Global trends in cutaneous malignant melanoma incidence and mortality.

Mortality from cutaneous malignant melanoma (CMM) increased in the past, but trends have been favorable in more recent years in many high-income countries. However, incidence has been increasing in several countries. We provided an up-to-date overview of mortality trends from CMM. We analyzed death certification data from the WHO in selected countries worldwide from 1980 to the most recent available calendar years. We also reported incidence data derived from Cancer Incidence in Five Continents from 1990 to 2012. Separate analyses were performed for young adults aged 20-44 and middle-aged adults aged 45-64 years. Mortality from CMM in all age groups showed a favorable pattern in the majority of the countries considered. Mortality trends declined by 40 to 50% in Australia over the last decades, confirming the importance of prevention measures. Considering young adults aged 20-44, Australia, New Zealand and Northern Europe reported the highest death rates for both sexes (>0.90/100 000 in men and >0.60/100 000 in women) while Japan, the Philippines, and Latin America the lowest ones (<0.50/100 000 and <0.35/100 000 in men and women, respectively). Incidence trends were stable or upward in most countries, with higher rates among women. Our study highlights a global reduction of CMM mortality over the last three decades. The increasing awareness of risk factors, mainly related to UV exposure, along with early diagnosis and progress in treatment for advanced disease played pivotal roles in reducing CMM mortality, particularly in Australia.

Metabolic Approaches for the Treatment of Dilated Cardiomyopathy.

In dilated cardiomyopathy (DCM), where the heart muscle becomes stretched and thin, heart failure (HF) occurs, and the cardiomyocytes suffer from an energetic inefficiency caused by an abnormal cardiac metabolism. Although underappreciated as a potential therapeutic target, the optimal metabolic milieu of a failing heart is still largely unknown and subject to debate. Because glucose naturally has a lower P/O ratio (the ATP yield per oxygen atom), the previous studies using this strategy to increase glucose oxidation have produced some intriguing findings. In reality, the vast majority of small-scale pilot trials using trimetazidine, ranolazine, perhexiline, and etomoxir have demonstrated enhanced left ventricular (LV) function and, in some circumstances, myocardial energetics in chronic ischemic and non-ischemic HF with a reduced ejection fraction (EF). However, for unidentified reasons, none of these drugs has ever been tested in a clinical trial of sufficient size. Other pilot studies came to the conclusion that because the heart in severe dilated cardiomyopathy appears to be metabolically flexible and not limited by oxygen, the current rationale for increasing glucose oxidation as a therapeutic target is contradicted and increasing fatty acid oxidation is supported. As a result, treating metabolic dysfunction in HF may benefit from raising ketone body levels. Interestingly, treatment with sodium-glucose cotransporter-2 inhibitors (SGLT2i) improves cardiac function and outcomes in HF patients with or without type 2 diabetes mellitus (T2DM) through a variety of pleiotropic effects, such as elevated ketone body levels. The improvement in overall cardiac function seen in patients receiving SGLT2i could be explained by this increase, which appears to be a reflection of an adaptive process that optimizes cardiac energy metabolism. This review aims to identify the best metabolic therapeutic approach for DCM patients, to examine the drugs that directly affect cardiac metabolism, and to outline all the potential ancillary metabolic effects of the guideline-directed medical therapy. In addition, a special focus is placed on SGLT2i, which were first studied and prescribed to diabetic patients before being successfully incorporated into the pharmacological arsenal for HF patients.

Performances of HEART score to predict 6-month prognostic of emergency department patients with chest pain: a retrospective cohort analysis.

