| 1. |
- Atefi, Seyed Reza, et al.
(author)
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Intracranial haemorrhage alters scalp potential distributions in bioimpedance cerebral monitoring applications : preliminary results from FEM simulation on a realistic head model and human subjects
- 2016
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In: Medical Physics. - : American Association of Physicists in Medicine. - 2473-4209 .- 0094-2405. ; 43:2, s. 675-686
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Journal article (peer-reviewed)abstract
- Purpose: Current diagnostic neuroimaging for detection of intracranial hemorrhage (ICH) is limited to fixed scanners requiring patient transport and extensive infrastructure support. ICH diagnosis would therefore benefit from a portable diagnostic technology, such as electrical bioimpedance (EBI). Through simulations and patient observation, the authors assessed the influence of unilateral ICH hematomas on quasisymmetric scalp potential distributions in order to establish the feasibility of EBI technology as a potential tool for early diagnosis. Methods: Finite element method (FEM) simulations and experimental leftright hemispheric scalp potential differences of healthy and damaged brains were compared with respect to the asymmetry caused by ICH lesions on quasisymmetric scalp potential distributions. In numerical simulations, this asymmetry was measured at 25 kHz and visualized on the scalp as the normalized potential difference between the healthy and ICH damaged models. Proof-of-concept simulations were extended in a pilot study of experimental scalp potential measurements recorded between 0 and 50 kHz with the authors custom-made bioimpedance spectrometer. Mean leftright scalp potential differences recorded from the frontal, central, and parietal brain regions of ten healthy control and six patients suffering from acute/subacute ICH were compared. The observed differences were measured at the 5% level of significance using the two-sample Welch ttest. Results: The 3D-anatomically accurate FEM simulations showed that the normalized scalp potential difference between the damaged and healthy brain models is zero everywhere on the head surface, except in the vicinity of the lesion, where it can vary up to 5%. The authors preliminary experimental results also confirmed that the leftright scalp potential difference in patients with ICH (e.g., 64 mV) is significantly larger than in healthy subjects (e.g., 20.8 mV; P < 0.05). Conclusions: Realistic, proof-of-concept simulations confirmed that ICH affects quasisymmetric scalp potential distributions. Pilot clinical observations with the authors custom-made bioimpedance spectrometer also showed higher leftright potential differences in the presence of ICH, similar to those of their simulations, that may help to distinguish healthy subjects from ICH patients. Although these pilot clinical observations are in agreement with the computer simulations, the small sample size of this study lacks statistical power to exclude the influence of other possible confounders such as age, ex, and electrode positioning. The agreement with previously published simulation-based and clinical results, however, suggests that EBI technology may be potentially useful for ICH detection.
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| 2. |
- Brugada, Josep, et al.
(author)
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Pharmacological and non-pharmacological therapy for arrhythmias in the pediatric population : EHRA and AEPC-Arrhythmia Working Group joint consensus statement
- 2013
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In: Europace. - : Oxford University Press (OUP). - 1099-5129 .- 1532-2092. ; 15:9, s. 1337-1382
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Journal article (peer-reviewed)abstract
- In children with structurally normal hearts, the mechanisms of arrhythmias are usually the same as in the adult patient. Some arrhythmias are particularly associated with young age and very rarely seen in adult patients. Arrhythmias in structural heart disease may be associated either with the underlying abnormality or result from surgical intervention. Chronic haemodynamic stress of congenital heart disease (CHD) might create an electrophysiological and anatomic substrate highly favourable for re-entrant arrhythmias.As a general rule, prescription of antiarrhythmic drugs requires a clear diagnosis with electrocardiographic documentation of a given arrhythmia. Risk-benefit analysis of drug therapy should be considered when facing an arrhythmia in a child. Prophylactic antiarrhythmic drug therapy is given only to protect the child from recurrent supraventricular tachycardia during this time span until the disease will eventually cease spontaneously. In the last decades, radiofrequency catheter ablation is progressively used as curative therapy for tachyarrhythmias in children and patients with or without CHD. Even in young children, procedures can be performed with high success rates and low complication rates as shown by several retrospective and prospective paediatric multi-centre studies. Three-dimensional mapping and non-fluoroscopic navigation techniques and enhanced catheter technology have further improved safety and efficacy even in CHD patients with complex arrhythmias.During last decades, cardiac devices (pacemakers and implantable cardiac defibrillator) have developed rapidly. The pacing generator size has diminished and the pacing leads have become progressively thinner. These developments have made application of cardiac pacing in children easier although no dedicated paediatric pacing systems exist.
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| 3. |
- Chubb, Henry, et al.
