Detection of dendritic cell subsets in the tumor microenvironment by multiplex immunohistochemistry.

Dendritic cells (DCs) are essential in antitumor immunity. In humans, three main DC subsets are defined: two types of conventional DCs (cDC1s and cDC2s) and plasmacytoid DCs (pDCs). To study DC subsets in the tumor microenvironment (TME), it is important to correctly identify them in tumor tissues. Tumor-derived DCs are often analyzed in cell suspensions in which spatial information about DCs which can be important to determine their function within the TME is lost. Therefore, we developed the first standardized and optimized multiplex immunohistochemistry panel, simultaneously detecting cDC1s, cDC2s, and pDCs within their tissue context. We report on this panel's development, validation, and quantitative analysis. A multiplex immunohistochemistry panel consisting of CD1c, CD303, X-C motif chemokine receptor 1, CD14, CD19, a tumor marker, and DAPI was established. The ImmuNet machine learning pipeline was trained for the detection of DC subsets. The performance of ImmuNet was compared with conventional cell phenotyping software. Ultimately, frequencies of DC subsets within several tumors were defined. In conclusion, this panel provides a method to study cDC1s, cDC2s, and pDCs in the spatial context of the TME, which supports unraveling their specific roles in antitumor immunity.

Standardised training for endoscopic mucosal resection of large non-pedunculated colorectal polyps to reduce recurrence (*STAR-LNPCP study): a multicentre cluster randomised trial.

OBJECTIVE: Endoscopic mucosal resection (EMR) is the preferred treatment for non-invasive large (≥20 mm) non-pedunculated colorectal polyps (LNPCPs) but is associated with an early recurrence rate of up to 30%. We evaluated whether standardised EMR training could reduce recurrence rates in Dutch community hospitals. DESIGN: In this multicentre cluster randomised trial, 59 endoscopists from 30 hospitals were randomly assigned to the intervention group (e-learning and 2-day training including hands-on session) or control group. From April 2019 to August 2021, all consecutive EMR-treated LNPCPs were included. Primary endpoint was recurrence rate after 6 months. RESULTS: A total of 1412 LNPCPs were included; 699 in the intervention group and 713 in the control group (median size 30 mm vs 30 mm, 45% vs 52% size, morphology, site and access (SMSA) score IV, 64% vs 64% proximal location). Recurrence rates were lower in the intervention group compared with controls (13% vs 25%, OR 0.43; 95% CI 0.23 to 0.78; p=0.005) with similar complication rates (8% vs 9%, OR 0.93; 95% CI 0.64 to 1.36; p=0.720). Recurrences were more often unifocal in the intervention group (92% vs 76%; p=0.006). In sensitivity analysis, the benefit of the intervention on recurrence rate was only observed in the 20-40 mm LNPCPs (5% vs 20% in 20-29 mm, p=0.001; 10% vs 21% in 30-39 mm, p=0.013) but less evident in ≥40 mm LNPCPs (24% vs 31%; p=0.151). In a post hoc analysis, the training effect was maintained in the study group, while in the control group the recurrence rate remained high. CONCLUSION: A compact standardised EMR training for LNPCPs significantly reduced recurrences in community hospitals. This strongly argues for a national dedicated training programme for endoscopists performing EMR of ≥20 mm LNPCPs. Interestingly, in sensitivity analysis, this benefit was limited for LNPCPs ≥40 mm. TRIAL REGISTRATION NUMBER: NTR7477.

Increased neuron density in the midbrain of a foveate bird, pigeon, results from profound change in tissue morphogenesis.

