bluuebunny/crossref_metadata_2025_split huggingface dataset:
Novel Trial Design: CHIEF-HF
Authors: Spertus John A. , Birmingham Mary C. , Butler Javed , Lingvay Ildiko , Lanfear David E. , Abbate Antonio , Kosiborod Mikhail N. , Fawcett Christina , Burton Paul , Damaraju C.V. , Januzzi James L. , Whang John 
Published: March 2021

Background:
The expense of clinical trials mandates new strategies to efficiently generate evidence and test novel therapies. In this context, we designed a decentralized, patient-centered randomized clinical trial leveraging mobile technologies, rather than in-person site visits, to test the efficacy of 12 weeks of canagliflozin for the treatment of heart failure, regardless of ejection fraction or diabetes status, on the reduction of heart failure symptoms.

Methods:
One thousand nine hundred patients will be enrolled with a medical record-confirmed diagnosis of heart failure, stratified by reduced (≤40%) or preserved (>40%) ejection fraction and randomized 1:1 to 100 mg daily of canagliflozin or matching placebo. The primary outcome will be the 12-week change in the total symptom score of the Kansas City Cardiomyopathy Questionnaire. Secondary outcomes will be daily step count and other scales of the Kansas City Cardiomyopathy Questionnaire.

Results:
The trial is currently enrolling, even in the era of the coronavirus disease 2019 (COVID-19) pandemic.

Conclusions:
CHIEF-HF (Canagliflozin: Impact on Health Status, Quality of Life and Functional Status in Heart Failure) is deploying a novel model of conducting a decentralized, patient-centered, randomized clinical trial for a new indication for canagliflozin to improve the symptoms of patients with heart failure. It can model a new method for more cost-effectively testing the efficacy of treatments using mobile technologies with patient-reported outcomes as the primary clinical end point of the trial.

Registration:

URL:
https://www.clinicaltrials.gov
; Unique identifier: NCT04252287.
Myocardial Fibrosis in Pediatric Patients With Ebstein’s Anomaly
Authors: Aly Safwat , Seed Mike , Yoo Shi-Joon , Lam Christopher , Grosse-Wortmann Lars 
Published: March 2021

Background:
Left ventricular dysfunction in Ebstein’s anomaly (EA) is associated with higher mortality. The health of the left ventricular myocardium in children and adolescents with EA has not been investigated in detail.

Methods:
Patients with unrepaired EA who had undergone cardiac magnetic resonance imaging including T1 mapping were retrospectively reviewed. Patients were compared with age- and sex-matched controls. EA severity index was calculated using volumetric measurements at end diastole ([right atrial+atrialized right ventricular volumes]/[functional right ventricular+left atrial+left ventricular volumes]). Global circumferential and radial strain and as well as strain rate were examined using cardiac magnetic resonance feature tracking.

Results:

Twelve EA patients and an equal number of controls were included. Functional and atrialized right ventricular end-diastolic volumes were 84±15 and 21±13 mL/m
2
, respectively. Late gadolinium enhancement, confined to the right ventricle, was found in 2 patients (16%). Left ventricular native T1 values and extracellular volume fractions were higher in patients compared with controls (1026±47 versus 956±40 ms,
P
=0.0004 and 28.5±3.4% versus 22.5±2.6%,
P
<0.001, respectively). Native T1 times correlated inversely with patients’ age, body surface area, and O
2
saturations (r=−0.63, −0.62, and −0.91, respectively;
P
=0.02,
P
=0.02, and
P
<0.0001, respectively). EA severity index ranged between 0.15 and 0.94 and correlated with T1 values (r=0.76,
P
=0.003). Native T1 correlated with global circumferential strain (r=0.58,
P
=0.04) but not ejection fraction (EF). EA patients had reduced maximum oxygen uptake (V
o
2
max). V
o
2
max correlated inversely with T1 values (r=−0.79,
P
=0.01).

Conclusions:

Children and adolescents with EA experience an abnormal degree of diffuse myocardial fibrosis. Its association with O
2
saturation points toward a role of hypoxemia in the pathogenesis of fibrosis. Larger and prospective studies are needed to evaluate the value of T1 mapping for risk stratification and monitoring in EA.
Acute and Short-Term Outcomes of Percutaneous Transcatheter Mitral Valve Replacement in Children
Authors: Maschietto Nicola , Prakash Ashwin , del Nido Pedro , Porras Diego 
Published: March 2021

Background:
Despite the improvement of surgical techniques for mitral valve (MV) repair in children, mitral valve replacement (MVR) is sometimes still necessary. MVR and redo-MVR continue to be burdened by early postoperative mortality and long-term morbidity with only about 75% of these patients being alive or transplant-free 10 years after the initial MVR. Although transcatheter MVR (TMVR) is a well-established intervention in high surgical risk adults, only a few pediatric valve-in-valve case reports have been published. The purpose of this study was to describe our initial experience with the off-label use of the Sapien S3 valve for TMVR in a highly selected pediatric patient population.

