Budd-Chiari syndrome (BCS): a challenging diagnosis not to be overlooked-single center report and pictorial essay.

Budd-Chiari syndrome (BCS) is a rare disease with a variable clinical presentation and often late diagnosis. Doppler ultrasonography (DUS) permits to determine the site of the obstructed venous tracts, the thrombotic or non-thrombotic nature of the obstruction with its morphologic features and the flow-pattern alterations. Other non-specific findings, which are seen in most of the other liver diseases, include ascites, hepatosplenomegaly and caudate hypertrophy. The aim of this study is to show our experience in BCS reporting retrospectively 15 cases referred to our hepatology center between 2017 and 2021. Four selected cases depict the extreme heterogeneous behaviour of BCS and highlight the importance of DUS as a diagnostic tool when there is a clinical suspicion. In patients, mainly young, who present with ascites and abdominal pain, BCS has to be considered and DUS is the first imaging technique to be performed to rule it out.

A pan-European ring trial to validate an International Standard for detection of Vibrio cholerae, Vibrio parahaemolyticus and Vibrio vulnificus in seafoods.

Globally, vibrios represent an important and well-established group of bacterial foodborne pathogens. The European Commission (EC) mandated the Comite de European Normalisation (CEN) to undertake work to provide validation data for 15 methods in microbiology to support EC legislation. As part of this mandated work programme, merging of ISO/TS 21872-1:2007, which specifies a horizontal method for the detection of V. parahaemolyticus and V. cholerae, and ISO/TS 21872-2:2007, a similar horizontal method for the detection of potentially pathogenic vibrios other than V. cholerae and V. parahaemolyticus was proposed. Both parts of ISO/TS 21872 utilized classical culture-based isolation techniques coupled with biochemical confirmation steps. The work also considered simplification of the biochemical confirmation steps. In addition, because of advances in molecular based methods for identification of human pathogenic Vibrio spp. classical and real-time PCR options were also included within the scope of the validation. These considerations formed the basis of a multi-laboratory validation study with the aim of improving the precision of this ISO technical specification and providing a single ISO standard method to enable detection of these important foodborne Vibrio spp.. To achieve this aim, an international validation study involving 13 laboratories from 9 countries in Europe was conducted in 2013. The results of this validation have enabled integration of the two existing technical specifications targeting the detection of the major foodborne Vibrio spp., simplification of the suite of recommended biochemical identification tests and the introduction of molecular procedures that provide both species level identification and discrimination of putatively pathogenic strains of V. parahaemolyticus by the determination of the presence of theromostable direct and direct related haemolysins. The method performance characteristics generated in this have been included in revised international standard, ISO 21872:2017, published in July 2017.

Halobacteriovorax isolated from marine water of the Adriatic sea, Italy, as an effective predator of Vibrio parahaemolyticus, non-O1/O139 V. cholerae, V. vulnificus.

AIM: To detect marine Bdellovibrio and like organisms (BALOs) which are able to infect Vibrio parahaemolyticus from seawater of the Adriatic, Italy. To test, prey specificity and predation efficiency of our Halobacteriovorax isolate, named HBXCO1, towards 17 Vibrio and 7 non-Vibrio strains linked to the Adriatic sea, Italy. METHODS AND RESULTS: Double layer agar plating technique was used to enumerate BALOs and to evaluate their prey specificity and predation efficiency. Transmission electron microscopy and 16S rRNA analysis were used to identify them. Means of BALOs counts ranged from 5·0 PFU per ml (March 2017) to 98·6 PFU per ml (August 2016). HBXCO1 had the ability to attack all tested prey strains of V. parahaemolyticus, Vibrio cholerae non-O1/O139 and Vibrio vulnificus, but it did not prey on non-Vibrio strains and V. alginolyticus under the tested conditions. CONCLUSIONS: Bdellovibrio and like organisms capable of infecting pathogenic vibrios are naturally present in seawater of the Adriatic, Italy. Isolate HBXCO1 shows prey specificity preferentially for the Vibrio genus and high predatory efficiency towards a wide range of pathogenic strains. SIGNIFICANCE AND IMPACT OF THE STUDY: The public impact of V. parahaemolyticus, non-O1/O139 V. cholerae and V. vulnificus in bivalves is relevant and current decontamination processes are not always effective. We believe that the predator HBXCO1 represents a potential candidate for the development of strategies of biocontrol of pathogenic vibrios in bivalves from harvesting to trade.

