Macrophages and Mast Cells in the Gastric Mucosa of Patients with Obesity Undergoing Sleeve Gastrectomy.

Background. Adipose tissue macrophages (ATMs) and mast cells (MCs) play a role in immune responses. More recently, their involvement in tumor angiogenesis and chronic inflammatory conditions in patients with obesity has been discovered. Furthermore, a higher BMI (Body Mass Index) value corresponds to a higher inflammatory state. In particular, gastric tissue in obesity (GTO) is characterized by Macrophages, Mast Cells Positive to Triptase (MCPT), and neo-formed microvessels (MVD). Materials and Methods. We collected gastric tissue samples from December 2021 to December 2022. The patients selected had a BMI > 35 kg/m2 with different comorbidities. Regarding the surgery, surgeons executed a Laparoscopic Sleeve Gastrectomy (LapSG). Gastric tissue was analyzed by immunohistochemistry and morphometrical assay, comparing "obese-related" gastric tissue to normal gastric tissue. Furthermore, tissue parameters were correlated with important clinicopathological features. Results. We collected thirty gastric tissue samples from thirty patients with obesity. Blood tests, Electrocardiogram (ECG), esophagogastroduodenoscopy (EGDS) associated with a urea breath test, and chest X.R. were performed. A significant correlation between ATMs, MCPT, MVD, and BMI was found in GTO. Pearson t-test analysis was conducted (r ranged from 0.67 to 0.71; p-value < 0.05). Conclusions. These preliminary data suggest that ATMs, MCPT, and MVD related to BMI can play a role in both gastric tissue angiogenesis and inflammation inducing a tissue change that could lead to gastric inflammation or cancer diseases.

Medically Treated Nonischemic Thin-Cap Fibroatheroma Lesions Versus Fractional Flow Reserve-Guided Complete Revascularization in Diabetic Patients.

Background: Fractional flow reserve (FFR) is an established method to guide decisions on revascularization; however, in patients with diabetes mellitus (DM), FFR-negative lesions carrying an optical coherence tomography-detected thin-cap fibroatheroma (TCFA) remain at high risk for adverse cardiac events. Methods: In this prespecified subanalysis of the COMBINE OCT-FFR trial, DM patients with ≥1 FFR-negative, TCFA-positive medically treated target lesions referred to as vulnerable plaque (VP group), were compared to patients with exclusively FFR-positive target lesions who underwent complete revascularization (CR group). The primary endpoint was first and recurrent event analysis for target lesion failure and the secondary endpoint was a composite of cardiac death, target vessel myocardial infarction, target lesion revascularization, or hospitalization due to unstable angina. Results: Among 550 patients enrolled, 98 belonged to the VP group while 93 to the CR group and were followed up to 5 years. The VP group had a higher occurrence of the primary endpoint (20.4% vs 8.6%; HR, 2.22; 95% CI, 0.98-5.04; P = .06). Recurrent event analysis showed that the VP group had significantly higher rates of the primary and secondary endpoints (9.17 vs 3.76 events per 100 PY; RR, 2.44; 95% CI, 1.16-5.60; P = .01 and 13.45 vs 5.63 events per 100 PY; RR, 2.39; 95% CI, 1.30-4.62; P < .01). Conclusions: In a population with DM, medically treated nonischemic, TCFA-carrying target lesions were associated with higher risk of reoccurring adverse cardiac events compared to target lesions that underwent complete revascularization, opening the discussion about whether a focal preventive revascularization strategy could be contemplated for highly vulnerable lesions.

Increased Incidence of Adverse Events in Diabetes Mellitus Patients with Combined Multiple Vulnerable Plaque Features. New Insights From the COMBINE OCT-FFR trial.

