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The reforming reactions of greenhouse gases require catalysts with high reactivity, coking resistance, and structural stability for efficient and durable use. Among the possible strategies, exsolution has been shown to demonstrate the requirements needed to produce appropriate catalysts for the dry reforming of methane, the conversion of which strongly depends on the choice of active species, its interaction with the support, and the catalyst size and dispersion properties. Here, we exploit the exsolution approach, known to produce stable and highly active nanoparticle-supported catalysts, to develop iridium-nanoparticle-decorated perovskites and apply them as catalysts for the dry reforming of methane. By studying the effect of several parameters, we tune the degree of exsolution, and consequently the catalytic activity, thereby identifying the most efficient sample, 0.5 atomic % Ir-BaTiO3, which showed 82% and 86% conversion of CO2 and CH4, respectively. By comparison with standard impregnated catalysts (e.g., Ir/Al2O3), we benchmark the activity and stability of our exsolved systems. We find almost identical conversion and syngas rates of formation but observe no carbon deposition for the exsolved samples after catalytic testing; such deposition was significant for the traditionally prepared impregnated Ir/Al2O3, with almost 30 mgC/gsample measured, compared to 0 mgC/gsample detected for the exsolved system. These findings highlight the possibility of achieving in a single step the mutual interaction of the parameters enhancing the catalytic efficiency, leading to a promising pathway for the design of catalysts for reforming reactions.
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Noninvasive detection of surface-enhanced Raman spectroscopy (SERS) signals from deep within tissue represents a common challenge in many biological and clinical applications including disease diagnosis and therapy monitoring. Such signals are typically weak and not readily discernible from often much larger Raman and fluorescence background signals (e.g., from surrounding tissue). Consequently, suboptimal sensitivity in the detection of SERS signals is often achieved in these situations. Similar issues can arise in SERS measurements in other diffusely scattering samples and complex matrices. Here, we propose a novel concept, active SERS, for the efficient retrieval of SERS signals from deep within complex matrices such as biological tissues that mitigates these issues. It relies on applying an external perturbation to the sample to alter the SERS signal from nanoparticles (NPs) deep inside the matrix. A measurement with and without, or before and after, such perturbation then can provide powerful contrasting data enabling an effective elimination of the matrix signals to reveal more clearly the desired SERS signal without the interfering background and associated artifacts. The concept is demonstrated using ultrasound (US) as an external source of perturbation and SERS NPs inserted deep within a heterogeneous tissue phantom mimicking a cluster of NPs accumulated within a small target lesion. The overall SERS signal intensity induced by the applied US perturbation decreased by â¼21% and the SERS signal contrast was considerably improved by eliminating subtraction artifacts present in a conventional measurement performed at a neighboring spatial location in a heterogeneous tissue sample. Although the technique was demonstrated with SERS gold NPs with a standard Raman label, it is envisaged that active SERS NPs (both the nanoscale metal geometry and Raman label) could be specifically designed to deliver an augmented response to the external stimulus to further enhance the achievable SERS signal contrast and yield even greater improvement in detection sensitivity. The method was demonstrated using transmission Raman spectroscopy; however, it is also applicable to other Raman implementations including spatially offset Raman spectroscopy and conventional Raman spectroscopy performed both at depth and at surfaces of complex matrices.
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Treatment of Charcot neuroarthropathy (CN) of the foot and ankle remains challenging for both patients and surgeons. Nonoperative treatment with cast/orthosis immobilization has long been the mainstay of treatment, but surgical intervention has gained interest to improve poor long-term outcomes. A review of existing data on the operative management of CN demonstrates the potential benefits but also the continued risks associated with treatment. Additionally, a retrospective review of cohorts managed with limited surgical interventions (wound debridements, exostectomies, and other surgical procedures) compared to reconstructive procedures provides additional insight into the surgical management of CN.
