Topical Pharmacological Treatment of Actinic Keratoses: Focus on Tirbanibulin 1% Ointment.

Actinic keratosis (AK) is a frequent precancerous skin lesion that mostly affects chronically sun-exposed areas. Chronic sun damage leads to various mutations in onco-suppressor and oncogenic genes which cause an uncontrolled proliferation of atypical keratinocytes. Untreated AKs may evolve in cutaneous squamous cell carcinoma (cSCC), with the consequent need for dermato-surgical excision or even for systemic immunotherapy in case of invasive/metastatic cSCCs. Epidemiology data on AK prevalence are various, however, the literature unanimously reports an increasing prevalence due to the aging of the population. Clinically AKs appear as a scaly, erythematous macule or papule or hyperkeratotic plaque. Management of AKs and the field of cancerization is important to avoid the natural evolution into squamous cell carcinomas (SCCs). Both physical and topical treatments are approved for managing AKs. Patient compliance with topical regimens is usually low due to the length of the posology and frequent skin adverse events. A recently approved tirbanibulin-based ointment, showed potential for inhibiting cell proliferation and blocking SRC-kinases, implicated in the progression of AKs in SCCs. The advantage of this new treatment is the practical posology, with a daily application for 5 consecutive days on AKs of the face-scalp area. Local skin reactions are usually mild and do not require treatment discontinuation. The short course of this new therapy and its excellent tolerance massively increased patient compliance. This article reviews what is currently known about this new therapy from its mechanism of action to clinical trial outcomes regarding safety, effectiveness, and patient adherence to the treatment.

Gender differences in the development of heart failure after acute coronary syndrome: Insight from the CORALYS registry.

BACKGROUND: Impact of gender on heart remodeling after acute coronary syndrome (ACS) and consequently on development of heart failure (HF) remains to be elucidated. METHODS: CORALYS is a multicenter, retrospective, observational registry enrolling consecutive patients admitted for ACS and treated with percutaneous coronary intervention. HF hospitalization was the primary endpoint while all-cause mortality and the composite endpoint of incidence of first HF hospitalization and cardiovascular mortality were the secondary ones. RESULTS: Among 14,699 patients enrolled in CORALYS registry, 4578 (31%) were women and 10,121 (69%) males. Women were older, had more frequently hypertension and diabetes and less frequently smoking habit. History of myocardial infarction (MI), STEMI at admission and multivessel disease were less common in women. After median follow up of 2.9 ± 1.8 years, women had higher incidence of primary and secondary endpoints and female sex was an independent predictor of HF hospitalization (HR 1.26;1.05-1.50; p = 0.011) and cardiovascular death/HF hospitalization (HR 1.18;1.02-1.37; p = 0.022). At multivariable analysis women and men share as predictors of HF diabetes, history of cancer, chronic kidney disease, atrial fibrillation, complete revascularization and left ventricular ejection fraction. Chronic obstructive pulmonary disease (HR 2.34;1.70-3.22, p < 0.001) and diuretics treatment (HR 1.61;1.27-2.04, p < 0.001) were predictor of HF in men, while history of previous MI (HR 1.46;1.08-1.97, p = 0.015) and treatment with inhibitors of renin-angiotensin system (HR 0.69;0,49-0.96 all 95% CI, p = 0.030) in women. CONCLUSIONS: Women are at increased risk of HF after ACS and gender seems to be an outcome-modifier of the relationship between a variable and primary outcome.

Acute coronary syndrome in very elderly patients-a real-world experience.

