Emerging evidence on the role of breast microbiota on the development of breast cancer in high-risk patients.

Cancer is a multi-factorial disease, and the etiology of breast cancer (BC) is due to a combination of both genetic and environmental factors. Breast tissue shows a unique microbiota, Proteobacteria and Firmicutes are the most abundant bacteria in breast tissue, and several studies have shown that the microbiota of healthy breast differs from that of BC. Breast microbiota appears to be correlated with different characteristics of the tumor, and prognostic clinicopathologic features. It also appears that there are subtle differences between the microbial profiles of the healthy control and high-risk patients. Genetic predisposition is an extremely important risk factor for BC. BRCA1/2 germline mutations and Li-Fraumeni syndrome are DNA repair deficiency syndromes inherited as autosomal dominant characters that substantially increase the risk of BC. These syndromes exhibit incomplete penetrance of BC expression in carrier subjects. The action of breast microbiota on carcinogenesis might explain why women with a mutation develop cancer and others do not. Among the potential biological pathways through which the breast microbiota may affect tumorigenesis, the most relevant appear to be DNA damage caused by colibactin and other bacterial-derived genotoxins, ß-glucuronidase-mediated estrogen deconjugation and reactivation, and HPV-mediated cancer susceptibility. In conclusion, in patients with a genetic predisposition, an unfavorable breast microbiota may be co-responsible for the onset of BC. Prospectively, the ability to modulate the microbiota may have an impact on disease onset and progression in patients at high risk for BC.

No-daily hormonal contraception today: general overview and application in specific clinical settings.

No-daily hormonal contraception includes short-acting reversible contraceptives (SARC), which contain estrogen and progestin (vaginal ring and transdermal patch), and long-acting reversible contraceptives (LARC), which contain only progestin (levonorgestrel-releasing intrauterine device and etonogestrel subdermal implant). No-daily hormonal contraceptives are reversible, avoid oral daily intake and have high contraceptive efficacy. They offer advantages over the traditional oral route, increasing user compliance, and reducing forgetfulness. Furthermore, they have several non-contraceptive benefits. This review aims to highlight the strengths of choices other than the traditional 'pill', with the goal of implementing contraceptive counseling, which should be personalized and tailored to each woman. Different subsets of patients may use no-daily contraception at different stages of their lives, with the option of either LARC or SARC. Specific contexts for its use are adolescence, perimenopause, obese women, eating disorders or intestinal malabsorption, breastfeeding, and post voluntary termination of pregnancy. Non-daily contraceptives can be an attractive alternative to the daily contraceptive pill, with benefits that are relevant to each woman desiring contraception, especially in unique and specific settings where customization of the contraceptive method is essential.

Axillary dissection in patients with preoperative positive nodal cytology: Genuine need or overtreatment?

Recent studies demonstrated the possibility to avoid axillary dissection (ALND) in selected patients with one or two metastatic nodes. Otherwise, patients with positive nodal ultrasound-guided fine-needle aspiration cytology (US-FNAC) currently undergo ALDN. The aim of this study is to quantify the nodal burden in patients with positive US-FNAC treated with ALND and to evaluate if clinical or pathological characteristics associated with low nodal involvement can be identified. This is a multicentric retrospective study involving 297 patients who underwent ALND because of a positive preoperative US-FNAC. A total of 157 patients showed bulky axillary lymph nodes at diagnosis, and 70% of them had three or more metastatic nodes. One hundred and forty patients had a clinically negative axilla and in 50% of them, 4 or more metastatic nodes were found with axillary dissection. Overall, the median number of metastatic nodes was 5. Favorable pathological characteristics of tumors were found in patients with only one or two metastatic nodes: smaller primary tumor, a lower proportion of grade 3, invasive lobular carcinomas and a higher proportion of low-Ki67 tumors. In the group of patients with clinically negative axilla and potentially meeting ACOSOG Z0011 criteria, 22 (31%) showed less than three metastatic axillary nodes. A preoperative positive axillary FNAC is associated with a metastatic nodal burden significantly higher than in patients with positive sentinel lymph node biopsy (SLNB). Nevertheless, about 30% of patients with cN0 axilla, positive axillary FNAC performed because of suspicious nodes on imaging, T1-2 primary tumor and breast-conserving surgery showed less than three metastatic axillary nodes, thus meeting ACOSOG Z0011 trial's criteria and therefore would be eligible for skipping ALND according to current guidelines.

