RESUMEN

Immunotherapy represents an emergent and heterogeneous group of anticancer treatments harnessing the human immune-surveillance system, including immune-checkpoint inhibitor monoclonal antibodies (mAbs), Chimeric Antigen Receptor T Cells (CAR-T) therapy, cancer vaccines and lymphocyte activation gene-3 (LAG-3) therapy. While remarkably effective against several malignancies, these therapies, often in combination with other cancer treatments, have showed unforeseen toxicity, including cardiovascular complications. The occurrence of immuno-mediated adverse (irAEs) events has been progressively reported in the last 10 years. These irAEs present an extended range of severity, from self-limiting to life-threatening conditions. Although recent guidelines in CardioOncology have provided important evidence in managing cancer treatments, they often encompass general approaches. However, a specific focus is required due to the particular etiology, unique risk factors, and associated side effects of immunotherapy. This review aims to deepen the understanding of the prevalence and nature of cardiovascular issues in patients undergoing immunotherapy, offering insights into strategies for risk stratification and management.

RESUMEN

We demonstrate subrecoil Sisyphus cooling using the long-lived ^{3}P_{0} clock state in alkaline-earth-like ytterbium. A 1388-nm optical standing wave nearly resonant with the ^{3}P_{0}→^{3}D_{1} transition creates a spatially periodic light shift of the ^{3}P_{0} clock state. Following excitation on the ultranarrow clock transition, we observe Sisyphus cooling in this potential, as the light shift is correlated with excitation to ^{3}D_{1} and subsequent spontaneous decay to the ^{1}S_{0} ground state. We observe that cooling enhances the loading efficiency of atoms into a 759-nm magic-wavelength one-dimensional (1D) optical lattice, as compared to standard Doppler cooling on the ^{1}S_{0}→^{3}P_{1} transition. Sisyphus cooling yields temperatures below 200 nK in the weakly confined, transverse dimensions of the 1D optical lattice. These lower temperatures improve optical lattice clocks by facilitating the use of shallow lattices with reduced light shifts while retaining large atom numbers to reduce the quantum projection noise. This Sisyphus cooling can be pulsed or continuous and is applicable to a range of quantum metrology applications.

RESUMEN

PURPOSE: To investigate the effects of the elemental composition and the manufacturing process of cobalt chromium-molybdenum (CoCr-Mo), cobalt chromium-tungsten (CoCr-W), and CoCr-Mo-W alloys on metal-ceramic bond strength. MATERIALS AND METHODS: Six CoCr-based alloys were included in this study, a were classified into three different groups depending on their elemental composition (Ν = 10, for each group). The first group had molybdenum (Mo) as the third alloying element, the second group contained tungsten (W) (without Mo), and the third group included both alloying elements. The groups were further divided by the manufacturing process (casting or selective laser melting, SLM). Interfacial analysis was carried out using backscattered electron imaging (BEI) and energy-dispersive X-ray microanalysis (EDX) operating in line scan mode. The metal-ceramic bond strength was tested by a 3-point bending test according to the ISO 9693 requirements. The fracture mode of all specimens was examined under a stereomicroscope. The bond strength results were statistically analyzed by 2-way ANOVA and Tukey's multiple comparison post hoc test (a = 0.05). RESULTS: A continuous interface with the porcelain was found without pores, debonding areas, or other defects. Of the major elements found at the interface, Co showed the highest diffusion rate, while titanium (Ti) had the lowest diffusion rate. No statistically significant differences were identified in metal-ceramic bond strength either among materials or between manufacturing processes. The fracture mode was found to be cohesive for all specimens. CONCLUSIONS: The metal-ceramic bond strength is independent of the current CoCr alloy type and manufacturing process when comparing conventional casting and SLM. Interfacial analysis revealed no differences between the tested groups.

