Lack of Syndecan-1 promotes the pathogenesis of experimental rheumatoid arthritis.

Syndecan-1 (Sdc-1), a transmembrane heparan sulfate protein, is implicated in several pathophysiological processes including rheumatoid arthritis (RA). The exact role of Syndican-1 in this autoimmune disease is still undetermined. This study explores the involvement level of Sdc-1 in the development of RA in a collagen II-induced arthritis mice model. RA was induced in two mice strains (wild-type BALB/c group and Sdc-1 knockout) by collagen II. Mice underwent regular clinical observations and scoring. After sacrifice, leg biopsies were taken from mice for histological examination, using a variety of stains. In addition, proteins were extracted, and molecular assessment of TNF-α was performed using the western blot technique. In the Sdc-1 knockout group, clinical scoring results showed a significantly more severe experimental RA; histology showed a significant increase in bone erosion, cartilage destruction, inflammation, and less granulated mast cells than the wild-type. In addition, molecular assessment of TNF-α showed more increase in expression in the Sdc-1 knockout models compared to the wild-type. Data suggest that lack of Sdc-1 enhances the inflammatory characteristics in RA. However, more molecular studies and investigations are needed to determine its exact role and possible mechanisms involved.

Probiotics, gut microbiome, and cardiovascular diseases: An update.

Cardiovascular diseases (CVD) are one of the most challenging diseases and many factors have been demonstrated to affect their pathogenesis. One of the major factors that affect CVDs, especially atherosclerosis, is the gut microbiota (GM). Genetics play a key role in linking CVDs with GM, in addition to some environmental factors which can be either beneficial or harmful. The interplay between GM and CVDs is complex due to the numerous mechanisms through which microbial components and their metabolites can influence CVDs. Within this interplay, the immune system plays a major role, mainly based on the immunomodulatory effects of microbial dysbiosis and its resulting metabolites. The resulting modulation of chronic inflammatory processes was found to reduce the severity of CVDs and to maintain cardiovascular health. To better understand the specific roles of GM-related metabolites in this interplay, this review presents an updated perspective on gut metabolites related effects on the cardiovascular system, highlighting the possible benefits of probiotics in therapeutic strategies.

The Mechanism and Potential Therapeutic Effects of Cyclosporin, Cyclophilin, Probiotics and Syndecan-1 in an Animal Model of Inflammatory Bowel Disease.

Background: Inflammatory bowel diseases (IBDs) have several treatment modalities including immunoregulators, like cyclosporine A, an immunosuppressant that interacts with cytoplasmic cyclophilin A, and probiotics. Aims: This study explored and compared the possible role of syndecan-1 in the IBD pathogenic process as well as the effectiveness of cyclophilin A, cyclosporine A, and their combination in the management of IBDs in the presence of probiotics. Methodology: IBD was induced in a total of 112 mice equally divided between syndecan-1 knock-out (KO) and Balb/c wild-type mice, using 2% dextran sulfate sodium (DSS) followed by intraperitoneal treatment with cyclosporine A, cyclophilin A, or a combination of both. In addition, a daily dose of probiotics was given in their drinking water. The animals were monitored for clinical signs and symptoms and checked for gross pathologies in the abdomen after 3 weeks. Descending and sigmoid colon biopsies were collected and fixed for routine microscopy or frozen for protein extraction and molecular testing for IL-6, CD3, CD147, and beta 1 integrins as well as pAkt expression. Results: The data showed that the induction of IBD in the syndecan-1 KO mice was more severe at the clinical, histological, and molecular levels than in the wild type. The combined CypA-CyA treatment showed no added inhibitory effect compared to single-drug treatment in both strains. Probiotics added to the combination was more effective in the wild type and, when used alone, its inhibition of IL-6 was the highest. As for the CD147 marker, there were more suppressions across the various groups in the KO mice except for the probiotics-alone group. Concerning CD3, it was significantly increased by the CypA-CyA complex, which led to more inflammation in the KO mice. Probiotics had little effect with the combination. In relation to beta 1 integrins, the CypA-CyA combination made no significant difference from CyA alone, and adding probiotics to the combination resulted in higher beta 1 integrin expression in the KO mice. As for pAkt, it was very well expressed and upregulated in both strains treated with DSS, but the effect was much larger in the KO mice. In brief, the CypA-CyA complex showed a decrease in the expression of pAkt, but there was no added effect of both drugs. Probiotics along with the complex had a similar reduction effects in both strains, with a greater effect in the wild-type mice, while probiotics alone led to a similar reduction in pAkt expressions in both strains. Conclusions: The differential effects of CyA, CypA, probiotics, and their combinations on the various inflammatory markers, as well as the histological alterations and clinical signs and symptoms, speak in favor of a clear role of syndecan-1 in reducing inflammation. However, probiotics need to be considered after more explorations into the mechanisms involved in the presence of CypA and CyA especially since pAkt is less active in their presence.

