CYP2U1: An emerging treatable neurometabolic disease with cerebral folate deficiency in 2 Chinese brothers.

With the rapid advancement of medical technologies in genomic and molecular medicine, the number of treatable neurometabolic diseases is quickly expanding. Spastic paraplegia 56 (SPG56), one of the severe autosomal recessive forms of neurodegenerative disorders caused by pathogenic variants in the CYP2U1 gene, has no reported specific targeted treatment yet. Here we report 2 Chinese brothers with CYP2U1 bi-allelic pathogenic variants with cerebral folate deficiency who were treated for over a decade with folinic acid supplement. Patients have remained stable under therapy.

Trends and outcomes associated with intravascular ultrasound use during femoropopliteal revascularization in the Vascular Quality Initiative.

OBJECTIVE: Intravascular ultrasound (IVUS) use in lower extremity interventions is growing in popularity owing to its imaging in the axial plane, superior detail in imaging lesion characteristics, and its enhanced ability to delineate lesion severity and extent compared with catheter angiograms. However, there are conflicting data regarding whether IVUS affects outcomes. The purpose of this study was to assess the effect associated with IVUS implementation in femoropopliteal interventions. METHODS: This retrospective cohort study used Vascular Quality Initiative data. Patients undergoing an index endovascular femoropopliteal revascularization from 2016 to 2021 were included. Patients were differentiated by whether or not IVUS was used to assess the femoropopliteal segment during intervention (no IVUS, IVUS). Propensity score matching, based on preoperative demographics and measures of disease severity was used. Primary outcomes were major amputation-free survival (AFS), femoropopliteal reintervention-free survival (RFS), and primarily patent survival (PPS) at 12 months. RESULTS: IVUS use grew steadily throughout the study period, comprising 0.6% of interventions in 2016 and increasing to 8.2% of interventions by 2021; growth was most dramatic in ambulatory surgical center or office-based laboratory settings where IVUS use grew from 4.4% to 43% to 47% of interventions. In unmatched cohorts, patients receiving interventions using IVUS tended to have lower prevalence of multiple cardiovascular comorbidities (eg, congestive heart failure, hypertension, diabetes, and dialysis dependence) and presented more often with claudication and less often with chronic limb-threatening ischemia (CLTI). Intraoperatively, IVUS was used more often in complex femoropopliteal lesions (Transatlantic Intersociety grade D vs A), and more often in conjunction with stenting and/or atherectomy. IVUS use was associated with improved AFS, but similar RFS and PPS at 12 months. However, in multivariable analysis IVUS was not associated with any of the primary outcomes independently; rather, all outcomes were influenced primarily by CLTI, dialysis dependence, and prior major amputation status; technical outcomes (ie, RFS and PPS loss) were further driven by complexity of lesion (worse in Transatlantic Intersociety grade D vs A lesions) and treatment setting (ie, ambulatory surgical center or office-based laboratory setting associated with increased hazard for RFS and PPS loss). CONCLUSIONS: IVUS implementation in femoropopliteal interventions is growing, with rapid adoption among interventions in ambulatory surgical centers and office-based laboratories. IVUS was not associated with an effect on technical outcomes at 12 months; improvement in major AFS was observed; however, multivariable analysis suggests this finding may be an effect of confounding by multiple factors highly associated with IVUS use, namely, in patients with lower prevalence of CLTI, dialysis dependence, and prior major amputations, thus conveying baseline lower risk for major amputation and death.

Physician-modified endografts are associated with a survival benefit over parallel grafting in thoracoabdominal aneurysms.

OBJECTIVE: Physician-modified endografts (PMEG) and parallel grafting (PG) are important techniques for endovascular repair of complex aortic aneurysms using off-the-shelf devices. However, there are few data regarding the relative efficacy and outcomes of these techniques in thoracoabdominal extent aneurysms. This study sought to compare the outcomes of PG and PMEG across different extents of thoracoabdominal aneurysms (TAAAs) for which they can be used. METHODS: The Society for Vascular Surgery Vascular Quality Initiative thoracic endovascular aortic repair/complex endovascular aortic repair module was queried for all patients undergoing repair of an unruptured, TAAA (extents I-IV) from 2012 to 2020; aneurysm types were defined by repair extent as determined by proximal and distal seal zones. Patients were differentiated based on whether they underwent repair with a PMEG or PG. The primary outcomes for this study were overall survival and freedom from aneurysm- or procedure-related mortality at 1 year determined via Kaplan-Meier analysis, with a Cox hazard regression analysis conducted to examine the independent association of repair modality with primary outcomes. RESULTS: There were 813 patients who met the inclusion criteria (TAAA I-III, n = 362; TAAA IV, n = 451; PG, n = 426; PMEG, n = 387). PMEG repairs were performed at centers with a nearly two- to three-fold higher annual volume of endovascular TAAA repairs. Type Ia endoleaks were reduced with PMEG repair, most significantly in TAAA IV (TAAA I-III, 2.2% PMEG vs 10% PG [P = .2]; TAAA IV, 1.2% PMEG vs 21.6% PG [P < .001]). Thoracoabdominal repairs demonstrated improved survival at 1 year with PMEG devices, significant for TAAA I to III repairs (TAAA I-III, PMEG 85% vs PG 74% [P = .01]; TAAA IV, 84% PMEG vs PG 78% [P = .08]). Freedom from aneurysm- or procedure-related mortality was also improved with PMEG repairs, remaining significant at 1 year in the case of TAAA IV (TAAA I-III:, PMEG 94% vs PG 86% [P = .06]; TAAA IV, PMEG 94% vs PG 88% [P = .02]). PMEG demonstrated decreases in several measures of postoperative morbidity, including stroke, death, major adverse cardiovascular events, and postoperative complications. In the multivariate analysis, repair modality was not associated with either primary outcome; rather, several perioperative complications conveyed the greatest hazard for both primary outcomes across repair extents. CONCLUSIONS: Survival after endovascular TAAA repair is improved with the use of PMEG compared with PG. Several key factors of this study demonstrate the shortcomings of PG in complex aneurysm repair, namely, high rates of critical endoleaks, the need for adjunctive access sites, and an increase in perioperative complications that influence longer term outcomes.

