DeepConsensus improves the accuracy of sequences with a gap-aware sequence transformer.

Circular consensus sequencing with Pacific Biosciences (PacBio) technology generates long (10-25 kilobases), accurate 'HiFi' reads by combining serial observations of a DNA molecule into a consensus sequence. The standard approach to consensus generation, pbccs, uses a hidden Markov model. We introduce DeepConsensus, which uses an alignment-based loss to train a gap-aware transformer-encoder for sequence correction. Compared to pbccs, DeepConsensus reduces read errors by 42%. This increases the yield of PacBio HiFi reads at Q20 by 9%, at Q30 by 27% and at Q40 by 90%. With two SMRT Cells of HG003, reads from DeepConsensus improve hifiasm assembly contiguity (NG50 4.9 megabases (Mb) to 17.2 Mb), increase gene completeness (94% to 97%), reduce the false gene duplication rate (1.1% to 0.5%), improve assembly base accuracy (Q43 to Q45) and reduce variant-calling errors by 24%. DeepConsensus models could be trained to the general problem of analyzing the alignment of other types of sequences, such as unique molecular identifiers or genome assemblies.

The central arterial stiffness parameters in decompensated versus compensated states of heart failure: a paired comparative cohort study.

BACKGROUND: Arterial stiffness is strongly linked to the pathogenesis of heart failure and the development of acute decompensation in patients with stable chronic heart failure. This study aimed to compare arterial stiffness indices in patients with heart failure with reduced ejection fraction (HFrEF) during the acute decompensated state, and three months later after hospital discharge during the compensated state. RESULTS: One hundred patients with acute decompensated HFrEF (NYHA class III and IV) and left ventricular ejection fraction ≤ 35% were included in the study. During the initial and follow-up visits, all patients underwent full medical history taking, clinical examination, transthoracic echocardiography, and non-invasive pulse wave analysis by the Mobil-O-Graph 24-h device for measurement of arterial stiffness. The mean age was 51.6 ± 6.1 years and 80% of the participants were males. There was a significant reduction of the central arterial stiffness indices in patients with HFrEF during the compensated state compared to the decompensated state. During the decompensated state, patients presented with NYHA FC IV (n = 64) showed higher AI (24.5 ± 10.0 vs. 16.8 ± 8.6, p < 0.001) and pulse wave velocity (9.2 ± 1.3 vs. 8.5 ± 1.2, p = 0.021) than patients with NYHA FC III, and despite the relatively smaller number of females, they showed higher stiffness indices than males. CONCLUSIONS: Central arterial stiffness indices in patients with HFrEF were significantly lower in the compensated state than in the decompensated state. Patients with NYHA FC IV and female patients showed higher stiffness indices in their decompensated state of heart failure.

Coronary tortuosity relation with carotid intima-media thickness, coronary artery disease risk factors, and diastolic dysfunction: is it a marker of early atherosclerosis?

BACKGROUND: Coronary tortuosity (C-Tor) is a common finding in coronary angiography (CAG). There are conflicting data about its link to atherosclerosis: one study found a negative relationship with coronary artery disease (CAD), although it had been linked to age and hypertension (HTN), which are CAD risk factors. Carotid intima-media thickness (C-IMT) is a measure of early atherosclerosis and a surrogate for CAD, diastolic dysfunction is also associated with CAD risk factors. In this retrospective case-control study, we investigated the relationship between C-Tor, C-IMT, diastolic dysfunction, and the other risk factors in patients undergoing CAG in a tertiary hospital between July 2017 and June 2018, after excluding patients with significant CAD. C-Tor was defined as the presence of ≥ 3 bends (≥ 45°) along the trunk of at least one main coronary artery in CAG. RESULTS: After excluding 663 patients due to exclusion criteria, 30 patients with C-Tor were compared with age and gender-matched controls. HTN was significantly more common in the C-Tor group (86.7% vs. 30%, p < 0.002); other clinical characteristics were similar. The C-IMT was abnormal in the C-Tor group only (p: 0.007). The diastolic dysfunction parameters differed between the two groups: the E/A ratio was < 1 in the C-Tor group and > 1 in the normal group (p: < 0.001); the E velocity and deceleration time were significantly lower in the C-Tor group (p: 0.001 and < 0.001 respectively); the E/E' ratio, A, and A' velocities were significantly higher (p: 0.005, < 0.001, < 0.001 respectively); while the S' velocity was similar in the 2 groups (p: 0.078). The C-Tor group had higher total cholesterol and LDL (p: 0.003 and 0.006 respectively). All C-Tor patients undergoing stress tests had positive results. The only independent C-Tor predictors in a regression analysis were HTN, total cholesterol, A-wave velocity, and deceleration time (DT) (odds ratio: 14.7, 1.03, 1.15, and 0.95, all p: < 0.05). A-wave velocity had the best area under the curve, sensitivity, and specificity for C-Tor prediction (0.88, 73.3%, and 96.7% respectively) followed by DT (0.86, 66.67%, and 96.6% respectively). CONCLUSION: C-Tor is associated with increased C-IMT, HTN, hyperlipidemia, and left ventricular diastolic dysfunction; all contributing to an ongoing atherosclerotic process. A-wave velocity and DT were independent predictors of C-Tor. C-Tor may cause microvascular ischemia that merits further investigation.

