Acceptance of diagnosis and management satisfaction of patients with "suspected Lyme borreliosis" after 12 months in a multidisciplinary reference center: a prospective cohort study.

INTRODUCTION: Because patients with a "suspicion of Lyme borreliosis (LB)" may experience medical wandering and difficult care paths, often due to misinformation, multidisciplinary care centers were started all over Europe a few years ago. The aim of our study was to prospectively identify the factors associated with the acceptance of diagnosis and management satisfaction of patients, and to assess the concordance of the medical health assessment between physicians and patients 12 months after their management at our multidisciplinary center. METHODS: We included all adults who were admitted to the Tick-Borne Diseases Reference Center of Paris and the Northern Region (TBD-RC) (2017-2020). A telephone satisfaction survey was conducted 12 months after their first consultation. It consisted of 5 domains and 13 items rated between 0 (lowest) and 10 (highest grade): (1)Reception; (2)Care and quality of management; (3)Information/explanations given to the patients; (4)Current medical condition and acceptance of the final diagnosis; (5)Overall appreciation. Factors associated with diagnosis acceptance and management satisfaction at 12 months were identified using logistic regression models. The concordance of the health status as assessed by doctors and patients was calculated using a Cohen's kappa test. RESULTS: Of the 569 patients who consulted, 349 (61.3%) answered the questionnaire. Overall appreciation had a median rating of 9 [8;10] and 280/349 (80.2%) accepted their diagnoses. Patients who were "very satisfied" with their care paths at TBD-RC (OR = 4.64;CI95%[1.52-14.16]) had higher odds of diagnosis acceptance. Well-delivered information was strongly associated with better satisfaction with the management (OR = 23.39;CI95%[3.52-155.54]). The concordance between patients and physicians to assess their health status 12 months after their management at TBD-RC was almost perfect in the groups of those with confirmed and possible LB (κ = 0.99), and moderate in the group with other diagnoses (κ = 0.43). CONCLUSION: Patients seemed to approve of this multidisciplinary care organization for suspected LB. It helped them to accept their final diagnoses and enabled a high level of satisfaction with the information given by the doctors, confirming the importance of shared medical decisions, which may help to reduce health misinformation. This type of structure may be useful for any disease with a complex and controversial diagnosis.

Comparison between different approaches to evaluate fibrous cap thickness in sequential optical coherence tomography studies.

BACKGROUND: In this in-vivo human study we tested the reproducibility for optical coherence tomography (OCT) assessment of lumen area (LA) and plaque components measurements, such as lipid arc extension and fibrous cap thickness (FCt). METHODS: We tested the variability of LA, lipid arc and FCt assessments in two repeated OCT pullbacks from the same diseased coronary segment matched using fiduciary anatomical landmarks. In particular, for the reliability of minimal FCt measurement we compared four different approaches based on continuous (longitudinal) or segmental (spot) individuation of smaller thickness: 1) comparison of single minimal FCt individuated alongside all plaque extension in the two pullbacks (Longitudinal (L)-spot minimal FCt value); 2) comparison of the mean FCt values of the plaque in the two pullbacks (L-plot mean FCt value); 3) comparison between the single minimal FCt value obtained in the first pullback and the single FCt obtained in the matched CS of second pullback (L-spot CS matched FCt value); 4) comparison of measurements obtained by visual selection of CS with minimal FCt s in the two pullbacks (single-spot minimal FCt value). RESULTS: From the paired analyses of 20 non culprit lesions (accounting for a total of 387 matched CS), we found a suboptimal in-segment correlation for LA (Intra-Class Coefficient [ICC] 0.731), but a good in-segment correlation for lipid arc (ICC 0.963). Regarding FCt measurement, a high reproducibility was obtained applying continuous assessment; in particular, the best correlation was observed with L-spot minimal FCt value and the L-plot mean FCt (ICC 0.893 and 0.952, respectively) with small inter-pullback differences (confidence intervals less than 0.04 mm). CONCLUSIONS: In this methodological study we observed a good reproducibility for quantitative plaque measurements with OCT confirming its reliability for serial assessment. In particular, longitudinal measurement in multiple adjacent frames seems to be the more accurate and reproducible approach for sequential FCt assessment.

Optical coherence tomography-derived lipid core burden index and clinical outcomes: results from the CLIMA registry.

