomised to adalimumab (160/80 mg, week 0/2; 40 mg, every other week thereafter) in ULTRA 2 who achieved clinical response at week 8 per partial Mayo score (Mayo score without endoscopy subscore) were assessed for week 52 clinical remission, clinical response, mucosal healing, steroid‐free remission and steroid discontinuation rates, overall and by prior anti‐TNF use. Benefit/risk balance for the overall ITT population (regardless of week 8 responder status) was assessed using ‘net efficacy adjusted for risk’ (NEAR) odds ratios. Safety was assessed using adverse event rates.ResultsOf 248 adalimumab‐treated patients, 123 (49.6%) achieved clinical response at week 8. Of these, 30.9%, 49.6%, and 43.1% achieved clinical remission, clinical response, and mucosal healing, respectively, at week 52. Of the week 8 responders using corticosteroids at baseline (N = 90), 21.1% achieved steroid‐free remission and 37.8% were steroid‐free at week 52. NEAR odds ratios indicated a positive benefit/risk balance for achievement of week 8 and week 52 response or remission without serious adverse events or serious infections. No safety concerns were identified.ConclusionsAdalimumab treatment was associated with a positive benefit/risk balance in the overall population of patients with moderately‐to‐severely active ulcerative colitis in ULTRA 2; early response was predictive of a positive outcome at 1 year (NCT00408629).