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Background and Aims: Hypoalbuminemia, as defined by serum albumin (SA) levels ≤35 g/L, is associated to venous and arterial thrombosis in general population and in patients at risk of cardiovascular disease. It is unknown if SA ≤35 g/L is also associated to portal vein thrombosis (PVT) in cirrhosis. Methods: Cirrhotic patients enrolled in the Portal vein thrombosis Relevance On Liver cirrhosis: Italian Venous thrombotic Events Registry (PRO-LIVER) study (n = 753), were followed-up for 2 years to assess the risk of PVT, that was diagnosed by Doppler ultrasonography. Child-Pugh classes, Model for End-Stage Liver Disease score, presence of hepatocellular carcinoma and laboratory variables including SA, D-dimer, and high-sensitivity C-reactive protein (hs-CRP) were measured at baseline. Results: SA ≤35 g/L was detected in 52% of patients. A logistic multivariate regression analysis showed that higher Child-Pugh class, hepatocellular carcinoma and thrombocytopenia were significantly associated to SA ≤35 g/L. In a subgroup of patients where data regarding hs-CRP and D-dimer were available, SA ≤35 g/L was inversely associated with hs-CRP and D-dimer. During the follow-up, a total of 61 patients experienced PVT. A Kaplan Meier survival analysis showed SA ≤35 g/L was associated to increased risk of PVT compared to SA >35 g/L (P = .005). A multivariate Cox proportional hazards regression analysis showed that male sex, lower platelet count, and SA ≤35 g/L remained associated to PVT after adjusting for confounding factors. Conclusion: Cirrhotic patients with SA ≤35 g/L are at higher risk of experiencing PVT compared to those with SA >35 g/L and could be considered as potential candidates to anticoagulant prophylaxis for PVT prevention.

Transthoracic echocardiography (TTE) is routinely required during pre-participation screening in the presence of symptoms, family history of sudden cardiac death or cardiomyopathies <40-year-old, murmurs, abnormal ECG findings or in the follow-up of athletes with a history of cardiovascular disease (CVD). TTE is a cost-effective first-line imaging modality to evaluate the cardiac remodeling due to long-term, intense training, previously known as the athlete's heart, and to rule out the presence of conditions at risk of sudden cardiac death, including cardiomyopathies, coronary artery anomalies, congenital, aortic and heart valve diseases. Moreover, TTE is useful for distinguishing physiological cardiac adaptations during intense exercise from pathological behavior due to an underlying CVD. In this expert opinion statement endorsed by the Italian Society of Sports Cardiology, we discussed common clinical scenarios where a TTE is required and conditions falling in the grey zone between the athlete's heart and underlying cardiomyopathies or other CVD. In addition, we propose a minimum dataset that should be included in the report for the most common indications of TTE in sports cardiology clinical practice., Competing Interests: Declaration of competing interest The authors report no relationships that could be construed as a conflict of interest. All authors have seen and approved the manuscript being submitted, have contributed significantly to the work, attest to the validity and legitimacy of the data and its interpretation, and agree to its submission to the International Journal of Cardiology., (Copyright © 2024. Published by Elsevier B.V.)

Background: For left-sided radiofrequency catheter ablation (LCA) in pediatrics, significant practice variability exists regarding anticoagulation and discharge practices. Given the lack of data in pediatric patients, the risks and benefits of these practices are not well defined., Objective: The purpose of this study was to evaluate the safety of same-day discharge and use of aspirin (ASA) in pediatric patients following LCA., Methods: We performed a retrospective cohort study of pediatric patients who underwent LCA from 2010 to 2020 at our institution. Discharge timing and ASA usage were based on operator preference. The primary outcome was incidence of postablation anticoagulation complications reported within 1 month of the procedure., Results: Three hundred seventy-six patients underwent LCA and met inclusion criteria. Median [25th, 75th percentiles] age was 13.9 [10.5, 16.2] years; 18 (4.7%) had a history of structural heart disease. The most common substrates for ablation were Wolff-Parkinson-White syndrome (183 patients [48.7%]), concealed accessory pathway (159 patients [42.3%]), and ectopic atrial tachycardia (10 patients [2.7%]). Three hundred thirty-eight patients (89.9%) were discharged on the day of LCA. Seventy-six patients (20.2%) were prescribed ASA at discharge. Of those who underwent follow-up (273 patients [72.6%]), 7 (2.7%) reported an anticoagulation complication (5 with hematoma, 2 with headache). One of these patients was prescribed ASA; none required readmission. There was no correlation between anticoagulation complications and same-day discharge or with ASA usage., Conclusion: Given the rare incidence of anticoagulation complications in pediatric patients undergoing LCAs, same-day discharge from the electrophysiology laboratory without anticoagulation should be considered., Competing Interests: Disclosures The authors have no conflicts of interest to disclose., (Copyright © 2024 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.)

Three-dimensional electroanatomical mapping (EAM) has the potential to identify the pathological substrate underlying ventricular arrhythmias (VAs) in different clinical settings by detecting myocardial areas with abnormally low voltages, which reflect the presence of different cardiomyopathic substrates. In athletes, the added value of EAM may be to enhance the efficacy of third-level diagnostic tests and cardiac magnetic resonance (CMR) in detecting concealed arrhythmogenic cardiomyopathies. Additional benefits of EAM in the athlete include the potential impact on disease risk stratification and the consequent implications for eligibility to competitive sports. This opinion paper of the Italian Society of Sports Cardiology aims to guide general sports medicine physicians and cardiologists on the clinical decision when to eventually perform an EAM study in the athlete, highlighting strengths and weaknesses for each cardiovascular disease at risk of sudden cardiac death during sport. The importance of early (preclinical) diagnosis to prevent the negative effects of exercise on phenotypic expression, disease progression, and worsening of the arrhythmogenic substrate is also addressed., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Molecular genetic testing is an increasingly available test to support the clinical diagnosis of inherited cardiovascular diseases through identification of pathogenic gene variants and to make a preclinical genetic diagnosis among proband's family members (so-called "cascade family screening"). In athletes, the added value of molecular genetic testing is to assist in discriminating between physiological adaptive changes of the athlete's heart and inherited cardiovascular diseases, in the presence of overlapping phenotypic features such as ECG changes, imaging abnormalities or arrhythmias ("grey zone"). Additional benefits of molecular genetic testing in the athlete include the potential impact on the disease risk stratification and the implications for eligibility to competitive sports. This position statement of the Italian Society of Sports Cardiology aims to guide general sports medical physicians and sports cardiologists on clinical decision as why and when to perform a molecular genetic testing in the athlete, highlighting strengths and weaknesses for each inherited cardiovascular disease at-risk of sudden cardiac death during sport. The importance of early (preclinical) diagnosis to prevent the negative effects of exercise on phenotypic expression, disease progression and worsening of the arrhythmogenic substrate is also addressed., (Copyright © 2022. Published by Elsevier B.V.)

