Low-Dose vs Standard Warfarin After Mechanical Mitral Valve Replacement: A Randomized Trial.

BACKGROUND: Current guidelines recommend a target international normalized ratio (INR) range of 2.5 to 3.5 in patients with a mechanical mitral prosthesis. The Prospective Randomized On-X Anticoagulation Clinical Trial (PROACT) Mitral randomized controlled noninferiority trial assessed safety and efficacy of warfarin at doses lower than currently recommended in patients with an On-X (Artivion, Inc) mechanical mitral valve. METHODS: After On-X mechanical mitral valve replacement, followed by at least 3 months of standard anticoagulation, 401 patients at 44 North American centers were randomized to low-dose warfarin (target INR, 2.0-2.5) or standard-dose warfarin (target INR, 2.5-3.5). All patients were prescribed aspirin, 81 mg daily, and encouraged to use home INR testing. The primary end point was the sum of the linearized rates of thromboembolism, valve thrombosis, and bleeding events. The design was based on an expected 7.3% event rate and 1.5% noninferiority margin. RESULTS: Mean patient follow-up was 4.1 years. Mean INR was 2.47 and 2.92 (P <.001) in the low-dose and standard-dose warfarin groups, respectively. Primary end point rates were 11.9% per patient-year in the low-dose group and 12.0% per patient-year in the standard-dose group (difference, -0.07%; 95% CI, -3.40% to 3.26%). The CI >1.5%, thus noninferiority was not achieved. Rates (percentage per patient-year) of the individual components of the primary end point were 2.3% vs 2.5% for thromboembolism, 0.5% vs 0.5% for valve thrombosis, and 9.13% vs 9.04% for bleeding. CONCLUSIONS: Compared with standard-dose warfarin, low-dose warfarin did not achieve noninferiority for the composite primary end point. (PROACT Clinicaltrials.gov number, NCT00291525).

Differences in kinetic variables between injured and uninjured rearfoot runners: A hierarchical cluster analysis.

Running is a popular form of physical activity with a high incidence of running-related injuries. However, the etiology of running-related injuries remains elusive, possibly due to the heterogeneity of movement patterns. The purpose of this study was to investigate whether different clusters existed within a large group of injured and uninjured runners based on their kinetic gait patterns. A sample of 134 injured and uninjured runners were acquired from an existing database and 12 discrete kinetic and spatiotemporal variables which are commonly associated with running injuries were extracted from the ground reaction force waveforms. A principal components analysis followed by an unsupervised hierarchical cluster analysis was performed. The results revealed two distinct clusters of runners which were not associated with injury status (OR = 1.14 [0.57, 2.30], χ2  = 0.143, p = 0.706) or sex (OR = 1.72 [0.85, 3.49], χ2  = 2.3258, p = 0.127). These results suggest that while there appeared to be evidence for two distinct clusters within a large sample of injured and uninjured runners, there is no association between the kinetic variables and running related injuries.

WITHDRAWN: Low-Dose Versus Standard Warfarin After Mechanical Mitral Valve Replacement: A Randomized Controlled Trial.

This article has been withdrawn at the request of the author(s) and/or editor. The Publisher apologizes for any inconvenience this may cause. The full Elsevier Policy on Article Withdrawal can be found at https://www.elsevier.com/about/our-business/policies/article-withdrawal.

"Coronavation: Keep Calm, and Carry On".

In this essay, I summarize a few ideas inspired by my involvement in the "Coronavation" working group, which spanned 2020's COVID-19 crisis. Health-care practitioners, computer scientists, and engineers alike, we strive to meet the challenges associated with practice under threat of pandemic with the same ideals driving the rapid, positive developments in health care today: innovation, collaboration and technology convergence, and acquisition of valuable data that leads to better approaches and new ideas. The ideas sketched here, forged by the need for practical pandemic responses, are rooted in those ideals.

Priorities in coronary artery bypass grafting: Is midterm survival more dependent on completeness of revascularization or multiple arterial grafts?