Elevated Neutrophil to Lymphocyte Ratio is Associated with Worse Outcomes after Carotid Endarterectomy in Asymptomatic Patients.

OBJECTIVE: Management of carotid artery stenosis (CAS) remains controversial and proper patient selection critical. Elevated neutrophil to lymphocyte ratio (NLR) has been associated with poor outcomes after vascular procedures. The effect of NLR on outcomes after carotid endarterectomy (CEA) in asymptomatic and symptomatic patients is assessed. MATERIALS AND METHODS: A retrospective review was conducted of all patients between 2010 and 2018 with carotid stenosis >70% as defined by CREST 2 criteria. A total of 922 patients were identified, of whom 806 were treated with CEA and 116 non-operatively with best medical therapy (BMT). Of patients undergoing CEA, 401 patients (290 asymptomatic [aCEA], 111 symptomatic [sCEA]) also had an available NLR calculated from a complete blood count with differential. All patients treated with BMT were asymptomatic and had a baseline NLR available. Kaplan-Meier analysis assessed composite ipsilateral stroke or death over 3 years. RESULTS: In sCEA group, the 3-year composite stroke/death rates did not differ between NLR < 3.0 (22.9%) vs NLR > 3.0 (38.1%) (P=.10). In aCEA group, patients with a baseline NLR >3.0 had an increased risk of 3-year stroke/death (42.6%) compared to both those with NLR <3.0 (9.3%, P<.0001) and those treated with BMT (23.6%, P=.003). In patients with NLR <3.0, aCEA showed a superior benefit over BMT with regard to stroke or death (9.3% vs. 26.2%, P=.02). However, in patients with NLR >3.0, there was no longer a benefit to prophylactic CEA compared to BMT (42.6% vs. 22.2%, P=.05). Multivariable analysis identified NLR >3.0 (HR, 3.23; 95% CI, 1.93-5.42; P<.001) and congestive heart failure (HR, 2.18; 95% CI, 1.33-3.58; P=.002) as independent risk factors for stroke/death in patients with asymptomatic carotid artery stenosis. CONCLUSIONS: NLR >3.0 is associated with an increased risk of late stroke/death after prophylactic CEA for asymptomatic carotid artery stenosis, with benefits not superior to BMT. NLR may be used to help with selecting asymptomatic patients for CEA. The effect of NLR and outcomes in symptomatic patients requires further study. Better understanding of the mechanism(s) for NLR elevation and medical intervention strategies are needed to modulate outcome risk in these patients.

High FGF-21 level in a cohort of 22 patients with Dravet Syndrome-Possible relationship with the disease outcomes.

OBJECTIVE: Dravet syndrome (DS) is a severe and intractable form of epilepsy with prolonged seizures which may evolve to other seizure types and associated with mild-to-severe intellectual disabilities. Fibroblast growth factor 21 (FGF-21) is a stress hormone mediating metabolic and oxidative stress and circulating level of FGF-21 had been shown to increase in some patients with impairment of oxidative phosphorylation in muscles. In DS, FGF-21 is of interest for further study as mitochondrial oxidative stress was identified previously in patients. METHODS: Plasma FGF-21 levels were compared between 22 DS patients and 22 normal controls, and their clinical characteristics of DS patients at the time of plasma sampling were studied retrospectively. Besides, the relationships of FGF-21 level with intellectual development, seizure frequency, valproate treatment, and types of SCN1A mutations were analyzed. Logarithmic transformation of FGF-21 levels was performed before comparison and statistical analysis. RESULTS: Mean of log10 FGF-21 level was significantly higher in DS patients when comparing with normal controls (P = .0042). Mean of log10 FGF-21 level was significantly higher in DS patients with normal-to-mild ID versus mild-to-severe ID (P = .0193) and with valproate treatment versus without valproate treatment (P = .015). No significant difference was shown in FGF-21 level in DS patients with missense versus truncating SCN1A variants, and no correlation could be demonstrated between seizure frequency and FGF-21 level. SIGNIFICANCE: Significantly higher level of plasma FGF-21 was identified in DS patients. The high FGF-21 levels were shown to be associated with developmental outcome and valproate treatment. These results support further investigation on the relationship of FGF-21 with the clinical outcomes of DS and other related mechanism which is important for possible therapeutic development for this epileptic encephalopathy.

