Reliable in vivo intravascular imaging plaque characterization: A challenge unmet.

Intravascular imaging has enabled in vivo assessment of coronary artery pathology and detection of plaque characteristics that are associated with increased vulnerability. Prospective invasive imaging studies of coronary atherosclerosis have demonstrated that invasive imaging modalities can detect lesions that are likely to progress and cause cardiovascular events and provided unique insights about atherosclerotic evolution. However, despite the undoubted value of the existing imaging techniques in clinical and research arenas, all the available modalities have significant limitations in assessing plaque characteristics when compared with histology. Hybrid/multimodality intravascular imaging appears able to overcome some of the limitations of standalone imaging; however, there are only few histology studies that examined their performance in evaluating plaque pathobiology. In this article, we review the evidence about the efficacy of standalone and multi-modality/hybrid intravascular imaging in assessing plaque morphology against histology, highlight the advantages and limitations of the existing imaging techniques and discuss the future potential of emerging imaging modalities in the study of atherosclerosis.

Hybrid intravascular imaging: recent advances, technical considerations, and current applications in the study of plaque pathophysiology.

Cumulative evidence from histology-based studies demonstrate that the currently available intravascular imaging techniques have fundamental limitations that do not allow complete and detailed evaluation of plaque morphology and pathobiology, limiting the ability to accurately identify high-risk plaques. To overcome these drawbacks, new efforts are developing for data fusion methodologies and the design of hybrid, dual-probe catheters to enable accurate assessment of plaque characteristics, and reliable identification of high-risk lesions. Today several dual-probe catheters have been introduced including combined near infrared spectroscopy-intravascular ultrasound (NIRS-IVUS), that is already commercially available, IVUS-optical coherence tomography (OCT), the OCT-NIRS, the OCT-near infrared fluorescence (NIRF) molecular imaging, IVUS-NIRF, IVUS intravascular photoacoustic imaging and combined fluorescence lifetime-IVUS imaging. These multimodal approaches appear able to overcome limitations of standalone imaging and provide comprehensive visualization of plaque composition and plaque biology. The aim of this review article is to summarize the advances in hybrid intravascular imaging, discuss the technical challenges that should be addressed in order to have a use in the clinical arena, and present the evidence from their first applications aiming to highlight their potential value in the study of atherosclerosis.

The Lipid-Rich Plaque Study of vulnerable plaques and vulnerable patients: Study design and rationale.

BACKGROUND: It has been hypothesized that the outcome post-PCI could be improved by the detection and subsequent treatment of vulnerable patients and lipid-rich vulnerable coronary plaques (LRP). A near-infrared spectroscopy (NIRS) catheter capable of detecting LRP is being evaluated in The Lipid-Rich Plaque Study. STUDY DESIGN: The LRP Study is an international, multicenter, prospective cohort study conducted in patients with suspected coronary artery disease (CAD) who underwent cardiac catheterization with possible ad hoc PCI for an index event. Patient level and plaque level events were detected by follow-up in the subsequent 2 years. Enrollment began in February 2014 and was completed in March 2016; a total of 1,562 patients were enrolled. Adjudication of new coronary event occurrence and de novo culprit lesion location during the 2-year follow-up is performed by an independent clinical end-points committee (CEC) blinded to NIRS-IVUS findings. The first analysis of the results will be performed when at least 20 de novo events have occurred for which follow-up angiographic data and baseline NIRS-IVUS measurements are available. It is expected that results of the study will be announced in 2018. SUMMARY: The LRP Study will test the hypotheses that NIRS-IVUS imaging to detect LRP in patients can identify vulnerable patients and vulnerable plaques. Identification of vulnerable patients will assist future studies of novel systemic therapies; identification of localized vulnerable plaques would enhance future studies of possible preventive measures.

Confirmation of the Intracoronary Near-Infrared Spectroscopy Threshold of Lipid-Rich Plaques That Underlie ST-Segment-Elevation Myocardial Infarction.