RESUMEN

Purpose: The aim of this study was to compare the efficacies levels of four cleaning solutions for removing debris from rotary Nickel-Titanium (Ni-Ti) endodontic instruments. Materials and methods: Twelve instruments that fractured during ex vivo instrumentation were used. Fractured surfaces were investigated by SEM before and after 3, 6 and 9 min of ultrasonic cleaning in 17 % EDTA.3NaOH (Group A), 2.5 % NaOCl (Group B), Dentasept 3H Rapide (Group C) and ZymeX™ (Group D) solutions. EDS analyses of selected files from all four groups of untreated and ultrasonically cleaned samples were performed to assess the elemental composition of the alloy surfaces. Results: SEM analysis revealed that after 9 min of ultrasonic agitation, all four investigated solutions had cleaned fractured surfaces. However, some low-atomic-number regions exhibited random distributions on the fractured surfaces. EDS analyses indicated that only C was retained on surface after 9 min of ultrasonic cleaning. This finding was common in all tested groups. Conclusions: All four investigated solutions substantially removed debris from the surfaces of the Ni-Ti files and were considered appropriate for clinical practice.

RESUMEN

This study aimed to investigate the differences in Religiosity (R), Mental Immunity (MI), and Psychological Well-Being (PWB) in patients with diabetes due to gender and age group variables, and to detect the best predictors of PWB in diabetic patients within the Bayesian framework. The study was conducted from May 2022 to February 2023 on a random sample of 186 Saudis diagnosed with diabetes. After obtaining participants' consent, they completed three R, MI, and PWB scales. Bayesian Independent Samples t-test was performed to identify differences, and Bayesian linear regression analysis was used to reveal the best prediction model of PWB. The results of the Bayesian independent samples t-test indicated strong evidence supporting the alternative hypothesis H1, suggesting differences between male and female diabetic patients in R, MI, and PWB, with Bayesian factor values exceeding 10 (8.338×10+23, 1.762×10+25, and 1.866×10+24), and Cohen's δ of (-1.866, -1.934, -1.884). These results indicated that females with diabetes have higher means of R, MI, and PWB compared to males. However, the results also suggested evidence for the null hypothesis H0 of no differences in R, MI, and PWB among diabetic patients due to age group, with Bayesian factor values (0.176, 0.181, and 0.187) less than 1.00 and small Cohen's δ of (-0.034, -0.050, -0.063). Bayesian linear regression analysis detected strong evidence that the model including MI is the best predictive model (BF10 for mental immunity is 1.00 and for the other two models are 0.07 and 4.249×10-16) for the PWB of diabetic patients, however, there is no evidence that the model including R or the interaction between R and MI is the best predictor of PWB for diabetic patients. These findings highlight the need for direct psychological care services for male diabetic patients and the urgent need to enhance IM in diabetic patients to improve their PWB. Furthermore, results recommended that healthcare providers in Saudi Arabia integrate MI interventions into diabetes care programs.

Asunto(s)

RESUMEN

BACKGROUND: Complete revascularization is associated with improved outcomes in patients with myocardial infarction and multivessel coronary artery disease. Quantitative flow ratio (QFR) represents an emerging angiography-based tool for functional lesion assessment. The present study investigated the prognostic impact of QFR-consistent complete revascularization in patients with myocardial infarction and multivessel disease. METHODS: A total of 792 patients with myocardial infarction and multivessel disease were enrolled in the analysis. Post-hoc QFR analyses of 1,320 nonculprit vessels were performed by investigators blinded to clinical outcomes. The primary endpoint was a composite of all-cause death, nonculprit vessel related nonfatal myocardial infarction, and ischemia-driven revascularization at 2 years after index myocardial infarction. Patients were stratified into a QFR-consistent PCI group (n = 646) and a QFR-inconsistent PCI group (n = 146), based on whether the intervention was congruent with the QFR-determined functional significance of the nonculprit lesions. RESULTS: The primary endpoint occurred in a total of 22 patients (3.4%) in the QFR-consistent PCI group and in 27 patients (18.5%) in the QFR-inconsistent group (HR 0.17, 95% CI 0.10-0.30, P < .001).The difference in the primary endpoint was driven by reduced rates of nonfatal myocardial infarction (2.0% vs. 15.1%; HR 0.13, 95% CI 0.06-0.25; P < .001) and ischemia-driven revascularization (1.2% vs. 5.5%; HR 0.21, 95% CI 0.08-0.57; P = .001) in the QFR-consistent PCI group. CONCLUSIONS: Among patients with myocardial infarction and multivessel disease, a QFR-consistent complete revascularization was associated with a reduced risk of all-cause mortality, nonfatal myocardial infarction, and ischemia-driven revascularization. These findings underline the value of angiography-based functional lesion assessment for personalized revascularization strategies.

