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Fabry disease (FD) is a rare X-linked lysosomal storage disorder with a broad spectrum of clinical manifestations, including severe complications, such as end-stage renal disease, hypertrophic cardiomyopathy, and cerebrovascular disease. Enzyme replacement therapy (ERT), when initiated early, has been shown to reduce the incidence of severe events and slow disease progression. In the classic form, characterized by the absence of α-galactosidase A (α-Gal A) enzyme activity, diagnosis is straightforward. However, when residual activity is present, the delayed and less obvious presentation can make diagnosis more challenging. Ophthalmological alterations, which can be detected through non-invasive examinations may play a crucial role in correctly assessing the patient in terms of diagnosis and prognosis, particularly in these atypical cases. Recognizing these ocular signs allows for timely intervention with ERT, leading to improved patient outcomes. This review highlights the importance of ophthalmological findings in FD, emphasizing their role in diagnosis and treatment planning. By raising awareness among ophthalmologists and healthcare specialists, this review aims to improve disease management, offering tools for early detection and better long-term prognosis in patients with FD. [ABSTRACT FROM AUTHOR]

Background: Newly generated cardiomyocytes (NGCs) concur with the recovery of human myocarditis occurring spontaneously in around 50% of cases. However, NGCs decline with age, and their modality of myocardial homing and integration are still unclear. Methods: We retrospectively assessed NGCs in 213 consecutive patients with endomyocardial biopsy denoting acute myocarditis, with normal coronaries and valves. Tissue samples were processed for histology (H&E), immunohistochemistry for the evaluation of inflammatory infiltrates, immunostaining for alpha-sarcomeric-actin, junctional connexin-43, Ki-67, and phosphorylated STAT3 (p-STAT3), and Western blot (WB) for HMGB1. Frozen samples were analyzed using polymerase chain reaction (PCR) for cardiotropic viruses. Controls included 20 normal surgical biopsies. Results: NGCs were defined as small myocytes (diameter < 10 µm) with nuclear positivity to Ki-67 and p-STAT3 and positive immunostaining for cytoplasmic α-sarcomeric actin and connexin-43. Their number/mm2 in relation to age and pathway of integration was evaluated. NGCs crossed the membrane and grew integrated within the empty necrotic myocytes. NGC mean diameter was 6.6 ± 3.34 vs. 22.5 ± 3.11 µm adult cells; their number, in comparison to LVEF, was 86.3 ± 10.3/mm2 in patients between 18 and 40 years, 50.4 ± 13.8/mm2 in those between 41 and 60, and 15.1 ± 5.7/mm2 in those between 61 and 80. Control NGCs' mean diameter was 0.2 ± 0.2 mm2. PCR was positive for viral genomes in 16% of cases; NGCs were not statistically different in viral and non-viral myocarditis. WB analysis revealed a higher expression of HMGB1 in myocarditis compared to myocardial controls. Conclusions: NGCs are constantly recognizable in acute human myocarditis. Their number declines with age. Their integration within necrotic myocytes allows for the preservation of the cardiac structure and function. [ABSTRACT FROM AUTHOR]

Background and Aims Contemporary multicentre data on clinical and diagnostic spectrum and outcome in myocarditis are limited. Study aims were to describe baseline features, 1-year follow-up, and baseline predictors of outcome in clinically suspected or biopsy-proven myocarditis (2013 European Society of Cardiology criteria) in adult and paediatric patients from the EURObservational Research Programme Cardiomyopathy and Myocarditis Long-Term Registry. Methods Five hundred eighty-one (68.0% male) patients, 493 adults, median age 38 (27–52) years, and 88 children, aged 8 (3–13) years, were divided into 3 groups: Group 1 (n = 233), clinically suspected myocarditis with abnormal cardiac magnetic resonance; Group 2 (n = 222), biopsy-proven myocarditis; and Group 3 (n = 126) clinically suspected myocarditis with normal or inconclusive or no cardiac magnetic resonance. Baseline features were analysed overall, in adults vs. children, and among groups. One-year outcome events included death/heart transplantation, ventricular assist device (VAD) or implantable cardioverter defibrillator (ICD) implantation, and hospitalization for cardiac causes. Results Endomyocardial biopsy, mainly right ventricular, had a similarly low complication rate in children and adults (4.7% vs. 4.9%, P = NS), with no procedure-related death. A classical myocarditis pattern on cardiac magnetic resonance was found in 31.3% of children and in 57.9% of adults with biopsy-proven myocarditis (P <.001). At 1-year follow-up, 11/410 patients (2.7%) died, 7 (1.7%) received a heart transplant, 3 underwent VAD (0.7%), and 16 (3.9%) underwent ICD implantation. Independent predictors at diagnosis of death or heart transplantation or hospitalization or VAD implantation or ICD implantation at 1-year follow-up were lower left ventricular ejection fraction and the need for immunosuppressants for new myocarditis diagnosis refractory to non–aetiology-driven therapy. Conclusions Endomyocardial biopsy was safe, and cardiac magnetic resonance using Lake Louise criteria was less sensitive, particularly in children. Virus-negative lymphocytic myocarditis was predominant both in children and adults, and use of immunosuppressive treatments was low. Lower left ventricular ejection fraction and the need for immunosuppressants at diagnosis were independent predictors of unfavourable outcome events at 1 year. [ABSTRACT FROM AUTHOR]