OBJECTIVE: In a previous exploratory analysis, intracoronary near-infrared spectroscopy (NIRS) found the majority of culprit lesions in ST-segment-elevation myocardial infarction (STEMI) to contain a maximum lipid core burden index in 4 mm (maxLCBI4mm) of >400. This initial study was limited by a small sample size, enrollment at a single center, and post hoc selection of the maxLCBI4mm ≥400 threshold. This study was designed a priori to substantiate the ability of NIRS to discriminate STEMI culprit from nonculprit segments and to confirm the performance of the maxLCBI4mm ≥400 threshold. APPROACH AND RESULTS: At 2 centers in the United States and Sweden, 75 STEMI patients underwent intracoronary NIRS imaging after establishing thrombolysis in myocardial infarction 3 flow, but before stenting. Blinded core laboratory analysis defined the culprit segment as the 10-mm segment distal to the proximal angiographic culprit margin. The remaining vessel was divided into contiguous 10-mm nonculprit segments. The maxLCBI4mm of culprit segments (median [interquartile range]: 543 [273-756]) was 4.4-fold greater than nonculprit segments (median [interquartile range]: 123 [0-307]; P<0.001). Receiver-operating characteristic analysis demonstrated that maxLCBI4mm differentiated culprit from nonculprit segments with high accuracy (c-statistic=0.83; P<0.001). A threshold maxLCBI4mm ≥400 identified STEMI culprit segments with a sensitivity of 64% and specificity of 85%. CONCLUSIONS: This study substantiates the ability of NIRS to accurately differentiate STEMI culprit from nonculprit segments and confirms that a threshold maxLCBI4mm ≥400 is detected by NIRS in the majority of STEMI culprits.

Near-Infrared Spectroscopy Enhances Intravascular Ultrasound Assessment of Vulnerable Coronary Plaque: A Combined Pathological and In Vivo Study.

OBJECTIVES: Pathological studies demonstrate the dual significance of plaque burden (PB) and lipid composition for mediating coronary plaque vulnerability. We evaluated relationships between intravascular ultrasound (IVUS)-derived PB and arterial remodeling with near-infrared spectroscopy (NIRS)-derived lipid content in ex vivo and in vivo human coronary arteries. APPROACH AND RESULTS: Ex vivo coronary NIRS and IVUS imaging was performed through blood in 116 coronary arteries of 51 autopsied hearts, followed by 2-mm block sectioning (n=2070) and histological grading according to modified American Heart Association criteria. Lesions were defined as the most heavily diseased 2-mm block per imaged artery on IVUS. IVUS-derived PB and NIRS-derived lipid core burden index (LCBI) of each block and lesion were analyzed. Block-level analysis demonstrated significant trends of increasing PB and LCBI across more complex atheroma (Ptrend <0.001 for both LCBI and PB). Lesion-based analyses demonstrated the highest LCBI and remodeling index within coronary fibroatheroma (Ptrend <0.001 and 0.02 versus all plaque groups, respectively). Prediction models demonstrated similar abilities of PB, LCBI, and remodeling index for discriminating fibroatheroma (c indices: 0.675, 0.712, and 0.672, respectively). A combined PB+LCBI analysis significantly improved fibroatheroma detection accuracy (c index 0.77, P=0.028 versus PB; net-reclassification index 43%, P=0.003), whereas further adding remodeling index did not (c index 0.80, P=0.27 versus PB+LCBI). In vivo comparisons of 43 age- and sex-matched patients (to the autopsy cohort) undergoing combined NIRS-IVUS coronary imaging yielded similar associations to those demonstrated ex vivo. CONCLUSIONS: Adding NIRS to conventional IVUS-derived PB imaging significantly improves the ability to detect more active, potentially vulnerable coronary atheroma.

A mobile CRISPRi collection enables genetic interaction studies for the essential genes of Escherichia coli.

Advances in gene editing, in particular CRISPR interference (CRISPRi), have enabled depletion of essential cellular machinery to study the downstream effects on bacterial physiology. Here, we describe the construction of an ordered E. coli CRISPRi collection, designed to knock down the expression of 356 essential genes with the induction of a catalytically inactive Cas9, harbored on the conjugative plasmid pFD152. This mobile CRISPRi library can be conjugated into other ordered genetic libraries to assess combined effects of essential gene knockdowns with non-essential gene deletions. As proof of concept, we probed cell envelope synthesis with two complementary crosses: (1) an Lpp deletion into every CRISPRi knockdown strain and (2) the lolA knockdown plasmid into the Keio collection. These experiments revealed a number of notable genetic interactions for the essential phenotype probed and, in particular, showed suppressing interactions for the loci in question.

