ABSTRACT
BACKGROUND: The treatment of patients with brain-spread renal cell carcinoma (RCC) is an unmet clinical need, although more recent therapeutic strategies have significantly improved RCC patients' life expectancy. Our multicenter, retrospective, observational study investigated a real-world cohort of patients with brain metastases (BM) from RCC (BMRCC). PATIENTS AND METHODS: A total of 226 patients with histological diagnosis of RCC and radiological evidence of BM from 22 Italian institutions were enrolled. Univariate and multivariate models were performed to investigate the impact of clinicopathological features and multimodal treatments on both overall survival (OS) from the BM diagnosis and intracranial progression-free survival (iPFS). RESULTS: The median OS from the BM diagnosis was 18.8 months (interquartile range: 6.2-43 months). Multivariate analysis confirmed the following as positive independent prognostic factors: a Karnofsky Performance Status >70% [hazard ratio (HR) = 0.49, 95% confidence interval (CI) 0.26-0.92, P = 0.0026] and a single BM (HR = 0.51, 95% CI 0.31-0.86, P = 0. 0310); in contrast, the following were confirmed as worse prognosis factors: progressive extracranial disease (HR = 1.66, 95% CI 1.003-2.74, P = 0.00181) and only one line of systemic therapy after the BM occurrence (HR = 2.98, 95% CI 1.62-5.49, P = 0.029). Subgroup analyses showed no difference in iPFS according to the type of the first systemic treatment [immunotherapy (IT) or targeted therapy (TT)] carried out after the BM diagnosis (HR = 1.033, 95% CI 0.565-1.889, P = 0.16), and revealed that external radiation therapy (eRT) significantly prolonged iPFS when combined with IT (10.7 months, 95% CI 4.9-48 months, P = 0.0321) and not when combined with TT (9.01 months, 95% CI 2.7-21.2 months, P = 0.59). CONCLUSIONS: Our results suggest a potential additive effect in terms of iPFS for eRT combined with IT and encourage a more intensive multimodal therapeutic strategy in a multidisciplinary context to improve the survival of BMRCC patients.
Subject(s)
Brain Neoplasms , Carcinoma, Renal Cell , Kidney Neoplasms , Humans , Carcinoma, Renal Cell/therapy , Kidney Neoplasms/therapy , Kidney Neoplasms/pathology , Retrospective Studies , Prognosis , Brain Neoplasms/therapy , Brain Neoplasms/secondaryABSTRACT
The objective of this study was to compare the biofilm-forming capabilities of different genotypes of Staphylococcus aureus dairy isolates from Switzerland and northern Italy, including Staph. aureus genotype B (GTB) and methicillin-resistant Staph.aureus (MRSA). We hypothesized that biofilm formation might be more pronounced in the contagious GTB isolates compared with other genotypes affecting individual animals. Twenty-four dairy isolates, including 9 MRSA, were further characterized by genotyping by using ribosomal spacer PCR, spa typing, biofilm formation under static and dynamic conditions, and scanning electron microscopy. The GTB isolates (n = 6) were more able to form biofilms than other genotypes at 37°C and at 20°C after 48 and 72 h of incubation in the static assay using polystyrene microtiter plates. This result was supported by scanning electron micrographs showing a GTB isolate producing strong biofilm with extracellular matrix in contrast to a genotype C isolate. Furthermore, none of the MRSA isolates formed strong biofilms in the static assay. However, some MRSA produced low or moderate amounts of biofilm depending on the applied conditions. Under dynamic conditions, a much more diverse situation was observed. The ability of GTB isolates to be strong biofilm formers was not observed in all cases, emphasizing the importance of growth conditions for the expression of biofilm-related genes. No specific genotype, spa type, or MRSA isolate could be categorized significantly into one level of biofilm formation. Nineteen percent of isolates behaved similarly under static and dynamic conditions. The results of this study expand our knowledge of different dairy-related Staph. aureus subtypes and indicate the benefit of genotyping when biofilms are studied.