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Artropatia Neurogênica , Humanos , Artropatia Neurogênica/cirurgia , Resultado do Tratamento , Articulação do Tornozelo/cirurgia , Procedimentos Ortopédicos/métodosRESUMO
Acidification of the airway surface liquid in the respiratory system could play a role in the pathology of Cystic Fibrosis, but its low volume and proximity to the airway epithelium make it a challenging biological environment in which to noninvasively collect pH measurements. To address this challenge, we explored surface enhanced Raman scattering microsensors (SERS-MS), with a 4-mercaptobenzoic acid (MBA) pH reporter molecule, as pH sensors for the airway surface liquid of patient-derived in vitro models of the human airway. Using air-liquid interface (ALI) cultures to model the respiratory epithelium, we show that SERS-MS facilitates the optical measurement of trans-epithelial pH gradients between the airway surface liquid and the basolateral culture medium. SERS-MS also enabled the successful quantification of pH changes in the airway surface liquid following stimulation of the Cystic Fibrosis transmembrane conductance regulator (CFTR, the apical ion channel that is dysfunctional in Cystic Fibrosis airways). Finally, the influence of CFTR mutations on baseline airway surface liquid pH was explored by using SERS-MS to measure the pH in ALIs grown from Cystic Fibrosis and non-Cystic Fibrosis donors.
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Regulador de Condutância Transmembrana em Fibrose Cística , Fibrose Cística , Análise Espectral Raman , Humanos , Análise Espectral Raman/métodos , Concentração de Íons de Hidrogênio , Regulador de Condutância Transmembrana em Fibrose Cística/genética , Regulador de Condutância Transmembrana em Fibrose Cística/metabolismo , Compostos de Sulfidrila/química , Benzoatos/químicaRESUMO
SUMMARY: Tibiotalocalcaneal (TTC) arthrodesis is a treatment option for several pathologies of the ankle and hindfoot, including acute trauma, posttraumatic arthritis, and Charcot neuroarthropathy. Traditional fixation options for TTC arthrodesis include intramedullary hindfoot nailing or internal fixation with plates and/or screws. In certain patients, either due to poor bone quality, impaired sensation, or concern for noncompliance, more robust fixation may be desired. In such patients, we have used a hybrid plate-nail construct with promising results. This article and the accompanying video demonstrate our technique for TTC arthrodesis using a plate-nail construct and review treatment decisions involved with management of these complex cases.
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Tornozelo , Fixação Intramedular de Fraturas , Humanos , Articulação do Tornozelo/diagnóstico por imagem , Articulação do Tornozelo/cirurgia , Placas Ósseas , Artrodese/métodos , Pinos Ortopédicos , Estudos RetrospectivosRESUMO
Historically, animal numbers have most often been in the hundreds for experiments designed to estimate the dose reduction factor (DRF) of a radiation countermeasure treatment compared to a control treatment. Before 2010, researchers had to rely on previous experience, both from others and their own, to determine the number of animals needed for a DRF experiment. In 2010, a formal sample size formula was developed by Kodell et al. This theoretical work showed that sample sizes for realistic, yet hypothetical, DRF experiments could be less than a hundred animals and still have sufficient power to detect clinically meaningful DRF values. However, researchers have been slow to use the formula for their DRF experiments, whether from ignorance to its existence or hesitancy to depart from "tried and true" sample sizes. Here, we adapt the sample size formula to better fit usual DRF experiments, and, importantly, we provide real experimental evidence from two independent DRF experiments that sample sizes smaller than what have typically been used can still statistically detect clinically meaningful DRF values. In addition, we update a literature review of DRF experiments which can be used to inform future DRF experiments, provide answers to questions that researchers have asked when considering sample size calculations rather than solely relying on previous experience, whether their own or others', and, in the supplementary material, provide R code implementing the formula, along with several exercises to familiarize the user with the adapted formula.