AIMS: To evaluate the individual as well as combined impact of OCT-detected vulnerability features (OCT-VFs) in the prediction of major adverse cardiovascular events (MACE) in non-ischemic lesions in patients with diabetes mellitus (DM). METHODS AND RESULTS: The COMBINE OCT-FFR (NCT02989740) was a prospective, double-blind, international, natural history study that included patients with DM having ≥1 lesions with a fractional flow reserve >0.80, undergoing systematic OCT assessment. Pre-specified OCT-VFs included TCFA, r-MLA, h-PB, and CP. The primary endpoint (MACE) was a composite of cardiac mortality, target vessel myocardial infarction, clinically driven target lesion revascularization or hospitalization for unstable angina up to 5 years, analyzed according to the presence of these OCT-VFs, both individually and in combination. TCFA, r-MLA, h-PB and CP were identified in 98 (25.1%), 159 (40.8%), 56 (14.4%), and 116 (29.8%) patients, respectively. The primary endpoint rate increased progressively from 6.9% to 50.0% (HR=10.10; 95%CI, 3.37 to 30.25, p<0.001) in patients without OCT-VFs compared to those with concomitant h-PB, r-MLA, CP, and TCFA. Importantly, while TCFA, h-PB, r-MLA and CP were individually associated with the primary endpoint, the presence of two or more OCT-VFs significantly increased the likelihood of adverse events at 5 years. CONCLUSIONS: In patients with DM and non-ischemic lesions, TCFA, h-PB, r-MLA and CP were predictors of adverse events. However, the presence of two or more OCT-VFs significantly increased the likelihood of MACE at 5 years. Further studies are warranted to confirm these findings and their potential clinical implications in a randomized fashion.

Surface-catalyzed liquid-liquid phase separation and amyloid-like assembly in microscale compartments.

Liquid-liquid phase separation is a key phenomenon in the formation of membrane-less structures within the cell, appearing as liquid biomolecular condensates. Protein condensates are the most studied for their biological relevance, and their tendency to evolve, resulting in the formation of aggregates with a high level of order called amyloid. In this study, it is demonstrated that Human Insulin forms micrometric, round amyloid-like structures at room temperature within sub-microliter scale aqueous compartments. These distinctive particles feature a solid core enveloped by a fluid-like corona and form at the interface between the aqueous compartment and the glass coverslip upon which they are cast. Quantitative fluorescence microscopy is used to study in real-time the formation of amyloid-like superstructures. Their formation results driven by liquid-liquid phase separation process that arises from spatially heterogeneous distribution of nuclei at the glass-water interface. The proposed experimental setup allows modifying the surface-to-volume ratio of the aqueous compartments, which affects the aggregation rate and particle size, while also inducing fine alterations in the molecular structures of the final assemblies. These findings enhance the understanding of the factors governing amyloid structure formation, shedding light on the catalytic role of surfaces in this process.

A Nutraceutical Combination of Bromelain and Boswellia Serrata Casperome® in Siben®: Effects on the Postoperative Course of Inguinal Hernioplasty with Mesh at One Year Follow up. A Randomized Multicentric Study.

AIM: We investigated the potential benefits of administering a nutraceutical combination of Bromelain (200 mg) and Boswellia serrata Casperome® (200 mg) on post-operative outcomes of hernioplasty with mesh. METHODS: One hundred eighty patients (27 females, 153 males) were enrolled to undergo open tension-free hernioplasty with the use of Progrip®. Patients were randomized to receive either one tablet of Siben® (study group) or placebo (control group) on an empty stomach, every twelve hours for eleven postoperative days. All patients filled out a medical questionnaire focused on postoperative pain, based on the Visual Analogue Scale (VAS) scale and the Short Form-36 (SF-36) questionnaire, at time T0 (day of surgery) and T28 (28th day after surgery). RESULTS: One-year results showed a significant improvement in the primary postoperative outcome in the study group. Perception of pain was significantly reduced in the Siben® group compared with controls, both on the seventh (p < 0.05) and the twenty-first (p < 0.05) postoperative day. Patients included in the Siben® group also resumed daily activities and returned to work earlier than the controls. Moreover, results of the SF-36 indicated better Quality of Life (QoL) scores in the study group compared to the placebo group. CONCLUSIONS: Our analysis effectively demonstrates that the use of Siben® in open inguinal hernia mesh repair may improve short- and long-term surgical outcomes, contributing to a better QoL.