Hydrogels based on short peptide molecules are interesting biomaterials with wide present and prospective use in biotechnologies. A well-known possible drawback of these materials can be their limited mechanical performance. In order to overcome this problem, we prepared Fmoc-Phe 3 self-assembling peptides by a biocatalytic approach, and we reinforced the hydrogel with graphene oxide nanosheets. The formulation here proposed confers to the hydrogel additional physicochemical properties without hampering peptide self-assembly. We investigated in depth the effect of nanocarbon morphology on hydrogel properties (i.e. morphology, viscoelastic properties, stiffness, resistance to an applied stress). In view of further developments towards possible clinical applications, we have preliminarily tested the biocompatibility of the composites. Our results showed that the innovative hydrogel composite formulation based on FmocPhe3 and GO is a biomaterial with improved mechanical properties that appears suitable for the development of biotechnological applications., (Copyright © 2021 The Author(s). Published by Elsevier B.V. All rights reserved.)

Competitive athletes of all skill levels are at risk of sudden cardiac death (SCD) due to certain heart conditions. Prior to engagement in high-intensity athletics, it is necessary to screen for these conditions in order to prevent sudden cardiac death. Cardiac-CT angiography (CCTA) is a reliable tool to rule out the leading causes of SCD by providing an exceptional overview of vascular and cardiac morphology. This allows CCTA to be a powerful resource in identifying cardiac anomalies in selected patients (i.e. unclear symptoms or findings at ECG or echocardiography) as well as to exclude significant coronary artery disease (CAD). With the advancement of technology over the last few years, the latest generations of computed tomography (CT) scanners provide better image quality at lower radiation exposures. With the amount of radiation exposure per scan now reaching the sub-millisievert range, the number of CT examinations it is supposed to increase greatly, also in the athlete's population. It is thus necessary for radiologists to have a clear understanding of how to make and interpret a CCTA examination so that these studies may be performed in a responsible and radiation conscious manner especially when used in the younger populations. Our work aims to illustrate the main radiological findings of CCTAs and highlight their clinical impact with some case studies. We also briefly describe critical features of state-of-the-art CT scanners that optimize different acquisitions to obtain the best quality at the lowest possible dose., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Heart transplantation (HTx) is considered the gold-standard therapy for the treatment of advanced heart failure (HF). The long-term survival in HTx is hindered by graft failure which represents one of the major limitations of the long-term efficacy of HTx. Endomyocardial biopsy (EMB) and the evaluation of donor-specific antibodies (DSA) are currently considered the essential diagnostic tools for surveillance of graft rejection. Recently, new molecular biomarkers (including cell-free DeoxyriboNucleic Acid, exosomes, gene profiling microarray, nanostring, reverse transcriptase multiplex ligation-dependent probe amplification, proteomics and immune profiling by quantitative multiplex immunofluorescence) provide useful information on mechanisms of graft rejection. The ambitious role of a similar change of perspective is aimed at a better and longer graft preservation., (Copyright © 2021. Published by Elsevier B.V.)

A wide range of microbial pathogens is capable of entering the gastrointestinal tract, causing infectious diarrhea and colitis. A finely tuned balance between different cytokines is necessary to eradicate the microbial threat and to avoid infection complications. The current study identified IL-33 as a critical regulator of the immune response to the enteric pathogen Citrobacter rodentium. We observed that deficiency of the IL-33 signaling pathway attenuates bacterial-induced colitis. Conversely, boosting this pathway strongly aggravates the inflammatory response and makes the mice prone to systemic infection. Mechanistically, IL-33 mediates its detrimental effect by enhancing gut permeability and by limiting the induction of protective T helper 17 cells at the site of infection, thus impairing host defense mechanisms against the enteric pathogen. Importantly, IL-33-treated infected mice supplemented with IL-17A are able to resist the otherwise strong systemic spreading of the pathogen. These findings reveal a novel IL-33/IL-17A crosstalk that controls the pathogenesis of Citrobacter rodentium-driven infectious colitis. Manipulating the dynamics of cytokines may offer new therapeutic strategies to treat specific intestinal infections.

Background: Ventricular arrhythmias (VAs) are the most common cause of death in athletes. The differences in the electroanatomic substrate in athletes and nonathletes with complex VA are unknown., Objective: The purpose of this study was to compare the electroanatomic substrate of complex VA in athletes vs nonathletes., Methods: The study prospectively enrolled young athletes and nonathletes with VA. Patients underwent 2-dimensional echocardiography, cardiac magnetic resonance (CMR) imaging, coronary angiography, 3-dimensional electroanatomic mapping (3D-EAM), and 3D-EAM-guided endomyocardial biopsy (EMB). Follow-up included 24-hour electrocardiographic Holter or implantable cardioverter-defibrillator/loop recorder interrogation for VA recurrence., Results: Thirty-three patients were enrolled: 18 competitive athletes (56%) and 15 nonathletes (44%). Left ventricular and right ventricular (RV) findings by echocardiography and CMR did not show structural disease. Nine athletes (50%) were asymptomatic compared to 1 nonathlete (7%; P <.05). Unifocal origin of VA was reported in 14 athletes (93%) and 17 nonathletes (94%). Athletes showed a larger RV unipolar than bipolar scar (18 ± 17 cm 2 vs 3 ± 3.8 cm 2 ; P = .04). Diagnostic yield of EMB was 50% in athletes and 40% in nonathletes. Among athletes, the final diagnosis was myocarditis in 2, arrhythmogenic ventricular right cardiomyopathy in 1, and focal replacement fibrosis in 1. Among nonathletes, EMB revealed focal replacement fibrosis in 4 cases. At median follow-up of 18.7 months, Kaplan-Meier curves showed lower VA recurrence in detrained athletes than nonathletes (53% vs 6%; P = .02)., Conclusion: This study showed the need for extensive diagnostic workup in apparently healthy young patients with complex VA in order to characterize concealed cardiomyopathies., (Copyright © 2019 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.)

