More atypical than atypical Alzheimer's disease phenotypes: a Treviso Dementia (TREDEM) registry case report

Background: A 57-year-old right-handed man was admitted to the Treviso Memory Clinic due to the presence of memory forgetfulness, repetition of the same questions, episodes of confusion, initial difficulties in performing complex tasks and easy distraction over the past two years, as well as recurrent and never-happened-before car accidents.Objective: We report a peculiar case of an early onset Alzheimer's disease (AD) with an unusual symptomatology, apparently not fitting in any of the categorized atypical forms of AD nor being representative of a typical amnestic AD.Methods: The patient underwent a neuropsychological, structural, and metabolic cerebral evaluation by MRI and F-18-FDG PET, together with the search for cerebral amyloid (amyloid PET), a genetic testing for dementia related genes and the dosage of CSF protein biomarkers of neurodegenerative conditions.Results: We observed a convergence of predominant frontal (dysexecutive, verbal disinhibition) and posterior (visuospatial) features of cognitive impairment. Structural MRI sequences showed subarachnoid spaces of the vault enlarged in the frontoparietal region with anterior and posterior cortical atrophy. The hippocampus appeared preserved. The 18F-FDG PET scans showed hypometabolism in the prefrontal, lateral temporal, posterior parietal, and occipital regions bilaterally. The F-18-Flutemetamol scan showed a diffused uptake of the amyloid tracer at the cerebral cortex. CSF biomarkers were compatible with Alzheimer's disease (AD).Conclusion: This case report presented with clinical phenotypic aspects atypical of AD, both frontal and posterior, never described as concomitant in the most accredited criteria for atypical AD, and appeared therefore more atypical than each of the atypical AD phenotypes already reported

Rip current evidence by hydrodynamic simulations, bathymetric surveys and UAV observation

Abstract. The prediction of the formation, spacing and location of rip currents is a scientific challenge that can be achieved by means of different complementary methods. In this paper the analysis of numerical and experimental data, including RPAS (remotely piloted aircraft systems) observations, allowed us to detect the presence of rip currents and rip channels at the mouth of Sele River, in the Gulf of Salerno, southern Italy. The dataset used to analyze these phenomena consisted of two different bathymetric surveys, a detailed sediment analysis and a set of high-resolution wave numerical simulations, completed with Google EarthTM images and RPAS observations. The grain size trend analysis and the numerical simulations allowed us to identify the rip current occurrence, forced by topographically constrained channels incised on the seabed, which were compared with observations

Geomorphology of Naples and the Campi Flegrei: human and natural landscapes in a restless land

Naples and its surroundings are a very young landscape, originated from 40 ka in response to strong and explosive volcanic processes, which created the Campi Flegrei, one of the largest volcanic fields of the world. Despite the repeated and continuous volcanic activity, this territory was selected for human settlements since Neolithic times and hosted some of the most important Greek and Roman towns in the Mediterranean area (e.g., Cuma, Parthenope, Neapolis, Baia and Puteoli). Geoarcheological data and historical chronicles testify to human coexistence with eruptions, bradyseismic ground motions, coastline changes, floods and landslides. With the aim of describing the geomorphological evolution of this area to a wide audience, including also non-experts, we constructed a synthetic geomorphological map of the area and sketches that synthesise the main stages of the geomorphological evolution of the historical centre of Naples and the coastal belt of the Gulf of Pozzuoli during the last millennia

Seroprevalence of group B Coxsackieviruses: retrospective study in an Italian population

Purpose Group B Coxsackieviruses (CVB) include 6 serotypes (B1‐6) responsible for a wide range of clinical diseases. Since no recent seroepidemiologic data are available in Italy, the study aim was to investigate CVB seroprevalence in a wide Italian population. Methods The study retrospectively included 2,459 subjects referring to a large academic hospital in Rome (Italy) in the period 2004‐2016. Seroprevalence rates and neutralizing antibodies (nAb) titers were evaluated in relation to years of observation and subjects’ characteristics. Results Positivity for at least one serotype was detected in 69.1% of individuals. Overall, the prevalent serotype was B4, followed by B3 (33.3%), B5 (26.2%), B1 (12.7%), B2 (11.0%), and B6 (1.7%). For B2, a significant decrease in seroprevalence over years was observed. Positivity to at least one virus was 25.2% in children aged 0‐2 years, but significantly increased in pre‐school (3‐5 yr) (50.3%) and school (6‐10 yr) children (70.4%). Higher nAb responses for B3 and B4 were observed in children aged 3‐5 years. Conclusion A high overall CVB prevalence was found. Type‐specific variations in prevalence over time probably reflect the fluctuations in circulation typical of Enteroviruses. Children are at greater risk for CVB infection given the high number of seronegative subjects aged 0‐10 years

Circulating methylated DNA to monitor the dynamics of RAS mutation clearance in plasma from metastatic colorectal cancer patients

The clearance of RAS mutations in plasma circulating tumor DNA (ctDNA) from originally RAS-mutant metastatic colorectal cancer (mCRC) has been recently demonstrated. Clinical trials investigating whether RAS mutant mCRC who “convert” to wild-type in plasma might benefit from EGFR blockade are ongoing. Detection of tumor-specific DNA methylation alterations in ctDNA has been suggested as a specific tool to confirm the tumoral origin of cell-free DNA. We monitored RAS clearance in plasma from patients with RAS-mutant mCRC at baseline (pre-treatment) (T0); after 4 months of first-line therapy (T1); at the time of first (T2) and second (T3) progression. A five-gene methylation panel was used to confirm the presence of ctDNA in samples in which RAS mutation clearance was detected. At T1 ctDNA analysis revealed wild-type RAS status in 83% of samples, all not methylated, suggesting at this time point the lack of ctDNA shedding. At T2 ctDNA analysis revealed wild-type RAS status in 83% of samples, of which 62.5% were found methylated. At T3 50% of wild-type-RAS samples were found methylated. Non-methylated samples were found in patients with lung or brain metastases. This five-gene methylation test might be useful to confirm the presence of ctDNA in RAS wild-type plasma samples