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Tamanho da Amostra , Animais , Estudos de ViabilidadeRESUMO
BACKGROUND: Black patients presenting to the catheterization laboratory have more risk factors and worse long-term outcomes. This sub-analysis of the Lipid Rich Plaque (LRP) study quantifies the plaque burden and composition of Black vs White patients and associated outcomes. METHODS: Patients with a singular, self-reported race presenting for cardiac catheterization were enrolled if near-infrared spectroscopy/intravascular ultrasound (NIRS-IVUS) imaging of non-stented, non-culprit (NC) vessels was performed. Lipidic content was quantified at the 4-mm region with maximum Lipid Core Burden Index (maxLCBI4mm). NC major adverse cardiac events (NC-MACE) were defined as: cardiac death, cardiac arrest, non-fatal myocardial infarction, acute coronary syndrome, revascularization, and hospital readmission for angina with >20 % disease progression through 2 years. RESULTS: Among 1346 patients with a singular, self-reported race, 182 were Black. Black vs White patients were more likely to be female, had higher rates of traditional risk factors, and were more likely to present acutely. Both patients and segments were more likely to have maxLCBI4mm > 400 (46.7 % vs 30.6 %, p < 0.001, respectively; 15.5 % vs 8.9 %, p < 0.001, respectively). Vessel size and plaque burden were larger for Black vs White patients. At 2 years, maxLCBI4mm > 400 and Black race were independently predictive of NC-MACE (hazard ratio [HR] maxLCBI4mm > 400: 2.37 [95 % confidence interval (CI) 1.50-3.76, p < 0.001], Black race: 2.8 [95 % CI 1.27-3.42, p = 0.004], pinteraction = 0.137). CONCLUSIONS: Compared to White patients, Black patients had more lipid-rich plaques with greater plaque burden. Both high lipidic burden and Black race were independently predictive of NC-MACE within 2 years. CLINICAL TRIAL REGISTRATION: https://clinicaltrials.gov/ct2/show/NCT02033694, NCT02033694.
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Doença da Artéria Coronariana , Infarto do Miocárdio , Placa Aterosclerótica , Feminino , Humanos , Masculino , Angiografia Coronária/efeitos adversos , Doença da Artéria Coronariana/diagnóstico por imagem , Doença da Artéria Coronariana/terapia , Doença da Artéria Coronariana/complicações , Vasos Coronários/diagnóstico por imagem , Lipídeos , Infarto do Miocárdio/etiologia , Valor Preditivo dos Testes , Ultrassonografia de Intervenção/métodos , Negro ou Afro-Americano , BrancosRESUMO
In this work we demonstrate an advanced concept of a charge-shifting charge-coupled device (CCD) read-out combined with shifted excitation Raman difference spectroscopy (SERDS) capable of operating at up to 10â kHz acquisition rates for the effective mitigation of fast-evolving interfering backgrounds in Raman spectroscopy. This rate is 10-fold faster than that achievable with an instrument we described previously and is overall 1000-fold faster than possible with conventional spectroscopic CCDs capable of operating at up to â¼10 Hz rates. The speed enhancement was realized by incorporating a periodic mask at the internal slit of an imaging spectrometer permitting a smaller shift of the charge on the CCD (8 pixels) to be required during the cyclic shifting process compared with the earlier design which employed an 80-pixel shift. The higher acquisition speed enables the more accurate sampling of the two SERDS spectral channels, enabling it to effectively tackle highly challenging situations with rapidly evolving interfering fluorescence backgrounds. The performance of the instrument is evaluated for heterogeneous fluorescent samples which are moved rapidly in front of the detection system aiming at the differentiation of chemical species and their quantification. The performance of the system is compared with that of the earlier 1â kHz design and a conventional CCD operated at its maximum rate of 5.4 Hz as previously. In all situations tested, the newly developed 10â kHz system outperformed the earlier variants. The 10â kHz instrument can benefit a number of prospective applications including: disease diagnosis where high sensitivity mapping of complex biological matrices in the presence of natural fluorescence bleaching restricts achievable limits of detection; accurate data acquisition from moving heterogeneous samples (or moving a handheld instrument in front of the sample during data acquisition) or data acquisition under varying ambient light conditions (e.g., due to casting shadows, sample or instrument movement). Other beneficial scenarios include monitoring rapidly evolving Raman signals in the presence of largely static background signals such as in situations where a heterogeneous sample is moving rapidly in front of a detection system (e.g., a conveyor belt) in the presence of static ambient light.
