Indications and Evolution of the Butterfly Graft in Nasal Valve Repair.

Persistent nasal airway obstruction from inadequately addressed nasal valve compromise is common. Many techniques exist to perform nasal valve repair. Historically, spreader grafts are the most commonly used, despite a relative lack of evidence demonstrating its superiority over other methods. The butterfly graft is an alternative method of nasal valve repair and detailed surgical description from over 20 years of innovation follows in this section. There is growing evidence to suggest that the butterfly graft may be superior to spreader grafts with similar acceptability of the esthetic outcomes.

Outcomes of fenestrated and branched endovascular aneurysm repair with an inverted contralateral limb.

OBJECTIVE: To report technical success and evaluate clinical outcomes of fenestrated and branched endovascular aortic repair (F/B-EVAR) incorporating a contralateral inverted limb. METHODS: Patients who underwent F/B-EVAR with a custom-made bifurcated device containing an inverted limb between January 2010 and September 2023 were retrospectively analyzed. Time-to-event data were analyzed using the Kaplan-Meier method. RESULTS: A total of 32 patients (26 men; mean age 77±6.2 years) were included in the analysis. Technical success was achieved in 28 patients (87.5%). Two technical failures resulted from misplaced contralateral limbs in patients with previous endovascular aortic repair (EVAR), necessitating one open conversion due to a type 3b endoleak, and one femoro-femoral crossover bypass after occlusion of a misplaced contralateral limb. Additionally, two technical failures were attributed to a type 3c endoleak and a type 1c endoleak, originating from a fenestrated device at the level of the left and right renal artery, respectively. One patient (3.1%) died <30 days post-operatively due to a subdural hemorrhage. Estimated patient survival after 1 and 2 years was 92.7%±5.1%, and 74.3%±10.1%, respectively. No aneurysm-related deaths were observed. During the median follow-up of 13 months, one (3.1%) inverted limb occluded, in addition to the occlusion resulting from a misplaced contralateral limb, and was treated with a femoro-femoral crossover bypass. One target vessel (right renal artery) occluded (0.9%), resulting in a permanent, significantly reduced renal function. Freedom from overall reintervention after 1 and 2 years was 73.5%±8.0% and 68.3%±9.0%, respectively. An additional four patients (12.5%) presented with a type 3c endoleak during follow-up scans, three of which originated from fenestrations at the level of the renal stents. There were no junctional problems between the inverted limb device and the main endograft, and no significant correlation was found between the one-sealing-stent inverted limb device design and the onset of type 3 endoleak (log-rank p=.064). CONCLUSION: F/B-EVAR incorporating an inverted limb can be a viable endovascular option to manage complex aneurysms with a short renal artery to bifurcation distance. However, using the inverted limb presents a notable technical challenge and could be associated with a higher need for reintervention. Carefully confirming correct cannulation of the inverted limb is warranted.

Effects of immunosuppression after limb fracture in mice on nociceptive, cognitive, and anxiety-related outcomes.

Introduction: Chronic pain is a common and problematic consequence of injuries with few proven methods for prevention or treatment. In addition to pain, functional limitations and neuropsychiatric changes such as cognitive impairment and anxiety worsen outcomes. Objectives: To determine whether inhibiting activation of the adaptive immune response after limb fracture would reduce pain, functional loss, memory changes, and anxiety. Methods: These experiments used a murine tibial fracture/cast immobilization model that develops these adverse outcomes. Adaptive immunity was blocked using the immunosuppressant FK506 beginning at the time of fracture. Results: The administration of FK506 reduced mechanical allodynia and hind limb unweighting for weeks after cast removal as well as nonevoked pain measures. Fracture was associated with working memory loss in the Y-maze assay in vehicle- but not FK506-treated mice. Object recognition memory was not improved with FK506 after fracture. Also, vehicle- but not FK506-treated mice developed an anxiety phenotype. Impaired running wheel performance after cast removal over the following 2 weeks was not improved with FK506 administration. In addition, FK506 treatment blocked Immunoglobulin M (IgM) accumulation in the skin of the fractured limbs, and hippocampal enhancement of matrix metalloproteinase-8 expression, a metalloproteinase associated with neuroplastic changes after injuries, was completely blocked. Conclusion: Taken together, our results show that blocking the adaptive immune response after limb trauma reduces the severity of nociceptive and biological changes. The same treatment may reduce the adverse consequences of anxiety and memory deficits using some measures, but other measures of memory are not affected, and activity is not enhanced.