Asunto(s)

RESUMEN

STATEMENT OF PROBLEM: Three Co-Cr alloy types (Co-Cr-Mo, Co-Cr-W, and Co-Cr-Mo-W) have been commonly used in the fabrication of dental prostheses. These alloys can be manufactured using either conventional casting or selective laser melting (SLM) techniques. Nevertheless, research that directly compares these materials and/or manufacturing processes in terms of their microstructural and mechanical characteristics is sparse. PURPOSE: The purpose of this in vitro study was to conduct microstructural and mechanical analysis via X-ray interpretation, optical microscopy, scanning electron microscopy/energy dispersive X-ray spectroscopy (SEM/EDS), image analysis, X-ray diffraction (XRD), instrumented indentation testing (IIT), and 3-point bending testing to characterize Co-Cr-Mo, Co-Cr-W, and Co-Cr-Mo-W alloys produced through conventional casting and SLM. MATERIAL AND METHODS: Six Co-Cr-based alloys were analyzed and divided into 3 types based on their elemental composition (Co-Cr-Mo, Co-Cr-W, and Co-Cr-Mo-W). Additionally, each group was categorized based on the manufacturing process used (casting or SLM). X-ray scans were used to assess porosity. The microstructures of the specimens were assessed through SEM/EDS examination and XRD analysis. IIT was used to determine the Martens hardness (HM) and elastic index (ηIT), while the elastic modulus (E) was estimated through the 3-point bending test. The mechanical properties were statistically analyzed using 2-way analysis of variance (ANOVA) and the Tukey multiple comparison post hoc test, with alloy type and manufacturing process as discriminating variables (α=.05). RESULTS: All cast groups exhibited gross porosity, while no pores or other flaws were found in the SLM groups. Based on the XRD results, the crystalline structure of all Co-Cr specimens consisted of the face-centered cubic γ phase (γ-fcc), along with the hexagonal close-packed ε phase (ε-hcp) and Cr23C6 carbide. Different microstructures were identified between the cast and SLM alloys. Significant differences were identified for the mean standard deviation HM (ranging from 2601 ±94 N/mm2 to 3633 ±61 N/mm2) and mean ±standard deviation ηIT (ranging from 16.8 ±0.3% to 20.9 ±0.3%) among alloys prepared by the same manufacturing process, while all SLM alloys had statistically higher HM and ηIT results than their cast counterparts (P<.05). No statistically significant differences were identified for the mean ±standard deviation Eb (ranging from 170 ±25 GPa to 244 ±36 GPa) among the groups prepared with the same manufacturing process (P>.05), but the SLM alloys had significantly higher results (P<.05) than the cast alloys. CONCLUSIONS: In general, the manufacturing procedure significantly affected the porosity, microstructure, and mechanical properties of the tested Co-Cr alloys. SLM decreased the internal porosity, provided a uniform microstructure, and improved the mechanical properties for all the tested alloy types.

Asunto(s)

RESUMEN

The Late Cretaceous was a time of high eustatic sea level that enabled extensive epicontinental seaways and carbonate platforms across the Tethyan Realm, providing favorable habitats for oyster communities to flourish. This study focuses on the Campanian Tethyan oysters from the North Eastern Desert of Egypt regarding taxonomy, palaeoecology, and palaeobiogeography. Three oyster species, Nicaisolopha nicaisei (Coquand, 1862), Pycnodonte (Phygraea) vesicularis (Lamarck, 1806), and Ambigostrea bretoni (Thomas and Peron, 1891), were identified from the Campanian succession in two studied sections. The sampled specimens of the genus Nicaisolopha have undergone a systematic palaeontological revision. As a result, N. tissoti (Thomas and Peron, 1891) is considered herein a junior synonym of N. nicaisei (Coquand, 1862). Palaeobiogeographically, the likely primary migration pattern of the studied oysters suggests an east-west trend along the Southern Tethys margin. All identified oysters in this study exhibit a Tethyan affinity and are primarily abundant in two main provinces: the Southern Tethys and the Western Tethys. The macrofaunal contents are categorized into two fossil associations: the Nicaisolopha nicaisei association of the middle-late Campanian age and the Pycnodonte vesicularis association of the late Campanian age. These macrofaunal associations indicate a deepening trend during the middle-late Campanian age, suggesting a transition from shallow inner neritic to middle neritic environments. Additionally, it is observed that Pycnodonteinae tend to grow larger under eutrophic conditions, low-energy environments, and nutrient-rich waters with high carbonate contents.