The intrinsically disordered tau protein plays a pivotal role in the pathogenesis of Alzheimer's disease (AD) and other human tauopathies. Abnormal post-translational modifications of tau, such as truncation, are causally involved in the onset/development of these neurodegenerative diseases. In this context, the AD-relevant N-terminal fragment mapping between 26 and 44 amino acids of protein (tau26-44) is interesting, being endowed with potent neurotoxic effects in vitro and in vivo. However, the understanding of the mechanism(s) of tau26-44 toxicity is a challenging task because, similarly to the full-length tau, it does not have a unique 3D structure but exists as dynamic ensemble of conformations. Here we use Atomic Force Spectroscopy, Small Angle X-ray Scattering and Molecular Dynamics simulation to gather structural and functional information on the tau26-44. We highlight the presence, the type and the location of its temporary secondary structures and we unveil the occurrence of relevant transient tertiary conformations that could contribute to tau26-44 toxicity. Data are compared with those obtained on the biologically-inactive, reverse-sequence (tau44-26 peptide) which has the same mass, charge, aminoacidic composition as well as the same overall unfolded character of tau26-44., (Copyright © 2019. Published by Elsevier B.V.)

The umbilical cord is a complex structure containing three vessels, one straight vein and two coiled arteries, encased by the Wharton Jelly (WJ) a spongy structure made of collagen and hydrated macromolecules. Fetal blood reaches the placenta through the arteries and flows back to the fetus through the vein. The role of the WJ in maintaining cord circulation proficiency and the ultimate reason for arterial coiling still lack of reasonable mechanistic interpretations. We performed biaxial tension tests and evidenced significant differences in the mechanical properties of the core and peripheral WJ. The core region, located between the arteries and the vein, resulted rather stiffer close to the fetus. Finite element modelling and optimization based inverse method were used to create 2D and 3D models of the cord and to simulate stress distribution in different hemodynamic conditions, compressive loads and arterial coiling. We recorded a facilitated stress transmission from the arteries to the vein through the soft core of periplacental WJ. This condition generates a pressure gradient that boosts the venous backflow circulation towards the fetus. Peripheral WJ allows arteries to act as pressure buffering chambers during the cardiac diastole and helps to dissipate compressive forces away from vessels. Altered WJ biomechanics may represent the structural basis of cord vulnerability in many high-risk clinical conditions., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

The composition of immune infiltrates strongly affects the prognosis of patients with colorectal cancer (CRC). Interleukin (IL)-33 and regulatory T cells (Tregs) in the tumor microenvironment have been separately implicated in CRC; however their contribution to intestinal carcinogenesis is still controversial. Here, we reveal that IL-33 signaling promotes CRC by changing the phenotype of Tregs. In mice with CRC, tumor-infiltrating Tregs preferentially upregulate IL-33 receptor (ST2), and IL-33/ST2 signaling positively correlates with tumor number and size. Transcriptomic and flow cytometry analyses demonstrate that ST2 expression induces a more activated and migratory phenotype in FOXP3 + Tregs, which favors their accumulation in the tumor environment. Consequently, genetic ablation of St2 reduces Treg infiltration and concomitantly enhances the frequencies of effector CD8 + T cells, thereby restraining CRC. Mechanistically, IL-33 curtails IL-17 production by FOXP3 + Tregs and inhibits Th17 differentiation. In humans, numbers of activated ST2-expressing Tregs are increased in blood and tumor lesions of CRC patients, suggesting a similar mode of regulation. Together, these data indicate a central role of IL-33/ST2 signaling in shaping an immunosuppressive environment during intestinal tumorigenesis. Blockade of this pathway may provide a strategy to modulate the composition of CRC immune infiltrates.

Background: Pre-participation screening (PPS) of athletes aged over 35 years (master athletes, MA) is a major concern in Sports Cardiology. In this population, sports-related sudden cardiac death is rare but usually due to coronary atherosclerosis (CA). Coronary CT Angiography (CCTA) has changed the approach to diagnosis/management of CA, but its role in this context still needs to be assessed., Methods and Results: We retrospectively examined 167 MA who underwent CCTA in our hospital since 2006, analyzing symptoms, stress-test ECG, cardiovascular risk profiles (SCORE) and CCTA findings. Among the whole enrolled population, 153 (91.6%) MA underwent CCTA for equivocal/positive stress-test ECG with/without symptoms, 13 (7.8%) just for clinical symptoms, 1 (0.6%) for the family history. The CCTA showed the presence of CA in 69 MA (41.3%), congenital coronary anomalies (anomalous origin or deep myocardial bridge) in 8 (4.8%), both in 7 (4.2%). A negative CCTA was observed in 83 MA (49.7%). The risk-SCORE (age, hypertension, hypercholesterolemia, smoking) was a good indicator for the presence of moderate/severe CA on CCTA. However, mild/moderate CA was present in 17.8% of MA clinically stratified at a low risk-SCORE., Conclusion: While coronary angiography is more indicated in athletes with positive stress-test ECG and high clinical risk, the CCTA may be useful in the evaluation of MA with an abnormal stress test ECG and/or clinical symptoms engaged in competitive sports with a high cardiovascular involvement. Age, gender, presence of symptoms and clinical risk-SCORE assessment may help sports physicians and cardiologists to decide whether to request a CCTA or not., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Aims: Although anomalous origin of left (AOLCA) and right coronary artery (AORCA) from the wrong sinus may cause sudden death (SD) in athletes, early diagnosis and management of these anomalies are still challenging. We analysed clinical/instrumental profiles of athletes identified with AOLCA/AORCA focusing our attention on diagnosis, management and follow-up., Methods and Results: We report 23 athletes (17 males, mean age 27±17yrs.), 6 with AOLCA and 17 with AORCA. Diagnosis was made by trans-thoracic echocardiography (TTE) in 21/23(91%). Symptoms were present only in 10(41%). Only 3 had an abnormal rest-ECG and 9(39%) an abnormal stress test ECG (3 ST-depression, 4 ventricular arrhythmias, 1 supraventricular arrhythmias, 1 rate-dependent left-bundle-branch-block). Anatomy of the anomalous coronary artery showed no significant correlation with clinical presentation, except for a tendency to higher occurrence of proximal hypoplasia in symptomatic athletes (83% vs 40%, p=0.09). All athletes were disqualified from competitive-sports and advised to avoid strenuous effort. Surgery was recommended to all athletes with AOLCA and 6 with AORCA, but only 6 underwent surgery. No major cardiac events or ischemic symptoms/signs occurred during a mean follow-up of 65±70months., Conclusions: Early diagnosis of AOLCA/AORCA in athletes is feasible by TTE. Typical symptoms/signs of myocardial ischemia are present only in one third of cases thus underlying the need of a high index of clinical suspicion to achieve the diagnosis. After exercise restriction, none had major cardiac events or ischemia symptoms/signs recurrence. There was no correlation between anatomical characteristics and clinical presentation with the possible exception of coronary hypoplasia., (Copyright © 2017 Elsevier B.V. All rights reserved.)

