Genetics of hypertrophic cardiomyopathy: A review of current state.

Hypertrophic cardiomyopathy (HCM) is the most common inherited cardiovascular disease. HCM is a highly complex and heterogeneous disease regarding not only the number of associated mutations but also the severity of phenotype, symptom burden, and the risk of complications, such as heart failure and sudden death. The penetrance is incomplete and it is age and gender dependent. It is accepted as a disease of the sarcomere. Sixty percent of HCM cases carry mutations in 1 of 8 sarcomere protein genes, mainly non-sense MYBPC3 and missense MYH7 variants. Young patients with severe phenotype and other clinical features are included in proposed scores for prediction of high positive genetic result. The number of genes reported as disease-causing has increased in the last few years, in some cases without robust evidence. Currently available in silico tools are not always useful for differentiation between benign and deleterious variants. There is enough information on genotype-phenotype correlations to start understanding the mechanisms of the disease. Genetic and environmental modifiers have been explored with some interesting insights from miRNA studies with potential as biomarkers and therapeutic agents. There is an additional value of genetic testing in HCM for prognosis. Knowledge about genetics and functional studies are the basis of near future therapies.

[Translated article] Necrotising fasciitis: Management experience over the last two decades in our hospital.

BACKGROUND: Necrotising fasciitis is a potentially life-threatening soft tissue infection that mainly affects the fascia and deep planes, with a very high mortality rate and severe related complications. AIM: To evaluate clinical and demographic characteristics of patients with necrotising fasciitis in our hospital and to describe their diagnostic and therapeutic management. MATERIAL AND METHODS: Retrospective review of medical records of 21 patients diagnosed with necrotising fasciitis with limb involvement between January 2003 and February 2021 in our hospital. Demographic data, clinical features and details of management and prognosis were collected for each patient. RESULTS: Of 21 patients included, 15 were male (71.43%), with a mean age at diagnosis of 54.38±19.55 years. The most frequent comorbidities were insulin-dependent diabetes mellitus in seven patients (33.33%) and a history of cancer in five patients (23.81%). Infection was monomicrobial in 14 cases (66.66%), with Streptococcus pyogenes being the most frequent microorganism; multiple pathogens were isolated in 2 patients (9.52%) and no microorganism was identified in 5 patients (23.81%). All patients underwent surgery at our hospital, with a mean of 4.14±3.98 surgeries. Only one patient underwent amputation of the affected limb. The mean hospital stay was 23.14±16.44 days, with an overall mortality of 47.62% (10 cases). CONCLUSIONS: Despite being a rare disease, necrotising fasciitis is a very aggressive pathology, with a high mortality rate, especially in immunocompromised patients. Advanced age and oncological disease are potential factors of worse prognosis in the evolution of this condition.

Blastoschizomyces capitatus infection in acute leukemia patients.

Blastoschizomyces capitatus (BC), a filamentous fungus of genus Trichosporum, is as an important opportunistic pathogen in the compromised host. Within the past 10 years, 47 cases of BC infection have been published. Most of the patients had acute leukemia (AL) or related disorders and had received chemotherapy treatment. Due to BC's resistance to currently used antifungal agents, this infection represents a therapeutic challenge and serious complication in the treatment of hematology malignancies. Here we report our experience with BC infection in four patients with acute leukemia or related disorders.

Sideroblastic anaemia with reactive thrombocytosis versus myelodysplastic/myeloproliferative disease.

The reported incidence of thrombocytosis among cases of refractory anaemia with ring sideroblasts (RARS) may be as high as 15%. We report four additional cases of this association, which appear to be hematologically heterogeneous. One patient clearly represents a case of RARS with reactive thrombocytosis. Two cases have features suggestive of the coincidental occurrence of essential thrombocythemia and RARS. The fourth case could be best classified as a subtype of myelodysplastic/myeloproliferative disease unclassifiable (MDS/MPD U). Only new biological or molecular markers will allow better differentiation between these disorders.

Use of cyclophosphamide in the treatment of thrombotic thrombocytopenic purpura complicating systemic lupus erythematosus: report of two cases.

Thrombotic thrombocytopenic purpura (TTP) is an unusual complication of systemic lupus erythematosus (SLE). There are no randomized, prospective studies of its treatment. The association of plasma infusions and (or) plasmapheresis with steroids improves survival when compared with steroid treatment alone, but these patients still have a higher mortality than those with "classic" TTP. The role of immunosuppressive drugs in the management of this disorder remains uncertain. We report two cases of TTP in SLE which presumably benefited from the addition of cyclophosphamide to the treatment with plasmapheresis and steroids.

B-lymphoproliferative disorders in patients with hepatitis C virus infection.

A cohort of 148 consecutive patients with hepatitis C virus infection were studied at the rheumatology out-patient clinic of a tertiary care teaching hospital. The diagnosis of hepatitis C virus infection was supported by detection of HCV RNA in the serum. Cryoglobulin screening was done in all patients and the presence of a monoclonal component was investigated when the cryocrit was higher than 1%. Patients with lymphoproliferative disorders were further investigated. Four patients had a B lymphoproliferative disorder, which represents a prevalence of 2.7% in this cohort of patients with hepatitis C virus infection. Mixed cryoglobulinemia (MC), with cryocrit higher than 1%, was found in 16 of 148 patients (11%). It was type III MC in 13 patients and type II MC in 3. All patients who developed a B lymphoproliferative disorder had mixed cryoglobulinemia, with a monoclonal component (type II MC) in two patients and without a monoclonal component (type III MC) in the other two. The incidence of B-lymphoproliferative disorders among this cohort of patients with hepatitis C virus infection seems to be significantly increased. However, the high frequency of asymptomatic, undiagnosed HCV infection among the apparently healthy general population may decrease the true significance of this association. Systematic screening of cryoglobulin production in patients with hepatitis C virus infection might clarify whether the risk of B lymphoproliferative disorders increases when type II or type III mixed cryoglobulinemia is present.