An international, expert-based, Delphi consensus document on controversial issues in the management of abdominal aortic aneurysms.

OBJECTIVE: As a result of conflicting, inadequate or controversial data in the literature, several issues concerning the management of patients with abdominal aortic aneurysms (AAAs) remain unanswered. The aim of this international, expert-based Delphi consensus document was to provide some guidance for clinicians on these controversial topics. METHODS: A three-round Delphi consensus document was produced with 44 experts on 6 prespecified topics regarding the management of AAAs. All answers were provided anonymously. The response rate for each round was 100%. RESULTS: Most participants (42 of 44 [95.4%]) agreed that a minimum case volume per year is essential (or probably essential) for a center to offer open or endovascular AAA repair (EVAR). Furthermore, 33 of 44 (75.0%) believed that AAA screening programs are (probably) still clinically effective and cost effective. Additionally, most panelists (36 of 44 [81.9%]) voted that surveillance after EVAR should be (or should probably be) lifelong. Finally, 35 of 44 participants (79.7%) thought that women smokers should (or should probably/possibly) be considered for screening at 65 years of age, similar to men. No consensus was achieved regarding lowering the threshold for AAA repair and the need for deep venous thrombosis prophylaxis in patients undergoing EVAR. CONCLUSIONS: This expert-based Delphi consensus document provides guidance for clinicians regarding specific unresolved issues. Consensus could not be achieved on some topics, highlighting the need for further research in those areas.

Implementation of low temperature spectrometers for the JET high resolution Thomson scattering diagnostic for disruption plasma measurements.

This work presents a system upgrade of the High Resolution Thomson Scattering (HRTS) diagnostic [Pasqualotto et al., Rev. Sci. Instrum. 75, 3891-3893 (2004)] on JET that allows it to measure low temperature (1-500 eV) plasma pre- and post-Thermal quench (TQ), which would help us further understand the Shattered Pellet Injection (SPI) physics. The upgrade was done by connecting optic fibers from the original HRTS system to four spectrometers specialized in measuring low temperature plasmas. The upgraded system allows for the measurement of low temperature plasma at up to 12 spatial points, which can be flexibly distributed throughout the JET outer midplane profile during the dedicated SPI experiments. In other JET experiments, four previously unused groups of fibers were used to measure the central plasma to provide disruption data without changing the standard HRTS system. The low temperature Thomson scattering system was installed, commissioned, and cross-calibrated against the standard HRTS diagnostic in a calibration pulse. The system worked reliably during the JET experiments and provided electron density and temperature profiles for pre- and post-TQ low temperature plasmas in the SPI campaign.

A phase 2, randomized, blinded, dose-finding, controlled clinical trial to evaluate the safety, tolerability, and immunogenicity of a 24-valent pneumococcal conjugate vaccine (VAX-24) in healthy adults 65 years and older.

Despite current polysaccharide and conjugate vaccine use, pneumococcal diseases remain prevalent in older adults. VAX-24 is a 24-valent pneumococcal conjugate vaccine (PCV) containing eCRM, a proprietary carrier protein with non-native amino acids (para-azidomethyl-L-phenylalanine) that undergo site-specific conjugation to pneumococcal polysaccharides that have been activated with a small-molecule linker (dibenzocyclooctyne). Site-specific conjugation utilizing click chemistry enables consistent exposure of T-cell epitopes, reduction in carrier protein to pneumococcal polysaccharide ratio, and enhances manufacturing process consistency to improve PCVs by increasing serotype coverage while minimizing carrier suppression. Healthy adults aged 65 or older were randomized in a 1:1:1:1 ratio to receive a single injection of VAX-24 at 1 of 3 dose levels (1.1, 2.2, or a mixed dose of 2.2 or 4.4 mcg) or Prevnar 20® (PCV20) in a phase 2, blinded study. Primary outcome measures were solicited local and systemic events within 7 days post-vaccination, unsolicited adverse events (AEs) within 1 month, and serious AEs, medically attended AEs, or new onset of chronic disease within 6 months of vaccination. Serotype-specific opsonophagocytic activity (OPA) and immunoglobulin G (IgG) were measured pre-vaccination and at 1 month post-vaccination. Of 207 participants enrolled, 200 completed the trial. Safety profiles were comparable across the three VAX-24 doses and PCV20. Robust OPA and IgG immune responses were seen for all 24 serotypes. On average, immune responses to VAX-24 2.2 mcg dose were similar or higher compared to PCV20. In adults ≥ 65 years, VAX-24 had a safety profile similar to PCV20 through six months post-vaccination and induced robust OPA and IgG responses to all 24 serotypes, supporting prior data showing that site-specific conjugation allows for increased serotype coverage with similar or higher immune response vs other PCVs. The outcome of this phase 2 study further supports use of VAX-24 2.2 mcg dose in phase 3 trials. Clinicaltrials.gov: NCT05297578.