BACKGROUND AND IMPORTANCE: Chest pain is a frequent cause of patient admissions in emergency departments (EDs). Clinical scores can help in the management of chest pain patients with an undefined impact on the appropriateness of hospitalization or discharge when compared to usual care. OBJECTIVES: The aim of this study was to assess the performances of the HEART score to predict the 6-month prognostic of patients presenting to the ED of a tertiary referral university hospital with non-traumatic chest pain. DESIGN, SETTINGS, AND PARTICIPANTS: From 7040 patients presenting with chest pain from 1 January 2015 to 31 December 2017, after applying exclusion criteria (ST-segment elevation >1 mm, shock, absence of telephone number) we selected a sample of 20% chosen randomly. We retrospectively assessed the clinical course, definitive diagnosis, and HEART score according to ED final report. Follow-up was made by telephone interview with discharged patients. In hospitalized patients, clinical records were analyzed to evaluate major adverse cardiac events (MACE) incidence. OUTCOME MEASURE AND ANALYSIS: The primary endpoint was MACE, comprising cardiovascular death, myocardial infarction, or unscheduled revascularization at 6 months. We assessed the diagnostic performance of the HEART score in ruling out MACE at 6 months. We also assessed the performance of ED usual care in the management of chest pain patients. RESULTS: Of 1119 screened, 1099 were included for analysis after excluding patients lost to follow-up; 788 patients (71.70%) had been discharged and 311 (28.30%) were hospitalized. Incident MACE was 18.3% ( n  = 205). The HEART score was retrospectively calculated in 1047 patients showing increasing MACE incidence according to risk category (0.98% for low risk, 38.02% for intermediate risk, and 62.21% for high risk). Low-risk category allowed to safely exclude MACE at 6 months with a negative predictive value (NPV) of 99%. Usual care diagnostic performance showed 97.38% sensitivity, 98.24% specificity, 95.5% positive predictive value, and 99% NPV, with an overall accuracy of 98.00%. CONCLUSIONS: In ED patients with chest pain, a low HEART score is associated with a very low risk of MACE at 6 months.

Long-term prognostic impact of subclinical myocardial dysfunction in patients recovered from COVID-19.

BACKGROUND: Cardiovascular sequelae may occur in patients recovered from coronavirus disease 2019 (COVID-19). Recent studies have detected a considerable incidence of subclinical myocardial dysfunction-assessed with speckle-tracking echocardiography-and of long-COVID symptoms in these patients. This study aimed to define the long-term prognostic role of subclinical myocardial dysfunction and long-COVID condition in patients recovered from COVID-19 pneumonia. METHODS: We prospectively followed up 110 patients hospitalized at our institution due to COVID-19 pneumonia in April 2020 and then recovered from SARS-CoV-2 infection. A 7-month clinical and echocardiographic evaluation was performed, followed by a 21-month clinical follow-up. The primary outcome was major adverse cardiovascular events (MACE), a composite of myocardial infarction, stroke, heart failure hospitalization, and all-cause mortality. RESULTS: A subclinical myocardial dysfunction-defined as an impairment of left ventricular global longitudinal strain (≥-18%)-was identified at a 7-month follow-up in 37 patients (34%), was associated with an increased risk of long-term MACE with a good discriminative power (area under the curve: .73) and resulted in a strong independent predictor of extended MACE in multivariate regression analyses. Long-COVID condition was not associated with a worse long-term prognosis, instead. CONCLUSIONS: In patients recovered from COVID-19 pneumonia, a subclinical myocardial dysfunction is present in one-third of the whole population at 7-month follow-up and is associated with a higher risk of MACE at long-term follow-up. Speckle-tracking echocardiography is a promising tool to optimize the risk-stratification in patients recovered from COVID-19 pneumonia, while the definition of a long-COVID condition has no prognostic relevance.

Aortic valve stenosis: drivers of disease progression and drug targets for therapeutic opportunities.

INTRODUCTION: Recommended therapy for calcific degenerative aortic stenosis (AS) is still aortic valve replacement (AVR), either transcatheter or surgical, since no conclusive efficacy has been determined in slowing the degenerative process by medical therapy. AREAS COVERED: This paper offers a brief overview of molecular mechanisms leading to calcification of aortic valve. It is then focused on potential markers of disease progression, as observed in many observational studies. Finally it provides a comprehensive review of drugs already tested in in vitro and human studies in order to slow aortic valve stenosis process. EXPERT OPINION: Despite research providing numerous molecular pathways underlying the calcification process, further efforts must be made to understand risk factors linked to disease progression. Some existing treatments that have already provided survival benefits in many features of cardiovascular diseases are currently being tested with promising results. In the near future new drugs acting on specific pathways by techniques such as monoclonal antibodies and RNA interference, are expected to provide better medical solutions for this ever growing number of patients.