Highlights on two decades with microbiota and inflammatory bowel disease from etiology to therapy.

Inflammatory Bowel diseases (IBDs) constitute a complex panel of disorders characterized with chronic inflammation affecting the alimentary canal along with extra intestinal manifestations. Its exact etiology is still unknown; however, it seems to be the result of uncharacterized environmental insults in the intestine and their immunological consequences along with dysbiosis, in genetically predisposed individuals. It was the main target of our team since 2002 to explore the etiology of IBD and the related role of bacteria. For almost two decades, our laboratory, among others, has been involved in the reciprocal interaction between the host gastrointestinal lining and the homing microbiota. In the first decade, the attention of scientists focused on the possible role of enteropathogenic E. coli and its relationship to the mechanistic pathways involved in IBD induced in both rats and mice by chemicals like Iodoacetamide, Dextran Sodium Sulfate, Trinitrobenzene, thus linking microbial alteration to IBD pathology. A thorough characterization of the various models was the focus of research in addition to exploring how to establish an active homeostatic composition of the commensal microbiota, including its wide diversity by restoration of gut microbiota by probiotics and moving from dysbiosis to eubiosis. In the last six years and in order to effectively translate such findings into clinical practice, it was critical to explore their relationship to colorectal cancer CRC both in solid tumors and chemically induced CRC. It was also critical to explore the degree of intestinal dysbiosis and linking to IBD, CRC and diabetes. Remarkably, the active mechanistic pathways were proposed as well as the role of microbiota or bacterial metabolites involved. This review covers two decades of investigations in our laboratory and sheds light on the different aspects of the relationship between microbiota and IBD with an emphasis on dysbiosis, probiotics and the multiple mechanistic pathways involved.

The chaperone system in cancer therapies: Hsp90.

The chaperone system (CS) of an organism is composed of molecular chaperones, chaperone co-factors, co-chaperones, and chaperone receptors and interactors. It is present throughout the body but with distinctive features for each cell and tissue type. Previous studies pertaining to the CS of the salivary glands have determined the quantitative and distribution patterns for several members, the chaperones, in normal and diseased glands, focusing on tumors. Chaperones are cytoprotective, but can also be etiopathogenic agents causing diseases, the chaperonopathies. Some chaperones such as Hsp90 potentiate tumor growth, proliferation, and metastasization. Quantitative data available on this chaperone in salivary gland tissue with inflammation, and benign and malignant tumors suggest that assessing tissue Hsp90 levels and distribution patterns is useful for differential diagnosis-prognostication, and patient follow up. This, in turn, will reveal clues for developing specific treatment centered on the chaperone, for instance by inhibiting its pro-carcinogenic functions (negative chaperonotherapy). Here, we review data on the carcinogenic mechanisms of Hsp90 and their inhibitors. Hsp90 is the master regulator of the PI3K-Akt-NF-kB axis that promotes tumor cell proliferation and metastasization. We discuss pathways and interactions involving these molecular complexes in tumorigenesis and review Hsp90 inhibitors that have been tested in search of an efficacious anti-cancer agent. This targeted therapy deserves extensive investigation in view of its theoretical potential and some positive practical results and considering the need of novel treatments for tumors of the salivary glands as well as other tissues.