Optimizing Treatment of Significant Carotid Artery Stenosis in Times of Logistic Restraints as a Result of COVID-19 Pandemic.

BACKGROUND: COVID-19 confronted medical care with many challenges. During the pandemic, several resources were limited resulting in renouncing or postponing medical care like carotid endarterectomy (CEA) for patients with significant carotid artery stenosis. Although according to international guidelines CEA is the first choice, carotid artery stenting (CAS) could potentially be a reasonable alternative especially during logistical restraints. PURPOSE: To evaluate outcomes of CAS versus CEA before, during and after the COVID-19 pandemic. Our hypothesis was that a CAS first approach yielded comparable outcomes compared to a CEA first approach. METHODS: Retrospective analysis of consecutive patients with significant carotid artery stenosis treated with CEA or CAS between September 2018 and March 2023. Each consecutive period of 1.5 year marked a new (treatment) period: pre-COVID (CEA first strategy), during COVID (CAS first strategy) and post-COVID (patient-tailored approach). Primary outcome was the composite endpoint of stroke, transient ischemic attack or death within 30 days. Secondary outcome consisted of the rate of technical success, cerebral hyperperfusion syndrome, myocardial infarction or other cardiac complications needing intervention, bleeding of the surgical site needing intervention, nerve palsy, unintended IC admission, pseudoaneurysm, restenosis, or occlusion. RESULTS: A total of 318 patients were included. Out of 137 patients treated with CEA, 55, 36 and 46 were treated pre-COVID, during COVID and post-COVID, respectively. Out of 181 CAS procedures, 38, 59 and 84, respectively, were performed in each time period. Primary outcome occurred in 5.5%, 0% and 2.2% in the CEA group and 0%, 1.7% and 3.6% in the CAS group (P = 0.27; P = 1.00; P = 1.00, respectively). Overall technical success was 100% for CEA and 99.4% for CAS (P = 1.00). Rate of restenosis was the only secondary outcome measure which was significantly better after CAS compared to CEA in the pre- and post-COVID period (CEA vs. CAS, 12.7% vs. 7.9%, and 23.9% vs. 4.8% with a P-value of 0.03 and 0.03, respectively). Hospital presentation to treatment interval did not differ significantly during the pandemic. CONCLUSIONS: Outcomes were comparable between CAS versus CEA in patients with significant carotid artery stenosis before, during and after the COVID-19 pandemic. CAS showed better results in terms of other complications (i.e., restenosis rate) in the pre- and post-COVID period compared to CEA. Our results may support a CAS first approach when no relevant contra-indications exist without exposing the patient to complications associated with an open surgical approach. Discussion in a multidisciplinary team is advised.

Antibody-mediated autoimmunity in symptom-based disorders: position statement and proceedings from an international workshop.