The increase of brain neuron number in relation with brain size is currently considered to be the major evolutionary path to high cognitive power in amniotes. However, how changes in neuron density did contribute to the evolution of the information-processing capacity of the brain remains unanswered. High neuron densities are seen as the main reason why the fovea located at the visual center of the retina is responsible for sharp vision in birds and primates. The emergence of foveal vision is considered as a breakthrough innovation in visual system evolution. We found that neuron densities in the largest visual center of the midbrain - i.e., the optic tectum - are two to four times higher in modern birds with one or two foveae compared to birds deprived of this specialty. Interspecies comparisons enabled us to identify elements of a hitherto unknown developmental process set up by foveate birds for increasing neuron density in the upper layers of their optic tectum. The late progenitor cells that generate these neurons proliferate in a ventricular zone that can expand only radially. In this particular context, the number of cells in ontogenetic columns increases, thereby setting the conditions for higher cell densities in the upper layers once neurons did migrate.

Proactive monitoring of drug-drug interactions between direct oral anticoagulants and small-molecule inhibitors in patients with non-small cell lung cancer.

BACKGROUND: Small-molecule inhibitors (SMIs) have revolutionised the treatment of non-small cell lung cancer (NSCLC). However, SMI-induced drug-drug interactions (DDIs) with frequently co-administered direct oral anticoagulants (DOACs), increase thromboembolic and bleeding risks. This study investigated and proactively managed the consequences of DOAC-SMI DDIs. METHODS: This prospective, observational study enrolled patients with NSCLC concomitantly using a DOAC and SMI. The primary outcome was the proportion of patients with DOAC plasma trough (Ctrough) and peak (Cpeak) concentrations outside expected ranges. Secondary outcomes included DOAC treatment modifications, incidence of bleeding and thromboembolic events and feasibility evaluation of pharmacokinetically guided DOAC dosing. RESULTS: Thirty-three patients were analysed. Thirty-nine percent (13/33) had DOAC Ctrough and/or Cpeak were outside the expected ranges in 39% (13/33). In 71% (5/7) of patients with DOAC concentrations quantified before and during concurrent SMI use, DOAC Ctrough and/or Cpeak increased or decreased >50% upon SMI initiation. In all patients in whom treatment modifications were deemed necessary, DOAC concentrations were adjusted to within the expected ranges. CONCLUSION: Proactive monitoring showed that a substantial proportion of patients had DOAC concentrations outside the expected ranges. DOAC concentrations were successfully normalised after treatment modifications. These results highlight the importance of proactive monitoring of DOAC-SMI DDIs to improve treatment in patients with NSCLC.

Prevalence of type II endoleak after elective endovascular aneurysm repair with polytetrafluoroethylene- or polyester-based endografts.

OBJECTIVE: Type II endoleak is the most frequent complication after endovascular abdominal aneurysm repair. Polytetrafluoroethylene and polyester (PE) are the two most commonly used graft materials in endovascular aneurysm repair (EVAR) devices. Biological properties of the material might influence the appearance and persistence of type II endoleak (T2EL). Therefore, the aim of this study was to evaluate potential differences in the prevalence of T2EL after EVAR between polytetrafluoroethylene (PTFE) and PE endografts in patients electively treated for an infrarenal abdominal aortic aneurysm. METHODS: A single-center, retrospective, observational study was conducted between January 2011 and January 2022. Preoperative, procedural, and follow-up data were derived from electronic health records. Imaging included computed tomography scans, and/or duplex ultrasound examination. The primary end point was the prevalence of T2EL diagnosed within 1 year after EVAR. Secondary end points included the prevalence of T2EL throughout follow-up, early (≤30 days) and late (>30 days) T2EL, the rate of T2EL disappearance during the follow-up period, the prevalence of type I and III endoleak, and T2EL-related reinterventions. RESULTS: Follow-up was available for 394 patients, 245 in the PE and 149 in the PTFE group. The prevalence of T2EL diagnosed within 1 year after endovascular repair was 11.8% in the PE group and 21.5% in the PTFE group (P = .010). There was no significant difference in early (≤30 days) and late (>30 days) T2EL between groups (P = .270 and P = .311). There was no difference in the freedom from endoleak type II reinterventions between groups (P = .877). CONCLUSIONS: The prevalence of T2EL after elective EVAR is significantly higher with the use of PTFE-based endografts compared with PE-based endografts. This difference is mostly based on T2EL diagnosed after 30 days of follow-up.