OBJECTIVE: Both completeness of revascularization and multiple arterial grafts (multiple arterial coronary artery bypass grafting) have been associated with increased midterm survival after coronary artery bypass grafting. The purpose of this study was to evaluate the relative impact of completeness of revascularization and multiple arterial coronary artery bypass grafting on midterm survival after coronary artery bypass grafting. METHODS: A retrospective review of 17,411 isolated, primary coronary artery bypass grafting operations from January 2002 to June 2016 at a US academic institution was performed. Patients were divided into groups based on complete or incomplete revascularization and number of arterial grafts. Inverse probability of treatment weighting based on the generalized propensity score was performed to minimize imbalance in preoperative characteristics. Between-group differences in outcomes were assessed using multivariable logistic and Cox regression analyses, incorporating the propensity score weights. RESULTS: Patients undergoing multiple arterial coronary artery bypass grafting in this study were younger, had fewer comorbid conditions, and had lower incidence of left main stenosis compared with patients undergoing single-arterial coronary artery bypass grafting. Short-term perioperative outcomes were similar between groups once propensity score weighting was used to minimize between-group differences in preoperative variables. Median follow-up in the entire population was 630 days, but was 1366 days in the cohort with data available from the Social Security Death Index. Multiple arterial coronary artery bypass grafting was protective for midterm survival compared with single arterial coronary artery bypass grafting, regardless of complete or incomplete revascularization or strategy (multiple arterial complete revascularization vs single-arterial complete revascularization: hazard ratio, 0.82; 95% confidence interval, 0.69-0.97; P = .02; multiple arterial incomplete revascularization vs single-arterial incomplete revascularization: hazard ratio, 0.70; 95% confidence interval, 0.53-0.90; P = .007). CONCLUSIONS: After controlling for preoperative comorbidities, multiple arterial coronary artery bypass grafting provides a modest midterm survival benefit over single-arterial coronary artery bypass grafting irrespective of completeness of revascularization, suggesting that when forced to choose, surgeons may elect to pursue multiple arterial conduits.

Evaluation of the In Vitro Damage Caused by Lipid Factors on Stem Cells from a Female Rat Model of Type 2 Diabetes/Obesity and Stress Urinary Incontinence.

Human stem cell therapy for type 2 diabetes/obesity (T2D/O) complications is performedwith stem cell autografts, exposed to the noxious T2D/O milieu, often with suboptimal results.We showed in the Obese Zucker (OZ) rat model of T2D/O that when their muscle-derived stemcells (MDSC) were from long-term T2D/O male rats, their repair ecacy for erectile dysfunctionwas impaired and were imprinted with abnormal gene- and miR-global transcriptional signatures(GTS). The damage was reproduced in vitro by short-term exposure of normal MDSC to dyslipidemicserum, causing altered miR-GTS, fat infiltration, apoptosis, impaired scratch healing, and myostatinoverexpression. Similar in vitro alterations occurred with their normal counterparts (ZF4-SC) fromthe T2D/O rat model for female stress urinary incontinence, and with ZL4-SC from non-T2D/O leanfemale rats. In the current work we studied the in vitro eects of cholesterol and Na palmitate aslipid factors on ZF4-SC and ZL4-SC. A damage partially resembling the one caused by the femaledyslipidemic serum was found, but diering between both lipid factors, so that each one appears tocontribute specifically to the stem cell damaging eects of dyslipidemic serum in vitro and T2D/Oin vivo, irrespective of gender. These results also confirm the miR-GTS biomarker value forMDSC damage.

Generation and Analysis of CCM Phenotypes in C. elegans.

This chapter presents methods for exploiting the powerful tools available in the nematode worm Caenorhabditis elegans to understand the in vivo functions of cerebral cavernous malformation (CCM) genes and the organization of their associated signaling pathways. Included are methods for assessing phenotypes caused by loss-of-function mutations in the worm CCM genes kri-1 and ccm-3, CRISPR-based gene editing techniques, and protocols for conducting high-throughput forward genetic and small molecule screens.

Affinity Purification and Preparation of Peptides for Mass Spectrometry from C. elegans.

Affinity purification of a target protein followed by mass spectrometry of the purified peptides can be used to identify physical interactors of the protein of interest. Using this biochemical approach on proteins from whole organisms such as C. elegans can reveal novel in vivo protein interactions that cannot be identified using homology-based predictions or in vitro approaches. Here we describe affinity purification of a GFP-tagged target protein from whole worm lysates, digestion of the purified proteins into peptides, and preparation of the peptides for analysis by mass spectrometry. This protocol has been optimized for ChromoTek GFP-Trap® Magnetic Agarose beads, but it may be used with other tags and antibody-conjugated beads.