Subject(s)
Biofilms , Cheese/microbiology , Milk/microbiology , Staphylococcus aureus/physiology , Animals , Biofilms/growth & development , Cattle , Genotype , Goats , Italy , Methicillin-Resistant Staphylococcus aureus/classification , Methicillin-Resistant Staphylococcus aureus/genetics , Methicillin-Resistant Staphylococcus aureus/isolation & purification , Methicillin-Resistant Staphylococcus aureus/physiology , Polymerase Chain Reaction , Sheep , Staphylococcus aureus/classification , Staphylococcus aureus/genetics , Staphylococcus aureus/isolation & purification , SwitzerlandABSTRACT
Cephalopods are an important source of nutrients and some of the most widely consumed marine foods. However, because of contamination of the oceans and the bioaccumulative nature of toxic metals, these foods may pose a health risk. For this reason, the concentrations of some trace elements (chromium [Cr], lithium, strontium [Sr], copper [Cu], and nickel) and toxic metals (aluminum [Al], cadmium, and lead) were determined in 65 frozen samples of cuttlefish, octopus, common squid, and shortfin squid by inductively coupled plasma optical emission spectrometry to evaluate dietary intake and toxic risk. Sr was the major trace element (3.03 mg/kg) in cuttlefish; however, Cu (1.57 mg/kg) was found in the highest concentration in common squid. Among the toxic metals, Al had the highest concentration (3.09 mg/kg) in common squid. Al can pose an important health risk to individuals with kidney problems and to children because these groups are most vulnerable to the toxic effects. Significant differences among the four cephalopod types were found in the concentrations of most of the metals examined. Taking into account the average consumption of cephalopods, the contribution of toxic metals does not pose a risk to the health of adults.
ABSTRACT
Androgen deprivation therapy (ADT) is the mainstay treatment for advanced prostate cancer (PC). Most patients eventually progress to a condition known as castration-resistant prostate cancer (CRPC), characterized by lack of response to ADT. Although new androgen receptor signaling (ARS) inhibitors and chemotherapeutic agents have been introduced to overcome resistance to ADT, many patients progress because of primary or acquired resistance to these agents. This comprehensive review aims at exploring the mechanisms of resistance and progression of PC, with specific focus on alterations which lead to the activation of androgen receptor (AR)-independent pathways of survival. Our work integrates available clinical and preclinical data on agents which target these pathways, assessing their potential clinical implication in specific settings of patients. Given the rising interest of the scientific community in cancer immunotherapy strategies, further attention is dedicated to the role of immune evasion in PC.
Subject(s)
Androgen Antagonists/therapeutic use , Prostatic Neoplasms, Castration-Resistant/drug therapy , Receptors, Androgen/physiology , Humans , Male , Signal Transduction/drug effectsSubject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Breast Neoplasms/drug therapy , Breast Neoplasms/metabolism , Protein Kinase Inhibitors/therapeutic use , Receptor, ErbB-2/biosynthesis , Aminopyridines/administration & dosage , Benzimidazoles/administration & dosage , Breast Neoplasms/enzymology , Cyclin-Dependent Kinases/antagonists & inhibitors , Estradiol/administration & dosage , Estradiol/analogs & derivatives , Female , Fulvestrant , Humans , Letrozole , Nitriles/administration & dosage , Piperazines/administration & dosage , Protein Kinase Inhibitors/administration & dosage , Purines/administration & dosage , Pyridines/administration & dosage , Randomized Controlled Trials as Topic , Receptors, Estrogen/biosynthesis , Risk Assessment , Triazoles/administration & dosageABSTRACT
BACKGROUND: There are no data regarding the management of advanced soft-tissue sarcoma (STS) in elderly patients. PATIENTS AND METHODS: We retrospectively reviewed the charts of patients ≥75 years old diagnosed with metastatic or unresectable STS between 1991 and 2011 in 11 French and American centers. RESULTS: The study included 361 patients. Of these, 223 patients (62%) received systemic therapy, whereas 123 patients (34%) were managed with best supportive care (BSC) only. Patients who received BSC were more likely to be ≥80 years, with performance status (PS) ≥ 2, Charlson comorbidity score ≥ 10, and metastatic disease. The median progression-free survival of patients treated with systemic therapy was 4 months (95% CI: 2.9-5.1). Thirty-six patients (16%) stopped chemotherapy because of toxicity. Median overall survival (OS) of patients managed with specific therapy was 10.9 months (95% CI: 8.3-13.5) versus 5.3 months (95% CI: 3.6-7.1) for patients managed with BSC (P = 0.001). On multivariate analysis, age ≥ 80 years, PS ≥ 2, and number of metastatic sites were the only independent factors associated with OS. CONCLUSION: A high proportion of elderly patients with advanced STS were denied chemotherapy. Further efforts are needed to define better the optimal care for fit and unfit elderly patients with STS.