Paclitaxel-coated peripheral arterial devices are associated with improved overall survival and limb salvage in patients with chronic limb-threatening ischemia.

OBJECTIVE: Paclitaxel (PTX)-coated peripheral arterial devices have been shown to decrease femoropopliteal artery restenosis and the need for reintervention compared with non-PTX-coated devices. The data regarding PTX efficacy and safety come from randomized controlled trials that almost exclusively enrolled patients with claudication. The outcomes of PTX treatment in patients who present with chronic limb-threatening ischemia (CLTI) are unknown. This study compares long-term outcomes in patients with CLTI treated with and without PTX. METHODS: We retrospectively reviewed 983 patients with CLTI treated with femoropopliteal artery angioplasty, atherectomy, stent, or combination between 2011 and 2019. Procedures were performed with additional proximal or distal tibial interventions as needed. Kaplan-Meier survival analysis and multivariable Cox-regression analysis compared overall survival (OS), amputation-free survival (AFS), freedom from major amputation (ff-MA), and freedom from target vessel revascularization (ff-TVR) between patients treated with and without PTX. RESULTS: Demographics, comorbidities, and Rutherford class were similar between 574 PTX (58.5%) and 409 non-PTX (41.6%) patients except that non-PTX patients were more likely to be male (56.2% vs 49.7%), dialysis dependent (19.6% vs 14.3%), and have higher average creatinine (2.3 vs 1.8 mg/dL). Through 4-year follow-up, the PTX group demonstrated a significant increase in OS (56.2% vs 43.9%, P = .013), AFS (52.6% vs 36.1%, P < .0001), ff-MA (87.4% vs 78.7%, P = .0007), and ff-TVR (77.6% vs 70.6%, P = .012). Multivariable Cox-regression analysis demonstrated that PTX treatment was associated with improved OS, AFS, ff-MA, and ff-TVR. CONCLUSIONS: In patients with CLTI, treatment with a PTX-coated device is associated with improved OS, AFS, ff-MA, and ff-TVR through 4-year follow-up. PTX-coated devices may be especially beneficial in patients who present with CLTI.

Elevated neutrophil to lymphocyte ratio is associated with decreased amputation-free survival after femoropopliteal percutaneous revascularization.

BACKGROUND: An elevated neutrophil-lymphocyte ratio (NLR) is a biomarker associated with adverse outcomes after cardiovascular surgery. This study evaluates the association of preoperative NLR with clinical outcomes after peripheral vascular intervention (PVI) of the femoropopliteal segments. METHODS: A retrospective review identified 488 patients who underwent percutaneous interventions of femoropopliteal arteries between 2011 and 2018 and had a pre-procedural complete blood count with differential with normal white blood cell count within 30 days prior to intervention. Amputation-free survival (AFS), survival, and freedom from major amputation were assessed using Kaplan-Meier methods. Cohorts of patients with NLR <3 (Low), 3-4 (Mid), and >4 (High) were compared using univariate and multivariable statistical models. In these analyses NLR was analyzed as a continuous variable to correlate with clinical outcomes. RESULTS: Mean age was 71.7±12.8 years and males constituted 55.5%. The majority of patients presented with chronic limb threatening ischemia (CLTI, 78.5%). Increasing NLR was correlated with increasing rates of comorbidities, except for smoking history. The 30-day mortality rates increased with increasing NLR: 1.4%, 4.3%, and 7.0% for low (<3), mid (3-4) and high (>4) NLR groups, respectively (P=0.005). Patients with a lower pre-operative NLR achieved significantly greater amputation-free survival at 4-year follow-up: low NLR, 65.5%; mid NLR, 37.5%; and high NLR, 17.6% (P<0.0001). By multivariable analysis, increasing NLR, advanced age, CLTI, and dialysis-dependent renal failure reduced AFS. CONCLUSIONS: Elevated NLR is an independent predictor of decreased AFS following percutaneous interventions of femoropopliteal segments. Further research on identification and modulation of risk factors for high NLR are warranted.

Systematic review of hemostatic agents used in vascular surgery.

BACKGROUND: Hemostatic agents are routinely used in vascular surgery to complement proper suture techniques and decrease the risk of perioperative bleeding. A relative lack of comparative research studies have left surgeons with the option of choosing hemostatic agents based on their personal experience. The present review has highlighted the efficacy and safety of hemostatic agents and categorized them according to their primary mechanism of action and cost. METHODS: A systematic search strategy encompassing hemostatic agent products was deployed in the PubMed database. Single-center and multicenter, randomized, controlled trials with >10 patients were included in the present study. RESULTS: We reviewed 12 studies on the efficacy and safety of hemostatic agents compared with manual compression or other hemostatic agents. Using the time to hemostasis as the primary end point, all studies had found hemostatic agents to be significantly more efficient than manual compression. Likewise, adhesives (high pressure sealants) and dual agents (containing biologically active and absorbable components) were found to be more efficient, but costlier, than agents with either biologically active or absorbable components only. Agents with porcine or bovine constituents were found to trigger anaphylactic reactions in rare cases. Additionally, the absence of fibrin stabilizing factor XIII in a brand of fibrin sealant was speculated to reduce the affinity of the fibrin sealant for the expanded polytetrafluoroethylene graft. The cost of agents varied greatly depending on their active ingredient. CONCLUSIONS: Hemostatic agents appear to be highly effective at decreasing the risk of bleeding during surgical procedures. Although some hemostatic agents were demonstrated to achieve hemostasis faster than others, most are able to control bleeding within <10 minutes. Based on the limited data, the least expensive agents might suffice for limited suture lines used in routine procedures.