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Análise Espectral Raman , Análise Espectral Raman/métodos , Espectrometria de Fluorescência/métodosRESUMO
Magnetoelastic sensors, which undergo mechanical resonance when interrogated with magnetic fields, can be functionalized to measure various physical quantities and chemical/biological analytes by tracking their resonance behaviors. The unique wireless and functionalizable nature of these sensors makes them good candidates for biological sensing applications, from the detection of specific bacteria to tracking force loading inside the human body. In this study, we evaluate the viability of magnetoelastic sensors based on a commercially available magnetoelastic material (Metglas 2826 MB) for wirelessly monitoring the attachment and growth of human mesenchymal stromal cells (hMSCs) in 2D in vitro cell culture. The results indicate that the changes in sensor resonance are linearly correlated with cell quantity. Experiments using a custom-built monitoring system also demonstrated the ability of this technology to collect temporal profiles of cell growth, which could elucidate key stages of cell proliferation based on acute features in the profile. Additionally, there was no observed change in the morphology of cells after they were subjected to magnetic and mechanical stimuli from the monitoring system, indicating that this method for tracking cell growth may have minimal impact on cell quality and potency.
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Células-Tronco Mesenquimais , Humanos , Proliferação de Células , Técnicas de Cultura de Células , Cultura , Campos MagnéticosRESUMO
Patient derived organoids have the potential to improve the physiological relevance of in vitro disease models. However, the 3D architecture of these self-assembled cellular structures makes probing their biochemistry more complex than in traditional 2D culture. We explore the application of surface enhanced Raman scattering microsensors (SERS-MS) to probe local pH gradients within patient derived airway organoid cultures. SERS-MS consist of solid polymer cores decorated with surface immobilised gold nanoparticles which are functionalised with pH sensitive reporter molecule 4-mercaptobenzoic acid (MBA). We demonstrate that by mixing SERS-MS into the extracellular matrix (ECM) of airway organoid cultures the probes can be engulfed by expanding organoids and report on local pH in the organoid lumen and ECM.
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Ouro , Nanopartículas Metálicas , Humanos , Ouro/química , Nanopartículas Metálicas/química , Células-Tronco , Organoides/metabolismo , Matriz Extracelular , Análise Espectral Raman , Concentração de Íons de HidrogênioRESUMO
As the topotactic synthetic precursor of the ubiquitous functional semiconductor anatase TiO2, ammonium fluoroxotitanates, such as NH4TiOF3 and (NH4)2TiOF4, have received lots of research interest as synthetic precursors. However, few of the existing studies focus on their properties and possible applications on their own. To fill this gap, both NH4TiOF3 and (NH4)2TiOF4 were studied in this work experimentally by material characterization and computationally via DFT calculations. Electronic structures of both materials from experimental and computational perspectives were mutually supportive. Based on these, immobilised NH4TiOF3 was preliminarily tested as a UV photocatalyst for dye degradation. Reasonable photocatalytic activities were observed.
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Total knee arthroplasty (TKA) results in substantial improvement for most patients with end-stage arthritis of the knee; however, approximately 20% of patients have an unsatisfactory result. Although many problems contributing to an unsatisfactory result after TKA are best addressed by revision TKA, some problems may be effectively addressed with arthroscopic treatment. The categories of pathology that can be addressed arthroscopically include peripatellar soft-tissue impingement (patellar clunk syndrome and patellar synovial hyperplasia), arthrofibrosis, and popliteus tendon dysfunction. Recognizing these disease entities and the role of arthroscopic surgery in the treatment of these lesions may be helpful in achieving a good outcome in certain patients who are unsatisfied with their knee arthroplasty.
