Long-Term Outcomes of Standard Endovascular Aneurysm Repair in Patients With Severe Neck Angulation

Objective: Severe neck angulation is associated with complications after endovascular aneurysm repair (EVAR). Newer endografts may overcome this limitation, but the literature lacks long-term results. We studied the long-term outcomes of EVAR in patients with severe neck angulation. Methods: A retrospective case-control study of a prospective multicenter database was performed. All measurements were made with dedicated software with center lumen line reconstruction. A study group including patients with neck length >15 mm, infrarenal angle (β) >75 degrees or suprarenal angle (α) >60 degrees, and neck length 10 to 15 mm with β >60 degrees or α >45 degrees was compared with a control group matched for demographics and other morphologic neck features. The primary end point was type IA endoleak (EL1A). Secondary end points were freedom from neck-related secondary interventions, primary clinical success, and overall survival. Results: Forty-five patients were included in the angulated neck group and compared with 65 matched patients. Median follow-up was 7.4 years (interquartile range, 4.8-8.5 years). In the angulated neck group, mean α was 51.4 degrees (±21.1 degrees) and the mean β was 80.8 degrees (±15.6 degrees); in the nonangulated group, these were 17.9 degrees (±17.0 degrees) and 35.4 degrees (±20.0 degrees), respectively. At 7 years, five patients in the angulated neck group and two nonangulated patients developed EL1A, yielding a freedom from EL1A of 86.1% (n = 14; standard error [SE], 0.069) and 96.6% (n = 34; SE, 0.023), respectively (P = .056). After exclusion of a patient who developed an EL1A secondary to an endograft infection, this difference was significant: 86.1% (n = 14; SE, 0.069) in the angulated neck group and 98.2% (n = 34; SE, 0.018) in the nonangulated group (P = .016). At 7 years, freedom from neck-related secondary interventions was 91.7% (n = 14; SE, 0.059) and 91.6% (n = 29; SE, 0.029), respectively. The 7-year primary clinical success estimates were 41.2% (n = 11; SE, 0.085) and 56.6% (n = 20; SE, 0.072) for the angulated neck and nonangulated groups, respectively (P = .12). The 7-year survival rates were 44.3% (n = 18; SE, 0.076) vs 66.7% (n = 42; SE, 0.059) for the angulated neck and nonangulated groups, respectively (P = .25). Device integrity failure was not observed. Conclusions: Despite satisfactory results early and in the midterm, a higher rate of EL1A was identified among patients with severely angulated necks in the long term. However, mortality was not affected by this difference. These findings suggest that EVAR should be used judiciously in patients with extreme angulation of the proximal neck and highlight the need for close follow-up of EVAR, especially in the long term and in patients treated outside instructions for use.info:eu-repo/semantics/publishedVersio

Anatomic Predictors for Late Mortality after Standard Endovascular Aneurysm Repair

Objective: Abdominal aortic aneurysm (AAA) management involves a decision process that takes into account anatomic characteristics, surgical risks, patients' preferences, and expected survival. Whereas larger AAA diameter has been associated with increased mortality after both standard endovascular aneurysm repair (EVAR) and open repair, it is unclear whether survival after EVAR is influenced by other anatomic characteristics. The purpose of this study was to determine the importance of baseline anatomic features on survival after EVAR. Methods: All patients treated at a tertiary teaching center with EVAR for intact standard infrarenal AAA from 2000 to 2014 were included. The civil data registry was queried to determine survival status; causes of death were obtained from death certificates. The primary study end point was to determine the impact of baseline morphologic features on all-cause and cardiovascular mortality after EVAR. Results: This study included 404 EVAR patients (12.1% women; mean age, 73 years) with a median follow-up of 5.8 years (interquartile range, 3.1-7.4 years). The 5- and 10-year overall survival rates for the entire population after EVAR were 70% (95% confidence interval [CI], 66%-75%) and 43% (95% CI, 37%-50%), respectively. Only AAA diameter >70 mm (hazard ratio [HR], 1.75; 95% CI, 1.20-3.56) was identified as an independent anatomic predictor of all-cause mortality. Death due to cardiovascular causes occurred in 60 (38.5%) patients. Aneurysm-related mortality was responsible for six of the cardiovascular-related deaths. In multivariable analysis, both neck diameter ≥30 mm (HR, 2.16; 95% CI, 1.05-4.43) and AAA diameter >70 mm (HR, 2.45; 95% CI, 1.34-4.46) were identified as independent morphologic risk factors for cardiovascular mortality, whereas >25% circumferential neck thrombus (HR, 0.32; 95% CI, 0.13-0.77) was protective. Conclusions: This study suggests that patients with AAA diameters >70 mm are at increased risk of all-cause and cardiovascular mortality. In addition, patients with infrarenal neck diameters ≥30 mm have a greater risk of cardiovascular mortality, although AAA-related deaths were not more frequent in this group of patients. Consequently, a more aggressive management of cardiovascular medical comorbidities may be warranted to improve survival after standard EVAR in these patients.info:eu-repo/semantics/publishedVersio