Shadows and Lights: Perspectives of Training and Education in Neurosurgery for Undergraduate Students.

Introduction: Neurosurgical education should start during medical school to involve more students, favoring the recruitment of the most prepared and motivated ones and spreading this subject to the future medical generations. Despite multiple investigations, a dedicated educational plan does not exist. This study aims to assess the undergraduates' interests, needs, and perceptions of this subject. Materials and Methods: The survey was structured to collect demographic data of the participants, and to explore their interest in neurosurgery, their consideration of its importance in medical school, their opinions about the role of this subject in medical education, their needs in this training, and, the usefulness of this subject for their future career. Results: A total of 156 students participated in the survey. Interest in neurosurgery was shown by 76 (48.7%) participants, however, this subject was also perceived as intimidating by 86 (55.1%). Attending the first 2 years of medical school (p < 0.02), previous interest in neuroscience (p < 0.01), and in a surgical subject (p < 0.01) were the factors associated with a greater interest in this subject. Neurosurgery should be included in all students' education, according to 117 (75.0%) participants and practical operating room training should involve all students, according to 96 (61.5%). The most effective learning methods were considered internship (134, 85.9%), followed by participation in meetings or seminars (113, 72.4%). Online seminars were considered useful by 119 participants (76.3%). Neurosurgery was assessed as a potentially interesting career by 99 students (63.5%), who also considered that it can increase their preparation for other subjects (116, 74.4%). Conclusions: Neurosurgery was positively considered by medicals students, who, however, also perceived it as intimidating and hardly approachable. Demonstration that knowledge of neurosurgical concepts can improve their preparation also in general medical settings and, not only in the field of neuroscience, can be useful to promote their interest toward this subject. A combination of lectures and practical internships is considered an effective learning method, which can be fruitfully associated with new technologies.

Transcatheter aortic valve replacement in aortic stenosis and cardiac amyloidosis: a systematic review and meta-analysis.

AIMS: Aortic stenosis (AS) and cardiac amyloidosis (CA) are typical diseases of the elderly. Up to 16% of older adults with severe AS referred to transcatheter aortic valve replacement (TAVR) have a concomitant diagnosis of CA. CA-AS population suffers from reduced functional capacity and worse prognosis than AS patients. As the prognostic impact of TAVR in patients with CA-AS has been historically questioned and in light of recently published evidence, we aim to provide a comprehensive synthesis of the efficacy and safety of TAVR in CA-AS patients. METHODS AND RESULTS: We performed a systematic review and meta-analysis of studies: (i) evaluating mortality with TAVR as compared with medical therapy in CA-AS patients and (ii) reporting complications and clinical outcomes of TAVR in CA-AS patients as compared with patients with AS alone. A total of seven observational studies were identified: four reported mortality with TAVR, and four reported complications and clinical outcomes after TAVR of patients with CA-AS compared with AS alone patients. In patients with CA-AS, the risk of mortality was lower with TAVR (n = 44) as compared with medical therapy (n = 36) [odds ratio (OR) 0.23, 95% confidence interval (CI) 0.07-0.73, I2  = 0%, P = 0.001, number needed to treat = 3]. The safety profile of TAVR seems to be similar in patients with CA-AS (n = 75) as compared with those with AS alone (n = 536), with comparable risks of stroke, vascular complications, life-threatening bleeding, acute kidney injury, and 30 day mortality, although CA-AS was associated with a trend towards an increased risk of permanent pacemaker implantation (OR 1.76, 95% CI 0.91-4.09, I2  = 0%, P = 0.085). CA is associated with a numerically higher rate of long-term mortality and rehospitalizations following TAVR in patients with CA-AS as compared with those with AS alone. CONCLUSIONS: TAVR is an effective and safe procedure in CA-AS patients, with a substantial survival benefit as compared with medical therapy, and a safety profile comparable with patients with AS alone except for a trend towards higher risk of permanent pacemaker implantation.

Vasostatin-1 as a potential novel circulating biomarker in patients with chronic systolic heart failure: A pilot study.

