Neurocomputational Underpinnings of Expected Surprise.

Predictive coding accounts of brain functions profoundly influence current approaches to perceptual synthesis. However, a fundamental paradox has emerged, that may be very relevant for understanding hallucinations, psychosis, or cognitive inflexibility: in some situations, surprise or prediction error-related responses can decrease when predicted, and yet, they can increase when we know they are predictable. This paradox is resolved by recognizing that brain responses reflect precision-weighted prediction error. This presses us to disambiguate the contributions of precision and prediction error in electrophysiology. To meet this challenge for the first time, we appeal to a methodology that couples an original experimental paradigm with fine dynamic modeling. We examined brain responses in healthy human participants (N = 20; 10 female) to unexpected and expected surprising sounds, assuming that the latter yield a smaller prediction error but much more amplified by a larger precision weight. Importantly, addressing this modulation requires the modeling of trial-by-trial variations of brain responses, that we reconstructed within a fronto-temporal network by combining EEG and MEG. Our results reveal an adaptive learning of surprise with larger integration of past (relevant) information in the context of expected surprises. Within the auditory hierarchy, this adaptation was found tied down to specific connections and reveals in particular precision encoding through neuronal excitability. Strikingly, these fine processes are automated as sound sequences were unattended. These findings directly speak to applications in psychiatry, where specifically impaired precision weighting has been suggested to be at the heart of several conditions such as schizophrenia and autism.SIGNIFICANCE STATEMENT In perception as Bayesian inference and learning, context sensitivity expresses as the precision weighting of prediction errors. A subtle mechanism that is thought to lie at the heart of several psychiatric conditions. It is thus critical to identify its neurophysiological and computational underpinnings. We revisit the passive auditory oddball paradigm by manipulating sound predictability and use a twofold modeling approach to simultaneous EEG-MEG recordings: (1) trial-by-trial modeling of cortical responses reveals a context-sensitive perceptual learning process; (2) the dynamic causal modeling (DCM) of evoked responses uncovers the associated changes in synaptic efficacy. Predictability discloses a link between precision weighting and self-inhibition of superficial pyramidal (SP) cells, a result that paves the way to a fine description of healthy and pathologic perception.

Effects on Mortality and Major Bleeding of Radial Versus Femoral Artery Access for Coronary Angiography or Percutaneous Coronary Intervention: Meta-Analysis of Individual Patient Data From 7 Multicenter Randomized Clinical Trials.

BACKGROUND: In some randomized clinical trials, transradial access (TRA) compared with transfemoral access (TFA) was associated with lower mortality in patients with coronary artery disease undergoing invasive management. We analyzed the effects of TRA versus TFA across multicenter randomized clinical trials and whether these associations are modified by patient or procedural characteristics. METHODS: We performed an individual patient data meta-analysis of multicenter randomized clinical trials comparing TRA with TFA among patients undergoing coronary angiography with or without percutaneous coronary intervention. The primary outcome was all-cause mortality and the co-primary outcome was major bleeding at 30 days. The primary analysis was conducted by 1-stage mixed-effects models on the basis of the intention-to-treat cohort. The effect of access site on mortality and major bleeding was assessed further by multivariable analysis. The relationship among access site, bleeding, and mortality was investigated by natural effect model mediation analysis with multivariable adjustment. RESULTS: A total of 21 600 patients (10 775 TRA, 10 825 TFA) from 7 randomized clinical trials were included. The median age was 63.9 years, 31.9% were women, 95% presented with acute coronary syndrome, and 75.2% underwent percutaneous coronary intervention. All-cause mortality (1.6% versus 2.1%; hazard ratio, 0.77 [95% CI, 0.63-0.95]; P=0.012) and major bleeding (1.5% versus 2.7%; odds ratio, 0.55 [95% CI, 0.45-0.67]; P<0.001) were lower with TRA. Subgroup analyses for mortality showed consistent results, except for baseline hemoglobin level (Pinteraction=0.003), indicating that the benefit of TRA was substantial in patients with moderate or severe anemia, whereas it was not significant in patients with milder or no baseline anemia. After adjustment, TRA remained associated with 24% and 51% relative risk reduction of all-cause mortality and major bleeding, respectively. A mediation analysis showed that the benefit of TRA on mortality was only partially driven by major bleeding prevention and ancillary mechanisms are required to fully explain the causal association. CONCLUSIONS: TRA is associated with lower all-cause mortality and major bleeding at 30 days compared with TFA. The effect on mortality was driven by patients with anemia. The reduction in major bleeding only partially explains the mortality benefit. REGISTRATION: URL: https://www.crd.york.ac.uk/prospero; Unique identifier: CRD42018109664.

