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Intraoperative surgical prosthetic heart valve (SHV) choice is a key determinant of successful surgery and positive postoperative outcomes. Currently, many controversies exist around the sizing and labelling of SHVs rendering the comparison of different valves difficult.To explore solutions, an expert Valve Labelling Task Force was jointly initiated by the European Association for Cardio-Thoracic Surgery (EACTS), The Society of Thoracic Surgeons (STS) and the American Association for Thoracic Surgery (AATS). The EACTS-STS-AATS Valve Labelling Task Force, comprising cardiac surgeons, cardiologists, engineers, regulators and representatives from the International Organization for Standardization (ISO) and major valve manufacturers, held its first in-person meeting in February 2018 in Paris, France. This article was derived from the meeting's discussions. The Task Force identified the following areas for improvement and clarification: reporting of physical dimensions and characteristics of SHVs determining and labelling of SHV size, in vivo and in vitro testing and reporting of SHV hemodynamic performance and thrombogenicity. Furthermore, a thorough understanding of the regulatory background and the role of the applicable ISO standards, together with close cooperation between all stakeholders (including regulatory and standard-setting bodies), is necessary to improve the current situation. Cardiac surgeons should be provided with appropriate information to allow for optimal SHV choice. This first article from the EACTS-STS-AATS Valve Labelling Task Force summarizes the background of SHV sizing and labelling and identifies the most important elements where further standardization is necessary. (C) 2019 by The Society of Thoracic Surgeons, The American Association for Thoracic Surgery, and the European Association for Cardio-Thoracic Surgery

Item does not contain fulltext Whole-body magnetic resonance imaging has emerged as a useful imaging tool in diagnosing and characterizing the progression of myopathies and muscular dystrophies. Whole-body MRI indications and diagnostic efficacy are becoming better defined with the increasing number of cases, publications and discussions within multidisciplinary working groups. Advanced Whole-body MRI protocols are rapid, lower cost, and well-tolerated by patients. Accurate interpretation of muscle Whole-body MRI requires a detailed knowledge of muscle anatomy and differential pattern of involvement in muscle diseases. With the surge in recently identified novel genetic myopathies, Whole-body MRI will become increasingly useful for phenotypic validation of genetic variants of unknown significance. In addition, Whole-body MRI will be progressively used as a biomarker for disease progression and quantify response to therapy with the emergence of novel disease modifying treatments. This review outlines Whole-body MRI indications and updates refined protocols and provides a comprehensive overview of the diagnostic utility and suggested methodology of Whole-body MRI for pediatric and adult patients with muscle diseases.

BackgroundQuantitative muscle MRI (water-T2 and fat mapping) is being increasingly used to assess disease involvement in muscle disorders, while imaging techniques for assessment of the dynamic and elastic muscle properties have not been translated yet into clinics.MethodsHere, we quantitatively characterized muscle deformation (strain) in patients affected by facioscapulohumeral muscular dystrophy (FSHD), a prevalent muscular dystrophy, by applying dynamic MRI synchronized with neuromuscular electrical stimulation (NMES). We evaluated the quadriceps muscles in 34 ambulatory patients and 12 healthy controls, at 6 month intervals.ResultsWe found that while a subgroup of patients behaved similarly to controls, for another subgroup the strain significantly decreased over time (50% over 1.5 years). Dynamic MRI parameters did not correlate with quantitative MRI.ConclusionsIn conclusion, our results suggest that the evaluation of muscle ability to contract by NMES-MRI could be used to explore the elastic properties and monitor muscle involvement in FSHD and other neuromuscular disorders.

Background: Despite the widespread use of transcatheter aortic valve implantation (TAVI), the role of sex on outcome after TAVI or surgical aortic valve replacement (AVR) has been poorly investigated. We investigated the impact of sex on outcome after TAVI or AVR. Methods: There were 2108 patients undergoing TAVI or AVR who were enrolled in the Italian Observational Multicenter Registry (OBSERVANT). Thirty-day mortality, major periprocedural morbidity, and transprosthetic gradients were stratified by sex according to interventions. Results: Female AVR patients showed a worse risk profile compared with male AVR patients, given the higher mean age, prevalence of frailty score of 2 or higher, New York Heart Association class of 3 or higher, lower body weight, and preoperative hemoglobin level (P ≤.02). Similarly, female TAVI patients had a different risk profile than male TAVI patients, given a higher age and a lower body weight and preoperative hemoglobin level (P ≤.005), but with a similar New York Heart Association class, frailty score, EuroSCORE (P = NS), a better left ventricular ejection fraction and a lower prevalence of left ventricular ejection fraction less than 30%, porcelain aorta, renal dysfunction, chronic obstructive pulmonary disease, arteriopathy, and previous cardiovascular surgery or percutaneous coronary intervention (P ≤.01). Women showed a smaller aortic annulus than men in both populations (P