(author)
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Long-Term Outcome Following Catheter Valvotomy for Pulmonary Atresia With Intact Ventricular Septum
- 2012
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In: Journal of the American College of Cardiology. - : Elsevier BV. - 0735-1097. ; 59:16, s. 1468-1476
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Journal article (peer-reviewed)abstract
- Objectives This study investigated the outcome for all patients undergoing catheter valve perforation for pulmonary atresia with intact ventricular septum (PAIVS) 21 years after the first procedure at their center. Background Catheter perforation for PAIVS is now an established procedure. However, the management of the borderline right ventricle (RV) is controversial, and there may be a place for novel techniques such as stenting of the arterial duct. Methods There were 37 successful valve perforations (total 39 patients). Median length of follow-up was 9.2 years (range 2.2 to 21.0 years). Seventeen patients had stenting of the arterial duct. The mean (SD) initial z-score for the tricuspid valve was -5.1 (+/- 3.4), and a further 142 sets of measurements were taken to assess the growth of the RV of survivors. Results There were 8 deaths (21%), and no deaths after the first 35 days. There were no late arrhythmias or ischemic events. Twenty-five patients (83% of survivors) have a biventricular circulation. For patients who had stenting of the arterial duct, significant reductions in early reintervention (0 vs. 7 patients, p = 0.009) and hospital stay (17.4 +/- 18.1 days vs. 33.8 +/- 28.6 days, p = 0.012) occurred, with no increase in mortality or morbidity. There was no catch-up growth of the RV in patients who had a biventricular outcome (z-score increase +0.08/year, p = 0.26). Conclusions Long-term survival is good, and even small RVs may be amenable to this procedure. Multiple interventions may be required to achieve biventricular circulation, but stenting of the arterial duct may reduce hospital stay and repeat procedures. (J Am Coll Cardiol 2012;59:1468-76) (C) 2012 by the American College of Cardiology Foundation
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| 4. |
- Gero, Daniel, et al.
(author)
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Defining Global Benchmarks in Bariatric Surgery A Retrospective Multicenter Analysis of Minimally Invasive Roux-en-Y Gastric Bypass and Sleeve Gastrectomy
- 2019
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In: Annals of Surgery. - : Lippincott Williams & Wilkins. - 0003-4932 .- 1528-1140. ; 270:5, s. 859-867
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Journal article (peer-reviewed)abstract
- Objective: To define “best possible” outcomes for bariatric surgery (BS)(Roux-en-Y gastric bypass [RYGB] and sleeve gastrectomy [SG]).Background: Reference values for optimal surgical outcomes in well-defined low-risk bariatric patients have not been established so far. Consequently, outcome comparison across centers and over time is impeded by heterogeneity in case-mix.Methods: Out of 39,424 elective BS performed in 19 high-volume academic centers from 3 continents between June 2012 and May 2017, we identified 4120 RYGB and 1457 SG low-risk cases defined by absence of previous abdominal surgery, concomitant procedures, diabetes mellitus, sleep apnea, cardiopathy, renal insufficiency, inflammatory bowel disease, immunosuppression, anticoagulation, BMI>50 kg/m2 and age>65 years. We chose clinically relevant endpoints covering the intra- and postoperative course. Complications were graded by severity using the comprehensive complication index. Benchmark values were defined as the 75th percentile of the participating centers’ median values for respective quality indicators.Results: Patients were mainly females (78%), aged 38±11 years, with a baseline BMI 40.8 ± 5.8 kg/m2. Over 90 days, 7.2% of RYGB and 6.2% of SG patients presented at least 1 complication and no patients died (mortality in nonbenchmark cases: 0.06%). The most frequent reasons for readmission after 90-days following both procedures were symptomatic cholelithiasis and abdominal pain of unknown origin. Benchmark values for both RYGB and SG at 90-days postoperatively were 5.5% Clavien-Dindo grade ≥IIIa complication rate, 5.5% readmission rate, and comprehensive complication index ≤33.73 in the subgroup of patients presenting at least 1 grade ≥II complication.Conclusion: Benchmark cutoffs targeting perioperative outcomes in BS offer a new tool in surgical quality-metrics and may be implemented in quality-improvement cycle.ClinicalTrials.gov Identifier NCT03440138
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| 5. |
- Lange, Leslie A, et al.
(author)
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Whole-Exome Sequencing Identifies Rare and Low-Frequency Coding Variants Associated with LDL Cholesterol.
- 2014
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In: American Journal of Human Genetics. - : Elsevier BV. - 0002-9297. ; 94:2, s. 233-245
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Journal article (peer-reviewed)abstract
- Elevated low-density lipoprotein cholesterol (LDL-C) is a treatable, heritable risk factor for cardiovascular disease. Genome-wide association studies (GWASs) have identified 157 variants associated with lipid levels but are not well suited to assess the impact of rare and low-frequency variants. To determine whether rare or low-frequency coding variants are associated with LDL-C, we exome sequenced 2,005 individuals, including 554 individuals selected for extreme LDL-C (>98(th) or <2(nd) percentile). Follow-up analyses included sequencing of 1,302 additional individuals and genotype-based analysis of 52,221 individuals. We observed significant evidence of association between LDL-C and the burden of rare or low-frequency variants in PNPLA5, encoding a phospholipase-domain-containing protein, and both known and previously unidentified variants in PCSK9, LDLR and APOB, three known lipid-related genes. The effect sizes for the burden of rare variants for each associated gene were substantially higher than those observed for individual SNPs identified from GWASs. We replicated the PNPLA5 signal in an independent large-scale sequencing study of 2,084 individuals. In conclusion, this large whole-exome-sequencing study for LDL-C identified a gene not known to be implicated in LDL-C and provides unique insight into the design and analysis of similar experiments.
