Intentional coverage of the left subclavian artery during endovascular repair of traumatic descending thoracic aortic transection

ObjectiveThis single-center, prospective study aimed to investigate the technical success and outcome of intentional coverage of the left subclavian artery (LSA) in patients undergoing thoracic endovascular aortic repair (TEVAR) for traumatic rupture of the aortic isthmus at a tertiary care medical center.MethodsFrom January 2005 to June 2011, patients who presented with traumatic aortic transection underwent TEVAR with coverage of the LSA when the distance between the artery and the rupture was <2 cm. At 12, 24, and 72 hours postoperatively, clinical and neurologic evaluation including transcranial Doppler insonation of the brachial artery was performed. A decrease in peak systolic velocity (PSV) >60% with respect to the contralateral one was considered relevant. Functional status of the left arm was evaluated using a provocative test. Thoracoabdominal computerized tomographic angiography was performed postoperatively at 3-, 6-, and 12-month follow-up.ResultsThirty-one patients (mean age 35 years) underwent emergency TEVAR for traumatic aortic transection with intentional LSA coverage during the study period. In four cases (12.9%) coverage was partial. Two patients (6.4%) died during the postoperative period due to associated lesions. No signs of vertebrobasilar insufficiency, stroke, or paraplegia were observed in any of the patients. Nine patients (36%) had severe arm claudication (ischemic pain within 60 seconds of beginning arm exercise and decrease of PSV between 50% and 60%). Risk factors for the condition were left vertebral artery diameter <3 mm (P < .0001). A significant correlation was found between the degree of PSV reduction and left arm symptoms (P < .0001). There was an improvement in ischemic arm symptoms (P < .0001) during mean follow-up of 36 months (range, 6-65 months), with only one patient (4.2%) presenting with severe claudication. Freedom from reintervention at 48 months was 93.5%. No signs of endoleaks or graft migrations were detected on computerized tomographic angiography control scans.ConclusionsCoverage of the LSA during TEVAR for traumatic aortic injuries appears to be a feasible, safe method for extending the endograft landing zone without increasing the risk of paraplegia, stroke, or left arm ischemia. Left vertebral artery diameter can be used to identify patients at risk for postoperative left arm ischemia

Characterization of antiseizure medications effects on the EEG neurodynamic by fractal dimension

Objectives: An important challenge in epilepsy is to define biomarkers of response to treatment. Many electroencephalography (EEG) methods and indices have been developed mainly using linear methods, e.g., spectral power and individual alpha frequency peak (IAF). However, brain activity is complex and non-linear, hence there is a need to explore EEG neurodynamics using nonlinear approaches. Here, we use the Fractal Dimension (FD), a measure of whole brain signal complexity, to measure the response to anti-seizure therapy in patients with Focal Epilepsy (FE) and compare it with linear methods. Materials: Twenty-five drug-responder (DR) patients with focal epilepsy were studied before (t1, named DR-t1) and after (t2, named DR-t2) the introduction of the anti-seizure medications (ASMs). DR-t1 and DR-t2 EEG results were compared against 40 age-matched healthy controls (HC). Methods: EEG data were investigated from two different angles: frequency domain—spectral properties in δ, θ, α, β, and γ bands and the IAF peak, and time-domain—FD as a signature of the nonlinear complexity of the EEG signals. Those features were compared among the three groups. Results: The δ power differed between DR patients pre and post-ASM and HC (DR-t1 vs. HC, p &lt; 0.01 and DR-t2 vs. HC, p &lt; 0.01). The θ power differed between DR-t1 and DR-t2 (p = 0.015) and between DR-t1 and HC (p = 0.01). The α power, similar to the δ, differed between DR patients pre and post-ASM and HC (DR-t1 vs. HC, p &lt; 0.01 and DR-t2 vs. HC, p &lt; 0.01). The IAF value was lower for DR-t1 than DR-t2 (p = 0.048) and HC (p = 0.042). The FD value was lower in DR-t1 than in DR-t2 (p = 0.015) and HC (p = 0.011). Finally, Bayes Factor analysis showed that FD was 195 times more likely to separate DR-t1 from DR-t2 than IAF and 231 times than θ. Discussion: FD measured in baseline EEG signals is a non-linear brain measure of complexity more sensitive than EEG power or IAF in detecting a response to ASMs. This likely reflects the non-oscillatory nature of neural activity, which FD better describes. Conclusion: Our work suggests that FD is a promising measure to monitor the response to ASMs in FE