E. faecalis and E. faecium cause urinary tract infections highly resistant to therapies due to a protective extracellular matrix. To exploit a new strategy able to treat infections without increasing antibiotic doses, we used enzymes targeting specific biofilm matrix components in combination with Vancomycin. We investigated the activity of Vancomycin combined with two matrix-degrading enzymes, Alginate Lyase (AlgL) and Deoxyribonuclease I (DNase I) against in vitro biofilm of E. faecalis and E. faecium clinical isolates. The heterogeneity of matrix composition leads to defined physiological responses of biofilm communities to their environment: we demonstrated that the use of DNase I and AlgL enzymes affects biofilm structure, cell viability and reduces MBEC values of Vancomycin in E. faecalis and E. faecium, respectively., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Dystroglycan (DG) serves as an adhesion complex linking the actin cytoskeleton to the extracellular matrix. DG is encoded by a single gene as a precursor, which is constitutively cleaved to form the α- and β-DG subunits. α-DG is a peripheral protein characterized by an extensive glycosylation that is essential to bind laminin and other extracellular matrix proteins, while β-DG binds the cytoskeleton proteins. The functional properties of DG depend on the correct glycosylation of α-DG and on the cross-talk between the two subunits. A reduction of α-DG glycosylation has been observed in muscular dystrophy and cancer while the inhibition of the interaction between α- and β-DG is associated to aberrant post-translational processing of the complex. Here we used confocal microscopy based techniques to get insights into the influence of α-DG glycosylation on the functional properties of the β-DG, and its effects on cell migration. We used epithelial cells transfected with wild-type and with a mutated DG harboring the mutation T190M that has been recently associated to dystroglycanopathy. We found that α-DG hypoglycosylation, together with an increased protein instability, reduces the membrane dynamics of the β-subunit and its clustering within the actin-rich domains, influencing cell migration and spontaneous cell movement. These results contribute to give novel insights into the involvement of aberrant glycosylation of DG in the developing of muscular dystrophy and tumor metastasis., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Exosomes are involved in intercellular communication. We previously reported that sodium butyrate-induced differentiation of HT29 colon cancer cells is associated with a reduced CD133 expression. Herein, we analyzed the role of exosomes in the differentiation of HT29 cells. Exosomes were prepared using ultracentrifugation. Gene expression levels were evaluated by real-time PCR. The cell proliferation rate was assessed by MTT assay and with the electric cell-substrate impedance sensing system, whereas cell motility was assessed using the scratch test and confocal microscopy. Sodium butyrate-induced differentiation of HT29 and Caco-2 cells increased the levels of released exosomes and their expression of CD133. Cell differentiation and the decrease of cellular CD133 expression levels were prevented by blocking multivesicular body maturation. Exosomes released by HT29 differentiating cells carried increased levels of miRNAs, induced an increased proliferation and motility of both colon cancer cells and normal fibroblasts, increased the colony-forming efficiency of cancer cells, and reduced the sodium butyrate-induced differentiation of HT29 cells. Such effects were associated with an increased phosphorylation level of both Src and extracellular signal regulated kinase proteins and with an increased expression of epithelial-to-mesenchymal transition-related genes. Release of exosomes is affected by differentiation of colon cancer cells; exosomes might be used by differentiating cells to get rid of components that are no longer necessary but might continue to exert their effects on recipient cells., (Copyright © 2017 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.)

Background & Aims: Sofosbuvir (SOF) and weight-based ribarivin (RBV) represented until recently the standard of care in hepatitis C virus (HCV) genotype (GT)2 patients. In registration studies 12-16weeks duration were associated with a 90% sustained virological response at 12weeks (SVR12). Real life cohorts showed lower SVR12 rates., Methods: SVR12 rates attained in an Italian real life cohort and possible benefits of a duration extended up to 20weeks was investigated in HCV GT2 patients with cirrhosis. The role of 2k/1b chimeras as potential predictor of treatment failure was also analysed., Results: Overall, 291 HCV GT2 infected patients with bridging fibrosis or cirrhosis were evaluated. Median age was 68years (18-87); 163 were treatment naïve. Of 168 cirrhotic patients, 149 had Child-Pugh score A and 19 B, 50 platelets count <100,000/mm 3 and 62 albumin <3.5g/dl. SVR12 were 95.53% overall, with 99.15% in non-cirrhotic patients and 93.06% in cirrhotic patients. In patients who completed treatment, SVR rates for cirrhotic patients resulted in 94.51%, and 94.94% after 16 or 20weeks respectively. Predictors of SVR were low platelet count and esophageal varices (OR 7.2; 95% CI 1.67-31.25; p=0.0022 and OR 0.1; 95% CI 0.01-0.72; p=0.0079, respectively). Anemia was mild in 12.4%, moderate in 3.4%, and severe in 2.4% of cases. Anemia was slightly more frequent among longer duration but not associated with treatment discontinuations. No 2k/1b strains or genotypes different from those at baseline were identified at relapse., Conclusions: In GT2 cirrhotic patients, SOF/RBV for 16 or 20weeks is associated with real life SVR12 rates of 95%., Lay Summary: A duration of treatment of 16-20weeks was recommended for treatment of HCV GT2 patients using the combination of sofosbuvir and ribavirin. Real life experiences, where patients received 12weeks of treatment regardless of the severity of liver disease, suggested that response rates are lower than expected, in particular in patients with liver cirrhosis. A misleading genotyping of a 2k/1b strain as GT2 was also hypothesized as a further explanation for less effectiveness. We demonstrated that using the recommended extended duration in patients with more severe disease 95% of patients with severe liver disease including cirrhosis can be cured and that 2k/1b strain plays only a secondary role in specific countries like Germany. Although this combination has been recently replaced by sofosbuvir and velpatasvir fixed dose combination as the standard of care for treating HCV GT2 patients, our findings may inform physicians from countries where the new regimen is not yet available., (Copyright © 2016 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.)

Background: In morbid obesity, optimisation of nutritional strategies impacting cardiovascular and metabolic risk profile is a desirable target in clinical practice., Objective: To assess in morbid obesity the feasibility, safety and efficacy of a nutritional cycle comprising a short-term carbohydrates-free diet delivered by nasogastric tube followed by an almost equivalent oral diet., Design: In our clinical practice, adults with body mass index (BMI)≥45kg/m(2), otherwise clinically healthy, signed informed consent for a 14-day stint of continuous and controlled carbohydrates-free nutritional regiment delivered via 8-Fr nasogastric tube (enteral nutrition, EN), followed by a 14-day stint of almost comparable oral nutrition (ON). Body metrics, insulin resistance, blood pressure (BP) and heart rate (HR), as well as parameters for safety were monitored., Results: In 112 patients, EN significantly reduced BMI and waist circumference (WC), BP, insulin resistance while it increased urine ketones and uric acid increased (all p<0.01 independent to confounders), but had no clinically significant impact on kidney and renal function, and coagulation parameters as well. With ON, findings were consistent. No major safety concerns were recorded during the nutritional treatment. In a subset of patients sharing clinical characteristics with the whole sample, the nutritional strategy reduced the mesenteric fat assessed by ultrasound., Conclusions: In morbid obesity, an aggressive nutritional cycle comprising a short-term ketogenic EN followed by an almost carbohydrates-free ON may be feasible, safe, and highly effective in reducing body weight, WC, BP and insulin resistance., (Copyright © 2015 Asia Oceania Association for the Study of Obesity. Published by Elsevier Ltd. All rights reserved.)

