Primary cerebral alveolar rhabdomyosarcoma in adult

Primary cerebral rhabdomyosarcomas are very rare and malignant tumors that occur predominantly in the posterior fossa of pediatric patients. We report a rare case of primary cerebral rhabdomyosarcoma located in the supratentorial compartment of a 51 year-old woman together with a review of the pertinent Literature especially regarding the histological diagnosis and pitfalls

Twelve Variants Polygenic Score for Low-Density Lipoprotein Cholesterol Distribution in a Large Cohort of Patients With Clinically Diagnosed Familial Hypercholesterolemia With or Without Causative Mutations

: Background A significant proportion of individuals clinically diagnosed with familial hypercholesterolemia (FH), but without any disease-causing mutation, are likely to have polygenic hypercholesterolemia. We evaluated the distribution of a polygenic risk score, consisting of 12 low-density lipoprotein cholesterol (LDL-C)-raising variants (polygenic LDL-C risk score), in subjects with a clinical diagnosis of FH. Methods and Results Within the Lipid Transport Disorders Italian Genetic Network (LIPIGEN) study, 875 patients who were FH-mutation positive (women, 54.75%; mean age, 42.47±15.00 years) and 644 patients who were FH-mutation negative (women, 54.21%; mean age, 49.73±13.54 years) were evaluated. Patients who were FH-mutation negative had lower mean levels of pretreatment LDL-C than patients who were FH-mutation positive (217.14±55.49 versus 270.52±68.59 mg/dL, P<0.0001). The mean value (±SD) of the polygenic LDL-C risk score was 1.00 (±0.18) in patients who were FH-mutation negative and 0.94 (±0.20) in patients who were FH-mutation positive (P<0.0001). In the receiver operating characteristic analysis, the area under the curve for recognizing subjects characterized by polygenic hypercholesterolemia was 0.59 (95% CI, 0.56-0.62), with sensitivity and specificity being 78% and 36%, respectively, at 0.905 as a cutoff value. Higher mean polygenic LDL-C risk score levels were observed among patients who were FH-mutation negative having pretreatment LDL-C levels in the range of 150 to 350 mg/dL (150-249 mg/dL: 1.01 versus 0.91, P<0.0001; 250-349 mg/dL: 1.02 versus 0.95, P=0.0001). A positive correlation between polygenic LDL-C risk score and pretreatment LDL-C levels was observed among patients with FH independently of the presence of causative mutations. Conclusions This analysis confirms the role of polymorphisms in modulating LDL-C levels, even in patients with genetically confirmed FH. More data are needed to support the use of the polygenic score in routine clinical practice

Spectrum of mutations in Italian patients with familial hypercholesterolemia: New results from the LIPIGEN study

Background Familial hypercholesterolemia (FH) is an autosomal dominant disease characterized by elevated plasma levels of LDL-cholesterol that confers an increased risk of premature atherosclerotic cardiovascular disease. Early identification and treatment of FH patients can improve prognosis and reduce the burden of cardiovascular mortality. Aim of this study was to perform the mutational analysis of FH patients identified through a collaboration of 20 Lipid Clinics in Italy (LIPIGEN Study). Methods We recruited 1592 individuals with a clinical diagnosis of definite or probable FH according to the Dutch Lipid Clinic Network criteria. We performed a parallel sequencing of the major candidate genes for monogenic hypercholesterolemia (LDLR, APOB, PCSK9, APOE, LDLRAP1, STAP1). Results A total of 213 variants were detected in 1076 subjects. About 90% of them had a pathogenic or likely pathogenic variants. More than 94% of patients carried pathogenic variants in LDLR gene, 27 of which were novel. Pathogenic variants in APOB and PCSK9 were exceedingly rare. We found 4 true homozygotes and 5 putative compound heterozygotes for pathogenic variants in LDLR gene, as well as 5 double heterozygotes for LDLR/APOB pathogenic variants. Two patients were homozygous for pathogenic variants in LDLRAP1 gene resulting in autosomal recessive hypercholesterolemia. One patient was found to be heterozygous for the ApoE variant p.(Leu167del), known to confer an FH phenotype. Conclusions This study shows the molecular characteristics of the FH patients identified in Italy over the last two years. Full phenotypic characterization of these patients and cascade screening of family members is now in progress

Fines, termini et limites. I confini nella formazione dello Stato fiorentino

I confini nella formazione dello Stato fiorentino. Nel processo di crescita e di maturazione dello Stato fiorentino, a partire almeno dalla fine del XIII secolo, l’attenzione nei confronti dei confini andò sempre più realizzandosi attraverso l’accentuazione dei caratteri di linearità delle demarcazioni, in netto contrasto con la dimensione zonale degli spazi confinari: per questo, laddove possibile, i confini sarebbero stati identificati con un tracciato stradale. Firenze andò affermando i limiti del proprio dominio con le altre realtà giurisdizionali, istituzionali e politiche circostanti, giungendo a ricercarne una legittimazione poi tradotta con precisione sul terreno e possibilmente concertata, come dimostrano i due accordi trecenteschi tra Firenze e il Comune bolognese qui presi in considerazione. La linea di condotta adottata dal Comune fiorentino in materia di tracciamento delle linee di confine con l’esterno sembra essere applicata come metodo anche all’interno del comitatus cittadino. Qui, l’espansione comunale aveva infatti lasciato pressoché intatte le ripartizioni territoriali preesistenti (comuni, plebati, ecc.) adeguandovi le esigenze istituzionali, amministrative, giurisdizionali comunali: sostanzialmente un disegno che doveva essere preservato e migliorato. Così, sempre più spesso – come nel caso del 1338 concernente due comunità vicine a Firenze qui illustrate – una precisa terminazione tracciata sul territorio si traduceva non solo nel tentativo di cancellare localmente un contenzioso tra universitates limitanee, ma anche in una garanzia per lo stabile assetto dell’intera organizzazione territoriale fiorentina

La Valdambra, Firenze e una Terranuova mai nata (sec. XIV)

Contestualizzazione di un fallito progetto di concentrazione di popolazione da parte del Comune fiorentino in area confinaria. Analisi dell'ambito demografico, sociale, politico e dei poteri locali e reazioni di fronte all'espansione politica di Firenze