The natural history of hypertrophic cardiomyopathy

In the early years of the disease recognition, hypertrophic cardiomyopathy (HCM) was viewed as an ominous disease with unfavourable prognosis and with an annual mortality between 4% and 6%. At that time, 73% of the patients reported in the literature came from only two referral centres. With the introduction of echocardiography, our understanding of HCM has improved and non-selected patient populations were assembled in several centres. A more benign prognostic profile was documented with an annual mortality rate of 1.5% or less. In the 2000s, important therapeutic interventions further improved the prognosis of patients with HCM: implantable-cardioverter defibrillator for prevention of sudden death, heart transplantation for treatment of severe refractory heart failure, and an extensive treatment with myectomy for relief of left ventricular outflow tract gradient. The natural history of HCM has changed substantially with contemporary treatment achieving an annual mortality rate less than 1% with extended longevity and a greatly improved quality of life

Metabolic disorders and cardiovascular risk in HIV-infected patients treated with antiretroviral agents.

The clinical management of HIV-infected individuals is based on highly active antiretroviral combination therapy, which provides significant clinical benefit in most patients, but causes in a high proportion of them a metabolic syndrome that includes body fat redistribution, hypercholesterolemia, hypertriglyceridemia, and insulin resistance. These effects are particularly evident in patients treated with protease inhibitors. It is likely that the metabolic disorders related to anti-HIV treatment will eventually translate into an increased cardiovascular risk in patients submitted to such regimens

Maternally inherited cardiomyopathy: clinical and molecula characterization of a large kindred harboring the A4300G point mutation in mtDNA

OBJECTIVES: The purpose of this study was to describe the clinical and molecular features of a large family with maternally inherited cardiomyopathy (MICM). BACKGROUND: Recently, several mitochondrial deoxyribonucleic acid (mtDNA) point mutations have been associated with MICM. However, the distinctive clinical and morphologic features of MICM are not fully appreciated. This is partially due to the small size of the reported pedigrees, often lacking detailed clinical and laboratory information. METHODS: Clinical and genetic analysis of the family was carried out. RESULTS: Echocardiography showed mostly symmetrical hypertrophic cardiomyopathy in 10 family members. The illness had an unfavorable course. Progressive heart failure occurred in three subjects, who eventually died; one individual underwent heart transplantation. Electrocardiographic or echocardiographic signs of cardiac hypertrophy in the absence of significant clinical complaints were observed in five subjects. Neurologic examination was normal. The mutation was detected in blood from all available subjects. Abundance of mutated molecules ranged between 13% and 100% of total mtDNA genomes. The severity of the disease could not be foreseen by the proportion of mutation in blood. CONCLUSIONS: This report contributes a better description of the clinical aspects of MICM and provides important clues to distinguish it from hypertrophic cardiomyopathy. We suggest that mtDNA mutations, particularly in the transfer ribonucleic acid for isoleucin, should be systematically searched in patients with MICM. The identification of an underlying maternally inherited mitochondrial DNA defect in familial cases of cardiomyopathy may considerably influence the management and genetic counseling of affected patients

Cytotoxic Activity and Composition of Petroleum Ether Extract from Magydaris tomentosa (Desf.) W. D. J. Koch (Apiaceae).

The petroleum ether extract of Magydaris tomentosa flowers (Desf.) W. D. J. Koch has been analyzed by GC-MS. It is mainly constituted by furanocoumarins such as xanthotoxin, xanthotoxol, isopimpinellin, and bergaptene. Other coumarins such as 7-methoxy-8-(2-formyl-2-methylpropyl) coumarin and osthole also occurred. The antiproliferative activity of Magydaris tomentosa flower extract has been evaluated in vitro on murine monocyte/macrophages (J774A.1), human melanoma (A375) and human breast cancer (MCF-7) tumor cell lines, showing a major activity against the latter

Real-world versus trial patients with transthyretin amyloid cardiomyopathy

Transthyretin (TTR) amyloid cardiomyopathy (ATTR‐AC) is caused either by single‐point mutations in the TTR gene (ATTRv‐AC) or by deposition of the wild‐type protein (ATTRwt‐AC).1 Long been considered a rare disease, ATTR‐AC has been increasingly recognized in recent years, particularly among the elderly,1 mostly due to the possibility of a non‐invasive diagnosis through bone scintigraph

