Italian S3-Guideline on the treatment of atopic eczema Part 2: non-systemic treatments and treatment recommendations for special AE patient populations, adapted from EuroGuiDerm by the Italian Society of Dermatology and STD (SIDEMAST), the Italian Association of Hospital Dermatologists (ADOI) and the Italian Society of Allergological and Occupational Dermatology (SIDAPA).

SIDeMaST (Società Italiana di Dermatologia Medica, Chirurgica, Estetica e delle Malattie Sessualmente Trasmesse) contributed to the development of the present guideline on the systemic treatment of chronic plaque psoriasis. With the permission of EuroGuiDerm, SIDeMaST adapted the guideline to the Italian healthcare context to supply a reliable and affordable tool to Italian physicians who take care of patients affected by atopic dermatitis. The evidence- and consensus-based guideline on atopic eczema was developed in accordance with the EuroGuiDerm Guideline and Consensus Statement Development Manual. Four consensus conferences were held between December 2020 and July 2021. Twenty-nine experts (including clinicians and patient representatives) from 12 European countries participated. This second part of the guideline includes recommendations and detailed information on basic therapy with emollients and moisturizers, topical anti-inflammatory treatment, antimicrobial and antipruritic treatment and UV phototherapy. Furthermore, this part of the guideline covers techniques for avoiding provocation factors, as well as dietary interventions, immunotherapy, complementary medicine and educational interventions for patients with atopic eczema and deals with occupational and psychodermatological aspects of the disease. It also contains guidance on treatment for pediatric and adolescent patients and pregnant or breastfeeding women, as well as considerations for patients who want to have a child. A chapter on the patient perspective is also provided. The first part of the guideline, published separately, contains recommendations and guidance on systemic treatment with conventional immunosuppressive drugs, biologics and janus kinase (JAK) inhibitors, as well as information on the scope and purpose of the guideline, and a section on guideline methodology.

Italian S3-Guideline on the treatment of Atopic Eczema - Part 1: Systemic therapy, adapted from EuroGuiDerm by the Italian Society of Dermatology and STD (SIDEMAST), the Italian Association of Hospital Dermatologists (ADOI) and the Italian Society of Allergological and Environmental Dermatology (SIDAPA).

SIDeMaST (Società Italiana di Dermatologia Medica, Chirurgica, Estetica e delle Malattie Sessualmente Trasmesse) contributed to the development of the present guideline on the systemic treatment of chronic plaque psoriasis. With the permission of EuroGuiDerm, SIDeMaST adapted the guideline to the Italian healthcare context to supply a reliable and affordable tool to Italian physicians who take care of patients affected by atopic dermatitis. The evidence- and consensus-based guideline on atopic eczema was developed in accordance with the EuroGuiDerm Guideline and Consensus Statement Development Manual. Four consensus conferences were held between December 2020 and July 2021. Twenty-nine experts (including clinicians and patient representatives) from 12 European countries participated. This first part of the guideline includes general information on its scope and purpose, the health questions covered, target users and a methods section. It also provides guidance on which patients should be treated with systemic therapies, as well as recommendations and detailed information on each systemic drug. The systemic treatment options discussed in the guideline comprise conventional immunosuppressive drugs (azathioprine, ciclosporin, glucocorticosteroids, methotrexate and mycophenolate mofetil), biologics (dupilumab, lebrikizumab, nemolizumab, omalizumab and tralokinumab) and janus kinase inhibitors (abrocitinib, baricitinib and upadacitinib). Part two of the guideline will address avoidance of provocation factors, dietary interventions, immunotherapy, complementary medicine, educational interventions, occupational and psychodermatological aspects, patient perspective and considerations for pediatric, adolescent, pregnant and breastfeeding patients.

Italian S3-Guideline on the treatment of atopic eczema - First Update, adapted from EuroGuiDerm by the Italian Society of Dermatology and STD (SIDEMAST), the Italian Association of Hospital Dermatologists (ADOI) and the Italian Society of Allergological and Occupational Dermatology (SIDAPA).