In recent years, an autoantibody directed against the 5′-citosolic nucleotidase1A (cN1A) was identified in the sera of sporadic inclusion body myositis (s-IBM) patients with widely variable sensitivity (33%–76%) and specificity (87%–100%). We assessed the sensitivity/specificity of anti-cN1A antibodies in an Italian cohort of s-IBM patients, searching for a potential correlation with clinical data. We collected clinical data and sera from 62 consecutive s-IBM patients and 62 other inflammatory myopathies patients. Testing for anti-cN1A antibodies was performed using a commercial ELISA. Anti-cN1A antibodies were detected in 23 s-IBM patients, resulting in a sensitivity of 37.1% with a specificity of 96.8%. Positive and negative predictive values were 92.0% and 60.6%, respectively. We did not find significant difference regarding demographic variables, nor quadriceps or finger flexor weakness. Nevertheless, we found that anti-cN1A-positive patients presented significantly lower scores in IBMFRS item 1 (swallowing, p = 0.045) and more frequently reported more severe swallowing problems, expressed as an IBMFRS item 1 score ≤ 2 (p &lt, 0.001). We confirmed the low sensitivity and high specificity of anti-cN1A Ab in s-IBM patients with a high positive predictive value. The presence of anti-CN1A antibodies identified patients with a greater risk of more severe dysphagia.

Background: Four main clinical phenotypes have been traditionally described in patients mutated in SCN4A, including sodium-channel myotonia (SCM), paramyotonia congenita (PMC), Hypokaliemic type II (HypoPP2), and Hyperkaliemic/Normokaliemic periodic paralysis (HyperPP/NormoPP); in addition, rare phenotypes associated with mutations in SCN4A are congenital myasthenic syndrome and congenital myopathy. However, only scarce data have been reported in literature on large patient cohorts including phenotypes characterized by myotonia and episodes of paralysis.Methods: We retrospectively investigated clinical and molecular features of 80 patients fulfilling the following criteria: (1) clinical and neurophysiological diagnosis of myotonia, or clinical diagnosis of PP, and (2) presence of a pathogenic SCN4A gene variant. Patients presenting at birth with episodic laryngospasm or congenital myopathy-like phenotype with later onset of myotonia were considered as neonatal SCN4A.Results: PMC was observed in 36 (45%) patients, SCM in 30 (37.5%), Hyper/NormoPP in 7 (8.7%), HypoPP2 in 3 (3.7%), and neonatal SCN4A in 4 (5%). The median age at onset was significantly earlier in PMC than in SCM (p < 0.01) and in Hyper/NormoPP than in HypoPP2 (p = 0.02). Cold-induced myotonia was more frequently observed in PMC (n = 34) than in SCM (n = 23) (p = 0.04). No significant difference was found in age at onset of episodes of paralysis among PMC and PP or in frequency of permanent weakness between PP (n = 4), SCM (n = 5), and PMC (n = 10). PP was more frequently associated with mutations in the S4 region of the NaV1.4 channel protein compared to SCM and PMC (p < 0.01); mutations causing PMC were concentrated in the C-terminal region of the protein, while SCM-associated mutations were detected in all the protein domains.Conclusions: Our data suggest that skeletal muscle channelopathies associated with mutations in SCN4A represent a continuum in the clinical spectrum.

