Infrainguinal vein graft stenosis: Cutting balloon angioplasty as the first-line treatment of choice

ObjectiveThe optimal treatment for hemodynamically significant infrainguinal vein bypass graft stenosis is not known. This study compares three options as first choice for the revision of failing infrainguinal vein grafts: cutting balloon angioplasty (CBA), standard percutaneous transluminal balloon angioplasty (PTA), and open surgical revision (OS).MethodsInfrainguinal vein bypass graft lesions treated in a single institution during a 12-year period were evaluated. Of these, 161 lesions in 124 infrainguinal bypasses (101 patients) were treated with OS (n = 42), PTA (n = 57), or CBA (n = 62). The initial indication for the bypass in these patients was limb salvage in 73% and claudication in 27%. The primary outcome of interest was the development of vein graft occlusion or significant stenosis (≥70%) as detected by surveillance duplex ultrasound scanning or arteriography some time after repair.ResultsThe stenosis-free patency rates at 48 months for OS, CBA, and PTA were 74%, 62%, and 34%, respectively. PTA was associated with an increased risk of treatment failure compared with both OS (hazard ratio [HR], 3.9; P < .0001) and CBA (HR, 3.1; P < .0001). There was no significant difference between OS and CBA (HR, 1.3 for CBA vs OS, P = .6). Pseudoaneurysms developed in two CBA patients. One ruptured and required interposition graft, and one was monitored.ConclusionCutting balloon angioplasty is a reasonable, initial treatment for infrainguinal vein graft stenosis in most patients. It is a safe, minimally invasive, outpatient procedure with patency rates that are comparable to OS and superior to PTA

Effect of ethnicity on access and device complications during endovascular aneurysm repair

AbstractIntroductionThere are no published reports on the association between ethnicity and outcome after aortoiliac stent grafting to treat aneurismal disease. Because Hawaii is a state with an ethnically diverse population, we conducted a retrospective study to examine this potential association. We hypothesized that individuals of Asian ancestry may have higher complication rates after endovascular repair compared with non-Asians.MethodsAll endovascular devices placed to treat aneurysm disease from 1996 to 2003 were evaluated in two institutions. The association between ethnicity and access-related and device-related complications, both periprocedural and delayed, was examined with logistic regression analysis.ResultsNinety-two aortoiliac endografts were placed during the study period, including 87 in patients with abdominal aortic aneurysms with or without iliac aneurysm disease, and five patients with isolated iliac artery aneurysms. Forty-four percent of patients were categorized as Asian, 39% as white, 16% as Pacific Islander, and 1% as African American. Access-related and device-related complications (ADRCs) occurred in 11 of 92 (12%) of these patients. The following parameters were significantly associated with ADRCs: Asian ethnicity (P =.015), age greater than 80 years (P = .02), and external iliac diameter smaller than 7.5 mm (P =.01). Asian patients were more likely to have experienced ADRCs than were non-Asian patients (odds ratio, 7.3; 95% confidence interval, 1.5-35.8; P = .015). Asians also had smaller external iliac artery diameters (P = .0003) and more tortuous iliac arteries (P = .03) compared with non-Asians. After adjusting for iliac artery diameter and tortuosity, the association between Asian ethnicity and ARDCs became nonsignificant (P = .074), which suggests that the association between race and complications may be at least in part due to small and tortuous iliac arteries. There was no association between age, gender, or ethnicity and postoperative detection of endoleak.ConclusionOur data indicate that individuals of Asian ancestry are far more likely to experience adverse access-related and device-related complications after aortoiliac stent grafting than are non-Asians. We found that this association is at least partly attributable to the smaller and more tortuous iliac arteries in persons of Asian ancestry

Thrombin-induced events in non-platelet cells are mediated by the unique proteolytic mechanism established for the cloned platelet thrombin receptor.