The potential underlying mechanisms during learning flights.

Hymenopterans, such as bees and wasps, have long fascinated researchers with their sinuous movements at novel locations. These movements, such as loops, arcs, or zigzags, serve to help insects learn their surroundings at important locations. They also allow the insects to explore and orient themselves in their environment. After they gained experience with their environment, the insects fly along optimized paths guided by several guidance strategies, such as path integration, local homing, and route-following, forming a navigational toolkit. Whereas the experienced insects combine these strategies efficiently, the naive insects need to learn about their surroundings and tune the navigational toolkit. We will see that the structure of the movements performed during the learning flights leverages the robustness of certain strategies within a given scale to tune other strategies which are more efficient at a larger scale. Thus, an insect can explore its environment incrementally without risking not finding back essential locations.

Radial and ulnar approach for carotid artery stenting with Roadsaver™ double layer micromesh stent: Early and long-term follow-up.

AIMS: We aimed to evaluate the feasibility and safety of carotid artery stenting (CAS) with a newly designed double-layer micromesh stent using wrist approach in patients with significant carotid disease. MATERIALS AND METHODS: Between January 2016 and December 2021, 105 patients undergoing CAS with Roadsaver™ stent were enrolled in a single center prospective study. Follow-up assessments included neurological exams, duplex ultrasound (DUS), and 12-lead ECG. The primary endpoint was the 30-day composite rate of stroke, death, and myocardial infarction. Secondary endpoints included procedure success, access site complications, device success, target lesion revascularization, and in-stent restenosis evaluated with DUS. Long-term outcomes up to 72 months of follow-up were assessed in all eligible patients. RESULTS: The study population was predominantly male (69.5%) with a median age of 68 ± 8 years. Patients were symptomatic in 80% of the cases, and 35% fulfilled the high-risk criteria for surgical endarterectomy. The right internal carotid artery was the target artery in 56 (53.4%), and the left in 49 (46.6%) of the cases. All procedures were successfully completed from the right wrist, with right radial access in 94 (89.5%) cases and ulnar artery access with previous radial artery occlusion in 11 (10.5%) cases. All patients were treated successfully with the study device. The primary endpoint was met with a 30-day major adverse event rate of 0.9% (1/105). Up to 72 months of follow-up (median 30 ± 20 months) there were no strokes, neurological deaths, or target lesion revascularization of the treated lesion. Doppler ultrasound examination revealed nonsignificant in-stent restenosis in two asymptomatic patients. There was no hand ischemia detected in any patient. CONCLUSION: Results from this study demonstrate the radial and ulnar access for CAS with double layer micromesh Roadsaver™ stent is safe and feasible and associated with favorable early and long-term follow-up.

Bumblebees perceive the spatial layout of their environment in relation to their body size and form to minimize inflight collisions.

Animals that move through complex habitats must frequently contend with obstacles in their path. Humans and other highly cognitive vertebrates avoid collisions by perceiving the relationship between the layout of their surroundings and the properties of their own body profile and action capacity. It is unknown whether insects, which have much smaller brains, possess such abilities. We used bumblebees, which vary widely in body size and regularly forage in dense vegetation, to investigate whether flying insects consider their own size when interacting with their surroundings. Bumblebees trained to fly in a tunnel were sporadically presented with an obstructing wall containing a gap that varied in width. Bees successfully flew through narrow gaps, even those that were much smaller than their wingspans, by first performing lateral scanning (side-to-side flights) to visually assess the aperture. Bees then reoriented their in-flight posture (i.e., yaw or heading angle) while passing through, minimizing their projected frontal width and mitigating collisions; in extreme cases, bees flew entirely sideways through the gap. Both the time that bees spent scanning during their approach and the extent to which they reoriented themselves to pass through the gap were determined not by the absolute size of the gap, but by the size of the gap relative to each bee's own wingspan. Our findings suggest that, similar to humans and other vertebrates, flying bumblebees perceive the affordance of their surroundings relative their body size and form to navigate safely through complex environments.