Methods:
We conducted a retrospective analysis of pediatric patients who underwent TMVR at Boston Children’s Hospital between October 2018 and July 2020.

Results:

Eight consecutive high surgical risk pediatric patients (median age, 9 years; range, 8–15) underwent TMVR (7 as valve-in-valve, 1 in a native MV). Each patient previously underwent multiple MV surgeries or MVR (median 4, range 2–5) and was highly symptomatic (Ross functional class 3 or 4). The indication for TMVR was mitral stenosis in 4 patients, regurgitation in 1, and mixed disease in 3. TMVR was successful in each patient, effectively reduced the left atrium and pulmonary hypertension (
P
=0.012 and 0.043 respectively), and was carried out without significant complications.

Conclusions:
TMVR is an attractive alternative to MVR in high surgical risk patients. In this small series, TMVR was acutely effective and safe, with very encouraging early results.
Recherches archéologiques sur les mines et la métallurgie de l’argent à Imiter (Maroc)
Authors: Fauvelle François-Xavier , Robion-Brunner Caroline , Fabre Jean-Marc , Baron Sandrine , Mensan Romain , Souhassou Mustapha 
Published: March 2021

Abstract
Imiter, mine d’argent de l’Anti-Atlas marocain encore en activité, possède des vestiges archéologiques de travaux miniers et métallurgiques. L’étude de textes anciens et d’artefacts a permis de la rapprocher de la mine d’argent de Todgha connue à l’époque médiévale (El Ajlaoui 1994). Entre 2011 et 2014, une équipe pluridisciplinaire (historien, géologue métallogéniste, géochimiste, archéologues) a entrepris des prospections en surface et en souterrain, la fouille de trois cuves de traitement du minerai ainsi que la caractérisation minéralogique et géochimique de minerais et déchets métallurgiques anciens. Les résultats des datations des cuves placent le dépôt après utilisation entre le IIe siècle cal BC et le VIe siècle cal AD, soit avant la période islamique. Cet article fait état des résultats de ces recherches, qui documentent pour la première fois une exploitation antique de l’argent dans les régions méridionales du Maroc, exploitation qui s’est poursuivie à l’époque médiévale.
Prevalence and management of people with eating disorders presenting to primary care: A national study
Authors: Ivancic Lorraine , Maguire Sarah , Miskovic-Wheatley Jane , Harrison Christopher , Nassar Natasha 
Published: March 2021

Objective: Primary care practitioners are well placed to support diagnosis and appropriate treatment of eating disorders as they are often the first point of contact with the health care system. However, little is known about management of eating disorders in primary care. We aimed to estimate the prevalence of management of eating disorders in primary care and identify how these disorders are managed. Methods: This study used data from the Bettering the Evaluation of Care of Health programme, which annually surveys 1000 randomly sampled general practitioners in Australia who each record details of 100 successive patient encounters. In total, data were utilised from 1,568,100 primary care encounters between 2000/2001 and 2015/2016. Results: Eating disorders were managed in less than 1% of primary care encounters between 2000/2001 and 2015/2016. When extrapolated to the Australian population, up to 0.32% of the population were managed in primary care for a primary or probable eating disorder. In the majority of encounters where an eating disorder was managed (58.5%), the encounter was initiated for reasons other than the eating disorder itself. Of a group of patients identified with a clinically significant low body mass index ( N = 5917), a small number ( n = 118) had either no other diagnosis or a related condition that may be indicative of an eating disorder. In encounters where an eating disorder was managed, referrals to a mental health specialist/service, medical specialist and nutritionist/dietician were provided in 20%, 8% and 6% of encounters, respectively. Mental health treatment plans, which provide subsidised access to mental health services, were ascribed in approximately 7.7% of encounters where an eating disorder was managed. Conclusion: Primary care provides an opportunity to improve detection and management of eating disorders, particularly when patients present for ‘other’ issues or with unexplained low body mass index and one or more symptoms related to an eating disorder.
Does Magnetic Resonance Imaging Grading Correlate With Return to Sports After Bone Stress Injuries? A Systematic Review and Meta-analysis
Authors: Hoenig Tim , Tenforde Adam S. , Strahl André , Rolvien Tim , Hollander Karsten 
Published: March 2021