Patent Foramen Ovale and Cryptogenic Stroke: Integrated Management.

Patent foramen ovale (PFO) is a common cardiac abnormality with a prevalence of 25% in the general population. PFO has been associated with the paradoxical embolism causing cryptogenic stroke and systemic embolization. Results from clinical trials, meta-analyses, and position papers support percutaneous PFO device closure (PPFOC), especially if interatrial septal aneurysms coexist and in the presence of large shunts in young patients. Remarkably, accurately evaluating patients to refer to the closure strategy is extremely important. However, the selection of patients for PFO closure is still not so clear. The aim of this review is to update and clarify which patients should be considered for closure treatment.

VEGF-A: A Novel Mechanistic Link Between CYP2C-Derived EETs and Nox4 in Diabetic Kidney Disease.

Diabetes is associated with decreased epoxyeicosatrienoic acid (EET) bioavailability and increased levels of glomerular vascular endothelial growth factor A (VEGF-A) expression. We examined whether a soluble epoxide hydrolase inhibitor protects against pathologic changes in diabetic kidney disease and whether the inhibition of the VEGF-A signaling pathway attenuates diabetes-induced glomerular injury. We also aimed to delineate the cross talk between cytochrome P450 2C (CYP2C)-derived EETs and VEGF-A. Streptozotocin-induced type 1 diabetic (T1D) rats were treated with 25 mg/L of 12-(3-adamantan-1-yl-ureido)-dodecanoic acid (AUDA) in drinking water for 6 weeks. In parallel experiments, T1D rats were treated with either SU5416 or humanized monoclonal anti-VEGF-A neutralizing antibody for 8 weeks. Following treatment, the rats were euthanized, and kidney cortices were isolated for further analysis. Treatment with AUDA attenuated the diabetes-induced decline in kidney function. Furthermore, treatment with AUDA decreased diabetes-associated oxidative stress and NADPH oxidase activity. Interestingly, the downregulation of CYP2C11-derived EET formation is found to be correlated with the activation of the VEGF-A signaling pathway. In fact, inhibiting VEGF-A using anti-VEGF or SU5416 markedly attenuated diabetes-induced glomerular injury through the inhibition of Nox4-induced reactive oxygen species production. These findings were replicated in vitro in rat and human podocytes cultured in a diabetic milieu. Taken together, our results indicate that hyperglycemia-induced glomerular injury is mediated by the downregulation of CYP2C11-derived EET formation, followed by the activation of VEGF-A signaling and upregulation of Nox4. To our knowledge, this is the first study to highlight VEGF-A as a mechanistic link between CYP2C11-derived EET production and Nox4. ARTICLE HIGHLIGHTS: Diabetes is associated with an alteration in cytochrome P450 2C11 (CYP2C11)-derived epoxyeicosatrienoic acid (EET) bioavailability. Decreased CYP2C11-derived EET bioavailability mediates hyperglycemia-induced glomerular injury. Decreased CYP2C11-derived EET bioavailability is associated with increased reactive oxygen species production, NADPH oxidase activity, and Nox4 expression in type 1 diabetes. Decreased CYP2C11-derived EET formation mediates hyperglycemia-induced glomerular injury through the activation of the vascular endothelial growth factor A (VEGF-A) signaling pathway. Inhibiting VEGF signaling using anti-VEGF or SU5416 attenuates type 1 diabetes-induced glomerular injury by decreasing NADPH oxidase activity and NOX4 expression.

Nerve growth factor and burn wound healing: Update of molecular interactions with skin cells.

