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Objective To diagnose the ring chromosome 13 (r(13)) in a fetus, and analyze the genotype–phenotype correlation. Case report A 26-year-old woman who was second pregnancy, underwent amniocentesis at 18 weeks of gestation because of the increased nuchal translucency (NT). Prenatal ultrasound showed the NT thickness was 3.5 mm at 12+1 weeks of gestation and nuchal fold (NF) was 6.1 mm at 18 weeks of gestation, and amniotic fluid karyotype analysis revealed mosaic r(13). CMA detected a 16.293 Mb duplication at 13q21.32q31.1 and 31.303 Mb deletion at 13q31.1q34. Conclusion R(13) is a very rare chromosomal abnormality. Cytogenetic examination combined with CMA can provide accurate diagnosis and effective information for genetic counseling.

Objective To indigenize the median of Down syndrome (DS) screening markers for first and second trimester, and compare the impact of the indigenized and built-in median data on the efficiency of DS screening. Materials and Methods Data derived from first and Second-trimester screening (FTS and STS) for DS, composed of selected pregnancies deemed to be normal, were examined in a retrospective study. Indigenization regression analysis was calculated by using five models to fit statistical the raw data. Multiple of median (MoM) values estimated by using indigenized medians were compared with those calculated by using built-in. Results This study established a regression equation which is more suitable for the median of each screening marker in the local pregnant women. The changes of median MoM of screening markers were statistically significant after indigenization. For FTS, the detection rate was 100% when the false positive rate was 5%, and the cut-off value was 1/262. On the other hand, for STS, the detection rate of the model with indigenized parameters was 77.42%, which is 16.13% higher than that of built-in parameters. Conclusion For the individual specific risk of pregnancy, when the indigenized parameters was used to calculate, is more accurately and screening effectiveness has been improved. This is a great reference significance for the current prenatal screening whether indigenized data should be used.

It remains uncertain whether intensive control of blood pressure (BP) results in a lower risk of atrial fibrillation (AF) in patients with hypertension. Using data from SPRINT (Systolic Blood Pressure Intervention Trial), which enrolled participants with hypertension at increased risk of cardiovascular disease, we examined whether intensive BP lowering (target systolic BP [SBP] P =0.037). This effect was consistent among prespecified subgroups of SPRINT participants stratified by age, sex, race, SBP tertiles, prior cardiovascular disease, and prior chronic kidney disease when interactions between treatment effect and these subgroups were assessed using Hommel adjusted P values. In conclusion, intensive treatment to a target of SBP Registration— URL: https://www.clinicaltrials.gov ; Unique identifier: NCT01206062.

Islet autoimmunity may contribute to β-cell dysfunction in type 2 diabetes (T2D). Its prevalence and clinical significance have not been rigorously determined. In this ancillary study to the Glycemia Reduction Approaches in Diabetes: A Comparative Effectiveness Study (GRADE), we investigated the prevalence of cellular and humoral islet autoimmunity in patients with T2D duration of 4.0 ± 3.0 years (HbA1c 7.5 ± 0.5% on metformin alone). We measured T-cell autoreactivity against islet proteins, islet autoantibodies against 65-kDa GAD antigen, IA-2, and zinc transporter-8, and β-cell function. Cellular islet autoimmunity was present in 41.3%, humoral islet autoimmunity in 13.5%, and both in 5.3%. β-Cell function calculated as incremental area under the curve of glucose from 0–120 min (iAUC-CG) and ΔC-peptide(0–30)/Δglucose(0–30) from an oral glucose tolerance test was lower among T-cell–positive (T+) than T-cell–negative (T−) individuals using two different adjustments for insulin sensitivity (iAUC-CG: 13.2% [95% CI 0.3, 24.4] or 11.4% [95% CI 0.4, 21.2] lower; ΔC-peptide[0–30]/Δglucose[0–30]: 19% [95% CI 3.1, 32.3] or 17.7% [95% CI 2.6, 30.5%] lower). T+ patients had 17% higher HbA1c (95% CI 0.07, 0.28) and 7.7 mg/dL higher fasting plasma glucose levels (95% CI 0.2, 15.3) than T− patients. We conclude that islet autoimmunity is much more prevalent in patients with T2D than previously reported. T-cell–mediated autoimmunity is associated with diminished β-cell function and worse glycemic control.

RATIONALE AND OBJECTIVE: The safety of intensive blood pressure (BP) targets is controversial for persons with chronic kidney disease (CKD). We studied the effects of hypertension treatment on cerebral perfusion and structure in those with and without CKD. STUDY DESIGN: Neuroimaging substudy of a randomized trial. SETTING & PARTICIPANTS: A subset of participants in the Systolic Blood Pressure Intervention Trial who underwent brain MRI studies. Presence of baseline CKD was assessed by estimated glomerular filtration rate (eGFR) and urine albumin to creatinine ratio (UACR). INTERVENTION: Participants were randomly assigned to intensive (systolic BP 30 mg/g (N=151), the effects of intensive versus standard BP treatment on change in global cerebral blood flow, WMLs and total brain volume were 1.91 ml/100g/min (95% CI −3.01, 6.82), 0.003 cm(3) (asinh transformed, 95% CI −0.13, 0.13), and −7.0 cm(3) (95% CI −13.3, −0.3), respectively. The overall treatment effects on cerebral blood flow and total brain volume were not modified by baseline eGFR or UACR; however the effect on WMLs was attenuated in participants with albuminuria (interaction p-value 0.04). LIMITATIONS: Measurement variability due to multi-site design. CONCLUSIONS: Among hypertensive adults with primarily early kidney disease, intensive versus standard blood pressure treatment did not appear to have a detrimental effect on brain perfusion or structure. The findings support the safety of intensive blood pressure treatment targets on brain health in persons with early kidney disease. FUNDING: The Systolic Blood Pressure Intervention Trial was funded by the National Institutes of Health (including the National Heart, Lung, and Blood Institute, the National Institute of Diabetes and Digestive and Kidney Diseases, the National Institute on Aging, and the National Institute of Neurological Disorders and Stroke), and this substudy was funded by the National Institutes of Diabetes and Digestive and Kidney Diseases. TRIAL REGISTRATION: SPRINT was registered at ClinicalTrials.gov with the study number NCT01206062.

Background Electrocardiographic left ventricular hypertrophy (ECG‐LVH) represents preclinical cardiovascular disease and predicts cardiovascular disease morbidity and mortality. While the newly developed Peguero‐Lo Presti ECG‐LVH criteria have greater sensitivity for LVH than the Cornell voltage and Sokolow–Lyon criteria, its short‐term repeatability is unknown. Therefore, we characterized the short‐term repeatability of Peguero‐Lo Presti ECG‐LVH criteria and evaluate its agreement with Cornell voltage and Sokolow–Lyon ECG‐LVH criteria. Methods Participants underwent two resting, standard, 12‐lead ECGs at each of two visits one week apart (n = 63). We defined a Peguero‐Lo Presti index as a sum of the deepest S wave amplitude in any single lead and lead V4 (i.e., SD + SV4) and defined Peguero‐Lo Presti LVH index as ≥ 2,300 µV among women and ≥ 2,800 µV among men. We estimated repeatability as an intraclass correlation coefficient (ICC), agreement as a prevalence‐adjusted bias‐adjusted kappa coefficient (κ), and precision using 95% confidence intervals (CIs). Results The Peguero‐Lo Presti index was repeatable: ICC (95% CI) = 0.94 (0.91–0.97). Within‐visit agreement of Peguero‐Lo Presti LVH was high at the first and second visits: κ (95% CI) = 0.97 (0.91–1.00) and 1.00 (1.00–1.00). Between‐visit agreement of the first and second measurements at each visit was comparable: κ (95% CI) = 0.90 (0.80–1.00) and 0.93 (0.85–1.00). Agreement of Peguero‐Lo Presti and Cornell or Sokolow–Lyon LVH on any one of the four ECGs was slightly lower: κ (95% CI) = 0.71 (0.54–0.89). Conclusion The Peguero‐Lo Presti index and LVH have excellent repeatability and agreement, which support their use in clinical and epidemiological studies.