DWI-MR and PET-CT Functional Imaging for Boost Tumor Volume Delineation in Neoadjuvant Rectal Cancer Treatment

BACKGROUND/AIM T2 weighted magnetic resonance (MR) imaging is the gold standard for locally advanced rectal cancer (LARC) staging. The potential benefit of functional imaging, as diffusion-weighted MR (DWI) and positron emission tomography-computed tomography (PET-CT), could be considered for treatment intensification strategies. Dose intensification resulted in better pathological complete response (pCR) rates. This study evaluated the inter-observer agreement between two radiation oncologists, and the difference in gross tumor volume (GTV) delineation in simulation-CT, T2-MR, DWI-MR, and PET-CT in patients with LARC. PATIENTS AND METHODS Two radiation oncologists prospectively delineated GTVs of 24 patients on simul-CT (CT$_{GTV}$), T2-weighted MR (T2$_{GTV}$), echo planar b1000 DWI (DWI$_{GTV}$) and PET-CT (PET$_{GTV}$). Observers' agreement was assessed using Dice index. Kruskal-Wallis test assessed differences between methods. RESULTS Mean CT$_{GTV}$, T2$_{GTV}$, DWI$_{GTV}$, and PET$_{GTV}$ were 41.3±26.9 cc, 25.9±15.2 cc, 21±14.8 cc, and 37.7±27.7 cc for the first observer, and 42.2±27.9 cc, 27.6±16.9 cc, 19.9±14.9cc, and 34.8±24.3 cc for the second observer, respectively. Mean Dice index was 0.85 for CT$_{GTV}$, 0.84 for T2$_{GTV}$, 0.82 for DWI$_{GTV}$, and 0.89 for PET$_{GTV}$, representative of almost perfect agreement. Kruskal-Wallis test showed a statistically significant difference between methods (p=0.009). Dunn test showed there were differences between DWI$_{GTV}$ vs. PET$_{GTV}$ (p=0.040) and DWI$_{GTV}$ vs. CT$_{GTV}$ (p=0.008). CONCLUSION DWI resulted in smaller volume delineation compared to CT, T2-MR, and PET-CT functional images. Almost perfect agreements were reported for each imaging modality between two observers. DWI-MR seems to remain the optimal strategy for boost volume delineation for dose escalation in patients with LARC

HER2/neu expression and hormonal therapy in early breast cancer: can muddy waters become clear?

We have read with great interest the paper by Love et al [1] about the relationship between HER2/neu expression and response to adjuvant endocrine therapy in premenopausal women with breast cancer. Whereas HER2/neu and estrogen receptor (ER) are believed to be important cell survival and cell death factors in human breast cancer, if and how they interact to confer resistance to hormone therapy is still in debate. Several observations are consistent with a major role for c-erbB2 in the development of endocrine resistance, considering also the HER2/neu acquired expression durin

Extraskeletal myxoid chondrosarcoma: a case report with adjuvant intraoperative treatment

Extraskeletal myxoid chondrosarcoma is a rare form of malignant mesenchymal neoplasm mainly localized into the limbs, particularly in the thigh and popliteal fossa. It has been classified as a low-grade sarcoma so far, but it shows a tendency to relapse and metastasize. In the early stage of disease, surgery represents the only chance of cure. In case of diffuse metastatic disease, systemic chemotherapy with anthracyclines is the standard of care. In this paper, we present a case of a patient affected by this rare disease and the analysis of radiological, surgical and histopathological aspects

Genomic landscape and survival analysis of ctDNA “neo-RAS wild-type” patients with originally RAS mutant metastatic colorectal cancer

Background: The term “neo-RAS wild-type” refers to the switch to RAS wild-type disease in plasma circulating tumor DNA (ctDNA) from originally RAS mutant colorectal cancers. Consistently, the hypothesis to re-determine RAS mutational status in ctDNA at disease progression in RAS mutant mCRC opened to a new perspective for clinically-based selection of patients to be treated with EGFR inhibitors. Currently, the genomic landscape of “neo-RAS wild-type” is unknown. This is a prospective study aimed to investigate clinical and genomic features associated with RAS mutation clearance in a large cohort of RAS mutant mCRC patients who converted to RAS wild- type in liquid biopsy at failure of first-line treatments. Secondary aim was to investigate the long term prognostic significance of “true neo-RAS wild- type”. Patients and methods: 70 patients with stage IV RAS mutant colorectal cancer were prospectively enrolled. Plasma samples were collected at progression from first-line treatment. RAS/BRAF mutations in plasma were assessed by RT-PCR. In RAS/BRAF wild-type samples, ctDNA was used to generate libraries using a 17 genes panel whose alteration has clinical relevance. To investigate the prognostic significance of RAS mutation clearance, test curves for PFS and OS were represented by Kaplan-Meier estimator plot and Log-rank test. Results: The most commonly detected actionable mutations in “neo-RAS wild-type” were: PIK3CA (35.7%); RET (11.9%); IDH1 (9.5%); KIT (7%); EGFR (7%); MET (4.7%); ERBB2 (4.7%); FGFR3 (4.7%). Both OS and post-progression survival were longer in patients with “neo-RAS wild-type” compared to those who remained RAS mutant (p<0.001 for both). Conclusions: De-novo-targetable mutations occured in a large percentage of “neo-RAS wild-type”, being PIK3CA the most commonly detected. RAS mutation clearance in ctDNA is associated with long- term improvement of overall survival