Twelve-week posttreatment follow-up predicts a sustained virological response to pegylated interferon and ribavirin therapy

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HCV genotype 3: An independent predictor of fibrosis progression in chronic hepatitis C

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Prothrombotic mutations, family history and the risk of thrombosis in postmenopausal women: implications for hormone replacement therapy

Objective Hormone replacement therapy (HRT) is acknowledged as the gold standard for the alleviation of climacteric vasomotor symptoms. Prothrombotic genetic variants have been suggested to increase thrombotic risk among HRT users. The aim of the study was to determine whether a positive family history may identify a genetic predisposition for thrombosis in women before prescribing HRT. Methods From January 2005 to May 2009, we consecutively enrolled 145 asymptomatic women (mean age 51.2+5.4 years) without previous episodes of venous and/or arterial thrombosis referred to our Genetics Research Unit before starting HRT. A detailed family history was reconstructed and we identified 48 women (33.1%) with a positive family history, defined as venous thromboembolism and/or stroke or heart attack, in first-degree relatives before 60 years for men and 65 years for women. A group of 121 women (mean age 54.0+9.1 years) with an episode of venous and/or arterial thrombosis was also included. Genetic screening for factor V Leiden, prothrombin G20210A and methylenetetrahydrofolate reductase C677T polymorphisms was performed. Results The frequency of factor V Leiden or prothrombin G20210A mutations was significantly higher both in asymptomatic women with a positive family history (16.7% vs. 2.1%, p?0.001) and in patients with thrombosis (12.4% vs. 2.1%; p?0.005) compared with asymptomatic women without a family history. Multivariate regression analysis showed a synergic effect between the presence of one prothrombotic mutation and family history on the risk of thrombosis (odds ratio 3.7, 95% confidence interval 1.9-7.2). Conclusions A positive family history of thrombosis is a sensitive indicator for selected genetic testing in high-risk women before starting HRT

Severe steatohepatitis in a patient with a rare neutral lipid storage disorder due to ABDH5 mutation

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Ribavirin Impairs Salivary gland function During Combination Treatment With Pegylated Interferon Alfa-2a In HEpatitis C patients

Background: Xerostomia is a common adverse event of unknown etiology observed during pegylated interferon (PegIFN)/Ribavirin (Rbv) treatment. Objectives: To assess the frequency and mechanisms of xerostomia during PegIFN/Rbv therapy. Patients and Methods: Thirty-one naive patients with chronic hepatitis C consecutively received PegIFN-alpha 2a (180 mu g/week) plus Rbv (800-1200 mg/day). The controls were 10 patients with chronic hepatitis B who received PegIFN-alpha 2a (180 mu g/week). During treatment and follow-up, all patients underwent basal and masticatory stimulated sialometry, otorhinolaryngoiatric (ORL) examination, and a questionnaire survey to subjectively assess symptoms of oral dryness. Results: Twenty-seven patients on PegIFN/Rbv and 4 on PegIFN (87% vs. 40%, P = 0.006) reported xerostomia. Thirty patients on PegIFN/Rbv combination therapy and 2 patients on monotherapy had ORL signs of salivary gland hypofunction (97% vs. 20%, P < 0.0001). Mean basal (A) and stimulated (B) salivary flow rates (mL/min) progressively decreased during PegIFN/Rbv treatment (A, 0.49 at baseline vs. 0.17 at the end of treatment, P < 0.0001; B,1.24 at baseline vs. 0.53 at the end of treatment, P = 0.0004). At week 24 following PegIFN/Rbv treatment, salivary flow rates were similar to baseline (A, 0.53 at the end of follow-up vs. 0.49 at baseline; B,1.19 at the end of follow-up vs. 1.24 at baseline). Salivary function was unaffected in monotherapy patients. Conclusions: Rbv causes salivary gland hypofunction in hepatitis C patients receiving PegIFN/Rbv therapy, which promptly reverts to normal upon cessation of treatment

IL-3 or IL-7 Increases ex Vivo Gene Transfer Efficiency in ADA-SCID BM CD34 + Cells while Maintaining in Vivo Lymphoid Potential

