Association of frailty index with perioperative mortality and in-hospital morbidity after elective lower extremity bypass

Objective

The frailty index has been linked to adverse outcomes after surgical procedures. In this study, we evaluated the association between frailty index and outcomes after elective lower extremity bypass (LEB) for lower extremity ischemia.

Tryptophan metabolites suppress the Wnt pathway and promote adverse limb events in chronic kidney disease

Chronic kidney disease (CKD) imposes a strong and independent risk for peripheral artery disease (PAD). While solutes retained in CKD patients (uremic solutes) inflict vascular damage, their role in PAD remains elusive. Here, we show that the dietary tryptophan-derived uremic solutes including indoxyl sulfate (IS) and kynurenine (Kyn) at concentrations corresponding to those in CKD patients suppress β-catenin in several cell types, including microvascular endothelial cells (ECs), inhibiting Wnt activity and proangiogenic Wnt targets in ECs. Mechanistic probing revealed that these uremic solutes downregulated β-catenin in a manner dependent on serine 33 in its degron motif and through the aryl hydrocarbon receptor (AHR). Hindlimb ischemia in adenine-induced CKD and IS solute–specific mouse models showed diminished β-catenin and VEGF-A in the capillaries and reduced capillary density, which correlated inversely with blood levels of IS and Kyn and AHR activity in ECs. An AHR inhibitor treatment normalized postischemic angiogenic response in CKD mice to a non-CKD level. In a prospective cohort of PAD patients, plasma levels of tryptophan metabolites and plasma’s AHR-inducing activity in ECs significantly increased the risk of future adverse limb events. This work uncovers the tryptophan metabolite/AHR/β-catenin axis as a mediator of microvascular rarefaction in CKD patients and demonstrates its targetability for PAD in CKD models.     

Hyperperfusion Syndrome after Carotid Endarterectomy

The hyperperfusion syndrome is a rare delayed postoperative complication of carotid endarterectomy (CEA) characterized by headache and seizure, with or without intracranial edema or hemorrhage. Between January 1996 and December 2003, 1,602 CEAs were performed. Six patients (0.4%) developed symptoms of hyperperfusion within 2 weeks of surgery. All patients had critical stenoses, five ≥90% and one 80-90%, with poor backbleeding from the distal internal carotid artery noted at operation in all cases. Five patients were asymptomatic prior to operation; one had a hemispheric transient ischemic attack. Three patients had severe contralateral internal carotid disease (two occlusions and one severe stenosis). Two patients developed severe, self-limiting headache that prolonged hospitalization. Three patients had ipsilateral intracranial bleeding, two occurring after an uneventful postoperative course. After initial discharge from the hospital, severe intracranial hemorrhage caused death in two patients. One patient experienced focal seizures 1 week after discharge. Hypertension did not appear to be related to the symptoms in any case. During the study period, the hyperperfusion syndrome caused three of five perioperative strokes (60%) and two of seven deaths (29%) in the entire endarterectomy population. Although rare, the hyperperfusion syndrome accounts for a significant percentage of the neurological morbidity and mortality following CEA.Presented at the Twenty-second Annual Meeting of the Southern California Vascular Surgery Society, La Jolla, CA, April 30-May 2, 2004.     

Prognostic value of global myocardial performance indices in acute myocardial infarction: comparison to measures of systolic and diastolic left ventricular function