Background: While some studies have failed to reveal any significant relationship between magnetic resonance imaging (MRI) grading and return to sports after bone stress injuries, others have reported either a linear or nonlinear relationship. Purpose: To evaluate the prognostic value of MRI grading for time to return to sports and rate of return to sports after bone stress injuries. Study Design: Systematic review and meta-analysis. Methods: A systematic search was performed in PubMed, Web of Science, SPORTDiscus, and Google Scholar. Studies reporting return to sports data after bone stress injuries using MRI grading systems were included in this review. The risk of bias was evaluated using the Quality in Prognosis Studies tool. Meta-analyses were performed to summarize the mean time to return to sports. The Pearson correlation was used to determine the relationship between time to return to sports and MRI grade. A meta-analysis of proportions was conducted to determine the percentage of athletes who successfully returned to sports. Results: A total of 16 studies with 560 bone stress injuries met inclusion criteria. Higher MRI-based grading was associated with an increased time to return to sports ( P < .00001). Pooled data revealed that higher MRI-based grading correlated with a longer time to return to sports ( r = 0.554; P = .001). Combining all anatomic locations, the mean time to return to sports was 41.7 days (95% CI, 30.6-52.9), 70.1 days (95% CI, 46.9-93.3), 84.3 days (95% CI, 59.6-109.1), and 98.5 days (95% CI, 85.5-112.6) for grade 1, 2, 3, and 4 injuries, respectively. Trabecular-rich sites of injury (eg, pelvis, femoral neck, and calcaneus) took longer to heal than cortical-rich sites of injury (eg, tibia, metatarsal, and other long-bone sites of injury). Overall, more than 90% of all athletes successfully returned to sports. Conclusion: The findings from this systematic review indicate that MRI grading may offer a prognostic value for time to return to sports after the nonsurgical treatment of bone stress injuries. Both MRI grade and location of injury suggest that individually adapted rehabilitation regimens and therapeutic decisions are required to optimize healing and a safe return to sports.
Musculoskeletal Injuries and Their Association With Previous Concussion History: A Prospective Study of High School Volleyball and Soccer Players
Authors: Biese Kevin M. , Kliethermes Stephanie A. , Watson Andrew M. , McGuine Timothy A. , Lang Pamela J. , Bell David R. , Alison Brooks M. 
Published: March 2021

Background: Sports-related concussions may have a neurobiological recovery period that exceeds the period of clinical recovery, and one consequence of an extended neurobiological recovery may be the risk of subsequent musculoskeletal injuries. Most literature citing an increased risk of musculoskeletal injury after a sports-related concussion has been reported in populations other than adolescent athletes. Purpose/Hypothesis: The purpose was to prospectively determine if incidence rates of musculoskeletal injury differ between adolescent athletes with and without a previous sports-related concussion, while controlling for sex, sport, and age. A secondary aim was to determine if this relationship differs between male and female athletes of the same sport. Our hypotheses were that acute-noncontact injury rates would be higher in athletes with a previous sports-related concussion when compared with athletes without a previous sports-related concussion, and that this relationship would exist only in female athletes and not male athletes. Study Design: Cohort study; Level of evidence, 2. Methods: High school soccer and volleyball players were recruited in 2 prospective cohort studies that observed 4837 athletes during their sporting season (females, 80%; soccer, 57%; mean [SD] age, 15.6 [1.1] years). At preseason, all participants self-reported demographics and previous sports-related concussion within the past 12 months. During the sport season, team athletic trainers electronically recorded athlete exposures and injury data, including injury characteristics. Injury rates per 1000 athlete exposures and injury rate ratios (IRRs) with 95% confidence intervals were calculated. All injury rates and IRRs were adjusted for sex, age, and sport. Results: The rate of acute-noncontact lower extremity injury was 87% greater (IRR, 1.87; 95% CI, 1.29-2.74) in participants with a previous sports-related concussion versus those without one. The acute-noncontact lower extremity injury rates (IRRs) for females and males with a previous sports-related concussion were 1.76 (95% CI, 1.19-2.59) and 2.83 (95% CI, 0.85-9.50), respectively. No difference was detected in acute-contact (IRR, 0.98; 95% CI, 0.56-1.73) or overuse (IRR, 1.09; 95% CI, 0.51-2.37) lower extremity injury rates by previous sports-related concussion. Conclusion: Female adolescent athletes who reported a sports-related concussion within the past 12 months were more likely to sustain an acute-noncontact lower extremity injury during their high school sports season when compared with female athletes without a previous sport-related concussion.
High Incidence of Barotrauma in Patients With Severe Coronavirus Disease 2019
Authors: Kahn Michael R. , Watson Richard L. , Thetford Jay T. , Wong Joseph Isaac , Kamangar Nader 
Published: March 2021