AIMS: The aim of this study was to assess the morphological characteristics and prognostic implications of the optical coherence tomography (OCT)-derived lipid core burden index (LCBI). METHODS AND RESULTS: OCT-LCBI was assessed in 1003 patients with 1-year follow-up from the CLIMA multicentre registry using a validated software able to automatically obtain a maximum OCT-LCBI in 4 mm (maxOCT-LCBI4mm). Primary composite clinical endpoint included cardiac death, myocardial infarction, and target-vessel revascularization. A secondary analysis using clinical outcomes of CLIMA study was performed. Patients with a maxOCT-LCBI4mm ≥ 400 showed higher prevalence of fibrous cap thickness (FCT) <75 µm [odds ratio (OR) 1.43, 95% confidence interval (CI) 1.03-1.99; P = 0.034], lipid pool arc >180° (OR 3.93, 95%CI 2.97-5.21; P < 0.001), minimum lumen area <3.5 mm2 (OR 1.5, 95%CI 1.16-1.94; P = 0.002), macrophage infiltration (OR 2.38, 95%CI 1.81-3.13; P < 0.001), and intra-plaque intimal vasculature (OR 1.34, 95%CI 1.05-1.72; P = 0.021). A maxOCT-LCBI4mm ≥400 predicted the primary endpoint [adjusted hazard ratio (HR) 1.86, 95%CI 1.1-3.2; P = 0.019] as well as the CLIMA endpoint (HR 2.56, 95%CI 1.24-5.29; P = 0.011). Patients with high lipid content and thin FCT < 75 µm were at higher risk for adverse events (HR 4.88, 95%CI 2.44-9.72; P < 0.001). CONCLUSIONS: A high maxOCT-LCBI4mm was related to poor outcome and vulnerable plaque features. This study represents a step further in the automated assessment of the coronary plaque risk profile.

Sex-specific features of optical coherence tomography detected plaque vulnerability related to clinical outcomes: insights from the CLIMA study.

PURPOSE: To investigate the different impact of optical coherence tomography (OCT)-derived vulnerable plaque features on future adverse events (AEs) according to the biological sex. METHODS: The prospective multicenter CLIMA study (ClinicalTrials.gov: NCT02883088) enrolled 1003 patients with OCT plaque analysis of non-treated coronary plaques located in the proximal left anterior descending artery. Sex-specific differences in plaque composition and vulnerable features were described. We investigated the incidence of AEs, including cardiac death, any myocardial infarction and target vessel revascularization at 1-year. RESULTS: Among 1003 patients, 24.6% were women. Women were older and more frequently affected by chronic kidney disease. Dyslipidemia, prior MI and smoking habit were more common in men. At OCT analysis, women had shorter plaque length (p < 0.001), ticker fibrous cap (p = 0.001), smaller maximum lipid arc (p = 0.019), lower macrophage infiltration (p < 0.001) and intra-plaque layered tissue (p = 0.007). During follow-up, 65 AEs were registered. The presence of a thin fibrous cap and a large macrophage infiltration (> 67°) predicted AEs in both sexes. The presence of macrophages (HR 3.38, p = 0.018) and a small minimum lumen area (HR 4.97, p = 0.002) were associated with AEs in women but not in men, while a large lipid arc (> 180°) was associated with AEs in men (HR 2.56, p = 0.003) but not in women. CONCLUSION: This subanalysis of the CLIMA study investigated for the first-time sex-specific OCT features of plaque vulnerability associated with AEs. Local inflammation was associated with AEs in women and a large lipid arc was predictive in men. OCT may help develop sex-specific risk stratification strategies.

Definition of Optimal Optical Coherence Tomography-Based Stent Expansion Criteria: In-Stent Minimum Lumen Area Versus Residual Stent Underexpansion.