We recently isolated a cDNA clone encoding a functional platelet thrombin receptor that defined a unique mechanism of receptor activation. Thrombin cleaves its receptor's extracellular amino terminal extension, unmasking a new amino terminus that functions as a tethered peptide ligand and activates the receptor. A novel peptide mimicking this new amino terminus was a full agonist for platelet secretion and aggregation, suggesting that this unusual mechanism accounts for platelet activation by thrombin. Does this mechanism also mediate thrombin's assorted actions on non-platelet cells? We now report that the novel thrombin receptor agonist peptide reproduces thrombin-induced events (specifically, phosphoinositide hydrolysis and mitogenesis) in CCL-39 hamster lung fibroblasts, a naturally thrombin-responsive cell line. Moreover, these thrombin-induced events could be recapitulated in CV-1 cells, normally poorly responsive to thrombin, after transfection with human platelet thrombin receptor cDNA. Our data show that important thrombin-induced cellular events are mediated by the same unusual mechanism of receptor activation in both platelets and fibroblasts, very likely via the same or very similar receptors

Indicators, security and sovereignty during COVID-19 in the global south

This paper considers the spread of COVID-19 as a telling moment or épreuve in contests over governance in global south states. Two distinct governance modes are engaged in this crisis: 1) indicators/metrics; and 2) securitization. Indicators have been a vehicle for the government of states, particularly in the global south, through the external imposition and internal self-application of standards and benchmarks and through the comparative rankings which ensue therefrom. Securitization refers to the performative calling-into-being of emergencies in the face of existential threats. National sovereignty is at stake in both modes: limited, superintended, and redirected by indicators on the one hand; articulated as originary and untrammelled through securitizing moves on the other. Health has been a key focus for analysts of each. We may hypothesize that COVID-19 is the occasion for an as yet undecided contest between de-spatialized health governmentality and the reassertion of territorial segmentation as the frame for an autochtonously defined national interest, a retreat, it is feared, from Post-Westphalian to Westphalian governance in global health. In what follows, I first sketch an outline of each governance mode, remarking on the application of each to health promotion in the global south. The purchase of this theoretical outline is then tested briefly through a focus on Kenya, and, in particular, its response to COVID-19 in the early months of the pandemic, between February and May 2020. Both modes were deployed in political and legal interventions during this period. It is clear that government ministers tended to adopt securitization language, while foreign and civil society actors drew on indicators and related benchmarks to support criticism of state action and inaction

Codes of Commitment to Crime and Resistance: Determining Social and Cultural Factors over the Behaviors of Italian Mafia Women

This article categorizes thirty-three women in four main Italian Mafia groups and explores social and cultural behaviors of these women. This study introduces the feminist theory of belief and action. The theoretical inquiry investigates the sometimes conflicting behaviors of women when they are subject to systematic oppression. I argue that there is a cultural polarization among the categorized sub-groups. Conservative radicals give their support to the Mafia while defectors and rebels resist the Mafia. After testing the theory, I assert that emancipation of women depends on the strength of their beliefs to perform actions against the Mafiosi culture

Neural Decision Boundaries for Maximal Information Transmission

We consider here how to separate multidimensional signals into two categories, such that the binary decision transmits the maximum possible information transmitted about those signals. Our motivation comes from the nervous system, where neurons process multidimensional signals into a binary sequence of responses (spikes). In a small noise limit, we derive a general equation for the decision boundary that locally relates its curvature to the probability distribution of inputs. We show that for Gaussian inputs the optimal boundaries are planar, but for non-Gaussian inputs the curvature is nonzero. As an example, we consider exponentially distributed inputs, which are known to approximate a variety of signals from natural environment.Comment: 5 pages, 3 figure

A Neurocomputational Model of Stimulus-Specific Adaptation to Oddball and Markov Sequences

Stimulus-specific adaptation (SSA) occurs when the spike rate of a neuron decreases with repetitions of the same stimulus, but recovers when a different stimulus is presented. It has been suggested that SSA in single auditory neurons may provide information to change detection mechanisms evident at other scales (e.g., mismatch negativity in the event related potential), and participate in the control of attention and the formation of auditory streams. This article presents a spiking-neuron model that accounts for SSA in terms of the convergence of depressing synapses that convey feature-specific inputs. The model is anatomically plausible, comprising just a few homogeneously connected populations, and does not require organised feature maps. The model is calibrated to match the SSA measured in the cortex of the awake rat, as reported in one study. The effect of frequency separation, deviant probability, repetition rate and duration upon SSA are investigated. With the same parameter set, the model generates responses consistent with a wide range of published data obtained in other auditory regions using other stimulus configurations, such as block, sequential and random stimuli. A new stimulus paradigm is introduced, which generalises the oddball concept to Markov chains, allowing the experimenter to vary the tone probabilities and the rate of switching independently. The model predicts greater SSA for higher rates of switching. Finally, the issue of whether rarity or novelty elicits SSA is addressed by comparing the responses of the model to deviants in the context of a sequence of a single standard or many standards. The results support the view that synaptic adaptation alone can explain almost all aspects of SSA reported to date, including its purported novelty component, and that non-trivial networks of depressing synapses can intensify this novelty response

