Anticancer Effects of Plasma-Treated Water Solutions from Clinically Approved Infusion Liquids Supplemented with Organic Molecules.

Water solutions treated by cold atmospheric plasmas (CAPs) currently stand out in the field of cancer treatment as sources of exogenous blends of reactive oxygen and nitrogen species (RONS). It is well known that the balance of RONS inside both eukaryotic and prokaryotic cells is directly involved in physiological as well as pathological pathways. Also, organic molecules including phenols could exert promising anticancer effects, mostly attributed to their pro-oxidant ability in vitro and in vivo to generate RONS like O2-, H2O2, and a mixture of potentially cytotoxic compounds. By our vision of combining the efficacy of plasma-produced RONS and the use of organic molecules, we could synergistically attack cancer cells; yet, so far, this combination, to the best of our knowledge, has been completely unexplored. In this study, l-tyrosine, an amino acid with a phenolic side chain, is added to a physiological solution, often used in clinical practice (SIII) to be exposed to plasma. The efficacy of the gas plasma-oxidized SIII solution, containing tyrosine, was evaluated on four cancer cell lines selected from among tumors with poor prognosis (SHSY-5Y, MCF-7, HT-29, and SW-480). The aim was to induce tumor toxicity and trigger apoptosis pathways. The results clearly indicate that the plasma-treated water solution (PTWS) reduced cell viability and oxygen uptake due to an increase in intracellular ROS levels and activation of apoptosis pathways in all investigated cancer cells, which may be related to the activation of the mitochondrial-mediated and p-JNK/caspase-3 signaling pathways. This research offers improved knowledge about the physiological mechanisms underlying cancer treatment and a valid method to set up a prompt, adequate, and effective cancer treatment in the clinic.

Plasma Treated Water Solutions in Cancer Treatments: The Contrasting Role of RNS.

Plasma Treated Water Solutions (PTWS) recently emerged as a novel tool for the generation of Reactive Oxygen and Nitrogen Species (ROS and RNS) in liquids. The presence of ROS with a strong oxidative power, like hydrogen peroxide (H2O2), has been proposed as the main effector for the cancer-killing properties of PTWS. A protective role has been postulated for RNS, with nitric oxide (NO) being involved in the activation of antioxidant responses and cell survival. However, recent evidences proved that NO-derivatives in proper mixtures with ROS in PTWS could enhance rather than reduce the selectivity of PTWS-induced cancer cell death through the inhibition of specific antioxidant cancer defenses. In this paper we discuss the formation of RNS in different liquids with a Dielectric Barrier Discharge (DBD), to show that NO is absent in PTWS of complex composition like plasma treated (PT)-cell culture media used for in vitro experiments, as well as its supposed protective role. Nitrite anions (NO2-) instead, present in our PTWS, were found to improve the selective death of Saos2 cancer cells compared to EA.hy926 cells by decreasing the cytotoxic threshold of H2O2 to non-toxic values for the endothelial cell line.

Degree of luminal narrowing and composition of thrombus in plaque erosion.

As the degree of luminal narrowing increases, shear stress increases, and high shear stress is known to activate platelets. However, the relationship between the degree of luminal narrowing and the composition of thrombus in patients with plaque erosion has not been studied. A total of 148 patients with plaque erosion and thrombus detected by optical coherence tomography were divided into tertiles based on the minimum lumen area (MLA) at the culprit lesion. Thrombus was categorized as platelet-rich or fibrin-rich. Among 148 patients, 50 (34%) were in the mild stenosis group, 49 (33%) were in the moderate stenosis group, and 49 (33%) were in the severe stenosis group. The composition of thrombus was significantly different among the 3 groups (prevalence of platelet-rich thrombus was 60% in the mild stenosis group; 78% in the moderate stenosis group; and 84% in the severe stenosis group; P = 0.021). The pattern of fibrin-rich thrombus showed the opposite: 40%, 22%, and 16%, respectively. In the multivariate analysis, current smoking was independently associated with fibrin-rich thrombus (odds ratio [OR] 2.364 [95% CI 1.004-5.567], P = 0.049). This study demonstrated that platelet-rich thrombus was the predominant type of thrombus in plaque erosion. The prevalence of fibrin-rich thrombus was highest in the mild stenosis group.