One-year follow-up after active aortic aneurysm sac treatment with shape memory polymer devices during endovascular aneurysm repair.

OBJECTIVE: To determine the safety and efficacy of treating abdominal aortic aneurysm (AAA) sacs with polyurethane shape memory polymer (SMP) devices during endovascular aneurysm repair (EVAR), using a technique to fully treat the target lumen after endograft placement (aortic flow volume minus the endograft volume). SMP devices self-expand in the sac to form a porous scaffold that supports thrombosis throughout its structure. METHODS: Two identical prospective, multicenter, single-arm studies were conducted in New Zealand and the Netherlands. The study population was adult candidates for elective EVAR of an infrarenal AAA (diameter of ≥55 mm in men and ≥50 mm in women). Key exclusion criteria were an inability to adequately seal a common iliac artery aneurysm, patent sac feeding vessels of >4 mm, and a target lumen volume of <20 mL or >135 mL. Target lumen volumes were estimated by subtracting endograft volumes from preprocedural imaging-based flow lumen volumes. SMP devices were delivered immediately after endograft deployment via a 6F sheath jailed in a bowed position in the sac. The primary efficacy end point was technical success, defined as filling the actual target lumen volume with fully expanded SMP at the completion of the procedure. Secondary efficacy outcome measures during follow-up were the change in sac volume and diameter, rate of type II endoleak and type I or III endoleaks, and the rate of open repair and related reinterventions, with data collection at 30 days, 6 months, and 1 year (to date). Baseline sac volumes and diameters for change in sac size analyses were determined from 30-day imaging studies. Baseline and follow-up volumes were normalized by subtraction of the endograft volume. RESULTS: Of 34 patients treated with SMP devices and followed per protocol, 33 patients were evaluable at 1 year. Preprocedural aneurysm volume was 181.4 mL (95% confidence interval [CI], 150.7-212.1 mL) and preprocedural aneurysm diameter was 60.8 mm (95% CI, 57.8-63.9 mm). The target lumen volume was 56.3 mL (95% CI, 46.9-65.8 mL). Technical success was 100% and the ratio of SMP fully expanded volume to estimated target lumen volume was 1.4 ± 0.3. Baseline normalized sac volume and diameter were 140.7 mL (95% CI, 126.6-154.9 mL) and 61.0 mm (95% CI, 59.7-62.3 mm). The adjusted mean percentage change in normalized volume at 1 year was -28.8% (95% CI, -35.3 to -22.3%; P < .001). The adjusted mean change in sac diameter at 1 year was -5.9 mm (95% CI, -7.5 to -4.4 mm; P < .001). At 1 year, 81.8% of patients (95% CI, 64.5%-93.0%) achieved a ≥10% decrease in normalized volume and 57.6% of patients (95% CI, 39.2%-74.5%) achieved a ≥5 mm decrease in diameter. No device- or study procedure-related major adverse events occurred through 1 year after the procedure. CONCLUSIONS: Treatment of AAA sacs with SMP devices during EVAR resulted in significant sac volume and diameter regression at 1 year with an acceptable safety profile in this prospective study.

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.

Clinical perspectives on serum tumor marker use in predicting prognosis and treatment response in advanced non-small cell lung cancer.

The optimal positioning and usage of serum tumor markers (STMs) in advanced non-small cell lung cancer (NSCLC) care is still unclear. This review aimed to provide an overview of the potential use and value of STMs in routine advanced NSCLC care for the prediction of prognosis and treatment response. Radiological imaging and clinical symptoms have shown not to capture a patient's entire disease status in daily clinical practice. Since STM measurements allow for a rapid, minimally invasive, and safe evaluation of the patient's tumor status in real time, STMs can be used as companion decision-making support tools before start and during treatment. To overcome the limited sensitivity and specificity associated with the use of STMs, tests should only be applied in specific subgroups of patients and different test characteristics should be defined per clinical context in order to answer different clinical questions. The same approach can similarly be relevant when developing clinical applications for other (circulating) biomarkers. Future research should focus on the approaches described in this review to achieve STM test implementation in advanced NSCLC care.

