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Competing Interests: Declaration of interests We declare no competing interests.

Acute myocarditis covers a wide spectrum of clinical presentations, from uncomplicated myocarditis to severe forms complicated by hemodynamic instability and ventricular arrhythmias; however, all these forms are characterized by acute myocardial inflammation. The term "chronic inflammatory cardiomyopathy" describes a persistent/chronic inflammatory condition with a clinical phenotype of dilated and/or hypokinetic cardiomyopathy associated with symptoms of heart failure and increased risk for arrhythmias. A continuum can be identified between these two conditions. The importance of early diagnosis has grown markedly in the contemporary era with various diagnostic tools available. While cardiac magnetic resonance (CMR) is valid for diagnosis and follow-up, endomyocardial biopsy (EMB) should be considered as a first-line diagnostic modality in all unexplained acute cardiomyopathies complicated by hemodynamic instability and ventricular arrhythmias, considering the local expertise. Genetic counseling should be recommended in those cases where a genotype-phenotype association is suspected, as this has significant implications for patients' and their family members' prognoses. Recognition of the pathophysiological pathway and clinical "red flags" and an early diagnosis may help us understand mechanisms of progression, tailor long-term preventive and therapeutic strategies for this complex disease, and ultimately improve clinical outcomes.

Hypertrophic cardiomyopathy (HCM) follows highly variable paradigms and disease-specific patterns of progression towards heart failure, arrhythmias and sudden cardiac death. Therefore, a generalized standard approach, shared with other cardiomyopathies, can be misleading in this setting. A multimodality imaging approach facilitates differential diagnosis of phenocopies and improves clinical and therapeutic management of the disease. However, only a profound knowledge of the progression patterns, including clinical features and imaging data, enables an appropriate use of all these resources in clinical practice. Combinations of various imaging tools and novel techniques of artificial intelligence have a potentially relevant role in diagnosis, clinical management and definition of prognosis. Nonetheless, several barriers persist such as unclear appropriate timing of imaging or universal standardization of measures and normal reference limits. This review provides an overview of the current knowledge on multimodality imaging and potentialities of novel tools, including artificial intelligence, in the management of patients with sarcomeric HCM, highlighting the importance of specific "red alerts" to understand the phenotype-genotype linkage.

Competing Interests: Dr Müller has received honoraria for advisory boards, consulting, and lectures/talks from Novartis, Gilead Sciences, Bristol Myers Squibb, and Janssen. Dr Matter has received consulting or speaker honoraria from Amgen and Novartis; and grants to the institution from Eli Lilly, AstraZeneca, Novartis, MSD, the Swiss National Science Foundation, and the Swiss Heart Foundation. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose.

Arrhythmogenic Right Ventricular Cardiomyopathy (ARVC) is a hereditary condition that can cause sudden cardiac death in young, frequently athletic individuals under the age of 35 due to malignant arrhythmias. Competitive and endurance exercise may hasten the onset and progression of ARVC, leading to right ventricular dysfunction and potentially fatal ventricular arrhythmias earlier in life. In this article, we present a novel, pathogenic, early truncating heterozygous variant in the PKP2 gene that causes biventricular arrhythmogenic cardiomyopathy and affects a family, of which the only member with the positive phenotype is a competitive endurance athlete.