Subject(s)
Anthracyclines/therapeutic use , Antineoplastic Agents/therapeutic use , Sarcoma/drug therapy , Soft Tissue Neoplasms/drug therapy , Aged , Aged, 80 and over , Disease-Free Survival , Female , Humans , Kaplan-Meier Estimate , Male , Palliative Care , Retrospective Studies , Sarcoma/mortality , Sarcoma/secondary , Soft Tissue Neoplasms/mortality , Soft Tissue Neoplasms/pathology , Treatment OutcomeABSTRACT
There is increasing concern about the impact on public health of methicillin-resistant Staphylococcus aureus (MRSA) associated with animal food products. MRSA remains a serious problem because of the high incidence and multidrug resistance of the strains, even for strains isolated from foods, food environments and food handlers. The objectives of this study are: (i) to evaluate the susceptibility of S. aureus strains isolated from food, food handlers and food-processing environments to 14 antibiotics currently used in veterinary and human therapy; (ii) to assess the presence of the mecA gene. A total of 1007 samples were collected from food, food handlers, and environments and were analyzed for the presence of S. aureus. S. aureus was present in 165 of the 1007 samples. A total of 157 isolates were methicillin-susceptible S. aureus (MSSA) and 8 isolates were MRSA. In particular, out of 8 MRSA strains detected, 4 strains harboured the mecA gene. All MRSA strains were resistant to at least one of the tested antibiotics and 6 strains demonstrated multi-resistance. Considering the high level of resistances in S. aureus and the isolation of MRSA strains, the surveillance of antimicrobial resistance and the spreading of this pathogen is of crucial importance in the food production chain. These data are useful in improving background data on antimicrobial resistance of S. aureus isolated from food, processing environments and food handlers, supporting the prudent use of antibiotics and the development of international control programs.
Subject(s)
Anti-Bacterial Agents/pharmacology , Food Industry , Food Microbiology , Methicillin-Resistant Staphylococcus aureus/drug effects , Drug Resistance, Bacterial , HumansABSTRACT
Any bacterial strain to be used as starter culture should have suitable characteristics, including a lack of amino acid decarboxylase activity. In this study, the decarboxylase activity of 76 bacterial strains, including lactic acid bacteria and gram-positive, catalase-positive cocci, was investigated. These strains were previously isolated from European traditional fermented sausages to develop autochthonous starter cultures. Of all the strains tested, 48% of the lactic acid bacteria strains and 13% of gram-positive, catalase-positive cocci decarboxylated one or more amino acids. Aminogenic potential was strain dependent, although some species had a higher proportion of aminogenic strains than did others. Thus, all Lactobacillus curvatus strains and 70% of Lactobacillus brevis strains had the capacity to produce tyramine and beta-phenylethylamine. Some strains also produced other aromatic amines, such as tryptamine and the diamines putrescine and cadaverine. All the enterococcal strains tested were decarboxylase positive, producing high amounts of tyramine and considerable amounts of beta-phenylethylamine. None of the staphylococcal strains had tyrosine-decarboxylase activity, but some produced other amines. From the aminogenic point of view, Lactobacillus plantarum, Lactobacillus sakei, and Staphylococcus xylosus strains would be the most suitable for use as autochthonous starter cultures for traditional fermented sausages.