A 2-day closed workshop was held in Liverpool, United Kingdom, to discuss the results of research concerning symptom-based disorders (SBDs) caused by autoantibodies, share technical knowledge, and consider future plans. Twenty-two speakers and 14 additional participants attended. This workshop set out to consolidate knowledge about the contribution of autoantibodies to SBDs. Persuasive evidence for a causative role of autoantibodies in disease often derives from experimental "passive transfer" approaches, as first established in neurological research. Here, serum immunoglobulin (IgM or IgG) is purified from donated blood and transferred to rodents, either systemically or intrathecally. Rodents are then assessed for the expression of phenotypes resembling the human condition; successful phenotype transfer is considered supportive of or proof for autoimmune pathology. Workshop participants discussed passive transfer models and wider evidence for autoantibody contribution to a range of SBDs. Clinical trials testing autoantibody reduction were presented. Cornerstones of both experimental approaches and clinical trial parameters in this field were distilled and presented in this article. Mounting evidence suggests that immunoglobulin transfer from patient donors often induces the respective SBD phenotype in rodents. Understanding antibody binding epitopes and downstream mechanisms will require substantial research efforts, but treatments to reduce antibody titres can already now be evaluated.

First Study of the

New astronomical observations point to a nucleosynthesis picture that goes beyond what was accepted until recently. The intermediate "i" process was proposed as a plausible scenario to explain some of the unusual abundance patterns observed in metal-poor stars. The most important nuclear physics properties entering i-process calculations are the neutron-capture cross sections and they are almost exclusively not known experimentally. Here we provide the first experimental constraints on the ^{139}Ba(n,γ)^{140}Ba reaction rate, which is the dominant source of uncertainty for the production of lanthanum, a key indicator of i-process conditions. This is an important step towards identifying the exact astrophysical site of stars carrying the i-process signature.

Preoperative cognitive performance and its association with postoperative complications in vascular surgery patients: A prospective study.

BACKGROUND: Cognitive impairment affects nearly half of vascular surgery patients, but its association with postoperative outcomes remains poorly understood. This study explores the link between preoperative cognitive performance and postoperative complications, including postoperative delirium, in vascular surgery patients. METHODS: A prospective cohort study was conducted on vascular surgery patients aged ≥65. Preoperative cognitive performance was assessed using the Montreal Cognitive Assessment, and postoperative complications were evaluated using the Comprehensive Complication Index. The association was analyzed through multivariable logistic regression. RESULTS: Among 110 patients (18.2 â€‹% female, mean age 73.8 â€‹± â€‹5.7 years), cognitive impairment was evident in 48.2 â€‹%. Of the participants, 29 (26.3 â€‹%) experienced postoperative complications, among which 11 (10 â€‹%) experienced postoperative delirium. The adjusted odds ratio for the association between cognitive performance and postoperative complications was 1.19 (95 â€‹% CI 1.02-1.38; p â€‹= â€‹0.02). CONCLUSION: Worse preoperative cognitive performance correlated with increased odds of postoperative complications and postoperative delirium in vascular surgery patients.

Biochemical Variability of Nasal Cartilages: Implications in Functional Rhinoplasty.

INTRODUCTION: Nasal valve compromise is a common issue for patients presenting to an otolaryngologist. Anatomically, the dorsal septal cartilage (DSA) articulates with the upper lateral nasal cartilage (ULC). When the ULC weakens, it is prone to collapse and may result in nasal obstruction. Our objectives were to analyze histological differences between quadrangular and DSA nasal cartilages and compare histological composition of these tissues among patients with diagnosis of nasal valve compromise (NVC) versus those without NVC (no NVC). METHODS: Prospective cross-sectional study of nasal cartilages from seventy-three (73) live donors. Quadrangular cartilage (QC), and DSA from patients undergoing septorhinoplasty were collected. Safranin O histochemical staining was used to observe glycosaminoglycans (GAGs) content and cell count. Masson's Trichrome staining was used to assess collagen content in these nasal cartilages. RESULTS: Mean GAG content was lower in DSA compared with QUAD cartilage (68.18% vs. 87.22%, p < 0.0001), and was lowest in DSA of patients with NVC (59.07%). Mean collagen content was higher in DSA compared with QUAD cartilage, (65.43% vs. 46.65%, p = 0.0002), and was highest in DSA of patients with NVC (74.86%). CONCLUSION: The DSA showed decreased GAG and increased collagen content compared with quadrangular cartilage. Within the DSA subsite, patients with presurgical NVC had the lowest GAG and highest collagen levels. This observation suggests that the biochemical composition of the DSA may contribute to its weakening, potentially resulting in its inability to withstand minor trauma and/or the effects of aging, ultimately leading to NVC. LEVEL OF EVIDENCE: N/A Laryngoscope, 2024.