Background: Direct oral anticoagulants (DOACs) have a favourable risk-benefit profile compared to vitamin K-antagonists (VKAs) in atrial fibrillation (AF). Dosing is based on age, weight and renal function, without need of routine monitoring., Methods and Results: In two prospective, multicentre AF cohorts (Swiss-AF, BEAT-AF) patients were stratified as receiving VKAs or adequately-, under- or overdosed DOACs, according to label. Primary outcome was a composite of major adverse clinical events (MACE), defined as cardiovascular death, myocardial infarction (MI), ischaemic stroke and systemic embolism. Secondary outcomes included major bleeding. Adjustment for confounding was performed. Median follow-up was 4 years. Of 3236 patients, 1875 (58%) were on VKAs and 1361 (42%) were on DOACs, of which 1137 (83%) were adequately-, 134 (10%) over- and 90 (7%) under-dosed. Compared to adequately dosed individuals, overdosed patients were more likely to be older and female. Underdosing correlated with concomitant aspirin therapy and coronary artery disease. Both groups had higher CHA 2 DS 2 -VASc scores. Patients on overdosed DOACs had higher incidence of MACE (HR 1.75; CI 1.10-2.79; adjusted-HR: 1.22) and major bleeding (HR 1.99; CI 1.14-3.48; adjusted-HR: 1.51). Underdosing was not associated with a higher incidence of MACE (HR 0.94; CI 0.46-1.92; adjusted-HR 0.61) or major bleeding (HR 1.07; CI 0.46-2.46; adjusted-HR 0.82). After adjustment, all CIs crossed 1.0., Conclusion: Inappropriate DOAC-dosing was more prevalent in multimorbid patients, but did not correlate with higher risks of adverse events after adjusting for confounders. DOAC prescription should follow label., Competing Interests: Declaration of Competing Interest None., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Background and Aims: Treatment with proprotein convertase subtilisin-kexin type 9 inhibitors (PCSK9i), in addition to statin therapy, reduces LDL-cholesterol (LDL-c) in some patients to extremely low levels (i.e.< 20 mg/dl or < 0.52 mmol/l). There is concern that at such low levels, the physiologic role of cholesterol may be impaired, e.g. the adrenal cortisol stress response might be compromised. We therefore evaluated the effect of PCSK9i therapy on the cortisol response to ACTH in patients with LDL-c down to extremely low levels., Methods: Nineteen patients on PCSK9i therapy and 18 controls matched for age, gender and comorbidities were included. The cortisol response to adrenocorticotropic hormone (ACTH) was tested after application of 250 μg ACTH., Results: LDL-c levels ranged from 0.42 to 3.32 mmol/l (mean 1.38 ± 0.84 mmol/l) in the PCSK9i group and 0.81-4.82 mmol/l (mean 2.10 ± 0.97) in the control group. By analysis of covariance (ANCOVA), the PCSK9i group had significantly lower cortisol response compared to the control group (- 97.26 nmol/l, -178.60 to -15.93, p = 0.02) after 60 min. There was a significant positive correlation between the duration of PCSK9i treatment and cortisol levels (r = 0.59, p = 0.009). Extremely low LDL-c levels down to 0.42 mmol/l were not associated with lower stimulated cortisol levels., Conclusions: Patients on PCSK9i therapy showed a significantly lower cortisol response to ACTH. Stimulated cortisol levels were lower in the first months of PCSK9i treatment, suggesting an adaptive phenomenon. We conclude that the adrenal stress response in patients on PCSK9 inhibitor therapy is reduced., (Copyright © 2021 Elsevier B.V. All rights reserved.)

The omega-3 fatty acid (n-3 FA) eicosapentaenoic acid (EPA) reduces stroke in patients with atherosclerotic cardiovascular disease. Whether EPA affects stroke or cerebral small vessel dis-ease in patients with atrial fibrillation (AF) remains uncertain. EPA, docosahexaenoic acid (DHA), docosapentaenoic acid (DPA), and alpha-linolenic acid (ALA) were determined by gas chromatography in 1657 AF patients from the Swiss Atrial Fibrillation study. All patients underwent brain MRI to detect ischemic brain infarcts, classified as large noncortical or cortical infarcts (LNCCIs); markers of small vessel disease, classified as small noncortical infarcts (SNCIs), number of microbleeds, and white matter lesion (WML) volumes. Individual and total n-3 FAs (EPA + DHA + DPA + ALA) were correlated with LNCCIs and SNCIs using logistic regression, with numbers of microbleeds using a hurdle model, and WML volumes using linear regression. LNCCIs were detected in 372 patients (22.5%). EPA correlated inversely with the prevalence of LNCCIs (odds ratio [OR] 0.51 per increase of 1 percentage point EPA, 95% confidence interval [CI] 0.29-0.90). DPA correlated with a higher LNCCI prevalence (OR 2.48, 95%CI 1.49-4.13). No associations with LNCCIs were found for DHA, ALA, and total n-3 FAs. Neither individual nor total n-3 FAs correlated with markers of small vessel disease. In conclusion, EPA correlates inversely with the prevalence of ischemic brain infarcts, but not with markers of small vessel disease in patients with AF.

Flucloxacillin (FLU) administered by the oral route is widely used for treating various infections, but there are no published retrospective or prospective trials of its efficacy, or its advantages or disadvantages compared to parenteral treatment or other antibiotics for treating osteomyelitis. Based on published in vitro data and expert opinions, other non-β-lactam oral antibiotics that have better bone penetration are generally preferred over oral FLU. We reviewed the literature for studies of oral FLU as therapy of osteomyelitis (OM), stratified by acute versus chronic and pediatric versus adult cases. In striking contrast to the prevailing opinions and the few descriptive data available, we found that treatment of OM with oral FLU does not appear to be associated with more clinical failures compared to other oral antibiotic agents. Because of its narrow antibiotic spectrum, infrequent severe adverse effects, and low cost, oral FLU is widely used in clinical practice. We therefore call for investigators to conduct prospective trials investigating the effectiveness and potential advantages of oral FLU for treating OM., Competing Interests: Competing Interests: The authors have declared that no competing interest exists., (© The author(s).)