Patients with Large Neck Diameter Have a Higher Risk of Type IA Endoleaks and Aneurysm Rupture after Standard Endovascular Aneurysm Repair

Objective: Standard endovascular aneurysm repair (EVAR) is the most common treatment of abdominal aortic aneurysms (AAAs). EVAR has been increasingly used in patients with hostile neck features. This study investigated the outcomes of EVAR in patients with neck diameters ≥30 mm in the prospectively maintained Endurant Stent Graft Natural Selection Global Postmarket Registry (ENGAGE). Methods: This is a retrospective study comparing patients with neck diameters ≥30 mm with patients with neck diameters <30 mm. The primary end point was type IA endoleak (EL1A). Secondary end points included secondary interventions to correct EL1A, aneurysm rupture, and survival. Results: This study included 1257 patients (mean age, 73.1 years; 89.4% male) observed for a median 4.0 years (interquartile range, 2.7-4.8 years). A total of 97 (7.7%) patients had infrarenal neck diameters ≥30 mm and were compared with the remaining 1160 (92.3%) with neck diameters <30 mm. At baseline, there were no differences between groups regarding demographics and comorbidities other than cardiac disease, which was more frequent in the ≥30-mm neck diameter group (P = .037). There were no significant differences between the groups regarding neck length, angulation, thrombus, or calcification. Mean preoperative AAA diameter was 64.6 ± 11.3 mm in the ≥30-mm neck diameter group and 60.0 ± 11.6 mm in the <30-mm neck diameter group (P < .001). Stent graft oversizing was significantly less in the ≥30-mm neck diameter group (12.2% ± 8.9% vs 22.1% ± 11.9%; P <. 001). Five patients (5.2%) in the ≥30-mm neck diameter group and 30 (2.6%) with neck diameters <30 mm developed EL1A, yielding a 4-year freedom from EL1A of 92.4% vs 96.6%, respectively (P = .09). Oversizing was 21.8% ± 13.0% for patients developing EL1A and 21.3% ± 12.4% for the remaining cohort (P = .99). In adjusting for neck length, AAA diameter, and device oversizing, patients with neck diameter ≥30 mm were at greater risk for development of EL1A (hazard ratio, 3.0; 95% confidence interval, 1.0-9.3; P = .05). Secondary interventions due to EL1A did not differ between groups (P = .36). AAA rupture occurred in three patients with neck diameter ≥30 mm (3.1%) and in eight patients with neck diameter <30 mm (0.7%; hazard ratio, 5.1; 95% confidence interval, 1.4-19.2; P = .016); two cases were EL1A related in each group. At 4 years, overall survival was 61.6% for the ≥30-mm neck diameter group and 75.2% for the <30-mm neck diameter group (P = .009), which remained significant on correcting for sex and AAA diameter (P = .016). Conclusions: In this study, patients with infrarenal neck diameter ≥30 mm had a threefold increased risk of EL1A and fivefold risk of aneurysm rupture after EVAR as well as worse overall survival. This may influence the choice of AAA repair and underlines the need for regular computed tomography-based imaging surveillance in this subset of patients. Furthermore, these results can serve as standards with which new, possibly improved technology, such as EndoAnchors (Medtronic, Santa Rosa, Calif), can be compared.info:eu-repo/semantics/publishedVersio

