Marche Polytechnic University

About: Marche Polytechnic University is a education organization based out in Ancona, Italy. It is known for research contribution in the topics: Population & Cancer. The organization has 5905 authors who have published 15769 publications receiving 382286 citations. The organization is also known as: Universitá Politecnica delle Marche & Universita Politecnica delle Marche.

Panitumumab versus cetuximab in patients with chemotherapy-refractory wild-type KRAS exon 2 metastatic colorectal cancer (ASPECCT): a randomised, multicentre, open-label, non-inferiority phase 3 study.

Abstract: Summary Background The anti-EGFR monoclonal antibodies panitumumab and cetuximab are effective in patients with chemotherapy-refractory wild-type KRAS exon 2 metastatic colorectal cancer. We assessed the efficacy and toxicity of panitumumab versus cetuximab in these patients. Methods For this randomised, open-label, phase 3 head-to-head study, we enrolled patients (from centres in North America, South America, Europe, Asia, Africa, and Australia) aged 18 years or older with chemotherapy-refractory metastatic colorectal cancer, an Eastern Cooperative Oncology Group (ECOG) performance status of 2 or less, and wild-type KRAS exon 2 status. Using a computer-generated randomisation sequence, we assigned patients (1:1; stratified by geographical region and ECOG performance status, with a permuted block method) to receive panitumumab (6 mg/kg once every 2 weeks) or cetuximab (initial dose 400 mg/m 2 ; 250 mg/m 2 once a week thereafter). The primary endpoint was overall survival assessed for non-inferiority (retention of ≥50% of the cetuximab treatment effect; historical hazard ratio [HR] for cetuximab plus best supportive care vs best supportive care alone of 0·55). The primary analysis included patients who received one or more dose of panitumumab or cetuximab, analysed per allocated treatment. Recruitment for this trial is closed. The trial is registered with ClinicalTrials.gov, number NCT01001377. Findings Between Feb 2, 2010, and July 19, 2012, we enrolled and randomly allocated 1010 patients, 999 of whom began study treatment: 499 received panitumumab and 500 received cetuximab. For the primary analysis of overall survival, panitumumab was non-inferior to cetuximab ( Z score −3·19; p=0·0007). Median overall survival was 10·4 months (95% CI 9·4–11·6) with panitumumab and 10·0 months (9·3–11·0) with cetuximab (HR 0·97; 95% CI 0·84–1·11). Panitumumab retained 105·7% (81·9–129·5) of the effect of cetuximab on overall survival seen in this study. The incidence of adverse events of any grade and grade 3–4 was similar across treatment groups. Grade 3–4 skin toxicity occurred in 62 (13%) patients given panitumumab and 48 (10%) patients given cetuximab. The occurrence of grade 3–4 infusion reactions was lower with panitumumab than with cetuximab (one [ vs nine [2%] patients), and the occurrence of grade 3–4 hypomagnesaemia was higher in the panitumumab group (35 [7%] vs 13 [3%]). We recorded one treatment-related fatal adverse event: a lung infection in a patient given cetuximab. Interpretation Our findings show that panitumumab is non-inferior to cetuximab and that these agents provide similar overall survival benefit in this population of patients. Both agents had toxicity profiles that were to be expected. In view of the consistency in efficacy and toxicity seen, small but meaningful differences in the rate of grade 3–4 infusion reactions and differences in dose scheduling can guide physician choice of anti-EGFR treatment. Funding Amgen Inc.

Transdifferentiation properties of adipocytes in the adipose organ

Abstract: Mammals have two types of adipocytes, white and brown, but their anatomy and physiology is different. White adipocytes store lipids, and brown adipocytes burn them to produce heat. Previous descriptions implied their localization in distinct sites, but we demonstrated that they are mixed in many depots, raising the concept of adipose organ. We explain the reason for their cohabitation with the hypothesis of reversible physiological transdifferentiation; they are able to convert one into each other. If needed, the brown component of the organ could increase at the expense of the white component and vice versa. This plasticity is important because the brown phenotype of the organ associates with resistance to obesity and related disorders. Another example of physiological transdifferetiation of adipocytes is offered by the mammary gland; the pregnancy hormonal stimuli seems to trigger a reversible transdifferentiation of adipocytes into milk-secreting epithelial glands. The obese adipose organ is infiltrated by macrophages inducing chronic inflamation that is widely considered as a causative factor for insulin resistance. We showed that the vast majority of macrophages infiltrating the obese organ are arranged around dead adipocytes, forming characteristic crown-like structures. We recently found that visceral fat is more infiltrated than the subcutaneous fat despite a smaller size of visceral adipocytes. This suggests a different susceptibility of visceral and subcutaneous adipocytes to death, raising the concept of smaller critical death size that could be important to explain the key role of visceral fat for the metabolic disorders associated with obesity.