Efficacy and Safety of Low-Dose Colchicine after Myocardial Infarction.

BACKGROUND: Experimental and clinical evidence supports the role of inflammation in atherosclerosis and its complications. Colchicine is an orally administered, potent antiinflammatory medication that is indicated for the treatment of gout and pericarditis. METHODS: We performed a randomized, double-blind trial involving patients recruited within 30 days after a myocardial infarction. The patients were randomly assigned to receive either low-dose colchicine (0.5 mg once daily) or placebo. The primary efficacy end point was a composite of death from cardiovascular causes, resuscitated cardiac arrest, myocardial infarction, stroke, or urgent hospitalization for angina leading to coronary revascularization. The components of the primary end point and safety were also assessed. RESULTS: A total of 4745 patients were enrolled; 2366 patients were assigned to the colchicine group, and 2379 to the placebo group. Patients were followed for a median of 22.6 months. The primary end point occurred in 5.5% of the patients in the colchicine group, as compared with 7.1% of those in the placebo group (hazard ratio, 0.77; 95% confidence interval [CI], 0.61 to 0.96; P = 0.02). The hazard ratios were 0.84 (95% CI, 0.46 to 1.52) for death from cardiovascular causes, 0.83 (95% CI, 0.25 to 2.73) for resuscitated cardiac arrest, 0.91 (95% CI, 0.68 to 1.21) for myocardial infarction, 0.26 (95% CI, 0.10 to 0.70) for stroke, and 0.50 (95% CI, 0.31 to 0.81) for urgent hospitalization for angina leading to coronary revascularization. Diarrhea was reported in 9.7% of the patients in the colchicine group and in 8.9% of those in the placebo group (P = 0.35). Pneumonia was reported as a serious adverse event in 0.9% of the patients in the colchicine group and in 0.4% of those in the placebo group (P = 0.03). CONCLUSIONS: Among patients with a recent myocardial infarction, colchicine at a dose of 0.5 mg daily led to a significantly lower risk of ischemic cardiovascular events than placebo. (Funded by the Government of Quebec and others; COLCOT ClinicalTrials.gov number, NCT02551094.).

Low-Dose Methotrexate for the Prevention of Atherosclerotic Events.

BACKGROUND: Inflammation is causally related to atherothrombosis. Treatment with canakinumab, a monoclonal antibody that inhibits inflammation by neutralizing interleukin-1ß, resulted in a lower rate of cardiovascular events than placebo in a previous randomized trial. We sought to determine whether an alternative approach to inflammation inhibition with low-dose methotrexate might provide similar benefit. METHODS: We conducted a randomized, double-blind trial of low-dose methotrexate (at a target dose of 15 to 20 mg weekly) or matching placebo in 4786 patients with previous myocardial infarction or multivessel coronary disease who additionally had either type 2 diabetes or the metabolic syndrome. All participants received 1 mg of folate daily. The primary end point at the onset of the trial was a composite of nonfatal myocardial infarction, nonfatal stroke, or cardiovascular death. Near the conclusion of the trial, but before unblinding, hospitalization for unstable angina that led to urgent revascularization was added to the primary end point. RESULTS: The trial was stopped after a median follow-up of 2.3 years. Methotrexate did not result in lower interleukin-1ß, interleukin-6, or C-reactive protein levels than placebo. The final primary end point occurred in 201 patients in the methotrexate group and in 207 in the placebo group (incidence rate, 4.13 vs. 4.31 per 100 person-years; hazard ratio, 0.96; 95% confidence interval [CI], 0.79 to 1.16). The original primary end point occurred in 170 patients in the methotrexate group and in 167 in the placebo group (incidence rate, 3.46 vs. 3.43 per 100 person-years; hazard ratio, 1.01; 95% CI, 0.82 to 1.25). Methotrexate was associated with elevations in liver-enzyme levels, reductions in leukocyte counts and hematocrit levels, and a higher incidence of non-basal-cell skin cancers than placebo. CONCLUSIONS: Among patients with stable atherosclerosis, low-dose methotrexate did not reduce levels of interleukin-1ß, interleukin-6, or C-reactive protein and did not result in fewer cardiovascular events than placebo. (Funded by the National Heart, Lung, and Blood Institute; CIRT ClinicalTrials.gov number, NCT01594333.).