Olaparib is the first poly(ADP-ribose) polymerase inhibitor approved as maintenance therapy of recurrent ovarian cancer (OC) patients with a BRCA mutation. To achieve the maximum clinical benefit, adherence to olaparib must be persistent. However, in clinical practice, this is challenged by the frequent suboptimal management of toxicities. In view of the expanding use of olaparib also in Italy, physicians must learn how to adequately and promptly manage drug toxicities not to unnecessarily interrupt or reduce the dose. The experts agreed that nausea,vomiting, anemia, and fatigue are the most frequent events experienced by OC patients on olaparib, and that these toxicities usually develop early during treatment, are mainly of grade 1-2 and transient and can be managed with simple non-pharmacological interventions. By sharing their real-world experiences, the panel prepared, for each toxicity, an algorithm organized by grade and besides the procedures indicated in the local label, included supportive care interventions based also on nutritional and lifestyle modifications and psycho-oncology consultation. Moreover, in view of the tablet entry into the Italian market, the full and reduced dosages of capsules and tablets were compared. This practical guidance is intended to be a tool to support especially less-experienced physicians in the management of these complex patients, with the aim to help preventing the worsening of patients' conditions and the unnecessary interruption/reduction of olaparib dosage, which may jeopardize treatment efficacy.

International audience; Purpose High throughput sequencing analysis has facilitated the rapid analysis of the entire titin (TTN) coding sequence. This has resulted in the identification of a growing number of recessive titinopathy patients. The aim of this study was to (1) characterize the causative genetic variants and clinical features of the largest cohort of recessive titinopathy patients reported to date and (2) to evaluate genotype-phenotype correlations in this cohort. Methods We analyzed clinical and genetic data in a cohort of patients with biallelic pathogenic or likely pathogenicTTNvariants. The cohort included both previously reported cases (100 patients from 81 unrelated families) and unreported cases (23 patients from 20 unrelated families). Results Overall, 132 causative variants were identified in cohort members. More than half of the cases had hypotonia at birth or muscle weakness and a delayed motor development within the first 12 months of life (congenital myopathy) with causative variants located along the entire gene. The remaining patients had a distal or proximal phenotype and a childhood or later (noncongenital) onset. All noncongenital cases had at least one pathogenic variant in one of the final threeTTNexons (362-364). Conclusion Our findings suggest a novel association between the location of nonsense variants and the clinical severity of the disease.

Therapeutic alliance and reflective functioning may be important for treatment outcomes for binge-eating disorder (BED). The current study examines: (1) growth in therapeutic alliance over 20 sessions of emotionally focused group therapy (EFGT) for BED, and (2) the association between change in reflective functioning and growth in therapeutic alliance in EFGT for BED, both of which may be important for improving BED outcomes. We hypothesize that: (1) growth in therapeutic alliance will be represented by a quadratic curve (i.e., follow a high-low-high pattern of growth), and (2) a quadratic growth in therapeutic alliance during EFGT will be associated with greater increase in reflective functioning from pre- to six months posttreatment. Italian women and men with BED (N = 118) attended EFGT for BED. They completed the Helping Alliance Questionnaire-II, a measure of therapeutic alliance to the therapist at the end of each session of EFGT, and the Adult Attachment Interview pre- and six months posttreatment. The quadratic model of therapeutic alliance growth was a significantly better fit to the data than the linear model, and the quadratic growth in therapeutic alliance during therapy was associated with greater positive change in reflective functioning at six months posttherapy. The current study provides additional support for the high-low-high pattern of therapeutic growth in short-term process- oriented psychotherapies, and that the growth of alliance to the therapist over the course of group therapy may be important for facilitating improved reflective functioning.

Laboratory stress tasks induce strong changes in linear and non-linear indices of heart rate variability (HRV) among healthy adults, due to a task-induced parasympathetic withdrawal. Previous findings suggested that negative affectivity and its correlates (i.e., depressive symptoms, anxiety, hostility, type D personality, and situational stress) could profoundly affect autonomic activity. However, to date no studies considered these psychological dimensions simultaneously while trying to disentangle their acute effects on HRV during a laboratory stress task. A total of 65 healthy participants completed a battery of questionnaires and later underwent a psychosocial stress protocol, which involves a stressful and a non-stressful mental arithmetic task, with the latter serving as a control condition for the former. During the entire procedure, autonomic activity was recorded through a portable ECG device. We analysed longitudinal changes in HRV indices using Mixed Models, taking into account respiration rates and the associations between psychophysiological variables through bivariate Pearson’s r (partial) correlation indices. We found significant changes in linear (e.g., HF power, RMSSD) and non-linear (e.g., Poincare Plot and Correlation Dimension D2) HRV indices during the procedure, with the lowest point reached during the stressful mental arithmetic task. Interestingly, only depressive symptomatology was significantly and positively related to a higher resting-state HRV and to a blunted reactivity to the stress task, even after controlling for baseline values. Results suggest that healthy individuals with higher levels of depressive symptoms could experience atypical cardiovascular responses to stressful events: several speculative interpretations, considering autonomic, behavioral, and motivational dysregulations, are discussed.

