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Aims: Underlying mechanisms responsible for acute coronary syndrome (ACS) in young patients compared with older counterparts are yet to be explored with optical coherence tomography (OCT). This study aims to explore underlying mechanisms of ACS in ≤35- (very young) and >35-year-old (older counterparts) ACS patients using OCT. Methods and results: This was a prospective, single-centre, investigational study. Patients were divided into groups according to age (≤35 and >35 years) and further subdivided according to the underlying mechanism i.e. plaque rupture (PR) and plaque erosion (PE). A total of 93 patients were analysed. Thin-cap fibroatheroma (TCFA) was significantly higher among older counterparts than very young patients for both PR (80.0% vs. 31.8%, P = 0.002) and PE (66.7% vs. 6.3%, P < 0.001) groups. Microchannels were also significantly more prevalent among older than very young patients for both PR (65.0% vs. 18.2%, P = 0.004) and PE groups (55.6% vs.12.5%, P = 0.013). Macrophages were significantly higher in older than very young patients for both PR (25.0% vs. 0%, P = 0.018) and PE (44.4% vs. 0%, P = 0.003) groups. In contrast, fibrous cap thickness was greater in very young than older patients for both PR (105.71 ± 48.02 vs. 58.00 ± 15.76â µm, P < 0.001) and PE (126.67 ± 48.22 vs. 54.38 ± 24.21â µm, P < 0.001) groups. Intimal thickness was greater in older than very young patients for both PR (728.00 ± 313.92 vs. 342.27 ± 142.02â µm, P < 0.001) and PE (672.78 ± 334.57 vs. 295.00 ± 99.60â µm, P < 0.001) groups. Conclusion: Frequency of TCFA, microchannels, macrophages, and intimal thickness was significantly higher in older ACS patients compared with very young patients. However, fibrous cap thickness was significantly greater in very young ACS patients compared with older patients.
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The clotting pathway involves intrinsic and extrinsic pathways converging into a common pathway. These pathways require activated factors that sequentially convert prothrombin to thrombin, which then converts fibrinogen to fibrin, forming a stable clot. Clotting factor deficiency impairs this cascade leading to excessive bleeding or bruising due to insufficient clot formation. Here, we present the case of a 47-year-old female who initially complained of epigastric pain. By the third day of admission, she experienced four to five episodes of bleeding gums, resulting in a blood loss of approximately 300 mL. The patient exhibited abnormal prothrombin time (PT) and international normalized ratio (INR) values, leading to a diagnosis of Factor X (FX) deficiency upon further evaluation. This case report emphasizes the need to diagnose coagulopathies such as FX deficiency and how early diagnosis will help not only in patient care and management but also in screening family members who may be affected.
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Coronary artery aneurysms and ST-segment elevation myocardial infarction are rare in clinical practice, presenting a management challenge. To the best of our knowledge, this case appears to be the first successful percutaneous treatment of a completely obstructed aneurysmal left main coronary artery.
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Salmonella is an unusual cause of spontaneous bacterial peritonitis (SBP). It is commonly seen in asymptomatic patients with normal or high ascitic fluid protein levels and an immunocompromised state such as AIDS and hematological and solid organ malignancies other than liver. SBP from non-typhoidal Salmonella species should be considered, even in the absence of underlying immunosuppression. Our patient presented with a history of high-grade fever and frequent loose stools with decompensated alcoholic liver cirrhosis. While evaluating the SBP etiology, ascitic fluid turned out positive for the non-typhoidal Salmonella species, which was red, turbid, and hemorrhagic due to portal vein and superior mesenteric vein thrombosis. We thus report an extremely rare case of SBP caused by Salmonella typhimurium in our patient.