Antiplatelet Effect of Low-Dose Prasugrel in Elderly Patients Undergoing Percutaneous Coronary Interventions.

BACKGROUND: Low-dose prasugrel (5 mg) has been proposed for patients with Acute Coronary Syndrome (ACS) and advanced age or low body weight. However, the routine use of dose-adjusted prasugrel in this high-risk subset of patients is still debated. AIM: This study aimed to assess the prevalence and predictors of HRPR among elderly patients treated with low-dose (5 mg) prasugrel to evaluate the routine use of dose-adjusted prasugrel in this high-risk subset of patients. METHODS: We included 59 elderly patients (≥75 years) treated with Dual Antiplatelet Therapy (DAPT: acetylsalicylic acid (ASA) 100-160 mg + prasugrel 5 mg) after Percutaneous Coronary Interventions (PCI) and undergoing platelet function assessment (by whole blood impedance aggregometry) 30-90 days post-discharge. RESULTS: At a median follow-up of 43 days (interquartile range-IQR: 32-54), high-on treatment residual platelet reactivity (HRPR) occurred in 25 patients (42.4%), who displayed a greater body mass index (BMI) (p=0.02), lower levels of vitamin D (p=0.05) and were more frequently treated with nitrates (p=0.03). After multivariate analysis, BMI was the only independent predictor of prasugrel HRPR, and a BMI >26 was the best cut-off for predicting HRPR (adjusted Odds Ratio - OR=8.6, 95%CI: 2.2-33.9, p=0.002). CONCLUSION: Among elderly patients receiving DAPT after PCI, HRPR is common with low-dose prasugrel. A greater BMI, especially for values ≥26, is the only independent predictor of HRPR with prasugrel 5 mg.

Vulnerable plaque features and adverse events in patients with diabetes mellitus: a post hoc analysis of the COMBINE OCT-FFR trial.

BACKGROUND: Thin-cap fibroatheroma (TCFA) lesions are associated with a high risk of future major adverse cardiovascular events. However, the impact of other optical coherence tomography-detected vulnerability features (OCT-VFs) and their interplay with TCFA in predicting adverse events remains unknown. AIMS: We aimed to evaluate the individual as well as the combined prognostic impact of OCT-VFs in predicting the incidence of the lesion-oriented composite endpoint (LOCE) in non-ischaemic lesions in patients with diabetes mellitus (DM). METHODS: COMBINE OCT-FFR (ClinicalTrials.gov: NCT02989740) was a prospective, double-blind, international, natural history study that included DM patients with ≥1 non-culprit lesions with a fractional flow reserve>0.80 undergoing systematic OCT assessment. OCT-VFs included the following: TCFA, reduced minimal lumen area (r-MLA), healed plaque (HP), and complicated plaque (CP). The primary endpoint, LOCE - a composite of cardiac mortality, target vessel myocardial infarction, or clinically driven target lesion revascularisation up to 5 years - was analysed according to the presence of these OCT-VFs, both individually and in combination. RESULTS: TCFA, r-MLA, HP and CP were identified in 98 (25.3%), 190 (49.0%), 87 (22.4%), and 116 (29.9%) patients, respectively. The primary endpoint rate increased progressively from 6.3% to 55.6% (hazard ratio 15.2, 95% confidence interval: 4.53-51.0; p<0.001) in patients without OCT-VFs as compared to patients with concomitant HP, r-MLA, CP, and TCFA. The coexistence of TCFA with other OCT-VFs resulted in an increased risk of the LOCE at 5 years. CONCLUSIONS: In DM patients with non-ischaemic lesions, TCFA was the strongest predictor of future LOCE events. However, lesions that present additional OCT-VFs are associated with a higher risk of adverse events than OCT-detected TCFA alone. Further randomised studies are warranted to confirm these findings and their potential clinical implications.

A machine learning predictive model for recurrence of resected distal cholangiocarcinoma: Development and validation of predictive model using artificial intelligence.