Very elderly population constitutes an increasingly larger proportion of patients admitted for acute coronary syndromes (ACS). Notably, age represents both a proxy of frailty and an exclusion criterion in clinical randomized trials, which probably contributes to lack of data and undertreatment of real-world elderly patients. The aim of the study is to describe patterns of treatment and outcome of very elderly patients with ACS. All consecutive patients aged ≥ 80 years old (yo) admitted between January 2017 and December 2019 with ACS were included. The primary endpoint was in-hospital occurrence of major adverse cardiovascular events (MACE), defined as the composite of cardiovascular death, new onset cardiogenic shock, definite/probable stent thrombosis, and ischemic stroke. The secondary endpoints were in-hospital incidence of Thrombolysis in Myocardial Infarction (TIMI) major/minor bleedings, contrast-induced nephropathy (CIN), six-month all-cause mortality, and unplanned readmission. One hundred ninety-three patients (mean age 84.1 ± 3.5 yo, 46% females) were included, of whom 86 (44.6%), 79 (40.9%), and 28 (14.5%) presented with ST elevation myocardial infarction (STEMI), non-ST elevation myocardial infarction (NSTEMI), and unstable angina (UA), respectively. The vast majority of patients received an invasive strategy, with 92.7% undergoing coronary angiography and 84.4% to percutaneous coronary intervention (PCI). Aspirin was administered to 180 (93.3%) patients, clopidogrel to 89 (46.1%) patients, and ticagrelor to 85 (44%) patients. In-hospital MACE occurred in 29 patients (15.0%), whereas 3 (1.6%) and 12 patients (7.2%) experienced in-hospital TIMI major and TIMI minor bleeding, respectively. Of the overall population, 177 (91.7%) were discharged alive. After discharge, 11 patients (6.2%) died of all-cause death, whereas 42 patients (23.7%) required a new hospitalization within six months. Invasive strategy of ACS in elderly patients seems safe and effective. Six-month new hospitalization appears inevitably related to age.

Association between hormone therapy and short-term cardiovascular events in women with spontaneous coronary artery dissection.

INTRODUCTION AND OBJECTIVES: Changes in sex hormone levels are a known triggering factor for spontaneous coronary artery dissection (SCAD) in women. However, it is unknown whether exposure to exogenous hormone therapy (HT) at the time of SCAD presentation modifies the clinical course of this condition. We investigated the association between HT in female patients presenting with SCAD and short-term clinical outcomes. METHODS: We enrolled consecutive patients presenting with SCAD from the DISCO-IT/SPA (dissezioni spontanee coronariche Italian-Spanish) registry. Women on HT (estrogens, progestagens, or gonadotropins) at the time of presentation were identified, and their clinical characteristics and short-term outcomes were compared with those not receiving active HT. The outcome measure was nonfatal myocardial infarction and/or unplanned percutaneous coronary intervention during the first 28 days after the index catheterization. RESULTS: Of 224 women presenting with SCAD (mean age 52.0±10.0 years), 39 (17.4%) were currently using HT while 185 (82.6%) were not. No significant differences were noted in the baseline demographics, clinical presentation, angiographic features, or initial treatment received between the 2 groups. All patients on systemic HT (n=36, 92%) discontinued it at the time of diagnosis. The composite outcome occurred in 7 (17.9%) patients with prior HT compared with 14 (7.6%) without (P=.039). After multivariable adjustment, HT remained associated with the composite outcome recorded in the first 28 days of follow-up (HR, 3.53; 95%CI, 1.30-9.61; P=.013). CONCLUSIONS: In women with SCAD, exposure to HT at the time of clinical presentation was associated with short-term recurrent cardiovascular events such as nonfatal myocardial infarction and/or unplanned percutaneous revascularization.

[ANMCO Position paper: Evidence and practical indications for the use of low-dose rivaroxaban in stable coronary artery disease and peripheral artery disease]. / Position paper ANMCO: Evidenze e indicazioni pratiche per l'impiego di rivaroxaban a bassa dose nella malattia coronarica stabile e nell'arteriopatia periferica.

In patients with atherosclerotic disease, the occurrence of atherothrombotic events is the main determinant of morbidity and mortality. Growing evidence suggests the involvement of the coagulation pathway in the atherosclerotic process and the benefit of antithrombotic agents, such as direct oral anticoagulants, which interfere with both platelet aggregation and the coagulation cascade. The COMPASS trial has shown that in patients with stable coronary artery disease (CAD) or peripheral artery disease (PAD), low-dose rivaroxaban (2.5 mg twice daily) added to acetylsalicylic acid (ASA) 100 mg reduces major vascular events and mortality, with an increase in major bleeding but not in fatal bleeding or involving a critical organ. The reduction in major cardiovascular events has been confirmed in the overall population with CAD and in both patients with and without a previous percutaneous coronary revascularization, and also in patients with previous coronary bypass surgery. In patients with PAD, the combination of rivaroxaban 2.5 mg twice daily and ASA was found to reduce both major adverse cardiovascular events and major adverse limb events, including major limb amputations. In clinical practice, the use of rivaroxaban 2.5 mg co-administered with ASA has been approved in both patients with CAD and symptomatic PAD at high risk of ischemic events. However, in Italy, the national health system reimbursement is provided only for patients with PAD. In patients treated with rivaroxaban 2.5 mg, assessment and monitoring of bleeding risk is crucial to achieve the maximum clinical benefit.