BACKGROUND: The mismatch between in-stent minimum lumen area (sMLA) and reference vessel lumen area, defined as stent underexpansion (SU), could be an important determinant of stent failure. We tested the clinical predictive value of absolute sMLA in comparison to relative SU in the context of the CLI-OPCI (Centro Per La Lotta Contro L'Infarto-Optimisation of Percutaneous Coronary Intervention) project registry. METHODS: We retrospectively analyzed end procedural optical coherence tomography findings in 1211 patients (1422 lesions) undergoing percutaneous coronary intervention, assessing the prevalence and magnitude of residual SU and exploring correlation with outcome in comparison with sMLA. RESULTS: In our series, both sMLA and SU were related to vessel size and anatomic lesion complexity. When compared with patients without adverse event at follow-up, those experiencing device-oriented cardiovascular events (composite of cardiac death, target vessel myocardial infarction, target lesion revascularization, and stent thrombosis) showed a lower sMLA (5.6±2.1 versus 6.1±2.1 mm2; P=0.011) but a comparable degree of SU (11.6±14.1% versus 11.2±13.3%; P=0.734). The prespecified cutoff value of sMLA <4.5 mm2, documented in 23.8% of cases, was confirmed as independent outcome predictor for device-oriented cardiovascular events (hazard ratio [HR], 2.05 [95% CI, 1.5-2.9]) including target lesion revascularization (HR, 2.43 [95% CI, 1.7-3.5]) and stent thrombosis (HR, 3.23 [95% CI, 1.7-6.3]). A residual SU of 10%, 20%, and 30% was observed in 38.0%, 18.2%, and 7.6% of cases, respectively. No grade of residual SU significantly increased the risk of stent failure, unless if an SU >20% was associated with an sMLA <4.5 mm2 (HR, 3.11 [95% CI, 1.7-5.6]). Finally, an association between stent overexpansion (ie, >110%) and device-oriented cardiovascular events was also observed (HR, 1.60 [95% CI, 1.1-2.3]). CONCLUSIONS: Final absolute sMLA and not relative SU was associated with an increased risk of stent failure. A variable grade of SU was common, but it resulted in being clinically relevant only when associated with an sMLA <4.5 mm2.

The Role of the Association Between Serum C-Reactive Protein Levels and Coronary Plaque Macrophage Accumulation in Predicting Clinical Events - Results from the CLIMA Registry.

The present investigation aims to study the interaction between systemic and intra-plaque inflammation in predicting cardiac events. We investigated C-reactive protein (CRP) levels as well as plaque inflammation with optical coherence tomography (OCT)-detected macrophages in the CLIMA study. 689 patients had admission CRP serum values reported, and high CRP values were defined as ≥ 2 mg/dl. The main study endpoint was a composite of cardiac death, myocardial infarction, and/or target vessel revascularization at 1-year follow-up. At multivariate Cox regression analysis, a large (hazard ratio [HR] 2.27, 95% confidence interval [CI] 1.2-4.3; p = 0.013) and superficial (HR 2.78, 95%CI 1.5-5.1; p = 0.001) macrophage arc was predicted of the main composite endpoint in patients with high CRP levels. Patients with large/superficial macrophage accumulation and low CRP levels were not at higher risk of adverse events. The presence of high CRP levels and large/superficial macrophage accumulation at OCT analysis identified patients at higher risk of clinical events.

Multidisciplinary Management of Suspected Lyme Borreliosis: Clinical Features of 569 Patients, and Factors Associated with Recovery at 3 and 12 Months, a Prospective Cohort Study.

Introduction. Because patients with a suspicion of Lyme borreliosis (LB) may have experienced difficult care paths, the Tick-Borne Diseases Reference Center (TBD-RC) was started in 2017. The aim of our study was to compare the clinical features of patients according to their final diagnoses, and to determine the factors associated with recovery in the context of multidisciplinary management for suspected LB. Methods. We included all adult patients who were seen at the TBD-RC (2017-2020). Four groups were defined: (i) confirmed LB, (ii) possible LB, (iii) Post-Treatment Lyme Disease Syndrome (PTLDS) or sequelae, and (iv) other diagnoses. Their clinical evolution at 3, 6, and 9-12 months after care was compared. Factors associated with recovery at 3 and at 9-12 months were identified using logistic regression models. Results. Among the 569 patients who consulted, 72 (12.6%) had confirmed LB, 43 (7.6%) possible LB, 58 (10.2%) PTLDS/sequelae, and 396 (69.2%) another diagnosis. A favorable evolution was observed in 389/569 (68.4%) at three months and in 459/569 (80.7%) at 12 months, independent of the final diagnosis. A longer delay between the first symptoms and the first consultation at the TBD-RC (p = 0.001), the multiplicity of the diagnoses (p = 0.004), and the inappropriate prescription of long-term antibiotic therapy (p = 0.023) were negatively associated with recovery, reflecting serial misdiagnoses. Conclusions. A multidisciplinary team dedicated to suspicion of LB may achieve a more precise diagnosis and better patient-centered medical support in the adapted clinical sector with a shorter delay, enabling clinical improvement and avoiding inappropriate antimicrobial prescription.