Bariatric surgery and cardiovascular outcome.

BACKGROUND: Obesity is recognized as a classic risk factor for atherosclerosis and subsequent cardiovascular disease (CVD). Weight loss after bariatric surgery has been associated with reduced CV mortality and total mortality in obese patients. Our aim was to study the impact of bariatric surgery on CV risk profile, cardiac structure, and function postoperatively. RESULTS: This prospective longitudinal study included 100 morbidly obese patients at final analysis. All patients were subjected to full clinical, laboratory, and echocardiographic examination at baseline and 6 months after bariatric surgery. The mean age of study population was 37.2 ± 10.49 with BMI of 47 ± 6.82. Females represented 84%. Sleeve gastrectomy and Roux-en-Y gastric bypass were performed in 79% and 21%, respectively. Surgery-related mortality and morbidity were 0.94% and 4.7%, respectively. After 6 months, there were significant decreases in BMI, heart rate, SBP, DBP, and Framingham risk score (P < 0.0001). The prevalence of risk factors decreased as follows: hypertension 24% vs. 12%, P = 0.0005; DM 21% vs. 11%, P = 0.002; dyslipidemia 32% vs. 7%, P < 0.0001; and metabolic syndrome 54% vs. 26%, P < 0.0001. Highly significant (P < 0.0001) decrease in fasting PG and 2 h PP-PG, HbA1c, ASL, ALT, fasting total cholesterol, LDL, TG, and increase in HDL were observed after bariatric surgery. There were significant shortening in QTc interval (P = 0.009), decrease in LV dimensions and LV mass index (P < 0.0001), and increase in LV EF% (P = 0.0003). BMI at follow-up showed significant positive correlation with age, Framingham risk score, and preoperative BMI (r = 0.289, P = 0.0036; r = 0.37, P = 0.0054; and r = 0.31, P = 0.0081, respectively). CONCLUSION: In addition to enabling patients to achieve a substantial weight loss, bariatric surgery provides a myriad of health benefits. Weight reduction was associated with a favorable improvement in cardiovascular risk profile, cardiac structure, and function.

Additional diagnostic accuracy of global longitudinal strain at peak dobutamine stress in patients with moderate pretest probability of coronary artery disease.

BACKGROUND: Previous studies confirmed the feasibility of 2D speckle tracking echocardiography (2D STE) during dobutamine stress echocardiography (DSE) in assessing myocardial ischemia in patients with previous myocardial infarction. It is unknown whether it improves the diagnostic accuracy in young patients with intermediate pretest probability for coronary artery disease (CAD) and no prior cardiovascular events. METHODS: We prospectively studied 101 patients by DSE and STE, followed by coronary angiography within 1 month. Significant CAD was defined as diameter stenosis ≥ 50%. Receiver operating characteristic analysis obtained global longitudinal strain (GLS) cutoff values of significant area under the curve (AUC). RESULTS: Mean age: 53 ± 8 years, 56% females, 49 had significant CAD (group 1) and 52 had normal/mild CAD (group 2); no significant baseline differences except more males in group 1 (P: .002). DSE sensitivity and specificity for CAD were 79.6% and 92.3%, respectively, positive predictive value (PPV): 90.6%, negative predictive value (NPV): 82.7%, and diagnostic accuracy: 86%. At peak stress, all strain parameters were significantly lower in group 1. However, GLS had the highest AUC: 0.88, P: <.001. GLS cutoff value ≤ -20.5 had 89.8% sensitivity, 84.6% specificity, 84.6% PPV, 89.8% NPV, and 87% diagnostic accuracy. Combining GLS cutoff with DSE had higher AUC than either alone (0.9, P < .001): 95.9% sensitivity, 84.6% specificity, 85.5% PPV, 95.7% NPV, and 90% diagnostic accuracy. CONCLUSION: 2D-STE-derived GLS increases DSE precision to detect CAD in intermediate pretest probability patients: It improves DSE sensitivity, NPV, and accuracy. It is reproducible and has comparable specificity.