The evidence- and consensus-based guideline on atopic eczema, published in JEADV on 18 August 2022 (part 1) and 3 September 2022 (part 2) was developed in accordance with the EuroGuiDerm Guideline and Consensus Statement Development Manual. Four consensus conferences were held between December 2020 and July 2021. Twenty-nine experts (including clinicians and patient representatives) from 12 European countries participated. To reflect the most recent evidence on novel systemic medications, an update was published in October 2022. According to the purpose of the Italian Society of Dermatology and STD (SIDEMAST), the Italian Association of Hospital Dermatologists (ADOI) and the Italian Society of Allergological and Environmental Dermatology (SIDAPA) to adapt the EuroGuiDerm guideline on the treatment of atopic eczema into the Italian Healthcare setting, the original update has been supplemented by inserting notes, well highlighted by the original text, to emphasize the laws, rules, procedures and suggestions of the Italian Ministry of Health and regional Health authorities.

Sun pain and solar dysesthesia: A new challenge in clinical practice.

BACKGROUND: A few patients report intense pain and other unpleasant sensations, such as burning, dysesthesia and hyperalgesia, after even brief exposure to the sun and in the absence of any skin lesion. Sometimes they also develop systemic symptoms, such as mild fever, fatigue, faintness and fainting. As a result, these patients carefully avoid even short-term sun exposure with a consequent severe negative impact on their lives. METHODS: We have reviewed the clinical findings and the results of photobiological investigations of 10 patients who presented this clinical picture. Six of these patients were previously described by our group with the diagnosis of sun pain. We have reviewed the similarities with other previously described disorders such as solar dysesthesia and PUVA pain and have evaluated possible pathogenetic mechanisms. RESULTS: During phototesting our patients experienced intense pain in the exposed area and in the surrounding skin, without any visible lesion, even with very low sub-erythemal doses. At follow-up, five patients were diagnosed with fibromyalgia, three with a major depressive disorder, one with bipolar syndrome and one with a conversion disorder. The pathogenesis remains unclear, but the use of a psychopharmacological treatment with antidepressants improved both the neuropsychiatric symptoms and sensitivity to the sun in most subjects. CONCLUSION: For patients with pain and other severe symptoms in the absence of skin lesions and clinical and laboratory manifestations of known photodermatoses, a neuropsychiatric evaluation should be suggested.

The realistic positioning of UVA1 phototherapy after 25 years of clinical experience and the availability of new biologics and small molecules: a retrospective clinical study.

Background: Since the early 1990s, Ultraviolet (UV) A1 phototherapy has been described as an effective and safe treatment of a multitude of skin disorders. However, after 30 years, its use has remained limited to few dermatological centers. Objective: To analyze the changes over the years and the current position of UVA1 phototherapy through a Real-World Evidence (RWE) study at a single tertiary referral center. Methods: We reviewed the medical files of 740 patients treated between 1998 and 2022. Treatment results were collected, efficacy was assessed by a grading scale and acute adverse effects were registered. Results: We treated patients with 26 different diseases. We registered marked improvement (MI) or complete remission (CR) in 42.8% of patients with morphea, 50% with Urticaria Pigmentosa, 40.7% with Granuloma annulare and 85.7% with skin sarcoidosis. Good results were obtained also in the treatment of chronic Graft Versus Host Disease (GVHD), Eosinophilic Fasciitis, Sclero-atrophic Lichen, skin manifestations of systemic lupus erythematosus and psoriasis of HIV+ patients. Systemic Sclerosis, Romberg's Syndrome, Bushke's Scleredema, Nephrogenic Fibrosing Dermopathy, REM Syndrome, Follicular Mucinosis, Pretibial Myxedema, Scleromyxedema, pemphigus foliaceus, chronic cutaneous lupus erythematosus, erythroderma of Netherton Syndrome and Necrobiosis Lipoidica were no or poorly responsive. In clinical indications where UVA1 was used as a second line phototherapy after narrow-band (NB)-UVB, we saw good MI or CR rates in Mycosis Fungoides (57% of patients), Atopic Dermatitis (33.9%), Pitiryasis Lichenoides chronica (50%), Pityriasis Lichenoides et varioliformis acute (75%) and Lymphomatod Papulosis (62.5%). Short-term adverse events were uncommon and mild. Conclusion: Over the past decade, the annual number of treated patients has progressively declined for several reasons. Firstly, UVA1 phototherapy has taken a backseat to the cheaper and more practical NB-UVB phototherapy, which has proven effective for common indications. Secondly, the emergence of new, safe, and effective drugs for conditions such as atopic dermatitis, GVHD, and connective tissue disorders. Finally, our research has shown that UVA1 therapy is often ineffective or minimally effective for some rare diseases, contrary to previous case reports and small case series. Nonetheless, UVA1 continues to be a valuable treatment option for patients with specific skin disorders.

