Feasibility study of preoperative microvessel evaluation and characterization in perforator flaps using various modes of color-coded duplex sonography (CCDS)

Background Color-coded duplex sonography (CCDS) is useful for perforator flap design showing the highest sensitivity in identifying microvessels. This prospective study evaluates the feasibility of different ultrasound (US) modes applied by the microsurgeon in daily practice suggesting quantifiable reference values. Methods Twenty-four patients aged between 17 and 68 years (mean 43.3 +/- 14.2 years) with 18 anterolateral thigh (ALT) and 6 superficial circumflex iliac artery (SCIP) flaps were included. Indications were traumatic (n= 12), infectious (n= 6), ischemic (n= 4), or tumor-associated defects (n= 2). Different US modes were evaluated regarding applicability using multifrequency linear probes (5-15 MHz). Vessels diameter, peak systolic velocity (PSV), end diastolic velocity (EDV), and resistance index (RI) were measured. Preoperative results were correlated to intraoperative findings. Results In the examined patient group with 24 perforator flaps a 100% correlation was seen when comparing perforators detected with CCDS/PD with intraoperative findings using optimized US settings. Sensitivity, PPV, and accuracy of CCDS were 100% respectively. Mean PSV of 16.99 +/- 6.07 cm/s, mean EDV of 5.01 +/- 1.84 cm/s and RI of 0.7 +/- 0.07 were measured in microvessels (PW-mode). CCDS proved to be superior compared to PD in correct diameter assessment showing a mean diameter of 1.65 +/- 0.45 mm, compared to PD-mode 1.31 +/- 0.24 mm. Mean PSV and EDV were higher in ALT than in SCIP flaps, RI was slightly higher in SCIP flaps (p > .05). There were no significant differences in size of different flaps' perforators (p > .05). Conclusion CCDS represents a highly valuable tool in the daily practice of free flap reconstructions using optimized low flow US settings and multifrequency linear probes

GWAS meta-analysis of over 29,000 people with epilepsy identifies 26 risk loci and subtype-specific genetic architecture

Epilepsy is a highly heritable disorder affecting over 50 million people worldwide, of which about one-third are resistant to current treatments. Here we report a multi-ancestry genome-wide association study including 29,944 cases, stratified into three broad categories and seven subtypes of epilepsy, and 52,538 controls. We identify 26 genome-wide significant loci, 19 of which are specific to genetic generalized epilepsy (GGE). We implicate 29 likely causal genes underlying these 26 loci. SNP-based heritability analyses show that common variants explain between 39.6% and 90% of genetic risk for GGE and its subtypes. Subtype analysis revealed markedly different genetic architectures between focal and generalized epilepsies. Gene-set analyses of GGE signals implicate synaptic processes in both excitatory and inhibitory neurons in the brain. Prioritized candidate genes overlap with monogenic epilepsy genes and with targets of current antiseizure medications. Finally, we leverage our results to identify alternate drugs with predicted efficacy if repurposed for epilepsy treatment

Genome-wide identification and phenotypic characterization of seizure-associated copy number variations in 741,075 individuals

Copy number variants (CNV) are established risk factors for neurodevelopmental disorders with seizures or epilepsy. With the hypothesis that seizure disorders share genetic risk factors, we pooled CNV data from 10,590 individuals with seizure disorders, 16,109 individuals with clinically validated epilepsy, and 492,324 population controls and identified 25 genome-wide significant loci, 22 of which are novel for seizure disorders, such as deletions at 1p36.33, 1q44, 2p21-p16.3, 3q29, 8p23.3-p23.2, 9p24.3, 10q26.3, 15q11.2, 15q12-q13.1, 16p12.2, 17q21.31, duplications at 2q13, 9q34.3, 16p13.3, 17q12, 19p13.3, 20q13.33, and reciprocal CNVs at 16p11.2, and 22q11.21. Using genetic data from additional 248,751 individuals with 23 neuropsychiatric phenotypes, we explored the pleiotropy of these 25 loci. Finally, in a subset of individuals with epilepsy and detailed clinical data available, we performed phenome-wide association analyses between individual CNVs and clinical annotations categorized through the Human Phenotype Ontology (HPO). For six CNVs, we identified 19 significant associations with specific HPO terms and generated, for all CNVs, phenotype signatures across 17 clinical categories relevant for epileptologists. This is the most comprehensive investigation of CNVs in epilepsy and related seizure disorders, with potential implications for clinical practice