Human monocyte-derived macrophages: Pathogenetic role in plaque rupture associated to systemic inflammation.

BACKGROUND: Macrophages play a key role in coronary plaque destabilization. In-vitro human monocyte-derived macrophages (MDMs) are used to study macrophages infiltrating tissue. Optical coherence tomography (OCT) provides an in-vivo insight of the coronary arteries. We compared the MDMs morpho-phenotype and culprit plaque features at OCT in acute coronary syndrome (ACS) patients according to the underlying plaque pathobiology. METHODS: Sixty-six patients undergoing coronary angiography and pre-angioplasty OCT of the culprit vessel were allocated to three groups according to mechanism of ACS at OCT and C-reactive protein levels (cut-off: 2 mg/Ll): 1) plaque rupture with systemic inflammation; 2) plaque rupture without systemic inflammation, 3) plaque with intact fibrous cap. A blood sample was collected to obtain MDMs, categorized as having "round" or "spindle" morphology. RESULTS: Thirty-two patients (48.5%) were assigned to Group 1, 10 (15.2%) to Group 2 and 24 (36.4%) to Group 3. The "round" MDMs were significantly more frequent in Group 1 (39.25 ± 4.98%) than in Group 2 (23.89 ± 3.10%) and Group 3 (23.02 ± 7.89%), p = 0.008. MDMs in Group 1 as compared to Groups 2 and 3 showed lower efferocytosis (8.74 ± 1.38 vs 9.74 ± 2.15 vs 11.41 ± 2.41; p = 0.012), higher tissue factor levels (369.84 ± 101.13 vs 301.89 ± 59.78 vs 231.74 ± 111.47; p = 0.001) and higher heme oxygenase-1 expression (678.78 ± 145.43 vs 419.12 ± 74.44 vs 409.78 ± 64.33; p = 0.008). CONCLUSIONS: MDMs of ACS patients show morpho-phenotypic heterogeneity with prevalence of pro-thrombotic and pro-oxidative properties in case of plaque rupture and systemic inflammation. Such MDMs subpopulation may take part to the cellular pathways leading to fibrous cap rupture with the subsequent thrombus formation.

Macrophage infiltrates in coronary plaque erosion and cardiovascular outcome in patients with acute coronary syndrome.

BACKGROUND AND AIMS: Plaque erosion (PE) is responsible for at least one-third of acute coronary syndrome (ACS), and inflammation plays a key role in plaque instability. We assessed the presence of optical coherence tomography (OCT)-defined macrophage infiltrates (MØI) at the culprit site in ACS patients with PE, evaluating their clinical and OCT correlates, along with their prognostic value. METHODS: ACS patients undergoing OCT imaging and presenting PE as culprit lesion were retrospectively selected. Presence of MØI at culprit site was assessed. The incidence of major adverse cardiac events (MACEs), defined as the composite of cardiac death, recurrent myocardial infarction and target-vessel revascularization (TVR), was assessed [follow-up median (interquartile range, IQR) time 2.5 (2.03-2.58) years]. RESULTS: We included 153 patients [median age (IQR) 64 (53-75) years, 99 (64.7%) males]. Fifty-one (33.3%) patients presented PE with MØI and 102 (66.7%) PE without MØI. Patients having PE with MØI compared with PE patients without MØI had more vulnerable plaque features both at culprit site and at non-culprit segments. MACEs were significantly more frequent in PE with MØI patients compared with PE without MØI [11 (21.6%) vs. 6 (5.9%), p = 0.008], mainly driven by a higher risk of cardiac death and TVR. At multivariable Cox regression, PE with MØI was an independent predictor of MACEs [HR = 2.95, 95% CI (1.09-8.02), p = 0.034]. CONCLUSIONS: Our study demonstrates that among ACS patients with PE the presence of MØI at culprit lesion is associated with more vulnerable plaque features, along with a worse prognosis at a long-term follow-up.

Healed Plaques in Patients With Stable Angina Pectoris.