Pre-analytical stability of the CEA, CYFRA 21.1, NSE, CA125 and HE4 tumor markers.

BACKGROUND: For lung cancer, circulating tumor markers (TM) are available to guide clinical treatment decisions. To ensure adequate accuracy, pre-analytical instabilities need to be known and addressed in the pre-analytical laboratory protocols. OBJECTIVE: This study investigates the pre-analytical stability of CA125, CEA, CYFRA 21.1, HE4 and NSE for the following pre-analytical variables and procedures; i) whole blood stability, ii) serum freeze-thaw cycles, iii) electric vibration mixing and iv) serum storage at different temperatures. METHODS: Left-over patient samples were used and for every investigated variable six patient samples were used and analysed in duplicate. Acceptance criteria were based on analytical performance specifications based on biological variation and significant differences with baseline. RESULTS: Whole blood was stable for at least 6 hours for all TM except for NSE. Two freeze-thaw cycles were acceptable for all TM except CYFRA 21.1. Electric vibration mixing was allowed for all TM except for CYFRA 21.1. Serum stability at 4°C was 7 days for CEA, CA125, CYFRA 21.1 and HE4 and 4 hours for NSE. CONCLUSIONS: Critical pre-analytical processing step conditions were identified that, if not taken into account, will result in reporting of erroneous TM results.

Comparing modeling strategies combining changes in multiple serum tumor biomarkers for early prediction of immunotherapy non-response in non-small cell lung cancer.

BACKGROUND: Patients treated with immune checkpoint inhibitors (ICI) are at risk of adverse events (AEs) even though not all patients will benefit. Serum tumor markers (STMs) are known to reflect tumor activity and might therefore be useful to predict response, guide treatment decisions and thereby prevent AEs. OBJECTIVE: This study aims to compare a range of prediction methods to predict non-response using multiple sequentially measured STMs. METHODS: Nine prediction models were compared to predict treatment non-response at 6-months (n = 412) using bi-weekly CYFRA, CEA, CA-125, NSE, and SCC measurements determined in the first 6-weeks of therapy. All methods were applied to six different biomarker combinations including two to five STMs. Model performance was assessed based on sensitivity, while model training aimed at 95% specificity to ensure a low false-positive rate. RESULTS: In the validation cohort, boosting provided the highest sensitivity at a fixed specificity across most STM combinations (12.9% -59.4%). Boosting applied to CYFRA and CEA achieved the highest sensitivity on the validation data while maintaining a specificity >95%. CONCLUSIONS: Non-response in NSCLC patients treated with ICIs can be predicted with a specificity >95% by combining multiple sequentially measured STMs in a prediction model. Clinical use is subject to further external validation.

Blood platelet RNA profiles do not enable for nivolumab response prediction at baseline in patients with non-small cell lung cancer.

BACKGROUND: Anti-PD-(L)1 immunotherapy has emerged as a promising treatment approach for non-small cell lung cancer (NSCLC), though the response rates remain low. Pre-treatment response prediction may improve patient allocation for immunotherapy. Blood platelets act as active immune-like cells, thereby constraining T-cell activity, propagating cancer metastasis, and adjusting their spliced mRNA content. OBJECTIVE: We investigated whether platelet RNA profiles before start of nivolumab anti-PD1 immunotherapy may predict treatment responses. METHODS: We performed RNA-sequencing of platelet RNA samples isolated from stage III-IV NSCLC patients before treatment with nivolumab. Treatment response was scored by the RECIST-criteria. Data were analyzed using a predefined thromboSeq analysis including a particle-swarm-enhanced support vector machine (PSO/SVM) classification algorithm. RESULTS: We collected and processed a 286-samples cohort, separated into a training/evaluation and validation series and subjected those to training of the PSO/SVM-classification algorithm. We observed only low classification accuracy in the 107-samples validation series (area under the curve (AUC) training series: 0.73 (95% -CI: 0.63-0.84, n = 88 samples), AUC evaluation series: 0.64 (95% -CI: 0.51-0.76, n = 91 samples), AUC validation series: 0.58 (95% -CI: 0.45-0.70, n = 107 samples)), employing a five-RNAs biomarker panel. CONCLUSIONS: We concluded that platelet RNA may have minimally discriminative capacity for anti-PD1 nivolumab response prediction, with which the current methodology is insufficient for diagnostic application.