Paclitaxel-Coated Peripheral Arterial Devices are Associated with Reduced Mortality in Younger Patients.

BACKGROUND: Paclitaxel-coated devices have been shown to decrease restenosis when used in the femoropopliteal artery. Recent reports have suggested a possible risk of increased late mortality in patients treated with paclitaxel. It has been suggested that younger patients and those with limited comorbidities may be at higher risk. Our objective was to analyze long-term mortality based on patient age comparing treatment with paclitaxel to uncoated devices. METHODS: We performed a retrospective review of 1,170 consecutive patients who underwent femoropopliteal percutaneous intervention by angioplasty, atherectomy, stent placement, or combination between 2011 and 2018. Patients were grouped by age at the time of procedure: <60 years old (n = 244, 20.9%), 60-80 years old (n = 635, 54.3%), and >80 years old (n = 291, 24.9%). Within each group, patients were further divided by use of paclitaxel. The primary outcome measure was survival assessed by Kaplan-Meier analysis. Differences between the groups were analyzed with analysis of variance. Multivariable analysis was performed using Cox proportional hazard models. RESULTS: Of the 1,170 patients who underwent femoropopliteal percutaneous intervention, 654 (55.9%) received a paclitaxel-coated device during treatment and 516 (44.1%) did not. Mean age of the overall patient cohort was 70.4 ± 12.6 years and 663 (56.7%) were male. When comparing the groups by age we found an increase in age but a decrease in the proportion of patients who smoke. The use of paclitaxel-coated devices was similar across the groups (<60 years old, 56.2%; 60-80 years old, 57.0%; >80 years old, 52.6%; P = 0.45). Demographics and comorbidities were similar between the patients treated with and without paclitaxel within each age group except more males in the <60-year-old group treated without paclitaxel and more patients with chronic limb threatening ischemia in the >80-year-old group treated with paclitaxel. In patients <60 and 60-80 years old paclitaxel use was associated with increased survival at 4 years: <60 (80.7% vs. 64.4%; P = 0.04); 60-80 (63.2% vs. 55.1%; P = 0.04). Survival was similar in the >80-year-old group (46.6% vs. 32.8%; P = 0.65). CONCLUSIONS: Our data suggest that the use of paclitaxel-coated arterial devices is not associated with increased mortality. On the contrary, our data show that younger patients treated with paclitaxel show improved survival compared with those treated without paclitaxel. Paclitaxel-coated devices may be used with continued caution especially in patients at high risk for restenosis.

Heparin-bonded versus standard polytetrafluoroethylene arteriovenous grafts: A Bayesian perspective on a randomized controlled trial for comparative effectiveness.

BACKGROUND: Heparin-bonded polytetrafluoroethylene grafts were marketed to improve hemodialysis access outcomes but are twice the cost of standard polytetrafluoroethylene. We launched a randomized trial of heparin-bonded polytetrafluoroethylene versus standard polytetrafluoroethylene for hemodialysis access to compare patency. Since the trial began, additional studies were published with heterogeneous findings. We performed an interim analysis by Bayesian methods using prior probability from meta-analysis of existing literature. METHODS: NCT01601873 is a randomized, blinded trial of heparin-bonded polytetrafluoroethylene versus standard polytetrafluoroethylene for dialysis access at 5 sites. Planned sample size was 200 with 1-year primary patency as the primary endpoint. At interim analysis (50% of sample size at 1 year), we also performed a meta-analysis for 1-year primary patency with a random effects model to compute summary rate ratio and standard-error estimates. Meta-analysis estimates formed a prior probability for a Bayesian Cox regression model, and trial data were reanalyzed to develop posterior probability of heparin-bonded polytetrafluoroethylene effectiveness at our hypothesized effect size. Futility analysis was conducted using posterior probability estimates. RESULTS: One hundred and five patients were enrolled at the time of interim analysis. One-year primary patency was 34.9% in the heparin-bonded-polytetrafluoroethylene group vs 32.7% in the standard-polytetrafluoroethylene group (P = .884). Summary rate ratio from the meta-analysis (1,209 patients) was 0.87 favoring heparin-bonded polytetrafluoroethylene (P = .33). Posterior hazard ratio from Cox regression was 0.90 (credible interval 0.70-1.13) favoring heparin-bonded polytetrafluoroethylene, which was not significant. Bayesian posterior probability of the a priori hypothesized 20% better patency with heparin-bonded polytetrafluoroethylene was 24%. Sample size to detect superiority with the small observed effect size would require about 3,800 subjects. CONCLUSION: Current evidence does not demonstrate sufficiently large benefit of heparin-bonded polytetrafluoroethylene over standard polytetrafluoroethylene for dialysis access to justify higher cost. Given similar 1-year patency rates, a conclusive finding of superiority was judged to be infeasible, and the trial was stopped for futility.