Three-Dimensional Geometric Analysis of Viabahn VBX Bridging Stent Grafts in Fenestrated Endovascular Aortic Repair: A Multicenter, Retrospective Cohort Study.

PURPOSE: The primary aim of this study was to assess the 3-dimensional flare geometry of the Gore Viabahn VBX balloon-expandable covered stent (BECS) after fenestrated endovascular aortic repair (FEVAR) and to determine and visualize BECS-associated complications. METHODS: This multicenter retrospective study included patients who underwent FEVAR between 2018 and 2022 in 3 vascular centers participating in the VBX Expand Registry. Patients with at least one visceral artery treated with the VBX and with availability of 2 post-FEVAR computed tomography angiography (CTA) scans (follow-up [FU] 1: 0-6 months; FU2: 9-24 months) were included. The flare geometry of the VBX, including flare-to-fenestration distance, flare-to-fenestration diameter ratio, flare angle, and apposition with the target artery were assessed using a vascular workstation and dedicated CTA applied software. RESULTS: In total, 90 VBX BECS were analyzed in 43 FEVAR patients. The median CTA FU for FU1 and FU2 was 35 days (interquartile range [IQR], 29-51 days) and 14 months (IQR, 13-15 months), respectively. The mean flare-to-fenestration distance was 5.6±2.0 mm on FU1 and remained unchanged at 5.7±2.0 mm on FU2 (p=.417). The flare-to-fenestration diameter ratio was 1.19±0.17 on FU1 and remained unchanged at 1.21±0.19 (p=.206). The mean apposition length was 18.6±5.3 mm on FU1 and remained 18.6±5.3 mm (p=.550). The flare angle was 31°±15° on FU1 and changed to 33°±16° (p=.009). On FU1, the BECS-associated complication rate was 1%, and the BECS-associated reintervention rate was 0%. On FU2, the BECS-associated complication rate was 3%, and the BECS-associated reintervention rate was 1%. CONCLUSIONS: The flare geometry of the VBX bridging stent did not change significantly during 14 months follow-up in this study. Three-dimensional geometric analysis of the flare may contribute to identify the origin of endoleaks and occlusions, but this should be confirmed in a larger study including enough patients and BECS to compare complicated and uncomplicated cases. CLINICAL IMPACT: The three-dimensional flare geometry of the Gore Viabahn VBX BECS was assessed on the first and second postoperative CTA scans, and geometrical changes during this period were identified. For BECS that were diagnosed with a type 3c endoleak or occlusion, the BECS geometry was analyzed to detect geometrical components that were related to the complication. Geometric analysis of the flare may help to better detect and identify the cause of such complications.

Comparison of Various Functional Assessment Tools to Identify Older Patients Undergoing Aortic Aneurysm Repair at Risk for Postoperative Complications.

BACKGROUND: To estimate whether the benefits of aortic aneurysm repair will outweigh the risks, determining individual risks is essential. This single-center prospective cohort study aimed to compare the association of functional tools with postoperative complications in older patients undergoing aortic aneurysm repair. METHODS: Ninety-eight patients (≥65 years) who underwent aortic aneurysm repair were included. Four functional tools were administered: the Montreal Cognitive Assessment (MoCA); the 4-Meter Walk Test (4-MWT); handgrip strength; and the Groningen Frailty Indicator (GFI). Primary outcome was the association between all tests and 30-day postoperative complications. RESULTS: After adjusting for confounders, the odds ratio for MoCA was 1.39 (95% confidence interval [CI] 0.450; 3.157; P = 0.723), for 4-MWT 0.63 (95% CI 0.242; 1.650; P = 0.348), for GFI 1.82 (95% CI 0.783; 4.323, P = 0.162), and for weak handgrip strength 4.78 (95% CI 1.338; 17.096, P = 0.016). CONCLUSIONS: Weak handgrip strength is significantly associated with the development of postoperative complications after aortic aneurysm repair. This study strengthens the idea that implementing a quick screening tool for risk assessment at the outpatient clinic, such as handgrip strength, identifies patients who may benefit from preoperative enhancement with help from, for example, Comprehensive Geriatric Assessment, eventually leading to better outcomes for this patient group.