Asunto(s)

RESUMEN

Recent advances in phase-retrieval-based x-ray imaging methods have demonstrated the ability to reconstruct 3D distortion vector fields within a nanocrystal by using coherent diffraction information from multiple crystal Bragg reflections. However, these works do not provide a solution to the challenges encountered in imaging lattice distortions in crystals with significant defect content that result in phase wrapping. Moreover, these methods only apply to isolated crystals smaller than the x-ray illumination, and therefore cannot be used for imaging of distortions in extended crystals. We introduce multi-peak Bragg ptychography which addresses both challenges via an optimization framework that combines stochastic gradient descent and phase unwrapping methods for robust image reconstruction of lattice distortions and defects in extended crystals. Our work uses modern automatic differentiation toolsets so that the method is easy to extend to other settings and easy to implement in high-performance computers. This work is particularly timely given the broad interest in using the increased coherent flux in fourth-generation synchrotrons for innovative material research.

RESUMEN

Purpose: This study aimed to perform a thorough failure analysis of two fractured narrow dental implants after medium-term in vivo use. Materials and methods: The top parts of two fractured Narrow Dental Implant (NDI) fixtures were retrieved from two different locations at two different times from the same patient. The NDI-specimen-1 was 12-months in service while the NDI-specimen-2 was 17-months in service. In both cases, the top parts of the fractured NDI fixtures that were attached to prosthetic components were retrieved and subjected to thorough, non-destructive and destructive testing. Results: Light Microscopy (LM) and Scanning Electron Microscopy (SEM) revealed that both the retrieved fractured NDIs failed because of fatigue, characterized by beach and ratchet marks. Macroscopic examination revealed that fatigue cracks initiated at the internal thread surfaces of the implants and propagated around them until final fracture. Both samples fractured near the end of the retaining screw and followed the root of the internal thread. Optical and SEM analyses revealed a uniform distribution of irregularly shaped grains (diameter = 2 to 5 µm). X -ray Energy Dispersive Spectroscopy (EDS) analysis showed that the NDI-specimen-1 was made using Ti-14%Zr with a Vickers Hardens (HV) of 288 ± 5. Conclusion: Since the fracture occurred by a fatigue; thus, an increase in fatigue resistance will be beneficial for the longevity of NDI.

RESUMEN

OBJECTIVE: To evaluate the effects of metal primer II (MP II) on the shear bond strength (SBS) of orthodontic brackets bonded to teeth and bis-acryl composite provisional material (Bis-Acryl). MATERIAL AND METHODS: Twenty extracted human premolars specimens and 20 premolar shaped Bis-Acryl specimens were obtained and randomly divided into two surface groups. The first group consisted of human premolars (T) bonded to brackets in the conventional way while in the second (T-MP) MP II was applied on the bracket base before bonding. Similarly, one group of provisional material (PM) was prepared according to conventional treatment and another with the application of MP-II metal bonder (PM-MP). In all cases Ortho-brackets (Victory Series, 3 M) were bonded employing Transbond XT resin cement. Then the brackets were debonded under shear and the results were statistically analyzed by two-way analysis of variance and Holm Sidak at α = .05. The debonded surfaces of all specimens were examined by light microscopy and the Adhesive Remnant Index (ARI) was recorded. RESULTS: The SBS results exhibited significant differences er (p < .001). For both the T and TM the application of MP-II increased the SBS compared to respective control groups (p < .001). The T-C group was found inferior compared to PM-C (p < .001) and the same is true for the comparison between T-MP and PM-MP (p < .001). ARI indexes demonstrated that the tooth groups were characterized by a predominantly adhesive failure at the resin-dentin interface. In contrast, the control group for provisional crowns (PM-C) showed a predominantly cohesive failure mode, which moved to predominantly adhesive after the application of MP II. CONCLUSION: The application of MP II enhances the SBS on both, human enamel and provisional crown materials.