STUDY OBJECTIVES: Assessment of global myocardial performance by a single index (ie, the myocardial performance index [MPI]) has been suggested as an appealing alternative to the individual assessment of systolic and diastolic left ventricular (LV) function We sought to test the prognostic value of MPI in comparison to clinical characteristics and echocardiographic parameters of LV filling and ejection in acute myocardial infarction (AMI). PATIENTS: Four hundred seventeen consecutive patients with AMI were examined within 24 h of hospital admission. INTERVENTIONS: Doppler echocardiographic measures of systolic, diastolic, and global myocardial performance were assessed within 24 h of hospital admission. In addition to MPI (ie, the sum of the isovolumic time intervals divided by ejection time), we determined the isovolumic/heterovolumic time ratio, which expresses the time "wasted" by the myocardium to generate and decrease LV pressure without moving blood. RESULTS: The end points of the study at 30 days were death (4.7%), congestive heart failure (23%), and recurrent infarction (4.8%), and occurred in 109 patients, who were compared as group B to 314 patients without an event (group A). Multivariate analysis identified only age (odds ratio [OR], 1.04; 95% confidence interval [CI], 1.02 to 1.07), LV ejection fraction (LVEF) < or = 40% (OR, 3.82; 95% CI, 2.15 to 6.87), and E-wave deceleration time (EDT) of < or = 130 ms (OR, 2.29; 95% CI, 1.0 to 5.21) as independent predictors of adverse events. CONCLUSION: LVEF and EDT are powerful and independent echocardiographic predictors of poor outcome following AMI, and are superior to indexes of global LV performance. Both parameters should be taken into consideration when deciding about the management of these patients.     

From the Cover: Orientation saliency without visual cortex and target selection in archer fish

Our visual attention is attracted by salient stimuli in our environment and affected by primitive features such as orientation, color, and motion. Perceptual saliency due to orientation contrast has been extensively demonstrated in behavioral experiments with humans and other primates and is believed to be facilitated by the functional organization of the primary visual cortex. In behavioral experiments with the archer fish, a proficient hunter with remarkable visual abilities, we found an orientation saliency effect similar to that observed in human subjects. Given the enormous evolutionary distance between humans and archer fish, our findings suggest that orientation-based saliency constitutes a fundamental building block for efficient visual information processing.     

Decorrelation of retinal response to natural scenes by fixational eye movements

Under natural viewing conditions the input to the retina is a complex spatiotemporal signal that depends on both the scene and the way the observer moves. It is commonly assumed that the retina processes this input signal efficiently by taking into account the statistics of the natural world. It has recently been argued that incessant microscopic eye movements contribute to this process by decorrelating the input to the retina. Here we tested this theory by measuring the responses of the salamander retina to stimuli replicating the natural input signals experienced by the retina in the presence and absence of fixational eye movements. Contrary to the predictions of classic theories of efficient encoding that do not take behavior into account, we show that the response characteristics of retinal ganglion cells are not sufficient in themselves to disrupt the broad correlations of natural scenes. Specifically, retinal ganglion cells exhibited strong and extensive spatial correlations in the absence of fixational eye movements. However, the levels of correlation in the neural responses dropped in the presence of fixational eye movements, resulting in effective decorrelation of the channels streaming information to the brain. These observations confirm the predictions that microscopic eye movements act to reduce correlations in retinal responses and contribute to visual information processing.Much effort has been devoted to understanding how the neural code of the retina and downstream neurons can represent visual information efficiently given the statistical structure of the natural world (1–6). Although these theories have contributed tremendously to current understanding of early visual processing, they do not consider the observer’s motor activity but rather rely on the simplifying assumption that the input to the retina is a stationary image. However, even during fixation on a single point, small movements of the eye, head, and other parts of the body continually modulate visual input signals. Experiments have shown that elimination of retinal image motion leads to fading of vision (7, 8). Therefore, eye movements are essential for the normal functioning of the visual system.It has been proposed that, rather than simply preventing adaptation in neural responses, fixational eye movements are a critical stage of information processing, in which predictable spatial correlations are discarded to enable encoding of luminance discontinuities by synchronous neural activity (9, 10). Thus, fixational eye movements counterbalance the spectral density of natural scenes and yield temporal modulations with equalized power over a broad range of spatial frequencies. Because spectral equalization is equivalent to decorrelation in space, this theory predicts that fixational eye movements should attenuate correlations in the responses of the retinal ganglion cells. Modeling results have provided support to this hypothesis (9, 10).