Background: Several concerns have emerged about the higher risk of very late stent thrombosis (ST) with first generation drug-eluting stent (DES), especially in ST-segment elevation myocardial infarction (STEMI) patients undergoing percutaneous coronary intervention (PCI). New generation DES have demonstrated reduction in ST at mid-term follow-up, however no data are available on long-term follow-up. Therefore, the aim of this study was to report long-term results of the RACES-MI trial conducted to compare Everolimus-Eluting Stent (EES) vs Sirolimus-Eluting Stent (SES) in patients undergoing primary PCI., Methods: The RACES-MI trial enrolled consecutive STEMI patients admitted within 12h of symptom onset, undergoing primary PCI with stent implantation at a tertiary center with 24-hour primary PCI capability, who were randomly assigned to SES or EES. Primary endpoint of this analysis is major adverse cardiac events (MACE) at long-term follow-up. Secondary endpoints are 1) death; 2) reinfarction; 3) definite or probable ST; 4) target-vessel revascularization (TVR) at long-term follow-up., Results: From April 2007 to May 2009 500 patients with STEMI were randomized to EES (n=250) or SES (n=250). No difference was observed between the groups either in baseline clinical characteristics, in the number of implanted stent or total stent length per patient. However, a larger reference diameter was observed with SES (3.35±0.51 mm vs 3.25±0.51 mm, p=0.001), whereas patients randomized to EES received Gp IIb-IIIa inhibitors more often (54.4% vs 42.4%, p=0.006). At long-term follow-up (2132±528 days), EES was associated with a significant reduction in MACE (23.8 vs 34.1%, adjusted p=0.028), ST (2.5% vs 7.7%, adjusted p=0.009), without any difference in death (8.7% vs 11.4%, adjusted p=0.47), reMI (9.3% vs 13.1%; adjusted p=0.18) and TVR (8.6% vs 12.3%, adjusted p=0.31)., Conclusions: This study shows that among STEMI patients undergoing primary PCI EES, as compared to SES, is associated with significant reduction in MACE and ST at long-term follow-up., (Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.)

Objectives: We sought a method for any reader to quantify the limit, imposed by variability, to sustainably observable R(2) between any baseline predictor and response marker. We then apply this to echocardiographic measurements of mechanical dyssynchrony and response., Background: Can mechanical dyssynchrony markers strongly predict ventricular remodeling by biventricular pacing (cardiac resynchronization therapy)?, Methods: First, we established the mathematical depression of observable R(2) arising from: 1) spontaneous variability of response markers; and 2) test-retest variability of dyssynchrony measurements. Second, we contrasted published R(2) values between externally monitored randomized controlled trials and highly skilled single-center studies (HSSCSs)., Results: Inherent variability of response markers causes a contraction factor in R(2) of 0.48 (change in left ventricular ejection fraction [ΔLVEF]), 0.50 (change in end-systolic volume [ΔESV]), and 0.40 (change in end-diastolic volume [ΔEDV]). Simultaneously, inherent variability of mechanical dyssynchrony markers causes a contraction factor of between 0.16 and 0.92 (average, 0.6). Therefore the combined contraction factor, that is, limit on sustainably observable R(2) between mechanical dyssynchrony markers and response, is ~0.29 (ΔLVEF), ~0.24 (ΔESV), and ~0.30 (ΔEDV). Many R(2) values published in HSSCSs exceeded these mathematical limits; none in externally monitored trials did so. Overall, HSSCSs overestimate R(2) by 5- to 20-fold (p = 0.002). Absence of bias-resistance features in study design (formal enrollment and blinded measurements) was associated with more overstatement of R(2)., Conclusions: Reports of R(2) > 0.2 in response prediction arose exclusively from studies without formally documented enrollment and blinding. The HSSCS approach overestimates R(2) values, frequently breaching the mathematical ceiling on sustainably observable R(2), which is far below 1.0, and can easily be calculated by readers using formulas presented here. Community awareness of this low ceiling may help resist future claims. Reliable individualized response prediction, using methods originally designed for group-mean effects, may never be possible because it has 2 currently unavailable and perhaps impossible prerequisites: 1) excellent blinded test-retest reproducibility of dyssynchrony; and 2) response markers reproducible over time within nonintervened individuals. Dispassionate evaluation, and improvement, of test-retest reproducibility is required before any further claims of strong prediction. Prediction studies should be designed to resist bias., (Copyright © 2012 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Background: Endothelial dysfunction may be related to increased left ventricular (LV) mass due to an association between endothelial dysfunction with increased arterial load. Therefore, we evaluated whether brachial artery flow-mediated dilation (FMD) is related to global arterial load., Methods: Pulse pressure/stroke index (PP/SVi, global arterial stiffness, prognostically validated), stroke volume/PP (SV/PP, global arterial compliance), and % of the predicted SV/PP by heart rate, age and body weight (confounder-adjusted global compliance, prognostically validated) were used as LV geometry-related indices of global arterial load., Results: Compared to normotensive participants (NT, n = 50), those with hypertension (HTN, n = 51) had lower FMD (8.3% ± 5.4 vs. 12.8% ± 6.5), higher PP/SVi (1.24 ± 0.34 vs. 1.04 ± 0.28 mmHg m(2)/ml), higher LV mass and higher relative wall thickness (all p < 0.01); in contrast, SV/PP and % of predicted SV/PP did not differ between NT and HTN (all p>0.1). Impaired FMD was 3-4-fold more prevalent than LV hypertrophy or increased arterial load both in NT and in HTN. Within NT and HTN separately, PP/SVi, SV/PP and % of predicted SV/PP were comparable among tertiles of FMD. Only in NT, lower FMD was associated with higher peak exercise systolic BP (p < 0.05). In multivariable regression models, FMD was not associated with indices of arterial load independently (all p > 0.1)., Conclusions: In young-to-middle-age subjects with cardiovascular risk factors, impaired FMD is more prevalent than traditional preclinical manifestation of cardiovascular disease, and may exist independent to increased arterial load. Thus, endothelial dysfunction assessment may refine cardiovascular risk profile and risk-reduction strategies based on detection of traditional target organ damage., (Copyright © 2010. Published by Elsevier Ireland Ltd.)