INTRODUCTION: Distal Cholangiocarcinoma (dCCA) represents a challenge in hepatobiliary oncology, that requires nuanced post-resection prognostic modeling. Conventional staging criteria may oversimplify dCCA complexities, prompting the exploration of novel prognostic factors and methodologies, including machine learning algorithms. This study aims to develop a machine learning predictive model for recurrence after resected dCCA. MATERIAL AND METHODS: This retrospective multicentric observational study included patients with dCCA from 13 international centers who underwent curative pancreaticoduodenectomy (PD). A LASSO-regularized Cox regression model was used to feature selection, examine the path of the coefficient and create a model to predict recurrence. Internal and external validation and model performance were assessed using the C-index score. Additionally, a web application was developed to enhance the clinical use of the algorithm. RESULTS: Among 654 patients, LNR (Lymph Node Ratio) 15, neural invasion, N stage, surgical radicality, and differentiation grade emerged as significant predictors of disease-free survival (DFS). The model showed the best discrimination capacity with a C-index value of 0.8 (CI 95 %, 0.77%-0.86 %) and highlighted LNR15 as the most influential factor. Internal and external validations showed the model's robustness and discriminative ability with an Area Under the Curve of 92.4 % (95 % CI, 88.2%-94.4 %) and 91.5 % (95 % CI, 88.4%-93.5 %), respectively. The predictive model is available at https://imim.shinyapps.io/LassoCholangioca/. CONCLUSIONS: This study pioneers the integration of machine learning into prognostic modeling for dCCA, yielding a robust predictive model for DFS following PD. The tool can provide information to both patients and healthcare providers, enhancing tailored treatments and follow-up.

Vitamin D and Cardiovascular Diseases: From Physiology to Pathophysiology and Outcomes.

Vitamin D is rightly recognized as an essential key factor in the regulation of calcium and phosphate homeostasis, affecting primary adequate bone mineralization. In the last decades, a more complex and wider role of vitamin D has been postulated and demonstrated. Cardiovascular diseases have been found to be strongly related to vitamin D levels, especially to its deficiency. Pre-clinical studies have suggested a direct role of vitamin D in the regulation of several pathophysiological pathways, such as endothelial dysfunction and platelet aggregation; moreover, observational data have confirmed the relationship with different conditions, including coronary artery disease, heart failure, and hypertension. Despite the significant evidence available so far, most clinical trials have failed to prove any positive impact of vitamin D supplements on cardiovascular outcomes. This discrepancy indicates the need for further information and knowledge about vitamin D metabolism and its effect on the cardiovascular system, in order to identify those patients who would benefit from vitamin D supplementation.

Could the mitotic count improve personalized prognosis in melanoma patients?

A number of studies have indicated that the mitotic rate may be a predictive factor for poor prognosis in melanoma patients. The aim of this study was to investigate whether the mitotic rate is associated with other prognostic clinical and anatomopathological characteristics. After adjusting for other anatomopathological characteristics, we then verified the prognostic value of the number of mitoses, determining in which population subgroup this variable may have greater prognostic significance on 3-year mortality. The Veneto Cancer Registry (Registro Tumori del Veneto-RTV), a high-resolution population-based dataset covering the regional population of approximately 4.9 million residents, served as the clinical data source for the analysis. Inclusion criteria included all incident cases of invasive cutaneous malignant melanoma recorded in the RTV in 2015 (1,050 cases) and 2017 (1,205 cases) for which the number of mitoses was available. Mitotic classes were represented by Kaplan-Meier curves for short-term overall survival. Cox regression calculated hazard ratios in multivariable models to evaluate the independent prognostic role of different mitotic rate cut-offs. The results indicate that the mitotic rate is associated with other survival prognostic factors: the variables comprising the TNM stage (e.g., tumor thickness, ulceration, lymph node status and presence of metastasis) and the characteristics that are not included in the TNM stage (e.g., age, site of tumor, type of morphology, growth pattern and TIL). Moreover, this study demonstrated that, even after adjusting for these prognostic factors, mitoses per mm2 are associated with higher mortality, particularly in T2 patients. In conclusion, these findings revealed the need to include the mitotic rate in the histological diagnosis because it correlates with the prognosis as an independent factor. The mitotic rate can be used to develop a personalized medicine approach in the treatment and follow-up monitoring of melanoma patients.