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Objectives We investigated the reproducibility of fractional flow reserve (FFR) of significant stenoses (≥70% narrowing) in the non-infarct related artery (NIRA) during the pharmaco-invasive percutaneous coronary intervention (PCI) in patients with ST-segment elevation myocardial infarction (STEMI) within 24 hours of thrombolysis and at a follow up of 2-3 weeks. Background STEMI with multivessel disease has worse outcomes. The benefits of FFR-directed PCI of NIRA at the time of primary PCI are yet controversial. Assessing the hemodynamic severity of the NIRA may help in deciding the management strategy of these lesions, save time, and avoid complications. Methods Thirty-one patients undergoing PCI for STEMI under a pharmaco-invasive approach were prospectively recruited. The FFR measurements in 34 stenoses (≥70% diameter stenosis) were obtained immediately after PCI of the culprit stenosis and were repeated at a mean follow-up of 17.6 ± 3.55 (14-21) days. In addition, time to thrombolysis, time from symptom onset to PCI, left ventricular ejection fraction (LVEF), quantitative coronary angiographic measurements of the non-culprit stenoses, and thrombolysis in myocardial infarction (TIMI) flow were recorded. Results There was a significant change in FFR values at follow-up as compared to baseline (0.78 ± 0.08 (0.68-0.93) to 0.77 ± 0.08 (0.67-0.93)) (p = 0.014). In four of the lesions, the FFR values differed by >0.05 at follow-up. The follow-up FFR values led to a change in the management strategy in 5 out of 31 patients (15%) of the lesions. The TIMI flow, percentage diameter stenosis, minimum lumen diameter, and LVEF did not change. There were no predictors of this change in FFR values. Conclusions During the acute phase of STEMI, the severity of non-culprit coronary artery stenoses can not be reliably assessed by FFR. The prolonged jeopardized state of myocardium in pharmaco-invasive PCI as compared to primary PCI seems to be responsible.
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Applying model-based predictive control in buildings requires a control-oriented model capable of learning how various control actions influence building dynamics, such as indoor air temperature and energy use. However, there is currently a shortage of empirical or synthetic datasets with the appropriate features, variability, quality and volume to properly benchmark these control-oriented models. Addressing this need, a flexible, open-source, Python-based tool, synconn_build, capable of generating synthetic building operation data using EnergyPlus as the main building energy simulation engine is introduced. The uniqueness of synconn_build lies in its capability to automate multiple aspects of the simulation process, guided by user inputs drawn from a text-based configuration file. It generates various kinds of unique random signals for control inputs, performs co-simulation to create unique occupancy schedules, and acquires weather data. Additionally, it simplifies the typically tedious and complex task of configuring EnergyPlus files with all user inputs. Unlike other synthetic datasets for building operations, synconn_build offers a user-friendly generator that selectively creates data based on user inputs, preventing overwhelming data overproduction. Instead of emulating the operational schedules of real buildings, synconn_build generates test signals with more frequent variation to cover a broader range of operating conditions. â¢Synconn_build is an open-source tool designed to address the lack of datasets for benchmarking control-oriented building dynamics prediction models.â¢The tool automates simulations, data acquisition, and EnergyPlus configuration, guided by user inputs.â¢Synconn_build prevents data overproduction by selectively creating data, offering a user-friendly approach to dataset generation.
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Key Clinical Message: The morphology of in-stent restenosis (ISR) in drug eluting stents varies greatly from that of bare metal stents. Optical coherence tomography (OCT) is a useful aid for identifying the nature of ISR and planning the treatment accordingly, which may be by intravascular lithotripsy, cutting balloon or Rotablator, which can be used upfront if OCT shows calcified neoatherosclerosis. Abstract: Restenosis is the decrease in the diameter of the vessel lumen after the performance of percutaneous intervention (PCI), which may or may not involve the implantation of a stent. The morphology of in-stent restenosis (ISR) in drug eluting stents (DES) vary greatly from that of bare metal stents (BMS). We present the case of a 60-years-old lady, who was a follow up case of PCI of the left anterior descending artery with DES and left circumflex artery using BMS 16 years ago. Optical coherence tomography (OCT) revealed both neoatherosclerosis and neointimal hyperplasia in both DES as well as BMS. The morphology of ISR in DES differed from that of BMS. PCI and pharmacological strategies form the main stream of management in case of neointimal hyperplasia. Detection of pattern of ISR on OCT can direct the management of a particular patient, which may be by the use of adjunct devices like intravascular lithotripsy, cutting balloon and Rotablator, which can be used upfront if OCT shows calcified neoatherosclerosis.