Relationship betweeen the amount and location of macrophages and clinical outcome: subanalysis of the CLIMA-study.

BACKGROUND: The ability of optical coherence tomography (OCT) to recognize intraplaque macrophage infiltration is now well acknowledged. This post-hoc analysis of the CLIMA study aimed to address the clinical impact of the circumferential extension of OCT-defined macrophages and their location at one year follow-up. METHODS: The multicentre CLIMA study enrolled 1003 patients undergoing OCT evaluation of the untreated proximal left anterior descending (LAD) coronary artery. Measurements of circumferential extension of macrophages and measurements of the distance from intima-lumen contour to macrophages string were performed at the plaque cross-section judged as containing the greatest amount of macrophages. The main study endpoint was a composite of cardiac death, myocardial infarction (MI) and/or target vessel revascularization (TVR). RESULTS: Patients with large macrophage arc (p = 0.001) and superficial macrophage arc (p < 0.001) showed a higher one-year incidence of the main one-year composite endpoint. Consistently hypertension (p = 0.018), family history of CAD (p = 0.046), diabetes mellitus (p = 0.036), lower ejection fraction (p = 0.009) and chronic kidney disease (p = 0.019) were more frequently found in patients experiencing the main composite endpoint. At multivariate Cox regression analysis, fibrous cap thickness < 75 µm (HR 2.51, 95% 1.46-4.32), presence of large (HR 1.97, 95%CI 1.16-3.35, p = 0.012) and superficial (HR 1.72, 95%CI 1.02-2.90; p = 0.040) macrophage arc remained independent predictors of the main composite endpoint. Large macrophage arc was associated with target LAD related MI. CONCLUSION: The present post-hoc analysis of the CLIMA showed that the circumferential extension of macrophages and their location are related to a composite endpoint of cardiac death, MI and/or TVR.

Perceptions, Representations, and Experiences of Patients Presenting Nonspecific Symptoms in the Context of Suspected Lyme Borreliosis.

BACKGROUND: Some subjective symptoms may be reported at all stages of Lyme borreliosis (LB) and may persist for several months after treatment. Nonspecific symptoms without any objective manifestation of LB are sometimes attributed by patients to a possible tick bite. The aim of our study was to explore the perceptions, representations, and experiences that these patients had of their disease and care paths. METHODS: We performed a qualitative study through individual interviews (October 2017-May 2018), based on grounded theory, following the COREQ checklist. A balanced sample of patients with diverse profiles was recruited at consultations with general practitioners and infectious disease physicians. RESULTS: Twelve patients were interviewed. Data saturation was reached at the twelfth interview. For codes, 293 were identified, and classified into 5 themes: (1) the experience of disabling nonspecific symptoms, especially pain, causing confusion and fear, (2) long and difficult care paths for the majority of the patients, experienced as an obstacle course, (3) a break with the previous state of health, causing a negative impact on every sphere of the patient's life, (4) empowerment of the patients and the self-management of their disease, and (5) the strong expression of a desire for change, with better listening, greater recognition of the symptoms, and simpler care paths. CONCLUSIONS: This study allows for the understanding of a patient's behaviours and the obstacles encountered, the way they are perceived, and the necessary solutions. The patients' expectations identified here could help physicians better understand the doctor-patient relationship in these complex management situations, which would reduce the burden of the disease. The current development of specialised reference centres could help meet the patients' demands and those of family physicians.

Adoption of a new automated optical coherence tomography software to obtain a lipid plaque spread-out plot.

