| 1. |
- Gkourogianni, Alexandra, et al.
(författare)
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Clinical characterization of patients with autosomal dominant short stature due to aggrecan mutations
- 2017
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Ingår i: Journal of Clinical Endocrinology and Metabolism. - Cary, USA : Oxford University Press. - 0021-972X .- 1945-7197. ; 102:2, s. 460-469
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Tidskriftsartikel (refereegranskat)abstract
- Context: Heterozygous mutations in the Aggrecan gene (ACAN) cause autosomal dominant short stature with bone age (BA) acceleration, premature growth cessation and minor skeletal abnormalities.Objective: Characterize the phenotypic spectrum, associated conditions and response to growth-promoting therapies.Design: Retrospective international cohort study.Patients: Information from 103 individuals (57 female, 46 male) from 20 families with confirmed heterozygous ACAN mutations were included.Methods: Families with autosomal dominant short stature and heterozygous ACAN mutations were identified and confirmed using whole-exome sequencing, targeted next generation sequencing, and/or Sanger sequencing. Clinical information was collected from medical records.Results: Identified ACAN variants showed perfect co-segregation with phenotype. Adult individuals had mildly disproportionate short stature (median height: -2.8 SDS, range: -5.9 to -0.9) and histories of early growth cessation. The condition was frequently associated with early-onset osteoarthritis (12 families) and intervertebral disc disease (9 families). There was no apparent genotype-phenotype correlation between type of ACAN mutation and presence of joint complaints. During childhood, height was less affected (median height: -2.0 SDS, range: -4.2 to -0.6). In contrast to most children with short stature, the majority of children had advanced BA (BA - CA, median: +1.3y; range +0.0 to +3.7y) reflecting a reduction in remaining growth potential. Nineteen individuals had received GH with some evidence of increased growth velocity.Conclusions Heterozygous ACAN mutations result in a phenotypic spectrum ranging from mild and proportionate short stature to a mild skeletal dysplasia with disproportionate short stature and brachydactyly. In several of the families, affected individuals developed early-onset osteoarthritis and degenerative disc disease requiring intervention, suggesting dysfunction of articular cartilage and intervertebral disc cartilage. Additional studies are needed to determine the optimal treatment strategy for these patients.
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| 2. |
- Maison-Blanche, Pierre, et al.
(författare)
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An open-label study to investigate the cardiac safety profile of cabazitaxel in patients with advanced solid tumors
- 2014
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Ingår i: Cancer Chemotherapy and Pharmacology. - : Springer Science and Business Media LLC. - 0344-5704 .- 1432-0843. ; 73:6, s. 1241-1252
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Tidskriftsartikel (refereegranskat)abstract
- This study assessed the cardiovascular safety of cabazitaxel, based on thorough evaluation of QT and non-QT variables, and the relationship between pharmacokinetic and pharmacodynamic electrocardiographic (ECG) profiles and the occurrence of Grade a parts per thousand yen3 cardiovascular adverse events. Patients with advanced solid tumors were treated with cabazitaxel 25 mg/m(2) every 3 weeks. Digital ECG recordings were obtained during Cycle 1 over 24 h after dosing. The primary end point was effect of cabazitaxel on QT interval corrected by the Fridericia formula (QTcF). Secondary end points were additional ECG parameters (QT, PR and QRS intervals, and heart rate), plasma pharmacokinetics of cabazitaxel and overall clinical safety. The pharmacodynamic (ECG) population included 94 patients. In 63 patients with a full 24-h ECG evaluation, the maximum upper bound of 90 % confidence interval (CI) for mean QTcF change from baseline was 7.46 ms (mean 4.8 ms), occurring at 1 h 30 min post-infusion. The slope of QTcF change from baseline versus cabazitaxel concentration was slightly negative (-0.012 [95 % CI -0.017; -0.008], equivalent to a 1.2 ms decrease per 100 ng/mL increase in cabazitaxel concentration). For non-QT variables, no effect was noted. No Grade a parts per thousand yen3 cardiac adverse events were observed; Grade a parts per thousand yen3 hypotension and lymphocele occurred in two patients and one patient, respectively. These results suggest that cabazitaxel has no clinically significant cardiovascular adverse effects in patients with advanced solid tumors.
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| 3. |
- Sörensen, Jens, et al.
(författare)
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Diagnosis of left ventricular hypertrophy using non-ECG-gated 15O-water PET
- 2022
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Ingår i: Journal of Nuclear Cardiology. - : Springer. - 1071-3581 .- 1532-6551. ; , s. 2361-2373
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Tidskriftsartikel (refereegranskat)abstract
- Aim: To develop a method for diagnosing left ventricular (LV) hypertrophy from cardiac perfusion 15O-water positron emission tomography (PET).Methods: We retrospectively pooled data from 139 subjects in four research cohorts. LV remodeling patterns ranged from normal to severe eccentric and concentric hypertrophy. 15O-water PET scans (n = 197) were performed with three different PET devices. A low-end scanner (66 scans) was used for method development, and remaining scans with newer devices for a blinded evaluation. Dynamic data were converted into parametric images of perfusable tissue fraction for semi-automatic delineation of the LV wall and calculation of LV mass (LVM) and septal wall thickness (WT). LVM and WT from PET were compared to cardiac magnetic resonance (CMR, n = 47) and WT to 2D-echocardiography (2DE, n = 36). PET accuracy was tested using linear regression, Bland–Altman plots, and ROC curves. Observer reproducibility were evaluated using intraclass correlation coefficients.Results: High correlations were found in the blinded analyses (r ≥ 0.87, P < 0.0001 for all). AUC for detecting increased LVM and WT (> 12 mm and > 15 mm) was ≥ 0.95 (P < 0.0001 for all). Reproducibility was excellent (ICC ≥ 0.93, P < 0.0001).Conclusion: 15O-water PET might detect LV hypertrophy with high accuracy and precision.
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| 4. |
- Sörensen, Jens, et al.
(författare)
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Diagnostic accuracy of 15O-water PET for left-ventricular hypertrophy
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- Aim: To develop and validate a method for diagnosing left ventricular (LV) hypertrophy from cardiac perfusion 15O-water positron emission tomography (PET).Methods:This was a retrospective study with pooled data from 139 subjects in four research cohorts. LV remodeling patterns ranged from normal to severe eccentric and concentric hypertrophy. 15O-water PET scans (n=197) were performed with three different PET devices. Data from a low-end scanner (66 scans) were used for method development, remaining scans were used for a blinded evaluation. Dynamic data were converted into parametric images of perfusable tissue fraction for semi-automatic delineation of the LV wall in the short axis view. The enclosed region was used to calculate LV mass (LVM) and septal wall thickness (WT). LVM and WT from PET were compared to cardiac magnetic resonance (CMR, n=47) and WT to 2D-echocardiography (2DE, n=36). PET accuracy was tested using linear regression, Bland-Altman plots, and ROC curves. Observer reproducibility were evaluated using intraclass correlation coefficients. Results: Correlations (PET-LVM and PET-WT towards CMR; PET-WT towards 2DE) were high (r≥0.87, P<0.0001 for all) with high-end scanners, and slightly lower for LVM (r=0.84) and WT (r=0.76, both P<0.0001) with a low-end scanner. There was no significant bias for WT, but a proportional bias for LVM was found. The area-under-the-curve for blinded detection of increased LVM and WT (>12 mm and >15 mm) diagnosed by conventional imaging was ≥0.95 (P<0.0001 for all). Reproducibility was excellent (ICC ≥ 0.93, P<0.0001). Conclusion: 15O-water PET might detect LV hypertrophy with high accuracy and precision.
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