BACKGROUND AND AIMS: Previous studies have shown that circulating chromogranin A (CgA) increases in patients with chronic systolic heart failure (HF). Aim of the present study is to evaluate the potential role of circulating vasostatin-1 (VS-1), a cardioregulatory fragment of CgA, as prognostic marker in patients with chronic HF. MATERIALS AND METHODS: The plasma levels of CgA and VS-1 were determined in 80 patients with chronic systolic HF. Patients were followed-up to evaluate the occurrence of cardiovascular (CV) events. RESULTS: CgA and VS-1 plasma levels were significantly higher in patients with CV events at follow-up. VS-1, but not CgA, was associated to NT-proBNP. No significant association of CgA and VS-1 with left ventricular ejection fraction (LVEF) was observed. CgA, NT-proBNP and age, but not VS-1, were independent predictors of CV events. CONCLUSION: In patients with chronic systolic HF those who experienced CV events had higher levels of VS-1 and CgA. Given its established effect on cardiac cells, the association of VS-1 levels with NT-proBNP levels but not with LVEF, suggests that this fragment might provide complementary information to NT-proBNP and CgA in HF patients.

Characterization of Myocardial Injury in Patients With COVID-19.

BACKGROUND: Myocardial injury is frequent among patients hospitalized with coronavirus disease-2019 (COVID-19) and is associated with a poor prognosis. However, the mechanisms of myocardial injury remain unclear and prior studies have not reported cardiovascular imaging data. OBJECTIVES: This study sought to characterize the echocardiographic abnormalities associated with myocardial injury and their prognostic impact in patients with COVID-19. METHODS: We conducted an international, multicenter cohort study including 7 hospitals in New York City and Milan of hospitalized patients with laboratory-confirmed COVID-19 who had undergone transthoracic echocardiographic (TTE) and electrocardiographic evaluation during their index hospitalization. Myocardial injury was defined as any elevation in cardiac troponin at the time of clinical presentation or during the hospitalization. RESULTS: A total of 305 patients were included. Mean age was 63 years and 205 patients (67.2%) were male. Overall, myocardial injury was observed in 190 patients (62.3%). Compared with patients without myocardial injury, those with myocardial injury had more electrocardiographic abnormalities, higher inflammatory biomarkers and an increased prevalence of major echocardiographic abnormalities that included left ventricular wall motion abnormalities, global left ventricular dysfunction, left ventricular diastolic dysfunction grade II or III, right ventricular dysfunction and pericardial effusions. Rates of in-hospital mortality were 5.2%, 18.6%, and 31.7% in patients without myocardial injury, with myocardial injury without TTE abnormalities, and with myocardial injury and TTE abnormalities. Following multivariable adjustment, myocardial injury with TTE abnormalities was associated with higher risk of death but not myocardial injury without TTE abnormalities. CONCLUSIONS: Among patients with COVID-19 who underwent TTE, cardiac structural abnormalities were present in nearly two-thirds of patients with myocardial injury. Myocardial injury was associated with increased in-hospital mortality particularly if echocardiographic abnormalities were present.

Long-term clinical effects of recanalization of chronic coronary total occlusions in patients with left ventricular systolic dysfunction.

OBJECTIVES: The aim of the present analysis is to evaluate the clinical impact of chronic total occlusions (CTOs) recanalization in patients with left ventricular (LV) systolic dysfunction. BACKGROUND: According to contemporary knowledge, patient selection for percutaneous CTO revascularization is not yet standardized. In particular, data on outcomes in patients with LV systolic dysfunction undergoing percutaneous coronary intervention (PCI) for CTO are scarce. METHODS: From a total of 2,421 consecutive patients with at least one CTO, 436 patients with ejection fraction (EF) ≤45%, who were referred for coronary angiography between January 1998 and September 2014, were selected. Patients with successful recanalization of the target CTO were assigned to CTO-revascularized group and those with failed or not attempted recanalization to the CTO-not revascularized (CTO-NR) group. Study endpoints were all-cause death, cardiac death, and occurrence of myocardial infarction on follow-up. RESULTS: Out of 436 CTO patients with reduced EF, 228 (52.3%) were successfully recanalized and 208 patients (47.7%) were not, either due to CTO-PCI failure (n = 106, 24.3%) or because CTO-PCI was not attempted (n = 102, 23.4%). At long-term follow-up, CTO-NR patients had significantly higher rate of overall (p = .021) and cardiac mortality (p = .035) compared to those successfully revascularized. CONCLUSION: In patients with systolic LV dysfunction (EF ≤ 45%), CTO revascularization was associated with significant lower rate of total and cardiac mortality compared to those with nonrevascularized CTO.