Improved Tensor Current Limit from

A precision measurement of the ß^{+} decay of ^{8}B was performed using the Beta-decay Paul Trap to determine the ß-ν angular correlation coefficient a_{ßν}. The experimental results were combined with new ab initio symmetry-adapted no-core shell-model calculations to yield the second-most precise measurement from Gamow-Teller decays, a_{ßν}=-0.3345±0.0019_{stat}±0.0021_{syst}. This value agrees with the standard model value of -1/3 and improves uncertainties in ^{8}B by nearly a factor of 2. By combining results from ^{8}B and ^{8}Li, a tight limit on tensor current coupling to right-handed neutrinos was obtained. A recent global evaluation of all other precision ß decay studies suggested a nonzero value for right-handed neutrino coupling in contradiction with the standard model at just above 3σ. The present results are of comparable sensitivity and do not support this finding.

Impact on Hospital Resource Utilization of Endoluminal Bypass Using the Viabahn Endoprosthesis with Heparin Bioactive Surface Compared With Surgical Femoropopliteal Bypass.

OBJECTIVE: To assess the impact of heparin-bonded endoprosthesis compared with femoropopliteal bypass on key hospital resources and revenues up to 1-year follow-up. DESIGN: A 2-arm scenario resource consumption data analysis was modeled based on a multicentre prospective randomized controlled trial. SETTING: Six centers in the Netherlands. PARTICIPANTS: A total of 100 patients were assigned to 2 arms (50 each arm). The first arm evaluated endovascular treatment using the heparin-bonded Viabahn endoprosthesis and the second the femoropopliteal bypass. Resource consumption rates were compared between arms. PRIMARY AND SECONDARY OUTCOMES MEASURES: Resource consumption rates, including hospital stay for bypass procedure, operating room time, type of anesthesia, number of used (endo)grafts, use of different types of bed locations (vascular ward, medium or intensive care), readmission for wound infections, and reinterventions over a period of 12 months. RESULTS: Endovascular repair used fewer hospital resources, with an overall difference of €149.983. Hospital stay was 118 days less (261 vs 379), including 21 fewer days in medium/intensive care (5 vs 26) and 50 fewer operating room hours (100 vs 150). Fewer patients required general anesthesia (31 vs 39), and there were less surgical site infections (3 vs 12). In the surgical bypass group, there were 18 fewer days of hospital stay related to reinterventions (80 vs 62), and the cost of the devices was €309.996, cheaper. The total monetary difference was € 160.013, in favor of the femoropopliteal bypass (€3.200, per patient). CONCLUSIONS: Endovascular repair of the superficial femoral artery reduces the use of valuable hospital resources. Its major limitation is the cost of the devices, which should be balanced against the reduction in peri-procedural morbidity and faster recovery. In the context of shortage of hospital beds, it offers capacity benefits, allowing for the treatment of more patients overall. These benefits may outweigh the fewer reinterventions in the surgical bypass group. REGISTRATION: The SuperB Trial was registered in clinicaltrials.gov; NCT-ID: NCT01220245. CLINICAL IMPACT: Modeling is a useful technique to predict the impact of treatment modalities on hospital resources and revenue. This study uses real-world data from the SuperB Trial to compare two treatment strategies of superficial femoral artery disease, reflecting actual clinical practice and patient outcomes. The analysis focused on direct costs associated with hospital resources and device usage without considering indirect costs or long-term cost-effectiveness. The analysis showed that endovascular repair reduces the use of valuable hospital resources. Its major limitation is device costs, which should be balanced against the reduction in peri-procedural morbidity and faster recovery. In the context of shortage of hospital beds, it offers capacity benefits, allowing for the treatment of more patients overall.

Post hoc analysis of the SuperB and Zilverpass trials for treatment of long and complex superficial femoral artery lesions.