OBJECTIVE: Healed plaques, signs of previous plaque destabilization, are frequently found in the coronary arteries. Healed plaques can now be diagnosed in living patients. We investigated the prevalence, angiographic, and optical coherence tomography features of healed plaques in patients with stable angina pectoris. Approach and Results: Patients with stable angina pectoris who had undergone optical coherence tomography imaging were included. Healed plaques were defined as plaques with one or more signal-rich layers of different optical density. Patients were divided into 2 groups based on layered or nonlayered phenotype at the culprit lesion. Among 163 patients, 87 (53.4%) had layered culprit plaque. Patients with layered culprit plaque had more multivessel disease (62.1% versus 44.7%, P=0.027) and more angiographically complex culprit lesions (64.4% versus 35.5%, P<0.001). Layered culprit plaques had higher prevalence of lipid plaque (83.9% versus 64.5%, P=0.004), macrophage infiltration (58.6% versus 35.5%, P=0.003), calcifications (78.2% versus 63.2%, P=0.035), and thrombus (28.7% versus 14.5%, P=0.029). Lipid index (P=0.001) and percent area stenosis (P=0.015) were greater in the layered group. The number of nonculprit plaques, evaluated using coronary angiograms, tended to be greater in patients with layered culprit plaque (4.2±2.5 versus 3.5±2.1, P=0.053). Nonculprit plaques in patients with layered culprit lesion had higher prevalence of layered pattern (P=0.002) and lipid phenotype (P=0.005). Lipid index (P=0.013) and percent area stenosis (P=0.002) were also greater in this group. CONCLUSIONS: In patients with stable angina pectoris, healed culprit plaques are common and have more features of vulnerability and advanced atherosclerosis both at culprit and nonculprit lesions.

Biological profile of monocyte-derived macrophages in coronary heart disease patients: implications for plaque morphology.

The prevalence of a macrophage phenotype in atherosclerotic plaque may drive its progression and/or instability. Macrophages from coronary plaques are not available, and monocyte-derived macrophages (MDMs) are usually considered as a surrogate. We compared the MDM profile obtained from coronary artery disease (CAD) patients and healthy subjects, and we evaluated the association between CAD MDM profile and in vivo coronary plaque characteristics assessed by optical coherence tomography (OCT). At morphological analysis, MDMs of CAD patients had a higher prevalence of round than spindle cells, whereas in healthy subjects the prevalence of the two morphotypes was similar. Compared to healthy subjects, MDMs of CAD patients had reduced efferocytosis, lower transglutaminase-2, CD206 and CD163 receptor levels, and higher tissue factor (TF) levels. At OCT, patients with a higher prevalence of round MDMs showed more frequently a lipid-rich plaque, a thin-cap fibroatheroma, a greater intra-plaque macrophage accumulation, and a ruptured plaque. The MDM efferocytosis correlated with minimal lumen area, and TF levels in MDMs correlated with the presence of ruptured plaque. MDMs obtained from CAD patients are characterized by a morpho-phenotypic heterogeneity with a prevalence of round cells, showing pro-inflammatory and pro-thrombotic properties. The MDM profile allows identifying CAD patients at high risk.

Activation of Nrf2/HO-1 Pathway and Human Atherosclerotic Plaque Vulnerability:an In Vitro and In Vivo Study.

Reactive oxygen species (ROS) induce nuclear factor erythroid 2-related factor 2 (Nrf2) activation as an adaptive defense mechanism, determining the synthesis of antioxidant molecules, including heme-oxygenase-1 (HO-1). HO-1 protects cells against oxidative injury, degrading free heme and inhibiting ROS production. HO-1 is highly expressed in macrophages during plaque growth. Macrophages are morpho-functionally heterogeneous, and the prevalence of a specific phenotype may influence the plaque fate. This heterogeneity has also been observed in monocyte-derived macrophages (MDMs), a model of macrophages infiltrating tissue. The study aims to assess oxidative stress status and Nrf2/HO-1 axis in MDM morphotypes obtained from healthy subjects and coronary artery disease (CAD) patients, in relation to coronary plaque features evaluated in vivo by optical coherence tomography (OCT). We found that MDMs of healthy subjects exhibited a lower oxidative stress status, lower Nrf2 and HO-1 levels as compared to CAD patients. High HO-1 levels in MDMs were associated with the presence of a higher macrophage content, a thinner fibrous cap, and a ruptured plaque with thrombus formation, detected by OCT analysis. These findings suggest the presence of a relationship between in vivo plaque characteristics and in vitro MDM profile, and may help to identify patients with rupture-prone coronary plaque.