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Introduction Morphological features of neointimal tissue play a pivotal role in the pathophysiology of in-stent restenosis (ISR) after percutaneous coronary intervention (PCI). This study was designed to qualitatively and quantitatively assess neointimal characteristics of lesions using optical coherence tomography (OCT) in patients presenting with ISR. Methods This was a single-center, prospective, observational study performed at a tertiary-care center in India. Patients diagnosed with stable angina and acute coronary syndrome with post-procedural angiographically documented restenosis (>50%) were included. Results A total of 34 patients with ISR were studied. Neointimal hyperplasia was classified as (i) homogenous group (n = 18) and (ii) non-homogenous group (n = 16). Fourteen (77.8%) diabetics belonged to the homogenous group. Predominant plaque characteristics such as neoatherosclerosis, cholesterol crystals, and calcium were documented in 14 (77.8%), 12 (66.7%), and 11 (61.1%) patients in the homogenous group and 10 (62.5%), 10 (62.5%), and 9 (56.2%) patients in the non-homogenous group, respectively. Unexpanded stent struts were identified in 11 (61.1%) and 11 (68.8%) patients in the homogenous and non-homogenous groups, respectively. Mean strut thickness was 93.73 ± 31.03 µm and 83.54 ± 18.0 µm, ISR was 72.50 ± 15.93% and 65.37 ± 21.69%, the neointimal thickness was 588.06 ± 167.82 µm and 666.25 ± 218.05 µm, and neointimal hyperplasia was 54.54 ± 11.23% and 59.26 ± 8.86% in the homogenous and non-homogenous groups, respectively. Conclusion Neoatherosclerosis and stent underexpansion were predominantly observed in our study and only diabetes was found to be significantly associated with homogenous neointimal hyperplasia.
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Direct ink writing, a versatile method of 3D and 4D printing, requires the precise placement of a nozzle just above the print surface to prevent fluid instabilities that cause deviations from the prescribed print path. But what if one could harness the instability associated with the spontaneously folding or coiling of a thin stream of viscous fluid, i.e. use the "fluid rope trick" to write specified patterns on a substrate? Here we use Deep Reinforcement Learning to derive control strategies for the motion of the extruding nozzle and thus the fluid patterns that are deposited on the surface. The method proceeds by having a learner (nozzle) repeatedly interact with the environment (a viscous filament simulator), and improves its strategy using the results of this experience. We demonstrate the outcome of the learned control instructions using experiments to manipulate a falling viscous jet and create cursive writing patterns and Pollockian paintings on substrates.
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Cancer is one of the most common causes of death. So, its lethal effect increases with time. Near about hundreds of cancers are known in humans. Cancer treatment is done to cure or prolonged remission, and shrinkage of the tumor. Cytotoxic agents, biological agents/targeted drugs, hormonal drugs, surgery, radiotherapy/proton therapy, chemotherapy, immunotherapy, and gene therapy are currently used in the treatment of cancer but their cost is high and cause various side effects. Seeing this, some new targeted strategies such as PROTACs are the need of the time. Proteolysis targeting chimera (PROTAC) has become one of the most discussed topics regarding cancer treatment. Few of the PROTAC molecules are in the trial phases. PROTACs have many advantages over other strategies such as modularity, compatibility, sub-stoichiometric activity, acting on undruggable targets, molecular design, and acts on intracellular targets, selectivity and specificity can be recruited for any cancer, versatility, and others. PROTACs are having some unclear questions on their pharmacokinetics, heavy-molecular weight, etc. PROTACs are anticipated to bring about a conversion in current healthcare and will emerge as booming treatments. In this review article we summarize PROTACs, their mechanism of action, uses, advantages, disadvantages, challenges, and future aspects for the successful development of potent PROTACs as a drug strategy.
