bluuebunny/crossref_metadata_2025_split huggingface dataset:
The longitudinal use of EmPHasis-10 and CAMPHOR questionnaire health-related quality of life scores in patients with pulmonary arterial hypertension and chronic thromboembolic pulmonary hypertension
Authors: Hendriks P , Van Thor M C J , Wapenaar M , Chandoesing P P , Van Den Toorn L , Van Den Bosch A E , Post M C , Boomars K A 
Published: October 2021

Abstract

Background
Health-related quality of life (HRQoL) is impaired in patients with pulmonary hypertension (PH). The EmPHasis-10 and CAMPHOR questionnaires are developed to evaluate HRQoL specifically in patients with PH. Data on the longitudinal use of both questionnaires are still limited.

Purpose
This paper will evaluate and compare the longitudinal value of two health-related quality of life questionnaires specific for patients with pulmonary hypertension (CAMPHOR and EmPHasis-10 questionnaires) using a broad spectrum of clinical anchor points. Furthermore we will establish minimal clinically important differences (MCID) for both questionnaires.

Methods
Sixty-one treatment naïve pulmonary arterial hypertension or chronic thromboembolic patients were prospectively included. Patients were treated according to the current ESC/ERS guidelines. We compared EmPHasis-10 and CAMPHOR scores between baseline, 6 and 12 months of follow-up and evaluated the correlation between these scores and a 5-scale symptom severity score, 5-scale overall health score, NYHA-classification, six minute walk test distance (6MWD), NT-proBNP and echocardiographic parameters. MCIDs were calculated using distribution and anchor based calculations.

Results
After one year of treatment a significant reduction in EmPHasis-10 score and CAMPHOR QoL and symptoms domain score was observed. Moderate to good correlations were observed between the questionnaires and the overall-health and symptom severity score and 6MWD. No relevant correlations were seen between the questionnaires and NT-pro-BNP and echocardiographic parameters. EmPHasis-10 scores showed strong correlations with all CAMPHOR domains. The MCID for the EmPHasis-10 questionnaire was −8. The MCIDs for the CAMPHOR domains were: activity −3, symptoms −4, QoL −3.

Conclusion
The EmPHasis-10 and CAMPHOR questionnaires are valid tools for the longitudinal measurement of HRQoL in patients with PH. The much shorter EmPHasis-10 correlates well with the CAMPHOR domain scores and with the clinical endpoints and it may be easier to use in daily practice. We established acceptable MCIDs.

Funding Acknowledgement
Type of funding sources: Private company. Main funding source(s): This research project was supported by an unrestricting grant by Actelion pharmaceuticals.
Cavin-1 modulates BMP/Smad signaling through the interaction of Caveolin-1 with BMPRII in pulmonary artery endothelial cells
Authors: Tomita S , Nakanishi N , Ogata T , Suga T , Tsuji Y , Sakamoto A , Higuchi Y , Matoba S 
Published: October 2021

Abstract

Background
Pulmonary hypertension (PH) is a progressive disease associated with poor outcomes. Caveolin-1 (Cav1) and Cavin-1 are components of caveolae, and Cav1 is identified as a related gene of pulmonary arterial hypertension (PAH). Gene mutations of bone morphogenetic protein type II receptor (BMPRII) is the most common cause of PAH. BMPRII is localized in caveolae and associates with Cav1. However, the role of the Caveolin-Cavin system on the BMP/Smad signaling and the PAH progression has not been well-known.

Purpose
Our study aims to investigate the relationship between Caveolin-Cavin system and BMP/Smad signaling pathway in pulmonary artery endothelial cells (PAECs). [Methods] Cav1 knockout mice were used to assess PH, and caveolae in PAECs were observed by electron microscope. After knocking down Cav1 and/or Cavin-1 in human PAECs (hPAECs) using siRNA, we evaluated the phosphorylation of Smad by Western blotting. Apoptosis was explored by flow cytometry. To assess the interaction between Cav1 and BMPRII, and the effect of Cavin-1 for this interaction and BMP/Smad signaling, we performed immunoprecipitation, Co-immunostaining, Proximal Ligation Assay (PLA), GST pulldown assay, and Western blotting.