Subject(s)
Aromatic-L-Amino-Acid Decarboxylases/metabolism , Consumer Product Safety , Food Handling/methods , Food Microbiology , Meat Products/microbiology , Amino Acids/analysis , Amino Acids/biosynthesis , Animals , Biogenic Amines/analysis , Biogenic Amines/biosynthesis , Colony Count, Microbial , Enterobacteriaceae/enzymology , Enterobacteriaceae/metabolism , Fermentation , Humans , Lactobacillus/enzymology , Lactobacillus/metabolism , Staphylococcus/enzymology , Staphylococcus/metabolism , Swine , Tyramine/analysis , Tyramine/biosynthesisSubject(s)
Food Irradiation , Lipids/chemistry , Meat Products/analysis , Meat Products/radiation effects , Adipose Tissue , Animals , Italy , SwineABSTRACT
Microbial ecosystems were surveyed in 314 environmental samples from 54 Southern and Eastern European small-scale processing units (PUs) manufacturing traditional dry fermented sausages. The residual microflora contaminating the surfaces and the equipment were analysed after cleaning and disinfection procedures. All the PU environments were colonised at various levels by spoilage and technological microflora with excessive contamination levels in some of the PUs. Sporadic contamination by pathogenic microflora was recorded. Salmonella and Listeria monocytogenes were detected in 4.8% and 6.7% of the samples, respectively, and Staphylococcus aureus was enumerated in 6.1% of the samples. Several critical points were identified, such as the machines for S. aureus and the tables and the knives for L. monocytogenes; this knowledge is crucial for the improvement of hygiene control systems in small and traditional meat processing industries. The variability of the residual contamination emphasized the different cleaning, disinfecting and manufacturing practices routinely followed by these small-scale processing units.
ABSTRACT
Due to the growing interest in organic products, a comparison between the chemical safety of organic and conventional products was undertaken. Milk and meat were the products chosen for study. The parameters evaluated to assess chemical safety were organochlorine pesticides, polychlorinated biphenyls (PCBs), lead, cadmium and mycotoxin contamination. Pesticides and PCBs residues in both organic and conventional milk and meat were lower than legal limits. Lead and cadmium residues were very low and did not differ between organic and conventional products. However, aflatoxin M1 contamination in some but not all samples of organic milk was significantly higher than those of conventional milk, although factors other than organic production might be implicated.
Subject(s)
Food Contamination/analysis , Food, Organic/analysis , Meat Products/analysis , Milk/chemistry , Aflatoxin M1/analysis , Animals , Food Analysis/methods , Humans , Italy , Metals, Heavy/analysis , Pesticide Residues/analysis , Polychlorinated Biphenyls/analysisABSTRACT
The effects of specific diets for commercial hybrids were investigated on 6 Casertana and 11 Mora Romagnola, two endangered Italian pig breeds. Average daily gain (ADG), feed conversion index (FCI), dressing percentage and meat and fat quality of animals bred under similar environmental and nutritional conditions were compared to define their optimal slaughtering weight. Animals were fed the same diets assuming that requirements of Mora Romagnola and Casertana did not differ, and changed every 30kg of weight gain. ADG and FCI were calculated every 15 days. Weight gains, divided into 5 groups based on live weight (LW) of animals (⩽60kg, 60
Subject(s)
Meat Products/analysis , Animals , Cattle , Color , Europe , Light , Meat Products/radiation effects , Swine , Thiobarbituric Acid Reactive Substances/analysisABSTRACT
A procedure for the simultaneous determination of the residues of seven beta-lactam antibiotics (penicillin G, ampicillin, oxacillin, amoxicillin, dicloxacillin, cephalexin, cephapirin) in bovine raw milk using tandem liquid chromatography mass spectrometry (LC-MS/MS) is described. The antibiotics were extracted by an acetic acid solution after centrifugation and filtration. The beta-lactams were separated using reversed-phase liquid chromatography. A triple quadrupole mass spectrometer was used in positive-ion mode as a detector via a Turbo Ionspray interface for electrospray ionization (ESI). The limits of detection and quantitation of the method were below the legal tolerances, except for ampicillin. The method was used to confirm 53 samples found positive by a microbial method (Delvotest SP) at the Istituto Zooprofilattico Sperimentale per la Lombardia e l'Emilia Romagna of Brescia during 2001. Penicillin G was found in 26 samples at concentrations ranging from less than 4 to 6240+/-550 microg x l(-1). Amoxicillin was found in three samples at concentrations ranging from 8.5+/-0.1 to 53.7+/-2.3 microg x l(-1). Cephapirin was found in two samples at 5.7+/-0.1 and 6.4+/-0.3 microg x l(-1).