Asunto(s)

RESUMEN

"Full moon" is a central calcification that occludes the entire vessel on coronary computed tomography angiography (CCTA). We examined the association of full moon calcification as identified by CCTA, on clinical and procedural outcomes of chronic total occlusion (CTO) percutaneous coronary intervention (PCI). We studied patients who underwent elective CTO-PCI in 2 European centers and had preprocedural CCTA. The primary end point was the inability to cross the lesion and/or the need for extensive debulking techniques. Secondary end points were procedural success, in-hospital cardiac mortality, the need for extensive debulking techniques, myocardial infarction, major adverse cardiac events (defined as in-hospital death, myocardial infarction, and clinically driven target vessel revascularization), and stent thrombosis. Secondary procedural end points included procedural time, fluoroscopy time, number of guidewires and balloons, stent length, number and diameter, and contrast volume. Multivariable logistic regression analysis was performed, identifying potential covariates related to the primary outcome according to knowledge and previous studies. Subsequently, a stepwise selection approach was performed to select factors with the greatest predictive value. Of 140 patients included, 28 (20%) had a full moon calcified CTO plaque. Patients in the full moon group were older and had more cardiovascular risk factors. There was not significant difference in the need for retrograde approach and anterograde dissection and reentry techniques between the full moon group and the other groups (32.1% vs 37.5%, p = 0.59 and 0% vs 1.7%, p = 0.47, respectively). Patients in the full moon group had greater incidence of the primary outcome than did those who did not have full moon morphology (53.5% vs 12.5%, p <0.001). On multivariable analysis that included chronic kidney failure and previous coronary artery bypass surgery, full moon calcification was associated with greater incidence of the primary end point (odds ratio 6.5, 95% confidence interval 2.1 to 20.5, p = 0.001). Moreover, less procedural success (71.4% vs 87.5%, p = 0.03), greater incidence of coronary perforations (14.2% vs 3.5%, p <0.02), and greater procedural (172.5 [118.0 to 237.5] vs 144.0 [108.50 to 174.75], p = 0.02) and fluoroscopic time (62.6 [38.1 to 83.0] vs 42.8 [29.5 to 65.7], p = 0.03) were observed in the full moon group. Overall major adverse cardiac events did not differ between the 2 groups (1 patient in the full moon group vs 1 patient in the non-full moon group; 3.5% vs 0.8%, p = 0.29). In conclusion, full moon calcification on CCTA was independently associated with procedural complexity and adverse outcomes in CTO-PCI.

Asunto(s)

RESUMEN

AIMS: A thorough characterization of the relationship between elevated lipoprotein(a) [Lp(a)] and coronary artery disease (CAD) is lacking. This study aimed to quantitatively assess the association of increasing Lp(a) levels and CAD severity in a real-world population. METHODS AND RESULTS: This non-interventional, cross-sectional, LipidCardio study included patients aged ≥21 years undergoing angiography (October 2016-March 2018) at a tertiary cardiology centre, who have at least one Lp(a) measurement. The association between Lp(a) and CAD severity was determined by synergy between PCI with taxus and cardiac surgery (SYNTAX)-I and Gensini scores and angiographic characteristics. Overall, 975 patients (mean age: 69.5 years) were included; 70.1% were male, 97.5% had Caucasian ancestry, and 33.2% had a family history of premature atherosclerotic cardiovascular disease. Median baseline Lp(a) level was 19.3 nmol/L. Patients were stratified by baseline Lp(a): 72.9% had < 65 nmol/L, 21.0% had ≥100 nmol/L, 17.2% had ≥125 nmol/L, and 12.9% had ≥150 nmol/L. Compared with the normal (Lp(a) < 65 nmol/L) group, elevated Lp(a) groups (e.g. ≥ 150 nmol/L) had a higher proportion of patients with prior CAD (48.4% vs. 62.7%; P < 0.01), prior coronary revascularization (39.1% vs. 51.6%; P = 0.01), prior coronary artery bypass graft (6.0% vs. 15.1%; P < 0.01), vessel(s) with lesions (68.5% vs. 81.3%; P = 0.03), diffusely narrowed vessels (10.9% vs. 16.5%; P = 0.01) or chronic total occlusion lesions (14.3% vs. 25.2%; P < 0.01), and higher median SYNTAX-I (3.0 vs. 5.5; P = 0.01) and Gensini (10.0 vs. 16.0; P < 0.01) scores. CONCLUSION: Elevated Lp(a) was associated with a more severe presentation of CAD. Awareness of Lp(a) levels in patients with CAD may have implications in their clinical management.