Biomechanics of graded running: Part II-Joint kinematics and kinetics.

Compared to level running (LR), different strategies might be implemented by runners to cope with specific challenges of graded running at different speeds. The changes in joint kinetics and kinematics associated with graded running have been investigated, but their interactions with speed are unknown. Nineteen participants ran on an instrumented treadmill at five grades (0°, ±5° and ± 10°) and three speeds (2.50, 3.33 and 4.17 m/s), while 3D motion and forces were recorded. Three speed × five-grade repeated-measures ANOVA was used to analyze kinetic and kinematic variables. A speed × grade interaction was observed for hip range of motion (ROM). Downhill running (DR) at fastest speed did not reduce ROM at the hip, compared to LR. Compared to LR, it was observed that the hip joint was responsible for a greater contribution of energy generation while running at the fastest speed at +10°. Speed × grade interactions were also observed for the energy absorption, peak moment, and peak power at the knee. Contrary to LR, running faster during UR did not require higher peak power at the knee. Finally, DR at the fastest speed did not increase peak negative power at the knee compared to LR. This study demonstrates that ankle, knee, and hip joint kinetics depend on speed and grade of running, while the effect of grade on joint kinematics was not substantially modulated by speed.

Biomechanics of graded running: Part I - Stride parameters, external forces, muscle activations.

Biomechanical alterations with graded running have only been partially quantified, and the potential interactions with running speed remain unclear. We measured spatiotemporal parameters, ground reaction forces, and leg muscle activations (EMG) in nineteen adults (10F/9M) running on an instrumented treadmills at 2.50, 3.33, and 4.17 m·s-1 and 0, ±5°, and ±10°. Step frequency illustrated a significant speed × grade interaction (P < .001) and was highest (+3%) at the steepest grade (+10°) and fastest speed (4.17 m·s-1 ) when compared to level running (LR) at the same speed. Significant interaction was also observed for ground reaction forces (all P ≤ .047). Peak ground reaction forces in the normal direction increased with running speed during downhill running (DR) only (+9% at -10° and 4.17 m·s-1 ). Impulse in the normal direction decreased at fastest speed and steepest DR (-9%) and uphill running (UR) (-17%) grades. Average normal loading rate increased and decreased at fastest speed and steepest DR (+52%) and UR (-28%) grades, respectively. Negative parallel impulse increased and decreased at fastest speed and steepest DR (+166%) and UR (-90%), respectively. Positive parallel impulse decreased and increased at fastest speed and steepest DR (-75%) and UR (+111%), respectively. EMG showed comparable u-shaped curves across the grades investigated, although only a change in vastus lateralis and tibilias anterior activity was detectable at the steepest grades and fastest speed. Overall, running grade and speed significantly influences spatiotemporal parameters, ground reaction forces, and muscle activations.

From invisibility to readability: Recovering the ink of Herculaneum.

The noninvasive digital restoration of ancient texts written in carbon black ink and hidden inside artifacts has proven elusive, even with advanced imaging techniques like x-ray-based micro-computed tomography (micro-CT). This paper identifies a crucial mistaken assumption: that micro-CT data fails to capture any information representing the presence of carbon ink. Instead, we show new experiments indicating a subtle but detectable signature from carbon ink in micro-CT. We demonstrate a new computational approach that captures, enhances, and makes visible the characteristic signature created by carbon ink in micro-CT. This previously "unseen" evidence of carbon inks, which can now successfully be made visible, is a discovery that can lead directly to the noninvasive digital recovery of the lost texts of Herculaneum.

From damage to discovery via virtual unwrapping: Reading the scroll from En-Gedi.

Computer imaging techniques are commonly used to preserve and share readable manuscripts, but capturing writing locked away in ancient, deteriorated documents poses an entirely different challenge. This software pipeline-referred to as "virtual unwrapping"-allows textual artifacts to be read completely and noninvasively. The systematic digital analysis of the extremely fragile En-Gedi scroll (the oldest Pentateuchal scroll in Hebrew outside of the Dead Sea Scrolls) reveals the writing hidden on its untouchable, disintegrating sheets. Our approach for recovering substantial ink-based text from a damaged object results in readable columns at such high quality that serious critical textual analysis can occur. Hence, this work creates a new pathway for subsequent textual discoveries buried within the confines of damaged materials.