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Neoplasms , Ubiquitin-Protein Ligases , Humans , Proteolysis , Ubiquitin-Protein Ligases/metabolism , Proteolysis Targeting Chimera , Ubiquitination , Neoplasms/drug therapyABSTRACT
Aims: Long term cardiovascular outcome comparison of multivessel coronary disease among patients with diabetes mellitus (DM) undergoing percutaneous coronary intervention (PCI) or coronary artery bypass graft (CABG) is limited. The objective of this study was to compare the long-term cardiovascular outcome PCI vs CABG among DM patients with multivessel disease. Method and results: Online databases were explored to identify studies that compared cardiovascular outcomes between PCI and CABG among patients with DM. The primary outcome was all-cause mortality. Secondary outcomes included major adverse cardiovascular and cerebrovascular events (MACCE), myocardial infarction (MI), rate of revascularization, cardiac death, and cerebrovascular accident (CVA). A total of 27 studies with 37,091 (PCI n = 19,838 (53 %) and CABG n = 17,253 (47 %)) patients were included. The mean age was 64 ± 5.9 years for PCI group and 63.8 ± 5.3 years for CABG group; and, predominantly male (71.22 % vs 74.29 %) for PCI and CABG respectively. The most common comorbidity was hypertension (64.35 % vs 62.88 %) in both PCI and CABG respectively. Compared with CABG, PCI group had a higher odds of overall all-cause mortality (OR 1.18, 95 % CI 1.02-1.37, p = 0.03), MACCE (OR 1.52, 95 % CI 1.31-1.75, p = 0.00), MI (OR 1.85, 95 % CI 1.46-2.36, p = 0.00), repeat revascularization (OR 3.08, 95 % CI 2.34-4.05, p = 0.00) and cardiac death (OR 1.27, 95 % 1.02-1.59, p = 0.04), while CVA (0.57, 95 % CI 0.37-0.86, p = 0.01) was higher with CABG. Conclusion: Diabetic patients with multivessel coronary artery disease have worse outcomes undergoing PCI as compared to CABG. However, CVA was significantly higher with CABG. CABG remains the preferred management among eligible patients with multivessel disease and DM.
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Left main coronary artery chronic total occlusion is an unusual finding discovered on coronary angiography. Historically, coronary artery bypass graft has been the preferred treatment. However, recent studies have revealed the role of left main percutaneous coronary intervention in selected patients. This is a case of staged left main coronary artery chronic total occlusion percutaneous coronary intervention. (Level of Difficulty: Advanced.).
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Out-of-plane polar domain structures have recently been discovered in strained and twisted bilayers of inversion symmetry broken systems such as hexagonal boron nitride. Here we show that this symmetry breaking also gives rise to an in-plane component of polarization, and the form of the total polarization is determined purely from symmetry considerations. The in-plane component of the polarization makes the polar domains in strained and twisted bilayers topologically non-trivial, forming a network of merons and antimerons (half-skyrmions and half-antiskyrmions). For twisted systems, the merons are of Bloch type whereas for strained systems they are of Néel type. We propose that the polar domains in strained or twisted bilayers may serve as a platform for exploring topological physics in layered materials and discuss how control over topological phases and phase transitions may be achieved in such systems.
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Hagfishes defend themselves from gill-breathing predators by producing large volumes of fibrous slime when attacked. The slime's effectiveness comes from its ability to clog predators' gills, but the mechanisms by which hagfish slime clogs are uncertain, especially given its remarkably dilute concentration of solids. We quantified the clogging performance of hagfish slime over a range of concentrations, measured the contributions of its mucous and thread components, and measured the effect of turbulent mixing on clogging. To assess the porous structure of hagfish slime, we used a custom device to measure its Darcy permeability. We show that hagfish slime clogs at extremely dilute concentrations like those found in native hagfish slime and displays clogging performance that is superior to three thickening agents. We report an extremely low Darcy permeability for hagfish slime, and an effective pore size of 10-300 nm. We also show that the mucous and thread components play distinct yet crucial roles, with mucus being responsible for effective clogging and low permeability and the threads imparting mechanical strength and retaining clogging function over time. Our results provide new insights into the mechanisms by which hagfish slime clogs gills and may inspire the development of ultra-soft materials with novel properties.