Genetic testing before epilepsy surgery - An exploratory survey and case collection from German epilepsy centers

BoSSelmann CM, Antonio-Arce VS, Schulze-Bonhage A, et al. Genetic testing before epilepsy surgery - An exploratory survey and case collection from German epilepsy centers. Seizure. 2021;95:4-10.INTRODUCTION: Genetic testing in people with epilepsy may support presurgical decision-making. It is currently unclear to what extent epilepsy centres use genetic testing in presurgical evaluation.; METHODS: We performed an exploratory survey among members of the German Society for Epileptology to study the current practice of genetic testing in presurgical evaluation at the respective sites. Survey participants contributed educational case reports.; RESULTS: The majority of participants consider genetic testing to be useful in individuals with familial syndromes or phenotypic features suggesting a genetic etiology. We report 25 cases of individuals with a confirmed genetic diagnosis that have previously undergone epilepsy surgery. Our cases demonstrate that a genetic diagnosis has an impact on both the decision-making process during presurgical evaluation, as well as the postoperative outcome.; CONCLUSION: Genetic testing as part of the presurgical work-up is becoming increasingly established in epilepsy centres across Germany. mTORopathies and genetic hypothalamic hamartomas seem to be associated with a generally favourable surgical outcome. Synaptopathies and channelopathies may be associated with a worse outcome and should be considered on a case-by-case level. Prospective studies are needed to examine the impact of an established genetic diagnosis on postsurgical outcome. Copyright © 2021 British Epilepsy Association. Published by Elsevier Ltd. All rights reserved

Absent pulmonary valve syndrome - diagnosis, associations and outcome in 71 prenatally diagnosed cases

To analyze the spectrum of prenatally diagnosed absent pulmonary valve syndrome (APVS) and the outcome from diagnosis onwards. Fetuses with APVS and tetralogy of Fallot (TOF/APVS) and with APVS and intact ventricular septum (APVS/IVS) were included.status: publishe

Consort 2010 checklist.

ObjectiveHypokalemia is associated with increased risk of arrhythmias and it is recommended to monitor plasma potassium (p-K) regularly in at-risk patients with cardiovascular diseases. It is poorly understood if administration of potassium supplements and mineralocorticoid receptor antagonists (MRA) aimed at increasing p-K also increases intracellular potassium.MethodsAdults aged≥18 years with an implantable cardioverter defibrillator (ICD) were randomized (1:1) to a control group or to an intervention that included guidance on potassium rich diets, potassium supplements, and MRA to increase p-K to target levels of 4.5–5.0 mmol/l for six months. Total-body-potassium (TBK) was measured by a Whole-Body-Counter along with p-K at baseline, after six weeks, and after six months.ResultsFourteen patients (mean age: 59 years (standard deviation 14), 79% men) were included. Mean p-K was 3.8 mmol/l (0.2), and mean TBK was 1.50 g/kg (0.20) at baseline. After six-weeks, p-K had increased by 0.47 mmol/l (95%CI:0.14;0.81), p = 0.008 in the intervention group compared to controls, whereas no significant difference was found in TBK (44 mg/kg (-20;108), p = 0.17). After six-months, no significant difference was found in p-K as compared to baseline (0.16 mmol/l (-0.18;0.51), p = 0.36), but a significant increase in TBK of 82 mg/kg (16;148), p = 0.017 was found in the intervention group compared to controls.ConclusionsIncreased potassium intake and MRAs increased TBK gradually and a significant increase was seen after six months. The differentially regulated p-K and TBK challenges current knowledge on potassium homeostasis and the time required before the full potential of p-K increasing treatment can be anticipated.Trial registrationwww.clinicaltrials.gov (NCT03833089).</div