Background: Reproducibility of Doppler echocardiography for assessment of inter-ventricular and intra-left ventricular (LV) dyssynchrony, and its clinical implications, have not been established., Methods: Twenty-eight subjects (heart failure stages A-C, 61% with QRS ≥ 120 ms, ejection fraction (EF) ≤ 35%) underwent two consecutive echo-studies within 24h to evaluate test-re-test reproducibility of inter-ventricular electromechanical delay (VV delay, by traditional pulsed-Doppler), and intra-LV electromechanical delay between opposite LV walls by color-coded Doppler tissue-velocity (COLOR-DTI), and by pulsed-Doppler tissue spectrum (PW-DTI). Reproducibility of LV internal diastolic diameter (LVIDD) and of EF (by Simpson's method) assessments was evaluated contextually for reference., Results: Intra-study and inter-study reproducibility of inter-ventricular and intra-LV electromechanical dyssynchrony was in general good, and comparable to the reproducibility of LVIDD and EF assessments. Between-study reproducibility of PW-TDI method was fair, but showed poor agreement with COLOR-TDI method. In repeated studies, agreement of significant electromechanical delay by COLOR-TDI was comparable to the agreement of EF ≤ 35%. In the 5 patients who had simultaneously large QRS, EF ≤ 35%, and significant inter- and intra-ventricular dyssynchrony at study #1, 3 had EF 36-40% and 1 showed no significant dyssynchrony by study #2., Conclusion: In serial echocardiographic studies, Doppler echocardiography showed a good test-re-test reproducibility for the identification of significant electromechanical delay. Planimetry for EF assessment was a source of variability as relevant as Doppler echocardiography, but COLOR-DTI may add meaningful and reproducible information to QRS duration for cardiac-resynchronization therapy., (Copyright © 2010 Japanese College of Cardiology. Published by Elsevier Ltd. All rights reserved.)

Background and Aim: To evaluate the prevalence of subclinical cardiovascular (CV) abnormalities in systemic lupus erythematosus (SLE) stratified according to SLE-related organ damage using the Systemic Lupus International Collaborating Clinics (SLICC) damage index., Methods and Results: We selected SLE patients without clinically overt CV events (n=45, 56% with SLICC=0, 44% with SLICC=1-4). CV evaluation was performed using cardiac and vascular echo-Doppler techniques. Post-ischemic flow-mediated dilation (FMD) over nitroglycerine-mediated dilation (NMD) of the brachial artery <0.70 defined endothelial dysfunction. The prevalence of preclinical CV abnormalities (CVAbn, including at least one of the following-carotid atherosclerosis, left ventricular (LV) hypertrophy, low arterial compliance, LV wall motion abnormalities, aortic regurgitation, FMD/NMD<0.70)-was 64% (16/25) in patients with SLICC=0 and 80% (16/20) in those with SLICC>0 (p=not significant (NS)). In particular, the prevalence of carotid atherosclerosis (28% vs. 16%), of LV hypertrophy (12% vs. 6%) and of LV wall motion abnormalities (15% vs. 12%), of low global arterial compliance (18% vs. 10%), prevalence of aortic regurgitation (30% vs. 18%) and/or aortic valve fibrosclerosis (10% vs. 8%), FMD<10% (14+/-5% vs. 14%+/-6) and prevalence of FMD/NMD<0.70 (53% vs. 52%) were comparable in SLE patients with SLICC>0 and in those with SLICC=0 (all p=NS). Of the SLE patients without carotid atherosclerosis, LV hypertrophy, low arterial compliance, LV wall motion abnormalities and aortic regurgitation (n=17), endothelial dysfunction was detected in 50% of those with SLICC=0 (6/12) and in 40% of those with SLICC>0 (2/5, p=NS)., Conclusions: SLE patients with SLICC=0 often have an elevated CV risk profile due to subclinical manifestations of CV disease detectable by cardiac and vascular echo-Doppler evaluations.

Introduction: Whether in patients with acute central sub-massive or non-massive pulmonary embolism, mild troponin I increase (>0.03 mug/L) predicts in-hospital occurrence of hemodynamic instability and death independent to prognostically relevant clinical, laboratory and echocardiographic information is not fully established., Methods and Results: We evaluated consecutively patients admitted to the Emergency Room for pulmonary embolism; those in stable hemodynamics in whom central pulmonary embolism was confirmed by spiral-computed tomography were recruited. All participants underwent standardized study protocol, including clinical and diagnostic evaluation for assessment of severity of pulmonary embolism; therapy was established accordingly; troponin I was measured, but treatment protocol was not affected by knowledge of troponin I levels. Of 90 patients enrolled in the study, 33 (37%) developed hemodynamic instability during hospitalization (on average, 90 h +/-20 from admission). Troponin I was >0.03 microg/L in 56% of the study population at admission, and predicted occurrence of hemodynamic instability during hospitalization (adjusted hazard ratio 9.8, 95% confidence interval 1.2-79.2), independent to age, gender, co-morbidity, systolic blood pressure, CK-MB, echocardiographic right ventricular dysfunction and other covariates. Twelve patients died during hospitalization (mean time to event 107 h +/-24 from admission); troponin I >0.03 microg/L predicted mortality in univariate analysis, but not after accounting for age, sex and clinical variables. Nevertheless, higher troponin as continuous variable correlated with higher likelihood of in-hospital death (adjusted likelihood ratio 2.2/microg/L, 95% confidence interval 1.1-4.3) in multivariate analysis. In a further multivariate model, CK-MB predicted mortality independent of covariates and troponin I., Conclusions: In patients with acute central sub-massive or non-massive pulmonary embolism, even mild increase in troponin I >0.03 microg/L may provide relevant short-term prognostic information independent to clinical, laboratory and echocardiographic data.