Midterm benefits of surgical pulmonary embolectomy for acute pulmonary embolus on right ventricular function.

OBJECTIVE: Surgical pulmonary embolectomy has been used for the successful treatment of massive and submassive pulmonary emboli. The purpose of this study is to document the short- and midterm echocardiographic follow-up of right ventricular function after surgical pulmonary embolectomy for acute pulmonary embolus. METHODS: A retrospective review of the local Society of Thoracic Surgeons database of patients who underwent surgical pulmonary embolectomy for acute pulmonary embolectomy was conducted from 1998 to 2014 at a US academic center. Patients with chronic thrombus were excluded. The institutional echocardiographic database was searched for follow-up studies to compare markers of right ventricular function. Unadjusted outcomes were described, and quantitative comparisons were made of short- and long-term echocardiographic data. RESULTS: A total of 44 patients were included for analysis; 35 patients (79.5%) had a submassive pulmonary embolectomy, and 9 patients (20.5%) had a massive pulmonary embolectomy and required preoperative inotropy. Mean cardiopulmonary bypass time was 68.0 ± 40.2 minutes, and 30 patients (68.2%) underwent procedures without aortic crossclamping. There was 1 in-hospital mortality (2.3%), and there were no permanent neurologic deficits. A total of 21 patients had echocardiography results available for follow-up. Perioperative echocardiographic data showed an immediate decrease in tricuspid regurgitant velocity and right ventricular pressure (P < .05). Mean midterm echocardiographic follow-up was 30 months in 12 patients. At midterm follow-up, improvements in right ventricular function observed postoperatively persisted. Only 1 patient had moderate right ventricular dysfunction, and no patient had worse than mild tricuspid regurgitation. Mean tricuspid valve regurgitant velocity was 2.4 ± 0.7 m/s, and mean pulmonary artery systolic pressure was 37.2 ± 14.2 mm Hg. CONCLUSIONS: Surgical pulmonary embolectomy may represent optimal therapy in selected patients for massive and submassive acute pulmonary emboli given the low morbidity and mortality rates. Echocardiographic follow-up shows preserved improvement in right ventricular function in the majority of patients.

Injury to the conduction system: management of life-threatening arrhythmias after penetrating cardiac trauma.

BACKGROUND: Life-threatening conduction abnormalities after penetrating cardiac injuries (PCIs) are rare, and rapid identification and treatment of these arrhythmias are critical to survival. This study highlights diagnosis and management strategies for conduction abnormalities after PCI. METHODS: Patients with life-threatening arrhythmias after PCI were identified at an urban, level I trauma center registry. RESULTS: Seventy-one patients survived to reach the hospital after PCI. Of these, 3 (4%) survivors (male = 3, mean age 41.3, median injury severity score = 25) had critical conduction abnormalities after cardiorrhaphy. All patients had multichamber and atrioventricular nodal injury. After initial cardiorrhaphy and control of hemorrhage, all patients had sustained hypotension with bradycardia from complete heart block. Two patients had ventricular septal defects requiring repair. All 3 patients survived. CONCLUSIONS: Rapid recognition of injury to the cardiac conduction system after PCI as a source of sustained hypotension is essential to early restoration of cardiac function and survival.

In vivo loading model to examine bone adaptation in humans: a pilot study.

Bone is typically well suited for its habitual loading environment because of its ability to adapt. Although characteristics of the mechanical loading environment predict the bone adaptive response in animals, this has not been prospectively validated in humans. Here, we describe an in vivo loading model in which women apply forces to the radius by leaning onto their hand. We characterized the strain environment imposed on the radius using cadaveric experimentation and conducted a prospective study in which 19 adult women loaded their distal radii 50 cycles/day, 3 days/week, for 28 weeks and seven additional adult women served as controls. In four cadaveric specimens, loading caused compressive principal strains of -1,695 ± 396 µÎµ with radial bending dorsally and towards the ulna. Prospective in vivo loading produced measurable improvements to bone and appeared to protect against bone loss associated with seasonal fluctuations in physical activity and sun exposure. Experimental subjects had significant gains to bone volume (BV) and moments of inertia, while, control subjects had significant losses in BMC and moments of inertia. The loading model is thus suitable as a model system for exploring bone adaptation in humans, and may eventually be clinically useful for strengthening the radius of women.