Molecular Crowding: The History and Development of a Scientific Paradigm.

It is now generally accepted that macromolecules do not act in isolation but "live" in a crowded environment, that is, an environment populated by numerous different molecules. The field of molecular crowding has its origins in the far 80s but became accepted only by the end of the 90s. In the present issue, we discuss various aspects that are influenced by crowding and need to consider its effects. This Review is meant as an introduction to the theme and an analysis of the evolution of the crowding concept through time from colloidal and polymer physics to a more biological perspective. We introduce themes that will be more thoroughly treated in other Reviews of the present issue. In our intentions, each Review may stand by itself, but the complete collection has the aspiration to provide different but complementary perspectives to propose a more holistic view of molecular crowding.

TransCatheter aortic valve implantation and fractional flow reserve-guided percutaneous coronary intervention versus conventional surgical aortic valve replacement and coronary bypass grafting for treatment of patients with aortic valve stenosis and multivessel or advanced coronary disease: The transcatheter valve and vessels trial (TCW trial): Design and rationale.

BACKGROUND: Patients with severe aortic stenosis (AS) frequently present with concomitant obstructive coronary artery disease (CAD). In those, current guidelines recommend combined coronary artery bypass grafting (CABG) and surgical aortic valve replacement (SAVR) as the preferred treatment option, although this surgical approach is associated with a high rate of clinical events. Combined transcatheter aortic valve implantation (TAVI) and percutaneous coronary intervention (PCI) with or without FFR have evolved as a valid alternative for cardiac surgery in patients with AS and multivessel or advanced CAD. To date, no dedicated trial has prospectively evaluated the outcomes of a percutaneous versus surgical treatment for patients with both severe AS and CAD. AIMS: To investigate whether fractional-flow reserve (FFR)-guided PCI and TAVI is noninferior to combined CABG and SAVR for the treatment of severe AS and multivessel or advanced CAD. METHODS: The Transcatheter Valve and Vessels (TCW) trial (clinicaltrial.gov: NCT03424941) is a prospective, randomized, controlled, open label, international trial. Patients ≥ 70 years with severe AS and multivessel (≥ 2 vessels) or advanced CAD, deemed feasible by the heart team for both; a full percutaneous or surgical treatment, will be randomised in a 1:1 fashion to either FFR-guided PCI followed by TAVI (intervention arm) vs. CABG and SAVR (control arm). The primary endpoint is a patient-oriented composite of all-cause mortality, myocardial infarction, disabling stroke, unscheduled clinically-driven target vessel revascularization, valve reintervention, and life threatening or disabling bleeding at 1 year. The TCW trial is powered for noninferiority, and if met, superiority will be tested. Assuming a primary endpoint rate of 30% in the CABG-SAVR arm, with a significance level α of 5%, a noninferiority limit delta of 15% and a loss to follow-up of 2%, a total of 328 patients are needed to obtain a power of 90%. The primary endpoint analysis is performed on an intention-to-treat basis. SUMMARY: The TCW Trial is the first prospective randomized trial that will study if a less invasive percutaneous treatment for severe AS and concomitant advanced CAD (i.e., FFR-guided PCI-TAVI) is noninferior to the guidelines recommended approach (CABG-SAVR).

The unexpected social cost of inguinal hernioplasty procedures derived from the COVID-19 pandemic: Surgical trend analysis based on an Italian hospital series.