Bumblebees display characteristics of active vision during robust obstacle avoidance flight.

Insects are remarkable flyers and capable of navigating through highly cluttered environments. We tracked the head and thorax of bumblebees freely flying in a tunnel containing vertically oriented obstacles to uncover the sensorimotor strategies used for obstacle detection and collision avoidance. Bumblebees presented all the characteristics of active vision during flight by stabilizing their head relative to the external environment and maintained close alignment between their gaze and flightpath. Head stabilization increased motion contrast of nearby features against the background to enable obstacle detection. As bees approached obstacles, they appeared to modulate avoidance responses based on the relative retinal expansion velocity (RREV) of obstacles and their maximum evasion acceleration was linearly related to RREVmax. Finally, bees prevented collisions through rapid roll manoeuvres implemented by their thorax. Overall, the combination of visuo-motor strategies of bumblebees highlights elegant solutions developed by insects for visually guided flight through cluttered environments.

TRIACCESS Study: Randomized Comparison Between Radial, Femoral, and Pedal Access for Percutaneous Femoro-popliteal Artery Angioplasty.

BACKGROUND: The aim of this randomized study was to compare the success and complication rates of different access sites for the treatment of superficial artery stenosis. METHODS AND RESULTS: A total of 180 consecutive patients were randomized in a prospective study to treat symptomatic superficial femoral artery stenosis via radial (RA), femoral (FA), or pedal artery (PA) access. Technical success was achieved in 96.7%, 100%, and 100% of the patients in the RA, FA, and PA groups, respectively (p=0.33). Secondary access sites were used in 30%, 3.3%, and 30% of the patients in the RA, FA, and PA access groups, respectively (p=0.0002). Recanalization for chronic total occlusion was performed in 34/36 (94.4%), 30/30 (100%), and 46/46 (100%) patients in the RA, FA, and PA groups, respectively (p=0.17). The X-ray dose was significantly lower in the PA group than that in the RA and FA access groups (63.1 vs 162 vs 153 Dyn, p=0.0004). The cumulative rates of access site complications in the RA, FA, and PA groups were 3.3% (0% major and 3.3% minor), 16.7% (3.3% major and 13.3% minor), and 3.3% (3.3% major and 0% minor) (p=0.0085), respectively. The cumulative incidence of MACEs at 6 months in the RA, FA, and PA groups was 5%, 6.7%, and 1.7%, respectively. The cumulative incidence of MALEs at 6 months in the RA, FA, and PA groups was 20%, 16.7%, and 9.2%, respectively (p=0.54). CONCLUSION: Femoral artery intervention can be safely and effectively performed using radial, femoral, and pedal access, but radial and pedal access is associated with a lower access site complication rate and hospitalization. Pedal access is associated with a lower X-ray dose than that with radial and femoral access.

Empirical Bayes evaluation of fused EEG-MEG source reconstruction: Application to auditory mismatch evoked responses.

We here turn the general and theoretical question of the complementarity of EEG and MEG for source reconstruction, into a practical empirical one. Precisely, we address the challenge of evaluating multimodal data fusion on real data. For this purpose, we build on the flexibility of Parametric Empirical Bayes, namely for EEG-MEG data fusion, group level inference and formal hypothesis testing. The proposed approach follows a two-step procedure by first using unimodal or multimodal inference to derive a cortical solution at the group level; and second by using this solution as a prior model for single subject level inference based on either unimodal or multimodal data. Interestingly, for inference based on the same data (EEG, MEG or both), one can then formally compare, as alternative hypotheses, the relative plausibility of the two unimodal and the multimodal group priors. Using auditory data, we show that this approach enables to draw important conclusions, namely on (i) the superiority of multimodal inference, (ii) the greater spatial sensitivity of MEG compared to EEG, (iii) the ability of EEG data alone to source reconstruct temporal lobe activity, (iv) the usefulness of EEG to improve MEG based source reconstruction. Importantly, we largely reproduce those findings over two different experimental conditions. We here focused on Mismatch Negativity (MMN) responses for which generators have been extensively investigated with little homogeneity in the reported results. Our multimodal inference at the group level revealed spatio-temporal activity within the supratemporal plane with a precision which, to our knowledge, has never been achieved before with non-invasive recordings.

Finding the optimal access for proximal upper limb artery (PULA) interventions: Lessons learned from the PULA multicenter registry.