Results
As in previous reports, Cav1 knockout mice exhibited PH with pulmonary vascular remodeling and right ventricular hypertrophy and PAECs isolated from Cav1 knockout mice showed caveolae disappearance. Cav1 knockdown in hPAECs reduced BMPRII at the plasma membrane and Smad 1/5/9 phosphorylation. Cav1 knockdown also significantly increased hypoxia-induced apoptosis in hPAECs. Co-immunostaining revealed that Cav1 was associated with BMPRII at the membrane of hPAECs. Cavin-1 inhibited the interaction of BMPRII with Cav1 and reduced BMPRII localization on the membrane of hPAECs. GST pulldown assay revealed that Cavin-1 and BMPRII were associated with Cav1 through the scaffolding domain in Cav1. These findings suggest that Cavin-1 and BMPRII are competitively associated with Cav1. Cavin-1 knockdown improved the interaction between Cav1 and BMPRII and inhibited both BMPRII reduction at the plasma membrane and Smad 1/5/9 dephosphorylation.

Conclusions
Cavin-1 affects the interaction of Cav1 with BMPRII at the plasma membrane and modulates BMP/Smad signaling in PAECs. The binding of Cavin-1 to Cav1 enhances the interaction between BMPR2 and Cav1, resulting in stabilization of BMPRII localization at the plasma membrane in PAECs and prevention of BMP/Smad signaling attenuation, which is important for PAH development.

Funding Acknowledgement
Type of funding sources: None.
Family history of aortic dissection is not a risk factor in Marfan syndrome with a FBN1 gene mutation
Authors: Tchitchinadze M , Milleron O , Eliahou L , Jadoui S , Ould Ouali N , Hanna N , Arnaud P , Boileau C , Gouya L , Jondeau G 
Published: October 2021

Abstract

Background
A history family of aortic dissection was considered as a risk factor for aortic dissection in patients with Marfan syndrome with a FBN1 mutation.

Objectives
Evaluate whether a family history of aortic dissection is a risk marker for dissection in this population

Methods
Retrospective study of patients coming to the reference centre between 1996 and 2018, carrying a FBN1 gene mutation. Pedigrees were obtained for each patient, and familial screening actively pursued. Patients with a family history of aortic dissection were compared with patients without family history of aortic dissection.

Results
1700 patients (age 33.2 (±17) years, 51% women) with a FBN1 gene mutation were included. 145 (8,5%) patients underwent aortic dissection at a mean age of 37.9 (±11.4) years and 323 (19%) patients had been operated at 33.8 (±13.9) years.
481 patients had a family history of aortic dissection, including 38 who dissected themselves, and 88 who underwent surgery. 1219 had no family history of aortic dissection, including 107 who dissected themselves, and 235 who underwent surgery.
Therefore, the personal risk for aortic dissection was similar in patients with and without a family history of aortic dissection (38/481, i.e. 7.9% vs 107/1219, i.e. 8.8%), as was the personal risk for prophylactic aortic surgery (88/481, i.e. 18.3% vs. 253/1219, i.e. 17.2%), and the risk for either aortic dissection or prophylactic aortic surgery (118/481, i.e. 24.5% vs. 328/1219, i.e. 26.9%).

Conclusions
In Marfan syndrome with a FBN1 gene mutation, a family history of aortic dissection is not a marker of aortic disease severity.

Funding Acknowledgement
Type of funding sources: None.
Genotype-phenotype correlations in Marfan syndrome patients with FBN1 mutations: a cohort study on 1575 patients
Authors: Arnaud P , Milleron O , Hanna N , Ropers J , Ould Ouali N , Affoune A , Langeois M , Eliahou L , Arnoult F , Renard P , Michelon-Jouneaux M , Cotillon M , Gouya L , Boileau C , Jondeau G 
Published: October 2021

Abstract

Background
Marfan syndrome (MFS) is a connective tissue disorder in which several systems are affected with great phenotypic variability. Although known to be associated with pathogenic variants in the FBN1 gene, few genotype-phenotype correlations have been found in probands' studies only.

Purpose
The aim of this study is to provide survival curves and genotype-phenotype correlations in all patients with FBN1 mutations, probands and relatives.

Methods
We established survival curves and sought genotype–phenotype correlations in a population of 1575 consecutive MFS patients with pathogenic class 4 or 5 variants in the FBN1 gene. This population represents the most comprehensive clinical database worldwide on MFS.