Definition of the Clinical Characteristics of Patients with Moderate and Severe Atopic Dermatitis for Whom Narrow-Band UVB (NB-UVB) and Medium-Dose UVA1 Phototherapies Are Still Valuable Treatment Options at the Age of Biologics.

Narrow-band (NB) UVB and UVA1 have been successfully used for the treatment of atopic dermatitis (AD) since the 1980s, but the clinical indications for their use "at the age of biologics" remain to be assessed. From 2013 to 2017, 145 patients underwent a first treatment cycle with phototherapy. They achieved a median final EASI score of 9.90 with UVA1 and 13.70 with NB-UVB. The rates of patients achieving an IGA score of 0/1 persistent for at least 6 months were 33% with UVA1 and 28% with NB-UVB, and the rates with an EASI90 improvement were 10.9% with UVA1 and 11.0% with NB-UVB. The cut-off baseline EASI values for a good probability to achieve a 0/1 IGA were 24.4 with UVA1 and 24.7 with NB-UVB. A 0/1 IGA persistent for at least 6 months was more likely to be achieved by patients with a history of flares interspersed with periods of mild or no disease. From 2018, we only enrolled patients with the above-mentioned characteristics. The number of treated patients was lower, but the final EASI score, the rate of patients achieving IGA 0/1 persistent for at least 6 months, and EASI90 were significantly higher. Medium-dose UVA1 and NB-UVB phototherapies remain useful for the treatment of AD patients with a baseline EASI score lower than 24.4 and 24.7, respectively, and a medical history of flares followed by prolonged periods of complete or near-complete remission.

Bath-PUVA still represents a valuable treatment option for the subsets of psoriatic patients who are not eligible to or rejecting systemic treatments and are not responsive to NB-UVB phototherapy.

BACKGROUND: Photochemotherapy with bathwater delivery of psoralens plus UVA exposures (bath-PUVA) is mainly used for those psoriatic patients who are not responsive to narrowband (NB)-UVB phototherapy and oral-PUVA therapy and belong to two categories (1) patients with psoriasis without systemic comorbidities who do not need long-term continuous treatment and (2) patients who have contraindications to immunosuppressive drugs and oral-PUVA or refuse systemic drugs, including oral ingestion of psoralens, for personal reasons. However, it is not known how many patients belong to the second group and how much bath-PUVA is effective and safe for them. METHODS: We have reviewed the treatment results of a cohort of 120 patients with clinical indication to bath-PUVA for the above-mentioned reasons between 2010 and 2019. These patients were selected among 2640 patients with moderate and severe psoriasis who were treated in our department in the same time interval. RESULTS: Ninety-six patients completed at least one treatment cycle with bath-PUVA. A per-protocol analysis showed that average number of treatment sessions was 21.3 ± 9.0 and the cumulative UVA dose was 80.4 ± 60.0 J/cm2 . The average PASI scores decreased from 20.8 ± 7.9 to 5.1 ± 5.4 (p < .01). Sixty-seven (69.7%) patients achieved at least a 75% improvement (PASI75 ) and, of them, 38 (39.6%) had an improvement greater than 90% (PASI90 ). Adverse effects were mild and transitory. CONCLUSION: These findings demonstrate that bath-PUVA is still a valuable treatment option for a high number of patients who reject systemic treatments or have contraindications to systemic immune-modifying drugs and have had a limited or no improvement with NB-UVB phototherapy.

Impact of Age on the Functional Evaluation of Intermediate Coronary Stenoses With Instantaneous Wave-Free Ratio and Fractional Flow Reserve.