OBJECTIVE: The multicenter proximal upper limb artery (PULA) Registry was created to study the optimal puncture sites for the interventions involving the subclavian, axillary, and innominate arteries. BACKGROUND: Little is known about the optimal vascular access for PULA interventions, despite the well-known technical complexity of these procedures. METHODS: We performed the retrospective analysis of consecutive patients treated for symptomatic steno-occlusive disease of the proximal upper limb arteries between January 2015 and December 2019 in three high-volume centers. Acute thrombotic occlusions were excluded from the study. RESULTS: Two hundred and seventy-two patients were treated for significant stenosis and 108 for total occlusion. The baseline patient's characteristics were similar, except for the higher median age of the stenotic patients: 68.5 years (31.1; 90.0) versus 64 years (38.0; 86.0) p = 0.0015. Successful revascularization rate was higher in the stenotic group 93.75% (255/272) versus 86.11% (93/108) p = 0.0230, while the procedure length 27 min (8; 133) versus 46 min (7; 140) p = 0.0001 and fluoroscopy times 439 s (92; 2993) versus 864 s (86; 4176) p = 0.0001 were higher in the occlusion group. The main adverse event rate was similarly low. Dual access was used more often to treat occlusions (60.19% (65/108) vs. 11.40% (31/272) p = 0.0001) without significantly increasing the complication rate. The safest access was ultrasound-guided distal radial artery puncture, significantly better than conventional radial access with 0% (0/31) versus 13.6% (18/131) p = 0.0253 complication. CONCLUSIONS: The percutaneous revascularization of proximal upper limb arteries is a safe and effective. Dual access can be applied to increase treatment efficacy, without significantly compromising safety.

Visual and movement memories steer foraging bumblebees along habitual routes.

One persistent question in animal navigation is how animals follow habitual routes between their home and a food source. Our current understanding of insect navigation suggests an interplay between visual memories, collision avoidance and path integration, the continuous integration of distance and direction travelled. However, these behavioural modules have to be continuously updated with instantaneous visual information. In order to alleviate this need, the insect could learn and replicate habitual movements ('movement memories') around objects (e.g. a bent trajectory around an object) to reach its destination. We investigated whether bumblebees, Bombus terrestris, learn and use movement memories en route to their home. Using a novel experimental paradigm, we habituated bumblebees to establish a habitual route in a flight tunnel containing 'invisible' obstacles. We then confronted them with conflicting cues leading to different choice directions depending on whether they rely on movement or visual memories. The results suggest that they use movement memories to navigate, but also rely on visual memories to solve conflicting situations. We investigated whether the observed behaviour was due to other guidance systems, such as path integration or optic flow-based flight control, and found that neither of these systems was sufficient to explain the behaviour.

Visually guided homing of bumblebees in ambiguous situations: A behavioural and modelling study.

Returning home is a crucial task accomplished daily by many animals, including humans. Because of their tiny brains, insects, like bees or ants, are good study models for efficient navigation strategies. Bees and ants are known to rely mainly on learned visual information about the nest surroundings to pinpoint their barely visible nest-entrance. During the return, when the actual sight of the insect matches the learned information, the insect is easily guided home. Occasionally, modifications to the visual environment may take place while the insect is on a foraging trip. Here, we addressed the ecologically relevant question of how bumblebees' homing is affected by such a situation. In an artificial setting, we habituated bees to be guided to their nest by two constellations of visual cues. After habituation, these cues were displaced during foraging trips into a conflict situation. We recorded bumblebees' return flights in such circumstances and investigated where they search for their nest entrance following the degree of displacement between the two visually relevant cues. Bumblebees mostly searched at the fictive nest location as indicated by either cue constellation, but never at a compromise location between them. We compared these experimental results to the predictions of different types of homing models. We found that models guiding an agent by a single holistic view of the nest surroundings could not account for the bumblebees' search behaviour in cue-conflict situations. Instead, homing models relying on multiple views were sufficient. We could further show that homing models required fewer views and got more robust to height changes if optic flow-based spatial information was encoded and learned, rather than just brightness information.

Distal Radial Artery Access for Superficial Femoral Artery Interventions.