Multidrug-resistant and epidemic clones of Escherichia coli from natural beds of Venus clam.

Epidemic Escherichia coli clones have been recovered in marine sediment along the coast of Marche, an Adriatic region in central Italy. In the present study, E. coli strains from the clam Chamelea gallina, sampled from seven natural beds in the same area, were detected. Selected E. coli isolates from all sampling sites were screened for antimicrobial susceptibility, genetic diversity and correlation. The majority (60%) belonged to phylogroups A or B1, 31% to the other groups (B2, C, D, E, F), 8% to cryptic clades, and 1% were untypable. Moreover, 33.3% of isolates were resistant to at least one drug and 11% were multidrug resistant (MDR). The most common resistance was to tetracycline, ampicillin, and streptomycin. No clonality was detected, but the strains' high genetic heterogeneity pointed at multiple sources of microbiological contamination. MLST analysis found potentially pathogenic and even epidemic MDR strains in clams collected in class A (ST746 and ST46) and class B (ST393, ST58 and ST131) areas, indicating that strains of clinical origin are detectable in clams. These data highlight that eating raw or lightly cooked clams may pose a health risk if purification is not performed or is ineffective.

An extensive investigation into the prevalence and the genetic and serological diversity of toxigenic Vibrio parahaemolyticus in Italian marine coastal waters.

The relationship between Vibrio parahaemolyticus strains isolated from the aquatic environment and those isolated from cases of infection in humans is poorly understood due to the low prevalence of tdh- and/or trh-positive strains in the environment. To address this concern, it would be useful to analyse the genetic relationships among environmental and food strains and with reference to clinical isolates, also applying molecular typing methods. The aim of this study was to evaluate the prevalence of toxigenic V.parahaemolyticus in Italian coastal waters and seafood, to examine intra-species variability and to identify, using serotyping and pulsed-field gel electrophoresis (PFGE), relationships among strains from different sources, geographical origin and period of isolation. Of the 192 V.parahaemolyticus strains isolated in different Italian areas and examined in this study, 25 (13.0%) proved to carry the trh gene while none of the strains proved positive to the search by PCR for tdh and Group-Specific-toxRS genes. The prevalence of toxigenic strains in the Tyrrhenian Sea was significantly lower than that calculated for the Ligurian coasts. Regarding the sources of isolation, the higher prevalence of trh-positive V.parahaemolyticus was revealed in fish, followed by clams, plankton, oysters, mussels and lastly seawater. Within the toxigenic strains, 16 serotypes and 20 distinct PFGE patterns were identified. Two clusters, which included a total of 8 V.parahaemolyticus strains, were specifically associated with the North Adriatic Sea area and were stable over time. Our results demonstrate that trh-positive V.parahaemolyticus strains circulated in Italy in the period 2002-2009 with a prevalence higher than that reported from other European and extra-European countries, confirming that toxigenic V.parahaemolyticus is an emerging public health concern in Italy, regardless of its pandemic potential.

Approach in glucocorticoid-induced osteoporosis prevention: results from the Italian multicenter observational EGEO study.