PURPOSE: Near infrared spectroscopy-Intravascular ultrasound (NIRS-IVUS) provide a fully automated Lipid Core Burden Index (LCBI). Optical coherence tomography (OCT) is potentially capable of measuring lipid longitudinal extension in a dedicated two-dimensional LCBI spread-out plot. The present study has been designed to validate an automated approach to assess OCT images, able of providing a dedicated LCBI spread-out plot. METHODS: We compared results obtained with conventional (manual) OCT, with those obtained with a novel automated OCT algorithm and with NIRS-IVUS in consecutive 40 patients. Our goal was to calculate the lipid core longitudinal extension in a dedicated two-dimensional LCBI spread-out plot. Three groups were identified according to the studied lesions: (1) culprit lesions in ACS patients (n = 16), (2) non-culprit lesions in ACS patients (n = 12) and (3) lesions in stable patients (n = 12). OCT (either manual and automated) and NIRS-IVUS assessment showed for culprit ACS plaques a more complex anatomy. RESULTS: A strong trend for increased LCBI was found in the culprit ACS group, regardless of the adopted imaging modality (either NIRS-IVUS or automated OCT). A fair correlation was obtained for the maximum 4 mm LCBI measured by NIRS-IVUS and automated OCT (r = 0.75). The sensitivity and specificity of automated OCT to detect significant LCBI (> 400) were 90.5 and 84.2 respectively. CONCLUSION: We developed an OCT automated approach that can provide a dedicated lipid plaque spread-out plot to address plaque vulnerability. The automated OCT software can promote and improve OCT clinical applications for the identification of patients at risk of hard events.

Prevalence and quantitative assessment of macrophages in coronary plaques.

Although optical coherence tomography (OCT) proved to be able to identify macrophage clusters, there are no available data on the possibility to obtain reproducible measurements of their circumferential extension and location. The purpose of the present post-hoc analysis of the CLIMA study was to revise the clinical and demographic variables of patients having coronary plaques with macrophages and to investigate the reproducibility of their quantitative assessment. A total of 577 patients out of 1003 undergoing OCT showed macrophage accumulation. Three groups were identified; group 1 (426 patients) without macrophages, group 2 (296) patients with low macrophage content (less than median value [67°] of circumferential arc) and group 3 (281) with high macrophage content arc [> 67°]. Patients with macrophages (groups 2 and 3) showed a higher prevalence of family history for coronary artery disease and hypercholesterolemia and had a significantly larger body mass index. Furthermore, group 3 had more commonly triple vessel disease and higher value of LDL cholesterol levels compared to the two other groups. The inter-observer agreement for macrophage interpretation was good: R values were 0.97 for the circumferential arc extension, 0.95 for the minimum distance and 0.98 for the mean distance. A non-significant correlation between circumferential extension of macrophages and hsCRP values was found (R = 0.013). Quantitative assessment of macrophage accumulations can be obtained with high reproducibility by OCT. The presence and amount of macrophages are poorly correlated with hsCRP and identify patients with more advanced atherosclerosis and higher LDL cholesterol levels.

Optical coherence tomography assessment of macrophages accumulation in non-ST-segment elevation acute coronary syndromes.

AIMS: To investigate in patients with non-ST-segment elevation acute coronary syndrome (NSTE-ACS) the prevalence and the features of optical coherence tomography (OCT)-detected macrophages accumulation in culprit plaques as compared with nonculprit plaques (NCP). METHODS: The study is a post-hoc analysis of a prospective study aimed at evaluating the relationship between aortic inflammation as assessed by F-fluorodeoxyglucose-PET and features of coronary plaque vulnerability as assessed by OCT. We enrolled 32 patients with first NSTE-ACS who successfully underwent three-vessel OCT. RESULTS: The median age was 65 (54-72) years and 27 patients (84%) were men. Culprit plaques were clinically defined. Overall, the rate of lipid plaques and lipid plaques containing macrophages were 6.4 and 4.2 per patient, respectively. Culprit plaques had a smaller minimal luminal area, a higher extension of lipid component and a thinner fibrous cap than NCPs. Macrophages accumulations were more likely found in culprit plaque (84 vs. 61%, P = 0.015) in which they had also a higher circumferential extension. On univariable analysis, macrophages accumulation extension had a higher association with culprit plaques (odds ratio = 4.42; 95% confidence interval; 2.54-9.15, P < 0.001) than the mere presence of macrophages accumulation (odds ratio = 3.36; 95% confidence interval; 1.30-8.66, P = 0.012). Culprit plaques with thrombus had a lower distance between macrophages accumulation and the luminal surface than culprit plaque with no thrombus (0.06 vs. 0.1 mm; P = 0.04). CONCLUSION: In patients with NSTE-ACS, macrophages accumulations are more likely present in culprit plaque in which they disclose also a greater extension compared with those observed in NCP. The distance between macrophages accumulation and the luminal surface is lower in thrombotic culprit plaque than that in nonthrombotic culprit plaque.

