First report outside Eastern Europe of West Nile virus lineage 2 related to the Volgograd 2007 strain, northeastern Italy, 2014

open11noWest Nile virus (WNV) is a Flavivirus transmitted to vertebrate hosts by mosquitoes, maintained in nature through an enzootic bird-mosquito cycle. In Europe the virus became of major public health and veterinary concern in the 1990s. In Italy, WNV re-emerged in 2008, ten years after the previous outbreak and is currently endemic in many areas of the country. In particular, the northeastern part of Italy experience continuous viral circulation, with human outbreaks caused by different genovariants of WNV lineage 1, Western-European and Mediterranean subcluster, and WNV lineage 2, Hungarian clade. Alongside the WNV National Surveillance Program that has been in place since 2002, regional surveillance plans were implemented after 2008 targeting mosquitoes, animals and humans.openRavagnan, Silvia; Montarsi, Fabrizio; Cazzin, Stefania; Porcellato, Elena; Russo, Francesca; Palei, Manlio; Monne, Isabella; Savini, Giovanni; Marangon, Stefano; Barzon, Luisa; Capelli, GioiaRavagnan, Silvia; Montarsi, Fabrizio; Cazzin, Stefania; Porcellato, Elena; Russo, Francesca; Palei, Manlio; Monne, Isabella; Savini, Giovanni; Marangon, Stefano; Barzon, Luisa; Capelli, Gioi

Spectrum of 5’UTR mutations in ANKRD26 gene in patients with inherited thrombocytopenia: c.-140C>G mutation is more frequent than expected

none8noneFerrari, Silvia; Lombardi, Anna Maria; Putti, Maria Caterina; Bertomoro, Antonella; Cortella, Irene; Barzon, Isabella; Girolami, Antonio; Fabris, FabrizioFerrari, Silvia; Lombardi, ANNA-MARIA; Putti, Maria Caterina; Bertomoro, Antonella; Cortella, Irene; Barzon, Isabella; Girolami, Antonio; Fabris, Fabrizi

Correlation between ADAMTS13 activity and neurological impairment in acute thrombotic microangiopathy patients

Differential diagnosis between thrombotic thrombocytopenic purpura (TTP) and other thrombotic microangiopathies (TMA) is usually difficult because of frequently overlapping clinical presentations. Severely depressed ADAMTS13 activity (<10\ua0%) seems distinctive for TTP because of its pathogenetic role. However a long debate exists in the literature about its sensibility and specificity. Our aim was to search for clinical differences between TMA patients referred to our laboratory, comparing them for protease activity\ua0<10 versus\ua0 6510\ua0%. ADAMTS13 activity\ua0 6510\ua0% patients (n\ua0=\ua073) showed a higher prevalence of drug- (p\ua0=\ua00.005) and cancer-associated (p\ua0<\ua00.001) TMA. Mean platelet count and renal dysfunction prevalence was lower (p\ua0<\ua00.001), while neurological impairment was more frequent (p\ua0=\ua00.001) in the\ua0<10\ua0% ADAMTS13 activity group (n\ua0=\ua0109), confirming previous literature findings. When taken neurological manifestations singularly, epilepsy (p\ua0=\ua00.04), focal motor deficit (p\ua0<\ua00.001) and cranial nerve palsy (p\ua0=\ua00.007) were more frequent in the\ua0<10\ua0% activity group. In our case series, a\ua0<10\ua0% ADAMTS13 activity depicts a group of patients with clinical features similar to TTP patients. Focal motor impairment or epileptic manifestations could further address toward a TTP diagnosis. Studies about treatment efficacy and follow-up are advised to determine whether laboratory findings can guide therapeutic decisions

Characterization of a novel complex BRAF mutation in a follicular variant papillary thyroid carcinoma

Introduction: Activating mutations of the BRAF oncogene are frequently detected in papillary thyroid carcinoma (PTC) and have been associated with a worse prognosis. The amino acid substitution V600E accounts for 90% of all oncogenic BRAF mutations and is typically detected in classic PTCs, whereas other less frequent BRAF mutations seem to be associated with other PTC histotypes. Case: Screening for activating BRAF mutations in a series of 83 PTCs identified the most common V600E mutation in 39 cases (histologically, 38 classic PTCs and I sclerosing variant PTC) and a complex in-frame mutation involving amino acids V600-S605 in a stage III multicentric follicular variant PTC, occurring in a 50-year-old female patient, who was affected by hypothyroidism in autoimmune thyroiditis and had a family history of PTC and autoimmune thyroiditis. Since the identified BRAF mutation was novel in the literature, bioinformatic modeling was performed to predict its impact on BRAF activity. Although the mutation resulted in loss of a phosphorylation site in the activation loop of BRAF, it was predicted to increase BRAF kinase activity by mimicking an activating phosphorylation. Conclusions: This study, which reports a new BRAF mutation, highlights the usefulness of bioinformatic modeling in the prediction of functional effects of new mutations and indicates that mutation-specific screening tests might miss some rare BRAF mutations. These facts should be taken into consideration in the molecular diagnosis of thyroid cancer and in the design of therapeutic protocols based on inhibitors of the BRAF pathway

Viral load of EBV DNAemia is a predictor of EBV-related post-transplant lymphoproliferative disorders in pediatric renal transplant recipients

BACKGROUND: Post-transplant lymphoproliferative disorder (PTLD) is a severe complication of solid organ transplantation that can be classified into two major subtypes, namely, early lesions and non-early lesions, based on histopathological findings. In the vast majority of cases, proliferating cells are B lymphocytes and, most frequently, proliferation is induced by Epstein-Barr virus (EBV) infection. METHODS: The aim of our study was to evaluate the natural history of EBV infection and its possible evolution toward PTLD in a pediatric cohort of patients who received a renal transplant between January 2000 and December 2013. A total of 304 patients were evaluated for this study, of whom 103 tested seronegative for EBV at transplantation. RESULTS: Following transplantation, 50 of the 103 seronegative patients (48.5%) developed a first EBV infection, based on the results of PCR assays for EBV DNA, with 19 of these patients ultimately reverting to the negative state (<3000 copies/μl). Among the 201 seropositive patients only 40 (19.9%) presented a reactivation of EBV. Non-early lesions PTLD was diagnosed in ten patients, and early lesions PTLD was diagnosed in five patients. In all cases a positive EBV viral load had been detected at some stage of the follow-up. Having a maximum peak of EBV viral load above the median value observed in the whole cohort (59,909.5 copies/μl) was a significant and independent predictor of non-early lesions PTLD and all PTLD onset. CONCLUSIONS: A high PCR EBV viral load is correlated with the probability of developing PTLD. The definition of a reliable marker is essential to identify patients more at risk of PTLD and to personalize the clinical approach to the single patient

Early start of seasonal transmission and co-circulation of West Nile virus lineage 2 and a newly introduced lineage 1 strain, northern Italy, June 2022

In spring 2022, Europe faced an unprecedented heat -wave, increasing the risk of West Nile virus (WNV) out-breaks. As early as 7 June 2022, WNV was detected in Culex mosquitoes in northern Italy, and -in the following days -in two blood donors, a patient with encephalitis, wild birds and additional mosquito pools. Genome sequencing demonstrated co-circulation of WNV lineage 2 and a newly introduced WNV lineage 1, which was discovered in the region in 2021