Small-for-gestational-age birth is linked to cardiovascular dysfunction in early childhood.

BACKGROUND: The aim of this study was to assess clinical and echographic markers of cardiovascular dysfunction in infants born small for gestational age (SGA) compared to a control group of subjects born adequate for gestational age (AGA). METHODS: This was a single-center cross-sectional case-control study. We recruited 20 SGA and 20 gestational age-matched AGA subjects at 24 months of age. The study population underwent anthropometric and Doppler 2-dimensional echocardiographic assessments, and carotid artery intima-media thickness (cIMT) and endothelium-dependent vasodilation evaluation (FMD). The pressure-volume curve during diastole was calculated using the algorithm for the elastance calculation on 1 single beat. RESULTS: SGA children showed lower stroke volume, lower left ventricle (LV) dimensions and volume, and greater LV thickness. Diastolic function was impaired in SGA with lower capacitance and higher elastance. Birth weight standard deviation score was positively associated with capacitance and negatively associated with E/E' ratio and elastance, and in SGA infants, the end-diastolic pressure-related volume curve was shifted to the left compared to AGA. cIMT and systemic vascular resistance were significantly higher, while FMD was lower, in SGA compared to AGA; birth weight standard deviation score was directly correlated with FMD and inversely correlated with cIMT. Finally, a longer breastfeeding duration was associated to a lower cIMT even after correction for confounding factors. CONCLUSIONS: This study shows that infants born SGA present an early and subtle cardiovascular dysfunction compared to AGA controls. These alterations are strongly related to weight at birth. Finally, breastfeeding exerts an important protective and beneficial cardiovascular effect.

A Real-Life Multicenter National Study on Nintedanib in Severe Idiopathic Pulmonary Fibrosis.

BACKGROUND: Two therapeutic options are currently available for patients with mild-to-moderate idiopathic pulmonary fibrosis (IPF): pirfenidone and nintedanib. To date, there is still insufficient data on the efficacy of these 2 agents in patients with more severe disease. OBJECTIVES: This national, multicenter, retrospective real-life study was intended to determine the impact of nintedanib on the treatment of patients with severe IPF. METHODS: All patients included had severe IPF and had to have at least 6 months of follow-up before and at least 6 months of follow-up after starting nintedanib. The aim of the study was to compare the decline in lung function before and after treatment. Patient survival after 6 months of therapy with nintedanib was assessed. RESULTS: Forty-one patients with a forced vital capacity (FVC) ≤50% and/or a diffusing capacity of the lung for carbon monoxide (DLCO) ≤35% predicted at the start of nintedanib treatment were enrolled. At the 6-month follow-up, the decline of DLCO (both absolute and % predicted) was significantly reduced compared to the pretreatment period (absolute DLCO at the -6-month, T0, and +6-month time points (5.48, 4.50, and 5.03 mmol/min/kPa, respectively, p = 0.03; DLCO% predicted was 32.73, 26.54, and 29.23%, respectively, p = 0.04). No significant beneficial effect was observed in the other functional parameters analyzed. The 1-year survival in this population was 79%, calculated from month 6 of therapy with nintedanib. CONCLUSIONS: This nationwide multicenter experience in patients with severe IPF shows that nintedanib slows down the rate of decline of absolute and % predicted DLCO but does not have significant impact on FVC or other lung parameters.

Can neuroimaging differentiate PFO and AF-related cardioembolic stroke from the other embolic sources? Clinical-radiological correlation on a retrospective study.

PURPOSE: The aim of this retrospective study was to map the specific ischemic lesion patterns of distribution in patent foramen ovale-related stroke (PFO-stroke) and atrial fibrillation-related stroke (AF-stroke) in patients with idiopatic ischemic stroke. MATERIALS AND METHODS: 750 ischaemic strokes were screened on basis of diagnostic imaging and tests: patients with known causes were excluded. 171 patients with unknown cause were selected and divided in two groups: AF-stroke (43 patients) and PFO-stroke (128 patients). Vascular territories of ischemic involvement were divided into four classes in each group: the anterior cerebral artery, the middle cerebral artery, the vertebro-cerebral artery (including the posterior cerebral artery) and multisite (MS) involvement. RESULTS: Infarcts in vertebro-basilar territory and multisite represented each one about 32% of infarcts in PFO-stroke group and their involvement are more frequent than AF-stroke group (p = 0.03). Ischemic lesions in PFO-group were predominantly cortical (34.3%), and in AF-group cortical-subcortical (60.4%). Multisite pattern of ischemic lesion was more frequent in patients with severe degree of right to left shunts (37.5%). CONCLUSION: In clinical practice, PFO may be considered a cause of cortical stroke on the basis of radiological findings, when VB vascular territory or MS brain involvement is present in younger patients (<50 age).