BACKGROUND: The majority of inguinal hernias are usually paucisymptomatic, so are restored electively. The main purpose of this study is to assess the trends in hernia repair surgery before and during the pandemic period, analyzing an Italian hospital series of 390 patients, in an attempt to quantify the negative impact regarding social costs derived from the Covid-19 outbreak. Moreover, we want to focus on the concept of apparently minor pathology as hernioplasty which could represent a life-threatening condition for patients. METHODS: The study population consisted of all patients operated for inguinal hernia in a General Surgery Unit from 2019 to 2021, divided into a pre-pandemic and a pandemic period. RESULTS: The Covid-19 pandemic increased urgent operations in a complicated setting. A statistically significant difference was found regarding the trend of hospitalization length as well as a strong positive correlation between the severity of hernia and the hospitalization length. CONCLUSIONS: During the pandemic, it has been registered a mishandling of inguinal hernias to the detriment of both the healthcare system and patients, due to multifactorial issues and, in particular, to the restrictions imposed by the regional government that erroneously declassed hernia pathology as a minor problem for public health. We do believe that patients, after diagnosis of inguinal hernia, should learn the Taxis maneuver for its feasibility and ease of execution, in order to reduce access to emergencies in many cases and likewise to better pain and discomfort perceived, even in the event of unexpected worldwide healthcare scenario.

Sutureless Repair for Open Treatment of Inguinal Hernia: Three Techniques in Comparison.

Currently, groin hernia repair is mostly performed with application of mesh prostheses fixed with or without suture. However, views on safety and efficacy of different surgical approaches are still partly discordant. In this multicentre retrospective study, three sutureless procedures, i.e., mesh fixation with glue, application of self-gripping mesh, and Trabucco's technique, were compared in 1034 patients with primary unilateral non-complicated inguinal hernia subjected to open anterior surgery. Patient-related features, comorbidities, and drugs potentially affecting the intervention outcomes were also examined. The incidence of postoperative complications, acute and chronic pain, and time until discharge were assessed. A multivariate logistic regression was used to compare the odds ratio of the surgical techniques adjusting for other risk factors. The application of standard/heavy mesh, performed in the Trabucco's technique, was found to significantly increase the odds ratio of hematomas (p = 0.014) and, most notably, of acute postoperative pain (p < 0.001). Among the clinical parameters, antithrombotic therapy and large hernia size were independent risk factors for hematomas and longer hospital stay, whilst small hernias were an independent predictor of pain. Overall, our findings suggest that the Trabucco's technique should not be preferred in patients with a large hernia and on antithrombotic therapy.

Cultural universality and specificity of teacher-student relationship: a qualitative study in Belgian, Chinese, and Italian primary school teachers.

Extensive evidence highlights the significant influence of dyadic, emotional teacher-student relationship (TSR) on students' cognitive functioning, socio-emotional development, and overall well-being. However, it remains unclear whether the TSR construct and its manifestations can be generalized across cultures. This qualitative study investigated TSR among 60 primary school teachers in Belgium, China, and Italy (i.e., countries with varying positions on the collectivistic-individualistic continuum of culture). Through semi-structured interviews and metatheme analysis, the study examined the similarities and differences in TSR across these countries, revealing a nuanced and diverse picture in various cultural contexts. The findings align with the existing TSR model by including dimensions of closeness, conflict, and dependency, while also extending the model to identify additional dimensions such as authority, balance, distance, fairness, increasing student motivation, patience, and strictness. Regarding cultural perspective, teachers from these three countries exhibited similar conceptualizations of closeness, conflict, fairness, increasing student motivation, patience, and strictness, whereas the conceptualization of dependency, authority, balance, and distance may be influenced by (collectivistic versus individualistic) culture. Moreover, the manifestations of TSR varied across countries, highlighting the influence of cultural factors such as cultural norms, collectivistic versus individualistic values, and the perceived legitimacy of teacher authority. These findings shed light on the complexities of TSR across countries and emphasize the significance of culturally sensitive approaches in fostering positive TSR in education.

Individualization of Duration of Dual Antiplatelet Therapy after Coronary Stenting: A Comprehensive, Evidence-Based Review.

Dual antiplatelet therapy (DAPT), comprising aspirin and a P2Y12 receptor inhibitor, is the cornerstone of post-percutaneous coronary intervention treatment to prevent stent thrombosis and reduce the risk of adverse cardiovascular events. The selection of an optimal DAPT regimen, considering the interplay of various antiplatelet agents, patient profiles, and procedural characteristics, remains an evolving challenge. Traditionally, a standard duration of 12 months has been recommended for DAPT in most patients. While contemporary guidelines provide general frameworks, DAPT modulation with longer or shorter treatment courses followed by aspirin or P2Y12 inhibitor monotherapy are evolving towards an individualized strategy to optimize the balance between efficacy and safety. This review comprehensively examines the current landscape of DAPT strategies after coronary stenting, with a focus on emerging evidence for treatment individualization.