Assessment of vascular stiffness using different modalities in patients with systemic lupus erythematosus: a case control study.

BACKGROUND: Cardiovascular disease is a major cause of morbidity and mortality in systemic lupus erythematosus (SLE) patients. Accurate risk stratification would require a simple, non-invasive index integrating all traditional and emerging risk factors. Vascular stiffness fulfills these requirements and has better predictive value for cardiovascular events than traditional risk factors in hypertensives and patients with coronary artery disease. Our aim was to determine whether arterial stiffness is increased in SLE patients compared to healthy controls and to correlate the arterial stiffness in SLE patients with cardiovascular risk factors, namely, hypertension and diabetes mellitus. RESULTS: This study included 50 SLE patients and 50 age- and gender-matched healthy individuals. SLE patients had higher median aortic stiffness index (SI) and lower strain and distensibility, compared to controls (p value for all < 0.001). SLE patients had significantly impaired flow-mediated dilation (FMD) compared to controls: the median (range) in SLE patients was 8.82 (2.5-21.87), compared to 19 (12-37.5) in controls (z = - 7.695, p ˂ 0.001). Regarding quality arterial stiffness (QAS) parameters, SLE patients had significantly lower median carotid distension, distensibility coefficient, and compliance coefficient, with higher median carotid SI, carotid pulse wave velocity (PWV), and augmentation index (AI), compared to controls (p value for all ≤ 0.001). SLE patients had a higher median cf-PWV 6.5 m/s (4.8-11.8), compared to a median of 4.6 m/s (3.8-6.9) in controls (z = - 8.193, p ˂ 0.001). Linear regression analysis to adjust for hypertension and diabetes mellitus yielded a statistically significant difference between both groups for all of the above parameters (p = 0.014 for maximum carotid intima media thickness (IMT) and < 0.001 for remaining parameters), with the exception of the maximum carotid augmentation index (p = 0.184). CONCLUSION: SLE patients have significantly increased arterial stiffness and impaired FMD compared to healthy controls. This is true even after adjusting for hypertension and diabetes mellitus, highlighting the fact that SLE could be an independent cardiovascular risk factor. These findings emphasize the need for early management of SLE together with aggressive risk factor modification.

Quantifying Sex Bias in Clinical Studies at Scale With Automated Data Extraction.

Importance: Analyses of female representation in clinical studies have been limited in scope and scale. Objective: To perform a large-scale analysis of global enrollment sex bias in clinical studies. Design, Setting, and Participants: In this cross-sectional study, clinical studies from published articles from PubMed from 1966 to 2018 and records from Aggregate Analysis of ClinicalTrials.gov from 1999 to 2018 were identified. Global disease prevalence was determined for male and female patients in 11 disease categories from the Global Burden of Disease database: cardiovascular, diabetes, digestive, hepatitis (types A, B, C, and E), HIV/AIDS, kidney (chronic), mental, musculoskeletal, neoplasms, neurological, and respiratory (chronic). Machine reading algorithms were developed that extracted sex data from tables in articles and records on December 31, 2018, at an artificial intelligence research institute. Male and female participants in 43 135 articles (792 004 915 participants) and 13 165 records (12 977 103 participants) were included. Main Outcomes and Measures: Sex bias was defined as the difference between the fraction of female participants in study participants minus prevalence fraction of female participants for each disease category. A total of 1000 bootstrap estimates of sex bias were computed by resampling individual studies with replacement. Sex bias was reported as mean and 95% bootstrap confidence intervals from articles and records in each disease category over time (before or during 1993 to 2018), with studies or participants as the measurement unit. Results: There were 792 004 915 participants, including 390 470 834 female participants (49%), in articles and 12 977 103 participants, including 6 351 619 female participants (49%), in records. With studies as measurement unit, substantial female underrepresentation (sex bias ≤ -0.05) was observed in 7 of 11 disease categories, especially HIV/AIDS (mean for articles, -0.17 [95% CI, -0.18 to -0.16]), chronic kidney diseases (mean, -0.17 [95% CI, -0.17 to -0.16]), and cardiovascular diseases (mean, -0.14 [95% CI, -0.14 to -0.13]). Sex bias in articles for all categories combined was unchanged over time with studies as measurement unit (range, -0.15 [95% CI, -0.16 to -0.13] to -0.10 [95% CI, -0.14 to -0.06]), but improved from before or during 1993 (mean, -0.11 [95% CI, -0.16 to -0.05]) to 2014 to 2018 (mean, -0.05 [95% CI, -0.09 to -0.02]) with participants as the measurement unit. Larger study size was associated with greater female representation. Conclusions and Relevance: Automated extraction of the number of participants in clinical reports provides an effective alternative to manual analysis of demographic bias. Despite legal and policy initiatives to increase female representation, sex bias against female participants in clinical studies persists. Studies with more participants have greater female representation. Differences between sex bias estimates with studies vs participants as measurement unit, and between articles vs records, suggest that sex bias with both measures and data sources should be reported.