Laparoscopic Treatment of Bulky Nodes in Primary and Recurrent Ovarian Cancer: Surgical Technique and Outcomes from Two Specialized Italian Centers.

(1) Background: Minimally invasive surgery (MIS) represents a feasible approach in early-stage ovarian cancer, while this question is still unsolved for advanced and recurrent disease. (2) Methods: In this retrospective, multicenter study, we present a series of 21 patients who underwent MIS for primitive or recurrent epithelial ovarian cancer (EOC) with bulky nodal metastasis and discuss surgical technique and outcomes in relation to the current literature. (3) Results: Complete cytoreduction at primary debulking surgery was obtained in 86% of cases. No complication occurred in our patients intraoperatively and only 11.1% of our patients experienced grade 2 and 3 postoperative complications. Notably, all the patients with isolated lymph nodal recurrence (ILNR) were successfully treated with a minimally invasive approach with no intra- or postoperative complications. (4) Conclusions: The results of our study are consistent with those reported in the literature, demonstrating that MIS may represent a safe approach in advanced and recurrent EOC with nodal metastasis if performed on selected patients by expert surgeons with an adequate setting and appropriate technique.

Bone modifying agents in postmenopausal breast cancer patients treated with aromatase inhibitors: beyond bone protection?

Estrogen-receptor positive tumours represent the majority of breast cancers in postmenopausal women. Adjuvant endocrine therapy with aromatase inhibitors (AIs), continued for up to 10 years in high-risk patients, reduces by 40% the risk of recurrence. However, this therapy, among other side effects, is burdened with a higher incidence of osteoporotic bone fractures. To date, both bisphosphonates and denosumab are recognized as first-line drugs in the primary prevention of osteoporotic fractures in patients treated with AIs. They have demonstrated their effectiveness in increasing bone mineral density and in reducing the incidence of fractures, but they have also been shown to improve disease free survival (DFS).

Adherence to Adjuvant Endocrine Therapy in Breast Cancer Patients.

BACKGROUND: Adjuvant endocrine therapy (AET) reduces breast cancer recurrence and mortality of women with hormone-receptor-positive tumors, but poor adherence remains a significant problem. The aim of this study was to analyze AET side effects and their impact on adherence to treatment. METHODS: A total of 373 breast cancer patients treated with AET filled out a specific questionnaire during their follow up visits at the Breast Unit of our Centre. RESULTS: Side effects were reported by 81% of patients, 84% of those taking tamoxifen and 80% of those taking aromatase inhibitors (AIs). The most common side effect in the tamoxifen group was hot flashes (55.6%), while in the AI group it was arthralgia (60.6%). The addition of GnRH agonists to both tamoxifen and AI significantly worsened all menopausal symptoms. Overall, 12% of patients definitively discontinued AET due to side effects, 6.4% during the first 5 years and 24% during extended therapy. Patients who had previously received chemotherapy or radiotherapy reported a significantly lower discontinuation rate. CONCLUSIONS: AET side effects represent a significant problem in breast cancer survivors leading to irregular assumption and discontinuation of therapy. Adherence to AET may be improved by trustful patient-physician communication and a good-quality care network.

Clinical, Pathological, and Prognostic Features of Male Breast Cancer: A Multicenter Study.