To systematically evaluate the efficacy and safety of Xinmailong Injection in the treatment of coronary heart disease complicated with heart failure. Seven databases,namely CNKI, VIP,WanFang,SinoMed,PubMed,EMbase,Cochrane Library, were retrieved by computer for collecting the randomized controlled trials about Xinmailong Injection in the treatment of coronary heart disease complicated with heart failure. The literatures were screened out, data was extracted, and the methodological quality evaluation was conducted by 2 researchers independently according to inclusion and exclusion criteria. RevMan 5.3 software was used for Meta-analysis and corresponding description analysis. A total of 19 studies involving 1 922 patients were included, including 967 cases in the trial group and 955 cases in the control group. All the clinical studies showed a low quality. Meta-analysis results showed that Xinmailong Injection combined with conventional treatment could better reduce the BNP level(SMD=-3.34, 95%CI[-4.06,-2.63]) in patients of coronary heart disease complicated with heart failure or NT-proBNP level, improve the cardiac function(RR=1.23,95%CI[1.18,1.29]) and LVEF(MD=6.85,95%CI[4.93,8.76]),increase 6 MWT(MD=24.34, 95%CI[16.05, 32.64]) and VEGF(MD=26.39,95%CI[24.30,28.49]),and decreased LVEDD(MD=-4.06, 95%CI[-6.33,-1.80]). And subgroup analysis suggested that the course of treatment may be related to the increase of LVEF. This study found that Xinmailong Injection for coronary heart disease complicated with heart failure can further alleviate clinical symptoms and relevant indicators, with no serious adverse reaction. However, it still needs the support of well-designed multicenter, double-blind and high-quality clinical trials.

Background Terminal duplication on chromosome 15q is a rare chromosomal variation. Affected individuals show similar features such as growth dysplasia or the development of frontal bossing, body deformities, facial abnormalities, and genitourinary or cardiovascular disorders. However, it is not yet clear whether such 15q repeats lead to identifiable patterns of clinical abnormalities. Therefore, the purpose of this study was to analyze the prenatal diagnostic results and clinical manifestations of a fetus with 15q duplication and to summarize the literature. Methods The case was a fetus at 28 weeks of gestation. The risk of Down syndrome from second‐trimester screening was 1/140. Prenatal ultrasound and amniocentesis were performed, and chromosomal microarray analysis (CMA) was used for genetic analysis. Results The fetus had abnormal clinical features, including intracardiac echogenic focus in the left ventricle, an aberrant right subclavian artery, and growth delay. The fetal chromosomal karyotype was 46,XX,15q?,12q?,21pstk+, and CMA revealed a 10.163 Mb duplication at 15q24.3‐q25.3. The couple chose to terminate the pregnancy after careful consideration. Conclusions The combination and rational application of cytogenetics technology and molecular genetics technology such as CMA will open up the field of clinical application and provide useful genetic counseling for parents of fetuses carrying such chromosomal duplications.

Objective To retrospectively analyze the incidence of chromosomal polymorphisms in prenatal cytogenetic diagnostic cases and the effect of the clinical manifestation of these fetuses. Materials and methods 490 fetuses with chromosomal polymorphisms among 9996 pregnant women who underwent prenatal cytogenetic diagnosis were included in this study and were set as group 1. Other 500 pregnant women, whose fetuses were with normal karyotypes, were randomly selected from the remaining pregnant women and set as group 2. Clinical information and outcomes and maternal serum screening results of group 1 were compared with group 2. Results The frequency of fetal chromosomal polymorphism was 4.90% (490/9996). The most common variants observed were 1/9/16 qh± (2.27%, 227/9996), followed by inv(9) (0.90%, 90/9996). 94.62% (264/279) of fetal chromosomal variants were inherited from parents. No statistical difference was found in clinical information and outcomes and maternal serum screening results between group 1 and group 2. Conclusion The fetus with chromosomal polymorphism has no impact on serum markers of second trimester screening and does not play an important role for the clinical outcome of the current pregnancy either, whether it is inherited from the parents or a de novo mutation.

The genetic basis of supraventricular and ventricular ectopy (SVE, VE) remains largely uncharacterized, despite established genetic mechanisms of arrhythmogenesis. To identify novel genetic variants associated with SVE/VE in ancestrally diverse human populations, we conducted a genome-wide association study of electrocardiographically identified SVE and VE in five cohorts including approximately 43,000 participants of African, European and Hispanic/Latino ancestry. In thirteen ancestry-stratified subgroups, we tested multivariable-adjusted associations of SVE and VE with single nucleotide polymorphism (SNP) dosage. We combined subgroup-specific association estimates in inverse variance-weighted, fixed-effects and Bayesian meta-analyses. We also combined fixed-effects meta-analytic t-test statistics for SVE and VE in multi-trait SNP association analyses. No loci reached genome-wide significance in trans-ethnic meta-analyses. However, we found genome-wide significant SNPs intronic to an apoptosis-enhancing gene previously associated with QRS interval duration (FAF1; lead SNP rs7545860; effect allele frequency = 0.02; P = 2.0 × 10−8) in multi-trait analysis among European ancestry participants and near a locus encoding calcium-dependent glycoproteins (DSC3; lead SNP rs8086068; effect allele frequency = 0.17) in meta-analysis of SVE (P = 4.0 × 10−8) and multi-trait analysis (P = 2.9 × 10−9) among African ancestry participants. The novel findings suggest several mechanisms by which genetic variation may predispose to ectopy in humans and highlight the potential value of leveraging pleiotropy in future studies of ectopy-related phenotypes.

Background Although time–domain measures of heart rate variability (HRV) are used to estimate cardiac autonomic tone and disease risk in multiethnic populations, the genetic epidemiology of HRV in Hispanics/Latinos has not been characterized. Objective The purpose of this study was to conduct a genome-wide association study of heart rate (HR) and its variability in the Hispanic Community Health Study/Study of Latinos, Multi-Ethnic Study of Atherosclerosis, and Women's Health Initiative Hispanic SNP-Health Association Resource project (n = 13,767). Methods We estimated HR (bpm), standard deviation of normal-to-normal interbeat intervals (SDNN, ms), and root mean squared difference in successive, normal-to-normal interbeat intervals (RMSSD, ms) from resting, standard 12-lead ECGs. We estimated associations between each phenotype and 17 million genotyped or imputed single nucleotide polymorphisms (SNPs), accounting for relatedness and adjusting for age, sex, study site, and ancestry. Cohort-specific estimates were combined using fixed-effects, inverse-variance meta-analysis. We investigated replication for select SNPs exceeding genome-wide (P Results Two genome-wide significant SNPs replicated in a European ancestry cohort, 1 one for RMSSD (rs4963772; chromosome 12) and another for SDNN (rs12982903; chromosome 19). A suggestive SNP for HR (rs236352; chromosome 6) replicated in an African-American cohort. Functional annotation of replicated SNPs in cardiac and neuronal tissues identified potentially causal variants and mechanisms. Conclusion This first genome-wide association study of HRV and HR in Hispanics/Latinos underscores the potential for even modestly sized samples of non-European ancestry to inform the genetic epidemiology of complex traits.