In-stent restenosis after percutaneous coronary intervention: emerging knowledge on biological pathways.

Percutaneous coronary intervention (PCI) has evolved significantly over the past four decades. Since its inception, in-stent restenosis (ISR)-the progressive reduction in vessel lumen diameter after PCI-has emerged as the main complication of the procedure. Although the incidence of ISR has reduced from 30% at 6 months with bare-metal stents to 7% at 4 years with drug-eluting stents (DESs), its occurrence is relevant in absolute terms because of the dimensions of the population treated with PCI. The aim of this review is to summarize the emerging understanding of the biological pathways that underlie ISR. In-stent restenosis is associated with several factors, including patient-related, genetic, anatomic, stent, lesion, and procedural characteristics. Regardless of associated factors, there are common pathophysiological pathways involving molecular phenomena triggered by the mechanical trauma caused by PCI. Such biological pathways are responses to the denudation of the intima during balloon angioplasty and involve inflammation, hypersensitivity reactions, and stem cell mobilization particularly of endothelial progenitor cells (EPCs). The results of these processes are either vessel wall healing or neointimal hyperplasia and/or neo-atherosclerosis. Unravelling the key molecular and signal pathways involved in ISR is crucial to identify appropriate therapeutic strategies aimed at abolishing the 'Achille's heel' of PCI. In this regard, we discuss novel approaches to prevent DES restenosis. Indeed, available evidence suggests that EPC-capturing stents promote rapid stent re-endothelization, which, in turn, has the potential to decrease the risk of stent thrombosis and allow the use of a shorter-duration dual antiplatelet therapy.

Characteristics of patients with recurrent acute myocardial infarction after MINOCA.

BACKGROUND: Myocardial infarction (MI) with non-obstructed coronary arteries (MINOCA) is an increasingly recognized condition with challenging management. Some MINOCA patients ultimately experience recurrent acute MI (re-AMI) during follow-up; however, clinical and angiographic factors predisposing to re-AMI are still poorly defined. METHODS: In this retrospective multicenter cohort study we enrolled consecutive patients fulfilling diagnostic criteria of MINOCA according to the IV universal definition of myocardial infarction; characteristics of patients experiencing re-AMI during the follow-up were compared to a group of MINOCA patients without re-AMI. RESULTS: 54 patients (mean age 66 ± 13) experienced a subsequent re-AMI after MINOCA and follow-up was available in 44 (81%). Compared to MINOCA patients without re-AMI (n = 695), on first invasive coronary angiography (ICA) MINOCA patients with re-AMI showed less frequent angiographically normal coronaries (37 versus 53%, p = 0.032) and had a higher prevalence of atherosclerosis involving 3 vessels or left main stem (17% versus 8%, p = 0.049). Twenty-four patients (44%) with re-AMI underwent a new ICA: 25% had normal coronary arteries, 12.5% had mild luminal irregularities (<30%), 20.8% had moderate coronary atherosclerosis (30-49%), and 41.7% showed obstructive coronary atherosclerosis (≥50% stenosis). Among patients undergoing new ICA, atherosclerosis progression was observed in 11 (45.8%), 37.5% received revascularization, only 4.5% had low-density lipoprotein cholesterol (LDL_C) under 55 mg/dL and 33% experienced a new cardiovascular disease (CVD) event (death, AMI, heart failure, stroke) at subsequent follow-up. CONCLUSIONS: In the present study, only a minority of MINOCA patients with re-AMI underwent a repeated ICA, nearly one out of two showed atherosclerosis progression, often requiring revascularization. Recommended LDL-C levels were achieved only in a minority of the cases, indicating a possible underestimation of CVD risk in this population.