Characterization of antiseizure medications effects on the EEG neurodynamic by fractal dimension

Objectives: An important challenge in epilepsy is to define biomarkers of response to treatment. Many electroencephalography (EEG) methods and indices have been developed mainly using linear methods, e.g., spectral power and individual alpha frequency peak (IAF). However, brain activity is complex and non-linear, hence there is a need to explore EEG neurodynamics using nonlinear approaches. Here, we use the Fractal Dimension (FD), a measure of whole brain signal complexity, to measure the response to anti-seizure therapy in patients with Focal Epilepsy (FE) and compare it with linear methods. Materials: Twenty-five drug-responder (DR) patients with focal epilepsy were studied before (t1, named DR-t1) and after (t2, named DR-t2) the introduction of the anti-seizure medications (ASMs). DR-t1 and DR-t2 EEG results were compared against 40 age-matched healthy controls (HC). Methods: EEG data were investigated from two different angles: frequency domain—spectral properties in δ, θ, α, β, and γ bands and the IAF peak, and time-domain—FD as a signature of the nonlinear complexity of the EEG signals. Those features were compared among the three groups. Results: The δ power differed between DR patients pre and post-ASM and HC (DR-t1 vs. HC, p &lt; 0.01 and DR-t2 vs. HC, p &lt; 0.01). The θ power differed between DR-t1 and DR-t2 (p = 0.015) and between DR-t1 and HC (p = 0.01). The α power, similar to the δ, differed between DR patients pre and post-ASM and HC (DR-t1 vs. HC, p &lt; 0.01 and DR-t2 vs. HC, p &lt; 0.01). The IAF value was lower for DR-t1 than DR-t2 (p = 0.048) and HC (p = 0.042). The FD value was lower in DR-t1 than in DR-t2 (p = 0.015) and HC (p = 0.011). Finally, Bayes Factor analysis showed that FD was 195 times more likely to separate DR-t1 from DR-t2 than IAF and 231 times than θ. Discussion: FD measured in baseline EEG signals is a non-linear brain measure of complexity more sensitive than EEG power or IAF in detecting a response to ASMs. This likely reflects the non-oscillatory nature of neural activity, which FD better describes. Conclusion: Our work suggests that FD is a promising measure to monitor the response to ASMs in FE

Human Hereditary Cardiomyopathy Shares a Genetic Substrate With Bicuspid Aortic Valve.