Background We estimated the incidence and mortality of nasopharyngeal carcinoma (NPC) in China in 2010 according to the data of 145 domestic population-based cancer registries in 2014, and no such reports since then. Hence, to further and better understand its epidemiology in China and to provide more precise scientific information for its control and prevention in China, we analyzed the NPC incidence and mortality of 255 domestic population-based cancer registries, and estimated the national rates in 2013 again. Methods NPC incidence and mortality data of 255 domestic cancer registries in 2013, accepted by the 2016 National Cancer Registry Annual Report, were collected and collated, and the indices of NPC such as the numbers of new cases and deaths, crude rates, age-standardized rates, and truncated rates of incidence and mortality were calculated and analyzed. The incidence and mortality in China and its constituent areas were estimated according to the national population in 2013. Results An estimated 42,100 new cases and 21,320 deaths were attributed to NPC in China in 2013, accounting for 1.14% of all new cancer cases and 0.96% of all cancer-related deaths that year in China. Crude incidence and mortality of NPC were 3.09/100,000 and 1.57/100,000, respectively. World age-standardized incidence and mortality were 2.17/100,000 and 1.08/100,000, respectively. The incidence and mortality of males were obviously higher than those of females and slightly higher in urban areas than in rural areas. Among seven Chinese administrative regions, NPC incidence and mortality were obviously higher in South China than in other regions and lowest in North China. Top 3 incidence and mortality provinces and registering areas all located in South China. The age-specific incidence and mortality rose quickly from age 25–29 and 35 to 39 years, respectively, peaked at different ages and varied by location. Conclusions These results demonstrated that NPC incidence and mortality in China in 2013 were also at high levels worldwide, which suggested that its control and prevention should be enhanced.

There is a lack of evidence regarding the economic effects of nutrition support in patients at nutritional risk. The aim of this study was to perform a cost-effectiveness analysis by comparing an adequate nutrition support cohort with a no-support cohort.A prospective observational study was performed in the surgical and medical gastroenterology wards. We identified patients at nutritional risk and the provision of nutrition support by the staff, unaware of the risk status, was recorded. Cost data were obtained from each patient's statement of accounts, and effectiveness was measured by the rate of infectious complication. To control for potential confounding variables, the propensity score method with matching was carried out. The incremental cost-effectiveness ratio was calculated based on the matched population.We screened 3791 patients, and 440 were recruited for the analysis. Patients in the nutrition support cohort had a lower incidence of infectious complications than those in the no-support cohort (9.1 versus 18.1%; P = 0.007). This result was similar in the 149 propensity matched pairs (9.4 versus 24.2%; P 0.001). The median hospital length of stay was significantly reduced among the matched nutrition support patients (13 versus 15 d; P 0.001). The total costs were similar among the matched pairs (US $6219 versus $6161). The incremental cost-effectiveness analysis suggested that nutrition support cost US $392 per patient prevented from having infectious complications.Nutrition support was associated with fewer infectious complications and shorter length of stay in patients at nutritional risk. The incremental cost-effectiveness ratio indicated that nutrition support had not increased costs significantly.

Background Many anthropometric studies of the normal glenohumeral relationship have been performed for the implant design and to identify reference points for the correct placement of the prosthesis in glenohumeral joint replacement. However, whether those implantation marks, which adopted from European or American, can achieve the same precision to Eastern Asian, specifically Chinese is still unknown. Materials and methods One hundred eighty healthy were scanned using CT. Their humeri were measured to determine humeral head retroversion and its relation to the location of the bicipital groove. The angle between the transepicondylar axis and the line connected the centre of the head sphere and the lateral lip point of the bicipital groove, and the plane through the humerus shaft axis and the lateral lip of the bicipital groove in the horizontal plane were measured and denoted by angle-α and angle-β, respectively. The biceps distance (BD) from the lateral lip of the bicipital groove proximally to the axis of humeral head in the horizontal plane was also measured. Results The average angle α and β was 40.08° (±11.15°) and 42.19° (±12.64°). The average BD was 7.15 mm (range 0.87–13.94 mm; SD 2.55 mm). The linear relationship between humeral head retroversion and the bicipital groove angle α can expressed as α = 0.7125 × retroversion + 24.8128 (R 2 = 0.5956). If the centre of the lateral aspect of the stem has a posteriorly offset of 20° from the lateral lip of the bicipital groove, the component would have a proximal 20° of retroversion. Conclusion The results indicate that the bicipital groove can be used as a landmark for prosthetic stem positioning in shoulder arthroplasty. Moreover, it is different from the current standard technique of cutting the proximal humerus at 30° of retroversion with the epicondyles or forearm used as a guide.

Ethnopharmacological relevance The heart wood of Dalbergia odorifera is a Chinese herbal medicine commonly used for the treatment of various ischemic diseases in Chinese medicine practice. Aim of the study In this study, therapeutic angiogenesis effects of the Dalbergia odorifera extract (DOE) were investigated on transgenic zebrafish in vivo and human umbilical vein endothelial cells (HUVECs) in vitro. Materials and methods The pro-angiogenic effects of DOE on zebrafish were examined by subintestinal vessels (SIVs) sprouting assay and intersegmental vessels (ISVs) injury assay. And the pro-angiogenic effects of DOE on HUVECs were examined by MTT, scratch assay, protein chip and western blot. Results In the in vivo studies, we found that DOE was able to dose-dependently promote angiogenesis in zebrafish SIVs area. In addition, DOE could also restore the injury in zebrafish ISVs area and upregulate the reduced mRNA expression of VEGFRs including kdr, kdrl and flt-1 induced by VEGF receptor kinase inhibitor II (VRI). In the in vitro studies, we observed that DOE promoted the proliferation, migration of HUVECs and also restored the injury induced by VRI. Moreover, protein chip and western blot experiments showed the PI3K/MAPK cell proliferation/migration pathway were activated by DOE. Conclusions DOE has a therapeutic effects on angiogenesis, and its mechanism may be related to adjusting the VEGFRs mRNA and activation of PI3K/MAPK signaling pathway. These results suggest a strong potential for Dalbergia odorifera to be developed as an angiogenesis-promoting therapeutic.