[Management of ST-elevation myocardial infarction in a patient with aspirin hypersensitivity without oral P2Y12 inhibitors]. / Gestione dell'infarto miocardico con sopraslivellamento del tratto ST in un paziente con ipersensibilità all'aspirina senza l'uso di inibitori orali del recettore P2Y12.

Aspirin hypersensitivity is a neglected issue, especially in the setting of ST-elevation myocardial infarction (STEMI). Nevertheless, in such context a prompt platelet inhibition remains crucial. We report the case of a patient presenting with STEMI, aspirin hypersensitivity and emesis causing inadequate intake of P2Y12 inhibitors managed with intravenous cangrelor therapy and aspirin desensitization. Possible options in the management of aspirin hypersensitivity in the acute phase are discussed. In selected patients with STEMI and aspirin hypersensitivity, particularly in the suspect of suboptimal enteric absorption of P2Y12 inhibitors, the use of cangrelor until aspirin desensitization is completed can be considered; bridge therapy to desensitization with glycoprotein IIb/IIIa inhibitors can be considered on a case by case basis, despite the scarce supporting evidence - bridge therapy with indobufen is not recommended due to the limited literature data.

Sepsis of Patients Infected by SARS-CoV-2: Real-World Experience From the International HOPE-COVID-19-Registry and Validation of HOPE Sepsis Score.

Background: Patients with sepsis with a concomitant coronavirus (COVID-19) infection are related to a high morbidity and mortality rate. We investigated a large cohort of patients with sepsis with a concomitant COVID-19, and we developed a risk score for the estimation of sepsis risk in COVID-19. Methods: We conducted a sub-analysis from the international Health Outcome Predictive Evaluation Registry for COVID-19 (HOPE-COVID-19-Registry, NCT04334291). Out of 5,837 patients with COVID-19, 624 patients were diagnosed with sepsis according to the Sepsis-3 International Consensus. Results: In multivariable analysis, the following risk factors were identified as independent predictors for developing sepsis: current smoking, tachypnoea (>22 breath per minute), hemoptysis, peripheral oxygen saturation (SpO2) <92%, blood pressure (BP) (systolic BP <90 mmHg and diastolic BP <60 mmHg), Glasgow Coma Scale (GCS) <15, elevated procalcitonin (PCT), elevated troponin I (TnI), and elevated creatinine >1.5 mg/dl. By assigning odds ratio (OR) weighted points to these variables, the following three risk categories were defined to develop sepsis during admission: low-risk group (probability of sepsis 3.1-11.8%); intermediate-risk group (24.8-53.8%); and high-risk-group (58.3-100%). A score of 1 was assigned to current smoking, tachypnoea, decreased SpO2, decreased BP, decreased GCS, elevated PCT, TnI, and creatinine, whereas a score of 2 was assigned to hemoptysis. Conclusions: The HOPE Sepsis Score including nine parameters is useful in identifying high-risk COVID-19 patients to develop sepsis. Sepsis in COVID-19 is associated with a high mortality rate.

The prevalence of TTR cardiac amyloidosis among patients undergoing bone scintigraphy.

BACKGROUND: Radiolabeled bisphosphonates bone scintigraphy is highly sensitive in detecting transthyretin (TTR) cardiac amyloidosis; data on the true prevalence of cardiac involvement in TTR amyloidosis are lacking. METHODS AND RESULTS: This retrospective observational, monocentric study aims to estimate the prevalence of positive bone scan suspect for TTR cardiac amyloidosis among an all-comers population who underwent a bone scintigraphy. ECG, echocardiography and clinical status of patients with unexpected cardiac uptake (Perugini score 2-3) who underwent bone scintigraphy with [99mTc]-HDP or [99mTc]-DPD at San Luigi Gonzaga University Hospital between January 2015 and May 2020 have been collected. The prevalence of bone scintigraphy suspect for cardiac involvement was 0.54% (23/4,228). The bone scintigraphy was mainly performed using [99mTc]-HDP (82.9%) and the dominant indication for the test was oncology in the 47.9% of cases. 8 Subjects had a history of neuropathy (34.8%) and 5 of carpal tunnel syndrome (21.7%). 11 Patients suffered a previous episode of heart failure (48%) while 5 patients (21.7%) were totally asymptomatic, without any sign or symptom before the bone scintigraphy making the nuclear examination crucial for an early diagnosis of TTR amyloidosis. CONCLUSION: Bone scintigraphy allows suspecting TTR amyloidosis in a pre-clinical stage of the disease in an all-comers population of patients undergoing bone scintigraphy mainly for oncology reasons.