Syntaxin 16 is a master recruitment factor for cytokinesis

Recently it was shown that both recycling endosome and endosomal sorting complex required for transport (ESCRT) components are required for cytokinesis, in which they are believed to act in a sequential manner to bring about secondary ingression and abscission, respectively. However, it is not clear how either of these complexes is targeted to the midbody and whether their delivery is coordinated. The trafficking of membrane vesicles between different intracellular organelles involves the formation of soluble N-ethylmalei­mide–sensitive factor attachment protein receptor (SNARE) complexes. Although membrane traffic is known to play an important role in cytokinesis, the contribution and identity of intracellular SNAREs to cytokinesis remain unclear. Here we demonstrate that syntaxin 16 is a key regulator of cytokinesis, as it is required for recruitment of both recycling endosome–associated Exocyst and ESCRT machinery during late telophase, and therefore that these two distinct facets of cytokinesis are inextricably linked

Stroke Correlates in Chagasic and Non-Chagasic Cardiomyopathies

BACKGROUND: Aging and migration have brought changes to the epidemiology and stroke has been shown to be independently associated with Chagas disease. We studied stroke correlates in cardiomyopathy patients with focus on the chagasic etiology. METHODOLOGY/PRINCIPAL FINDINGS: We performed a cross-sectional review of medical records of 790 patients with a cardiomyopathy. Patients with chagasic (329) and non-chagasic (461) cardiomyopathies were compared. There were 108 stroke cases, significantly more frequent in the Chagas group (17.3% versus 11.1%; p<0.01). Chagasic etiology (odds ratio [OR], 1.79), pacemaker (OR, 2.49), atrial fibrillation (OR, 3.03) and coronary artery disease (OR, 1.92) were stroke predictors in a multivariable analysis of the entire cohort. In a second step, the population was split into those with or without a Chagas-related cardiomyopathy. Univariable post-stratification stroke predictors in the Chagas cohort were pacemaker (OR, 2.73), and coronary artery disease (CAD) (OR, 2.58); while atrial fibrillation (OR, 2.98), age over 55 (OR, 2.92), hypertension (OR, 2.62) and coronary artery disease (OR, 1.94) did so in the non-Chagas cohort. Chagasic stroke patients presented a very high frequency of individuals without any vascular risk factors (40.4%; OR, 4.8). In a post-stratification logistic regression model, stroke remained associated with pacemaker (OR, 2.72) and coronary artery disease (OR, 2.60) in 322 chagasic patients, and with age over 55 (OR, 2.38), atrial fibrillation (OR 3.25) and hypertension (OR 2.12; p = 0.052) in 444 non-chagasic patients. CONCLUSIONS/SIGNIFICANCE: Chagas cardiomyopathy presented both a higher frequency of stroke and an independent association with it. There was a high frequency of strokes without any vascular risk factors in the Chagas as opposed to the non-Chagas cohort. Pacemaker rhythm and CAD were independently associated with stroke in the Chagas group while age over 55 years, hypertension and atrial fibrillation did so in the non-Chagas cardiomyopathies

HIPK2 and extrachromosomal histone H2B are separately recruited by Aurora-B for cytokinesis

Cytokinesis, the final phase of cell division, is necessary to form two distinct daughter cells with correct distribution of genomic and cytoplasmic materials. Its failure provokes genetically unstable states, such as tetraploidization and polyploidization, which can contribute to tumorigenesis. Aurora-B kinase controls multiple cytokinetic events, from chromosome condensation to abscission when the midbody is severed. We have previously shown that HIPK2, a kinase involved in DNA damage response and development, localizes at the midbody and contributes to abscission by phosphorylating extrachromosomal histone H2B at Ser14. Of relevance, HIPK2-defective cells do not phosphorylate H2B and do not successfully complete cytokinesis leading to accumulation of binucleated cells, chromosomal instability, and increased tumorigenicity. However, how HIPK2 and H2B are recruited to the midbody during cytokinesis is still unknown. Here, we show that regardless of their direct (H2B) and indirect (HIPK2) binding of chromosomal DNA, both H2B and HIPK2 localize at the midbody independently of nucleic acids. Instead, by using mitotic kinase-specific inhibitors in a spatio-temporal regulated manner, we found that Aurora-B kinase activity is required to recruit both HIPK2 and H2B to the midbody. Molecular characterization showed that Aurora-B directly binds and phosphorylates H2B at Ser32 while indirectly recruits HIPK2 through the central spindle components MgcRacGAP and PRC1. Thus, among different cytokinetic functions, Aurora-B separately recruits HIPK2 and H2B to the midbody and these activities contribute to faithful cytokinesis