BACKGROUND In pregnant women with advanced maternal age (AMA) and fetuses with ultrasonographic (USG) soft markers it is always challenging to decide whether to implement chromosomal microarray analysis (CMA) or not. It is unclear whether CMA should be used in the fetuses with isolated USG soft markers, and there is still a lack of extensive sample research. MATERIAL AND METHODS We enrolled 1521 cases in our research and divided them into 3 groups as follows: pregnant women with isolated AMA (group 1, n=633), pregnant women whose fetuses had isolated USG soft markers (group 2, n=750), and pregnant women with AMA whose fetuses had isolated USG soft markers (group 3, n=138). All pregnant women underwent prenatal ultrasound and amniocentesis, and fetal cells in the amniotic fluid were used for genetic analysis of CMA. All participants signed a written informed consent prior to CMA. RESULTS Abnormal findings were detected by CMA in 330 (21.70%) fetuses, including 37 (2.43%) clinically significant copy number variations (CNVs), 52 (3.42%) benign or likely benign CNVs, and 240 (15.78%) variants of unknown significance. The frequency of clinically significant CNVs in group 1 and group 2 were significantly lower than that in group 3 (2.37% and 2.0% vs 5.07%, P

Background The increasing incidence of radiation-induced osteosarcoma of the maxilla and mandible (RIOSM) has become a significant problem that can limit long-term survival. The purpose of this study was to analyze the association of clinicopathologic characteristics with treatment outcomes and prognostic factors of patients who developed RIOSM after undergoing radiotherapy for nasopharyngeal carcinoma (NPC). Methods We reviewed the medical records of 53,760 NPC patients admitted to Sun Yat-sen University Cancer Center during the period August 1964 to August 2012. Of these patients, 47 who developed RISOM and met inclusion criteria were included in this study. Two of these 47 patients refused treatment and were then excluded. Results For all patients treated for NPC at Sun Yat-sen University Cancer Center during the study period, the total incidence of RIOSM after radiotherapy was 0.084% (47/53,760). Two patients (4.4%) had metastases at the diagnosis of RIOSM. Thirty-nine of the 45 (86.7%) patients underwent surgery for RIOSM; most patients (24/39; 61.5%) who underwent resection had gross clear margins, with 15 patients (38.5%) having either a gross or microscopic positive margin. All patients died. The 1-, 2-, and 3-year overall survival (OS) rates for the entire cohort of 45 patients were 53.3%, 35.6% and 13.5%, respectively. The independent prognostic factors associated with high OS rate were tumor size and treatment type. Conclusions RISOM after radiotherapy for NPC is aggressive and often eludes early detection and timely intervention. Surgery combined with postoperative chemotherapy might be an effective treatment to improve patient survival.

Although advanced interatrial block (aIAB) is an established electrocardiographic phenotype, its prevalence, incidence, and prognostic significance in the general population are unclear. We examined the prevalence, incidence, and prognostic significance of aIAB in 14,625 (mean age = 54 ± 5.8 years; 26% black; 55% female) participants from the Atherosclerosis Risk in Communities (ARIC) study. aIAB was detected from digital electrocardiograms recorded during 4 study visits (1987 to 1989, 1990 to 1992, 1993 to 1995, and 1996 to 1998). Risk factors for the development of aIAB were examined using multivariable Poisson regression models with robust variance estimates. Cox regression was used to compute hazard ratios and 95% CIs for the association between aIAB, as a time-dependent variable, and atrial fibrillation (AF). AF was ascertained from study electrocardiogram data, hospital discharge records, and death certificates thorough 2010. A total of 69 participants (0.5%) had aIAB at baseline, and 193 (1.3%) developed aIAB during follow-up. The incidence for aIAB was 2.27 (95% CI 1.97 to 2.61) per 1,000 person-years. Risk factors for aIAB development included age, male gender, white race, antihypertensive medication use, low-density lipoprotein cholesterol, body mass index, and systolic blood pressure. In a Cox regression analysis adjusted for sociodemographics, cardiovascular risk factors, and potential confounders, aIAB was associated with an increased risk for AF (hazard ratio 3.09, 95% CI 2.51 to 3.79). In conclusion, aIAB is not uncommon in the general population. Risk factors for developing aIAB are similar to those for AF, and the presence of aIAB is associated with an increased risk for AF.

AIMS The main objective of our study was to evaluate the associations between different categories of bundle branch blocks (BBBs) and mortality and to consider possible impact of QRS prolongation in these associations. METHODS This analysis included 15 408 participants (mean age 54 years, 55.2% women, and 26.9% blacks) from the Atherosclerosis Risk in Communities study. We used Cox regression to examine associations between left BBB (LBBB), right BBB (RBBB) and indetermined type of ventricular conduction defect [intraventricular conduction defect (IVCD)] with coronary heart disease (CHD) death and all-cause mortality. RESULTS During a mean 21 years of follow-up, 4767 deaths occurred; of these, 728 were CHD deaths. Compared to No-BBB, LBBB and IVCD were strongly associated with increased CHD death (hazard ratios 4.11 and 3.18, respectively; P

Background— Race and sex differences in silent myocardial infarction (SMI) are not well established. Methods and Results— The analysis included 9498 participants from the Atherosclerosis Risk in Communities (ARIC) study who were free of cardiovascular disease at baseline (visit 1, 1987–1989). Incident SMI was defined as ECG evidence of MI without clinically documented MI (CMI) after the baseline until ARIC visit 4 (1996–1998). Coronary heart disease and all-cause deaths were ascertained starting from ARIC visit 4 until 2010. During a median follow-up of 8.9 years, 317 participants (3.3%) developed SMI and 386 (4.1%) developed CMI. The incidence rates of both SMI and CMI were higher in men (5.08 and 7.96 per 1000-person years, respectively) than in women (2.93 and 2.25 per 1000-person years, respectively; P P =0.217), but whites had higher rate of CMI than blacks (5.04 versus 3.24 per 1000-person years; P =0.002). SMI and CMI (compared with no MI) were associated with increased risk of coronary heart disease death (hazard ratio, 3.06 [95% confidence interval, 1.88–4.99] and 4.74 [95% confidence interval, 3.26–6.90], respectively) and all-cause mortality (hazard ratio, 1.34 [95% confidence interval, 1.09–1.65] and 1.55 [95% confidence interval, 1.30–1.85], respectively). However, SMI and CMI were associated with increased mortality among both men and women, with potentially greater increased risk among women (interaction P =0.089 and 0.051, respectively). No significant interactions by race were detected. Conclusions— SMI represents >45% of incident MIs and is associated with poor prognosis. Race and sex differences in the incidence and prognostic significance of SMI exist that may warrant considering SMI in personalized assessments of coronary heart disease risk.

Aims The aim of this study was to examine the bidirectional association between atrial fibrillation and congestive heart failure (CHF) in older adults. Methods We studied the association of atrial fibrillation at entry with incident CHF (N = 5281; 85% white, 42% male) and the association of CHF at entry with incident atrial fibrillation (N = 5233; 85% white, 42% male) in the Cardiovascular Health Study (CHS). Baseline atrial fibrillation was identified during the study electrocardiogram and by self-reported history, and incident cases were identified during subsequent study electrocardiograms and hospitalization data. Baseline CHF was identified by self-reported history and adjudication of medical records, and incident cases were identified using hospitalization data. Cox regression was used to compute hazard ratios and 95% confidence intervals (CIs) for the association between atrial fibrillation and incident CHF, and CHF and incident atrial fibrillation, separately. Results Over a median follow-up of 12.6 years, 534 (10%) participants developed atrial fibrillation. CHF was associated with an increased risk of atrial fibrillation (hazard ratio 2.0, 95% CI 1.4, 3.0). A total of 1692 (32%) participants developed CHF over a median follow-up of 11.7 years and atrial fibrillation was associated with an increased risk of CHF (hazard ratio 1.9, 95% CI 1.5, 2.2). Conclusion Our results suggest that a bidirectional relationship exists between atrial fibrillation and CHF, with each condition influencing the development of the other.