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Artroplastia do Joelho , Artropatias , Humanos , Artroscopia/métodos , Articulação do Joelho , Artroplastia do Joelho/efeitos adversos , Artropatias/etiologia , Patela/cirurgiaRESUMO
We present a deep proteogenomic profiling study of 87 lung adenocarcinoma (LUAD) tumors from the United States, integrating whole-genome sequencing, transcriptome sequencing, proteomics and phosphoproteomics by mass spectrometry, and reverse-phase protein arrays. We identify three subtypes from somatic genome signature analysis, including a transition-high subtype enriched with never smokers, a transversion-high subtype enriched with current smokers, and a structurally altered subtype enriched with former smokers, TP53 alterations, and genome-wide structural alterations. We show that within-tumor correlations of RNA and protein expression associate with tumor purity and immune cell profiles. We detect and independently validate expression signatures of RNA and protein that predict patient survival. Additionally, among co-measured genes, we found that protein expression is more often associated with patient survival than RNA. Finally, integrative analysis characterizes three expression subtypes with divergent mutations, proteomic regulatory networks, and therapeutic vulnerabilities. This proteogenomic characterization provides a foundation for molecularly informed medicine in LUAD.
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Adenocarcinoma de Pulmão , Neoplasias Pulmonares , Proteogenômica , Humanos , Proteômica , Adenocarcinoma de Pulmão/genética , Neoplasias Pulmonares/genética , RNA/uso terapêuticoRESUMO
Metal-organic frameworks (MOFs) with ratiometric sensing properties are desirable for many applications due to their intrinsic self-calibration. We report the re-assessment of the sensing properties of a MOF, originally reported as containing europium(III) and 2-hydroxyterephtalic acid, and having fluorescent ratiometric iron(III) sensing properties. Synchrotron single-crystal X-ray diffraction and proton nuclear magnetic resonance (1H NMR) spectroscopy revealed that the MOF is composed of 2-methoxyterephthalate, not 2-hydroxyterephthalate as originally reported. We found that the MOF exhibits a sensor turn-off response towards Fe3+ ion concentrations in the range 0.5-3.7 ppm (band 425 nm), and a turn-on response towards a decrease of pH from 5.4 to 3.0 (band 375 nm), both resulting from the addition of acidic Fe3+ salt solution to a MOF suspension. Thus, the ratiometric sensing properties and the originally proposed mechanism no longer apply; our work reveals a dynamic quenching mechanism for the fluorescence turn-off response due to the presence of Fe3+ ions, and a ligand protonation mechanism for the turn-on response to a decrease in pH. Our work highlights the importance of a thorough investigation of the structure of any newly synthesized MOF, and, in the case of potential sensors, their selectivity and any environmental effects on their sensing behavior.
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Estruturas Metalorgânicas , Európio/química , Compostos Férricos , Concentração de Íons de Hidrogênio , Íons , Estruturas Metalorgânicas/químicaRESUMO
Background: The Lipid Rich Plaque (LRP) study demonstrated that near-infrared spectroscopy imaging of non-obstructive lesions identified patients and segments at higher risk for subsequent non-culprit major adverse cardiac events (NC-MACE). Whether this is true for both men and women is not known. In this post hoc analysis of the LRP study, we sought to investigate whether the maximum 4-mm Lipid Core Burden Index (maxLCBI4mm) was of similar predictive value in men and women for NC-MACE. Methods: Patients with an evaluable maxLCBI4mm were stratified on the basis of sex at birth. A Cox proportional-hazards model was used to assess the predictive value of maxLCBI4mm on future NC-MACE at the patient and plaque levels. The primary endpoint was cumulative incidence of NC-MACE at 24 months. Results: Among 1271 patients, 388 (30.5%) were women. Women were older and had a higher cardiovascular risk profile. Cumulative incidence of NC-MACE at 24 months was 10.3% for women and 7.6% for men (log-rank p = 0.11). When comparing maxLCBI4mm > 400 to maxLCBI4mm ≤ 400, the hazard ratio (HR) for future NC-MACE was not significantly different between sexes: 2.10 (95% confidence interval [CI]: 1.28-3.44; p = 0.003) for men and 2.24 (95% CI: 1.18-4.28; p = 0.014) for women (p = 0.87). At the plaque level, the HR comparing maxLCBI4mm > 400 to maxLCBI4mm ≤ 400 was 3.49 (95% CI: 1.60-7.60, p = 0.002) for men and 4.79 (95% CI: 2.02-11.38, p < 0.001) for women, which was not significantly different (p = 0.57). Conclusions: The maxLCBI4mm was of similar predictive value for NC-MACE within 24 months in men and women.