Efficacy and Safety of Upadacitinib Treatment in Adolescents With Moderate-to-Severe Atopic Dermatitis

Importance: Atopic dermatitis onset usually occurs in childhood. Persistence of disease into adolescence and adulthood is common. It is important to evaluate new treatment options in adolescents because of the high unmet need in this population. Objective: To assess the efficacy and safety of upadacitinib to treat moderate-to-severe atopic dermatitis in adolescents. Design, setting, and participants: Prespecified analysis of adolescents enrolled in 3 randomized, double-blind, placebo-controlled phase 3 clinical trials in more than 20 countries across Europe, North and South America, Oceania, the Middle East, and the Asia-Pacific region from July 2018 through December 2020. Participants were adolescents aged 12 to 17 years with moderate-to-severe atopic dermatitis. Data analysis was performed from April to August 2021. Interventions: Patients were randomized (1:1:1) to once-daily oral upadacitinib 15 mg, upadacitinib 30 mg, or placebo alone (Measure Up 1 and Measure Up 2) or with topical corticosteroids (AD Up). Main outcomes and measures: Safety and efficacy, including at least a 75% improvement in the Eczema Area and Severity Index from baseline and validated Investigator Global Assessment for Atopic Dermatitis score of 0 (clear) or 1 (almost clear) at week 16 (coprimary end points). Results: A total of 552 adolescents (290 female; 262 male) were randomized. Mean (SD) age was 15.4 (1.8), 15.5 (1.7), and 15.3 (1.8) years for adolescents in Measure Up 1, Measure Up 2, and AD Up, respectively. In Measure Up 1, Measure Up 2, and AD Up, respectively, a greater proportion of adolescents (% [95% CI]) achieved at least 75% improvement in the Eczema Area and Severity Index at week 16 with upadacitinib 15 mg (73% [63%-84%], 69% [57%-81%], 63% [51%-76%]), and upadacitinib 30 mg (78% [68%-88%], 73% [62%-85%], 84% [75%-94%]), than with placebo (12% [4%-20%], 13% [5%-22%], 30% [19%-42%]; nominal P < .001 for all comparisons vs placebo). Similarly, a greater proportion of adolescents treated with upadacitinib achieved a validated Investigator Global Assessment for Atopic Dermatitis score of 0 or 1 at week 16 and improvements in quality of life with upadacitinib than with placebo. Upadacitinib was generally well tolerated in adolescents. Acne was the most common adverse event, and all acne events were mild or moderate. Conclusions and relevance: In this analysis of 3 randomized clinical trials, upadacitinib was an effective treatment for adolescents with moderate-to-severe atopic dermatitis, with an acceptable safety profile.info:eu-repo/semantics/publishedVersio

Resting heart rate as a predictor of metabolic dysfunctions in obese children and adolescents

<p>Abstract</p> <p>Background</p> <p>Recent studies have identified that a higher resting heart rate (RHR) is associated with elevated blood pressure, independent of body fatness, age and ethnicity. However, it is still unclear whether RHR can also be applied as a screening for other risk factors, such as hyperglycemia and dyslipidemia. Thus, the purpose of the presented study was to analyze the association between RHR, lipid profile and fasting glucose in obese children and adolescents.</p> <p>Methods</p> <p>The sample was composed of 180 obese children and adolescents, aged between 7-16 years. Whole-body and segmental body composition were estimated by Dual-energy X-ray absorptiometry. Resting heart rate (RHR) was measured by heart rate monitors. The fasting blood samples were analyzed for serum triglycerides, total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), and glucose, using the colorimetric method.</p> <p>Results</p> <p>Fasting glucose, TC, triglycerides, HDL-C, LDL-C and RHR were similar in both genders. The group of obese subjects with a higher RHR presented, at a lower age, higher triglycerides and TC. There was a significant relationship between RHR, triglycerides and TC. In the multivariate model, triglycerides and TC maintained a significant relationship with RHR independent of age, gender, general and trunk adiposity. The ROC curve indicated that RHR has a high potential for screening elevated total cholesterol and triglycerides as well as dyslipidemia.</p> <p>Conclusion</p> <p>Elevated RHR has the potential to identify subjects at an increased risk of atherosclerosis development.</p