Target-controlled Infusion of Remimazolam in Healthy Volunteers Shows Some Acute Tolerance.

BACKGROUND: Remimazolam exhibits sedative properties by binding to γ-aminobutyric acid type A receptors. Remimazolam is administered as a bolus dose or continuous infusion, but has not been studied using target-controlled infusion (TCI). The study quantified the relationship between the remimazolam concentration, Modified Observer's Assessment of Alertness and Sedation (MOAAS) score, and bispectral index (BIS) using TCI. METHODS: The authors performed a three-period, crossover, dose-ranging clinical trial in 24 healthy volunteers using age and sex stratification. Data collected in the first period, where remimazolam was administered alone using a step-up and step-down TCI protocol, were used for this analysis. Remimazolam concentrations, MOAAS scores, and BIS values were collected at each step at steady state. Data were analyzed using nonlinear mixed-effects modeling methodology. RESULTS: The relationship between remimazolam, BIS, and MOAAS differed between step-up and step-down infusions at similar remimazolam target concentrations. Tolerance, driven by remimazolam or CNS7054, significantly improved overall model fit (P < 0.01) for both BIS and MOAAS models. After 30 min of repeated bolus dosing, mimicking the regimen in the label for procedural sedation, the BIS and probability of MOAAS 2/3 were predicted to be 54 (95% prediction interval, 44 to 67) and 2% (95% prediction interval, 0 to 32%) versus 58 (95% prediction interval, 48 to 70) and 8% (95% prediction interval, 0 to 36%) in a model without and with tolerance, respectively. After 60 min of continuous infusion, mimicking the regimen in the label for general anesthesia, the BIS and probability of MOAAS 0 were predicted to be 40 (95% prediction interval, 33 to 50) and 87% (95% prediction interval, 18 to 100%) versus 50 (95% prediction interval, 41 to 60) and 59% (95% prediction interval, 6 to 99%) in a model without and with tolerance, respectively. CONCLUSIONS: In this study, it was shown that remimazolam-induced sedation is prone to tolerance development, which is potentially mediated by the CNS7054 concentration. The clinical consequences are, however, limited in situations where remimazolam is titrated to effect.

Machine learning enables automated screening for systematic reviews and meta-analysis in urology.

PURPOSE: To investigate and implement semiautomated screening for meta-analyses (MA) in urology under consideration of class imbalance. METHODS: Machine learning algorithms were trained on data from three MA with detailed information of the screening process. Different methods to account for class imbalance (Sampling (up- and downsampling, weighting and cost-sensitive learning), thresholding) were implemented in different machine learning (ML) algorithms (Random Forest, Logistic Regression with Elastic Net Regularization, Support Vector Machines). Models were optimized for sensitivity. Besides metrics such as specificity, receiver operating curves, total missed studies, and work saved over sampling were calculated. RESULTS: During training, models trained after downsampling achieved the best results consistently among all algorithms. Computing time ranged between 251 and 5834 s. However, when evaluated on the final test data set, the weighting approach performed best. In addition, thresholding helped to improve results as compared to the standard of 0.5. However, due to heterogeneity of results no clear recommendation can be made for a universal sample size. Misses of relevant studies were 0 for the optimized models except for one review. CONCLUSION: It will be necessary to design a holistic methodology that implements the presented methods in a practical manner, but also takes into account other algorithms and the most sophisticated methods for text preprocessing. In addition, the different methods of a cost-sensitive learning approach can be the subject of further investigations.