Subject(s)
Anti-Bacterial Agents/analysis , Drug Residues/analysis , Food Contamination/analysis , Milk/chemistry , Animals , Cattle , Chromatography, High Pressure Liquid/methods , Chromatography, Liquid/methods , Food Analysis/methods , Mass Spectrometry/methods , beta-LactamsABSTRACT
Lipid and colour oxidative changes in Milano-type fermented sausages were studied in relation to packing conditions and extended storage under fluorescent light. Matured sausages were sliced and packed under vacuum or in protective atmosphere (100% N(2)) and exposed in a display cabinet to mimic commercial conditions of light and temperature for 2 months. Lipid oxidation was measured by the determination of thiobarbituric acid reactive substances (TBARS) and cholesterol oxidation products (COP), whereas the oxidation of nitrosylmyoglobin was evaluated by a trained sensory panel. Lipid oxidation and discolouration were positively related in vacuum-packed sausages: TBARS and COP values increased significantly concurrently with increasing brown scores. Protective atmosphere came out to be more efficient than vacuum in controlling fatty acid oxidation and, to a lesser extent, cholesterol and pigment degradation: TBARS values remained constant during the whole storage period whereas cholesterol oxides and brown colour scores gradually increased but remained lower than those of vacuum-packed sausages. Higher residual oxygen in vacuum packing could be responsible for the observed differences in oxidative stability.
ABSTRACT
A commercial production was analysed at six stages during ripening. Water content, pH and bacterial counts were followed, and volatile compounds from sausages were extracted by dynamic headspace sampling and analysed by gas chromatography/mass spectrometry. Total concentrations of all classes increased during ripening. Pepper compound concentrations peaked in the middle of the ripening period. Lipid oxidation products increased especially towards the end of ripening, in particular, the compounds 2-heptanol, 1-octen-3-ol, 2-heptanone and 2-nonanone. Surface moulds probably caused 4-heptanone to appear late in the processing. Benzeneacetaldehyde was absent in fresh mince, but increased to become one of the most abundant volatiles. Compounds from carbohydrate catabolism disappeared during the processing.
ABSTRACT
An investigation has been carried out on the effect of dietary supplementation with vitamin E and oleic acid on oxidative stability of Italian representative pork products. Fatty acid composition of deposited fat was modified in the oil supplemented groups with negative effects on fat firmness. Oil supplementation significantly increased vitamin E content of muscles, as well. Oxidative stability of fat, evaluated by TBARS and cholesterol oxides, has not shown significant differences between dietary treatments but, although the differences were not significant, the tendency was sufficiently clear, especially in salame Milano, towards a lower oxidation level in vitamin E enriched meat. Cholesterol oxidation was found to vary in general around 0.1% of total cholesterol and the only cholesterol oxides observed were 7ß-hydroxycholesterol, 5,6α-epoxycholesterol and 7-ketocholesterol. Aldehydes content and distribution appeared to be linked, firstly, to the specific processing technology of the product and, secondly, to the changed fatty acid composition.
ABSTRACT
The relationship between extracted volatiles of Milano salami, one of the main dry-cured sausages produced in Italy, and their olfactory properties was studied. Volatile compounds were extracted by a purge-and-trap method, quantified using a flame ionisation detector and identified by mass spectrometry. Olfactory analysis was performed by sniffing the gas chromatographic effluent. Nearly 80 compounds were identified and quantified: most came from spices (60.5%), 18.9% from lipid oxidation, 11.8% from amino acid catabolism and 4.9% from fermentation processes. Panellists detected 19 odours by sniffing. These odours were associated with spices, lipid oxidation or fermentation and were in agreement with the contributions of each reaction to the overall aroma of the product.
ABSTRACT
Research has been conducted on the effects of feed supplementation with vitamin E, oleic acid (sunflower oil) and copper on some quality characteristics of pork chops. The study was based on the measurement of pH 45' and 24 hr post mortem, proximate composition, colour both objective and sensory, colour stability after packing in oxygen permeable film and protective atmosphere, copper and iron contents, vitamin E content in fresh and cooked chops, peroxide and TBARS value in raw and cooked meat, total cholesterol, cholesterol oxides and aldehydes in cooked meat, sensory evaluation of the eating quality of cooked chops and iodine number of subcutaneous fat. Vitamin E content was significantly higher with oil and vitamin supplementation. No variation has been observed in copper and iron contents. A higher stability of the colour of meat packed under modified atmosphere has been observed with increasing vitamin E content, but the same did not apply with meat packed in oxygen permeable film. No differences have been observed on fatty acid oxidative stability of fresh m. longissimus dorsi and cooked chops (peroxide and TBARS values), on cholesterol oxidation and aldehydes production of cooked chops with increasing vitamin E content. Iodine number in supplemented animals reached levels normally considered at risk for fat firmness.