Diagnostic value of whole-exome sequencing in Chinese pediatric-onset neuromuscular patients.

BACKGROUND: Neuromuscular disorders (NMDs) comprise a group of heterogeneous genetic diseases with a broad spectrum of overlapping the clinical presentations that makes diagnosis challenging. Notably, the recent introduction of whole-exome sequencing (WES) is introducing rapid changes on the genetic diagnosis of NMDs. We aimed to investigate the diagnostic value of WES for pediatric-onset NMDs. METHODS: We applied integrated diagnostic approach and performed WES in 50 Chinese subjects (30 males, 20 females) with undiagnosed pediatric-onset NMDs despite previous specific tests. The patients were categorized in four subgroups according to phenotyping and investigation findings. Variants on NMDs gene list and open exome analysis for those with initial negative findings were identified. RESULTS: WES identified causative variants in ACTA1 (n = 2), POMT1, COL6A1 (n = 2), MTMR2, LMNA, SELENON, DNM2, TGFB1, MPZ, IGHMBP2, and LAMA2 in 13 patients. Two subjects have variants of uncertain significance (VUSs) in TTN and SCN11A, unlikely to be pathogenic due to incompatible phenotypes. The mean interval time from symptom onset to genetic diagnosis was 10.4 years (range from 1 month to 33 years). The overall diagnostic yield of WES in our cohort was 26%. Open exome analysis was necessary to identify the pathogenic variant in TGFB1 that caused skeletal dysplasia with neuromuscular presentation. CONCLUSION: Our study shows a clear role of WES in the pathway of integrated diagnostic approach to shorten the diagnostic odyssey in patients with rare NMDs.

Anatomic criteria in the selection of treatment modality for atherosclerotic carotid artery disease.

OBJECTIVE: Three procedures are currently available to treat atherosclerotic carotid artery stenosis: carotid endarterectomy (CEA), transfemoral carotid artery stenting (TF-CAS), and transcarotid artery revascularization (TCAR). Although there is considerable debate evaluating each of these in a head-to-head comparison to determine superiority, little has been mentioned concerning the specific anatomic criteria that make one more appropriate. We conducted a study to define anatomic criteria in relation to inclusion and exclusion criteria and relative contraindications. METHODS: A retrospective review was conducted of 448 carotid arteries from 224 consecutive patients who underwent a neck and head computed tomography arteriography (CTA) scan before carotid intervention for significant carotid artery stenosis. Occlusion of the internal carotid artery (ICA) occurred in 15, yielding 433 arteries for analysis. Anatomic data were collected from CTA images and demographic and comorbidities from chart review. Eligibility for CEA, TF-CAS, and TCAR was defined on the basis of anatomy, not by comorbidity. RESULTS: CTA analysis revealed that 92 of 433 arteries (21%) were ineligible for CEA because of carotid lesions extending cephalad to the second cervical vertebra. Overall, 26 arteries (6.0%) were not eligible for any type of carotid artery stent because of small ICA diameter (n = 11), heavy circumferential calcium (n = 14), or combination (n = 1). An additional 126 arteries were ineligible for TF-CAS on the basis of a hostile aortic arch (n = 115) or severe distal ICA tortuosity (n = 11), yielding 281 arteries (64.9%) that were eligible. In addition to the 26 arteries ineligible for any carotid stent, TCAR was contraindicated in 39 because of a clavicle to bifurcation distance <5 cm (n = 17), common carotid artery diameter <6 mm (n = 3), or significant plaque at the TCAR sheath access site (n = 20), yielding 368 arteries (85.0%) that were eligible for TCAR. CONCLUSIONS: A significant proportion of patients who present with carotid artery stenosis have anatomy that makes one or more carotid interventions contraindicated or less desirable. Anatomic factors should play a key role in selecting the most appropriate procedure to treat carotid artery stenosis. Determination of superiority for one procedure over another should be tempered until anatomic criteria have been assessed to select the best procedural options for each patient.

Elevated neutrophil-lymphocyte ratio predicts mortality following elective endovascular aneurysm repair.