Patients with coronary artery disease (CAD) suffer with progressive plaque buildup in the walls of coronary blood vessels, which restricts blood flow and may result in serious cardiovascular outcomes such as chest pain (angina) and heart attacks (myocardial infarction). In this study, we assessed whether elevated levels of lipoprotein(a) [Lp(a)­a lipoprotein found in blood] are associated with more severe illness. We observed that elevated Lp(a) was associated with a higher proportion of patients with prior CAD, prior interventions on coronary blood vessels, and more diseased blood vessels. These collectively form what is considered a 'severe' clinical presentation of CAD, meaning a greater likelihood of adverse clinical outcomes.

Asunto(s)

RESUMEN

An 80-year-old post-coronary artery bypass graft (CABG) patient had an acute coronary syndrome with non-ST-segment elevation myocardial infarction (ACS-NSTE) with saphenous vein graft (SVG)-obtuse marginal stenosis. High-definition intravascular ultrasound revealed an underexpanded SVG stent with a hyperechoic structure. Optical coherence tomography confirmed surgical clip causing compression, resolved by post-dilation. This case underscores ACS-NSTE complexity post-CABG and the critical role of coronary imaging in optimizing interventions by addressing surgical clip-induced compression.

RESUMEN

Melanoma, a highly invasive type of skin cancer that penetrates the entire dermis layer, is associated with increased mortality rates. Excessive exposure of the skin to sunlight, specifically ultraviolet radiation, is the underlying cause of this malignant condition. The appearance of unique skin moles represents a visible clue, referred to as the "ugly duckling" sign, indicating the presence of melanoma and its association with cellular DNA damage. This research aims to explore potential biomarkers derived from microarray data, employing bioinformatics techniques and methodologies, for a thorough investigation of melanoma skin cancer. The microarray dataset for melanoma skin cancer was obtained from the GEO database, and thorough data analysis and quality control measures were performed to identify differentially expressed genes (DEGs). The top 14 highly expressed DEGs were identified, and their gene information and protein sequences were retrieved from the NCBI gene and protein database. These proteins were further analyzed for domain identification and network analysis. Gene expression analysis was conducted to visualize the upregulated and downregulated genes. Additionally, gene metabolite network analysis was carried out to understand the interactions between highly interconnected genes and regulatory transcripts. Molecular docking was employed to investigate the ligand-binding sites and visualize the three-dimensional structure of proteins. Our research unveiled a collection of genes with varying expression levels, some elevated and others reduced, which could function as promising biomarkers closely linked to the development and advancement of melanoma skin cancer. Through molecular docking analysis of the GINS2 protein, we identified two natural compounds (PubChem-156021169 and PubChem-60700) with potential as inhibitors against melanoma. This research has implications for early detection, treatment, and understanding the molecular basis of melanoma.

