Resistance Patterns, mcr-4 and OXA-48 Genes, and Virulence Factors of Escherichia coli from Apennine Chamois Living in Sympatry with Domestic Species, Italy

The aim of this study was to determine and characterize potential resistance mechanisms against selected Critically Important Antibiotics in Escherichia coli isolates collected from wild and domestic ruminants living in the Maiella National Park, in Central Italy. A total of 38 isolates were obtained from red deer, Apennine chamois, cattle, sheep, and goats grazing in lands with different levels of anthropic pressure. Antimicrobial susceptibility was determined by Minimal Inhibitory Concentration testing, showing phenotypic resistance to colistin, meropenem, or ceftazidime in 9 isolates along with one bacterial strain being resistant to three of the tested antibiotics. In addition, the biomolecular assays allowed the amplification of the genes conferring the colistin (mcr-4), the carbapenems (OXA-48), penicillins and cephalosporins (TEM, SHV, CMY-1, CMY-2) resistance. In order to describe the potential pathogenicity of isolates under study, virulence genes related to Shiga toxin-producing (STEC) and enteropathogenic (EPEC) pathovars were identified. This study is the first report of mcr-4 and OXA-48 genes in resistant E. coli harboring virulence genes in Italian wildlife, with special regard to Apennine chamois and red deer species. The multidisciplinary approach used in this study can improve the early detection of emerging antibiotic resistance determinants in human-animal-environment interfaces by means of wildlife monitoring

THE MANAGEMENT OF THE DOMESTIC REFRIGERATION: HYGIENIC AND SANITARY CHARACTERISTICS OF REFRIGERATORS FROM NORTHEN AND CENTRAL ITALY

This study aimed to provide information on the consumer management of refrigerated food. N° 469 interviews were carried out and the results obtained were subjected to descriptive statistical analysis and further processed with the Multiple Correspondence Analysis and Cluster Analysis. Five homogeneous groups were obtained. In each of them a significant number of refrigerators (60) were tested to assess the temperature and the microbiological status (TVC, Enterobacteriaceae, Salmonella spp. and Listeria spp.). Listeria monocytogenes and Salmonella spp. were not recovered; Listeria innocua was recovered (3.3%). Regarding the TVC values, the 30% of the tested refrigerators was classified as not appropriate (28.3%) or not acceptable (1.7%). Consumer education should be focused in order to reduce foodborne disease. Only safety-conscious consumers can become active partners within the food safety chain

Potential clinical implications of CD4+CD26high T cells for nivolumab treated melanoma patients

Background Nivolumab is an anti-PD1 antibody that has dramatically improved metastatic melanoma patients’ outcomes. Nevertheless, many patients are resistant to PD-1 inhibition, occasionally experiencing severe of-target immune toxicity. In addition, no robust and reproducible biomarkers have yet been validated to identify the correct selection of patients who will beneft from anti-PD-1 treatment avoiding unwanted side efects. However, the strength of CD26 expression on CD4+ T lymphocytes permits the characterization of three subtypes with variable degrees of responsiveness to tumors, suggesting that the presence of CD26-expressing T cells in patients might be a marker of responsiveness to PD-1-based therapies. Methods The frequency distribution of peripheral blood CD26-expressing cells was investigated employing multiparametric fow cytometry in 69 metastatic melanoma patients along with clinical characteristics and blood count parameters at baseline (W0) and compared to 20 age- and sex-matched healthy controls. Percentages of baseline CD4+CD26high T cells were correlated with the outcome after nivolumab treatment. In addition, the frequency of CD4+CD26high T cells at W0 was compared with those obtained after 12 weeks (W1) of therapy in a sub-cohort of 33 patients. Results Circulating CD4+CD26high T cells were signifcantly reduced in melanoma patients compared to healthy subjects (p=0.001). In addition, a signifcant association was observed between a low baseline percentage of CD4+CD26high T cells (<7.3%) and clinical outcomes, measured as overall survival (p=0.010) and progression-free survival (p=0.014). Moreover, patients with clinical beneft from nivolumab therapy had signifcantly higher frequencies of circulating CD4+CD26high T cells than patients with non-clinical beneft (p=0.004) at 12 months. Also, a higher pre-treatment proportion of circulating CD4+CD26high T cells was correlated with Disease Control Rate (p=0.014) and best Overall Response Rate (p=0.009) at 12 months. Interestingly, after 12 weeks (W1) of nivolumab treatment, percentages of CD4+CD26high T cells were signifcantly higher in comparison with the frequencies measured at W0 (p<0.0001), aligning the cell counts with the ranges seen in the blood of healthy subjects

THE MANAGEMENT OF THE DOMESTIC REFRIGERATION: HYGIENIC AND SANITARY CHARACTERISTICS OF REFRIGERATORS FROM NORTHEN AND CENTRAL ITALY