OBJECTIVE: In two randomized controlled trials, the outcomes of endovascular treatment of complex femoropopliteal arterial lesions were compared with bypass surgery and considered a valid alternative treatment. The aim of this study was to compare both endovascular treatment options with the hypothesis that implantation of heparin-bonded self-expanding covered stents (Viabahn [SECS]) or drug-eluting stents (ZilverPTX [DES]) are related to similar clinical outcomes at 1-year follow-up. METHODS: In a post-hoc analysis, the SuperB trial and Zilverpass databases were merged. Patients in the endovascular treatment arms were included, and data was analyzed in an intention-to-treat (ITT) and a per-protocol (PP) fashion. Data included baseline and lesion characteristics, procedural details, and follow-up data. The primary endpoint of this study was primary patency at 1-year follow-up. The secondary endpoints were secondary patency, target lesion revascularization (TLR), limb loss, and all-cause mortality. RESULTS: A total of 176 patients were included; 63 in the SECS arm and 113 in the DES arm. Through 1-year follow-up, there were no significant differences in primary patency (ITT: 63.4% vs 71.1%: P = .183 and PP: 60.8% vs 71.1%; P = .100). Secondary patency rates were not significantly different in the ITT analysis (86.5% vs 95.1%; P = .054), but in the PP analysis, there was a significant difference in favor of the DES group (SECS, 85.6% vs DES, 95.1%; P = .038). There was no significant difference in freedom from TLR between groups (79.6% vs 77.0%; P = .481). No major amputations were performed in the SECS group, and two were performed in the DES group (1.8%). Survival rate was 98.2% in the SECS group, and 91.3% in the DES group after 1-year follow-up (P = .106). Based on diagnosis (intermittent claudication vs chronic limb-threatening ischemia) no differences between patients with intermittent claudication and chronic limb-threatening ischemia were observed in primary patency, secondary patency and freedom from TLR. CONCLUSIONS: Treatment of complex femoropopliteal arterial disease with the heparin-bonded Viabahn endoprosthesis and the Zilver PTX drug-eluting stent are related to similar primary and secondary patency, and TLR rates at 1 year, except for secondary patency in the PP analysis. This study further supports the endovascular treatment of long complex lesions in the femoropopliteal artery.

Designer Receptor Exclusively Activated by Designer Drug (DREADD)-Mediated Activation of the Periaqueductal Gray Restores Nociceptive Descending Inhibition After Traumatic Brain Injury in Rats.

Traumatic brain injury (TBI) patients frequently experience chronic pain that can enhance their suffering and significantly impair rehabilitative efforts. Clinical studies suggest that damage to the periaqueductal gray matter (PAG) following TBI, a principal center involved in endogenous pain control, may underlie the development of chronic pain. We hypothesized that TBI would diminish the usual pain control functions of the PAG, but that directly stimulating this center using a chemogenetic approach would restore descending pain modulation. We used a well-characterized lateral fluid percussion model (1.3 ± 0.1 atm) of TBI in male rats (n = 271) and measured hindpaw mechanical nociceptive withdrawal thresholds using von Frey filaments. To investigate the role of the PAG in pain both before and after TBI, we activated the neurons of the PAG using a Designer Receptor Exclusively Activated by Designer Drug (DREADD) viral construct. Immunohistochemical analysis of brain tissue was used to assess the location and confirm the appropriate expression of the viral constructs in the PAG. Activation of the PAG DREADD using clozapine N-oxide (CNO) caused hindpaw analgesia that could be blocked using opioid receptor antagonist, naloxone, in uninjured but not TBI rats. Due to the importance of descending serotonergic signaling in modulating nociception, we ablated spinal serotonin signaling using 5,7-DHT. This treatment strongly reduced CNO-mediated anti-nociceptive effects in TBI but not uninjured rats. To define the serotonergic receptor(s) required for the CNO-stimulated effects in TBI rats, we administered 5-HT7 (SB-269970) and 5-HT1A (WAY-100635) receptor antagonists but observed no effects. The selective 5-HT2A receptor antagonist ketanserin, however, blocked CNO's effects in the DREADD expressing TBI but not DREADD expressing sham TBI animals. Blockade of alpha-1 adrenergic receptors with prazosin also had no effect after TBI. Descending pain control originating in the PAG is mediated through opioid receptors in uninjured rats. TBI, however, fundamentally alters the descending nociceptive control circuitry such that serotonergic influences predominate, and those are mediated by the 5-HT2A receptor. These results provide further evidence that the PAG is a key target for anti-nociception after TBI.