Objective.: To report the high incidence of barotrauma in critically ill patients admitted to the intensive care unit (ICU) with coronavirus disease 2019 (COVID-19) and to discuss its implications. Design.: Retrospective cohort study. Setting.: ICU of an academic county hospital in Los Angeles, CA admitted from March 15-June 20, 2020. Patients.: 77 patients with COVID-19 pneumonia. 75 patients met inclusion criteria. Results.: 21% of patients with severe COVID-19 sustained barotrauma (33% of patients receiving IMV, 8% of patients receiving (NIV). There were no differences between the barotrauma and non-barotrauma groups regarding demographics, illness severity, or medications received, nor tidal volume or average/peak airway pressures in those receiving IMV. In the barotrauma group there was a greater proportion of patients receiving therapeutic anticoagulation (81% vs. 47%, p = 0.023) and ventilated using airway pressure release ventilation mode (13% vs. 0%, p = 0.043). Barotrauma was associated with increased likelihood of receiving a tracheostomy (OR 2.58 [0.23-4.9], p = 0.018]), longer median ICU length of stay (17 days vs. 7 days, p = 0.03), and longer median length of hospitalization (26 days vs. 14 days, p < 0.001). There was also a trend toward prolonged median duration of IMV (12.5 days vs 7 days, p = 0.13) and higher average mortality (56% vs 37%, p = 0.25). Conclusions.: Barotrauma is seen in 5-12% of patients with ARDS receiving IMV and is exceedingly rare in patients receiving NIV. We report a high incidence of barotrauma observed in critically ill patients with COVID-19 requiring either NIV or IMV. While there was a trend toward increased mortality in patients with barotrauma, this did not reach statistical significance. The increased incidence of barotrauma with COVID-19 may be a product of the pathophysiology of this disease state and a heightened inflammatory response causing rampant acute lung injury. Evidence-based medicine and lung-protective ventilation should remain the mainstay of treatment.
Endothelial deletion of PKCδ prevents VEGF inhibition and restores blood flow reperfusion in diabetic ischemic limb
Authors: Croteau Laura , Mercier Clément , Fafard-Couture Étienne , Nadeau Alexandre , Robillard Stéphanie , Breton Valérie , Guay Andréanne , Lizotte Farah , Despatis Marc-Antoine , Geraldes Pedro 
Published: March 2021

Aims: Peripheral artery disease is a complication of diabetes leading to critical hindlimb ischemia. Diabetes-induced inhibition of VEGF actions is associated with the activation of protein kinase Cδ (PKCδ). We aim to specifically investigate the role of PKCδ in endothelial cell (EC) function and VEGF signaling. Methods: Nondiabetic and diabetic mice, with ( ec-Prkcd−/−) or without ( ec-Prkcdf/f) endothelial deletion of PKCδ, underwent femoral artery ligation. Blood flow reperfusion was assessed up to 4 weeks post-surgery. Capillary density, EC apoptosis and VEGF signaling were evaluated in the ischemic muscle. Src homology region 2 domain-containing phosphatase-1 (SHP-1) phosphatase activity was assessed in vitro using primary ECs. Results: Ischemic muscle of diabetic ec-Prkcdf/f mice exhibited reduced blood flow reperfusion and capillary density while apoptosis increased as compared to nondiabetic ec-Prkcdf/f mice. In contrast, blood flow reperfusion and capillary density were significantly improved in diabetic ec-Prkcd−/− mice. VEGF signaling pathway was restored in diabetic ec-Prkcd−/− mice. The deletion of PKCδ in ECs prevented diabetes-induced VEGF unresponsiveness through a reduction of SHP-1 phosphatase activity. Conclusions: Our data provide new highlights in mechanisms by which PKCδ activation in EC contributed to poor collateral vessel formation, thus, offering novel therapeutic targets to improve angiogenesis in the diabetic limb.
Chagas disease is an independent predictor of stroke and death in a cohort of heart failure patients
Authors: Cerqueira-Silva Thiago , Gonçalves Beatriz MM , Pereira Camila B , Porto Louise M , Marques Maria EL , Santos Leila SB , Oliveira Murilo A , Félix Iuri F , de Sousa Paulo RS P , Muiños Pedro JR , Maia Renata M , Catto Marília B , Andrade Alisson L , Jesus Pedro AP , Aras Roque , Oliveira-Filho Jamary 
Published: March 2021