Burn wound healing is a very intricate and complex process that conventionally includes three interrelated and overlapping stages of hemostasis/inflammation, proliferation and remodeling. This review aims to explore the molecular interactions of NGF with the most prominent cell types in the skin and their respective secretory products during wound healing, particularly burn wound healing. Different types of cells such as, nerve cells, endothelial cells, mast cells, macrophages, neutrophils, keratinocytes and fibroblasts all come into play through a plethora of cytokines and growth factors including nerve growth factor (NGF). NGF is a pleiotropic molecule that exerts its effects on all the aforementioned cells using two types of receptors (TrkA and p75) and affects wound healing by decreasing healing time and improving the quality of the scar. Both receptors mediate cellular proliferation, survival and apoptosis through complex signaling molecules. During the inflammatory phase, macrophages and mast cells secrete ample cytokines and growth factors, including NGF, which participate in the inflammatory reaction and induction of other cells targeting a homeostatic state. The proliferative phase follows, and NGF promotes angiogenesis through VEGF and FGF expression in endothelial cells. NGF also stimulates keratinocyte proliferation and neurite extension through the TrkA-PI3K/Akt pathway. Other molecules such as TGF-ß1, IL-1ß and TNF-α increase NGF expression in fibroblasts through dynamic interactions with Smads and MAPK molecules. Stimulated fibroblasts induce new collagen production to form the granulation tissue. In the remodeling phase, NGF regulates fibroblasts and induces their differentiation into myofibroblasts ultimately leading to wound contracture. In addition, NGF stimulates melanocytes and enhances hair growth and pigmentation. Such data depict the mechanisms of action of NGF implicated in the various stages of the healing process and support its applicability as a new targeted therapeutic molecule effective in burn wound healing but with some limitations.

Transit time flow measurement guiding the surgical treatment for anomalous origin of the right coronary artery: A case report.

Anomalous origin of a coronary artery from the opposite sinus of Valsalva (ACAOS) in symptomatic patients is a rare but serious finding whose treatment consists of a surgical correction. The surgical treatment has a level of complexity that could vary from unroofing and ostioplasty to coronary artery bypass grafting. We present our management of a 59-year-old woman presenting with chest pain and dyspnea for right ACAOS with an interarterial route. The right coronary artery (RCA) was bypassed with the right internal thoracic artery. An intraoperative transit time flowmetry (TTFM) showed a competitive flow from the native RCA. RCA proximal ligation site was identified intraoperatively, considering the best mean graft flow (MGF) and the absence of ischemic events. The patient was discharged after a week without adverse events. The 1-year follow-up was uneventful. The intraoperative use of TTFM could guide the surgeon's hand making straightforward the surgical treatment for ACAOS.

Evaluation of the Efficacy Duration of Topical Therapies in Eyes with Primary Open-Angle Glaucoma.

Background: To investigate the efficacy interval of the topical therapies available for primary open-angle glaucoma (POAG) and the ocular and systemic features potentially associated. Methods: This retrospective study included 190 patients with POAG undergoing first topical therapy, throughout a follow-up of 15 years. The patients started one topical intraocular pressure (IOP)-lowering drug within single molecules such betablockers, prostaglandin or dorzolamide, or fixed combinations such as betablockers + prostaglandin, betablockers + dorzolamide, or betablockers + brimonidine. Efficacy duration was measured as the time between the start of the therapy and the change due to IOP increase or visual field worsening. For each patient, ocular and systemic features and comorbidities were analysed to detect any significant correlation with the length of effectiveness of every drug used. Results: The molecules explored showed some discrepancies in terms of mean duration of efficacy; however, no significant differences were demonstrated (p > 0.05). Furthermore, when evaluating the overall cohort, no systemic or ocular features correlated significantly with the effectiveness of the molecules explored. However, the same analysis carried out upon stratifying the different groups according to the IOP-lowering drops they received, demonstrated that the drug efficacy could be influenced by several ocular and systemic features. Conclusion: Data observed in this study suggest that there is no difference in using one of the medications evaluated as first choice of treatment of POAG if the patients are accurately evaluated and the most recent guidelines are adopted.

The Chaperone System in Salivary Glands: Hsp90 Prospects for Differential Diagnosis and Treatment of Malignant Tumors.