To improve maintenance and gene transfer of human lymphoid progenitors for clinical use in gene therapy of adenosine deaminase (ADA)-deficient SCID we investigated several gene transfer protocols using various stem cell-enriched sources. The lymphoid differentiation potential was measured by an in vitro clonal assay for B/NK cells and in the in vivo SCID-hu mouse model. Ex vivo culture with the cytokines TPO, FLT3-ligand, and SCF (T/F/S) plus IL-3 or IL-7 substantially increased the yield of transduced bone marrow (BM) CD34+ cells purified from ADA-SCID patients or healthy donors, compared to T/F/S alone. Moreover, the use of IL-3 or IL-7 significantly improved the maintenance of in vitro B cell progenitors from ADA-SCID BM cells and allowed the efficient transduction of B and NK cell progenitors. Under these optimized conditions transduced CD34+ cells were efficiently engrafted into SCID-hu mice and gave rise to B and T cell progeny, demonstrating the maintenance of in vivo lymphoid reconstitution capacity. The protocol based on the T/F/S + IL-3 combination was included in a gene therapy clinical trial for ADA-SCID, resulting in long-term engraftment of stem/progenitor cells. Remarkably, gene-corrected BM CD34+ cells obtained from one patient 4 and 11 months after gene therapy were capable of repopulating the lymphoid compartment of SCID-hu hosts

A novel LMNA mutation (R189W) in familial dilated cardiomyopathy: evidence for a 'hot spot' region at exon 3: a case report

We describe a case of a patient with idiopathic dilated cardiomyopathy and cardiac conduction abnormalities who presented a strong family history of sudden cardiac death. Genetic screening of lamin A/C gene revealed in proband the presence of a novel missense mutation (R189W), near the most prevalent lamin A/C mutation (R190W), suggesting a "hot spot" region at exon 3

Case report: Primary Ewing sarcoma of the ureter, an exceptional finding of unique manifestation of disease

Ewing sarcoma (ES) is the second most common malignant bone tumor in children and has also been described in adults with highly aggressive behavior. ES belongs to the small round blue cell tumor family and presents the distinctive translocation of FET-ETS family genes (85% with EWSR1), generating gene fusions. Extraskeletal ES mainly occurs in soft tissues; the urogenital tract is rarely affected, and ureteral localization is an exceptional event with only 4 cases described in the literature. Here we report the first Italian case of primary ES of the ureter, a 24-year-old young man with lower back pain and a narrowed left ureteral lumen on CT scan. ES of the urogenital tract is an almost unique condition with a nonspecific clinical presentation and a challenging diagnosis for pathologists. We encourage awareness of these exceptional events in the differential diagnosis of ureteral lesions in young patients

Fatal Takotsubo syndrome in critical COVID-19 related pneumonia

COVID-19 can involve several organs and systems, often with indirect and poorly clarified mechanisms. Different presentations of myocardial injury have been reported, with variable degrees of severity, often impacting on the prognosis of COVID-19 patients. The pathogenic mechanisms underlying cardiac damage in SARS-CoV-2 infection are under active investigation. We report the clinical and autopsy findings of a fatal case of Takotsubo Syndrome occurring in an 83-year-old patient with COVID-19 pneumonia. The patient was admitted to Emergency Department with dyspnea, fever and diarrhea. A naso-pharyngeal swab test for SARS-CoV-2 was positive. In the following week his conditions worsened, requiring intubation and deep sedation. While in the ICU, the patient suddenly showed ST segment elevation. Left ventricular angiography showed decreased with hypercontractile ventricular bases and mid-apical ballooning, consistent with diagnosis of Takotsubo syndrome (TTS). Shortly after the patient was pulseless. After extensive resuscitation maneuvers, the patient was declared dead. Autopsy revealed a subepicardial hematoma, in absence of myocardial rupture. On histology, the myocardium showed diffuse edema, multiple foci of contraction band necrosis in both ventricles and occasional coagulative necrosis of single cardiac myocytes. Abundant macrophages CD68+ were detected in the myocardial interstitium. The finding of diffuse contraction band necrosis supports the pathogenic role of increased catecholamine levels; the presence of a significant interstitial inflammatory infiltrate, made up by macrophages, remains of uncertain significance