Strange case of biventricular heart failure.

Acute heart failure (HF) is commonly caused by a cardiomyopathy with one or more precipitating factor. Here, a case in which a cardiomyopathy is precipitated by pulmonary embolism (PE). A 77-year-old man is admitted for breathlessness and leg swelling. A mild reduction of left ventricular (LV) ejection fraction is found, with moderately increased LV wall thickness and pulmonary hypertension; clinical examination revealed signs of congestion with bilateral leg swelling, and mild signs of left HF with the absence of pulmonary congestion on chest X-ray. The ECG showed Mobitz I second-degree atrioventricular block. The clinical scenario led us to the diagnosis of infiltrative cardiomyopathy due to cardiac amyloidosis (CA) precipitated by PE. Pulmonary embolism is an overlooked precipitant of HF and can be the first manifestation of an underlying misdiagnosed cardiomyopathy, especially CA. 3,3-Diphosphono-1,2-propanodicarboxylic acid scan is a cornerstone in the diagnosis of Transthyretin amyloidosis (ATTR) cardiac amyloidosis.

Mortality risk assessment in Spain and Italy, insights of the HOPE COVID-19 registry.

Recently the coronavirus disease (COVID-19) outbreak has been declared a pandemic. Despite its aggressive extension and significant morbidity and mortality, risk factors are poorly characterized outside China. We designed a registry, HOPE COVID-19 (NCT04334291), assessing data of 1021 patients discharged (dead or alive) after COVID-19, from 23 hospitals in 4 countries, between 8 February and 1 April. The primary end-point was all-cause mortality aiming to produce a mortality risk score calculator. The median age was 68 years (IQR 52-79), and 59.5% were male. Most frequent comorbidities were hypertension (46.8%) and dyslipidemia (35.8%). A relevant heart or lung disease were depicted in 20%. And renal, neurological, or oncological disease, respectively, were detected in nearly 10%. Most common symptoms were fever, cough, and dyspnea at admission. 311 patients died and 710 were discharged alive. In the death-multivariate analysis, raised as most relevant: age, hypertension, obesity, renal insufficiency, any immunosuppressive disease, 02 saturation < 92% and an elevated C reactive protein (AUC = 0.87; Hosmer-Lemeshow test, p > 0.999; bootstrap-optimist: 0.0018). We provide a simple clinical score to estimate probability of death, dividing patients in four grades (I-IV) of increasing probability. Hydroxychloroquine (79.2%) and antivirals (67.6%) were the specific drugs most commonly used. After a propensity score adjustment, the results suggested a slight improvement in mortality rates (adjusted-ORhydroxychloroquine 0.88; 95% CI 0.81-0.91, p = 0.005; adjusted-ORantiviral 0.94; 95% CI 0.87-1.01; p = 0.115). COVID-19 produces important mortality, mostly in patients with comorbidities with respiratory symptoms. Hydroxychloroquine could be associated with survival benefit, but this data need to be confirmed with further trials. Trial Registration: NCT04334291/EUPAS34399.

Role of Invasive and Non-invasive Imaging Tools in the Diagnosis and Optimal Treatment of Patients with Spontaneous Coronary Artery Dissection.

PURPOSE OF REVIEW: Spontaneous coronary artery dissection (SCAD) is a serious non-atherosclerotic disease, most frequently presenting as an acute coronary syndrome and affecting female patients. Considering that diagnosis of SCAD is often elusive, and its interventional treatment is associated to a higher rate of complications than obstructive atherosclerotic disease, we aim to review all the imaging tools currently available for the optimal diagnosis and treatment of this condition. RECENT FINDINGS: The developments in both invasive and non-invasive imaging alternatives to coronary angiography, such as intravascular ultrasound, optical coherence tomography, and computed coronary angiography, have largely contributed to appraise the epidemiology of SCAD, understand its causative pathophysiological mechanisms, and improve our ability to confirm doubtful cases of SCAD. Intracoronary imaging is also a valuable in deciding the best therapeutic approach and in guiding interventions in those patients requiring percutaneous treatment. Furthermore, non-invasive imaging is a key tool in ruling out significant extracoronary vascular abnormalities which frequently occur in patients with underlying conditions like fibromuscular dysplasia who develop SCAD. Main imaging tools employed in SCAD cases could have advantages and drawbacks. Focusing on different types of SCAD, operators should be able to choose the best imaging technique for diagnosis, management, and follow-up.