Coronary inflammation: why searching, how to identify and treat it.

Inflammation plays an important role in the development of atherosclerotic lesions. A variety of stimuli promote atherosclerosis, including increased LDL cholesterol in blood, exposure to tobacco, diabetes mellitus, hypertension, or rheological stress. Inflammatory cells have an established role in the growth of atherosclerotic lesions. Macrophages recognize and internalise ox-LDL to eventually become lipid-laden foam cells, the hallmark cellular component of atheroma. Infiltrating CD4-T cells have a role too, by interacting with ox-LDL and other antigens. Cytokines secreted by inflammatory cells stimulate smooth muscle cells migration whilst macrophages produce metalloprotease that lead to fibrous cap rupture. The necrotic debris of died macrophages and smooth muscle cells help to continue the inflammatory process. The inflammatory response can also directly activate platelets and promote thrombus formation at the surface of complicated coronary plaques. The CANTOS trial can be waived as an innovative study promoting a novel approach of personalized medicine. In patients with previous myocardial infarction, high-sensitivity C-reactive protein level of 2 mg and normal LDL level (<70 mg/dL), canakinumab a therapeutic monoclonal antibody targeting interleukin-1ß, at a dose of 150 mg every 3 months, led to a significant reduction of the primary efficacy end point: nonfatal myocardial infarction, nonfatal stroke, or cardiovascular death at 48 months. Based on the CANTOS results, patients on statins and residual inflammatory risk as assessed by means of a high-sensitivity CRP >2 mg/l at baseline have a high risk of future cardiac events, comparable to that of statin-treated patients with suboptimal cholesterol LDL level. The inhibition of interleukin-1ß by means of canakinumab, which is only one of many potential anti-inflammatory pathways, open new perspectives, showing that a selective inhibition of the inflammatory pathway may be beneficial in reducing cardiovascular risk. In a process of personalized medicine, there is need to accurately identify patients at high risk of events, to be treated with potent statins or anti-inflammatory drugs. Perhaps in the near future a more specific assessment of coronary inflammations, possibly obtained with imaging modalities (either invasive or non-invasive), will better select patients at risk of events. In this scenario, in the setting of secondary prevention, OCT may serve the scope of identifying vulnerable plaques with local aggregates of inflammatory cells. Future studies are needed to understand the clinical effectiveness of strategies based on invasive coronary assessment.

Clinical outcomes of calcified nodules detected by optical coherence tomography: a sub-analysis of the CLIMA study.

AIMS: The goal of the present post hoc analysis of the CLIMA registry was to establish the relationship between calcified nodules (CNs) with (CND) or without (CNWD) disruption of the superficial intimal fibrous layer and one-year occurrence of target lesion myocardial infarction (MI) and/or cardiac death. METHODS AND RESULTS: CND and CNWD were identified based on the presence or absence of superficial irregularities indicative of disruption of the intimal fibrous layer, with possible overlying local thrombus. In total, 222 CNs were found in the 1,776 non-culprit LAD plaques. CND had larger maximum calcific arc and smaller lumen area. Cardiac death and MI occurred in 20% of patients in the CND group versus 2.7% in the CNWD group and 3.3% in the group without CN (p<0.001). This figure was mainly due to the 13.3% incidence of cardiac death in the CND group versus 2.0% in the CNWD group and versus 2.2% in the group without CN (p<0.001). The presence of CND was confirmed as an independent predictor of events (HR 6.58, 95% CI: 2.7-15.8, p<0.001). CONCLUSIONS: The presence of CND was associated with a high one-year incidence of cardiac death and/or target lesion MI.

HYPNOTIZABILITY AND PAIN MODULATION: A Body-Mind Perspective.

The study investigated whether the cardiac activity and cognitive-emotional traits sustained by the behavioral inhibition/activation system (BIS/BAS) may contribute to hypnotizability-related pain modulation. Nociceptive stimulation (cold-pressor test) was administered to healthy participants with high (highs) and low (lows) hypnotizability in the presence and absence of suggestions for analgesia. Results showed that heart rate increased abruptly at the beginning of nociceptive stimulation in all participants. Then, only in highs heart rate decreased for the entire duration of hand immersion. During stimulation with suggestions of analgesia, pain threshold negatively correlated with heart rate. BIS/BAS activity partially accounted for the observed hypnotizability-related differences in the relation between cardiac interoception and pain experience.