Assessment of left ventricular regional wall motion abnormalities using regional time-volume curves obtained by real time three-dimensional echocardiography.

BACKGROUND: Three-dimensional echocardiography provides a volumetric measurement of global and regional left ventricular (LV) function. It avoids the subjectivity of 2D echocardiography in the assessment of regional wall motion abnormalities (RWMA). PURPOSE: Evaluate the feasibility and practicality of 3D echocardiography in the evaluation of ischemic patients with abnormal regional LV contractility. METHODS: The study included 40 patients with ischemic heart disease and RWMA as well as 30 control subjects. They underwent routine clinical examination and conventional 2D echocardiographic assessment. Segments were categorized as; normal, hypokinetic; akinetic or dyskinetic. Three-dimensional echocardiographic images were acquired and later on analyzed offline. Global LV function was semi-automatically calculated by the machine using volumetric measurements. Regional LV function was calculated manually for the 17 LV segments by detecting the end-diastolic (EDD) and end-systolic (ESD) points on the specific segment volume curve and the regional ejection fraction (EF) was calculated by the following formula {(EDDx-ESDx)/EDDx}, where x represents the specific segment. Regional EF was compared between patients and control subjects. RESULTS: The mean age was 55.0 ±â€¯8.0 and 32.6 ±â€¯8.5 years (P < 0.001) in patients and control groups, respectively. No statistically significant difference in EF between 2D and 3D images (47.3 ±â€¯10.5 vs 48.0 ±â€¯8.0, p = 0.6). There was a good correlation between the 2D-RWMA and 3D-regional EF, and this correlation was consistent in the whole 17 segments. CONCLUSION: Three-dimensional echocardiography is an easy, non-invasive and objective tool to detect regional wall motion abnormalities in ischemic patients. It shows comparable results with conventional 2D images with the advantage of quantitative assessment of regional myocardial function.

Early postoperative paravalvular leak among Egyptian population: An observational study.

OBJECTIVES: Several reports described the incidence of postoperative paravalvular leakage (PVL) early after valve replacement surgery, however, there is a paucity of data regarding the outcomes and complications correlated to the severity of PVL. The aim of the current study was to evaluate the incidence, causes, and short term outcome of early postoperative PVL. METHODS: Data were collected from patients presenting to the cardiovascular department at Cairo University Hospital for aortic and/or mitral valve replacement surgery from May 2014 to May 2015. Transthoracic echocardiography (TTE) was done for all patients early postoperative. Transesophageal echocardiography (TEE) was done if diagnosis was not confirmed by TTE. All patients with detected PVL were subjected to TTE and TEE after a 3 month follow-up period. RESULTS: Two hundred patients were enrolled in the study. Seventy five percent of patients were known to have rheumatic heart disease, while 16.5% had infective endocarditis. The mitral valve was replaced in 40% of patients, the aortic valve was replaced in 36%, and other patients had both valves replaced. Early postoperative period PVL was detected in 25 patients. The most common underlying etiologies were rheumatic heart disease and infective endocarditis. PVL was common in patients with both valves replaced compared with either mitral or aortic valve replacement. Infective endocarditis as underlying valve disease was significantly high in patients with PVL compared with those without (p < 0.001). CONCLUSION: The incidence of PVL was high in patients with both valves replaced compared with either mitral or aortic valve replacement. Moreover, every patient with PVL should be properly investigated for infective endocarditis. Surgical intervention, although associated with high morbidity and mortality, reduces PVL recurrence.