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Hagfishes , Animals , Hagfishes/chemistry , Gills , Mucus/chemistryABSTRACT
BACKGROUND: ST-elevation myocardial infarction (STEMI) refers to a clinical syndrome that features symptoms of myocardial ischemia with consequent ST-elevation on electrocardiography and an associated rise in cardiac biomarkers. Rapid restoration of brisk flow in the coronary vasculature is critical in reducing mortality and morbidity. In patients with STEMI who could not receive primary percutaneous coronary intervention (PCI) on time, pharmacoinvasive strategy (thrombolysis followed by timely PCI within 3-24 h of its initiation) is an effective option. AIM: To analyze the role of delayed pharmacoinvasive strategy in the window period of 24-72 h after thrombolysis. METHODS: This was a physician-initiated, single-center prospective registry between January 2017 and July 2017 which enrolled 337 acute STEMI patients with partially occluded coronary arteries. Patients received routine pharmacoinvasive therapy (PCI within 3-24 h of thrombolysis) in one group and delayed pharmacoinvasive therapy (PCI within 24-72 h of thrombolysis) in another group. The primary endpoint was major adverse cardiac and cerebrovascular events (MACCE) within 30 d of the procedure. The secondary endpoints included major bleeding as defined by Bleeding Academic Research Consortium classification, angina, and dyspnea within 30 d. RESULTS: The mean age in the two groups was comparable (55.1 ± 10.1 years vs 54.2 ± 10.5 years, P = 0.426). Diabetes was present among 20.2% and 22.1% of patients in the routine and delayed groups, respectively. Smoking rate was 54.6% and 55.8% in the routine and delayed groups, respectively. Thrombolysis was initiated within 6 h of onset of symptoms in both groups (P = 0.125). The mean time from thrombolysis to PCI in the routine and delayed groups was 16.9 ± 5.3 h and 44.1 ± 14.7 h, respectively. No significant difference was found for the occurrence of measured clinical outcomes in the two groups within 30 d (8.7% vs 12.9%, P = 0.152). Univariate analysis of demographic characteristics and risk factors for patients who reported MACCE in the two groups did not demonstrate any significant correlation. Secondary endpoints such as angina, dyspnea, and major bleeding were non-significantly different between the two groups. CONCLUSION: Delayed PCI pharmacoinvasive strategy in a critical diseased but not completely occluded artery beyond 24 h in patients who have been timely thrombolyzed seems a reasonable strategy.
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The present study sought to assess the clinical outcomes of the Mozec™ Non-compliant (NC) Rx PTCA balloon dilatation catheter (BDC) (Meril Life Sciences Pvt. Ltd., Vapi, India) for dilatation of coronary lesions. This was a post-marketing, single-centre, single-arm, retrospective study. In total, 57 patients who had undergone post-dilatation with the Mozec™ NC Rx PTCA balloon dilatation catheter were evaluated. The primary endpoint was procedural success defined as (i) successful delivery of the investigational device to and across the target lesion; (ii) successful inflation, deflation, and withdrawal of the investigational device; (iii) absence of vessel perforation, flow-limiting vessel dissection, increase in thrombolysis in myocardial infarction (TIMI) flow from baseline, clinically significant arrhythmia requiring medical treatment; and (iv) achievement of final TIMI flow grade 3 after percutaneous coronary intervention of the target lesion after single or multiple attempts to cross the target lesion. Procedural success was achieved in 57 (100%) patients. There were no incidences of major adverse cardiac events (MACE)/target lesion failure (TLF). Mozec™ NC Rx PTCA balloon dilatation catheter has demonstrated favourable outcomes for the dilatation of routine and complex coronary lesions in a small cohort, as evidenced by its 100% procedural success rate and absence of MACE.