Management of aspirin intolerance in patients undergoing percutaneous coronary intervention. The role of mono-antiplatelet therapy: a retrospective, multicenter, study.

BACKGROUND: The optimal management of patients with aspirin intolerance undergoing stent implantation represents a challenge for physicians. The aim of this study was to assess the overall number of patients discharged with mono antiplatelet therapy after percutaneous coronary intervention (PCI). The most frequent aspirin intolerance symptoms in this population and the overall incidence of patient-oriented composite endpoints (POCE). METHODS: From January 2006 to June 2016 all patients discharged with mono-antiplatelet therapy because of aspirin intolerance/hypersensitivity/allergy and treated by means of PCI were included. Data about percutaneous treatments and aspirin intolerance were collected. POCE were evaluated at a twelve-month clinical follow-up comparing safety and efficacy of clopidogrel monotherapy versus new P2Y12 inhibitors. RESULTS: We collected 70 patients, that is 0.3% of the total amount of PCI in the considered period, 25 (35%) of them were women and the remaining 45 (65%) were men. An acute coronary syndrome (ACS) was the clinical presentation in 47 (67.1%) patients, with NSTEMI in 19 (27.1%) of them. Forty-six patients (65.7%) were treated with clopidogrel and 24 (34.3%) with new P2Y12 inhibitors. At one-year follow-up, 18 (25.7%) patients suffered a new clinically relevant adverse event, 5 (7.1%) died, 3 (4.3%) required a target vessel revascularization and 10 (14.3%) patients a target lesion revascularization. CONCLUSIONS: Our study evaluated patients with ACS or stable coronary artery disease undergoing PCI and treated with mono-antiplatelet therapy with P2Y12 inhibitors due to aspirin intolerance shows a 25% incidence of POCE at one year. Further studies with adequate sample size are required to evaluate the efficacy and safety of mono antiplatelet therapy in this clinical scenario.

What is the optimal treatment for symptomatic patients with isolated coronary myocardial bridge? A systematic review and pooled analysis.

BACKGROUND: Myocardial bridging is a common coronary anomaly, with few severe adverse events but a relevant symptom burden. Myocardial bridging treatment, however, remains uncertain because of the lack of randomized trials. MATERIAL: MEDLINE/PubMed was systematically screened for studies reporting on isolated myocardial bridging diagnosed at coronary angiography or with coronary computed tomography in patients admitted for suspected angina or with an acute coronary syndrome. Baseline, treatment and outcome data were appraised and pooled according to treatment (medical therapy, bypass surgery/myotomy or stenting). RESULTS: A total of 899 patients in 18 studies were included with a low prevalence of traditional risk factors, especially diabetes (15.6%, interquartile range 2.5-21.5). After a median of 31.0 months (interquartile range 12.4-37.1), major cardiovascular events (composite of death, myocardial infarction or target vessel revascularization) occurred in only 3.4% of the study patients and 78.7% [70.5-86.9; 95% confidence intervals (CI)] were managed conservatively and free of symptoms. When an invasive strategy was planned, freedom from angina was higher in patients treated with surgery [84.5% (78.4-90.7; 95% CI)] than in those treated with stenting [54.7% (38.9-70.6; 95% CI)]. Patients in the stenting group experienced a high incidence of major cardiovascular events related to target vessel revascularization [40.07% (19.83-60.32; 95% CI)]. Meta-regression showed that patients treated with beta-blockers or with a history of hypertension were more likely to remain free from angina (B -0.6, P = 0.013; B -0.66, P = 0.006). CONCLUSION: Patients with symptomatic isolated myocardial bridging generally have a good long-term prognosis. Pharmacological treatment alone, especially with beta-blockers, is able to improve angina in most cases. Surgical treatment appears to be more effective than stenting in nonresponders.