OBJECTIVE: The neutrophil-lymphocyte ratio (NLR) is an inexpensive and useful inflammatory marker that incorporates the balance of the innate (neutrophil) and adaptive (lymphocyte) immune responses. Data exist on the association between NLR and mortality in various coronary diseases and in cancer surgery, but there is a paucity of data on the impact of preoperative NLR on vascular surgical outcomes. The aim of this study was to evaluate the relationship between preoperative NLR and elective endovascular aortic aneurysm repair (EVAR) outcome. METHODS: A retrospective review of all patients who underwent elective EVAR at a single institution between 2010 and 2018 was conducted (n = 373). Only patients who had a preoperative complete blood count with differential within 30 days of their operation were included. The NLR was computed by dividing the absolute neutrophil count by the absolute lymphocyte count. A receiver operating characteristic curve was used to determine the optimal cutoff value of NLR with the strongest association with mortality. NLR was dichotomized so that patients with NLR above the threshold were at increased risk of mortality compared with those below it. Continuous variables were analyzed using Wilcoxon nonparametric signed-rank test and categorical variables with the Fisher exact test. A comparison of NLR and mortality was completed using Kaplan-Meier survival analysis. Cox regression analysis was used to evaluate factors associated with mortality through 5-year follow-up. RESULTS: Overall, 108 patients were included in this study. An NLR ≥ 4.0 was found to be associated with mortality (P < .0001). Thirty-two patients composed the High-NLR (NLR ≥ 4.0) group and the remaining 76 patients formed the Low-NLR (NLR < 4.0) group. Baseline characteristics were similar between groups, except that the High-NLR group was older (77.9 vs 74.4; P = .047). At a mean of 36.4 months follow-up, the overall mortality rate was 32.4%. Although there were no differences in the perioperative period, the Kaplan-Meier estimates of mortality were significantly greater in the High-NLR group at 1, 2, and 5 years postoperatively (P < .0001). The mean preoperative NLR of the deceased was higher (5.94 ± 5.20; median, 4.75; interquartile range, 3.17-7.83) than those who survived (2.87 ± 1.61; median, 2.53; interquartile range, 1.97-3.49) (P < .0001). Secondary interventions and sac enlargement rates were similar between groups. On univariable analysis, NLR (hazard ratio [HR], 1.17; 95% confidence interval [CI], 1.10-1.23; P < .0001), age (HR, 1.06; 95% CI, 1.02-1.11; P = .004), and aneurysm diameter (HR, 1.04; 95% CI, 1.01-1.07; P = .003) were associated with mortality. On multivariable analysis, NLR (HR, 1.19; 95% CI, 1.12-1.27; P < .0001), age (HR, 1.06; 95% CI, 1.01-1.11; P = .026), and aneurysm diameter (HR, 1.04; 95% CI, 1.02-1.07; P = .003) were associated with mortality. CONCLUSIONS: Patients with an elevated preoperative NLR, irrespective of other comorbidities, may represent a previously unrecognized subset of patients who are at heightened risk of mortality after elective EVAR. A complete blood count with differential is an inexpensive test that may be used as a prognostic indicator for outcome after EVAR. Further research is warranted to identify clinical, pathological, or anatomical factors associated with an elevated NLR and to determine modifiable factors, which may help improve long-term survival.

Frequency of perigraft hygroma after open aortic reconstruction.

OBJECTIVE: The incidence of perigraft hygroma (PGH) development after aortic reconstruction remains poorly defined and its clinical relevance is questionable. This study was designed to establish the incidence of and determine the risk factors associated with PGH formation and its outcomes. METHODS: Patients who underwent open aortic reconstruction for either aneurysmal or occlusive disease with an expanded polytetrafluoroethylene (ePTFE) or polyester graft from 2004 to 2018 were retrospectively reviewed (n = 262). Only those who had follow-up imaging 3 or more months after repair were included. Patients with mixed graft types were excluded. PGH was defined as a perigraft fluid collection of 30 mm or greater in diameter with a radiodensity of 30 or fewer Hounsfield units on computed tomography at a minimum of 3 postoperative months. Analysis was conducted between patients with and without PGH. RESULTS: One hundred forty patients met the inclusion criteria: 88 were treated with ePTFE and 52 with polyester grafts. Twenty-three patients (16.4%) were found to have radiologic evidence of PGH. PGH developed more frequently in patients with ePTFE (21/88 [23.9%]) compared with those with polyester grafts (2/52 [3.8%]) (P = .002). Mean PGH size was 63.5 ± 36.4 mm (range, 33-153 mm) and the average time to PGH detection 27.7 months (range, 3-112 months). Baseline characteristics were similar between the groups. Patients who developed PGH had larger aneurysms, more often received ePTFE grafts, had larger graft diameters, and had bifurcated grafts. The overall mortality was 32.1% at a mean follow-up of 5.2 years. The 5-year mortality rates were similar between patients with and without PGH (26.1% vs 18.8%; P = .41). Of the 23 patients with PGH, 4 (all with ePTFE) presented with symptoms related to the PGH. The average size of symptomatic and asymptomatic PGH were 11.5 and 4.8 cm, respectively. Mortality rates overall were similar between those with and without symptoms (50.0% vs 36.8%; P = .99). CONCLUSIONS: Nearly one-quarter of aortic reconstructions with ePTFE are associated with PGH formation compared with 4% with polyester. Clinically significant PGH-related symptom development occurs in 20%. Patient education and close surveillance are warranted. Manufacturer's device modification is needed.

Paclitaxel-coated peripheral artery devices are not associated with increased mortality.