Background and Aims: Knowledge of cardiovascular disease (CVD) risk factors in young patients who experienced myocardial infarction (MI) is poorly described., Methods and Results: Knowledge of traditional CVD risk factors, non-fatal cardiovascular events and of non-pharmacological factors able to reduce CVD risk and education level were evaluated by questionnaires in subjects who visited their family doctors. Sixty-one participants with history of MI in age <50 years (MI+) were compared with 3749 subjects with age <50 years, from the same population source, but without history of MI (MI-). MI+ were more frequently men (p<0.01), did not have significantly higher prevalences of family history of CVD, diabetes and hypertension. MI+ individuals reported previous non-fatal stroke (13% vs. 0.5%, p<0.001), overweight, diabetes, and hypercholesterolemia (all p<0.001) more frequently than controls, whereas prevalence of arterial hypertension, smoking habit and physical inactivity did not differ between the two groups; MI+ and MI- individuals did not differ in terms of the proportion of those who were unaware of being hypertensive, diabetic or hypercholesterolemic. MI+ participants reported more frequently lower education level than controls (p<0.05). Knowledge of non-pharmacological approach for CVD risk reduction was similar in MI+ and MI-. In a logistic multivariate analysis, male gender (adjusted odds ratio=5.8) and high cholesterol level (adjusted odds ratio 2.8, both p<0.01) were independent correlates of MI+. CVD risk factors distribution was similar between participants with juvenile MI+ and MI in age >or=50 years (n=167) extracted from the same population source; however, stroke was reported more frequently in juvenile MI+ than in those who had MI at age >or=50 years/old (13% vs. 4%, p<0.01)., Conclusions: Juvenile non-fatal MI was associated with metabolic CVD risk factors, with higher cerebrovascular co-morbidity and lower education level.

Background: The relationship between peripheral circulation and blood pressure (BP) response to maximal exercise is an intriguing and not yet well defined topic., Aims: Aims of the present study were to investigate in well trained young healthy males the possible relationships between the endothelial or the smooth muscle component of the peripheral circulation and 1) the BP response to physical exercise on treadmill 2) the body mass composition., Subjects and Methods: Fifteen subjects (18-36 years), regularly performing physical activity 3 times weekly underwent the following examinations: body composition by bioelectrical impedance analysis; measurement of the forearm blood flow (FBF) at rest and during post-ischemic hyperemia by strain-gauge plethysmography at the upper arm; measurement of brachial artery diameter (BAD) at rest and after 4-min ischemia by echography; BP response to maximal exercise on treadmill with the determination of maximal oxygen consumption and the measurement of lactic acid serum concentration., Results: BAD was significantly increased during post-ischemic hyperemia up to the 4th minute of observation with a peak at 60 s (+8.5%); FBF increased at 30 s after ischemia (+210%) and returned to baseline levels at the 2nd minute. In the linear correlation analysis, systolic BP increase at the end of the maximal exercise was significantly and inversely related to the increase in FBF (r=-0.663, p<0.01) and to the early FMD (r=0.503, p<0.05). In the multiple regression analysis, however, only FBF independently affected SBP increase during exercise (t=-3.268, p<0.02). Systolic BP increase at the end of the maximal exercise was significantly related to the increase in FBF but not to that of BAD. Among parameters of body composition, fat-free mass was closely related to changes only in BAD., Conclusions: These data indicate that FBF, which depends on the smooth muscle component of the peripheral circulation, is closely related to BP response to exercise while the endothelial function, which has been determined as changes in BAD, is related to the fat-free mass of the body, possibly through the peripheral insulin sensitivity.

Background and Aim: The numerous guidelines and multiple approaches to managing cardiovascular risk factors have reduced the number of fatal events but not the incidence of cardiovascular disease (CVD). One rarely explored aspect is the extent to which individuals perceive their own risk in relation to their education and history of CVD. Furthermore, Italy has a State-based Health System, in which family doctors (FDs) may be an extremely useful and relatively low cost resource for risk management, but the degree of their involvement in individual CVD risk management has not been previously assessed., Methods and Results: The Department of Clinical and Experimental Medicine of Federico II University, Naples, Italy, and the Neapolitan Section of the Italian Society of Family Doctors (SIMG), developed an epidemiological survey to evaluate the level and awareness of CVD risk in subjects in the urban area of Naples, and the degree of involvement of FDs in CVD risk management. During a period of a few months, the subjects who visited their FDs were invited to respond to a standard self-explanatory questionnaire, and the FDs were required to provide quantitative information concerning the CVD risk factors of each enrolled subject from their databases in order to assess global CVD risk. The data included cholesterol and blood pressure (BP) levels, and had to be collected within six months of the visit; if the date were missing, the fact was recorded. The present analysis was based on data concerning the 5,687 subjects who had entered the study by January 2002, 7.6% of whom reported CVD (myocardial infarction (MI), stroke, angina, cerebral transient ischemic attack: CD+) and 92.4% did not (CVD-). MI was the most frequent CVD, and 18% of the CVD+ cases reported more than one non-fatal cardiovascular event. On average, the CVD+ subjects were older and more often men. After adjusting for age and FD, they also had a higher body mass index (BMI) and prevalence of obesity, higher self-reported BP, a lower education level, and more often referred high cholesterol levels, hypertension and diabetes. On the contrary, the proportion of smokers was higher in the CVD- group. Among the subjects who declared that they did not have a high cholesterol level, 11% reported recent values of > 200 mg/dL. The FDs of 36% of the cases were unable to assess the individual global CV risk level using quantitative data from their electronic databases. The most frequently missing information was the level of total cholesterol. Missing data were more frequent in the CVD- than the CVD+ subjects, regardless of age and FD., Conclusions: The results of our study suggest that the awareness of CVD risk among subjects is somewhat vague. The FDs were generally able to provide a quantitative assessment of CVD risk in their patients. CVD risk prevention programmes may be more successful if they stress knowledge and awareness in the population, and stimulate FDs to undertake more stringent quantitative assessments of CVD risk factors.

Background and Aims: To investigate whether insulin-resistance influences echocardiographic markers of preclinical disease, independent of significant confounders., Methods and Results: We examined 1,471 (59 +/- 8 years) non-diabetic individuals (WHO criteria) with available echocardiograms from the Strong Heart Study cohort. Among them, 530 subjects had arterial hypertension (62% on medications), 152 had impaired glucose tolerance (GT) and 460 were normotensive, non-obese with normal GT. Insulin resistance was estimated by the Homeostasis Model Assessment (HOMA). LV mass, systolic function measured at the endocardium and the midwall (also correcting for circumferential wall stress) and arterial compliance (stroke volume/pulse pressure as a percent of predicted from body weight, age and heart rate [delta %SV/PP]) were measured by echocardiography, as prognostically validated markers of preclinical disease. HOMA-index was related positively to body mass index (BMI), waist/hip ratio (WHR), blood pressure, left ventricular (LV) mass, and negatively to arterial compliance (all p < 0.005) in the whole population, as well as in separate normotensive or hypertensive groups. In multiple regression models, relation of HOMA-index with the markers of risk was adjusted for age, sex, WHR, body mass index, presence of hypertension and number of antihypertensive medications. In this analysis, neither LV mass nor indices of systolic function were independently related to HOMA-index. In contrast, HOMA-index maintained a significant negative association with delta %SV/PP, independent of demographics, hypertension, treatment and body fat distribution. Also, HOMA-index maintained an independent relation with LV mass, when WHR and BMI were not included in the regression model., Conclusions: After accounting for relevant biological covariates, including body mass and fat distribution, insulin-resistance measured by HOMA is not an independent correlate of LV mass and function, but negatively influences arterial compliance.