Upside-Down Gore Excluder as an Endoprosthesis for Aortoiliac Aneurysm Exclusion: A Retrospective Multicenter Study.

OBJECTIVE: The upside-down configuration of a Gore Excluder contralateral leg endoprosthesis has been used to overcome diameter differences in the endovascular treatment of aortoiliac aneurysms. Our goal was not to describe the technique but to study the applicability and safety. MATERIAL AND METHODS: Patients were retrospectively enrolled. The indication and details of the procedure were at the discretion of the treating physicians. A case report form was completed including baseline characteristics, indication for treatment, procedural data, and outcomes during follow-up. RESULTS: A total of 31 subjects were enrolled with a range of indications, including 3 patients treated in the emergency setting (9.7%). In 64.5% (n=20), it was a primary intervention for a common iliac aneurysm (n=10), internal iliac aneurysm (n=4), or abdominal aortic aneurysm (n=6). In 11 subjects (35.5%), treatment was performed after previous aortoiliac interventions, including anastomotic iliac artery aneurysm (n=5), type III endoleak (n=3), and endograft thrombus (n=3). Median follow-up was 13 months (range=1-142 months). During follow-up, 2 patients required an upside-down contralateral leg-related secondary intervention, one for an occlusion and another for a type Ia endoleak. There was no type Ib or III endoleak, and no migration, kinking/stenosis, or conversion to open repair was observed. The aneurysm-related mortality was 3.3% (n=1). CONCLUSION: An upside-down contralateral leg is a valuable technique that can be used to achieve adequate aneurysm exclusion or resolve complications. It is associated with a limited number of complications. CLINICAL IMPACT: This article studies the use of an upside-down iliac endograft. We describe a wide range of indications in which this previously published technique has been applied. In elective and acute settings and as primary and revision intervention an upside-down iliac endograft was performed successfully. Furthermore, follow-up data is presented showing the effectiveness of the technique. Knowledge of this procedure is a valuable addition to the skillset of every interventionalist.

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.

Five-Year Outcomes of the SuperB Trial: A Multicenter Randomized Controlled Trial Comparing Heparin-Bonded Endograft to Surgical Femoropopliteal Bypass.

OBJECTIVE: This study aims to compare the 5-year outcomes of endoluminal bypass (EB) using heparin-bonded self-expanding covered stents versus bypass surgery for extensive femoropopliteal disease, including technical and clinical outcomes and health status. BACKGROUND: The surgical femoropopliteal bypass was the gold standard to treat peripheral arterial disease (PAD) for decades; however, endovascular treatment modalities are now recommended for most femoropopliteal lesions. One-year data of a randomized controlled trial comparing EB with surgical bypass (SB) have shown a faster recovery, less morbidity, and comparable patency rates between the two techniques. To date, long-term randomized controlled data regarding both techniques are lacking. METHODS: Five-year results of a multicenter randomized controlled trial comparing EB with SB in patients with femoropopliteal artery disease were evaluated based on intention-to-treat and per-protocol analyses. RESULTS: At 5-year follow-up, primary, primary-assisted, and secondary patency rates were 36.2%, 52.4%, and 68.1% for EB and 49.4%, 72.2%, and 77.8% for SB, respectively (p=0.608). Freedom from target lesion revascularization (fTLR) was 34.1% for EB and 57.6% for SB (p=0.365). In both groups, the ankle-brachial index, Rutherford classification, and walking distance significantly improved compared with baseline without differences between groups at follow-up. Freedom from major amputation rate was 92.6% in the EB group and 96.2% in the SB group (p=0.361). The 36-Item Short-Form Health Survey showed no significant differences between groups. CONCLUSION: Treatment of extensive femoropopliteal disease with self-expanding covered stents provides comparable clinical-related and health-related questionnaire outcomes when compared with SB through 5 years of follow-up. However, the EB is related to a higher number of reinterventions. CLINICAL IMPACT: This present study is the first to report five-year outcomes comparing an endoluminal (EB) using heparin-bonded self-expanding covered stents with surgical bypass (SB) for long and complex femoropopliteal disease. Although the advantages of treatment with EB are mostly seen in the early period after treatment, the outcomes support the use of EB for this indication and seems to be a valid and safe alternative for bypass surgery. Future trials comparing various endovascular strategies may provide further guidance for the development of an evidence-based treatment algorithm.