Results
Global survival was 90% at 60 years. However, lifelong aortic event rate (either dissection or surgery) and survival were impacted by the genotype. Premature termination codons (PTC), resulting in haploinsufficiency, were associated with a shorter life expectancy and a high lifelong risk of an aortic event (83%). Interestingly, these variants were also associated with the highest risk of severe scoliosis (52%) and with a lower risk for ectopia lentis (EL) surgery (13%). Dominant negative in-frame pathogenic variants could be subdivided according to their impact on the cysteine content of fibrillin-1: cysteine loss (–Cys) was associated with high aortic risk (73%) and a higher frequency of EL surgery (43%); cysteine addition was associated with moderate aortic risk (29%) and the highest frequency of EL surgery (48%); unchanged cysteine content was associated with high aortic risk (61%) and lower frequency of EL surgery (23%). No gene-region effect was observed, except for a more severe phenotype for in-frame variants with cysteine loss within the “neonatal region”. Aortic risk was greater for males in all subgroups, and probands were more severely affected.

Conclusions
MFS genotype-phenotype correlations related to pathogenic FBN1 variants exist for aortic and extra-aortic features. This leads us to propose new tools to refine the prognosis in this population. Preventive therapy with β-blockers and restricted exercise should be proposed regardless of the aortic diameter in the high aortic risk groups (PTC and –Cys variants). These results have major consequences on genetic counseling and personalized medicine for patients carrying a FBN1 mutation. This study also improves the overall understanding of the role of FBN1 in various organs.

Funding Acknowledgement
Type of funding sources: Foundation. Main funding source(s): Fondation Coeur et Recherche, Paris, FranceFédération Française de Cardiologie, Paris, France Patients with PTC vs. in-frame mutationsDifferences within in-frame mutations
Soluble urokinase-type plasminogen activator receptor (suPAR) is associated with risk for thromboembolic complications and mortality in patients with COVID-19
Authors: Luo S , Samelko B , Du-Fay-De-Lavallaz J M , Gomez J M D , Zemke A M , Suboc T , Williams K A , Fugar S , Simmons J A , Volgman A S , Hayek S , Reiser J 
Published: October 2021

Abstract

Background/Introduction
The high prevalence of thromboembolism in patients with COVID-19 causes significant morbidity and mortality. The soluble urokinase-type plasminogen activator receptor (suPAR), a known inflammatory and immune mediator in several renal and cardiovascular conditions, has recently been shown to correlate with acute kidney injury and severe respiratory failure in COVID-19. To date, no study has investigated the association between suPAR and thromboembolism in COVID-19.

Purpose
To evaluate associations between suPAR, thromboembolic complications, and mortality in COVID-19.

Methods
We conducted a retrospective cohort study of a random sample of 109 patients among those hospitalised at a tertiary medical centre comprising three hospitals between March and June 2020 for COVID-19 who had blood samples collected and stored on admission. Serum suPAR was measured using a commercially available enzyme immunoassay. Baseline (hospital admission) variables extracted from electronic medical records included age, sex, race/ethnicity, body mass index (BMI), history of cardiovascular disease (including deep venous thrombosis [DVT] and pulmonary embolism [PE]), serum creatinine, serum D-dimer, incident DVT/PE, and death during hospitalization. Patients were subsequently grouped by suPAR quartiles. Associations between suPAR, thromboembolic complications (PE and/or DVT), and overall mortality were evaluated using multivariable logistic regression.

Results
Among the 109 patients, mean age was 56 (standard deviation [SD], 16) years, 34 (39%) were women, mean BMI was 35 (SD, 8) kg/m2, 78 (71%) had coexisting cardiovascular disease, median creatinine level was 1.2 (interquartile range [IQR]: 0.8–2.3) mg/dl, median D-dimer level was 1.5 (IQR, 0.8–6.4) μg/ml, and median suPAR level was 10.1 (IQR: 4.1–14.4) pg/mL. Seven (6%) patients were found to have PE, 18 (17%) developed PE/DVT, and 22 (20%) died during the admission (Table). Per quartile higher suPAR level, there was higher risk for PE or DVT (OR=2.02, 95% CI 1.07–3.83, p=0.03). Compared to those in the lowest suPAR quartile, patients in the highest quartile had 11.1 times higher risk for PE/DVT (OR=11.1, 95% CI 1.51–81.8, p=0.02, Figure). SuPAR is also associated with overall mortality, with 2.25 times higher risk of death seen per quartile increase in suPAR level (OR= 2.25, 95% CI 1.24–4.06, p=0.007).

Conclusion
Higher suPAR levels at the time of hospital admission is associated with higher risk for thromboembolic complications i.e., PE and DVT, as well as mortality in patients with COVID-19.