Aims: The aim of the study was to retrospectively evaluate safety and patient satisfaction of same-day discharge after elective radial coronary angiography/percutaneous coronary intervention (PCI) after the implementation of a radial lounge facility., Methods: All patients admitted to our radial lounge with a planned same-day discharge after an uncomplicated coronary angiography/PCI, having a co-living caregiver, were day enrolled in the study. Rates of same-day discharge, unplanned overnight stay, and in-hospital and first complications [death, myocardial infarction (MI), unplanned coronary angiography, access site hematoma, bleedings requiring hospitalization] were analysed; satisfaction was also evaluated through a questionnaire., Results: From February 2015 to January 2016, 312 patients with a mean age of 66.6 ± 10.8 years were admitted to the radial lounge (coronary angiography, n = 232; PCIs, n = 80). Of them, 245 (78.5%) were discharged the same day. Mean radial lounge monitoring was 6:35 h (interquartile range 5:30-7:30 h). No episodes of death/MI/unplanned coronary angiography were observed both in same-day discharged and postponed patients. Reasons to postpone discharge were: PCI deemed to need prolonged monitoring in 31, patient's preference in 14, femoral shift in 13, surgery in four, chest pain in four, and bleeding in one. At day 1, 11 access site hematoma and one hospitalization for access site bleeding were reported. Patients reported complete satisfaction in 97% of cases. Unplanned overnight stay was common among PCIs patients (RR 6.2, 95% CI 3.9-9.9, P < 0.001)., Conclusion: A low rate of minor complications was observed in elective radial coronary angiography and PCIs showing the feasibility and safety of the development of an institutional protocol for same-day discharge after the implementation of a radial lounge facility.

Background: Chronic rhinosinusitis (CRS) is a frequent disease with high social impact and multifactorial pathogenesis. Recently, single nucleotide polymorphisms within the TAS2R38 gene have been implicated as possible contributors to the complex gene-environment interactions in CRS. The purpose of this study was to confirm the proposed correlation between TAS2R38 genotype, CRS and related comorbidities., Methods: Fifty-three CRS patients and 39 healthy individuals were genotyped at the TAS2R38 locus. CRS patients were treated by endoscopic sinus surgery and medical therapies and subdivided in CRS with nasal polyps (CRSwNPs) and CRS without nasal polyps (CRSsNPs). The effect of genotype on CRS and CRS-related comorbidities was assessed., Results: The distribution of the different genotypes at the TAS2R38 locus was not significantly different between CRS patients, either with or without nasal polyps, and controls. Besides, no association was found between the different genotypes at the TAS2R38 locus and CRS-related comorbidities., Conclusions: No association was found between TAS2R38 alleles or genotypes and CRS, thus questioning its role in the pathogenesis of CRS.

Background: Rotavirus is the major cause of acute gastroenteritis and severe dehydrating diarrhea in young children., Methods: To estimate the proportion of hospital admissions for rotavirus acute gastroenteritis and identify the circulating G and P genotypes among children under five years of age, we conducted a prospective observational study from January to December 2008, recruiting children consecutively admitted to six hospitals in Milan and nearby towns in northern Italy. Typing was done on stool samples by reverse transcriptase polymerase chain reaction amplification., Results: Of the 521 stool samples from children with acute gastroenteritis, 34.9% (95%CI, 30.8 to 39.2%) were rotavirus-positive. Two thirds (67.6%) were under two years of age, and 13.2% were under six months. The predominant G type was G1 (40.7%), followed by G9 (22.5%), G2 (13.2%), G3 (5.5%), G4 (3.8%) and G10 (1.6%). Twenty-one (11.7%) mixed-G infections were identified: G1+G10 (8.8%); G1+G9 (1.6%); and G2+G10 (1.2%). Only P[8] (67.6%) and P[4] (12.6%) types were P genotyped. The predominant single G/P combination was G1P[8] (39.7%), followed by G9P[8] (25.3%), G2P[4] (14.3%), and G3P[8] (4.1%). All G-mixed types combined with P[8]., Conclusions: These findings show an high prevalence of rotavirus infections among children admitted to hospital for acute gastroenteritis caused by different rotavirus strains circulating in the area studied.

Gitelman syndrome (GS) is a heritable renal disorder characterized by hypokalemia, hypomagnesemia, metabolic alkalosis and hypocalciuria. Patients with GS usually have mild symptoms as muscular weakness and cramps, and they often are diagnosed in older age during routine investigation. We report a 11 year old boy with GS.

The Authors examined 2.382 babies who were between 4 and 6 weeks old using the seven postural reactions proposed by Vojta for neuromotor screening. They followed the progress of 2.295 (96,35%) babies up to the age of 1 year. 100% of the babies judged to be normal after the first visit were normal after a year. The Authors describe the evolution of the babies who were abnormal at the first visit, and clarify the results obtained with early physiotherapeutic treatment.

For many years molds have considered to be important causes of rhinitis and asthma but since they have been poorly studied many questions remain unanswered. Allergological and epidemiological considerations have been made by the authors concerning the role of the Alternaria tenuis in respiratory diseases in children. 253 subjects were skin tested, 9.48 percent had an immediate reaction, 3.55 were also positive to the fungus only. Good correlation was observed between positive skin tests and RAST (66%). This study confirmed that probably Alternaria tenuis has an important role as immunopathogen for rhinitis and asthma in children. The authors discuss epidemiological considerations and related problems.