The optimal strategy for assessing the ischemic significance of intermediate coronary stenoses with adenosine-induced fractional flow reserve (FFR) and instantaneous wave-free ratio (iFR) is still debated. Few studies have previously assessed the impact of age on FFR and iFR, which was the aim of our study. Patients undergoing FFR and iFR evaluation for intermediate (40%-70%) coronary lesions were included and divided according to age. Fractional flow reserve was performed by intracoronary boluses of adenosine (60-1440 µg). Instantaneous wave-free ratio was automatically calculated. Among 148 patients undergoing FFR measurement of 166 lesions, 45.3% were ≥70 years. Elderly patients had higher minimal lumen diameter (P = .03). We also observed a linear relationship between iFR and FFR independently of age. Fractional flow reserve values were higher in the elderly patients, whereas iFR was not related to age. A total of 33 lesions had a positive iFR with no difference for age (17.3% vs 22%, P = .56), while FFR <0.80 was more infrequent in the elderly patients (17.1% vs 34.8%, P = .02). In intermediate coronary stenoses, iFR and FFR correlation is unaffected by age. Fractional flow reserve is higher in the elderly patients, whereas iFR is less affected by age. Future large-scale studies are needed to define whether iFR should be the preferred choice in elderly patients.

Impact of uric acid on immature platelet fraction in patients undergoing percutaneous coronary intervention.

INTRODUCTION: Reticulated platelets have been involved in the pathophysiology of coronary artery disease (CAD). Immature platelet fraction (IPF) allows their measurement in daily clinical practice, although the factors conditioning their elevation are still largely unexplored. Serum uric acid (SUA) is the end product of purine metabolism, displaying a pro-oxidant and pro-inflammatory action and increasing the cardiovascular risk. The aim of our study was to investigate the impact of SUA on IPF levels in patients undergoing percutaneous coronary intervention (PCI), and their relationship with CAD. METHODS: We enrolled a cohort of consecutive patients undergoing coronary angiography in a single center. Hyperuricemia was defined by SUA ≥ 6.5 mg/dl. Significant CAD was defined as at least 1 vessel stenosis >50%, while severe CAD was defined as left main and/or three-vessel disease. IPF was measured at admission by routine blood cells count (A Sysmex XE-2100). RESULTS: We included in our study 2217 patients, of whom 544 had high levels of SUA, while 1673 had normal levels. Hyperuricemics were older, with higher percentage of renal failure, hypertension, dilated cardiomyopathy or valvular disease as indication to angiography, higher levels of creatinine and C-reactive protein (p < 0.001, respectively) when compared to normouricemics. Immature platelet fraction (IPF) was significant higher in hyperuricemic patients (3.96% vs 3.59%, p = 0.004). A progressive direct increase in the IPF values was observed in relation to SUA levels (r = 0.101, p < 0.001), although at multivariate analysis, hyperuricemia did not result as an independent predictor of IPC in 3rd tertile (adjusted OR [95%CI] = 1.21 [0.85-1.71] P = 0.288). When stratifying hyperuricemics and normouricemics according to IPF tertiles (<2.3%; 2.3-3.9%; ≥ 4%), reticulated platelets were not associated to the prevalence of CAD (SUA ≥6.5:80.9 vs 79.3% vs 78.6%, p = 0.60; SUA < 6.5: 79.3% vs 81.3% vs 78.9%, p = 0.878) or severe CAD (SUA ≥6.5: 34.9% vs 38.9% vs 35.2%, p = 0.99; SUA < 6.5: 30.4% vs 33.5% vs 34%, p = 0.192), and the results were confirmed at multivariate analysis for CAD (SUA ≥6.5: adjusted OR [95%CI] = 1.11 [0.81-1.51] P = 0.524, SUA < 6.5: adjusted OR [95%CI] = 0.89 [0.75-1.05] P = 0.170) or severe CAD (SUA ≥6.5: adjusted OR [95%CI] = 1.03 [0.81-1.31] P = 0.795; SUA < 6.5: adjusted OR [95%CI] = 1.10 [0.96-1.26] P = 0.192). CONCLUSIONS: In the present study we found a direct relationship between SUA levels and IPF values; however, hyperuricemia did not result as an independent predictor of higher IPF tertile values. Neither in hyperuricemics nor in normouricemics higher IPF were independently associated to the prevalence of CAD or severe CAD.