Innovations in therapies for heart valve disease.

The burden of heart valve disease among adults is enormous in the developed world. Increased life expectancy and age-related valvular degeneration remain the predominant contributors to heart valve dysfunction, which if uncorrected lead to congestive heart failure and increased morbidity and mortality. Clinical evidence on the detrimental impact of valve disease on both pediatric and adult populations has fueled growing interest in diagnosis and therapy for heart valve disease, and also significant financial investment from hospitals and medical device manufacturers in hybrid operating rooms and novel medical device technologies. A wide array of surgical, minimally invasive and percutaneous heart valve technologies are available today, which have significantly enlarged the surgeon's armamentarium, and revolutionized the traditional role of a surgeon in correcting such lesions. Amid this revolution in heart valve technologies, we present recent advances in heart valve therapies, critically appraise their clinical need, and finally discuss the clinical experience and outcomes of some of these technologies. The expected outcome of this review is to provide the clinical reader with a reasonable scientific basis to enable appropriate adoption of these technologies into their clinical practice.

Total aortic arch replacement for the treatment of Kommerell's diverticulum in a Jehovah's Witness.

The treatment of Kommerell's diverticulum continues to evolve given advances in aortic surgery, cardiopulmonary bypass management, and endovascular techniques. This case report details the repair of a diverticulum of Kommerell in a Jehovah's witness with a right-sided aortic arch and reviews the surgical literature.

The Impact of Chronic Liver Diseases on the Level of Heart-Type Fatty Acid-Binding Protein (H-FABP) Concentrations.

OBJECTIVES: Heart-type fatty acid binding-protein (H-FABP) has been reported to be a potential novel biochemical marker for the early diagnosis of acute myocardial infarction (AMI). The presence of H-FABP in the liver has not been reported. The aim of this study was to compare the effect of chronic liver diseases on the level of H-FABP concentrations. METHODS: The effects of chronic liver diseases including infective hepatitis and cirrhosis on the concentration of H-FABP was studied in a small group of patients (n=10, mean age ±SD = 58.33 ± 7.19 years). The serum concentrations of the following markers were measured: H-FABP, alanine aminotransferase (ALT) and bilirubin and compared with a reference control group (20 healthy blood donors, mean age ±SD = 63.8 ±8.01). RESULTS: The serum concentrations of these markers in the control group as compared to patients with chronic liver disease were as follows (mean ± SD): H-FABP = 6.86 ±2.21 µg/L versus 6.44 ±3.06 µg/L (p = NS); ALT = 29.8 ±14.7 U/L versus ALT = 198.67 ±122.89 U/L (p < 0.0005) and bilirubin = 9.6 ±4.0 µmol/L versus bilirubin = 100.89 ±87.85 µmol/L (p < 0.0001). CONCLUSION: These data illustrate clearly that there is no significant interference with the normal concentration of H-FABP in the presence of liver diseases, despite the significant elevation of liver enzymes and proteins. These data may support a useful role of H-FABP for the diagnosis of myocardial injury in patients with liver diseases.

Serum level of heart-type Fatty Acid-binding protein in patients with chronic renal failure.

OBJECTIVES: Heart-type fatty acid binding-protein (H-FABP) has been reported to be a potential novel biochemical marker for the early diagnosis of acute myocardial infarction (AMI). The effect of kidney diseases on the renal handling of H-FABP has not yet been fully evaluated. The aim of this study was to compare the effect of renal failure on the level of H-FABP and cardiac troponin (cTnT) concentrations. METHODS: The study population was a small group of 16 patients with renal failure (6 females, 10 males aged 30-70 years) on routine regular haemodialysis or peritoneal dialysis. RESULTS: The mean ±SD of serum urea and creatinine concentration in this group of patients was 19 ±9.6 mmol/L and 531.3 ±231.2 mmol/L respectively. H-FABP was increased in all 16 patients (81 ±53.3µg/L). The cTnT was increased ≥ 0.1µg/L in 8 patients (50%), ≥ 0.2µg/L in 5 patients (31.3%), and ≥ 0.3µg/L in 1 patient (6%). CONCLUSION: The diagnostic efficiency of H-FABP and cTnT for the diagnosis of AMI in the presence of renal failure may be limited and such patients may have high levels even in the absence of AMI.