Salivary gland tumors represent a serious medical problem and new tools for differential diagnosis and patient monitoring are needed. Here, we present data and discuss the potential of molecular chaperones as biomarkers and therapeutic targets, focusing on Hsp10 and Hsp90. The salivary glands are key physiological elements but, unfortunately, the information and the means available for the management of their pathologies, including cancer, are scarce. Progress in the study of carcinogenesis has occurred on various fronts lately, one of which has been the identification of the chaperone system (CS) as a physiological system with presence in all cells and tissues (including the salivary glands) that plays a role in tumor-cell biology. The chief components of the CS are the molecular chaperones, some of which belong to families of evolutionarily related molecules named heat shock protein (Hsp). We are quantifying and mapping these molecular chaperones in salivary glands to determine their possible role in the carcinogenetic mechanisms in these glands and to assess their potential as diagnostic biomarkers and therapeutic targets. Here, we report recent findings on Hsp10 and Hsp90 and show that the quantitative and topographic patterns of tissue Hsp90 are distinctive of malignant tumors and differentiate benign from malignant lesions. The Hsp90 results show a correlation between quantity of chaperone and tumor progression, which in turn calls for negative chaperonotherapy, namely, elimination/inhibition of the chaperone to stop the tumor. We found that in vitro, the Hsp90 inhibitor Ganetespib is cytotoxic for the salivary gland UM-HACC-2A cell line. The drug, by interfering with the pro-survival NF-κB pathway, hampers cellular proliferation and migration, and favors apoptosis, and can, therefore, be considered a suitable candidate for future experimentation to develop a treatment for salivary gland tumors.

Update on Management of Cardiovascular Diseases in Women.

Cardiovascular diseases (CVD) have a lower prevalence in women than men; although, a higher mortality rate and a poorer prognosis are more common in women. However, there is a misperception of CVD female risk since women have commonly been considered more protected so that the real threat is vastly underestimated. Consequently, female patients are more likely to be treated less aggressively, and a lower rate of diagnostic and interventional procedures is performed in women than in men. In addition, there are substantial sex differences in CVD, so different strategies are needed. This review aims to evaluate the main gender-specific approaches in CVD.

Heat Shock Proteins Alterations in Rheumatoid Arthritis.

Rheumatoid arthritis (RA) is a chronic inflammatory and autoimmune disease characterized by the attack of the immune system on the body's healthy joint lining and degeneration of articular structures. This disease involves an increased release of inflammatory mediators in the affected joint that sensitize sensory neurons and create a positive feedback loop to further enhance their release. Among these mediators, the cytokines and neuropeptides are responsible for the crippling pain and the persistent neurogenic inflammation associated with RA. More importantly, specific proteins released either centrally or peripherally have been shown to play opposing roles in the pathogenesis of this disease: an inflammatory role that mediates and increases the severity of inflammatory response and/or an anti-inflammatory and protective role that modulates the process of inflammation. In this review, we will shed light on the neuroimmune function of different members of the heat shock protein (HSPs) family and the complex manifold actions that they exert during the course of RA. Specifically, we will focus our discussion on the duality in the mechanism of action of Hsp27, Hsp60, Hsp70, and Hsp90.

Probiotics Properties: A Focus on Pregnancy Outcomes.