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| 6. |
- Mantz, Amy, et al.
(author)
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Free Polyethylenimine Enhances Substrate-Mediated Gene Delivery on Titanium Substrates Modified With RGD-Functionalized Poly(acrylic acid) Brushes
- 2019
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In: Frontiers in Chemistry. - : FRONTIERS MEDIA SA. - 2296-2646. ; 7
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Journal article (peer-reviewed)abstract
- Substrate mediated gene delivery (SMD) is a method of immobilizing DNA complexes to a substrate via covalent attachment or nonspecific adsorption, which allows for increased transgene expression with less DNA compared to traditional bolus delivery. It may also increase cells receptivity to transfection via cell-material interactions. Substrate modifications with poly(acrylic) acid (PM) brushes may improve SMD by enhancing substrate interactions with DNA complexes via tailored surface chemistry and increasing cellular adhesion via moieties covalently bound to the brushes. Previously, we described a simple method to graft PM brushes to Ti and further demonstrated conjugation of cell adhesion peptides (i.e., RGD) to the PM brushes to improve biocompatibility. The objective of this work was to investigate the ability of Ti substrates modified with PM-RGD brushes (PM-RGD) to immobilize complexes composed of branched polyethyleneimine and DNA plasmids (bPEI-DNA) and support SMD in NIH/3T3 fibroblasts. Transfection in NIH/3T3 cells cultured on bPEI-DNA complexes immobilized onto PM-RGD substrates was measured and compared to transfection in cells cultured on control surfaces with immobilized complexes including Flat Ti, PM brushes modified with a control peptide (RGE), and unmodified PM. Transfection was two-fold higher in cells cultured on PM-RGD compared to those cultured on all control substrates. While DNA immobilization measured with radiolabeled DNA indicated that all substrates (PM-RGD, unmodified PM, Flat Ti) contained nearly equivalent amounts of loaded DNA, ellipsometric measurements showed that more total mass (i.e., DNA and bPEI, both complexed and free) was immobilized to PM and PM-RGD compared to Flat Ti. The increase in adsorbed mass may be attributed to free bPEI, which has been shown to improve transfection. Further transfection investigations showed that removing free bPEI from the immobilized complexes decreased SMD transfection and negated any differences in transfection success between cells cultured on PM-RGD and on control substrates, suggesting that free bPEI may be beneficial for SMD in cells cultured on bPEI-DNA complexes immobilized on PM-RGD grafted to Ti. This work demonstrates that substrate modification with PM-RGD is a feasible method to enhance SMD outcomes on Ti and may be used for future applications such as tissue engineering, gene therapy, and diagnostics.
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| 7. |
- Thomas, Minta, et al.
(author)
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Genome-wide Modeling of Polygenic Risk Score in Colorectal Cancer Risk.
- 2020
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In: American Journal of Human Genetics. - Cambridge : Elsevier BV. - 0002-9297 .- 1537-6605. ; 107:3, s. 432-444
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Journal article (peer-reviewed)abstract
- Accurate colorectal cancer (CRC) risk prediction models are critical for identifying individuals at low and high risk of developing CRC, as they can then be offered targeted screening and interventions to address their risks of developing disease (if they are in a high-risk group) and avoid unnecessary screening and interventions (if they are in a low-risk group). As it is likely that thousands of genetic variants contribute to CRC risk, it is clinically important to investigate whether these genetic variants can be used jointly for CRC risk prediction. In this paper, we derived and compared different approaches to generating predictive polygenic risk scores (PRS) from genome-wide association studies (GWASs) including 55,105 CRC-affected case subjects and 65,079 control subjects of European ancestry. We built the PRS in three ways, using (1) 140 previously identified and validated CRC loci; (2) SNP selection based on linkage disequilibrium (LD) clumping followed by machine-learning approaches; and (3) LDpred, a Bayesian approach for genome-wide risk prediction. We tested the PRS in an independent cohort of 101,987 individuals with 1,699 CRC-affected case subjects. The discriminatory accuracy, calculated by the age- and sex-adjusted area under the receiver operating characteristics curve (AUC), was highest for the LDpred-derived PRS (AUC = 0.654) including nearly 1.2 M genetic variants (the proportion of causal genetic variants for CRC assumed to be 0.003), whereas the PRS of the 140 known variants identified from GWASs had the lowest AUC (AUC = 0.629). Based on the LDpred-derived PRS, we are able to identify 30% of individuals without a family history as having risk for CRC similar to those with a family history of CRC, whereas the PRS based on known GWAS variants identified only top 10% as having a similar relative risk. About 90% of these individuals have no family history and would have been considered average risk under current screening guidelines, but might benefit from earlier screening. The developed PRS offers a way for risk-stratified CRC screening and other targeted interventions.
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| 8. |
- Thomas, Minta, et al.
(author)
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Response to Li and Hopper
- 2021
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In: American Journal of Human Genetics. - : Elsevier BV. - 0002-9297 .- 1537-6605. ; 108:3, s. 527-529
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Journal article (peer-reviewed)
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