Glucocorticoid-induced osteoporosis (GIO) is the most frequent cause of secondary osteoporosis. GIO is linked to glucocorticoids (GC) daily assumption with maximum effect within first months of treatment and decreasing to basal levels as the therapy is discontinued. In Italy, primary prevention of GIO is suggested when GC therapy (prednisone >5 mg/day or equivalent) is taken for longer than 3 months. Lazio GISMO (Italian Group for Study and Diagnosis of Bone Metabolism Diseases) group organized the GC and Osteoporosis Epidemiology study (EGEO) to evaluate physician's approach in preventing GIO. The study involved 19 osteoporosis centers. Patients taking long-term GC therapy were recruited and information collected: medical history and anthropometric data, GC therapy, primary disease, physician's specialty, osteopororosis screening, and pharmacological intervention. The study included 1334 patients. Mean age was 63 ± 13 yr; 243 (18%) patients had a history of falls from standing position in the previous 12 months, 78 (35%) vertebral fractures, 91 (41%) fractures other than vertebral, 27 (12%) femoral fractures, and 27 (12%) multiple sites fractures. The molecules of GC more often prescribed were prednisone and 6-metil prednisolone. One thousand and forty patients (78%) were taking GC for more than 6 months. GC therapy was prescribed more frequently by rheumatologists (62%). Antiosteoporotic drugs for GIO prevention were prescribed in 431 patients (32%). Among the patients, only 27% (360) received calcium and vitamin D supplements, and 39% (319) treated by rheumatologists received anti-resorptive drugs. In conclusion, our data show that in Italy, as already described elsewhere, only a small subpopulation of GC-treated patients was supported by an anti-osteoporotic therapy, indicating the need to further stimulate awareness of both patients and specialists, prescribing GC therapy, to an appropriate and prompt GIO prevention.

Vibrio virulence genes in fishes collected from estuarine waters in Italy.

AIMS: The aim of this study was to investigate the presence of Vibrio vulnificus and potentially pathogenic strains of Vibrio parahaemolyticus in mullets collected from estuarine environment in Italy. METHODS AND RESULTS: Two hundred and ninety-five mullets were analysed by culture using the selective medium thiosulfate citrate bile salt sucrose agar, during a monitoring period of 2 years (2008-2009). Presumptive Vibrio colonies were initially identified by using biochemical tests, and strains identified as V. parahaemolyticus and V. vulnificus were subsequently examined by PCR for the presence of species-specific and virulence genes (toxR, trh, tdh and vvh). V. parahaemolyticus was found in 55% (162/295) of fishes and V. vulnificus in 1% (3/295) with a higher presence in summer months. The trh+/tdh- strains were detected in 16% (47/295) of samples and only one strain resulted trh+/tdh+. One of the V. parahaemolyticus trh+ strains isolated belonged to the O1:KUT (K untypeable), a serotype recently associated to gastroenteritis in Italy. CONCLUSIONS: This is the first report demonstrating a high percentage of potential pathogenic V. parahaemolyticus trh+ strains in estuarine fishes of the Mediterranean area. SIGNIFICANCE AND IMPACT OF THE STUDY: These findings indicate the potential human health risk associated with the presence of pathogenic Vibrio spp. in wild fishes.

Spontaneous imbibition in disordered porous solids: a theoretical study of helium in silica aerogels.

We present a theoretical study of spontaneous imbibition of liquid (4)He in silica aerogels focusing on the effect of porosity on the fluid dynamical behavior. We adopt a coarse-grained three-dimensional lattice-gas description like in previous studies of gas adsorption and capillary condensation and use a dynamical mean-field theory, assuming that capillary disorder predominates over permeability disorder as in recent phase-field models of spontaneous imbibition. Our results reveal a remarkable connection between imbibition and adsorption as also suggested by recent experiments. The imbibition front is always preceded by a precursor film, and the classical Lucas-Washburn √t scaling law is generally recovered, although some deviations may exist at large porosity. Moreover, the interface roughening is modified by wetting and confinement effects. Our results suggest that the interpretation of the recent experiments should be revised.

Histone deacetylases: novel targets for prevention of colitis-associated cancer in mice.

OBJECTIVE: Inhibition of histone deacetylases, well known for its antiproliferative efficacy in vivo, was recently shown to ameliorate inflammation in experimental colitis. Since inflammatory bowel disease is associated with an increased risk of developing colon cancer, here the combined anti-inflammatory and proapoptotic efficacy of histone deacetylase inhibitors was studied in mouse models. METHODS: The novel histone deacetylase inhibitor ITF2357 was compared with suberoylanilide hydroxamic acid in models of experimental colitis. Effects on tumour growth were studied after treatment of mice with azoxymethane and dextran sulphate sodium, and in interleukin 10 (IL10) knockout mice, respectively. Possible underlying mechanisms involving apoptosis and nuclear factor (NF)-kappaB activation were addressed by flow cytometry and western blot. RESULTS: In dextran sulphate sodium- and trinitrobenzene sulphonic acid-induced colitis, treatment with ITF2357 was superior to suberoylanilide hydroxamic acid as shown by macroscopic and histological amelioration of inflammation, by reduced production of interferon gamma (IFN gamma) and by increased production of IL10. In both models of inflammation-mediated tumourigenesis, inhibition of histone deacetylases resulted in a significant suppression of tumour growth in terms of size and number, along with reduced signs of inflammation. As for potential mechanisms of ITF2357 action, increased acetylation of histone 3, reduced production of IFN gamma and enhanced apoptosis in lamina propria mononuclear cells were found to accompany a histone deacetylase-dependent activation of NF-kappaB. CONCLUSIONS: These results indicate that inhibition of histone deactylases can attenuate inflammation-mediated tumour growth, which is paralled by an inhibition of NF-kappaB. Thus histone deacetylase inhibitors provide a promising strategy that combines anti-inflammatory and proapoptotic modes of action.