Improving Access and Quality of Behavioral Health Services for Health Care Employees.

OBJECTIVE: To describe key features and the initial implementation of an employer-sponsored program designed to increase access to quality mental health treatment for employees of a large health care system. Methods: Retrospective data were collected on employer's efforts to develop a programmatic solution to address barriers to accessing quality mental health treatment among its employees and on initial program implementation. Results: Data from the initial cohort ( N = 1049) of program participants support the use of low threshold digital tools to enhance access to care, the importance of care navigation and a robust curated provider network in matching employees to appropriate care options, and the value of providing online, evidence-based psychotherapy to facilitate high rates of treatment engagement. Conclusions: Findings can help inform employers about approaches to improve access to quality mental health treatment for their employees.

Alterations in performance and discriminating power of the death/suicide implicit association test across the lifespan.

The Death/Suicide Implicit Association Test (d/s-IAT) has differentiated individuals with prior and prospective suicide attempts in previous studies, however, age effects on test results remains to be explored. A three-site study compared performance on the d/s-IAT among participants aged 16-80 years with depression and prior suicide attempt (n = 82), with depression and no attempts (n = 80), and healthy controls (n = 86). Outcome measures included the standard difference (D) score, median reaction times, and error rates. Higher D scores represent a stronger association between death/suicide and self, while lower scores represent a stronger association between life and self. The D scores differed significantly among groups overall. Participants with depression exhibited higher scores compared to healthy controls, but there was no difference between participants with and without prior suicide attempts(F[2,242]=8.76, p<.001). Response times for participants with prior attempts differed significantly from other groups, with no significant differences in error rates. The D score was significantly affected by age (ß =-0.007, t = 3.65, p<.001), with slowing of response times in older ages. Results suggest reaction time d/s-IAT D scores may not distinguish implicit thinking about suicide as response times slow with age, but slowed response times may be sensitive to suicide risk potentially indicating basic information processing deficits.

Automated, tailored adaptive mobile messaging to reduce alcohol consumption in help-seeking adults: A randomized controlled trial.

AIMS: To test differential outcomes between three 6-month text-messaging interventions to reduce at-risk drinking in help-seeking adults. DESIGN: A three-arm single-blind randomized controlled trial with 1-, 3-, 6- and 12-month follow-ups. SETTING: United States. A fully remote trial without human contact, with participants recruited primarily via social media outlets. PARTICIPANTS: Seven hundred and twenty-three adults (mean = 39.9 years, standard deviation = 10.0; 62.5% female) seeking to reduce their drinking were allocated to 6 months of baseline 'tailored statically' messaging (TS; n = 240), 'tailored adaptive' messaging (TA; n = 239) or 'drink tracking' messaging (DT; n = 244). INTERVENTIONS: TS consisted of daily text messages to reduce harmful drinking that were tailored to demographics and alcohol use. TA consisted of daily, tailored text messages that were also adapted based on goal achievement and proactive prompts. DT consisted of a weekly assessment for self-reported drinking over the past 7 days. MEASUREMENTS: The primary outcome measure was weekly sum of standard drinks (SSD) at 6-month follow-up. Secondary outcome measures included drinks per drinking day (DDD), number of drinking days (NDD) per week and heavy drinking days (HDD) at 1-, 3-, 6- and 12-month follow-ups. FINDINGS: At 6 months, compared with DT, TA resulted in significant SSD reductions of 16.2 (from 28.7 to 12.5) drinks [adjusted risk ratio (aRR) = 0.80, 95% confidence interval (CI) = 0.71, 0.91] using intent-to-treat analysis. TA also resulted in significant improvements in DDD (aRR = 0.84; 95% CI = 0.77-0.92) and drinking days per week (b = -0.39; 95% CI = -0.67, -0.10), but not HDD compared with DT at 6 months. TA was not significantly different from TS at any time-point, except DDD at 6 months. All groups made improvements in SSD at 12-month follow-up compared with baseline with an average reduction of 12.9 drinks per week across groups. CONCLUSIONS: Automated tailored mobile messaging interventions are scalable solutions that can reduce weekly alcohol consumption in remote help-seeking drinkers over time.