The Experiences in Close Relationship Scale (ECR) is one of the most commonly used self-report instruments of adult attachment and has been widely adopted in psychotherapy research. Composed of two subscales, namely Attachment Avoidance and Anxiety, the ECR was recently shortened to a 12-items version, called the ECR-12. Given the importance of extending knowledge on its applicability in understudied populations, our aim was to validate the ECR-12 in a large sample of Italian native-speakers. A total of 1197 participants (73.2% females; mean age=28.53±11.37 years) completed the ECR-12. Each participant also completed other measures of attachment, psychopathology, interpersonal distress, coping strategies, and well-being. An Exploratory Structural Equation Modeling analysis showed an excellent fit of the data, providing support for the two-dimensional orthogonal structure of the ECR-12. In addition, the measurement model was invariant across genders. Both attachment anxiety and attachment avoidance subscales demonstrated good internal reliability, with McDonald’s Omegas and Cronbach’s Alphas above the suggested 0.8 cut-off. Finally, the Italian version of ECR-12 showed adequate convergent, concurrent, and divergent validity. Highly anxious individuals reported the highest levels of maladaptive interpersonal functioning and coping strategies, resulting in lower well-being. Interestingly, both attachment insecurity dimensions predicted higher levels of psychopathology, even after controlling for demographic variables and levels of self-reported relational difficulties. Given the good psychometric properties of the ECR-12, researchers and practitioners in Italy are encouraged to adopt the ECR-12 in their future research on adult attachment in psychotherapy.

The therapeutic alliance in individual and group psychotherapy is associated with treatment outcomes for a variety of disorders. However, debate persists about the centrality of the alliance in determining positive outcomes. We examined the alliance-outcome relationship across 20 sessions of emotionally focused group therapy (EFGT) for binge-eating disorder (BED). We hypothesized that (1) previous session alliance increase will predict lower subsequent session binge eating level while controlling for previous session binge eating level; and (2) previous session binge eating decline will predict higher subsequent session alliance level while controlling previous session alliance level. Participants were 118 individuals with BED who received 20 sessions of EFGT in 8 groups. Levels of binge eating and therapeutic alliance to the therapist were measured weekly. Linear growth in alliance during group therapy was associated with reduced binge eating at 6 months' posttreatment. We also found that the group's and the individual's alliance scores and binge-eating episodes were significantly associated across treatment, suggesting a mutual influence of the group's and individual's experience of the alliance with the therapist. Regarding the first hypothesis, previous session alliance increase was significantly associated with lower subsequent session binge eating. Regarding the second hypothesis, previous session binge-eating decline was not significantly related to higher subsequent session alliance. The findings provide evidence in a group therapy context for a model in which alliance change influences subsequent symptom levels, but not the other way around. (PsycINFO Database Record

The current study examines change in attachment variables from pre- to six months post-emotionally focused group therapy (EFGT) for binge eating disorder (BED). A clinical sample of 118 women and men with BED attended 20 sessions of EFGT and completed the Adult Attachment Interview pre- and six months post-treatment. There was a significant increase in secure attachment style classification, significant increases in Coherence of Mind and Reflective Functioning scores, and significant decreases in both unresolved/disorganized attachment style classification and scale scores from pre- to six months post-treatment. Interventions specific to EFGT, common therapeutic factors and group process interventions may have contributed to changes in these attachment variables. The current study demonstrated that EFGT is a promising treatment for facilitating change in attachment in women and men with BED.