Association between coronary atherosclerosis progression and in-stent neoatherosclerosis in patients with ST-elevation myocardial infarction at five-year follow-up.

AIMS: The aim of the study was to investigate the association between in-stent neoatherosclerosis (NA) and atherosclerosis progression (AP) in non-culprit segments in patients with ST-elevation myocardial infarction at five years. METHODS AND RESULTS: Sixty-two out of 169 consecutive patients included in the EXAMINATION study underwent optical coherence tomography (OCT) at five years. NA plaques were observed in 13 (21.0%), signal-rich bands (SRB) in 22 (35.5%) and AP in 11 (17.7%). NA plaques were more frequently observed in patients treated with two stents (53.8% vs. 20.4%; p=0.02). SRB were more frequently observed with longer stent length (29.8±11.6 vs. 22.5±9.1 mm; p<0.01), larger stent size (3.4±0.4 vs. 3.1±0.4 mm; p<0.01) and with bare metal stents (BMS) (68.2% vs. 40.0%; p=0.03). Patients with AP had higher levels of LDL-cholesterol (108.3±27.1 vs. 86.3±27.6 mg/dl; p=0.02). QCA of 744 non-culprit segments showed no association between NA plaques or SRB and reduction of lumen diameters. By multivariate analysis, NA plaques were associated with stent length; SRB were associated with stent length and BMS. AP was associated with mean LDL-cholesterol levels. CONCLUSIONS: NA and SRB had no association with AP or with LDL-cholesterol. NA and SRB were associated with stent-related factors such as stent length and BMS. AP was associated with LDL-cholesterol levels.

Unprotected Replication Forks Are Converted into Mitotic Sister Chromatid Bridges.

Replication stress and mitotic abnormalities are key features of cancer cells. Temporarily paused forks are stabilized by the intra-S phase checkpoint and protected by the association of Rad51, which prevents Mre11-dependent resection. However, if a fork becomes dysfunctional and cannot resume, this terminally arrested fork is rescued by a converging fork to avoid unreplicated parental DNA during mitosis. Alternatively, dysfunctional forks are restarted by homologous recombination. Using fission yeast, we report that Rad52 and the DNA binding activity of Rad51, but not its strand-exchange activity, act to protect terminally arrested forks from unrestrained Exo1-nucleolytic activity. In the absence of recombination proteins, large ssDNA gaps, up to 3 kb long, occur behind terminally arrested forks, preventing efficient fork merging and leading to mitotic sister chromatid bridging. Thus, Rad52 and Rad51 prevent temporarily and terminally arrested forks from degrading and, despite the availability of converging forks, converting to anaphase bridges causing aneuploidy and cell death.

Reproducibility of serial optical coherence tomography measurements for lumen area and plaque components in humans (The CLI-VAR [Centro per la Lotta Contro l'Infarto-variability] II study).

Frequency-domain optical coherence tomography (FD-OCT) is a promising intracoronary imaging technique to study atherosclerosis. Indeed, its unprecedented spatial resolution allows the assessment of fibrous cap thickness, lipid pool and features of plaque vulnerability. Aim of this study was to determine the reproducibility of the in vivo FD-OCT measurements of lumen area and plaque components in serial studies. Twenty-six patients undergoing FD-OCT assessment of intermediate lesion during coronary angiography were included in this study. FD-OCT pullbacks were acquired twice from the same coronary segment at interval of 5 min without additional intervention and analyzed off-line at an independent imaging core laboratory. Lumen diameter (LD), lumen area (LA), fibrous cap (FC) thickness and lipid pool (LP) arc extension measurements were compared in 440 matched frames. Both the per-segment and per-frame analyses showed excellent correlation coefficients for the inter-pullback comparisons for all parameters explored (R > 0.95 and p < 0.001 in all cases). Accordingly, the Bland-Altman estimates of bias showed non-significant differences in the inter-pullback comparisons at all levels. Per-frame analysis showed a slightly variations of LA in 45.8% of cases with changes greater than 2% likely related to different phases of cardiac cycle. Nevertheless, nor FC thickness or circumferential arc of LP were affected by LA changes during serial FD-OCT acquisition. This study showed an excellent reproducibility of lumen and plaque component measurements obtained with FD-OCT in vivo. Thus, this intracoronary imaging technique could be used to assess atherosclerosis progression and describe accurate plaque evolution in repeated serial studies.