Impacts of COVID-19 on alcohol use among help-seeking adults.

The coronavirus (COVID-19) pandemic has been associated with both increased and decreased alcohol use. Authors explored reasons for increased and decreased alcohol use since the COVID-19 lockdown (March 2020) in a sample of help-seeking adults (HSA) participating in a remote-based alcohol reduction text-messaging intervention in the USA. At the time of recruitment, the HSA in this study were interested in reducing rather than stopping their alcohol consumption. An optional self-report questionnaire was completed by 324 participants (mean age 41.6 ± 10.2 years; 71.5% female; 83.9% White) in February 2021. Survey questions assessed sociodemographic factors, social stressors (quarantine conditions, employment status, changes to daily routine), and drinking patterns. Authors fit two ordinal logistic regression models: one for increased drinking and one for decreased drinking, as functions of the potential predictors and control variables. Most participants (n = 281; 87.0%) reported drinking more than usual since COVID-19 lockdown began. The most common self-reported reasons for drinking more were increased stress/anxiety (74.7%), boredom (69.4%), and spending more time at home (65.5%) whereas reasons for drinking less were less socializing (33.7%) and worrying about how alcohol would impact the immune system (31.5%). Identifying as female, severity of changes to daily routine, and increased access to alcohol were significantly associated with drinking more than usual. These data suggest that the general consequences of the pandemic in the general population (e.g., boredom) led to greater alcohol use among help-seeking adults attempting to reduce their drinking. Identifying these factors may help create more targeted interventions during public health crises.

Smoked Cannabis Effects in Cannabis Users at Clinical High-Risk for Psychosis: A Further Investigation of Cognition and Reward.

Objective: Some adverse cannabis effects are greater in individuals on the psychosis spectrum compared to healthy individuals. We have previously reported that smoked cannabis acutely worsened psychotic- like states and reduced cognitive performance selectively in cannabis users at clinical high-risk (CHR) for psychosis. The objective of the present study was to further investigate the acute effects of cannabis on cognition and reward processing in CHR cannabis users. Methods: Six CHR cannabis users and six psychiatrically-healthy cannabis users comparable in intellectual, demographic, and cannabis use characteristics (including nontreatment-seeking status), participated in the study. Objective and subjective measures of cognition and cannabis reward, were completed before and after smoking half of an active (5.5% Δ9tetrahydrocannabinol [Δ9-THC]) or half of a placebo (0.0% Δ9-THC) cannabis cigarette, under randomized/double-blind conditions. Repeated measures ANOVA tested main effects of drug condition (active vs. placebo) and/or the drug condition × time (baseline vs. post-administration) interactions; groups were analyzed separately due to the small sample size. Results: CHR participants exhibited evidence of decreased objective response inhibition and aversive intoxication following active cannabis, relative to placebo. Psychomotor speed and cannabis-related attentional bias were also affected by cannabis intoxication. No such effects were observed in psychiatrically-healthy cannabis users. Conclusion: These findings provide further preliminary evidence of a deleterious cognitive and reward- related response to cannabis in individuals with preexisting risk for psychosis.

Ketamine vs midazolam: Mood improvement reduces suicidal ideation in depression.