Real-Life Indications to Sacubitril/Valsartan Treatment in Patients With Chronic Systolic Heart Failure.

OBJECTIVE: International guidelines recommend the introduction of sacubitril/valsartan (Entresto) in patients with heart failure (HF) and reduced ejection fraction (EF), who remain symptomatic, despite optimal uptitrated therapy. The purpose of the following analysis is to verify the real-life eligibility for sacubitril/valsartan in a population of patients suffering from chronic HF, regularly monitored in a single HF clinic and treated according to guideline-directed medical therapy (GDMT). METHODS: From a total of 1070 patients regularly monitored in our HF Clinic between January 2011 and September 2017, the clinical records of 224 patients with HF and reduced EF on optimized GDMT were retrospectively analyzed. RESULTS: Of 224 analyzed patients, 75 improved their EF or were asymptomatic after uptitration of GDMT during follow-up; 50 were not on angiotensin-converting enzyme inhibitor or angiotensin receptor blocker for different reasons; 13 patients had systolic blood pressure ≤100 mm Hg, so they were not eligible for sacubitril/valsartan introduction. The remaining patients were still symptomatic (NYHA ≥2), and therefore, sacubitril/valsartan introduction was indicated in these 86 patients (38.4%) of 224 enrolled. CONCLUSION: In patients with HF and reduced EF, where GDMT is appropriately achieved, indication to sacubitril/valsartan treatment is around 38%.

Real-life indications to ivabradine treatment for heart rate optimization in patients with chronic systolic heart failure.

: Ivabradine is a selective and specific inhibitor of If current. With its pure negative chronotropic action, it is recommended by European Society of Cardiology and American College of Cardiology/American Heart Association guidelines in symptomatic heart failure patients (NYHA ≥ 2) with ejection fraction 35% or less, sinus rhythm and heart rate (HR) at least 70 bpm, despite maximally titrated ß-blocker therapy. Data supporting this indication mainly derive from the SHIFT study, in which ivabradine reduced the combined endpoint of mortality and hospitalization, despite the fact that only 26% of patients enrolled were on optimal ß-blocker doses. The aim of the present analysis is to establish the real-life eligibility for ivabradine in a population of patients with systolic heart failure, regularly attending a single heart failure clinic and treated according to guideline-directed medical therapy (GDMT). The clinical cards of 308 patients with heart failure with reduced ejection fraction (HFrEF) through a 68-month period of observation were retrospectively analyzed. GDMT, including ß-blocker up-titration to maximal tolerated dose, was implemented during consecutive visits at variable intervals. Demographic, clinical and echocardiographic data were collected at each visit, together with 12-leads ECG and N-terminal pro-B-type natriuretic peptide levels. Out of 308 analyzed HFrEF patients, 220 (71%) were on effective ß-blocker therapy, up-titrated to effective/maximal tolerated dose (55 ±â€Š28% of maximal dose) (HR 67 ±â€Š10 bpm). Among the remaining 88 patients, 10 (3.2%) were on maximally tolerated ß blocker and ivabradine; 21 patients (6.8%), despite being on maximal tolerated ß-blocker dose, had still HR ≥70 bpm, ejection fraction 35% or less and were symptomatic NYHA ≥2, being therefore eligible for ivabradine treatment. The remaining 57 (18%) patients were not on ß blocker due to either intolerance or major contraindications. Among them, 13 (4%) were taking ivabradine alone. Of the final 44 (14%) patients, 27 (9%) showed an inadequate HR control (74 ±â€Š6 bpm). Of these, only eight (3%) patients resulted to be eligible for ivabradine introduction according to HR and ejection fraction parameters. Overall ivabradine was indicated in 52 patients (16.8%) out of 308 enrolled.In conclusion, in a carefully managed population of patients with moderate and stable HFrEF, in which optimal GDMT is properly attained, indication to ivabradine treatment is around 17%.