Comparison between intermediate and severe coronary stenoses and clinical outcomes of an OCT-guided PCI strategy.

AIMS: We compared optical coherence tomography (OCT) features of intermediate and severe coronary stenoses in patients with stable angina and acute coronary syndrome (ACS), and tested the clinical impact of an OCT-based strategy for treating intermediate stenoses. METHODS: The study enrolled 135 consecutive patients with either ACS or stable angina and a single de-novo coronary stenosis. Patients were divided into two groups: intermediate stenosis defined as quantitative coronary angiography percentage narrowing less than 70%, or presence of angiographic vessel haziness and severe stenosis with percentage narrowing more than 70%. OCT was performed to assess features of plaque vulnerability and to measure the minimal lumen area. We also appraised the 12-month rate of major adverse event (MACE) of an OCT-guided strategy of percutaneous coronary intervention (PCI) based on the presence of thrombus and/or minimal lumen area less than 3.0 mm. RESULTS: Fifty-six patients had intermediate stenoses, whilst 79 had severe stenoses. In the 'intermediate stenosis group', patients with stable angina had a lower asymmetric index (P = 0.02) and a greater calcific arc (P = 0.0001). In the 'severe stenosis group', intermediate lesions of patients with ACS exhibited a greater lipid arc as compared with patients with stable angina (P = 0.03). A higher prevalence of thin cap fibroatheroma was seen in patients with ACS of both groups. The incidence of MACE was not significantly different between patients with an intermediate stenosis who received PCI vs. optimal medical therapy on the basis of OCT findings (P = 0.26). CONCLUSIONS: Intermediate coronary stenoses showed distinctive OCT-based features according to the initial clinical presentation. The adoption of an OCT-guided PCI strategy, based on the presence of coronary thrombus and significant vessel narrowing, led to encouraging results.

Randomized evaluation of intralesion versus intracoronary abciximab and aspiration thrombectomy in patients with ST-elevation myocardial infarction: The COCTAIL II trial.

BACKGROUND: Thrombus burden and distal embolization are predictive of no-reflow during primary percutaneous coronary intervention (PCI) in patients with acute ST-elevation myocardial infarction (STEMI). We sought to compare the efficacy of pharmacological and catheter-based strategies for thrombus in patients with STEMI and high atherothrombotic burden. METHODS: Between January 2012 and December 2013, 128 STEMI patients undergoing primary PCI at 5 centers were randomly assigned in a 2 × 2 factorial design to intracoronary (IC) abciximab bolus (via the guide catheter) versus intralesion (IL) abciximab bolus, each with versus without aspiration thrombectomy (AT). Study end points were residual intrastent atherothrombotic burden, defined as the number of cross-sections with residual tissue area >10% as assessed by optical coherence tomography, and indices of angiographic and myocardial reperfusion. RESULTS: Residual intrastent atherothrombotic burden did not significantly differ with IL versus IC abciximab (median [interquartile range] 6.0 [1-15] vs 6.0 [2-11], P = .806) and with AT versus no aspiration (6.0 [1-13] vs 6.0 [2-12], P = .775). Intralesion abciximab administration was associated with improved angiographic myocardial reperfusion in terms of thrombolysis in myocardial infarction (TIMI) flow (3 [3-3] vs 3 [2-3], P = .040), corrected TIMI frame count (12 ± 5 vs 17 ± 16, P = .021), and myocardial blush grade (3 [2-3] vs 3 [2-3], P = .035). In particular, IL abciximab was associated with higher occurrence of final TIMI 3 flow (90% vs 73.8%, P = .032) and myocardial blush grade 3 (71.6% vs 52.4%, P = .039). Conversely, AT had no significant effect on indices of angiographic or myocardial reperfusion. CONCLUSIONS: In patients with STEMI and high thrombotic burden, neither IL versus IC abciximab nor AT versus no aspiration reduced postprocedure intrastent atherothrombotic burden in patients with STEMI undergoing primary PCI. However, IL abciximab improved indices of angiographic and myocardial reperfusion compared to IC abciximab, benefits not apparent with AT.