The purpose of this study was to assess the interrelation between cortical, cardiovascular, behavioural, and psychological responses to acute stressors in a large sample of healthy individuals. To date, there are only preliminary evidences for a significant association among these psychophysiological indexes during a stress task. 65 participants completed psychological questionnaires (Beck Depression Inventory and State-Trait Anxiety Inventory) and underwent a psychosocial math stress task, consisting of a control and an experimental (i.e. stressful) condition. Prefrontal and autonomic activities were recorded using respectively a 2-channel near-infrared spectroscopy (NIRS) device and a portable ECG monitoring system. Results evidenced an increased activation of both frontal areas assessed by NIRS, and a positive association between the right NIRS channel and heart rate changes from baseline, during both control and experimental conditions. Subjective stress increased during the procedure, reaching its maximum during the experimental condition. Behavioural performances during the task (e.g. response time) did not correlate with anxiety or depression. Autonomic data evidenced, as expected, an overall reduction of vagal tone during the experimental condition. Finally, severity of depressive and anxious symptoms predicted an increase in parasympathetic activity both at rest and during the task, even when controlling for respiration rate. Results support the hypothesis of an integration between right sectors of frontopolar or dorsolateral PFC and cardiac regulation. Trait anxiety and depression predicted an increase in vagal tone during the entire procedure. The implication of these findings is discussed.

We used West and Kenny's (2011) Truth-and-Bias (TB) model to examine how accurately group therapists' judge their group members' alliances, and the effects of therapist-patient congruence in alliance ratings on patient outcomes. Were considered: (a) directional bias - therapists' tendency to over- or underrate their clients' alliances, (b) truth strength - clients' alliance ratings, and (c) bias strength - therapists' tendency to conflate their alliance ratings for a specific group member with the average alliance ratings for the other members of the group. There were 118 obese adult patients with binge-eating disorder that were treated by 8 therapists with Emotionally Focused Group Therapy. Outcomes were operationalized as pre- to postchanges in: health-related quality of life, binge eating, and psychological distress. Patients' and therapists' working alliance were assessed after the 2nd, 10th, and last (20th) group therapy sessions. (a) There was no significant congruence between group therapists' and members' ratings of alliance; (b) therapists' ratings of an individual group member's alliance were significantly related to therapists' ratings of the other group members' alliance in early sessions but unrelated in later sessions; and (c) the relationship between therapists' alliance ratings and bias strength was weaker when patient binge eating outcomes improved. Group therapists adopted a "better safe than sorry" strategy by underestimating the strength of their group members' alliances. Therapists had a tendency to judge each group member's individual alliance based on the aggregated alliance of the other group members. Improvement in patient binge eating outcomes was related to therapists overcoming this tendency. (PsycINFO Database Record

OBJECTIVE: To apply next-generation sequencing (NGS) for the investigation of the genetic basis of undiagnosed muscular dystrophies and myopathies in a very large cohort of patients. METHODS: We applied an NGS-based platform named MotorPlex to our diagnostic workflow to test muscle disease genes with a high sensitivity and specificity for small DNA variants. We analyzed 504 undiagnosed patients mostly referred as being affected by limb-girdle muscular dystrophy or congenital myopathy. RESULTS: MotorPlex provided a complete molecular diagnosis in 218 cases (43.3%). A further 160 patients (31.7%) showed as yet unproven candidate variants. Pathogenic variants were found in 47 of 93 genes, and in more than 30% of cases, the phenotype was nonconventional, broadening the spectrum of disease presentation in at least 10 genes. CONCLUSIONS: Our large DNA study of patients with undiagnosed myopathy is an example of the ongoing revolution in molecular diagnostics, highlighting the advantages in using NGS as a first-tier approach for heterogeneous genetic conditions. Objective: To apply next-generation sequencing (NGS) for the investigation of the genetic basis of undiagnosed muscular dystrophies and myopathies in a very large cohort of patients. Methods: We applied an NGS-based platform namedMotorPlex to our diagnostic workflow to test muscle disease genes with a high sensitivity and specificity for small DNA variants. We analyzed 504 undiagnosed patients mostly referred as being affected by limb-girdle muscular dystrophy or congenital myopathy. Results: MotorPlex provided a complete molecular diagnosis in 218 cases (43.3%). A further 160 patients (31.7%) showed as yet unproven candidate variants. Pathogenic variants were found in 47 of 93 genes, and in more than 30%of cases, the phenotype was nonconventional, broadening the spectrum of disease presentation in at least 10 genes. Conclusions: Our large DNA study of patients with undiagnosed myopathy is an example of the ongoing revolution in molecular diagnostics, highlighting the advantages in using NGS as a first-tier approach for heterogeneous genetic conditions.

Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) may involve many target organs with relevant variability among affected individuals. We performed a multi-organ assessment tapping nervous system, skeletal muscle and cardiovascular system in thirty-nine individuals belonging to 16 families from Central Italy sharing the same R1006C CADASIL mutation. Stroke prevalence was larger in female patients (66.7%) than in males (23.8%); high levels of CKemia were quite frequent (21.6%) and were related to a myopathy without mitochondrial alterations; several individuals had atrial septal aneurysm (10.3%). No specific relationships between common cardiovascular risk factors and clinical manifestations were found. The present systematic study thus identified several gender-related, myopathic and cardiovascular peculiarities of R1006C mutation. This kind of comprehensive approach is necessary to define clinical course, prognosis and treatment options for a multi-organ disease such as CADASIL.

Highlights • We have carried out the largest screening of the ANO5 gene. • We identified 33 patients (4%) with pathogenic changes in both alleles and 23 heterozygotes (3%). • The identification of a ANO5 carrier is not to be considered an uncommon finding. • The anoctaminopathies have an extremely high genetic and phenotypic heterogeneity. • NGS-based strategies are perfect to dissect the clinical variability in NMDs., We studied 786 undiagnosed patients with LGMD or nonspecific myopathic features to investigate the role of ANO5 mutations in limb-girdle muscular dystrophies (LGMDs) and in nonspecific myopathies using the next generation sequencing (NGS) approach. In 160 LGMD patients, we first sequenced hotspot exons 5 and 20 and then sequenced the remaining part of the coding region. Another 626 patients, recruited using broader inclusion criteria, were directly analyzed by targeted NGS. By combining NGS and Sanger sequencing, we identified 33/786 (4%) patients carrying putative pathogenic changes in both alleles and 23 ANO5 heterozygotes (3%). The phenotypic spectrum is broader than expected, from hyperCKemia to myopathies, with lack of genotype/phenotype correlations. In particular, this is currently the largest screening of the ANO5 gene. The large number of heterozygotes for damaging mutations suggests that anoctaminopathies should be frequent and often nonpenetrant. We propose the multiple genetic testing by targeted NGS as a first step to analyze patients with nonspecific myopathic presentations. This represents a straightforward approach to overcome the difficulties of clinical heterogeneity of ANO5 patients, and to test, at the same time, many other genes involved in neuromuscular disorders.

Objective: We provide a nationwide population study of patients with congenital muscular dystrophy in Italy. Methods: Cases were ascertained from the databases in all the tertiary referral centers for pediatric neuromuscular disorders and from all the genetic diagnostic centers in which diagnostic tests for these forms are performed. Results: The study includes 336 patients with a point prevalence of 0.563 per 100,000. Mutations were identified in 220 of the 336 (65.5%). The cohort was subdivided into diagnostic categories based on the most recent classifications on congenital muscular dystrophies. The most common forms were those with α-dystroglycan glycosylation deficiency (40.18%) followed by those with laminin α2 deficiency (24.11%) and collagen VI deficiency (20.24%). The forms of congenital muscular dystrophy related to mutations in SEPN1 and LMNA were less frequent (6.25% and 5.95%, respectively). Conclusions: Our study provides for the first time comprehensive epidemiologic information and point prevalence figures for each of the major diagnostic categories on a large cohort of congenital muscular dystrophies. The study also reflects the diagnostic progress in this field with an accurate classification of the cases according to the most recent gene discoveries.