Plasma-activated medium triggers cell death and the presentation of immune activating danger signals in melanoma and pancreatic cancer cells.

Over the past decade, cold atmospheric plasmas have shown promising application in cancer therapy. The therapeutic use of plasma-activated media is a topic addressed in an emerging field known as plasma pharmacy. In oncology, plasma-activated media are  used to harness the therapeutic effects of oxidant species when they come in contact with cancer cells. Among several factors that contribute to the anticancer effect of plasma-activated liquid media (PALM), H2O2 and NO derivatives likely play a key role in the apoptotic pathway. Despite the significant amount of literature produced in recent years, a full understanding of the mechanisms by which PALM exert their activity against cancer cells is limited. In this paper, a sealed dielectric-barrier discharge was used to disentangle the effect of reactive nitrogen species (RNS) from that of reactive oxygen species (ROS) on cancer cells. Two cancers characterized by poor prognosis have been investigated: metastatic melanoma and pancreatic cancer. Both tumour models exposed to PALM rich in H2O2 showed a reduction in proliferation and an increase in calreticulin exposure and ATP release, suggesting the potential use of activated media as an inducer of immunogenic cell death via activation of the innate immune system.

Coronary Atherosclerotic Phenotype and Plaque Healing in Patients With Recurrent Acute Coronary Syndromes Compared With Patients With Long-term Clinical Stability: An In Vivo Optical Coherence Tomography Study.

Importance: At one end of the coronary artery disease (CAD) spectrum, there are patients with multiple recurrent acute coronary syndromes (rACS), and at the other end there are those with long-standing clinical stability. Predicting the natural history of these patients is challenging because unstable plaques often heal without resulting in ACS. Objective: To assess in vivo the coronary atherosclerotic phenotype as well as the prevalence and characteristics of healed coronary plaques by optical coherence tomography (OCT) imaging in patients at the extremes of the CAD spectrum. Design, Setting, and Participants: This is an observational, single-center cohort study with prospective clinical follow-up. From a total of 823 consecutive patients enrolled in OCT Registry of the Fondazione Policlinico A. Gemelli-IRCCS, Rome, Italy, from March 2009 to February 2016, 105 patients were included in the following groups: (1) patients with rACS, defined as history of at least 3 acute myocardial infarctions (AMIs) or at least 4 ACS with at least 1 AMI; (2) patients with long-standing stable angina pectoris (ls-SAP), defined as a minimum 3-year history of stable angina; and (3) patients with a single unheralded AMI followed by a minimum 3-year period of clinical stability (sAMI). Data were analyzed from January to August 2018. Exposures: Intracoronary OCT imaging of nonculprit coronary segments. Main Outcomes and Measures: Coronary plaque features and the prevalence of healed coronary plaques in nonculprit segments as assessed by intracoronary OCT imaging. Results: Of 105 patients, 85 were men (81.0%); the median (interquartile range) age was 68 (63-75) years. Median (interquartile range) time of clinical stability was 9 (5.0-15.0) years in the ls-SAP group and 8 (4.5-14.5) years in the sAMI group. Patients in the rACS and sAMI groups showed similar prevalence of lipid-rich plaque and thin-cap fibroatheroma, which was significantly higher than in those with ls-SAP (lipid-rich plaque 80.0% [n = 24 of 30] vs 76.3% [n = 29 of 38] vs 37.8% [n = 14 of 37], respectively; P < .001; thin-cap fibroatheroma 40.0% [n = 12 of 30] vs 34.2% [n = 13 of 38] vs 8.1% [n = 3 of 37], respectively; P = .006). Spotty calcifications were more frequently observed in patients with rACS than in those with ls-SAP and sAMI (70.0% [n = 21 of 30] vs 40.5% [n = 15 of 37] vs 44.7% [n = 17 of 38], respectively; P = .04). Healed coronary plaques were rarely observed in patients with rACS, whereas their prevalence was significantly higher in patients with ls-SAP and sAMI (3.3% [n = 1 of 30] vs 29.7% [n = 11 of 37] vs 28.9% [n = 11 of 38], respectively; P = .01). Conclusions and Relevance: Patients with rACS have a distinct atherosclerotic phenotype compared with those with ls-SAP, including higher prevalence of thin-cap fibroatheroma and lower prevalence of healed coronary plaques, suggesting that atherosclerotic profile and plaque healing may play a role in leading the natural history of patients with CAD.