Myocarditis is an inflammatory disease of the myocardium caused by infectious and noninfectious agents. Clinical manifestations range from mildly symptomatic forms to acute heart failure, cardiogenic shock, life-threatening arrhythmias and sudden death. Myocarditis is still a challenging diagnosis because of its wide variability in clinical presentation and unpredictable course. Moreover, a standardized, specific treatment in not yet available. Immunosuppressive treatment for virus-negative lymphocytic myocarditis is still controversial. Conversely, immunosuppression is well established in sarcoidosis, eosinophilic, giant-cell, drug hypersensitivity, and trauma-related myocarditis as well as lymphocytic myocarditis associated with connective tissue diseases or with the rejection of a transplanted heart. Recently, immunosuppressive therapy has been also recognized as an effective treatment in virus-negative inflammatory cardiomyopathy. The aim of this review is to underline the role of immunomodulating and immunosuppressive therapies in patients with immune-mediated myocarditis and illustrate the different treatment strategies depending on the etiology. An endomyocardial biopsy remains the gold standard for the diagnosis of myocarditis as well as for a tailored treatment. [ABSTRACT FROM AUTHOR]

Background and aimsPolishing may increase the surface roughness of composites, with a possible effect on bacterial growth and material properties. This preliminary in vitro study evaluates the effect of three different polishing systems (PoGo polishers, Enhance, Venus Supra) on six direct resin composites (Gradia Direct, Venus, Venus Diamond, Enamel Plus HFO, Tetric Evoceram, Filtek Supreme XT).Materials and methodsFor each composite, 12 square specimens were prepared: 9 specimens were polished, three for each different method, while three specimens were used as controls. Surface roughness was determined with AFM by measuring Root Mean Square (RMS) of average height.ResultsPoGo polisher determined a significantly rougher surface, versus controls, in 5 out of 6 composites evaluated. Some significant differences from unpolished controls were observed also for Enhance polishing. Polishing with Venus Supra did not result in any significant difference in surface roughness versus controls. No differences were observed between different polishing systems.ConclusionsThese preliminary results suggest that Venus Supra polishing system could determine a smoother composite surface if compared to the other polishing systems tested. On this basis, we are conducting an in vivo study to evaluate bacterial colonization on some combinations of composites and polishing protocols.

Introduction: Fabry's disease (FD) is a genetic X-linked systemic and progressive rare disease characterized by the accumulation of globotriaosylceramide (GB3) into the lysosomes of many tissues. FD is due to loss-of-function mutations of α-galactosidase, a key-enzyme for lysosomal catabolism of glycosphingolipids, which accumulate as glycolipid bodies (GB). In homozygous males the progressive deposition of GB3 into the cells leads to clinical symptoms in CNS, skin, kidney, etc. In testis GB accumulation causes infertility and alterations of spermatogenesis. However, the precise damaging mechanism is still unknown. Our hypothesis is that GB accumulation reduces blood vessel lumen and increases the distance of vessels from both stromal cells and seminiferous parenchyma; this, in turn, impairs oxygen and nutrients diffusion leading to subcellular degradation of seminiferous epithelium and sterility. Methods: To test this hypothesis, we have studied a 42-year-old patient presenting a severe FD and infertility, with reduced number of spermatozoa, but preserved sexual activity. Testicular biopsies were analyzed by optical (OM) and transmission electron microscopy (TEM). Activation and cellular localization of HIF-1α and NFκB was analyzed by immunofluorescence (IF) and RT-PCR on homogeneous tissue fractions after laser capture microdissection (LCMD). Results: OM and TEM showed that GB were abundant in vessel wall cells and in interstitial cells. By contrast, GB were absent in seminiferous epithelium, Sertoli's and Leydig's cells. However, seminiferous tubular epithelium and Sertoli's cells showed reduced diameter, thickening of basement membrane and tunica propria, and swollen or degenerated spermatogonia. IF showed an accumulation of HIF-1α in stromal cells but not in seminiferous tubules. On the contrary, NFκB fluorescence was evident in tubules, but very low in interstitial cells. Finally, RT-PCR analysis on LCMD fractions showed the expression of proinflammatory genes connected to the HIF-1α/NFκB inflammatory-like pathway. Conclusion: Our study demonstrates that infertility in FD may be caused by reduced oxygen and nutrients due to GB accumulation in blood vessels cells. Reduced oxygen and nutrients alter HIF-1α/NFκB expression and localization while activating HIF-1α/NFκB driven-inflammation-like response damaging seminiferous tubular epithelium and Sertoli's cells. [ABSTRACT FROM AUTHOR]