Gemtuzumab ozogamicin, cytosine arabinoside, G-CSF combination (G-AraMy) in the treatment of elderly patients with poor-prognosis acute myeloid leukemia.

BACKGROUND: Gemtuzumab ozogamicin (GO) is effective as single agent in the treatment of acute myeloid leukemia (AML). We evaluated efficacy and safety of a chemotherapy including growth factors, cytarabine, and GO (G-AraMy) in the treatment of poor-prognosis AML in elderly patients. PATIENTS AND METHODS: In three Italian hematology departments from September 2003 to September 2006, 53 elderly patients [median age 69 years (range 65-77)] with untreated or primary refractory/relapsed AML were enrolled on the combination G-AraMy administered according to two consecutive schedules (G-AraMy1 and G-AraMy2), with intensified consolidation in the second. Twenty-three of 53 patients had a secondary acute myeloid leukemia (sAML). RESULTS: The overall response rate was 57%. The most common adverse event was myelosuppression. Seven patients died in induction (13%). No differences for response rate and toxicity profile were observed between untreated and primary resistant/relapsed patients, de novo AML and sAML, and in the two treatment trials. Median disease-free survival and overall survival were 8 months (range 2-23+) and 9 months (range 2-24+). CONCLUSIONS: G-AraMy therapy may be considered an useful treatment approach for poor-risk elderly AML patients, with a complete remission rate comparable to literature data with reduced side-effects, also in a poor-prognosis population.

Multilocus genetic analysis of Cryptosporidium in naturally contaminated bivalve molluscs.

AIMS: To evaluate the application of discriminatory multilocus PCR procedures for the characterization of Cryptosporidium in samples of naturally contaminated bivalve molluscan shellfish. METHODS AND RESULTS: Nucleic acid was extracted from 22 shellfish previously identified as contaminated with Cryptosporidium spp. and subjected to PCR-based analysis for two independent fragments of the Cryptosporidium oocyst wall protein (COWP) gene, three microsatellite markers (ML 1, GP 15 and MS 5) and an extra-chromosomal small double-stranded RNA (dsRNA). Overall, at least one COWP gene fragment was amplified from all 22 samples, 21 amplified the dsRNA and 14 at least one of the three microsatellite loci. More than one dsRNA or microsatellite allele was detected in 50% of samples. The majority of samples were contaminated with Cryptosporidium parvum types circulating in both humans and livestock. A novel dsRNA element was identified in one sample, which did not amplify any of the three microsatellite loci investigated. CONCLUSIONS: Multilocus analysis of Cryptosporidium can be applied to DNA extracted from naturally contaminated shellfish. SIGNIFICANCE AND IMPACT OF STUDY: This multilocus genetic analysis highlights that filter feeder molluscs are a potential source of cryptosporidial oocysts, which may be infectious to humans.

The histone deacetylase inhibitor ITF2357 has anti-leukemic activity in vitro and in vivo and inhibits IL-6 and VEGF production by stromal cells.