This study aimed to provide information on the consumer management of refrigerated food. N° 469 interviews were carried out and the results obtained were subjected to descriptive statistical analysis and further processed with the Multiple Correspondence Analysis and Cluster Analysis. Five homogeneous groups were obtained. In each of them a significant number of refrigerators (60) were tested to assess the temperature and the microbiological status (TVC, Enterobacteriaceae, Salmonella spp. and Listeria spp.). Listeria monocytogenes and Salmonella spp. were not recovered; Listeria innocua was recovered (3.3%). Regarding the TVC values, the 30% of the tested refrigerators was classified as not appropriate (28.3%) or not acceptable (1.7%). Consumer education should be focused in order to reduce foodborne disease. Only safety-conscious consumers can become active partners within the food safety chain

baseline predictive factors for efficacy of anti pd1 used in first line in melanoma patients an italian melanoma intergroup study

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Immune checkpoint inhibitor associated vitiligo and its impact on survival in patients with metastatic melanoma: an Italian Melanoma Intergroup study

Background: Checkpoint inhibitors in melanoma can lead to self-immune side-effects such as vitiligo-like depigmentation (VLD). Beyond the reported association with favorable prognosis, there are limited data regarding VLD patient features and their echo on the therapeutic outcomes. Methods: To assess the association between VLD and a series of clinical and biological features as well as therapeutic outcomes, we built an observational cohort study by recruiting patients who developed VLD during checkpoint inhibitors. Results: A total of 148 patients from 15 centers (101 men, median age 66 years, BRAF mutated 23%, M1c 42%, Eastern Cooperative Oncology Group (ECOG) status 0/1 99%, normal lactate dehydrogenase 74%) were enrolled. VLD was induced by ipilimumab, programmed cell death-1 (PD-1) inhibitors, and their combination in 32%, 56%, and 12%, respectively. The median onset was 26 weeks and it was associated with other skin and nonskin toxicities in 27% and 28%, respectively. After 3 years of VLD onset, 52% (95% confidence interval 39% to 63%) were progression free and 82% (95% confidence interval 70% to 89%) were still alive. The overall response rate was 73% with 26% complete response. Univariable analysis indicated that BRAF V600 mutation was associated with a better overall survival (P = 0.028), while in multivariable analysis a longer progression-free survival was associated with BRAF V600 (P = 0.093), female sex (P = 0.008), and M stage other than 1a (P = 0.024). When VLD occurred, there was a significant decrease of white blood cell (WBC) count (P = 0.05) and derived WBC-to-lymphocytes ratio (dWLR; P = 0.003). A lower monocyte count (P = 0.02) and dWLR (P = 0.01) were also reported in responder patients. Conclusions: Among VLD population, some features might help to identify patients with an effective response to immunotherapy, allowing clinicians to make more appropriate choices in terms of therapeutic options and duration

Safety of extended interval dosing immune checkpoint inhibitors: a multicenter cohort study

BACKGROUND: Real-life spectrum and survival implications of immune-related adverse events (irAEs) in patients treated with extended interval dosing (ED) immune checkpoint inhibitors (ICIs) are unknown. METHODS: Characteristics of 812 consecutive solid cancer patients who received at least 1 cycle of ED monotherapy (pembrolizumab 400 mg Q6W or nivolumab 480 mg Q4W) after switching from canonical interval dosing (CD; pembrolizumab 200 mg Q3W or nivolumab 240 mg Q2W) or treated upfront with ED were retrieved. The primary objective was to compare irAEs patterns within the same population (before and after switch to ED). irAEs spectrum in patients treated upfront with ED and association between irAEs and overall survival were also described. RESULTS: A total of 550 (68%) patients started ICIs with CD and switched to ED. During CD, 225 (41%) patients developed any grade and 17 (3%) G3 or G4 irAEs; after switching to ED, any grade and G3 or G4 irAEs were experienced by 155 (36%) and 20 (5%) patients. Switching to ED was associated with a lower probability of any grade irAEs (adjusted odds ratio [aOR] = 0.83, 95% confidence interval [CI] = 0.64 to 0.99; P = .047), whereas no difference for G3 or G4 events was noted (aOR = 1.55, 95% CI = 0.81 to 2.94; P = .18). Among patients who started upfront with ED (n = 232, 32%), 107 (41%) developed any grade and 14 (5%) G3 or G4 irAEs during ED. Patients with irAEs during ED had improved overall survival (adjusted hazard ratio [aHR] = 0.53, 95% CI = 0.34 to 0.82; P = .004 after switching; aHR = 0.57, 95% CI = 0.35 to 0.93; P = .025 upfront). CONCLUSIONS: Switching ICI treatment from CD and ED did not increase the incidence of irAEs and represents a safe option also outside clinical trials