A healthy microbiome plays an important role in the prevention of illness and maintenance of overall health, including reproductive health. Although the therapeutic advantages of probiotics have been shown to run across multiple organ systems, their role in pregnancy is not well explored. The aim of this review is to highlight the potential advantages and adverse effects of probiotics in pregnancy. Data were collected from the literature over the past decade using PubMed, Medline, Google Scholar, Ovid, Scopus, and Science Direct. A total of 40 articles were utilized in this review. Collected data indicated that prenatal and post-natal supplementation with lactobacilli alone or lactobacilli with Bifidobacterium spp. seems to be protective. Probiotics may improve insulin resistance and consequently reduce the risk of gestational diabetes. Probiotics may also reduce anxiety and depression by influencing brain activity. Additionally, they interfere with vaginal flora to make it friendlier to beneficial bacteria, and enhance anti-inflammatory or reduce pro-inflammatory cytokines. They may also decrease eczema in breastfed infants and prevent allergic reactions by downregulating Th2 responses to specific allergens from mid to late gestation. Leveraging the cervicovaginal microbiota could promote a number of positive pregnancy-related health outcomes. Caution should be exercised in the selection, dosing, and monitoring of probiotics administration. More comprehensive randomized clinical trials are needed to reach a more meaningful evidence-based clinical knowledge.

Molecular Mechanisms Leading from Periodontal Disease to Cancer.

Periodontitis is prevalent in half of the adult population and raises critical health concerns as it has been recently associated with an increased risk of cancer. While information about the topic remains somewhat scarce, a deeper understanding of the underlying mechanistic pathways promoting neoplasia in periodontitis patients is of fundamental importance. This manuscript presents the literature as well as a panel of tables and figures on the molecular mechanisms of Porphyromonas gingivalis and Fusobacterium nucleatum, two main oral pathogens in periodontitis pathology, involved in instigating tumorigenesis. We also present evidence for potential links between the RANKL-RANK signaling axis as well as circulating cytokines/leukocytes and carcinogenesis. Due to the nonconclusive data associating periodontitis and cancer reported in the case and cohort studies, we examine clinical trials relevant to the topic and summarize their outcome.

Comparison of IOP obtained in different kind of eyes with contact and no contact tonometers.

BACKGROUND: The aim of this study is to analyze and compare the intraocular pressure (IOP) values measured in three different kinds of participants such as healthy subjects (HS), keratoconus patients (KP), and those who underwent myopic photorefractive keratectomy (MPRK). The devices used in this study are the Goldmann Applanation Tonometry (GAT), the dynamic contour tonometry (DCT), the ocular response analyzer (ORA), and the Corvis ST (CST). SUBJECTS AND METHODS: This research included 92 eyes of 92 h, 63 eyes of 63 KP, and 58 eyes of 58 MPRKM. Each participant underwent a complete ophthalmic evaluation and IOP measurement with GAT, DCT, ORA, and CST. A statistical analysis was conducted to detect possible differences and correlations. RESULTS: First, according to the observed data, HS eyes displayed mean IOP values measured with GAT, DCT, ORA, and CST, respectively, 15.82 ± 2.74 mmHg, 17.63 ± 2.28 mmHg, 16.24 ± 3.14 mmHg, and 17.31 ± 3.21 mmHg. Then, KP eyes showed mean IOP values measured with GAT, DCT, ORA, and CST of, respectively, 14.89 ± 1.64 mmHg, 16.97 ± 2.08 mmHg, 13.09 ± 3.12 mmHg, and 13.78 ± 2.11 mmHg. Finally, MPRK eyes showed mean IOP values measured with GAT, DCT, ORA, and CST of, respectively, 13.92 ± 1.34 mmHg, 15.39 ± 2.86 mmHg, 16.63 ± 2.51 mmHg, and 15.06 ± 1.56 mmHg. CONCLUSION: According to the observed data, ORA and GAT might be used interchangeably in HS, whereas GAT, ORA, and CST in KP eyes. Moreover, it has been noticed that in those eyes that previously undergone a myopic PRK, GAT provided lower values of IOP in comparison with other devices.

Hsp27 and Hsp60 in human submandibular salivary gland: Quantitative patterns in healthy and cancerous tissues with potential implications for differential diagnosis and carcinogenesis.