OBJECTIVE: Long-term safety concerns have been raised that the use of paclitaxel-coated balloons and stents is linked to excess mortality. Our objective was to compare outcomes in patients treated with paclitaxel vs uncoated devices and to analyze long-term mortality. METHODS: We conducted a retrospective single-institution review of 1170 consecutive patients who underwent femoropopliteal percutaneous revascularization by angioplasty, atherectomy, stent placement, or combination between 2011 and 2018. The primary outcome measure was all-cause mortality. Groups were divided into patients who received paclitaxel (n = 652) and those who did not (n = 518). Categorical variables were assessed using χ2 analysis and continuous variables with the Wilcoxon signed rank test. A multivariable analysis was performed using multivariable logistic regression models. Mortality was compared using Kaplan-Meier survival analysis. RESULTS: Demographics, risk factors, and Rutherford class were similar between the groups, except that the paclitaxel group was more likely to have diabetes (60.9% vs 55.0%; P = .04), was less likely to be on dialysis (10.7% vs 14.9%; P = .04), and had lower average creatinine concentration (1.6 ± 1.8 mg/dL vs 2.0 ± 2.3 mg/dL; P = .003). There were no differences in all-cause mortality through 2 years between paclitaxel and no-paclitaxel cohorts (25.5% vs 30.3%; log-rank, P = .098). At 3 years and 3.5 years, mortality was significantly lower in the paclitaxel group: year 3, 32.1% vs 39.4% (log-rank, P = .041); year 3.5, 35.2% vs 43.9% (log-rank, P = .027). Survival rates were not significantly different in examining subgroups by diabetes, chronic kidney disease, presence of chronic limb-threatening ischemia, or paclitaxel-coated balloon manufacturer. Multivariable analysis demonstrated that age, dialysis, chronic limb-threatening ischemia, chronic kidney disease, and congestive heart failure were independent risk factors for mortality, whereas paclitaxel use was associated with lower mortality. CONCLUSIONS: The use of paclitaxel-coated balloons and stents does not increase mortality compared with uncoated devices out to 3.5 years. Paclitaxel-coated devices can be used with continued caution, especially in patients at increased risk of restenosis. Further long-term studies are needed to determine the risk of late mortality.

Oral health status of children with epilepsy in Hong Kong.

AIM: This study assessed and compared the oral health status, dental trauma experience and oral health habits of children with and without epilepsy. METHODS: Thirty-five children with epilepsy aged 3-18 years old were recruited from the pediatric neurology clinics of 2 university-affiliated district hospitals. A sample of 35 age- and gender-matched healthy children was recruited as controls. Clinical data on caries, gingival health, oral hygiene level and dental trauma were collected and compared between the groups. Information about children's oral health habits and reported dental trauma experience were obtained by structured questionnaire. RESULTS: Children with epilepsy had significantly poorer gingival health than healthy controls. No significant differences in dental caries experience, oral hygiene level, dental trauma experience, oral health habits and dental care service utilization were observed between the children with and without epilepsy. Among the children with epilepsy, those taking more than 1 antiepileptic drug had a greater prevalence of dental caries when compared with those receiving mono-antiepileptic drug therapy. The presence of gingival hyperplasia indicated poorer gingival health in epileptic children. CONCLUSION: The study shows that children with epilepsy had poorer oral health status in terms of gingival health than those without epilepsy.

The Gestalt of functioning in autism spectrum disorder: Results of the international conference to develop final consensus International Classification of Functioning, Disability and Health core sets.

Autism spectrum disorder is associated with diverse social, educational, and occupational challenges. To date, no standardized, internationally accepted tools exist to assess autism spectrum disorder-related functioning. World Health Organization's International Classification of Functioning, Disability and Health can serve as foundation for developing such tools. This study aimed to identify a comprehensive, a common brief, and three age-appropriate brief autism spectrum disorder Core Sets. Four international preparatory studies yielded in total 164 second-level International Classification of Functioning, Disability and Health candidate categories. Based on this evidence, 20 international autism spectrum disorder experts applied an established iterative decision-making consensus process to select from the candidate categories the most relevant ones to constitute the autism spectrum disorder Core Sets. The consensus process generated 111 second-level International Classification of Functioning, Disability and Health categories in the Comprehensive Core Set for autism spectrum disorder-one body structure, 20 body functions, 59 activities and participation categories, and 31 environmental factors. The Common Brief Core Set comprised 60 categories, while the age-appropriate core sets included 73 categories in the preschool version (0- to 5-year-old children), 81 in the school-age version (6- to 16-year-old children and adolescents), and 79 in the older adolescent and adult version (⩾17-year-old individuals). The autism spectrum disorder Core Sets mark a milestone toward the standardized assessment of autism spectrum disorder-related functioning in educational, administrative, clinical, and research settings.

Spinal Muscular Atrophy With Respiratory Distress Type 1-A Child With Atypical Presentation.

The authors report a child with spinal muscular atrophy with respiratory distress type 1 (SMARD1). She presented atypically with hypothyroidism and heart failure due to septal defects that required early heart surgery and microcephaly in association with cerebral atrophy and thin corpus collosum. The subsequent asymmetrical onset of diaphragmatic paralysis, persistent hypotonia, and generalized muscle weakness led to the suspicion of spinal muscular atrophy with respiratory distress type 1. Sanger sequencing confirmed a compound heterozygous mutation in the Immunoglobulin Mu Binding Protein 2 (IGHMBP2) gene, with a known mutation c.2362C > T (p.Arg788*) and a novel frameshift mutation c.2048delG (p.Gly683A1afs*50). Serial nerve conduction study and electromyography confirmed progressive sensorimotor polyneuropathy and neuronopathy. In summary, this case report describes a child with spinal muscular atrophy with respiratory distress type 1 also with congenital cardiac disease and endocrine dysfunction, expanding the phenotypic spectrum of this condition. A high index of suspicion is needed in diagnosing this rare condition to guide the management and genetic counseling.