Asunto(s)

RESUMEN

AIMS: Coronary microevaginations (CMEs) represent an outward bulge of coronary plaques and have been introduced as a sign of adverse vascular remodelling following coronary device implantation. However, their role in atherosclerosis and plaque destabilization in the absence of coronary intervention is unknown. This study aimed to investigate CME as a novel feature of plaque vulnerability and to characterize its associated inflammatory cell-vessel-wall interactions. METHODS AND RESULTS: A total of 557 patients from the translational OPTICO-ACS study programme underwent optical coherence tomography imaging of the culprit vessel and simultaneous immunophenotyping of the culprit lesion (CL). Two hundred and fifty-eight CLs had a ruptured fibrous cap (RFC) and one hundred had intact fibrous cap (IFC) acute coronary syndrome (ACS) as an underlying pathophysiology. CMEs were significantly more frequent in CL when compared with non-CL (25 vs. 4%, P < 0.001) and were more frequently observed in lesions with IFC-ACS when compared with RFC-ACS (55.0 vs. 12.7%, P < 0.001). CMEs were particularly prevalent in IFC-ACS-causing CLs independent of a coronary bifurcation (IFC-ICB) when compared with IFC-ACS with an association to a coronary bifurcation (IFC-ACB, 65.4 vs. 43.7%, P = 0.030). CME emerged as the strongest independent predictor of IFC-ICB (relative risk 3.36, 95% confidence interval 1.67-6.76, P = 0.001) by multivariable regression analysis. IFC-ICB demonstrated an enrichment of monocytes in both culprit blood analysis (culprit ratio: 1.1 ± 0.2 vs. 0.9 ± 0.2, P = 0.048) and aspirated culprit thrombi (326 ± 162 vs. 96 ± 87 cells/mm2, P = 0.017), while IFC-ACB confirmed the accumulation of CD4+ T cells, as recently described. CONCLUSION: This study provides novel evidence for a pathophysiological involvement of CME in the development of IFC-ACS and provides first evidence for a distinct pathophysiological pathway for IFC-ICB, driven by CME-derived flow disturbances and inflammatory activation involving the innate immune system. TRIAL REGISTRATION: Registration of the study at clinicalTrials.gov (NCT03129503).

Asunto(s)

RESUMEN

BACKGROUND: Cholesterol crystals (CCs) represent a feature of advanced atherosclerotic plaque and may be assessed by optical coherence tomography (OCT). Their impact on cardiovascular outcomes in patients presenting with acute coronary syndromes (ACS) is yet unknown. METHODS: The culprit lesion (CL) of 346 ACS-patients undergoing preintervention OCT imaging were screened for the presence of CCs and divided into two groups accordingly. The primary end-point was the rate of major adverse cardiac events plus (MACE+) consisting of cardiac death, myocardial infarction, target vessel revascularization and re-hospitalization due to unstable or progressive angina at two years. RESULTS: Among 346 patients, 57.2% presented with CCs at the CL. Patients with CCs exhibited a higher prevalence of ruptured fibrous caps (RFC-ACS) (79.8% vs. 56.8%; p < 0.001) and other high-risk features such as thin cap fibroatheroma (80.8% vs. 64.9%; p = 0.001), presence of macrophages (99.0% vs. 85.1%; p < 0.001) as well as a greater maximum lipid arc (294.0° vs. 259.3°; p < 0.001) at the CL as compared to patients without CCs. MACE+ at two years follow-up occurred more often in CC-patients (29.2% vs. 16.1%; p = 0.006) as compared to patients without CCs at the culprit site. Multivariable cox regression analysis identified CCs as independent predictor of MACE+ (HR 1.705; 1.025-2.838 CI, p = 0.040). CONCLUSIONS: CCs were associated with conventional high-risk plaque features and associated with increased MACE+-rates at two years follow up. The identification of CCs might be useful as prognostic marker in patients with ACS and assist "precision prevention" in the future.

Asunto(s)