Interface between Bats and Pigs in Heavy Pig Production.

Bats are often claimed to be a major source for future viral epidemics, as they are associated with several viruses with zoonotic potential. Here we describe the presence and biodiversity of bats associated with intensive pig farms devoted to the production of heavy pigs in northern Italy. Since chiropters or signs of their presence were not found within animal shelters in our study area, we suggest that fecal viruses with high environmental resistance have the highest likelihood for spillover through indirect transmission. In turn, we investigated the circulation of mammalian orthoreoviruses (MRVs), coronaviruses (CoVs) and astroviruses (AstVs) in pigs and bats sharing the same environment. Results of our preliminary study did not show any bat virus in pigs suggesting that spillover from these animals is rare. However, several AstVs, CoVs and MRVs circulated undetected in pigs. Among those, one MRV was a reassortant strain carrying viral genes likely acquired from bats. On the other hand, we found a swine AstV and a MRV strain carrying swine genes in bat guano, indicating that viral exchange at the bat-pig interface might occur more frequently from pigs to bats rather than the other way around. Considering the indoor farming system as the most common system in the European Union (EU), preventive measures should focus on biosecurity rather than displacement of bats, which are protected throughout the EU and provide critical ecosystem services for rural settings.

Impact of the rs73598374 polymorphism of the adenosine deaminase gene on platelet reactivity and long-term outcomes among patients with acute coronary syndrome treated with ticagrelor.

BACKGROUND: The positive interaction of ticagrelor with the metabolism of adenosine has been claimed for the large antithrombotic and antiischemic benefits of this antiplatelet agent in acute coronary syndromes (ACS). Adenosine catabolism is regulated by the activity of the adenosine deaminase enzyme (ADA), for which several polymorphisms have been identified. Therefore, the aim of our study was to explore the impact of the rs73598374 polymorphism of ADA gene on platelet reactivity in ACS patients treated with ticagrelor. METHODS: We included consecutive patients receiving ASA and ticagrelor after an ACS and coronary intervention. Platelet reactivity was evaluated by impedance aggregometry at 30-90 days post-discharge. The genetic analysis was carried out by PCR and RFLP. Clinical endpoints were mortality, cardiovascular death, recurrent myocardial infarction or coronary revascularization at the maximum available follow-up. RESULTS: Our population is represented by 464 patients, of whom 33.4% were A-heterozygotes and 6 homozygotes. A-allele carriers showed a greater prevalence of renal failure (p = 0.02) and a lower rate of previous coronary artery bypass graft (p = 0.03) and statin treatment (p = 0.02). No differences in the mean values of platelet reactivity or HRPR on ticagrelor were found according to the ADA genotype (11.3%vs13.9%, p = 0.45; adjusted OR[95% CI] = 1.17[0.64-2.14], p = 0.61). At follow up, patients carrying the A-allele showed a non-significantly lower incidence of ACS and repeated unplanned revascularization, although with no effect on mortality. CONCLUSIONS: In the present study the rs73598374 polymorphism of the ADA gene did not affect platelet reactivity or the long-term prognosis in patients with ACS receiving dual antiplatelet therapy with ASA and ticagrelor.

Impact of gender on immature platelet count and its relationship with coronary artery disease.