Plasma-Deposited Nanocapsules Containing Coatings for Drug Delivery Applications.

Coatings consisting in gentamicin-containing nanocapsules have been synthetized by means of an aerosol-assisted atmospheric pressure plasma deposition process. The influence of different parameters affecting the process has been extensively investigated by means of a morphological and chemical characterization of the coatings. Scanning electron microscopy highlighted the presence of nanocapsules whose size and abundance depend on power input and deposition time. A detailed analysis carried out with matrix-assisted laser desorption ionization coupled to high-resolution mass spectrometry allowed to detect and identify the presence of gentamicin embedded in the coatings and its rearrangement, as a result of the interaction with the plasma. The release of gentamicin in water has been monitored by means of UV-vis fluorescence spectroscopy, and its biological activity has been evaluated as well by the disk diffusion assay against Staphylococcus aureus and Pseudomonas aeruginosa. It is confirmed that the antibacterial activity of gentamicin is preserved in the plasma-deposited coatings. Preliminary cytocompatibility investigations indicated that eukaryotic cells well tolerate the release of gentamicin from the coatings.

Preparation and Characterization of Soybean Oil-Based Polyurethanes for Digital Doming Applications.

Polyurethane-resin doming is currently one of the fastest growing markets in the field of industrial graphics and product identification. Semi-rigid bio-based polyurethanes were prepared deriving from soybean oil as a valuable alternative to fossil materials for digital doming and applied to digital mosaic technology. Bio-resins produced can favorably compete with the analogous fossil polymers, giving high-quality surface coatings (ascertained by SEM analyses). In addition, polyurethane synthesis was accomplished by using a mercury- and tin-free catalyst (the commercially available zinc derivative K22) bringing significant benefits in terms of cost efficiency and eco-sustainability.

Long-Term Survival and Quality of Life of Patients Undergoing Emergency Coronary Artery Bypass Grafting for Postinfarction Cardiogenic Shock.

BACKGROUND: This study evaluated the long-term outcome of patients undergoing emergency coronary artery bypass grafting (eCABG) for cardiogenic shock after acute myocardial infarction. METHODS: Sixty-seven consecutive patients underwent eCABG for cardiogenic shock at 2 European institutions during an 11-year period. Preoperative, intraoperative, postoperative, and long-term follow-up data of all patients were prospectively collected. RESULTS: Hospital survival was 86% (58 of 67), with all deaths due to cardiac causes. At a mean follow-up of 78 ± 48 months (range, 1 to 153 months), 43 of the 58 patients (74%) discharged from the hospital were alive. Causes of death in 9 of the 15 follow-up deaths (60%) were noncardiac. Overall survival rate at the end of follow-up was 64% (43 of 67). Of the 43 survivors, 41 (95%) were in New York Heart Association Functional Classification I to II, ischemia free, had a Karnofsky performance status exceeding 80, and an excellent quality of life as assessed by the Seattle Angina Questionnaire. The use of cardiopulmonary bypass and the internal thoracic artery were associated with significantly better long-term survival. CONCLUSIONS: The long-term survival and quality of life of patients who undergo eCABG for cardiogenic shock after acute myocardial infarction are good, and eCABG should be considered a valuable therapeutic option in this setting. The use of cardiopulmonary bypass and the internal thoracic artery at the time of the operation are strongly advocated.

Prognostic role of multiple biomarkers in stable patients undergoing fractional flow reserve-guided coronary angioplasty.