PURPOSE: To compare the acute success and complication rates of distal radial (DR) vs proximal radial (PR) artery access for superficial femoral artery (SFA) interventions. MATERIALS AND METHODS: Between 2016 and 2019, 195 consecutive patients with symptomatic SFA stenosis were treated via DR (n=38) or PR (n=157) access using a sheathless guide. Secondary access was achieved through the pedal artery when necessary. The main outcomes were technical success, major adverse events (MAEs), and access site complications. Secondary outcomes were treatment success, fluoroscopy time, radiation dose, procedure time, and crossover rate to another puncture site. RESULTS: Overall technical success was achieved in 188 patients (96.4%): 37 of 38 patients (97.3%) in the DR group and 151 of 157 patients (96.2%) in the PR group (p=0.9). Dual (transradial and transpedal) access was used in 14 patients (36.8%) in the DR group and 28 patients (18.9%) in the PR group (p<0.01). Chronic total occlusions were recanalized in 25 of 26 DR patients (96.1%) and in 79 of 81 PR patients (92.6%) (p=0.57). The crossover rate to femoral access was 0% in the DR group vs 3.2% in the PR group (p=0.59). Stents were implanted in the SFA in 15 DR patients (39.4%) and in 39 patients (24.8%) in the PR group (p=0.1). The contrast volume, fluoroscopy time, radiation dose, and procedure time were not statistically different between the DR and PR groups, nor were the rates of access site complications (2.6% and 7.0%, respectively). The cumulative incidences of MAE at 6 months in the DR and PR groups were 15.7% vs 14.6%, respectively (p=0.8). CONCLUSION: SFA interventions can be safely and effectively performed using PR or DR access with acceptable morbidity and a high technical success rate. DR access is associated with few access site complications.

What's in Your Gamma? Activation of the Ventral Fronto-Parietal Attentional Network in Response to Distracting Sounds.

Auditory attention operates through top-down (TD) and bottom-up (BU) mechanisms that are supported by dorsal and ventral brain networks, respectively, with the main overlap in the lateral prefrontal cortex (lPFC). A good TD/BU balance is essential to be both task-efficient and aware of our environment, yet it is rarely investigated. Oscillatory activity is a novel method to probe the attentional dynamics with evidence that gamma activity (>30 Hz) could signal BU processing and thus would be a good candidate to support the activation of the ventral BU attention network. Magnetoencephalography data were collected from 21 young adults performing the competitive attention task, which enables simultaneous investigation of BU and TD attentional mechanisms. Distracting sounds elicited an increase in gamma activity in regions of the BU ventral network. TD attention modulated these gamma responses in regions of the inhibitory cognitive control system: the medial prefrontal and anterior cingulate cortices. Finally, distracting-sound-induced gamma activity was synchronous between the auditory cortices and several distant brain regions, notably the lPFC. We provide novel insight into the role of gamma activity 1) in supporting the activation of the ventral BU attention network and 2) in subtending the TD/BU attention balance in the PFC.

Time-to-treatment initiation of colchicine and cardiovascular outcomes after myocardial infarction in the Colchicine Cardiovascular Outcomes Trial (COLCOT).

AIMS: The COLchicine Cardiovascular Outcomes Trial (COLCOT) demonstrated the benefits of targeting inflammation after myocardial infarction (MI). We aimed to determine whether time-to-treatment initiation (TTI) influences the beneficial impact of colchicine. METHODS AND RESULTS: In COLCOT, patients were randomly assigned to receive colchicine or placebo within 30 days post-MI. Time-to-treatment initiation was defined as the length of time between the index MI and the initiation of study medication. The primary efficacy endpoint was a composite of cardiovascular death, resuscitated cardiac arrest, MI, stroke, or urgent hospitalization for angina requiring coronary revascularization. The relationship between endpoints and various TTI (<3, 4-7 and >8 days) was examined using multivariable Cox regression models. Amongst the 4661 patients included in this analysis, there were 1193, 720, and 2748 patients, respectively, in the three TTI strata. After a median follow-up of 22.7 months, there was a significant reduction in the incidence of the primary endpoint for patients in whom colchicine was initiated < Day 3 compared with placebo [hazard ratios (HR) = 0.52, 95% confidence intervals (CI) 0.32-0.84], in contrast to patients in whom colchicine was initiated between Days 4 and 7 (HR = 0.96, 95% CI 0.53-1.75) or > Day 8 (HR = 0.82, 95% CI 0.61-1.11). The beneficial effects of early initiation of colchicine were also demonstrated for urgent hospitalization for angina requiring revascularization (HR = 0.35), all coronary revascularization (HR = 0.63), and the composite of cardiovascular death, resuscitated cardiac arrest, MI, or stroke (HR = 0.55, all P < 0.05). CONCLUSION: Patients benefit from early, in-hospital initiation of colchicine after MI. TRIAL REGISTRATION: COLCOT ClinicalTrials.gov number, NCT02551094.