Background: Anorexia nervosa is associated with lower left ventricular mass (LVM) and systolic dysfunction. Whether these abnormalities reflect chronic protein-energy malnutrition or are primarily related to lower cardiac workload is unclear., Objective: The objective of the study was to verify whether low LVM in anorexia nervosa is explained by low hemodynamic load., Design: Ninety-one women with anorexia nervosa [macro x +/- SD age: 20.5 +/- 6.1 y; body mass index (in kg/m(2)): 15.6 +/- 1.9; group 1] and 62 normal-weight female control subjects (age: 22.5 +/- 5.5 y; body mass index: 20.9 +/- 1.2; group 2) underwent Doppler echocardiography. LVM was evaluated as the percentage predicted by body height, sex, and stroke work (systolic blood pressure x stroke volume)., Results: The left ventricular chamber dimension was smaller and the chamber walls were thinner in group 1 than in group 2, which resulted in significantly lower LVM and LVM indexes (P < 0.0001). Ejection fraction, heart rate, stroke volume, and cardiac output were significantly (P < 0.007) lower in group 1, but peripheral resistance was substantially higher (P < 0.0001). The deviation of LVM from predicted values was lower and the proportion of subjects with inadequate LVM was significantly higher in group 1 than in group 2 (P < 0.0001). This difference was attenuated after adjustment for body weight and heart rate. There were no relations between LVM and laboratory tests in group 1., Conclusions: Anorexia nervosa is a condition of low hemodynamic load that leads to low LVM. Even with adjustment for stroke work, however, LVM is lower than would be predicted by height, because of the effect of body weight reduction (ie, wasting of lean body mass).

Background: Anomalous origin of coronary arteries (AOCA) is a rare congenital disease. Although it may have a benign course, it has been identified as a frequent cause of sports-related sudden death. Unfortunately, in vivo detection of AOCA is not easy, as individuals with this anomaly often are asymptomatic and show no signs of myocardial ischemia. Presently, transthoracic two-dimensional echocardiography (TTE) is the only noninvasive, widely available tool to visualize the ostia and first tracts of coronary arteries., Objective: To assess the efficacy of TTE in the screening of AOCA in a large athletic population., Study Design: In a prospective study, we assessed the ostia and first tracts of coronary arteries in 3,650 subjects (mean age, 30+/-12 years) practicing different sports at various competitive levels. Subjects underwent a TTE examination in our laboratory for scientific or diagnostic purposes., Results: Technically satisfactory echocardiograms were obtained in 3,504 subjects (96%); a clear visualization of the ostia and first tracts of both coronary arteries was obtained in 3,150 cases (90%). Three asymptomatic athletes (0.09%) were suspected to have an AOCA; two with a right coronary artery origin from the left sinus, and one with a left coronary artery origin from the right sinus. Diagnosis was confirmed by coronary angiography., Conclusions: Our study indicated that AOCA is rare in asymptomatic athletes. Systematic and accurate exploration of coronary anatomy in athletes referred for a diagnostic TTE examination may be useful in identifying those with AOCA.

Gallbladder motility was studied by ultrasound in 100 healthy adult volunteers and 150 gallstone patients, in a subgroup of whom gallstone burden, type and number, gallbladder histology and tensiometric responses of gallbladder strips to cholecystokinin octapeptide were evaluated. Patients were divided into contractors (n = 108) and hypocontractors (n = 42), according to their gallbladder motility pattern in vivo. Contractors showed slower gallbladder emptying and increased fasting and postprandial residual volumes, although the ejected amount of bile was greater than that of controls (20.2 +/- SEM 1.1 vs 16.0 +/- 0.7 ml; p < 0.001). In contrast, hypocontractors exhibited slower and less complete gallbladder emptying than controls with a reduction in the absolute amount of ejected bile. Although gallbladder wall inflammation was mild and comparable in specimens from both groups of patients, the thickness of the muscular layer was greater in hypocontractors than in contractors (1073 +/- 76 vs 745 +/- 75 microns, p < 0.01) and related inversely to postprandial ejected volume (r = -0.42; p < 0.03; n = 32) but positively to gallstone volume (r = 0.40; p < 0.03; n = 32). Compared to contractors, gall-bladder muscle strips of hypocontractors exhibited a decrease in frequency and amplitude of spontaneous contraction and in maximal stress and receptor sensitivity to cholecystokinin octapeptide (0.1 nM-1 microM). Postprandial gallbladder evaculation was unaffected by stone number, and by the presence or absence of stone calcification. Gallstone volume was larger in hypocontractors (19.4 +/- 3.0 ml vs 9.6 +/- 0.9 ml, p < 0.001) than contractors. The comparison of in vitro contractility patterns between cholesterol, mixed and pigment stone patients showed a more severe defect in patients with cholesterol and mixed stones than in those with pigment calculi. In conclusion, in gallstone patients: (i) gallbladder motor dysfunction manifests mainly with increased fasting and postprandial residual volumes in contractors and with markedly increased postprandial residual volumes and decreased gallbladder emptying in hypocontractors; (ii) gallbladder kinetics seem to be influenced by stone volume and cholesterol content of calculi but not stone number, calcification or mild chronic cholecystitis; (iii) a form of hypertrophic leiomyopathy is observed in gallstone patients with the most impaired gallbladder motor function.

We report the clinical and instrumental data, including the endomyocardial biopsy findings, of six young athletes presenting with minor arrhythmias and/or echocardiographic abnormalities. In one of them, a left ventricular dilation with moderate depression of the systolic function had been attributed to an athlete's heart. A diagnosis of arrhythmogenic right ventricular dysplasia had been made in three others, one with right ventricular dilation and apical hypokinesia, and two with ventricular arrhythmias with QRS morphology of left bundle branch block. A myocarditis could be unequivocally established in four athletes (two with and two without fibrosis). In the remaining two, with a clinical history strongly suggesting a previously acute myocarditis, the endomyocardial biopsy specimen revealed a nonspecific fibrosis compatible but not definitely pathognomonic of a healed myocarditis. Our report suggests that a myocarditis may be a cause of minor rhythm disturbances and/or echocardiographic abnormalities in athletes. A prevalent localization of the inflammatory process in the right ventricle with or without the occurrence of ventricular arrhythmias with left bundle branch block morphology can mimic an arrhythmogenic right ventricular dysplasia. An early diagnosis of myocarditis in athletes is useful to avoid the risk of fatal arrhythmias, also considering that rest still keeps on being one of the most effective strategies in myocarditis management.