OBJECTIVE: Studies demonstrate rapid antidepressant and anti-suicidal ideation effects of subanesthetic ketamine. The specific subcomponents of depression that are most closely tied to reduction of suicidal ideation with ketamine treatment are less explored. METHODS: Exploratory, post hoc analysis of data from a randomized clinical trial of ketamine vs midazolam in patients with major depressive disorder (MDD) and clinically significant suicidal ideation examined changes in factor analysis-derived symptom clusters from standard measures of depression (Hamilton Depression Rating Scale, HDRS; Beck Depression Inventory, BDI) and mood disturbance (Profile of Mood States, POMS), and their relationship to severity of suicidal ideation (Beck Scale for Suicidal Ideation; SSI). Ratings obtained before and one day after blinded intravenous infusion were decomposed into component factors or published subscales. Treatment effects on factors/subscales were compared between drugs, correlations with changes in suicidal ideation were tested, and stepwise regression was used to derive predictors of change in SSI. RESULTS: Factor scores for HDRS Psychic Depression, HDRS Anxiety, BDI Subjective Depression, POMS Depression and POMS Fatigue improved more with ketamine than midazolam. Stepwise regression showed across both drugs that improvement in HDRS Psychic Depression, POMS Depression, and HDRS Anxiety predicted 51.6% of the variance in reduction of suicidal ideation. LIMITATIONS: Secondary analysis of clinical trial data. CONCLUSIONS: Ketamine's rapid effects on suicidal ideation appear to be mostly a function of its effects on core mood and anxiety symptoms of MDD, with comparatively little contribution from neurovegetative symptoms with the potential exception of vigor/fatigue. TRIAL REGISTRATION: Data used in this secondary analysis came from ClinicalTrials.gov identifier: NCT01700829.

Robust quantitative assessment of collagen fibers with picrosirius red stain and linearly polarized light as demonstrated on atherosclerotic plaque samples.

Collagen is an important component in maintaining structural integrity and functionality of tissues and is modulated in various biological processes. Its visualization and possible quantification using histopathological stains can be important for understanding disease progression or therapeutic response. Visualization of collagen fiber with the histological stain picrosirius red (PSR) is enhanced with polarized light and quantitative analysis is possible using circular polarizers. However, linear polarizers are more commonly available and easier to optically align. The objective of the present study is to demonstrate a novel image acquisition technique and analysis method using linearly polarized light. The proposed imaging technique is based on image acquisition at multiple slide rotation angles, which are co-registered to form a composite image used for quantitative analysis by pixel intensity or pixel counting. The technique was demonstrated on multiple human coronary samples with varying histopathologies and developed specifically to analyze cap collagen in atherosclerotic plaque. Pixel counting image analysis was found to be reproducible across serial tissue sections and across different users and sufficiently sensitive to detect differences in cap structural integrity that are likely relevant to prediction of rupture risk. The benefit of slide rotation angle under linear polarization to acquire images represents a feasible and practical implementation for expanding the general utility of PSR for quantitative analysis.

Effects of Ketamine Versus Midazolam on Neurocognition at 24 Hours in Depressed Patients With Suicidal Ideation.

Objective: Subanesthetic ketamine rapidly reduces depressive symptoms and suicidal ideation in some depressed patients. Its effects on neurocognitive functioning in such individuals with significant suicidal ideation is not well understood, even though certain neurocognitive deficits are associated with suicide behavior beyond clinical symptoms.Methods: In this study, depressed patients with clinically significant suicidal ideation (n = 78) underwent neuropsychological testing before and 1 day after double-blind treatment with intravenous ketamine (n = 39) or midazolam (n = 39). A subgroup randomized to midazolam whose ideation did not remit after initial infusion received open ketamine and additional neurocognitive testing a day after this treatment. The primary outcome was change in performance on this neurocognitive battery. The study was conducted between November 2012 and January 2017.Results: Blinded ketamine produced rapid improvement in suicidal ideation and mood in comparison to midazolam, as we had reported previously. Ketamine, relative to midazolam, was also associated with specific improvement in reaction time (Choice RT) and interference processing/cognitive control (computerized Stroop task)-the latter a measure that has been associated with past suicide attempt in depression. In midazolam nonremitters later treated with open ketamine and retested, reaction time and interference processing/cognitive control also improved relative to both of their prior assessments. Neurocognitive improvement, however, was not correlated with changes in depression, suicidal thinking, or general mood.Conclusions: Overall, ketamine was found to have a positive therapeutic effect on neurocognition 1 day after treatment on at least 1 measure associated with suicidal behavior in the context of depression. Results suggest additional independent therapeutic effects for ketamine in the treatment of depressed patients at risk for suicidal behavior.Trial Registration: ClinicalTrials.gov identifier: NCT01700829.