Male breast cancer (BC) represents less than 1% of male tumors. Little is known about male BC characteristics, management, and survival, with many studies based on a small number of cases. Consequently, the treatment of male BC lacks specific guidelines. The aims of the study are to compare male and female breast cancer (FBC) in terms of cancer clinical and anatomopathological features and treatment approach, and to identify differences between male BC and FBC in terms of survival. Patients and methods: Data from 2006 to 2018 were retrospectively acquired. Amounts of 49 males and 680 postmenopausal females with primary non-metastatic BC who underwent breast surgery at Mauriziano Hospital or IRCCS Candiolo (TO-Italy) were included. The mean age at diagnosis for male BC was 68.6 years, and males presented a smaller tumor size than women (p < 0.05) at diagnosis. Most male BC patients received adjuvant endocrine therapy (AET) with tamoxifen (73.5%). AET drop-out rate due to side effects was 16.3% for males compared to 7.6% for women (p = 0.04). Comparing FBC and male BC, no differences have been identified in terms of DFS and OS, with a similar 10-year-relapse rate (12% male BC vs. 12.4% FBC). Propensity Score Matching by age, nodal status, pT, and molecular subtype had been performed and no differences in OS and DFS were seen between male BC and FBC. In conclusion, male BC and FBC have similar prognostic factors and survival outcomes. The drop-out rate of AET was higher in males, and side effects were the main reason for drug discontinuation.

Return towards normality in admissions for myocardial infarction after the lockdown removal for COVID-19 outbreak in Italy.

BACKGROUND: Investigations demonstrated a decrease of admissions for myocardial infarction (MI) during the CoronaVirus Disease-19 (COVID-19) outbreak. No study has evaluated the time required to reverse this downward curve of MI admissions. METHODS: This is a retrospective analysis on patients (N = 2415) admitted to the Emergency Departments for acute MI in nine Italian centers. Primary endpoint was the incidence rates (IRs) of MI admissions in the post-lockdown COVID-19 period (case-period: from May 4 to July 12, 2020) vs. the following control periods: January 1-February 19, 2020 (pre-lockdown period); February 20-May 3, 2020 (intra-lockdown period); May 4-July 12, 2019 (inter-year non-COVID-19 period). RESULTS: IR of admissions for MI in the post-lockdown period was higher than the intra-lockdown period (IR ratio, IRR: 1.60, 95% CI 1.42-1.81; p = 0.0001), was lower than the pre-lockdown period (IRR: 0.86, 0.77-0.96; p = 0.009) and similar to the inter-year non-COVID-19 period (IRR: 0.96, 0.87-1.07; p = 0.47). Within the case period, the increase in MI admissions was more pronounced in earlier vs later weeks (IRR 1.19, 95% CI 1.02-1.38, p = 0.024) and, compared to the inter-year control period, was significant for non ST-segment elevation MI (IRR: 1.25, 95% CI 1.08-1.46, p = 0.004), but was not observed for ST-segment elevation MI (STEMI), where hospitalizations were reduced (IRR 0.76, 95% CI 0.65-0.88, p = 0.0001). CONCLUSIONS: Our study first indicates an increase in the number of admissions for MI after the removal of the national lockdown for COVID-19 in Italy. This increase was prevalent in the first weeks following the lockdown removal, but was under-represented in STEMI patients.

The prognostic role of Gender-Age-Physiology system in idiopathic pulmonary fibrosis patients treated with pirfenidone.

INTRODUCTION: Gender, age, physiology (GAP) system have proven to be an easy tool for predicting disease stages and survival in idiopathic pulmonary fibrosis (IPF) patients. OBJECTIVE: To validate mortality risk as determined by the GAP system in a real-life multicentre IPF population treated with pirfenidone. METHODS: The study included patients who received pirfenidone for at least 6 months. The GAP calculator and the GAP index were determined. The primary outcome was all-cause mortality. The prognostic accuracy of the GAP system was evaluated with respect to calibration and discrimination. RESULTS AND CONCLUSION: Sixty-eight IPF patients were enrolled in the study. The median follow-up was 2.4 years (range 0.1-7.4 years). A total of 22 deaths as first event (32%) and of 10 lung transplantation (15%) were recorded. The cumulative incidence of mortality at 1, 2 and 3 years was 10.4%, 22.4% and 38.4%, respectively. The differences between the predicted and observed mortality were not significant for the GAP index while the observed mortality become comparable to that predicted by the GAP calculator only in the third year of follow-up. The C-index for the GAP index was 0.74 (95% CI 0.57-0.93) while the C-statistic value for the GAP calculator was 0.77 (95% CI 0.59-0.95).