Clinical translation of genetic testing in TTR Amyloidosis. genotype-phenotype correlations, management of asymptomatic carriers and familial screening

Transthyretin (TTR)-related amyloidosis (ATTR) is a heterogeneous disease with different organ involvement depending on the type of TTR infiltration [mutated (vTTR) or wild-type (wtTTR)]. Genetic testing in ATTR is required to define diagnosis and identify asymptomatic at-risk family members. Since new therapies are maximally effective in the early stages of the disease, there is a growing agreement about the need for close monitoring of genotype-positive, phenotype-negative individuals to assure a prompt treatment when minor disease signs are detected. This review summarizes the complexity of genotype-phenotype correlation and revises the current indications with respect to familiar screening and management of asymptomatic carriers

Virilizing Leydig-Sertoli cell ovarian tumor associated with endometrioid carcinoma of the endometrium in a postmenopausal patient: Case report and general considerations

Sertoli-Leydig cell tumors (SLCTs) are rare tumors mostly occurring in young women. Here we report an unusual case of a SLCT with simultaneous occurrence of endometrioid adenocarcinoma of the endometrium in a woman in menopause

Oratio laudatoria pro Francisco Valesio rege Francorum Christianissimo, pacis & belli artium peritissimo, per L. Campestrum canonicum regularem pres. In fine addita Europae lamentatio ad regem christianissimo carmen heroico eleganter scripta autore Huberto Susanneo Suessionensi, miré orationi alludens

30, °2! p. ; 4º Laurentius Campester è lo pseudonimo di Laurens van de Velde Opera di incerto autore attribuito erroneamente a Laurentius Campester, cfr. Bibliotheca Belgica, Bruxelles 1964, vol.1 p.436 Data della pref.: 1538 Cors. ; rom Segn.: a-d⁴ L'ultima c. bianca Iniziali e fregi xil

Clinical Outcome of Discordant Empirical Therapy and Risk Factors Associated to Treatment Failure in Children Hospitalized for Urinary Tract Infections

With the spread of antibiotic resistance in pediatric urinary tract infections (UTIs), more patients are likely to be started empirically on antibiotics to which pathogens are later found to be resistant (discordant therapy). However, in-vivo effectiveness may be different from in-vitro susceptibility. Aims of this study were to describe clinical outcomes of discordant empirical treatments in pediatric UTIs and to investigate risk factors associated to treatment failure. This observational, retrospective study was conducted on children hospitalized for febrile UTIs with positive urine culture and started on discordant empirical therapy. Failure rates of discordant treatments and associated risk factors were investigated. A total of 142/1600 (8.9%) patients were treated with inadequate empirical antibiotics. Clinical failure was observed in 67/142 (47.2%) patients, with no fatal events. Higher failure rates were observed for combinations of penicillin and beta-lactamase inhibitors (57.1%). Significant risk factors for failure of discordant treatment were history of recurrent UTIs (95% CI: 1.13–9.98, OR: 3.23, p < 0.05), recent use of antibiotics (95% CI: 1.46–21.82, OR: 5.02, p < 0.01), infections caused by Pseudomonas aeruginosa (95% CI: 1.85–62.10, OR: 7.30, p < 0.05), and empirical treatment with combinations of penicillin and beta-lactamase inhibitors (95% CI: 0.94–4.03, OR: 1.94, p = 0.05). This study showed that discordant empirical treatments may still be effective in more than half of pediatric UTIs. Clinical effectiveness varies between different discordant antibiotics in pediatric UTIs, and patients presenting risk factors for treatment failure may need a differentiated empirical approach

Genetic dynamics in untreated CLL patients with either stable or progressive disease: A longitudinal study

Clonal evolution of chronic lymphocytic leukemia (CLL) often follows chemotherapy and is associated with adverse outcome, but also occurs in untreated patients, in which case its predictive role is debated. We investigated whether the selection and expansion of CLL clone(s) precede an aggressive disease shift. We found that clonal evolution occurs in all CLL patients, irrespective of the clinical outcome, but is faster during disease progression. In particular, changes in the frequency of nucleotide variants (NVs) in specific CLL-related genes may represent an indicator of poor clinical outcome