A novel fiber-optic based 0.014″ pressure wire: Designs of the OptoWire™, development phases, and the O2 first-in-man results.

OBJECTIVES: To review the technical limitations of available pressure-wires, present the design evolution of a nitinol fiber-optic pressure wire and to summarize the First-in-Man (FIM) O2 pilot study results. BACKGROUND: Despite increasing use of physiology assessment of coronary lesions, several technical limitations persist. We present technical details, design evolution and early clinical results with a novel 0.014" nitinol fiber-optic based pressure-wire. METHODS AND RESULTS: The 0.014' OptoWire™ (Opsens Medical, Quebec, Canada) was designed to combine improved handling properties compared to standard pressure-wires and to offer extremely reliable pressure recording and transmission due to fiber-optic properties compared to piezo-electric sensors and electrical wires. In vitro assessment showed that OptoWire™ steerability, pushability and torquability properties were closer to regular PCI wires than standard electrical pressure wires. In the First-in-Man O2 study, 60 patients were recruited at 2 centers in Canada. A total of 103 lesions were assessed with the OptoWire™ and OptoMonitor™, 75 lesions at baseline and 28 lesions post-PCI (without disconnection). In all crossed lesions (n = 100, 97%), mean Pd/Pa and FFR could be adequately measured. In 11 cases assessed successively with OptoWire™ and Aegis™ (Abbott Vascular, USA) bland-Altman analysis showed a mean difference of 0.002 ± 0.052 mmHg (p = .91) for Pd/Pa and 0.01 ± 0.06 for FFR calculation (p = .45). There was no device-related complication. Upon these initial results, several design changes aimed to improve overall performance including torquability, stiffness, resistance to kink and pressure drift were completed. CONCLUSION: The novel 0.014" fiber-optic OptoWire™ provides superior wire handling with reduced risk of pressure drift allowing reliable pre- and post-PCI physiology assessment.

Direct transpedal pressure measurement during transpedal below-the-knee interventions in critical limb ischemia.

AIM: The aim of this study was to assess the feasibility of the distal pressure measurement during transpedal below-the-knee interventions in chronic limb-threatening ischemia (CLTI) and to assess the hemodynamic response after percutaneous transluminal angioplasty. METHODS: The clinical and angiographic data of 137 consecutive patients treated via transpedal access in CLTI (Rutherford 4-6) were evaluated. Distal pedal pressure (PP) at the end of the pedal sheath was measured and the pedal-to-aortic pressure index (PAPI) was also calculated before and after the intervention. RESULTS: Good angiographic results was achieved in 131 patients (95.6%) in the femoro-popliteal and at least in one below-the-knee artery. Significant differences were found in PP and PAPI between before- and after-intervention values (103.2 ± 41.6 mmHg vs. 138.2 ± 37.8 mmHg and 0.74 ± 0.29 vs. 1.03 ± 0.34), respectively. Post-procedural PP and PAPI were significantly higher in patients who underwent good and borderline/unsuccessful intervention 141.7 [135.8-147.6] versus 82.6 [33.8-131.5] mmHg and 1.05 [1-1.1] versus 0.53 [0.2-0.8], respectively. PP's are significantly different in various Rutherford classification groups. Among the studied parameters, postprocedural PAPI was found to have the best discriminatory power to predict 3-month amputation (c-statistic: 0.749, 95% CI: 0.546-0.952, p = .016, sensitivity: 57.1%, specificity: 92.3% using the cut-off criterion ≤0.58). Major adverse event was detected in 17 patients at 3 months follow up (12.4%), including 7 major amputations (5.1%). CONCLUSION: Transpedal pressure and pedal-to-aortic pressure index significantly increased during transpedal below-the-knee angioplasty and final pressure and index correlates significantly with limb salvage.