AIMS: Fractional flow reserve (FFR)-guided percutaneous coronary intervention (PCI), along with optimal medical therapy, improves clinical outcome by targeting ischemia-inducing stenosis. Yet, plaque progression or stent failure may cause recurring cardiac events. We assessed the potential prognostic role of different inflammatory biomarkers, known to be associated with plaque progression or stent failure, in patients undergoing FFR-guided PCI. METHODS: We prospectively enrolled 169 stable angina patients with intermediate coronary stenosis at angiography undergoing FFR-guided PCI. PCI was performed if FFR was 0.80 or less, deferred if FFR was more than 0.80. Serum baseline levels of high-sensitivity C-reactive protein (hs-CRP), eosinophil cationic protein (ECP), cystatin-C (Cys-C), and thromboxane A2 (TXA2) were assessed. Rate of major adverse cardiovascular events (MACE), defined as a composite of cardiovascular death, recurrent myocardial infarction, and target vessel revascularization (TVR), was evaluated. RESULTS: PCI was performed in 78 patients (46%) (mean age 69 ±â€Š10 years, men 73%) and deferred in 91 patients (54%) (mean age 64 ±â€Š11 years, men 53%). Mean clinical follow-up was 31 ±â€Š11 months. Within the PCI group, patients with MACE (n = 14 [18%]) had significantly higher ECP levels than those without (14.4 [9.3-19.5] vs. 4.9 [2.8-10.9] mg/l, P < 0.001), and ECP was a significant predictor of MACE (hazard ratio: 1.05, 95% confidence interval [1.01-1.09], P = 0.021). Within the deferred group, patients with MACE (n = 8 [9%]) had significantly higher CRP levels than those without (15 [6.5-31.9] vs. 1.6 [0.9-2.9] mg/l, P < 0.001) and CRP was a significant predictor of MACE (hazard ratio: 1.04, 95% confidence interval [1.01-1.07], P = 0.015). Cys-C and TXA2 were not significantly different between the two groups. CONCLUSION: Assessing inflammatory biomarkers allows the identification of patients remaining at residual higher risk of MACE after FFR-guided PCI.

Impact of accuracy of fractional flow reserve to reduction of microvascular resistance after intracoronary adenosine in patients with angina pectoris or non-ST-segment elevation myocardial infarction.

Our study aimed to elucidate mechanisms underlying discordance between fractional flow reserve (FFR) and hyperemic stenosis resistance (hSR) in some patient subsets. To do this, we enrolled 30 consecutive patients with stable angina or non-ST elevation myocardial infarction (non-STEMI) and with a nonculprit intermediate coronary lesion (40% to 70%) by coronary angiography. We measured aortic pressure, flow velocity, and pressure distal to lesion simultaneously at basal level and during adenosine-induced (fixed intracoronary dose of 120 µg) hyperemia using a dual-sensor-equipped guidewire. Microvascular resistance (MR; pressure distal to lesion/flow velocity, mm Hg/cm/s) and variation (Δ) in MR levels were calculated both at baseline and after hyperemia, whereas FFR (cutoff <0.80) and hSR [(aortic pressure - pressure distal to lesion)/flow velocity, cutoff >0.80 mm Hg/cm/s] were assessed after intracoronary adenosine. Twenty-three patients (76.7%) showed concordance and 7 patients (23.3%) showed discordance between FFR and hSR (all cases with FFR >0.80 and hSR >0.80). Discordant patients presented more frequently with non-STEMI (85.7% vs 39.1%, p = 0.04), significantly higher C-reactive protein serum levels (median [interquartile range] 5.9 [5.1 to 6.8] vs 4.9 [3.7 to 6.2] mg/L, p = 0.007), and lower ΔMR (p = 0.03) values compared with concordant patients. In conclusion, patients with non-STEMI and those with increased C-reactive protein levels show a lower reduction in MR after intracoronary adenosine-induced hyperemia, leading to FFR underestimation.

Patients with microvascular obstruction after primary percutaneous coronary intervention show a gp91phox (NOX2) mediated persistent oxidative stress after reperfusion.