We have investigated the activity of ITF2357, a novel hydroxamate histone deacetylase inhibitor, on multiple myeloma (MM) and acute myelogenous leukemia (AML) cells in vitro and in vivo. ITF2357 induced apoptosis in 8/9 MM and 6/7 AML cell lines, as well as 4/4 MM and 18/20 AML freshly isolated cases, with a mean IC(50) of 0.2 microM. ITF2357 activated the intrinsic apoptotic pathway, upregulated p21 and downmodulated Bcl-2 and Mcl-1. The drug induced hyperacetylation of histone H3, H4 and tubulin. When studied in more physiological conditions, ITF2357 was still strongly cytotoxic for the interleukin-6 (IL-6)-dependent MM cell line CMA-03, or for AML samples maximally stimulated by co-culture on mesenchymal stromal cells (MSCs), but not for the MSCs themselves. Interestingly, ITF2357 inhibited the production of IL-6, vascular endothelial growth factor (VEGF) and interferon-gamma by MSCs by 80-95%. Finally, the drug significantly prolonged survival of severe combined immunodeficient mice inoculated with the AML-PS in vivo passaged cell line already at the 10 mg/kg oral dose. These data demonstrate that ITF2357 has potent anti-neoplastic activity in vitro and in vivo through direct induction of leukemic cell apoptosis. Furthermore, the drug inhibits production of growth and angiogenic factors by bone marrow stromal cells, in particular IL-6 and VEGF.

Genetic analysis of Cryptosporidium from 2414 humans with diarrhoea in England between 1985 and 2000.

The characterization of Cryptosporidium using DNA extracted from whole faecal samples collected from 2414 humans with diarrhoea in England between 1985 and 2000 where cryptosporidial oocysts were detected using conventional methods is described. Characterization was achieved by PCR/RFLP and DNA sequencing of fragments of the Cryptosporidium oocyst wall protein and the 18S rDNA genes. Cryptosporidium parvum was detected in 56.1 % of cases, Cryptosporidium hominis in 41.7 % and a mixture of C. parvum and C. hominis in 0.9 %. In the remainder of cases, Cryptosporidium meleagridis (0.9 %), Cryptosporidium felis (0.2 %), Cryptosporidium andersoni (0.1 %), Cryptosporidium canis (0.04 %), Cryptosporidium suis (0.04 %) and the Cryptosporidium cervine type (0.04 %) were detected.

Epstein-Barr virus-associated post-transplant lymphoproliferative disease with central nervous system involvement after unrelated allogeneic hematopoietic stem cell transplantation.

Post-transplant lymphoproliferative disorders (PTLD) represent an heterogeneous group of abnormal lymphoid proliferation related to Epstein-Barr virus (EBV) reactivation that arise early after allogeneic hematopoietic stem cell transplant (HSCT). PLTD with central nervous system (CNS) involvement has been reported in few cases. We describe the case of a 31-year-old-man who developed an EBV-related PTLD with CNS involvement 2 months after an allogeneic unrelated HSCT for acute myeloid leukemia in first complete remission who was successfully treated with rituximab, cidofovir and intrathecal infusion of methotrexate and methylprednisolone.

Low dose Velcade, thalidomide and dexamethasone (LD-VTD): an effective regimen for relapsed and refractory multiple myeloma patients.

From January 2004, R/R MM cases referred to the Institution received LD-VTD regimen. Patients, irrespective of age, PS and life expectancy, were enrolled in the study once they had a measurable disease. Planned therapy: Velcade 1.0 mg m(-2) i.v. twice weekly for 2 weeks of a 28-day cycle for up to 6 cycles, oral Dexamethasone 24 mg on the day of and the day following each Velcade dose and Thalidomide 100 mg each evening. DVT prophylaxis with warfarin to maintain international normalized ratio between 2.0-3.0 was planned in all patients. As of 1 June 2005, 18 were the treated patients: median age 63 years, median time from diagnosis 5.8 years, a median of 4 previous therapy lines. Seventeen were the valuable patients and 9 (53%) were the responders: 2 CR, 6 PR, 1 MR. Six were the stable disease and 2 the progressive ones. Median time to best response was 2 months. Toxicity was negligible. No case of DVT was recorded. Except for the first cycle, subsequent cycles were delivered on an outpatient basis. After a median follow-up of 11 months, 12 patients were alive and 5 died (3 disease progression, 1 heart failure, 1 intestinal bleeding). Thus, the LD-VTD regimen applied appears feasible and effective in elderly and heavily pre-treated R/R myeloma patients.