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Magnetoelastic sensors, typically made of magnetostrictive and magnetically-soft materials, can be fabricated from commercially available materials into a variety of shapes and sizes for their intended applications. Since these sensors are wirelessly interrogated via magnetic fields, they are good candidates for use in both research and industry, where detection of environmental parameters in closed and controlled systems is necessary. Common applications for these sensors include the investigation of physical, chemical, and biological parameters based on changes in mass loading at the sensor surface which affect the sensor's behavior at resonance. To improve the performance of these sensors, optimization of sensor geometry, size, and detection conditions are critical to increasing their mass sensitivity and detectible range. This work focuses on investigating how the geometry of the sensor influences its resonance spectrum, including the sensor's shape, size, and aspect ratio. In addition to these factors, heterogeneity in resonance magnitude was mapped for the sensor surface and the effect of the magnetic bias field strength on the resonance spectrum was investigated. Analysis of the results indicates that the shape of the sensor has a strong influence on the emergent resonant modes. Reducing the size of the sensor decreased the sensor's magnitude of resonance. The aspect ratio of the sensor, along with the bias field strength, was also observed to affect the magnitude of the signal; over or under biasing and aspect ratio extremes were observed to decrease the magnitude of resonance, indicating that these parameters can be optimized for a given shape and size of magnetoelastic sensor.
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Técnicas BiossensoriaisRESUMO
BACKGROUND/PURPOSE: The Lipid Rich Plaque (LRP) study demonstrated the association between coronary plaque lipid content and outcomes. In this LRP substudy, we assessed the impact of optimal medical therapy (OMT) on the occurrence of non-culprit major adverse cardiac events (NC-MACE). Advanced intracoronary imaging modalities are able to identify patients with vulnerable coronary lesion morphology associated with future events. METHODS/MATERIALS: A total of 1270 patients who underwent cardiac catheterization for suspected coronary artery disease (CAD) with evaluable maxLCBI4mm in non-culprit vessels and known medical therapy after discharge were followed for 2 years. OMT was defined as the use of a statin and dual antiplatelet therapy (DAPT). RESULTS: Among the 1270 patients included in this substudy, 1110 (87.7%) had PCI for an index event, and 1014 (80%) patients received OMT. Estimated cumulative incidence functions of NC-MACE did not differ significantly between patients treated with or without OMT (log-rank p-value = 0.876). In patients labeled high risk (maxLCBI4mm > 400), cumulative incidence function also did not differ between patients treated with vs without OMT (log-rank p-value = 0.19). CONCLUSIONS: In the current LRP analysis, we could not identify a beneficial effect of OMT in the reduction of NC-MACE rate, even in patients with high-risk plaques, during 24-month follow-up.