Background and Aims Chagas disease is a common cause of heart failure (HF) and death in developing countries. Although stroke is known to occur in these patients, an accurate estimate of stroke incidence is lacking. We aimed to determine the incidence of stroke and death in patients with HF, comparing Chagas and non-Chagas etiologies. Methods Cohort of stroke-free patients with HF (Framingham criteria) followed in a university-based outpatient clinic in Brazil. Baseline characteristics included sociodemographic, risk factor assessment, echocardiographic and electrocardiographic findings. Chagas disease was defined by appropriate serologic tests. Cause-specific Cox regression was used to search for predictors of stroke or death as separate outcomes. Results We studied 565 patients with HF between January 2003 and December 2018, mean age 54.3 ± 12.9 years, 305 (54.0%) females, 271/535 (50.7%) with Chagas disease. Chagas patients were older (55.5 vs. 53.1 years), more frequently women (60.5% vs. 47.3%), less frequently harbored coronary artery disease (14.5% vs. 34.1%) when compared to non-Chagas patients. Echocardiography showed more severe disease among non-Chagas patients [median left ventricle ejection fraction (LVEF) 37.3% vs. 47.0%]. Over a mean 42.9 (±34.4) months, we followed 404 (71.5%) patients, completing 1442 patient-years of follow-up. Stroke incidence was higher in Chagas when compared to non-Chagas patients (20.2 vs. 13.9 events per 1000 patient-years), while death rate was similar (41.6 vs. 43.1 deaths per 1000 patient-years). In the multivariable analysis for stroke outcome adjusted for LVEF and arrhythmias, cause-specific hazard ratio (CSHR) for Chagas was 2.54 (95% confidence interval 1.01–6.42, p = 0.048). Chagas disease was also associated with increased risk of death (CSHR 1.83; 95% confidence interval 1.04–3.24, p = 0.037). Conclusion Chagas disease is associated with increased risk of stroke and death when compared to other etiologies of HF, independently of HF severity or cardiac arrhythmias, suggesting other factors contribute to increased stroke risk and mortality in Chagas disease. Early prevention and treatment of Chagas disease is imperative to reduce a later risk of stroke in endemic areas.
Effect of genetic liability to visceral adiposity on stroke and its subtypes: A Mendelian randomization study
Authors: Yan Bin , Yang Jian , Qian Li , Gao Fengjie , Bai Ling , Wang Gang , Ma Xiancang 
Published: March 2021

Background Observational studies have found an association between visceral adiposity and stroke. Aims The purpose of this study was to investigate the role and genetic effect of visceral adipose tissue accumulation on stroke and its subtypes. Methods In this two-sample Mendelian randomization study, genetic variants (221 single nucleotide polymorphisms; P < 5 × 10−8) using as instrumental variables for Mendelian randomization analysis was obtained from a genome-wide association study of visceral adipose tissue. The outcome datasets for stroke and its subtypes were obtained from the MEGASTROKE consortium (up to 67,162 cases and 453,702 controls). Mendelian randomization standard analysis (inverse variance weighted method) was conducted to investigate the effect of genetic liability to visceral adiposity on stroke and its subtypes. Sensitivity analyses (Mendelian randomization-Egger, weighted median, Mendelian randomization-pleiotropy residual sum and outlier) were also utilized to assess horizontal pleiotropy and remove outliers. Multi-variable Mendelian randomization analysis was employed to adjust potential confounders. Results In the standard Mendelian randomization analysis, genetically determined visceral adiposity (per 1 SD) was significantly associated with a higher risk of stroke (odds ratio (OR) 1.30; 95% confidence interval (CI) 1.21–1.41, P = 1.48× 10−11), ischemic stroke (OR 1.30; 95% CI 1.20–1.41, P = 4.01 × 10−10) and large artery stroke (OR 1.49; 95% CI 1.22–1.83, P = 1.16 × 10−4). The significant association was also found in sensitivity analysis and multi-variable Mendelian randomization analysis. Conclusions Genetic liability to visceral adiposity was significantly associated with an increased risk of stroke, ischemic stroke, and large artery stroke. The effect of genetic susceptibility to visceral adiposity on the stroke warrants further investigation.