State of the art in interstitial pneumonia with autoimmune features: a systematic review on retrospective studies and suggestions for further advances.

The term interstitial pneumonia with autoimmune features (IPAF) has been proposed to define patients with interstitial lung disease (ILD) associated with autoimmune signs not classifiable for connective tissue diseases (CTDs). This new definition overcomes previous nomenclatures and provides a uniform structure for prospective studies through specific classification criteria.This work evaluates the characteristics of IPAF patients reported in the literature, to highlight potential limits through a comparative analysis and to suggest better performing classification criteria.Four retrospective studies on the IPAF population have been considered. The study subjects differed in age, sex, smoking habit, ILD pattern and outcomes. Another important difference lies in the diverse items considered in the classification criteria. The retrospective design of the studies and the absence from some of them of a rheumatologist clearly involved in the diagnosis may have influenced the data, but current IPAF criteria seem to include a rather heterogeneous population. To overcome these discrepancies, this review suggests a limitation in the use of single items and the exclusion of extremely specific CTD criteria. This should avoid the definition of IPAF for those diseases at different stages or at early onset. The investigation of a functional or morphological cut-off of pulmonary involvement would be useful.

Root bark of Discaria americana attenuates pain: A pharmacological evidence of interaction with opioidergic system and TRP/ASIC channels.

ETHNOPHARMACOLOGICAL RELEVANCE: Discaria americana (Rhamnaceae) root bark infusion have been used in traditional medicine as antipyretic, tonic, ameliorative of stomach and skin diseases and diabetes. This study was designed to investigate whether the methanolic extract of the root bark of Discaria americana (MEDa) exhibits antinociceptive effects in mice. Furthermore, it was investigated the involvement of the opioidergic system in MEDa mechanism of action as well the interactions with TRP/ASIC channels in its effect. MATERIALS AND METHODS: The antinociceptive effect of intra-gastric gavage (i.g.) of MEDa (0.3-300 mg/kg) was evaluated in mice subjected to acute chemical (acetic-acid, formalin, glutamate, capsaicin, cinnamaldehyde, and acidified saline) or thermal (hot plate) tests of pain. The involvement of opioid system was evaluated in the formalin test. A nonspecific effect of MEDa was observed by measuring locomotor activity and exploratory behavior in open field test. RESULTS: MEDa significantly reduced the number of writhing induced by acetic acid and inhibited the nociception in the two phases of formalin. These effects were inhibited by pretreatment with naloxone. The nociception induced by hot plate and intraplantar injection of glutamate, capsaicin, cinnamaldehyde and acidified saline were significantly inhibited by MEDa. Only the dose of 300 mg/kg altered the locomotor activity. CONCLUSIONS: Our results demonstrated, for the first time, that the methanolic extract of the root bark of Discaria americana presents antinociceptive effect in chemical and thermal stimuli and its analgesic properties can be due activation of the opioidergic system. These results support the use of Discaria americana in traditional medicine and demonstrate that this plant presents a therapeutic potential for the development of phytomedicines with antinociceptive profile.

Incremental value of right atrial strain for early diagnosis of hemodynamic deterioration in pulmonary hypertension: a new noninvasive tool for a more comprehensive diagnostic paradigma.

AIMS: Increased right atrial size is related to adverse prognosis in pulmonary hypertension. The potential incremental value of right atrial function assessment is still unclear. We tested the relationship between right atrial two-dimensional speckle-tracking echocardiography impairment and hemodynamic, functional and clinical deterioration in patients with pulmonary hypertension. METHODS: We prospectively evaluated 36 patients (27 female, 9 male; mean age 68 ±â€Š13 years) with suspected pulmonary hypertension undergoing right heart catheterization and 16 matched controls. All patients underwent baseline evaluation by New York Heart Association functional class, 6-min walking test, brain natriuretic peptide (BNP), and standard two-dimensional echocardiography in less than 48 h of right heart catheterization. Right atrial two-dimensional speckle-tracking echocardiography was assessed by averaging all segments in standard four-chamber apical view. RESULTS: Right atrial global integral strain was significantly lower in patients compared with controls (11.40 ±â€Š5.22% vs. 25.72 ±â€Š5.95 P < 0.001). Moreover, right atrial global strain, but not right atrial area or volume, was correlated with invasively measured cardiac index (CI) (r = 0.72; P < 0.0001) and pulmonary vascular resistances in all patients, even though stronger in subjects with precapillary pulmonary hypertension (r = -0.42, P = 0.018; r = -0.54, P = 0.007 respectively; P = 0.007). It was also correlated with New York Heart Association (P = 0.027), BNP (P = 0.002), and 6-min walking test (P = 0.006). After multivariate analysis including right atrial volume, tricuspid annular plane systolic excursion, left atrial strain, and BNP, right atrial global strain showed the strongest correlation with CI. Area under the curve optimal cutoff for predicting CI at least 2.4 l/min/m was 17% (area under the curve: 0.83, sensitivity: 90%, specificity: 54%). CONCLUSION: Right atrial global strain can identify right atrial functional impairment before structural changes and may be implemented in a comprehensive, noninvasive right heart assessment for diagnosis and follow-up of pulmonary hypertension patients.