Lipid plaque burden in NSTE-ACS patients with or without COPD: insights from the SCAP Trial.

BACKGROUND: Chronic obstructive pulmonary disease (COPD) patients have higher recurrence of adverse events and worse prognosis after acute coronary syndrome (ACS). The underlying pathophysiological mechanism is not fully elucidated. METHODS: In screening for COPD in ACS (SCAP) Trial (NCT02324660), ACS patients with smoking habit underwent a predischarge screening procedure to detect undiagnosed chronic obstructive pulmonary disease (UCOPD) confirmed with spirometry at 60 days. Patients were then categorized as UCOPD or no-COPD. In 65 NSTE-ACS patients, we performed near infrared spectroscopy (NIRS) in the culprit and at least one non-culprit vessel (151 vessels overall), and we calculated the SYNTAX I Score. Primary endpoint was max lipid core burden index (LCBI) 4 mm. Secondary endpoints were SYNTAX Score I and vessel LCBI. RESULTS: Max LCBI 4 mm and vessel LCBI were significantly higher in the UCOPD compared to the no-COPD group (UCOPD 388±122, no-COPD 264±131, P<0.001; UCOPD 118±50, no-COPD 82±42, P<0.001, respectively). UCOPD patients showed higher max LCBI 4 mm and LCBI vessel both in culprit and non-culprit vessels. SYNTAX Score I was comparable between the two groups (UCOPD: 13.5 [5.5-24], no-COPD: 12.5 [5-24.5], P=0.7). CONCLUSIONS: NSTE-ACS patients with UCOPD showed a higher LCBI compared to those without COPD, while SYNTAX Score I was comparable between the two groups.

Author Correction: Large-scale variation in density of an aquatic ecosystem indicator species.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Integrated Lipidomics and Proteomics Point to Early Blood-Based Changes in Childhood Preceding Later Development of Psychotic Experiences: Evidence From the Avon Longitudinal Study of Parents and Children.

BACKGROUND: The identification of early biomarkers of psychotic experiences (PEs) is of interest because early diagnosis and treatment of those at risk of future disorder is associated with improved outcomes. The current study investigated early lipidomic and coagulation pathway protein signatures of later PEs in subjects from the Avon Longitudinal Study of Parents and Children cohort. METHODS: Plasma of 115 children (12 years of age) who were first identified as experiencing PEs at 18 years of age (48 cases and 67 controls) were assessed through integrated and targeted lipidomics and semitargeted proteomics approaches. We assessed the lipids, lysophosphatidylcholines (n = 11) and phosphatidylcholines (n = 61), and the protein members of the coagulation pathway (n = 22) and integrated these data with complement pathway protein data already available on these subjects. RESULTS: Twelve phosphatidylcholines, four lysophosphatidylcholines, and the coagulation protein plasminogen were altered between the control and PEs groups after correction for multiple comparisons. Lipidomic and proteomic datasets were integrated into a multivariate network displaying a strong relationship between most lipids that were significantly associated with PEs and plasminogen. Finally, an unsupervised clustering approach identified four different clusters, with one of the clusters presenting the highest case-control ratio (p < .01) and associated with a higher concentration of smaller low-density lipoprotein cholesterol particles. CONCLUSIONS: Our findings indicate that the lipidome and proteome of subjects who report PEs at 18 years of age are already altered at 12 years of age, indicating that metabolic dysregulation may contribute to an early vulnerability to PEs and suggesting crosstalk between these lysophosphatidylcholines, phosphatidylcholines, and coagulation and complement proteins.

Large-scale variation in density of an aquatic ecosystem indicator species.