Background It has been recently reported that the Romhilt-Estes (R-E) score, originally proposed for detection of left ventricular hypertrophy from the electrocardiogram, is a strong predictor of all-cause mortality. Whether the R-E score is also predictive of cardiovascular disease (CVD) and whether its individual components differ in their ability to predict different CVD outcomes are not well established. Methods This analysis includes 13,261 participants from the ARIC study who were free of CVD at baseline (1987-1989). Incident CVD, coronary heart disease (CHD), heart failure (HF), and stroke were ascertained by an adjudication committee through December 2010. The R-E left ventricular hypertrophy score was measured from automatically processed baseline electrocardiogram data. Cox proportional hazard models were used to examine the association between baseline the R-E overall score (overall) and each of its 6 individual components separately, with each of the CVD outcomes. Results During a median follow-up of 21.8 years, 3,579, 2,205, 1,814, and 731 CVD, CHD, HF, and stroke events, respectively, occurred. In multivariable adjusted models, R-E score ≥4 points (compared with 0 points) was associated with increased risk of CVD, CHD, HF, and stroke (hazard ratio [95% CI] 1.66 [1.41-1.96], 1.66 [1.34-2.07], 1.97 [1.60-2.43], and 1.49 [1.07-2.07], respectively). The 6 component of the R-E score varied in their relationship to different CVD outcomes. Conclusions The R-E score is predictive of CVD outcomes. The 6 R-E score components differ in their associations with different CVD outcomes, indicating that they may be electrical biomarkers of different physiological events within the myocardium.

Objectives The aim of this study is to validate the Global Leadership Initiative on Malnutrition (GLIM) criteria and determine the number of Nutritional Risk Screening 2002 (NRS2002)–positive patients who do not meet the GLIM, as well as examine whether these patients would benefit from nutritional support therapy. Methods A reanalysis of a published prospective observational study was performed. The subjects were rediagnosed per the NRS2002 and GLIM criteria. The prevalence of malnutrition was reported, and the difference in rate of infection complications and total complications between the nutritional support therapy and glucose-electrolyte cohorts was calculated. Results Among 1831 cases in the original database, 827 cases (45.2%) were NRS2002-positive. A total of 391 cases were identified by the GLIM criteria as malnourished (21.4%) and of these, subjects in the nutritional support therapy cohort had fewer infection complications than those in the glucose-electrolyte cohort (13.0% vs. 23.0%; P = 0.010). The remaining 436 patients were NRS2002 positive but GLIM negative (23.8%). The rate of infection was also significantly lower in the support cohort than in the nonsupport cohort (8.0% vs. 15.7%; P = 0.011). Nutritional support was proven o be a protective factor for infection complications in both GLIM-positive (odds ratio: 0.407; 95% confidence interval, 0.232–0.714; P = 0.002) and NRS2002-positive/GLIM-negative patients [odds ratio: 0.314; 95% confidence interval, 0.161–0.612; P = 0.001). Conclusions The GLIM criteria have been validated, and are useful in identifying malnourished patients who may have fewer infection complications due to nutritional support therapy. However, the criteria neglected half of the patients identified by NRS2002, among whom nutritional support therapy also decreased the rate of infection complications.

Background To investigate the clinical and molecular characteristics of Chinese children with maturity onset diabetes of the young (MODY). Methods A total of 42 Chinese patients suspected MODY referred to our unit from 2014 to 2018 were enrolled. Mutational analysis of monogenic diabetes mellitus genes was performed by next-generation sequencing and confirmed by Sanger sequencing. Results There were 28 males (66.7%) and 14 females (33.3%) with a mean age of 9.49 ± 3.46 years (range, 1.4–15.3 years) and a mean birth weight of 3.38 ± 0.49 kg (range, 2.55–4.90 kg). Among these patients, 15 patients had polyuria, polydipsia or weight loss. Two patients (4.8%) were obese and six (14.3%) were overweight. Moreover, 13 patients (30.9%) had a family history of diabetes. Thirty variants were identified in 28 patients. Twenty-six variants in 25 patients were pathogenic or likely pathogenic genes (59.5%, 25/42), including 15 patients (60.0%, 15/25) with GCK mutation, four (16.0%, 4/25) with PAX4 mutation, three (12.0%, 3/25) with HNF4A mutation, one (4.0%, 1/25) with INS mutation, one (4.0%, 1/25) with NEUROD1 mutation and one (4.0%, 1/25) with HNF1A mutation. Nine mutations (36.0%, 9/25) were novel. There was no difference between mutation-suspected patients and MODY-confirmed patients except for a 2-h glucose increment in an oral glucose tolerance test (OGTT), while the GCK-MODY had lower glycated hemoglobin (HbA1c) and a significantly smaller 2-h glucose increment in an OGTT compared with transcription factor MODYs. The GCK-MODY was identified by incidental hyperglycemia without glycosuria. GCK-MODY without drug management and hepatocyte nuclear factor-1 alpha (HNF4A) or HNF1A-MODY with sulfonylurea therapy obtained good glucose controlling. Conclusions Mutation of the GCK gene is the most common in MODY patients in China followed by PAX4. The screening criteria can improve the cost-effectiveness of disease diagnosis and treatment. A precise molecular diagnosis would lead to optimal treatment of the patients.

To investigate theA total of 302 pregnant women with the history of adverse pregnancy were chosen as respondents (an experimental group) in the hospital from March 2012 to December 2015, and 197 pregnant women without the history of adverse pregnancy as a control group. TOX-IgG and TOX-IgM were detected by using ELISA in two groups. The risk factors ofThe total positive rate of[摘要] 目的调查河北省霸州地区不良妊娠史孕妇弓形虫感染状况及其危险因素。

To compare survival effects of comprehensive neck dissection (CND) and selective neck dissection (SND) for patients with nasopharyngeal carcinoma (NPC) with only regional failure.A total of 294 recurrent T0N1-3M0 NPC patients who underwent neck dissection in Sun Yat-Sen University Cancer Center, Guangzhou, People's Republic of China, between January 1984 and February 2014, were enrolled in the survival and interaction analyses. Using propensity scores to adjust for potential prognostic factors, an additional well-balanced cohort of 210 patients was constructed by matching each patient who received SND with one patient who underwent CND (1:1); the differences were then compared between SND and CND in terms of overall survival (OS), local recurrence-free survival (LRFS), regional recurrence-free survival (RRFS), and distant metastasis-free survival (DMFS).Both univariate and multivariate analyses showed that SND was not inferior to CND (P 0.05) but demonstrated that extracapsular spread (ECS) (hazard ratio [HR] 3.49, 95% confidence interval [CI] 2.30-5.29, P 0.001), recurrent N stage (rN stage) (HR 1.96, 95% CI 1.29-2.97, P = 0.002), and positive margins (HR 3.67, 95% CI 2.40-5.62, P 0.001) were independent poor prognostic factors for OS. The interaction effects between the dissection style and each independent factor were not significant for OS, LRFS, RRFS, or DMFS (P 0.05). Furthermore, no survival differences were found between SND and CND in the case-matched cohort in terms of OS, LRFS, RRFS, or DMFS (P = 0.550, 0.930, 0.214, and 0.146, respectively).With a similar radical dissection extent around the tumor rather than dissection of extensive lymph region distal to the lesion, SND is not inferior to CND for patients with NPC with only cervical failure. ECS, rN stage, and positive margins were adverse independent prognostic factors for patients with NPC.4 Laryngoscope, 129:387-395, 2019.