Long Term Outcomes of the Gore Excluder Low Permeability Endoprosthesis for the Treatment of Infrarenal Aortic Aneurysms.

OBJECTIVE: This study evaluated the long term outcomes of endovascular aneurysm repair using the Gore Excluder Low Permeability (LP) endoprosthesis across high volume Dutch hospitals. METHODS: A retrospective analysis was conducted of patients treated with the Excluder LP for infrarenal abdominal aortic aneurysm (AAA) in four hospitals between 2004 and 2017. Primary outcomes were overall survival, freedom from re-interventions (overall, inside and outside instructions for use, IFU), and AAA sac dynamics: growth (> 5 mm), stabilisation, and regression (< 5 mm). Secondary outcomes were technical success (device deployment), procedural parameters, and re-interventions. Follow up visits were extracted from patient files, with imaging assessed for complications and AAA diameter. RESULTS: Five hundred and fourteen patients were enrolled, with a median (IQR) follow up of 5.0 (2.9, 6.9) years. Survival rates were 94.0% at one year, 73.0% at five years, and 37.0% at 10 years, with freedom from re-interventions of 89.0%, 79.0%, and 71.0%, respectively. 37.9% were treated outside IFU, leading to significantly more re-interventions over 10 years compared with those treated inside IFU (36.0% vs. 25.0%, respectively; p = .044). The aneurysm sac regressed by 53.5% at one year, 65.8% at five years, and 77.8% at 10 years, and grew by 9.8%, 14.3%, and 22.2%, respectively. Patients with one year sac growth had significantly worse survival (p = .047). Seven patients (1.4%) had a ruptured aneurysm during follow up. Over 15 years, type 1a endoleak occurred in 5.3%, type 1b in 3.1%, type 3 in 1.9%, type 4 in 0.2%, and type 2 in 35.6% of patients. CONCLUSION: This multicentre study of real world endovascular aneurysm repair data using the Gore Excluder LP endoprosthesis demonstrated robust long term survival and re-intervention rates, despite 37.9% of patients being treated outside IFU, with type 4 endoleak being rare. Treatment outside IFU significantly increased re-intervention rates and one year sac growth was associated with statistically significantly worse survival.

Geometric Analysis of the Gore Excluder Conformable Endoprosthesis in the Infrarenal Aortic Neck: One Year Results of the EXCeL Registry.

OBJECTIVE: The Gore Excluder Conformable Endoprosthesis (CEXC) is designed to treat challenging infrarenal anatomy because of its active angulation control, repositionability, and enhanced conformability. This study evaluated 30 day and one year position and apposition of the CEXC in the infrarenal neck. METHODS: Patients treated with the CEXC between 2018 and 2022 with an available 30 day computed tomography angiogram (CTA) were selected from four hospitals in a prospective registry. Endograft apposition (shortest apposition length [SAL]) and position (shortest fabric distance [SFD]) were assessed on the 30 day and one year CTAs. Maximum infrarenal aortic curvature was compared between the pre- and post-operative CTAs to evaluate conformability of the CEXC. RESULTS: There were 87 patients with a 30 day CTA, and for 56 of these patients the one year CTA was available. Median (interquartile range [IQR]) pre-operative neck length was 22 mm (IQR 15, 32) and infrarenal angulation was 52° (IQR 31, 72). Median SAL was 21.2 mm (IQR 14.0, 29.3) at 30 days for all included patients. The SAL in 13 patients (15%) was < 10 mm at 30 days, and one patient had a SAL of 0 mm and a type Ia endoleak. There was no significant difference in SAL between patients within and outside instructions for use. The SAL significantly increased by 1.1 mm (IQR -2.3, 4.7; p = .042) at one year. The SAL decreased in seven patients (13%), increased in 13 patients (23%), and remained stable in 36 patients (64%). Median SFD was 2.0 mm (IQR 0.5, 3.6) at 30 days, which slightly increased by 0.3 mm (IQR -0.5, 1.8; p = .019) at one year. One patient showed migration (SFD increase ≥ 5 mm). Median endograft tilt was 15.8° (IQR 9.7, 21.4). Pre-operative maximum infrarenal curvature was 36 m-1 (IQR 26, 56) and did not significantly change thereafter. CONCLUSION: In most patients, the CEXC was implanted close to the renal arteries, and sufficient (≥ 10 mm) post-operative apposition was achieved at 30 days, which slightly increased at one year. Post-operative endograft tilt was relatively low, and aortic geometry remained unchanged after implantation of the CEXC, probably due to its high conformability.