Centronuclear myopathies (CNMs) are a group of clinically and genetically heterogeneous muscle disorders. To date, mutation in 7 different genes has been reported to cause CNMs but 30 % of cases still remain genetically undefined. Genetic investigations are often expensive and time consuming. Clinical and morphological clues are needed to facilitate genetic tests and to choose the best approach for genetic screening. We aimed to describe genotype–phenotype correlation in an Italian cohort of patients affected by CNMs, to define the relative frequencies of its defined genetic forms and to draw a diagnostic algorithm to address genetic investigations. We recruited patients with CNMs from all the Italian tertiary neuromuscular centers following clinical and histological criteria. All selected patients were screened for the four ‘canonical’ genes related to CNMs: MTM1, DNM2, RYR1 and BIN1. Pathogenetic mutations were found in 38 of the 54 screened patients (70 %), mostly in patients with congenital onset (25 of 30 patients, 83 %): 15 in MTM1, 6 in DNM2, 3 in RYR1 and one in TTN. Among the 13 patients with a childhood–adolescence onset, mutations were found in 6 patients (46 %), all in DNM2. In the group of the 11 patients with adult onset, mutations were identified in 7 patients (63 %), again in DNM2, confirming that variants in this gene are relatively more common in late-onset phenotypes. The present study provides the relative molecular frequency of centronuclear myopathy and of its genetically defined forms in Italy and also proposes a diagnostic algorithm to be used in clinical practice to address genetic investigations.

Mutations in dynamin 2 (DNM2) gene cause autosomal dominant centronuclear myopathy and occur in around 50% of patients with centronuclear myopathy. We report clinical, morphological, muscle imaging and genetic data of 10 unrelated Italian patients with centronuclear myopathy related to DNM2 mutations. Our results confirm the clinical heterogeneity of this disease, underlining some peculiar clinical features, such as severe pulmonary impairment and jaw contracture that should be considered in the clinical follow-up. of these patients. Muscle MRI showed a distinct pattern of involvement, with predominant involvement of soleus and tibialis anterior in the lower leg muscles, followed by hamstring muscles and adductor magnus at thigh level and gluteus maximus. The detection of three novel DNM2 mutations and the first case of somatic mosaicism further expand the genetic spectrum of the disease. (C) 2013 Elsevier B.V. All rights reserved

Hereditary myopathy with early respiratory failure (HMERF) is a rare disorder characterized by severe respiratory involvement at onset, muscle weakness starting in the early adulthood, and cytoplasmic bodies with peculiar immunohistochemical reactivity on muscle biopsy. Here we describe a patient who presented with hypercapnic coma at age 32. A detailed light and electron microscopy analysis on muscle biopsy was performed and, together with clinical data, led to the diagnosis. The R279W mutation in the TTN gene was excluded. This report expands the geographical region of incidence and encourages additional studies to clarify the genetic heterogeneity of the condition.

It is generally believed that increase in adult contractile cardiac mass can be accomplished only by hypertrophy of existing myocytes. Documentation of myocardial regeneration in acute stress has challenged this dogma and led to the proposition that myocyte renewal is fundamental to cardiac homeostasis. Here we report that in human aortic stenosis, increased cardiac mass results from a combination of myocyte hypertrophy and hyperplasia. Intense new myocyte formation results from the differentiation of stem-like cells committed to the myocyte lineage. These cells express stem cell markers and telomerase. Their number increased >13-fold in aortic stenosis. The finding of cell clusters with stem cells making the transition to cardiogenic and myocyte precursors, as well as very primitive myocytes that turn into terminally differentiated myocytes, provides a link between cardiac stem cells and myocyte differentiation. Growth and differentiation of these primitive cells was markedly enhanced in hypertrophy, consistent with activation of a restricted number of stem cells that, through symmetrical cell division, generate asynchronously differentiating progeny. These clusters strongly support the existence of cardiac stem cells that amplify and commit to the myocyte lineage in response to increased workload. Their presence is consistent with the notion that myocyte hyperplasia significantly contributes to cardiac hypertrophy and accounts for the subpopulation of cycling myocytes.