Introduction We evaluated repolarization-related predictors of coronary heart disease (CHD) death and sudden cardiac death (SCD) in men and women with cardiovascular disease (CVD) in the Atherosclerosis Risk in Communities (ARIC) study. Methods and results Hazard ratios (HR) from Cox regression were computed for 11 ECG measures of repolarization in 1384 subjects (50% women) 45 to 65 years of age. The average follow-up was 14 years. Based on electrophysiological considerations the spatial angle between Tpeak and normal repolarization reference vector [Ѳ(Tp|Tref)], STJV6 amplitude, QRS duration and Tonset and Tpeak vector magnitude ratio (ToV/TpV) were considered as primary candidates for independent mortality predictors, and as an alternative set TaVR and TV1 amplitudes and the spatial angle between the initial and terminal T vectors [Ѳ(Tinit|Tterm)]. From the primary set [Ѳ(Tp|Tref)] was a strong independent predictor for CHD death (nearly 4-fold increased risk in men and 2-fold increased risk in women) and for SCD [Ѳ(Tinit|Tterm)] in men (3.4-fold increased risk) and (ToV/TpV) in women (7.76-fold increased risk). From the alternative set of independent predictors TaVR amplitude negativity reduced to less than 150 μV (1.5 mm) was a strong mortality predictor with an approximately 3-fold increased risk for CHD death and SCD in men and women. Conclusions The strongest independent predictors of CHD death were [Ѳ(Tp|Tref)] in men and TaVR in women and of SCD were [Ѳ(Tp|Tref)] in men and ToV/TpV in women. Overall, TaVR amplitude negativity reduced to less than 150 μV (1.5 mm) was the most consistent mortality predictor in all subgroups. These ECG variables may warrant consideration for identification of high risk men and women for more intense preventive intervention.

The prevalence and determinants of QRS transition zones are not well established.We examined the distributions of Normal, clockwise (CW) and counterclockwise (CCW)) QRS transition zones and their relations to disease, body size and demographics in 4624 black and white men and women free of cardiovascular disease and major ECG abnormalities enrolled in the NHANES-III survey.CW transition zones were least observed (6.2%) and CCW were most prevalent (60.1%) with Normal in an intermediate position (33.7%). In multivariable logistic regression analysis, the adjusted, significant predictors for CCW compared to Normal were a greater proportion of blacks and women, fewer thin people (BMI20, thin), a greater ratio of chest depth to chest width, and an LVMass index80g. By contrast, CW persons were older, had larger QRS/T angles, smaller ratio of chest depth to chest width, had a greater proportion of subjects with low voltage QRS, more pulmonary disease, a greater proportion with high heart rates, shorter QRS duration and were more obese (BMI≥30).Normal rather than being the most prevalent transition zone was intermediate in frequency between the most frequently encountered CCW and the least frequently encountered transition zone CW. Differences in the predictors of CW and CCW exist. This requires further investigation to examine how far these differences explain the differences in the published prognostic differences between CW and CCW.

Ambient particulate matter (PM) air pollution exposure has been associated with increases in QT interval duration (QT). However, innate susceptibility to PM-associated QT prolongation has not been characterized.To characterize genetic susceptibility to PM-associated QT prolongation in a multi-racial/ethnic, genome-wide association study (GWAS).Using repeated electrocardiograms (1986–2004), longitudinal data on PM10 μm in diameter (PMA common variant (rs1619661; coded allele:The findings suggest that biologically plausible genetic factors may alter susceptibility to PM

Reduced cardiac vagal control reflected in low heart rate variability (HRV) is associated with greater risks for cardiac morbidity and mortality. In two-stage meta-analyses of genome-wide association studies for three HRV traits in up to 53,174 individuals of European ancestry, we detect 17 genome-wide significant SNPs in eight loci. HRV SNPs tag non-synonymous SNPs (in NDUFA11 and KIAA1755), expression quantitative trait loci (eQTLs) (influencing GNG11, RGS6 and NEO1), or are located in genes preferentially expressed in the sinoatrial node (GNG11, RGS6 and HCN4). Genetic risk scores account for 0.9 to 2.6% of the HRV variance. Significant genetic correlation is found for HRV with heart rate (−0.74, Heart rate variability (HRV) describes the individual variation in cardiac cycle duration and is a measure of vagal control of heart rate. Here, the authors identify seventeen single-nucleotide polymorphisms associated with HRV, lending new insight into the vagal regulation of heart rhythm.

Involuntary unemployment due to job loss has been associated with increased risk of cardiovascular events. Whether it also is associated with increased risk of atrial fibrillation (AF) is currently unknown. Therefore, we examined this association in 8,812 participants residing mainly in the Southeastern United States (mean age 58.1 ± 7.8 years; 63.2%; women; 43.2% black) with data on employment status who were enrolled in the REasons for Geographic And Racial Differences in Stroke study between 2003 and 2007 after excluding those with voluntary unemployment (retiree, homemakers, and students). AF was identified by electrocardiogram and past medical history at the same period. The cross-sectional association between status and type of unemployment with AF was examined in multivariable logistic regression models. Additional analysis in 4,273 participants without baseline AF and with data on incident AF collected in a follow-up visit occurred after a median of 9.4 years from baseline was also conducted. In a model adjusted for socio-demographics, health insurance, income, perceived stress, and cardiovascular risk factors, unemployment was associated with 60% increased odds of AF (odds ratio [95% confidence interval] 1.60 (1.24, 2.07)). This association was consistent in subgroups stratified by median age, gender, race, education, income, and health insurance status. Similarly, unemployment was associated with AF in those without AF at baseline who developed incident AF (odds ratio [95% confidence interval] 1.54 (1.04, 2.37)). In conclusion, involuntary unemployment is associated with increased risk of AF. This may call for considering socioeconomic determinants such as unemployment as part of the preventive strategies for AF.

Background— The P wave on an ECG is a measure of atrial electric function, and its characteristics may serve as predictors for atrial arrhythmias. Increased mean P-wave duration and P-wave terminal force traditionally have been used as markers for left atrial enlargement, and both have been associated with increased risk of atrial fibrillation. Here, we explore the genetic basis of P-wave morphology through meta-analysis of genome-wide association study results for P-wave duration and P-wave terminal force from 12 cohort studies. Methods and Results— We included 44 456 individuals, of which 6778 (16%) were of African ancestry. Genotyping, imputation, and genome-wide association study were performed at each study site. Summary-level results were meta-analyzed centrally using inverse-variance weighting. In meta-analyses of P-wave duration, we identified 6 significant ( P − 8 ) novel loci and replicated a prior association with S CN10A. We identified 3 loci at SCN5A , TBX5 , and CAV1/CAV2 that were jointly associated with the PR interval, PR segment, and P-wave duration. We identified 6 novel loci in meta-analysis of P-wave terminal force. Four of the identified genetic loci were significantly associated with gene expression in 329 left atrial samples. Finally, we observed that some of the loci associated with the P wave were linked to overall atrial conduction, whereas others identified distinct phases of atrial conduction. Conclusions— We have identified 6 novel genetic loci associated with P-wave duration and 6 novel loci associated with P-wave terminal force. Future studies of these loci may aid in identifying new targets for drugs that may modify atrial conduction or treat atrial arrhythmias.