The impact of platelet parameters on the cardiovascular risk is still debated. Gender differences in platelet volume indexes and turnover have been previously reported, potentially conditioning their role in the development of coronary artery disease (CAD). However, few studies have addressed, so far, the impact of gender on the immature platelet fraction (IPF) and count (IPC) and their relationship with CAD. We enrolled consecutive patients undergoing coronary angiography in a single centre. IPF and platelet indexes were measured at admission. Significant CAD was defined as the presence of at least one coronary stenosis more than 50%. A total of 2550 patients were included, 1835 (72%) were males, and 715 (28%) were females. Female patients were older (p < 0.001), with lower BMI (p = 0.002), lower prevalence of active smoking (p < 0.001), previous MI, previous PCI and CABG (p = 0.001, p = 0.001, p < 0.001), whilst a higher prevalence of renal failure (p = 0.02), acute presentation (p < 0.001) and CAD (p < 0.001). Platelet count was higher in females (p < 0.001), as well as the IPC levels (838.38 ± 562.05 vs 792.24 ± 535.66, p = 0.05) with no difference in the levels of immature platelet fraction (3.67 ± 2.68% vs 3.74 ± 2.6%, p = 0.55) or the prevalence of patients with IPF ≥ 3rd tertile (33.7% vs 35.2%, p = 0.26). At multivariate analysis, after correction for baseline confounders, gender did not emerge as an independent predictor of higher IPF (adjusted OR [95% CI] = 0.82 [0.64-1.06], p = 0.13). When dividing our patients according to the levels of IPF, in women we observed an inverse association between IPF ≥ 3rd tertile and coronary calcifications (p = 0.025) and a higher prevalence of restenosis (p = 0.003), but no difference in CAD (65.6% vs 66.9%, p = 0.71) or severe CAD (28.1% vs 24.7%, p = 0.31). In males, the IPF ≥ 3rd tertile related with a lower TIMI flow (p = 0.001). Males with lower IPF had a significantly higher percentage of CAD (87.7% vs 83.3%, p = 0.007; adjusted OR: 0.699 [95% CI] = [0.54-0.91], p = 0.008) but not for severe CAD (36.5% vs 39.9%, p = 0.134). The present study shows that among patients undergoing coronary angiography, gender is not associated to the levels of immature platelet fraction. Moreover, we found no association between IPF and the prevalence and extent of CAD in female gender, whereas in male gender the IPF was inversely related with the prevalence of CAD.

Impact of aging on immature platelet count and its relationship with coronary artery disease.

Despite the fact that elderly patients represent a prevalent and challenging population in the current practice, few data exist on the impact of platelet parameters on cardiovascular risk in these patients. Therefore, the aim of the present study was to evaluate the impact of age on the immature platelet count (IPC) and their relationship with CAD. We included a total of 2236 consecutive patients undergoing coronary angiography in a single center. Elderly patients (age ≥ 75 years) were 756 (33.7%). IPC was measured at admission. Elderly patients were more often females (p < .001), with lower BMI and prevalence of smokers (p < .001), and a more complex cardiovascular risk profile and coronary disease (p = .02). Platelet count decreased with aging (p = .05), whereas no difference in the mean IPC was found between patients < or ≥75 years. In fact, advanced age did not emerge as an independent predictor of IPC above III tertile (≥8.6*10^6/ml), (adjusted OR[95%CI] = 0.97[0.78-1.21], p = .79). When considering elderly patients according to tertiles values of IPC (<5.1,5.1-8.59; ≥8.6*10^6/ml), we found no impact of IPC on the prevalence of CAD (81.1% vs 84.5% vs 81.5%, p = .92; adjusted OR[95%CI] = 1.08[0.67-1.72], p = .75) and its extent (37.7% vs 34.5% vs 40.2%, p = .57; adjusted OR[95%CI] = 1.22[0.85-1.73], p = .28). However, we observed a higher rate of calcified and type C lesions in elderly patients with higher IPC (p = .03 and p < .001, respectively). Therefore, advanced age is not associated with higher immature platelet count and the prevalence and severity of CAD. Moreover, IPC does not contribute to explain the higher prevalence and extent of coronary artery disease observed in elderly patients.

The "Chauffeur Fracture": Historical Origins of an Often-Forgotten Eponym.

This article describes the origin of the term "chauffeur fracture" used to indicate an oblique fracture of the radial styloid process with extension into the wrist joint. This kind of fracture was originally described by the British surgeon Jonathan Hutchinson in 1866. The invention of the automobile increased the incidence of this fracture among chauffeurs and cabdrivers. Indeed, at the beginning of the 20th century, motor vehicles were started by means of a crank-handle connected to the engine, which needed to be turned vigorously clockwise by hand. If the motor started unexpectedly, the crank-handle could jerk back violently and thereby cause a wrist injury due to sudden hyperextension. We retrospectively reviewed the literature and historical articles to better define the historical origins of an often-forgotten eponym. In 1904, the French surgeon Just Lucas-Championnière first evidenced the occupational origin of this fracture, so introducing the term "chauffeur fracture" to identify this injury.

Impact of active smoking on the immature platelet fraction and its relationship with the extent of coronary artery disease.