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Doença da Artéria Coronariana , Inibidores de Hidroximetilglutaril-CoA Redutases , Intervenção Coronária Percutânea , Placa Aterosclerótica , Doença da Artéria Coronariana/complicações , Doença da Artéria Coronariana/diagnóstico por imagem , Doença da Artéria Coronariana/terapia , Humanos , Inibidores de Hidroximetilglutaril-CoA Redutases/efeitos adversos , Lipídeos , Intervenção Coronária Percutânea/efeitos adversos , Intervenção Coronária Percutânea/métodos , Placa Aterosclerótica/patologia , Inibidores da Agregação Plaquetária/efeitos adversos , Resultado do TratamentoRESUMO
AIMS: The left anterior descending (LAD) artery is the most frequently affected site by coronary artery disease. The prospective Lipid Rich Plaque (LRP) study, which enrolled patients undergoing imaging of non-culprits followed over 2 years, reported the successful identification of coronary segments at risk of future events based on near-infrared spectroscopy-intravascular ultrasound (NIRS-IVUS) lipid signals. We aimed to characterize the plaque events involving the LAD vs. non-LAD segments. METHODS AND RESULTS: LRP enrolled 1563 patients from 2014 to 2016. All adjudicated plaque events defined by the composite of cardiac death, cardiac arrest, non-fatal myocardial infarction, acute coronary syndrome, revascularization by coronary bypass or percutaneous coronary intervention, and rehospitalization for angina with >20% stenosis progression and reported as non-culprit lesion-related major adverse cardiac events (NC-MACE) were classified by NIRS-IVUS maxLCBI4 mm (maximum 4-mm Lipid Core Burden Index) ≤400 or >400 and association with high-risk-plaque characteristics, plaque burden ≥70%, and minimum lumen area (MLA) ≤4 mm2. Fifty-seven events were recorded with more lipid-rich plaques in the LAD vs. left circumflex and right coronary artery; 12.5% vs. 10.4% vs. 11.3%, P = 0.097. Unequivocally, a maxLCBI4 mm >400 in the LAD was more predictive of NC-MACE [hazard ratio (HR) 4.32, 95% confidence interval (CI) (1.93-9.69); P = 0.0004] vs. [HR 2.56, 95% CI (1.06-6.17); P = 0.0354] in non-LAD segments. MLA ≤4 mm2 within the maxLCBI4 mm was significantly higher in the LAD (34.1% vs. 25.9% vs. 13.7%, P < 0.001). CONCLUSION: Non-culprit lipid-rich segments in the LAD were more frequently associated with plaque-level events. LAD NIRS-IVUS screening may help identify patients requiring intensive surveillance and medical treatment.
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Doença da Artéria Coronariana , Placa Aterosclerótica , Angiografia Coronária , Doença da Artéria Coronariana/complicações , Doença da Artéria Coronariana/diagnóstico por imagem , Doença da Artéria Coronariana/terapia , Vasos Coronários/diagnóstico por imagem , Humanos , Lipídeos , Placa Aterosclerótica/complicações , Estudos Prospectivos , Ultrassonografia de Intervenção/métodosRESUMO
AIMS: Diabetes mellitus (DM) is associated with increased cardiovascular morbidity and mortality. The multicentre, prospective Lipid-Rich Plaque trial (LRP) examined non-culprit (NC) non-obstructive coronary segments with a combined near-infrared spectroscopy (NIRS)-intravascular ultrasound (IVUS) catheter. This study assessed the differences in NC plaque characteristics and their influence on major adverse cardiac events (MACE) in diabetic and non-diabetic patients. METHODS AND RESULTS: Patients with known DM status were divided into no diabetes, diabetes not treated with insulin (non-ITDM), and insulin-treated diabetes (ITDM). The association between presence and type of DM and NC-MACE was assessed at both the patient and coronary segment levels by Cox proportional regression modelling. Out of 1552 patients enrolled, 1266 who had their diabetes status recorded were followed through 24 months. Female sex, hypertension, chronic kidney disease, peripheral vascular disease, and high body mass index were significantly more frequent in diabetic patients. The ITDM group had more diseased vessels, at least one NC segment with a maxLCBI4 mm ≥400 in 46.2% of patients, and maxLCBI4 mm ≥400 in nearly one out of six Ware segments (15.2%, 125/824 segments). The average maxLCBI4 mm significantly increased from non-diabetic patients (NoDM) to non-insulin-treated diabetic patients (non-ITDM) to insulin-treated diabetic patients (ITDM; 137.7 ± 161.9, 154.8 ± 173.6, 182.9 ± 193.2, P < 0.001, respectively). In patients assigned to follow-up (692 ± 129 days), ITDM doubled the incidence of NC-MACE compared with the absence of diabetes (15.7% vs. 6.9%, P = 0.0008). The presence of maxLCBI4 mm>400 further increased the NC-MACE rate to 21.6% (Kaplan-Meier estimate). CONCLUSION: Cholesterol-rich NC plaques detected by NIRS-IVUS were significantly more frequent in diabetic patients, especially those who were insulin-treated, and were associated with an increased NC-MACE during follow-up.