Everolimus plus aromatase inhibitors vs aromatase inhibitors as maintenance therapy after first-line chemotherapy in HR+/HER2- metastatic breast cancer: Final results of the phase III randomized MAIN-A trial

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Brodalumab for the treatment of plaque psoriasis in a real-life setting: a 3 years multicenter retrospective study—IL PSO (Italian landscape psoriasis)

Introduction: Brodalumab is a monoclonal antibody that targets the subunit A of the interleukin-17A receptor (IL17RA), inhibiting the signaling of various isoforms of the IL-17 family. It has been approved for the treatment of moderate-to-severe plaque psoriasis after being evaluated in three Phase-3 trials. However, long-term data on brodalumab in a real-life setting are still limited

Genetic determinants in a critical domain of ns5a correlate with hepatocellular carcinoma in cirrhotic patients infected with hcv genotype 1b

HCV is an important cause of hepatocellular carcinoma (HCC). HCV NS5A domain‐1 interacts with cellular proteins inducing pro‐oncogenic pathways. Thus, we explore genetic variations in NS5A domain‐1 and their association with HCC, by analyzing 188 NS5A sequences from HCV genotype‐1b infected DAA‐naïve cirrhotic patients: 34 with HCC and 154 without HCC. Specific NS5A mutations significantly correlate with HCC: S3T (8.8% vs. 1.3%, p = 0.01), T122M (8.8% vs. 0.0%, p < 0.001), M133I (20.6% vs. 3.9%, p < 0.001), and Q181E (11.8% vs. 0.6%, p < 0.001). By multivariable analysis, the presence of >1 of them independently correlates with HCC (OR (95%CI): 21.8 (5.7–82.3); p < 0.001). Focusing on HCC‐group, the presence of these mutations correlates with higher viremia (median (IQR): 5.7 (5.4–6.2) log IU/mL vs. 5.3 (4.4–5.6) log IU/mL, p = 0.02) and lower ALT (35 (30–71) vs. 83 (48–108) U/L, p = 0.004), suggesting a role in enhancing viral fitness without affecting necroinflammation. Notably, these mutations reside in NS5A regions known to interact with cellular proteins crucial for cell‐cycle regulation (p53, p85‐PIK3, and β‐ catenin), and introduce additional phosphorylation sites, a phenomenon known to ameliorate NS5A interaction with cellular proteins. Overall, these results provide a focus for further investigations on molecular bases of HCV‐mediated oncogenesis. The role of these NS5A domain‐1 mutations in triggering pro‐oncogenic stimuli that can persist also despite achievement of sustained virological response deserves further investigation

The rapid spread of SARS-COV-2 Omicron variant in Italy reflected early through wastewater surveillance

The SARS-CoV-2 Omicron variant emerged in South Africa in November 2021, and has later been identified worldwide, raising serious concerns. A real-time RT-PCR assay was designed for the rapid screening of the Omicron variant, targeting characteristic mutations of the spike gene. The assay was used to test 737 sewage samples collected throughout Italy (19/21 Regions) between 11 November and 25 December 2021, with the aim of assessing the spread of the Omicron variant in the country. Positive samples were also tested with a real-time RT-PCR developed by the European Commission, Joint Research Centre (JRC), and through nested RT-PCR followed by Sanger sequencing. Overall, 115 samples tested positive for Omicron SARS-CoV-2 variant. The first occurrence was detected on 7 December, in Veneto, North Italy. Later on, the variant spread extremely fast in three weeks, with prevalence of positive wastewater samples rising from 1.0% (1/104 samples) in the week 5-11 December, to 17.5% (25/143 samples) in the week 12-18, to 65.9% (89/135 samples) in the week 19-25, in line with the increase in cases of infection with the Omicron variant observed during December in Italy. Similarly, the number of Regions/Autonomous Provinces in which the variant was detected increased from one in the first week, to 11 in the second, and to 17 in the last one. The presence of the Omicron variant was confirmed by the JRC real-time RT-PCR in 79.1% (91/115) of the positive samples, and by Sanger sequencing in 66% (64/97) of PCR amplicons. In conclusion, we designed an RT-qPCR assay capable to detect the Omicron variant, which can be successfully used for the purpose of wastewater-based epidemiology. We also described the history of the introduction and diffusion of the Omicron variant in the Italian population and territory, confirming the effectiveness of sewage monitoring as a powerful surveillance tool

A New Classification of Diabetic Gait Pattern Based on Cluster Analysis of Biomechanical Data

Background The diabetic foot, one of the most serious complications of diabetes mellitus and a major risk factor for plantar ulceration, is determined mainly by peripheral neuropathy. Neuropathic patients exhibit decreased stability while standing as well as during dynamic conditions. A new methodology for diabetic gait pattern classification based on cluster analysis has been proposed that aims to identify groups of subjects with similar patterns of gait and verify if three-dimensional gait data are able to distinguish diabetic gait patterns from one of the control subjects. Method The gait of 20 nondiabetic individuals and 46 diabetes patients with and without peripheral neuropathy was analyzed [mean age 59.0 (2.9) and 61.1(4.4) years, mean body mass index (BMI) 24.0 (2.8), and 26.3 (2.0)]. K-means cluster analysis was applied to classify the subjects' gait patterns through the analysis of their ground reaction forces, joints and segments (trunk, hip, knee, ankle) angles, and moments. Results Cluster analysis classification led to definition of four well-separated clusters: one aggregating just neuropathic subjects, one aggregating both neuropathics and non-neuropathics, one including only diabetes patients, and one including either controls or diabetic and neuropathic subjects. Conclusions Cluster analysis was useful in grouping subjects with similar gait patterns and provided evidence that there were subgroups that might otherwise not be observed if a group ensemble was presented for any specific variable. In particular, we observed the presence of neuropathic subjects with a gait similar to the controls and diabetes patients with a long disease duration with a gait as altered as the neuropathic one

EMG analysis across different tasks improves prevention screenings in diabetes: a cluster analysis approach

The aim of this work was twofold: on one side to determine the most suitable parameters of surface electromyography (sEMG) to classify diabetic subjects with and without neuropathy and discriminate them from healthy controls and second to assess the role of the task acquired in the classification process. For this purpose 30 subjects were examined (10 controls, 10 diabetics with and 10 without neuropathy) whilst walking and stair ascending and descending. The electrical activity of six muscles was recorded bilaterally through a 16-channel sEMG system synchronised with a stereophotogrammetric system: Rectus Femoris, Gluteus Medius, Tibialis Anterior, Peroneus Longus, Gastrocnemius Lateralis and Extensor Digitorum. Spatiotemporal parameters of gait and stair climbing and the following sEMG parameters were extracted: signal envelope, activity duration, timing of activation and deactivation. A hierarchical clustering algorithm was applied to the whole set of parameters with different distances and linkage methods. Results showed that only by applying the Ward agglomerative hierarchical clustering (Hamming distance) to the all set of parameters extracted from both tasks, 5 well-separated clusters were obtained: cluster 3 included only DS subjects, cluster 2 and 4 only controls and cluster 1 and 5 only DNS subjects. This method could be used for planning rehabilitation treatments