Repolarization abnormalities in the setting of bundle branch blocks (BBB) are generally ignored. We used Cox regression models to determine hazard ratios (HRs) with 95% confidence intervals (CIs) for incident heart failure (HF) associated with wide spatial and frontal QRS/T angle (upper twenty-fifth percentile of each) in men and women with and without BBB. This analysis included 14,478 participants (54.6% women, 26.4% blacks, 377 [2.6%] with BBB) from the Atherosclerosis Risk in Communities Study who were free of HF at baseline. Using No-BBB with normal spatial QRS/T angle as the reference group, the risk for HF in multivariable adjusted models was increased 51% for No-BBB with wide spatial QRS/T angle (HR 1.51, 95% CI 1.37 to 1.66), 48% for BBB with normal spatial QRS/T angle (HR 1.48, 95% CI 1.17 to 1.88), and the risk for incident HF was increased more than threefold for BBB with wide spatial QRS/T angle (HR 3.37, 95% CI 2.47 to 4.60). The results were consistent across subgroups by gender. Similar results were observed for the frontal plane QRS/T angle. In the pooled BBB group excluding right BBB, a positive T wave in lead aVR and heart rate 70 bpm and higher were also potent predictors of incident HF similar to the QRS/T angles. In conclusion, both BBB and wide QRS/T angles are predictive of HF, and concomitant presence of both carries a much higher risk than for either predictor alone. These findings suggest that repolarization abnormalities in the setting of BBB should not be considered benign or an expected consequence of BBB.

Data are limited about race-and sex-associated differences in prognostically important ECG measures of regional repolarization.The normal reference group from the Atherosclerosis Risk in Communities (ARIC) study included 8,676 white and African-American men and women aged 40-65 years. Exclusion criteria included cardiovascular disease, hypertension, diabetes and major ECG abnormalities. Notable sex differences (p0.001) were observed in the upper 98% limits for rate-adjusted QTend (QTea) which was 435 ms in white and African-American men and 445 ms in white and African-American women, and for left ventricular epicardial repolarization time (RTepi) which was 345 ms in white and African-American men and 465 ms in white and African-American women. These sex differences reflect earlier onset and end of repolarization in men than in women. Upper normal limits for STJ amplitude in V2-V3 were 100 μV in white and African-American women, 150 μV in white men and 200 μV in African-American men (p0.001 for sex differences), and for other chest leads, aVL and aVF 50 μV in white women, 100 μV in African-American women, 100 μV in white men and 150 μV in African-American men (p0.001 for sex and race differences).Shorter QTea and RTepi in men than in women reflect earlier onset and end of repolarization in men. STJ amplitudes in African-American men were higher than in other subgroups by race and sex. These sex and race differences need to be considered in clinical and epidemiological applications of normal standards.

Double eyelidplasty has 3 key factors: motor power, connecting tissue, and skin adhesion.To create natural double eyelid, new anatomy structure should be rebuilt according to physiological double eyelid in these 3 aspects.Levator aponeurosis is used as "connecting tissue" to transmit dynamic "motor power" of levator muscle to upper eyelid, and "skin adhesion" is induced between levator aponeurosis and skin in a plane manner. Postoperation evaluation includes stability of double eyelid, asymmetry, double fold curve, and scar formation.A total of 119 patients were operated on in this study. Two hundred fourteen eyes (89.9%) showed good fold curve and 13 eyes (5.5%) showed fair results. No scar on the upper eyelid was encountered, 24 patients (20.2%) had fair scar formation and 89 patients (74.8%) had no prominent scar.This novel surgical technique utilized pretarsal levator aponeurosis as the connecting material to bridge levator muscle and upper eyelid skin; by establishing a direct force transmission mechanism, palpebral crease is created in a more natural way in terms of anatomy and physiology. Furthermore, skin adhesion is formed between levator aponeurosis and dermis in a planar manner, allowing for more stable palpebral crease and more preserved orbicularis oculi in situ, thereby minimizing eyelid scar formation.

The risk of incident hospitalized heart failure (HF) was evaluated for 23 electrocardiographic (ECG) variables in men and women free from cardiovascular disease. The hazard ratios with 95% confidence intervals were determined from Cox regression analysis for 13,428 participants 45 to 65 years old in the Atherosclerosis Risk in Communities (ARIC) study. New-onset HF during a 14-year follow-up period occurred in 695 men (11.9%) and 721 women (9.5%). Several ECG variables were significant predictors of incident HF when evaluated as single ECG variables. Predominant among them were spatial angles, reflecting deviations of the direction of the repolarization sequence from the normal reference direction. After controlling for collinearity among the ECG variables, the spatial angle between T peak and normal T reference vectors, Ө(T p |T ref ), was a significant independent predictor in men (HF risk increased 31%) and women (HF risk increased 46%). Other independent predictors in men included epicardial repolarization time (62% increased risk) and T wave peak to T wave end (T p T e ) interval, reflecting global dispersion of repolarization (27% increased risk). The independent predictors in women, in addition to Ө(T p |T ref ), were Ө(R|STT) the spatial angle between the mean QRS and STT vectors (54% increased risk) and QRS nondipolar voltage (46% increased risk). In conclusion, wide Ө(T p |T ref ), wide Ө(R|STT), and increased QRS nondipolar voltage in women and wide Ө(T p |T ref ), increased epicardial repolarization time, prolonged T p T e interval and T wave complexity in men were independent predictors of incident HF, and the presence of these abnormal findings could warrant additional diagnostic evaluation for possible preventive action for HF.

Background Genome-wide association studies have identified several genetic loci associated with variation in resting heart rate in European and Asian populations. No study has evaluated genetic variants associated with heart rate in African Americans. Objective To identify novel genetic variants associated with resting heart rate in African Americans. Methods Ten cohort studies participating in the Candidate-gene Association Resource and Continental Origins and Genetic Epidemiology Network consortia performed genome-wide genotyping of single nucleotide polymorphisms (SNPs) and imputed 2,954,965 SNPs using HapMap YRI and CEU panels in 13,372 participants of African ancestry. Each study measured the RR interval (ms) from 10-second resting 12-lead electrocardiograms and estimated RR-SNP associations using covariate-adjusted linear regression. Random-effects meta-analysis was used to combine cohort-specific measures of association and identify genome-wide significant loci ( P ≤2.5×10 −8 ). Results Fourteen SNPs on chromosome 6q22 exceeded the genome-wide significance threshold. The most significant association was for rs9320841 (+13 ms per minor allele; P = 4.98×10 −15 ). This SNP was approximately 350 kb downstream of GJA1 , a locus previously identified as harboring SNPs associated with heart rate in Europeans. Adjustment for rs9320841 also attenuated the association between the remaining 13 SNPs in this region and heart rate. In addition, SNPs in MYH6 , which have been identified in European genome-wide association study, were associated with similar changes in the resting heart rate as this population of African Americans. Conclusions An intergenic region downstream of GJA1 (the gene encoding connexin 43, the major protein of the human myocardial gap junction) and an intragenic region within MYH6 are associated with variation in resting heart rate in African Americans as well as in populations of European and Asian origin.