Funding Acknowledgement
Type of funding sources: Public hospital(s). Main funding source(s): Rush University Medical Center
Impact of peripheral angioplasty on wound oxygenation measured with near-infrared spectroscopy in patients with critical limb ischemia
Authors: Foerster R , Stern M , Heinen Y , Baasen S , Sansone R , Heiss C , Kelm M , Busch H L 
Published: October 2021

Abstract

Impact of peripheral angioplasty on wound oxygenation measured with near-infrared spectroscopy in patients with critical limb ischemia
Abstract

Background
Near-infrared Spectroscopy (NIRS) has been proposed as a promising noninvasive tool for the assessment of hemoglobin oxygen saturation (StO2) in complex wounds in patients with critical limb ischemia (CLI).

Objective
Up today, NIRS measurements are undertaken at single points near the wound, but not in the wound.

Methods
In this prospective, single center study, 34 patients with PAD Rutherford stage 4–6 were included. We analyzed StO2 maps in and around the wound at baseline one day before and one day after angioplasty using a NIRS camera; macrovascular function was assessed by Doppler ultrasound with spectral analysis including ankle-brachial index (ABI).

Results
Baseline StO2 of the wound area was 63% (± 3.66 [SE]) and 34% in the wound (± 4.8 [SE]). After successful angioplasty, wound area StO2 significantly increased to 71% (± 3.09 [SE]; p&lt;0.001) and wound StO2 increased even more pronounced to 42% (± 4,77 [SE]; p&lt;0.001). Likewise, ABI increased in the treated leg (before 0.74±0.03 [SE]; after 0.87±0.02 [SE]; p=0.008).

Conclusion
This is the first study to assess oxygenation in the wound using a NIRS camera after peripheral angioplasty. NIRS monitoring of wound oxygenation in patients undergoing endovascular treatment is a promising tool to monitor tissue perfusion.

Funding Acknowledgement
Type of funding sources: Public hospital(s). Main funding source(s): Department of Cardiology, Pulmonology, and Vascular Medicine, University Duesseldorf, Medical Faculty, Duesseldorf, Germany
Impact of polyvascular disease on the prognosis of acute coronary syndrome
Authors: Laraba N , Menzou F , Aitali M , Krim M , Berrah A 
Published: October 2021

Abstract

The polyvascular disease reflects a diffuse atherosclerotic disease. By a prospective and descriptive study, recruiting three hundred thirty-six inpatient coronary care unit for acute coronary syndrome, the aim is to estimate the prevalence, to identify predictors factors and to assess the impact of the polyvascular disease in term of mortality and cardiovascular events (MACE 4points) at one, six and twelve months after discharge.
The polyvascular disease is defined by the presence of cerebrovascular disease or peripheral artery disease. The cerebrovascular disease is defined in patients with documented stroke or carotid stenosis assessed by ultrasound; the peripheral artery disease is defined by an anchle brachial index (ABI) inferior to 0.9.
The prevalence of polyvascular disease in patients with acute coronary syndrome (Men = 69,0%; mean age = 63,3y) is 28.9%. In our study population, 20.8% have cerebrovascular disease. A significant carotid stenosis is seen in 57 patients (16,7%), half of which have bilateral stenosis. 16.1% of patients have a peripheral artery disease. an ABI less than 0.45 is found in 7 patients (2,1%). 1.8% of patients have abdominal aortic aneurysm.
Many factors statistically associated with the polyvascular disease are identified. High blood pressure, thinness, advanced age, prolonged smoking and diabetes are the most powerful predictors. On admission, the polyvascular patients have more likely a KILLIP than or equal to two, anemia and kidney failure. They have an ejection fraction of the left ventricle lower than patients with only coronary artery disease. Their coronary artery disease appears more severe and extensive in coronary angiography.
Polyvascular disease appears as an independent and powerful predictor of mortality and cardiovascular events in the short and medium term in patients with acute coronary syndrome. The hazard ratio of polyvascular disease mortality at day 30, 6 months and 12 months of hospitalization are respectively 6.16, 4.44 and 5.91. The hazard ratio for disease polyvascular for cardiovascular events at 6 months and 12 months of hospitalization are 2.79 and 2.90 respectively.