Comparison of patient-specific factors and outcomes for one- and two-stage basilic vein transposition fistulas.

OBJECTIVE: The decision to perform a one- or two-stage basilic vein transposition (BVT) arteriovenous fistula often depends on factors such as the vessel's diameter, the patient's disposition, and the surgeon's preference. This study's aim was to analyze patency by BVT staging technique and to identify patient-specific characteristics associated with outcomes. METHODS: A retrospective review of all patients who underwent one- or two-stage BVT at our institution between 2008 and 2013 was performed. Comparisons of age, sex, race, and associated comorbidities were made. Clinical course was followed for 2 years after fistula construction, comparing maturation rate, thrombosis, stenosis, steal, and catheter infections. Continuous variables were expressed as means or medians and compared across stage and maturation groups by t-test; differences between categorical variables were assessed using Fisher exact test. A Kaplan-Meier survival analysis was performed to calculate patency rates and compared by log-rank test. RESULTS: There were 49 one-stage and 169 two-stage BVTs examined. The mean age of the patients at time of construction was 58 years and 61 years for one-stage and two-stage patients, respectively. There was no difference in mean proximal, mid, or distal basilic vein diameters between the groups. Fistula maturation was similar between stage groups, with primary failure affecting 26.5% of one-stage and 24.3% of two-stage BVTs (P = .78). Across one- and two-stage BVTs, 2-year primary patency rates were 51% and 52%, respectively (P = .68); primary assisted patency, 66% and 85% (P = .05); and secondary patency, 64% and 78% (P = .26). Multivariate logistic regression showed a trend toward diabetics at higher risk for primary failure (odds ratio, 1.60; 95% confidence interval, 0.95-2.55; P = .07). For two-stage BVT, the median interstage period between operations lasted 105.00 (interquartile range, 77.00-174.50) days and was associated with a large proportion of the overall primary failures (19/41 [46%]) and catheter-related infections (12/20 [60%]). CONCLUSIONS: This study demonstrates similar maturation, primary patency, primary assisted patency, secondary patency, and complication rates in a large series of BVTs constructed using a one- or two-stage transposition technique regardless of vein diameter. Diabetes was associated with primary failure by either technique. High proportions of overall primary failures and catheter-related infections observed in two-stage BVT occurred during the interstage, suggesting that a one-stage technique should be considered over a two-stage approach to minimize the risk of catheter infection and to decrease time to maturity.

Anti-N-methyl-d-aspartate receptor encephalitis in children: Incidence and experience in Hong Kong.

AIM: The study aims to analyze the incidence, clinical features, investigation findings and treatment outcomes of anti-N-methyl-d-aspartate receptor encephalitis in children from Hong Kong. METHOD: A retrospective study was carried out on paediatric patients diagnosed with anti-NMDAR encephalitis in Hong Kong from January 2009 to December 2015. RESULTS: Fifteen patients (67% female, 93% Chinese) were identified over seven years and the estimated incidence in Hong Kong was 2.2/million children per year (95% CI 1.2-3.6). The median age of presentation was 12 years (range 1-17 years). The most common symptom groups observed were abnormal psychiatric behavior or cognitive dysfunction (14/15, 93%) and seizures (14/15, 93%), followed by speech dysfunction (13/15, 87%), movement disorders (12/15, 80%), decreased level of consciousness (10/15, 67%) and autonomic dysfunction or central hypoventilation (5/15, 33%). The median number of symptom groups developed in each patient was 5 (range 3-6). All patients were treated with intravenous immunoglobulin and/or steroids. Three patients (20%) with more severe presentation required additional plasmapheresis and rituximab. Outcome was assessable in 14 patients. Among those eleven patients who had only received intravenous immunoglobulin and/or steroids, nine patients (82%) achieved full recovery. One patient (9%) had residual behavioral problem, while another one (9%) who developed anti-NMDAR encephalitis after herpes simplex virus encephalitis was complicated with dyskinetic cerebral palsy and epilepsy. Among those three patients who required plasmapheresis and rituximab, one (33%) had full recovery and two (66%) had substantial recovery. The median duration of follow up was 20.5 months (range 3-84 months). CONCLUSION: Anti-NMDAR encephalitis is an acquired, severe, but potentially treatable disorder. Ethnicity may play a role in the incidence of anti-NMDAR encephalitis and we have provided a local incidence with the majority of patients being Chinese. The diagnosis of anti-NMDAR encephalitis should be considered in children presenting with a constellation of symptoms including psychiatric and neurological manifestations. Patients may respond to first line immunotherapy. For those who do not, second line therapy is indicated in order to achieve a better outcome.