Objective The aim of this study was to analyze whether pathologic complete response (PCR) to neoadjuvant chemotherapy (NAC) affected long-term survival in advanced head and neck squamous cell carcinoma (HNSCC) patients. Materials All patients with advanced HNSCC were previously untreated and underwent NAC followed by surgery. The 5-year overall survival, disease-free survival, local control rate, and reasons for treatment failure were analyzed. Results A total of 101 cases were included, and the response rate to NAC was 67.3%, including 17 patients (16.8%) who achieved PCR. The 5-year overall survival (OS) of the PCR group (82.4%; histologically complete response group [HCG]) was higher than that of the pathologic incomplete responder group (45.4%; histologically incomplete response group [HICG]) (P = 0.045). No statistically significant difference was noted between the two groups in terms of local recurrence and nodal recurrence, but the local control rate in HCG (88.2%) was higher than that in HICG (62.7%) (P = 0.034). Conclusions Achieving PCR could improve locoregional control and long-term survival in patients with advanced HNSCC.

Background— Ethnic differences in cardiac arrhythmia incidence have been reported, with a particularly high incidence of sudden cardiac death and low incidence of atrial fibrillation in individuals of African ancestry. We tested the hypotheses that African ancestry and common genetic variants are associated with prolonged duration of cardiac repolarization, a central pathophysiological determinant of arrhythmia, as measured by the electrocardiographic QT interval. Methods and Results— First, individual estimates of African and European ancestry were inferred from genome-wide single-nucleotide polymorphism (SNP) data in 7 population-based cohorts of African Americans (n=12 097) and regressed on measured QT interval from ECGs. Second, imputation was performed for 2.8 million SNPs, and a genome-wide association study of QT interval was performed in 10 cohorts (n=13 105). There was no evidence of association between genetic ancestry and QT interval ( P =0.94). Genome-wide significant associations ( P –8 ) were identified with SNPs at 2 loci, upstream of the genes NOS1AP (rs12143842, P =2×10 –15 ) and ATP1B1 (rs1320976, P =2×10 –10 ). The most significant SNP in NOS1AP was the same as the strongest SNP previously associated with QT interval in individuals of European ancestry. Low probability values ( P –5 ) were observed for SNPs at several other loci previously identified in genome-wide association studies in individuals of European ancestry, including KCNQ1 , KCNH2 , LITAF , and PLN . Conclusions— We observed no difference in duration of cardiac repolarization with global genetic indices of African American ancestry. In addition, our genome-wide association study extends the association of polymorphisms at several loci associated with repolarization in individuals of European ancestry to include individuals of African ancestry.

Higher resting heart rate (RHR) is associated with increased risk of all-cause and cardiovascular mortality, with some reports showing the magnitude of association with all-cause mortality being stronger than that with cardiovascular mortality. This suggests that RHR association with mortality may not be limited to cardiovascular death. We compared the association between RHR with cardiovascular and noncardiovascular mortality in 6,743 participants (mean age 58.7 years, 52% women, 48% non-Hispanic whites) from the Third National Health and Nutrition Examination Survey (NHANES-III) after excluding those on antiarrhythmic drugs or with missing data. RHR data were obtained from standard 12-lead electrocardiogram recorded on the NHANES participants during a physical examination. National Death Index was used to identify the date and cause of death. Multivariable Cox proportional hazards analysis was used to calculate the hazard ratios (HRs) and 95% CIs for cardiovascular mortality and noncardiovascular mortality, separately, associated with 10 beats/min increase in RHR. During a median follow-up of 13.9 years, 906 cardiovascular deaths and 1,306 noncardiovascular deaths occurred. In models adjusted for age, gender, race, hypertension, diabetes, obesity, dyslipidemia, previous cardiovascular disease, smoking, cancer, chronic obstructive airway disease, thyroid disease, and serum creatinine, higher RHR was associated with increased risk of both cardiovascular mortality and noncardiovascular mortality with a relatively similar magnitude of risk (HR 1.19, 95% CI 1.12 to 1.26 and HR 1.23, 95% CI 1.17 to 1.29, respectively). In conclusion, higher RHR is associated with both cardiovascular mortality and noncardiovascular mortality suggesting that RHR is probably a marker of overall well-being rather than a marker of cardiovascular health.

© The Author 2016. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com. The electrocardiographic QRS duration, a measure of ventricular depolarization and conduction, is associated with cardiovascular mortality. While single nucleotide polymorphisms (SNPs) associated with QRS duration have been identified at 22 loci in populations of European descent, the genetic architecture of QRS duration in non-European populations is largely unknown. We therefore performed a genome-wide association study (GWAS) meta-analysis of QRS duration in 13,031 African Americans from ten cohorts and a transethnic GWAS meta-analysis with additional results from populations of European descent. In the African American GWAS, a single genome-wide significant SNP association was identified (rs3922844, P = 4 × 10-14) in intron 16 of SCN5A, a voltage-gated cardiac sodium channel gene. The QRS-prolonging rs3922844 C allele was also associated with decreased SCN5A RNA expression in human atrial tissue (P = 1.1 × 10-4). High density genotyping revealed that the SCN5A association region in African Americans was confined to intron 16. Transethnic GWAS meta-analysis identified novel SNP associations on chromosome 18 in MYL12A (rs1662342, P = 4.9 × 10-8) and chromosome 1 near CD1E and SPTA1 (rs7547997, P = 7.9 × 10-9). The 22 QRS loci previously identified in populations of European descent were enriched for significant SNP associations with QRS duration in African Americans (P = 9.9 × 10-7), and index SNP associations in or near SCN5A, SCN10A, CDKN1A, NFIA, HAND1, TBX5 and SETBP1 replicated in African Americans. In summary, rs3922844 was associated with QRS duration and SCN5A expression, two novel QRS loci were identified using transethnic meta-analysis, and a significant proportion of QRS-SNP associations discovered in populations of European descent were transferable to African Americans when adequate power was achieved.

Background Frontal QRS-T angle reflects changes in regional action potential duration and the direction of repolarization. Although it has been suggested that abnormal ventricular repolarization predisposes to atrial arrhythmias, it is unknown whether abnormal frontal QRS-T angle is associated with an increased risk of atrial fibrillation (AF). Methods We examined the association between frontal QRS-T angle and AF in 4282 participants (95% white; 41% male) from the Cardiovascular Health Study (CHS). QRS-T angle was computed from baseline electrocardiogram data. Abnormal QRS-T angle was defined as values greater than the sex-specific 95th percentile (men >131°; women: >104°). AF cases were identified from study electrocardiograms and from hospitalization discharge data through December 31, 2010. Cox regression was used to compute hazard ratios (HR) and 95% confidence intervals (CI) for the association between abnormal QRS-T angle and AF. Results Over a median follow-up of 12.1 years, a total of 1276 (30%) participants developed AF. In a Cox regression model, adjusted for socio-demographics and known AF risk factors, abnormal QRS-T angle was associated with a 55% increased risk of AF (HR = 1.55, 95%CI = 1.23, 1.97). When QRS-T angle was examined as a continuous variable, each 10° increase was associated with a 3% increased risk of AF (HR = 1.03, 95%CI = 1.01, 1.05). This finding was consistent in subgroups stratified by age, sex, and race. Conclusion Our findings suggest that an abnormal frontal QRS-T angle on the electrocardiogram provides important prognostic information regarding AF risk in the elderly, and further implicate ventricular repolarization abnormalities in the pathogenesis of AF.