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Angioplasty, Balloon, Coronary , Percutaneous Coronary Intervention , Humans , Angioplasty, Balloon, Coronary/adverse effects , Coronary Angiography , Retrospective Studies , Treatment OutcomeABSTRACT
Background: Several lines of evidence have supported small dense low-density lipoproteins (sd-LDL) as a marker of cardiovascular disease. The present study assessed the relationship between lipid profile and sd-LDL levels with demographic, clinical, angiographic, and therapeutic variables in acute coronary syndrome (ACS) patients. Methods: This was a single-centre, prospective, cross-sectional study conducted from September 2014 to September 2015. Patients with a diagnosis of ACS were included in this study. High-density lipoprotein cholesterol (HDL-C) and low-density lipoprotein cholesterol (LDL-C) were determined by direct homogenous assay and sd-LDL levels were calculated using an earlier described equation by Srisawadi et al. Results: A total of 200 patients with a diagnosis of ACS were studied. Males constituted 78% of the population cohort and almost 45% of participants were aged <45 years. Patients aged ≤45 years displayed higher mean sd-LDL levels of 30.40 ± 14.18 mg/dL versus patients aged >45 years with mean sd-LDL levels of 28.01 ± 11.58 mg/dL, but the difference was not statistically significant (p = 0.19). Females also displayed higher mean sd-LDL levels, but the difference also failed to achieve statistical significance (30.95 ± 13.44 mg/dL and 28.54 ± 12.64, respectively; p = 0.185). Diabetics had higher mean sd-LDL levels (33.64 ± 13.01 mg/dL and 28.07 ± 12.60 mg/dL; p = 0.273) whilst smokers had lower mean levels (27.21 ± 12.12 mg/dL and 30.51 ± 13.21 mg/dL, respectively; p = 0.071). However, the ratio of sd-LDL/lb-LDL (large buoyant LDL) was significantly higher in diabetics (0.48 vs. 0.39; p = 0.023). In the angiography cohort (n = 88), single-vessel disease was the most predominant overall while among patients aged >45 years, triple-vessel disease was significantly higher (p = 0.005). Similarly, the sd-LDL levels were 33.12 ± 11.13 mg/dL, 27.68 ± 9.80 mg/dL, and 31.65 ± 15.26 mg/dL among patients with single, double, and triple-vessel disease and did not differ significantly (p = 0.262). Prior statin users had significantly lower mean sd-LDL levels of 24.79 ± 12.23 mg/dL compared to statin-naïve patients with a mean sd-LDL of 30.01 ± 12.79 mg/dL (p = 0.027). Non-HDL levels were also significantly lower in prior statin users (112.83 mg/dL vs. 128.9 mg/dL; p = 0.017). Conclusion: In this cohort of ACS patients, age, sex, diabetes, smoking, and the angiographic severity of coronary artery disease had no significant impact on sd-LDL levels, while prior statin usage led to significantly lower sd-LDL levels. Diabetic patients, however, did have significantly higher sd-LDL/lb-LDL ratios.
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INTRODUCTION: Levels of lipoprotein (LP) (a) are useful marker for risk stratification of cardiovascular disease. This genetic biomarker is suggestive of patient predisposition to acute coronary event. The present study was to study correlation of LP(a) levels and plaque morphology in very young patients (<35 years) with acute coronary syndrome (ACS). METHODS: A prospective, single-center, observational study consisting of very young patients with ACS and fit for optical coherence tomography (OCT) guided invasive coronary angiography was conducted at tertiary-care centre. LP(a) levels were compared between healthy controls and very young ACS patients. Correlation of LP(a) levels and plaque characteristics in very young ACS patients was done using OCT imaging. RESULTS: Out of enrolled 80 subjects, 40 were very young ACS and 40 were matched healthy controls. In very young patients, plaque rupture and erosion were mechanism of ACS in 67.5% and 32.5% patients, respectively. Mean levels of LP(a) were 28.10 ± 13.96 nmol/l in healthy controls and 47.19 ± 29.85 nmol/l in very young patients with ACS (p = 0.022). Among very young ACS patients, patients with LP(a) levels<75 nmol/l and ≥75 nmol/l had mean thin cap fibroatheroma thickness of 117.08 ± 52.542 µm and 95.00 ± 36.286 µm, respectively (p = 0.2355). CONCLUSION: Higher levels of LP(a) were seen in younger patients with ACS compared with matched healthy individuals. Plaque rupture was the commonest mechanism of ACS in very young ACS patients. Patients with high LP(a) levels had lesser thickness of fibrous cap in OCT imaging compared with low levels of LP(a).