Funding Acknowledgement
Type of funding sources: Public hospital(s). Main funding source(s): University hospital of Bab ElOued AlgiersUniversity hospital of Douéra Algiers
Derivation and validation of a pretest probability score for deep vein thrombosis before surgery
Authors: Hamamoto Y , Tokushige A , Yuasa T , Horizoe Y , Yasuda H , Kubozono T , Ikeda Y , Ohishi M 
Published: October 2021

Abstract

Background
Venous thromboembolism represents a crucial perioperative complication and causes morbidity and mortality. It is important to predict deep vein thrombosis (DVT) before surgery under general anesthesia.

Purpose
We developed a pretest probability score for predicting DVT with perioperative clinical and laboratory variables.

Methods
Total 7435 patients were planed surgery under general anesthesia between 2017 and 2018. 1313 patients were performed whole leg ultrasonography suspected DVT using cutoff point of D-dimer ≥1μg/ml. We excluded age &lt;18 years, ongoing anticoagulant therapy, other thrombosis, protein C deficiency, disseminated intravascular coagulation, central venous catheter, pregnancy and aneurysm. We enrolled 971 patients, we divided into the derivation cohort or the validation cohort. The association of DVT with multiple variables was characterized in a derivation cohort of 651 patients. The score validated in an independent cohort of 322 patients from the same study. We also performed a validation of this model in an independent cohort of patients derived from the same observational study.

Results
We found 6 clinical and 1 laboratory parameters that predicted DVT in patients before surgery. The prediction rule for DVT assigned 2 points for D-dimer more than 1.44 μg/ml and 1 point for age ≥60 years, female, ongoing steroid, active cancer with high risk of DVT, prolong immobility and antipsychotic drug. In derivation and validation cohorts, area under the curve was 0.73 and 0.70, respectively. New preoperative risk model with these parameters stratified patients into 3 individual categories corresponding to the risk of DVT. Rates of DVT in the derivation and validation cohorts, respectively, were 6% and 7% in low-risk (score 0–2), 22% and 21% in intermediate-risk (score 3–4), and 49% and 47% in high-risk (score ≥5) category. Rates of fresh DVT were 1% and 3% in low-risk, 10% and 9% in intermediate-risk, and 33% and 19% in high-risk category.

Conclusion
This score stratifies perioperative DVT risk and may detect effectively DVT. The findings should be considered with the further prospective research.

Funding Acknowledgement
Type of funding sources: None. Rate of DVT
Association of rs12122341 polymorphism with the development of acute cerebrovascular event
Authors: Chernova A , Nikulina S , Nikulin D 
Published: October 2021

Abstract

Purpose
To study SNP rs12122341 (C&gt; G) with development of Acute Cerebrovascular Event in the patients with cardiovascular pathology and risk factors of its development who are representatives of the east Siberian population.

Material and methods
260 patients with Acute Cerebrovascular Event participated in a research (age [57.0; 51.0–62.0]) and 272 patients of control group (age [55.0; 51.0–62.0].). Among the patients who transferred Acute Cerebrovascular Event, 157 men and 103 women. The control group included 170 men and 102 women. Inspection of the main group included: collecting complaints, anamnesis, clinical examination, computer tomography of a brain, electrocardiography, echo, ultrasonic of arteries, daily monitoring of arterial blood pressure and cardiac rhythm, analysis of a coagulant system of blood. Patients of the main group had the following cardiovascular pathology and risk factors: arterial hypertension, supraventricular tachycardia, dislipidemiya, atherosclerosis brachiocephalic of arteries, disturbances of a system of a hemostasis. The control group is examined within the international HAPIEE project. The molecular and genetic research was conducted by PCR method in real time. Statistical processing of material was carried out with use of set of the Statistica for Windows 7.0, Excel and SPSS 22 application programs.

Results
As a result of a research gender differences in functions of genotypes of SNP rs12122341 are set (C&gt; G). So, for males risk factor of Acute Cerebrovascular Event is the genotype of CC, for female persons – CG genotype. In the general group of patients with Acute Cerebrovascular Event and also in subgroups of patients with different cardiovascular pathology and risk factors of statistically significant differences in frequencies of genotypes and alleles it is not revealed.

Conclusion
A genotype of the CC SNP rs12122341 (C&gt; G) the risk of development of Acute Cerebrovascular Event in males in comparison with genotypes of CG and GG (p=0.009 raises; OR 1.83, 95% of CI: 1.16–2.91). The genotype of CG performs protective function concerning development of Acute Cerebrovascular Event in males. At female persons risk factor of development of Acute Cerebrovascular Event is CG genotype.

Funding Acknowledgement
Type of funding sources: None.