Acute limb ischemia: role of preoperative and postoperative duplex in differentiating acute embolic from thrombotic ischemia.

BACKGROUND: Acute limb ischemia (ALI) represents an emergency in which delayed intervention results in significant morbidity, and potentially, death. PURPOSE: To assess the role of duplex in differentiating embolic from thrombotic ALI. METHODS AND MATERIALS: We prospectively recruited 57 patients; with 62 non-traumatic ALI. We measured the diameter at the occluded site (dO) and the corresponding contralateral healthy side (dC). The absolute (∆) and percent change (∆%) between the two diameters were calculated as: (dO-dC) and [(∆/dC)×100] respectively. According to the reference standard (contrast angiography or surgery), limbs were classified into embolic (E-group:37 limbs) and thrombotic (T-group:25 limbs) groups. Postoperative duplex was done in 34 patients after embolectomy and the absolute (∆P) and percent change (∆P%) between the postoperative (dP) and preoperative (dO) diameters at the occlusion were calculated as: (dP-dO) and [(∆P/dO)×100] respectively. RESULTS: The baseline clinical characteristics were similar between both groups. However, in the E-group, (∆%) was 21.96±17.53% vs. -11.03±16.16% in the T-group, (p<0.001). A cutoff value of >1.41% for (∆%) had 100% sensitivity and 76% specificity for the diagnosis of embolic vs. thrombotic occlusion with AUC 0.95 (95% CI: 0.901-0.999, p<0.00l). Postoperatively (∆P%) was -11.8±8.2% with a significant negative correlation found between (∆) and (∆P); Spearman's coefficient (rho)=-0.912, P<0.001. CONCLUSIONS: A cut off value of 1.41% as percent dilatation or diminution in the diameter of occluded artery is the most important duplex sign for predicting embolic or thrombotic ALI respectively. Postoperative reduction in the diameter of occluded artery after embolectomy confirms this sign.

Value of duplex scanning in differentiating embolic from thrombotic arterial occlusion in acute limb ischemia.

BACKGROUND: Management of acute limb ischemia (ALI) is largely based on the etiology of arterial occlusion (embolic vs. thrombotic). To our knowledge, the ability of duplex scanning to differentiate embolic from thrombotic occlusion has not been previously reported. PURPOSE: To determine the ability of duplex scanning to differentiate embolic from thrombotic acute arterial occlusion. METHODS: We prospectively recruited 97 patients (50.3 ± 19.7 years; 55% males) with 107 nontraumatic ALI in native arteries. All patients underwent surgical revascularization. Preoperative duplex scan detected arterial occlusion in the following arteries: iliac (11), femoral (38), popliteal (38), infrapopliteal (3), subclavian (3), axillary (1), brachial (9), and forearm arteries (4). We measured the arterial diameters at the site of occlusion (d(occl)) and at the corresponding contralateral healthy side (d(CONTRA)). The difference (Δ) between the two diameters was calculated as d(OCCL)-d(CONTRA). Duplex scan was also used to assess the state of the arterial wall whether healthy or atherosclerotic and the presence of calcification or collaterals. According to surgical findings, limbs were classified into embolic (E group=55 limbs) and thrombotic (T group=52 limbs) groups. RESULTS: Both groups were comparable regarding age, diabetes, hypertension, smoking, atrial fibrillation, and time of presentation. The status of arterial wall at the site of occlusion and presence of calcification or collaterals were all similar in both groups. Δ in the E group was 0.95 ± 0.92 mm vs. -0.13 ± 1.02 mm in the T group (P<.001). A value of ≥ 0.5 mm for Δ had 85% sensitivity and 76% specificity for the diagnosis of embolic occlusion (CI 0.72-0.90, P<.001), whereas a value of less than -0.5 mm for Δ had 85% sensitivity and 76% specificity for thrombotic occlusion (CI 0.72-0.90, P<.001). CONCLUSION: In acute arterial occlusion, ≥ 0.5 mm dilatation or diminution in the occluded artery diameter is a useful duplex sign for diagnosing embolic or thrombotic occlusion, respectively.