A Randomized Trial Comparing Short versus Prolonged Hemostasis with Rescue Recanalization by Ipsilateral Ulnar Artery Compression: Impact on Radial Artery Occlusion-The RESCUE-RAO Trial.

BACKGROUND: Despite the enormous benefits of radial access, this route is associated with a risk of radial artery occlusion (RAO). OBJECTIVE: We compared the incidence of RAO in patients undergoing transradial coronary angiography and intervention after short versus prolonged hemostasis protocol. Also we assessed the efficacy of rescue 1-hour ipsilateral ulnar artery compression if RAO was observed after hemostasis. Material and Methods. Patients referred for elective transradial coronary procedures were eligible. After 6 F radial sheath removal, patients were randomized to short (3 hours) (n = 495) or prolonged (8 hours) (n = 503) hemostasis and a simple bandage was placed over the puncture site. After hemostasis was completed, oximetry plethysmography was used to assess the patency of the radial artery. RESULTS: One thousand patients were randomized. Baseline characteristics were similar between both groups with average age 61.4 ± 9.4 years (71% male) and PCI performed on half of the patients. The RAO rate immediately after hemostasis was 3.2% in the short hemostasis group and 10.1% in the prolonged group (p < 0.001). Rescue recanalization was successful only in the short group in 56.2% (11/19); at hospital discharge, RAO rates were 1.4% in the short group and 10.1% in the prolonged group (p < 0.001). CONCLUSION: Shorter hemostasis was associated with significantly less RAO compared to prolonged hemostasis. Rescue radial artery recanalization was effective in > 50%, but only in the short hemostasis group.

Effect of e-Cigarettes Plus Counseling vs Counseling Alone on Smoking Cessation: A Randomized Clinical Trial.

Importance: Electronic cigarettes (e-cigarettes) for smoking cessation remain controversial. Objective: To evaluate e-cigarettes with individual counseling for smoking cessation. Design, Setting, and Participants: A randomized clinical trial enrolled adults motivated to quit smoking from November 2016 to September 2019 at 17 Canadian sites (801 individuals screened; 274 ineligible and 151 declined). Manufacturing delays resulted in early termination (376/486 participants, 77% of target). Outcomes through 24 weeks (March 2020) are reported. Interventions: Randomization to nicotine e-cigarettes (n = 128), nonnicotine e-cigarettes (n = 127), or no e-cigarettes (n = 121) for 12 weeks. All groups received individual counseling. Main Outcomes and Measures: The primary end point was point prevalence abstinence (7-day recall, biochemically validated using expired carbon monoxide) at 12 weeks, changed from 52 weeks following early termination. Participants missing data were assumed to be smoking. The 7 secondary end points, examined at multiple follow-ups, were point prevalence abstinence at other follow-ups, continuous abstinence, daily cigarette consumption change, serious adverse events, adverse events, dropouts due to adverse effects, and treatment adherence. Results: Among 376 randomized participants (mean age, 52 years; 178 women [47%]), 299 (80%) and 278 (74%) self-reported smoking status at 12 and 24 weeks, respectively. Point prevalence abstinence was significantly greater for nicotine e-cigarettes plus counseling vs counseling alone at 12 weeks (21.9% vs 9.1%; risk difference [RD], 12.8 [95% CI, 4.0 to 21.6]) but not 24 weeks (17.2% vs 9.9%; RD, 7.3 [95% CI, -1.2 to 15.7]). Point prevalence abstinence for nonnicotine e-cigarettes plus counseling was not significantly different from counseling alone at 12 weeks (17.3% vs 9.1%; RD, 8.2 [95% CI, -0.1 to 16.6]), but was significantly greater at 24 weeks (20.5% vs 9.9%; RD, 10.6 [95% CI, 1.8 to 19.4]). Adverse events were common (nicotine e-cigarette with counseling: 120 [94%]; nonnicotine e-cigarette with counseling: 118 [93%]; counseling only: 88 [73%]), with the most common being cough (64%) and dry mouth (53%). Conclusions and Relevance: Among adults motivated to quit smoking, nicotine e-cigarettes plus counseling vs counseling alone significantly increased point prevalence abstinence at 12 weeks. However, the difference was no longer significant at 24 weeks, and trial interpretation is limited by early termination and inconsistent findings for nicotine and nonnicotine e-cigarettes, suggesting further research is needed. Trial Registration: ClinicalTrials.gov Identifier: NCT02417467.