The complex genetics underlying human cardiac disease is evidenced by its heterogenous manifestation, multigenic basis, and sporadic occurrence. These features have hampered disease modeling and mechanistic understanding. Here, we show that 2 structural cardiac diseases, left ventricular noncompaction (LVNC) and bicuspid aortic valve, can be caused by a set of inherited heterozygous gene mutations affecting the NOTCH ligand regulator MIB1 (MINDBOMB1) and cosegregating genes. We used CRISPR-Cas9 gene editing to generate mice harboring a nonsense or a missense MIB1 mutation that are both found in LVNC families. We also generated mice separately carrying these MIB1 mutations plus 5 additional cosegregating variants in the ASXL3, APCDD1, TMX3, CEP192, and BCL7A genes identified in these LVNC families by whole exome sequencing. Histological, developmental, and functional analyses of these mouse models were carried out by echocardiography and cardiac magnetic resonance imaging, together with gene expression profiling by RNA sequencing of both selected engineered mouse models and human induced pluripotent stem cell-derived cardiomyocytes. Potential biochemical interactions were assayed in vitro by coimmunoprecipitation and Western blot. Mice homozygous for the MIB1 nonsense mutation did not survive, and the mutation caused LVNC only in heteroallelic combination with a conditional allele inactivated in the myocardium. The heterozygous MIB1 missense allele leads to bicuspid aortic valve in a NOTCH-sensitized genetic background. These data suggest that development of LVNC is influenced by genetic modifiers present in affected families, whereas valve defects are highly sensitive to NOTCH haploinsufficiency. Whole exome sequencing of LVNC families revealed single-nucleotide gene variants of ASXL3, APCDD1, TMX3, CEP192, and BCL7A cosegregating with the MIB1 mutations and LVNC. In experiments with mice harboring the orthologous variants on the corresponding Mib1 backgrounds, triple heterozygous Mib1 Apcdd1 Asxl3 mice showed LVNC, whereas quadruple heterozygous Mib1 Cep192 Tmx3;Bcl7a mice developed bicuspid aortic valve and other valve-associated defects. Biochemical analysis suggested interactions between CEP192, BCL7A, and NOTCH. Gene expression profiling of mutant mouse hearts and human induced pluripotent stem cell-derived cardiomyocytes revealed increased cardiomyocyte proliferation and defective morphological and metabolic maturation. These findings reveal a shared genetic substrate underlying LVNC and bicuspid aortic valve in which MIB1-NOTCH variants plays a crucial role in heterozygous combination with cosegregating genetic modifiers.This study was supported by grants PID2019-104776RB-I00 and PID2020-120326RB-I00, CB16/11/00399 (CIBER CV) financed by MCIN/AEI/10.13039/501100011033, a grant from the Fundación BBVA (Ref. BIO14_298), and a grant from Fundació La Marató de TV3 (Ref. 20153431) to J.L.d.l.P. M.S.-A. was supported by a PhD contract from the Severo Ochoa Predoctor-al Program (SVP-2014-068723) of the MCIN/AEI/10.13039/501100011033. J.R.G.-B. was supported by SEC/FEC-INV-BAS 21/021. A.R. was funded by grants from MCIN (PID2021123925OB-I00), TerCel (RD16/0011/0024), AGAUR (2017-SGR-899), and Fundació La Marató de TV3 (201534-30). J.M.P.-P. was supported by RTI2018-095410-B-I00 (MCIN) and PY2000443 (Junta de Andalucía). B.I. was supported by the European Commission (H2020-HEALTH grant No. 945118) and by MCIN (PID2019-107332RB-I00). DO’R was sup-ported by the Medical Research Council (MC-A658-5QEB0) and KAMcG by the British Heart Foundation (RG/19/6/34387, RE/18/4/34215). The cost of this publication was supported in part with funds from the European Regional Devel-opment Fund. The Centro Nacional de Investigaciones Cardiovasculares is sup-ported by the ISCIII, the MCIN, and the Pro Centro Nacional de Investigaciones Cardiovasculares Foundation and is a Severo Ochoa Center of Excellence (grant CEX2020001041-S) financed by MCIN/AEI/10.13039/501100011033. For the purpose of open access, the authors have applied a CC BY public copyright license to any Author Accepted Manuscript version arising.S

Prognostic Implications of 18-FDG Positron Emission Tomography/Computed Tomography in Resectable Pancreatic Cancer

There are currently no known preoperative factors for determining the prognosis in pancreatic cancer. The aim of this study was to examine the role of 18-fluorodeoxyglucose (18-FDG) positron emission tomography/computed tomography (18-FDG-PET/CT) as a prognostic factor for patients with resectable pancreatic cancer. Data were obtained from a retrospective analysis of patients who had a preoperative PET scan and then underwent pancreatic resection from January 2007 to December 2015. The maximum standardized uptake value (SUVmax) of 18-FDG-PET/CT was calculated. Patients were divided into high (>3.65) and low (3.65) SUVmax groups, and compared in terms of their TNM classification (Union for International Cancer Contro classification), pathological grade, surgical treatment, state of resection margins, lymph node involvement, age, sex, diabetes and serum Carbohydrate Antigen 19-9 (CA 19-9) levels. The study involved 144 patients, 82 with high SUVmax pancreatic cancer and 62 with low SUVmax disease. The two groups\u2019 disease-free and overall survival rates were significantly influenced by tumor stage, lymph node involvement, pathological grade, resection margins and SUVmax. Patients with an SUVmax 3.65 had a significantly better survival than those with SUVmax > 3.65 (p < 0.001). The same variables were independent predictors of survival on multivariate analysis. The SUVmax calculated with 18-FDG-PET/CT is an important prognostic factor for patients with pancreatic cancer, and may be useful in decisions concerning patients\u2019 therapeutic management

Effect Of Branch Length And Tortuosity On The Outcomes Of Branched Endovascular Repair Of Thoracoabdominal Aneurysms Using Self Expandable bridging stent-graft

To investigate the effect of length and tortuosity of directional branches on the mid-term outcomes of branched endovascular aneurysm repair (BEVAR) for thoracoabdominal aortic aneurysms (TAAA)