An innovative polysaccharide nanobased nail formulation for improvement of onychomycosis treatment.

Tioconazole-loaded nanocapsule suspensions and its coating with a cationic polymer were developed for nail drug delivery. The colloidal systems presented a nanometric size around 155nm for uncoated nanoparticles and 162nm for those with the cationic coating, with negative and positive zeta potential values, respectively. Both nanosuspensions showed drug content close to theoretical values (1mgmL-1), association efficiency close to 100% (HPLC) and were able to control tioconazol release. The developed formulations showed in vitro antifungal activity (agar diffusion method) against C. albicans. The cationic nanocapsules were considered bioadhesive, showed higher viscosity and were chosen to be incorporated into an ungueal formulation. Pullulan nanobased nail formulation showed adequate viscosity for nail application and drug content close to the theoretical values. It was equivalent to the commercial formulation Trosid® in preventing nail infection by T. rubrum in an in vitro onychomycosis model. The nanocapsule suspensions and Pullulan nanobased nail formulation showed lower irritant potential than the commercial formulation and than free drug in an in vitro evaluation. Pullulan nanobased nail formulation is promising for the treatment of onychomycosis.

Out-of-hospital cardiac arrest: always coronary angiography?

INTRODUCTION: Out-of-hospital cardiac arrest (OHCA) remains one of the principle challenges in the setting of critical care medicine and emergency cardiology. Areas covered: Long-term survival rates even after successful resuscitation are variable but increasing in the recent years; due to the improvement of base and advanced cardiac life support techniques an increasing number of resuscitated patients are admitted to the hospital. Recent data suggested that patients surviving to hospital discharge after OHCA presented long-term outcome similar to patients with ST-elevation myocardial infarction. However, limited and incompletely clear data are available in the literature about the selection and risk stratification of patients to be subjected to coronary angiography, particularly in patients who have unfavorable clinical features in whom procedures may be futile and may affect public reporting of morality. Recently the ESC and AHA addressed appropriate treatments for ST-elevation myocardial infarction (STEMI) patients with out-of-hospital cardiac arrest. Expert commentary: Immediate coronary intervention in the setting of OHCA appears to be associated with better survival to discharge; the documentation of an occluded coronary artery in medium 25% of patients without signs of STEMI at ECG helps to explain why early angiography can improve outcomes. In the treatment of OHCA we can find some ethical issues; for example a combination of comorbidities with advanced age and prolonged ischemia indicated by severe lactic acidosis may signify a high enough chance of multiorgan failure or anoxic brain injury and where the benefit of coronary reperfusion therapy appears minimal.

Ticagrelor: Long-Term Therapy in Patients with Coronary Artery Disease.