Representation of Time-Varying Stimuli by a Network Exhibiting Oscillations on a Faster Time Scale

Sensory processing is associated with gamma frequency oscillations (30–80 Hz) in sensory cortices. This raises the question whether gamma oscillations can be directly involved in the representation of time-varying stimuli, including stimuli whose time scale is longer than a gamma cycle. We are interested in the ability of the system to reliably distinguish different stimuli while being robust to stimulus variations such as uniform time-warp. We address this issue with a dynamical model of spiking neurons and study the response to an asymmetric sawtooth input current over a range of shape parameters. These parameters describe how fast the input current rises and falls in time. Our network consists of inhibitory and excitatory populations that are sufficient for generating oscillations in the gamma range. The oscillations period is about one-third of the stimulus duration. Embedded in this network is a subpopulation of excitatory cells that respond to the sawtooth stimulus and a subpopulation of cells that respond to an onset cue. The intrinsic gamma oscillations generate a temporally sparse code for the external stimuli. In this code, an excitatory cell may fire a single spike during a gamma cycle, depending on its tuning properties and on the temporal structure of the specific input; the identity of the stimulus is coded by the list of excitatory cells that fire during each cycle. We quantify the properties of this representation in a series of simulations and show that the sparseness of the code makes it robust to uniform warping of the time scale. We find that resetting of the oscillation phase at stimulus onset is important for a reliable representation of the stimulus and that there is a tradeoff between the resolution of the neural representation of the stimulus and robustness to time-warp. Author Summary Sensory processing of time-varying stimuli, such as speech, is associated with high-frequency oscillatory cortical activity, the functional significance of which is still unknown. One possibility is that the oscillations are part of a stimulus-encoding mechanism. Here, we investigate a computational model of such a mechanism, a spiking neuronal network whose intrinsic oscillations interact with external input (waveforms simulating short speech segments in a single acoustic frequency band) to encode stimuli that extend over a time interval longer than the oscillation's period. The network implements a temporally sparse encoding, whose robustness to time warping and neuronal noise we quantify. To our knowledge, this study is the first to demonstrate that a biophysically plausible model of oscillations occurring in the processing of auditory input may generate a representation of signals that span multiple oscillation cycles.National Science Foundation (DMS-0211505); Burroughs Wellcome Fund; U.S. Air Force Office of Scientific Researc

Association Between Plasma Monocyte Chemoattractant Protein-1 Concentration and Cardiovascular Disease Mortality in Middle-Aged Diabetic and Nondiabetic Individuals

OBJECTIVE Monocyte chemoattractant protein-1 (MCP-1/CCL2) is a chemokine involved into the pathogenesis of atherosclerosis and has prognostic value in the acute and chronic phases in patients with acute coronary syndromes. RESEARCH DESIGN AND METHODS MCP-1/CCL2 concentration was measured in plasma fractions of 363 middle-aged overweight/obese individuals (aged 61 \ub1 12 years, BMI 30.1 \ub1 6.6 kg/m2, 15% with type 2 diabetes, and 12% with impaired glucose tolerance) of a population survey carried out in 1990\u20131991 in Lombardy, Italy (Cremona Study), and cardiovascular disease (CVD) mortality was assessed in 2006 through Regional Health Registry files. RESULTS At baseline MCP-1/CCL2 was increased in individuals with type 2 diabetes (P < 0.05) and showed significant correlations with biochemical risk markers of atherosclerosis. After 15 years, among the 363 subjects, there were 82 deaths due to CVD. In univariate analysis age, sex, fasting glucose and insulin, fibrinogen, glucose tolerance status, smoking habit, and MCP-1/CCL2 were associated with CVD mortality. Age, sex, fasting serum glucose, MCP-1/CCL2, and smoking habit maintained an independent association with CVD mortality in multiple regression analysis. In a subgroup of 113 subjects in whom data for C-reactive protein (CRP) were available, its level was not predictive of CVD mortality. CONCLUSIONS In middle-aged overweight/obese individuals MCP-1/CCL2 was independently associated with CVD mortality. Further studies will be necessary to establish its role as a surrogate biomarker and as a potential therapeutic target