Deep-Sea Biodiversity in the Mediterranean Sea: The Known, the Unknown, and the Unknowable

Abstract: Deep-sea ecosystems represent the largest biome of the global biosphere, but knowledge of their biodiversity is still scant. The Mediterranean basin has been proposed as a hot spot of terrestrial and coastal marine biodiversity but has been supposed to be impoverished of deep-sea species richness. We summarized all available information on benthic biodiversity (Prokaryotes, Foraminifera, Meiofauna, Macrofauna, and Megafauna) in different deepsea ecosystems of the Mediterranean Sea (200 to more than 4,000 m depth), including open slopes, deep basins, canyons, cold seeps, seamounts, deep-water corals and deep-hypersaline anoxic basins and analyzed overall longitudinal and bathymetric patterns. We show that in contrast to what was expected from the sharp decrease in organic carbon fluxes and reduced faunal abundance, the deep-sea biodiversity of both the eastern and the western basins of the Mediterranean Sea is similarly high. All of the biodiversity components, except Bacteria and Archaea, displayed a decreasing pattern with increasing water depth, but to a different extent for each component. Unlike patterns observed for faunal abundance, highest negative values of the slopes of the biodiversity patterns were observed for Meiofauna, followed by Macrofauna and Megafauna. Comparison of the biodiversity associated with open slopes, deep basins, canyons, and deep-water corals showed that the deep basins were the least diverse. Rarefaction curves allowed us to estimate the expected number of species for each benthic component in different bathymetric ranges. A large fraction of exclusive species was associated with each specific habitat or ecosystem. Thus, each deep-sea ecosystem contributes significantly to overall biodiversity. From theoretical extrapolations we estimate that the overall deep-sea Mediterranean biodiversity (excluding prokaryotes) reaches approximately 2805 species of which about 66% is still undiscovered. Among the biotic components investigated (Prokaryotes excluded), most of the unknown species are within the phylum Nematoda, followed by Foraminifera, but an important fraction of macrofaunal and megafaunal species also remains unknown. Data reported here provide new insights into the patterns of biodiversity in the deep-sea Mediterranean and new clues for future investigations aimed at identifying the factors controlling and threatening deep-sea biodiversity.

Preliminary criteria for the very early diagnosis of systemic sclerosis: results of a Delphi Consensus Study from EULAR Scleroderma Trials and Research Group

Abstract: Objective: To identify a core set of preliminary items considered as important for the very early diagnosis of systemic sclerosis (SSc). Methods: A list of items provided by European League Against Rheumatism (EULAR) Scleroderma Trial and Research(EUSTAR) centres were subjected to a Delphi exercise among 110 experts in the field of SSc. In round 1, experts were asked to choose the items they considered as the most important for the very early diagnosis of SSc. In round 2, experts were asked to reconsider the items accepted after the first stage. In round 3, the clinical relevance of selected items and their importance as measures that would lead to an early referral process were rated using appropriateness scores. Results: Physicians from 85 EUSTAR centres participated in the study and provided an initial list of 121 items. After three Delphi rounds, the steering committee, with input from external experts, collapsed the 121 items into three domains containing seven items, developed as follows: skin domain (puffy fingers/puffy swollen digits turning into sclerodactily);vascular domain (Raynaud's phenomenon, abnormal capillaroscopy with scleroderma pattern) and laboratory domain (antinuclear, anticentromere and antitopoisomerase-I antibodies). Finally, the whole assembly of EUSTAR centres ratified with a majority vote the results in a final face-to-face meeting. Conclusion: The three Delphi rounds allowed us to identify the items considered by experts as necessary for the very early diagnosis of SSc. The validation of these items to establish diagnostic criteria is currently ongoing in a prospective observational cohort.