RESUMEN

BACKGROUND AND AIMS: Spotty calcium deposits (SCD) represent a vulnerable plaque feature which seems to result - as based on recent invitro studies - from inflammatory vessel-wall interactions. SCD can be reliably assessed by optical coherence tomography (OCT). Their prognostic impact is yet unknown. Therefore, the aims of this translational study were to comprehensively characterize different plaque calcification patterns, to analyze the associated inflammatory mechanisms in the microenvironment of acute coronary syndrome (ACS)-causing culprit lesions (CL) and to investigate the prognostic significance of SCD in a large cohort of ACS-patients. METHODS: CL of the first 155 consecutive ACS-patients from the translational OPTICO-ACS-study program were investigated by OCT-characterization of the calcium phenotype at ACS-causing culprit lesions. Simultaneous immunophenotyping by flow-cytometric analysis and cytokine bead array technique across the CL gradient (ratio local/systemic levels) was performed and incidental major adverse cardiovascular events plus (MACE+) at 12 months after ACS were assessed. RESULTS: SCD were observed within 45.2% of all analyzed ACS-causing culprit lesions (CL). Culprits containing spotty calcium were characterized by an increased culprit ratio of innate effector cytokines interleukin (IL)-8 [2.04 (1.24) vs. 1.37 (1.10) p < 0.05], as well as TNF (tumor necrosis factor)-α [1.17 (0.93) vs. 1.06 (0.89); p < 0.05)] and an increased ratio of circulating neutrophils [0.96 (0.85) vs. 0.91 (0.77); p < 0.05] as compared to culprit plaques without SCD. Total monocyte levels did not differ between the two groups (p = n.s.). However, SCD-containing CLs were characterized by an increased culprit ratio of intermediate monocytes [(1.15 (0.81) vs. 0.96 (0.84); p < 0.05)] with an enhanced surface expression of the integrin receptor CD49d as compared to intermediate monocytes derived from SCD-free CLs [(1.06 (0.94) vs. 0.97 (0.91)] p < 0.05. Finally, 12 months rates of MACE+ were higher in patients with, as compared to patients without SCD at CL (16.4% vs. 5.3%; p < 0.05). CONCLUSIONS: This study for the first time identified a specific inflammatory profile of CL with SCD, with a predominance of neutrophils, intermediate monocytes and their corresponding effector molecules. Hence, this study advances our understanding of ACS-causing CL and provides the basis for future personalized anti-inflammatory, therapeutic approaches to ACS.

Asunto(s)

RESUMEN

Chronic total occlusions (CTO) in coronary angiographies present a significant challenge nowadays. Intravascular ultrasound (IVUS) is a valuable tool during CTO-PCI, aiding in planning and achieving procedural success. However, the impact of IVUS on clinical and procedural outcomes in CTO-PCI remains uncertain. This meta-analysis aimed to compare IVUS-guided and angiography-guided approaches in CTO-PCI. The study included five studies and 2320 patients with stable coronary artery disease (CAD) and CTO. The primary outcome of major adverse cardiac events (MACE) did not significantly differ between the groups (p = 0.40). Stent thrombosis was the only secondary clinical outcome that showed a significant difference, favoring the IVUS-guided approach (p = 0.01). Procedural outcomes revealed that IVUS-guided procedures had longer stents, larger diameters, and longer procedure and fluoroscopy times (p = 0.007, p < 0.001, p = 0.03, p = 0.002, respectively). Stent number and contrast volume did not significantly differ between the approaches (p = 0.88 and p = 0.33, respectively). In summary, routine IVUS use did not significantly improve clinical outcomes, except for reducing stent thrombosis. Decisions in CTO-PCI should be individualized based on patient characteristics and supported by a multi-parametric approach.

RESUMEN

Gold nanoparticles (Au-NPs) have been used for a long time to target cancer cells. Different modalities have been suggested to utilize Au-NPs in cancer patients. We construct both normal and cancer cell membranes to simulate the Au-NP entry to understand better how it can penetrate the cancer cell membrane. We use molecular dynamics simulation (MDS) on both normal and cancer cell membrane models for 150 ns. At the same time, we prepared the Au-NP of spherical shape (16 nm radius) capped with citrate using MDS for 100 ns. Finally, we added the Au-NP close to the membranes and moved it using 1000 kJ mol-1 nm-1 force constant during the 7.7 ns MDS run. We analyzed the membranes in the presence and absence of the Au-NP and compared normal and cancer membranes. The results show that normal cell membranes have higher stability than cancer membranes. Additionally, Au-NP forms pore in the membranes that facilitate water and ions entry during the movement inside the lipid bilayer region. These pores are responsible for the enhanced response of Au-NP-loaded chemotherapeutic agents in cancer treatment.

Asunto(s)