BACKGROUND: Persistent oxidative stress may play a key role in microvascular obstruction (MVO). We aimed at assessing the role of platelet gp91phox (NOX2), the catalytic subunit of NADPH oxidase in MVO. METHODS: We enrolled 40 patients with ST-elevation myocardial infarction (STEMI) undergoing primary percutaneous coronary intervention within 12 h from symptoms onset, either with angiographic MVO (n=20) or good angiographic myocardial reperfusion (MR) (n=20). Angiographic MVO was defined as a final thrombolysis in myocardial infarction (TIMI) flow ≤2 or TIMI flow of 3 with myocardial blush grade <2. NOX2 and isoprostanes (8-iso-PGF2α) levels, as assessed by enzyme-linked immunoadsorbent assay (ELISA) or by an enzyme immunoassays, respectively, were measured on admission, at 24 h and pre-discharge. RESULTS: NOX2 levels increased from baseline to pre-discharge in patients with angiographic MVO (20.25 (15-24.75) pg/ml vs 25.50 (17-29.25) pg/ml, p=0.02), but not in MR patients (p=0.45), with a significant interaction between baseline and pre-discharge levels among the two groups (p=0.04). The levels of 8-iso-PGF2α showed a trend to increase from baseline to pre-discharge in angiographic MVO patients (295 (183.50-389.25) pmol/l vs 322 (206-370) pmol/l, p=0.06), but not in patients with MR (p=0.56), with a trend for interaction between baseline and pre-discharge levels among the two groups (p=0.09). CONCLUSION: Patients with MVO, but not those with myocardial reperfusion, have a sustained increase of NOX2 and 8-iso-PGF2α. Therapies targeting NOX2 or high dosage antioxidants should be tested for MVO prevention and treatment.

Case-control registry of excimer laser coronary angioplasty versus distal protection devices in patients with acute coronary syndromes due to saphenous vein graft disease.

Laser atherectomy might decrease procedural complications during percutaneous coronary intervention (PCI) of degenerated saphenous vein grafts (SVGs) in case of unstable or thrombotic lesions because of its ability to debulk and vaporize thrombus. We aimed at prospectively evaluating the safety and efficacy of excimer laser coronary angioplasty (ELCA) as a primary treatment strategy in consecutively unstable patients undergoing PCI of degenerated SVG lesions. Seventy-one consecutive patients with non-ST elevation acute coronary syndrome (mean age 69 ± 10 years, 66 men [89%]) undergoing PCI of degenerated SVG were enrolled in a prospective case-control registry, using 2 different distal protection devices (DPDs; FilterWire EZ [Boston Scientific, Natick, Massachusetts; n = 24] and SpiderRX [Ev3, Plymouth, Minnesota; n = 23]) or ELCA (n = 24). Primary end points of the study were incidence of angiographic microvascular obstruction (Thrombolysis In Myocardial Infarction flow grade of <3 or Thrombolysis In Myocardial Infraction flow grade of 3 with myocardial blush grade 1 to 2) and incidence of type IVa myocardial infarction. Angiographic microvascular obstruction incidence tended to be less in ELCA-treated patients compared with DPD-treated patients (3 [13%] vs 15 [32%], p = 0.09). Type IVa myocardial infarction incidence was more in DPD-treated patients compared with ELCA-treated patients (23 [49%] vs 5 [21%], p = 0.04). In conclusion, in patients with non-ST elevation acute coronary syndrome undergoing PCI of degenerated SVG, ELCA compared with DPD, is associated with a trend for better myocardial reperfusion and a lesser incidence of periprocedural necrosis. Controlled randomized trials are warranted to confirm these early observations.

Current interventional coronary applications of excimer laser.

Excimer laser utilization as an adjunctive device for percutaneous coronary intervention has increased in the last few years. Many technical advancements have led to better results in terms of efficacy and safety with a low complication rate. In particular, excimer laser for thrombus-containing lesions is able to achieve rapid thrombus removal and plaque debulking along with subsequent facilitation of stent angioplasty and a low rate of microvascular obstruction. Other indications for laser angioplasty embrace in-stent restenosis, chronic total occlusions, saphenous vein graft lesions and new potential applications, such as stent expansion optimization and bifurcation lesions. As for other medical devices, however, excimer laser should be tested in future randomized studies against current standard of therapy in order to better define its role for each of the indications summarized above.

Colon-like right coronary artery.

Coronary aneurysmatic dilatation may be localized to a segment or may involve multiple segments. We herein report a case of a diffuse aneurysmatic dilatation of the right coronary artery.