Congestive heart failure is a lethal condition that affects an increasing number of patients. In recent years a great amount of data have accumulated on the pathophysiology and medical and surgical therapy of this condition. In spite of the advances in its management and the great number of patients affected, common errors are still made by internists and cardiologists in the use of drugs and therapeutic strategies. Digitalis has only recently been shown to affect hemodynamics, exercise capacity, and clinical symptoms, but the effects on survival still have to be demonstrated. Loop diuretics, eventually combined with thiazides and antialdosterone drugs in patients with clinical signs and symptoms of fluid retention, are the mainstays of therapy of congestive heart failure. In order to make diuretic therapy efficacious, moderate salt and water intake restriction is mandatory. Angiotensin-converting enzyme (ACE) inhibitors are now considered unavoidable drugs in the management of heart failure, and an attempt to reach the doses that have been shown to be efficacious for survival in the large trials has to be made in every patient with this condition. Other vasodilators, such as hydralazine and nitrates, which show a less pronounced effect on survival but more effective hemodynamic actions than ACE inhibitors, may be used to control mitral insufficiency or to improve hemodynamics in very sick patients. Hemodynamic instability refractory to increasing doses of vasodilators and diuretics is a severe condition that requires hospital admission to administer drugs parenterally. These patients are usually treated with the combination of catecholamines and phosphodiesterase inhibitors associated with intravenous diuretics until clinical stability is again achieved and oral therapy is resumed and restructured. The use of aggressive pharmacological therapy and phosphodiesterase inhibitors has reduced the need for assisted circulatory support in these patients. Beta-blockers have shown promising results when administered to patients with heart failure, although a definitive demonstration of their effects on survival is still lacking. Other additional measures that need to be considered in patients with end-stage congestive heart failure are the use of antiarrhythmic drugs and anticoagulation.

Background Myosin heavy chain 7 (MYH7)-related myopathies are emerging as an important group of muscle diseases of childhood and adulthood, with variable clinical and histopathological expression depending on the type and location of the mutation. Mutations in the head and neck domains are a well-established cause of hypertrophic cardiomyopathy whereas mutation in the distal regions have been associated with a range of skeletal myopathies with or without cardiac involvement, including Laing distal myopathy and Myosin storage myopathy. Recently the spectrum of clinical phenotypes associated with mutations in MYH7 has increased, blurring this scheme and adding further phenotypes to the list. A broader disease spectrum could lead to misdiagnosis of different congenital myopathies, neurogenic atrophy and other neuromuscular conditions. Results As a result of a multicenter Italian study we collected clinical, histopathological and imaging data from a population of 21 cases from 15 families, carrying reported or novel mutations in MYH7. Patients displayed a variable phenotype including atypical pictures, as dropped head and bent spine, which cannot be classified in previously described groups. Half of the patients showed congenital or early infantile weakness with predominant distal weakness. Conversely, patients with later onset present prevalent proximal weakness. Seven patients were also affected by cardiomyopathy mostly in the form of non-compacted left ventricle. Muscle biopsy was consistent with minicores myopathy in numerous cases. Muscle MRI was meaningful in delineating a shared pattern of selective involvement of tibialis anterior muscles, with relative sparing of quadriceps. Conclusion This work adds to the genotype-phenotype correlation of MYH7-relatedmyopathies confirming the complexity of the disorder. Electronic supplementary material The online version of this article (doi:10.1186/s13023-016-0476-1) contains supplementary material, which is available to authorized users.

Background: The Trifecta aortic bioprosthesis (St. Jude Medical, Inc., St. Paul, MN, USA) is a stented pericardial heart valve with excellent preliminary results. Aim of the study was to evaluate its early clinical and hemodynamic performances in a multicenter regional registry. Methods: Between January 2011 and June 2012, 178 consecutive patients undergoing aortic valve replacement with the Trifecta bioprosthesis were prospectively enrolled at 9 Italian centers. Clinical and echocardiographic data were collectedat discharge, 6-months and at 1-year postoperatively. Results: The average age was 75.4 +/- 7.7 years, and 95 (53 %) were men. Indication for valve replacement included stenosis in 123 patients (69 %), mixed lesions in 25 (14 %), and regurgitation in 30 (17 %). Ninety-three (52 %) patients were in NYHA functional class III/IV. Hospital mortality accounted for 5 (2.8 %) patients. No valve-related perioperative complications were encountered. Median follow-up was 20.5 months (range: 1-34). Early (6 months) thromboembolic events and two endocarditis (1 explant) were registered. No valve thrombosis or structural deterioration were observed after discharge. At 30-months, freedom from all-cause mortality was 87 %, freedom from valve-related mortality 99.4 %, freedom from endocarditis 97.5 %, and freedom from valve explants 98 %. At 1-year, mean gradients ranged from 8 to 16 mmHg, and effective orifice area indexes from 1.0 to 1.2 cm(2)/m(2) for valve sizes from 19 to 27 mm, respectively. No patients had severe prosthesis-patient mismatch. Conclusions: Trifecta bioprosthesis provided favourable clinical and hemodynamic results over time.