INTRODUCTION: Smoking represents a major cardiovascular risk factor, due to the induction of oxidative stress and low-grade, continuous, inflammation that contribute to promote atherothrombosis. However, the mechanisms leading to increased platelet aggregability associated with smoking are only partially defined. A potential role has been hypothesized for immature platelets, a younger and potentially more reactive fraction, previously associated with the main determinants of coronary artery disease (CAD). Therefore, the aim of our study was to define the impact of smoking on the immature platelet fraction (IPF) and its relationship with prevalence and extent of coronary artery disease. METHODS: We enrolled a cohort of consecutive patients undergoing coronary angiography in a single centre. Significant CAD was defined as at least 1 vessel stenosis >50%, while severe CAD was defined as left main and/or three-vessel disease. IPF was measured at admission by routine blood cell count (Sysmex XE-2100). RESULTS: We included in our study 2553 patients who were divided according to smoking status (active smokers: 512; nonactive smokers: 2041). Smokers were younger, more frequent males, with lower rate of diabetes mellitus, previous PCI and previous CABG (P < .001, respectively) and were in treatment less often with ARB, BB, nitrates, statins, ASA, clopidogrel, CCB and diuretics (P < .001, respectively) as compared to nonactive smokers. Higher percentage of smokers was observed in patients with higher IPF values, and at multivariate analysis, active smoking resulted as an independent predictor of higher IPF (adjusted OR [95% CI] = 1.59[1.03-2.45], P = .035). Among smokers, higher IPF was associated with lower ejection fraction (P = .034), percentage of acute coronary syndrome (P = .002) and platelet count (P < .001) compared to ones with lower IPF. However, the IPF (according to quartiles values) was not associated with the prevalence and extent of CAD (82.5%, 80.4%, 86.1% and 80.9%, from 1st to 4th quartile, respectively, adjusted OR[95% CI] = 0.98[0.79-1.23], P = .89) and severe CAD (31%, 31.1%, 39.1% and 35.2%, from 1st to 4th quartile, respectively, adjusted OR[95% CI] = 1.03[0.86-1.23], P = .76). CONCLUSION: The present study shows an independent association between active smoking and the levels of immature platelet fraction in patients undergoing coronary angiography. However, among active smokers, IPF did not result as an independent predictor of CAD or severe CAD.

Homocysteine levels and platelet reactivity in coronary artery disease patients treated with ticagrelor.

BACKGROUND AND AIM: Recurrent atherothrombotic events have been reported in certain higher risk subsets of patients even with ticagrelor, a potent first-line antiplatelet agent for the management of patients with acute coronary syndrome (ACS). Hyperhomocysteinemia is a known determinant of platelet function abnormalities. Therefore, the aim of our study was to evaluate the impact of homocysteine (Hcy) levels on platelet reactivity in patients receiving Ticagrelor. METHODS AND RESULTS: Patients with ACS undergoing percutaneous coronary revascularization and on dual antiplatelet therapy with ASA + Ticagrelor (90mg/twice a day) were scheduled for platelet function assessment 30-90 days post-discharge. Aggregation tests were performed by Multiple Electrode Aggregometry (MEA). Suboptimal platelet inhibition HRPR-high residual platelet reactivity was defined if above the lower limit of normality (417 AU*min). We included 432 patients, divided according to Hcy tertiles. Higher Hcy levels were associated with age, renal failure, creatinine levels and use diuretics (p < 0.001). Patients with higher Hcy levels displayed a higher platelet reactivity at COL test (p = 0.002), and ADP test (p = 0.04), with a linear relationship between Hcy and platelet aggregation after stimulation with collagen (r = 0.202, p < 0.001), thrombin receptor peptide (r = 0.104, p = 0.05) and ADP (r = 0.145, p = 0.006). However, Hcy levels did not significantly affect the rate of HRPR with Ticagrelor (9.9% vs 13.7% vs 10.7%, p = 0.89; adjusted OR [95% CI] = [0.616-1.51], p = 0.99). CONCLUSIONS: Among patients with ACS, despite the elevated platelet reactivity associated to hyperhomocysteinemia, DAPT with ticagrelor could overcome such phenomenon, achieving an adequate platelet inhibition in the majority of the patients.