Monitoring indicator species is a pragmatic approach to natural resource assessments, especially when the link between the indicator species and ecosystem state is well justified. However, conducting ecosystem assessments over representative spatial scales that are insensitive to local heterogeneity is challenging. We examine the link between polychlorinated biphenyl (PCB) contamination and population density of an aquatic habitat specialist over a large spatial scale using non-invasive genetic spatial capture-recapture. Using American mink (Neovison vison), a predatory mammal and an indicator of aquatic ecosystems, we compared estimates of density in two major river systems, one with extremely high levels of PCB contamination (Hudson River), and a hydrologically independent river with lower PCB levels (Mohawk River). Our work supports the hypothesis that mink densities are substantially (1.64-1.67 times) lower in the contaminated river system. We demonstrate the value of coupling the indicator species concept with well-conceived and spatially representative monitoring protocols. PCBs have demonstrable detrimental effects on aquatic ecosystems, including mink, and these effects are likely to be profound and long-lasting, manifesting as population-level impacts. Through integrating non-invasive data collection, genetic analysis, and spatial capture-recapture methods, we present a monitoring framework for generating robust density estimates across large spatial scales.

The lack of meaningful association between depression severity measures and neurocognitive performance.

BACKGROUND: Neurocognitive deficits are common in depression, but most prior studies have not found strong associations between standard measures of symptom severity and the extent of these neurocognitive deficits. Diagnostic heterogeneity, or the lack of specific questions about neurocognition in these measures, may be undermining these associations. METHOD: Neuropsychological performance was assessed via 10 tasks in a sample of 262 unmedicated patients with Major Depressive Disorder (MDD) and compared to that in healthy volunteers (n = 140), then correlated with (1) standard measures of depression severity including the Hamilton Depression Rating Scale and Beck Depression Inventory, (2) previously established, factor-analytically derived symptom factors that characterize the heterogeneity of these scales, and (3) a separate measure of cognitive complaint (Cognitive Failures Questionnaire) that was included to address the absence of specific questions about cognition in standard rating scales. RESULTS: Neurocognitive performance in these unmedicated MDD patients was not significantly associated with either total scores on the depression severity measures, any of their derived symptom factors, or the degree of subjective cognitive complaint - which itself was most strongly associated with mood disturbance. LIMITATIONS: Depressed patients with the most prominent neurovegetative symptoms may be underrepresented in this sample. CONCLUSIONS: Neurocognitive deficits were only weakly associated with standard depression symptom ratings, and not captured by self-report ratings of cognitive complaint. Neurocognitive deficits appear to be a separate symptom dimension that cannot be inferred from overall depression severity and require their own assessment, given that they have prognostic value for functional outcomes, suicide risk, and differential therapeutics.

Intravascular ultrasound and near-infrared spectroscopic features of coronary lesions with intraplaque haemorrhage.

AIMS: Intraplaque haemorrhage is considered a major contributor to lesion progression. We assessed coronary lesions with intraplaque haemorrhage using intravascular ultrasound (IVUS) and near-infrared spectroscopy (NIRS). METHODS AND RESULTS: We evaluated coronary arteries from autopsy hearts using 40MHz IVUS and NIRS and compared the imaging findings to histopathology. A total of 2324 2-mm long histological segments from 101 coronary arteries from 56 autopsy hearts were included. Intraplaque haemorrhage was found pathologically in 0.8% (18/2324) of segments. Segments with intraplaque haemorrhage had more fibroatheromas (FAs) with a greater IVUS plaque burden, a greater prevalence of IVUS echolucent zones, and a higher NIRS-lipid core burden index (LCBI) compared to segments without intraplaque haemorrhage (FAs: 72.2% vs. 18.3%, P < 0.0001; plaque burden: 59.7% [95% confidence interval: 55.5, 64.0] vs. 48.6% [45.8, 51.3], P < 0.0001; echolucent zones: 88.9% vs. 2.8%, P < 0.0001; NIRS-LCBI: 176 [88, 264] vs. 72 [53, 91], P = 0.02). The 16 IVUS superficial echolucent zones with intraplaque haemorrhage had more late FAs but shorter echolucent zone lengths (0.9 mm [0.7, 1.1] vs. 1.7 mm [1.5, 1.9], P < 0.0001) compared to 65 IVUS superficial echolucent zones without intraplaque haemorrhage. CONCLUSIONS: Intracoronary imaging features consistent with intraplaque haemorrhage included a greater plaque burden, a higher NIRS-LCBI, and a greater prevalence of IVUS echolucent zones compared to lesions without intraplaque haemorrhage.