The Effect of One Year Aneurysm Sac Dynamics on Five Year Mortality and Continued Aneurysm Sac Evolution.

OBJECTIVE: One year aneurysm sac dynamics after endovascular abdominal aortic aneurysm repair (EVAR) were independently associated with a greater all cause mortality risk in prior registry studies but were limited in completeness and granularity. This retrospective analysis aimed to study the impact of sac dynamics on survival within the Endurant Stent Graft Global Registry (ENGAGE) with five year follow up. METHODS: A total of 1 263 subjects were enrolled in the ENGAGE Registry between March 2009 and April 2011. One year aneurysm sac changes were calculated between the one month post-operative imaging scans and the scan closest to the time of one year follow up. Sac regression was defined as a sac decrease of ≥ 5 mm and sac expansion as aneurysm sac growth ≥ 5 mm. The primary outcome was the five year all cause mortality rate. Kaplan-Meier estimates for freedom from all cause death were calculated. Multivariable Cox regression was used to determine the association between sac dynamics and all cause death. RESULTS: At one year, 441 of the 949 study participants with appropriate imaging (46%) had abdominal aortic aneurysm sac regression, 462 (49%) remained stable, and 46 (4.8%) had sac expansion. For patients with sac regression, the five year all cause mortality rate was 20%, compared with 28% for stable sac (p = .007) and 37% for the sac expansion (p = .010) cohorts. After adjustment, the sac expansion and stable sac cohorts were associated with a greater all cause mortality rate (expansion: hazard ratio [HR] 1.8; 95% CI 1.1 - 3.2; p = .032; stable: HR 1.4; 95% CI 1.1 - 1.9; p = .019). CONCLUSION: In the ENGAGE Global Registry, the one year rate of sac regression was 46%, and one year sac regression was observed to be associated with greater five year survival, corroborating prior findings using data from vascular registries. Sac regression could become the new standard for success after EVAR.

Haze factor of silver nanowires in variable refractive index environment: experimental and simulation approaches.

While silver nanowires (Ag NWs) have been demonstrated as a highly efficient transparent conducting material, they suffer from strong light scattering, which is quantified by a large haze factor (HF) in the optical spectrum. Here we investigate the influence of the dielectric environment on the light scattering of Ag NWs by comparing experimental measurements and simulations. In air, two peaks on the HF spectra are observed experimentally at the wavelength ofλI= 350 nm andλII= 380 nm and are attributed by simulations to the influence of the Ag NWs pentagonal shape on the localized surface plasmon resonance. The relative intensity between the two peaks is found to be dependent on whether the Ag NWs are in contact with the glass substrate or not. The HF behaviour in the near IR region seems to be dominated by Rayleigh scattering following simulations results. Dielectric environments of Ag NWs with various refractive indexes were obtained experimentally by the conformal deposition of different metal oxide coatings using atomic layer deposition, including Al-doped zinc oxide, Al2O3and SiO2coatings. The HF is found to be correlated with the refractive index environment in terms of HF peaks position, intensity and broadening. This trend of HF peaks is supported by a theoretical model to understand the optical mechanism behind this phenomenon.