Tumors of the submandibular salivary gland (SMG) are uncommon but sufficiently frequent for the physician to consider them in routine examinations and for the pathologist to be prepared to differentiate them from other tissue abnormalities. However, scarcity of specimens makes training difficult, a situation compounded by the lack of accepted universal diagnostic guidelines. Furthermore, there is little information on the chaperone system (CS) of the gland, despite the increasing evidence of its participation in carcinogenesis as a biomarker for diagnosis and patient follow up, and in the mechanisms by which the tumor cells thrive. We are investigating this aspect of various tumors, and here we describe standardized methods for assessing the tissue levels of two chaperones, Hsp27 and Hsp60, in normal SMG and its tumors. We present illustrative results obtained with immunohistochemistry (IHC) and immunofluorescence-confocal microscopy (IF-CM), which we propose as a platform onto which a data base could be built by adding new information and which would provide material for developing guidelines for tumor identification and monitoring. The initial findings are encouraging in as much as the tumors surveyed showed quantitative patterns of Hsp27 and Hsp60 that distinguished tumoral from normal tissue and certain tumors from the others, and the results from IHC were confirmed by IF-CM.

Salivary gland proteins alterations in the diabetic milieu.

Salivary glands are considered the chief exocrine glands of the mouth and physiologically contribute to the maintenance of the homeostasis of the oral cavity. They consist of the parotid, submandibular and sublingual glands, which come in pairs and are collectively called the major glands, and the minor glands, which are much smaller and are dispersed throughout the buccal cavity. Salivary glands are distinguished by their size, amount of saliva secretion and their location in the oral cavity. Salivary glands pathophysiology has been a subject of interest in various worldwide metabolic disorders, including diabetes mellitus. Diabetes mellitus (DM), a global health concern, with a pathological imprint involved in vasculature, promotes microvascular and macrovascular complications among which periodontitis ranks sixth. Indeed, DM has also been directly associated with oral health lesions. Specifically, salivary glands in the context of diabetes have been a focal point of study and emphasis in the research field. There is evidence that relates salivary secretion content and diabetes progression. In this review, we present all the reported evidence of the deregulation of specific salivary proteins associated with the progression of diabetes in parallel with changes in salivary gland morphology, cellular architecture, and salivary secretion and composition more generally.

Italian Multicenter Registry of Bare Metal Stent Use in Modern Percutaneous Coronary Intervention Era (AMARCORD): A multicenter observational study.

OBJECTIVES: We aimed to evaluate the use of bare metal stent (BMS) implantation in current percutaneous coronary intervention (PCI) era, focusing on indications for use and clinical outcomes. BACKGROUND: Limited data on BMS usage in current clinical practice are available. METHODS: All patients who underwent PCI with at least one BMS implantation in 18 Italian centers from January 1, 2013 to December 31, 2017, were included in our registry. Rates of BMS use and reasons for BMS implantations were reported for the overall study period and for each year. Primary outcomes were mortality, bleeding (Bleeding Academic Research Consortium-BARC and Thrombolysis in Myocardial Infarction-TIMI non-CABG definitions), and major adverse cardiac events (MACE) defined as the composite of all-cause and cardiac death, any myocardial infarction, target vessel revascularization, or any stent thrombosis. RESULTS: Among 58,879 patients undergoing PCI in the study period, 2,117 (3.6%) patients (mean age 73 years, 69.7% males, 73.3% acute coronary syndrome) were treated with BMS implantation (2,353 treated lesions). The rate of BMS implantation progressively decreased from 10.1% (2013) to 0.3% (2017). Main reasons for BMS implantation were: ST-elevation myocardial infarction (STEMI) (23.1%), advanced age (24.4%), and physician's perception of high-bleeding risk (34.0%). At a mean follow-up of 2.2 ± 1.5 years, all-cause and cardiac mortality were 25.6 and 12.7%, respectively; MACE rate was 35.3%, any bleeding rate was 13.0% (BARC 3-5 bleeding 6.3%, TIMI non-CABG major bleeding 6.1%). CONCLUSION: In a large, contemporary, real-world, multicenter registry, BMS use progressively reduced over the last 5 years. Main reasons for BMS implantation were STEMI, advanced age, and physician's perception of high-bleeding risk. High rates of mortality and MACE were observed in this real-world high-risk population.