INTRODUCTION: Atherothrombosis and coronary artery disease affect more than 13 million individuals only in the United States, about 8 millions in Europe and are the major causes of death worldwide. In particular chronic stable angina impairs patient quality of life, is associated with an important health spending and increased patient mortality; it is a prominent symptom of coronary artery disease (CAD), the latter being prevalent worldwide in patients. A key role in pathophysiology of cardiovascular acute events is played by activated platelets. Aspirin and adenosine diphosphate antagonist in addition to it is recommended for 1 year for reduction of cardiovascular events in patients with prior myocardial infarction with a weak recommendation to continue thereafter. P2Y12 receptor antagonists, in addition to aspirin, have been shown in the last years, to reduce ischemic events in patients with acute coronary syndrome but their role in secondary prevention is still new and unclear. The aim of our paper is to review the long-term effect of therapy with ticagrelor on the basis of recent evidence based data. METHODS: We performed an online search on the major search engines. All the randomized controlled trials were summarized in the table. RESULTS: We included in our paper six randomized controlled trials and we mentioned about ten post - hoc analysis, sub studies and registries. All studies included the type the therapy and a mid or long term clinical follow up. CONCLUSIONS: The studies reported in our paper and in particular PEGASUS - TIMI 54 study showed the merit to placing attention of prevention secondary ischemic events after acute coronary syndrome in the context of treatment with dual anti - platelet therapy; it proved a clinical benefit in patients treated with ticagrelor (60 mg x 2) for 3 years. Nevertheless, the effectiveness of these results cannot be generalized to patients with higher bleeding risk or low ischemic risk. In fact prolonged therapy with ticagrelor 60 mg in combination with aspirin could be considered valuable in patients with repeated acute ischemic events or with several coronary revascularizations over time (especially in patients with lower bleeding risk).

Intracoronary vs intravenous bivalirudin bolus in ST-elevation myocardial infarction patients treated with primary angioplasty.

BACKGROUND: Intracoronary bolus administration may provide high local bivalirudin concentration without changing the global dose, potentially offering a more favorable antithrombotic effect in the infarct related artery (IRA). OBJECTIVES: The purpose of this study was to investigate the feasibility and safety of intracoronary bolus administration of bivalirudin followed by the standard intravenous infusion in ST-elevation myocardial infarction (STEMI) patients undergoing primary percutaneous coronary intervention (PCI). METHODS: In 245 consecutive patients treated with primary PCI, bivalirudin bolus was given directly in the IRA, followed by a standard intravenous infusion. Clinical reperfusion markers, postprocedural coronary flow indexes, and bleeding events of the intracoronary group were compared with a propensity score-matched cohort of primary PCI patients (n=245) treated with the standard bivalirudin protocol of intravenous bolus and infusion. RESULTS: Higher rates of ⩾70% ST-segment resolution (72.7% vs 60.0%, p=0.004), lower postprocedural peak CK-MB levels (188.3±148.7 vs 242.1±208.1 IU/dl, p=0.025) and better Thrombolysis in Myocardial Infarction (TIMI) frame count values (14.7 vs 17.9, p=0.001) were observed in the IC bolus group compared with the standard intravenous bolus group. Rates of bleeding were similar between groups. Only three cases of acute stent thrombosis were observed, all in the intravenous bolus group (p=0.25). CONCLUSIONS: Intracoronary bivalirudin bolus administration during primary PCI is safe and improves ST-segment resolution, postprocedural coronary flow and enzymatic infarct size compared with the standard intravenous route.

Ivabradine for Treatment of Coronary Artery Disease: From Last Chance Resort to Mainstem of a Reasoned Therapy.

Heart rate is a fundamental determinant of cardiac oxygen consumption and plays a pivotal role in the pathophysiology of chronic stable angina (CSA). Ivabradine selectively and specifically inhibits the sino-atrial If current, slowing selectively heart rate without other significant haemodynamic effects. The consequent clinical effects are a sinus rate reduction similar to that obtained with beta-blockers, but without the related haemodynamic side effects. Ivabradine clinical benefits have been demonstrated both in patients with stable coronary artery disease (CAD) with associated systolic left ventricular dysfunction or in patients with congestive heart failure (HF). In this review we focused on the pharmacology and clinical research about ivabradine in the context of anti-ischemic therapy for CAD patients. Actually most guidelines suggest ivabradine therapy as last resort antianginal drugs in patients with uncontrolled symptoms or excessive heart rate despite maximum tolerated beta-blockade. However, the peculiar pharmacologic effects of the drug suggest that most patients with CAD might benefit from adding ivabradine to their therapeutic schemata. In fact, even if the recently released main analysis of the SIGNIFY study seems not to support an employ of ivabradine in primary prevention, it is easy to imagine a future wider use of this drug in elderly patients with incomplete myocardial revascularization and in patients with total chronic coronary occlusions and failure or unacceptable risk for percutaneous or surgical coronary revascularization.