Yeast-Derived Formulations Are Differentially Fermented by the Canine and Feline Microbiome As Assessed in a Novel in Vitro Colonic Fermentation Model

The current study evaluated the effect of five yeast-derived formulations (T1-T5) on microbial metabolism and composition of the canine and feline gut microbiota using a novel in vitro colonic incubation approach. This novel in vitro model allowed for growth of the entire spectrum of dog- and cat-derived bacteria from the inoculum, thus offering an excellent platform to evaluate effects of nutritional interventions on the gut microbiota. Further, yeast-derived ingredients differentially increased production of acetate, propionate, butyrate, ammonium, and branched short-chain fatty acids, with T5 and T1 consistently stimulating propionate and butyrate, respectively. 16S-targeted Illumina sequencing coupled with flow cytometry provided unprecedented high-resolution quantitative insights in canine and feline microbiota modulation by yeast-derived ingredients, revealing that effects on propionate production were related to Prevotellaceae, Tannerellaceae, Bacteroidaceae, and Veillonellaceae members, while effects on butyrate production were related to Erysipelotrichaceae, Lachnospiraceae, Ruminococcaceae, and Fusobacteriaceae. Overall, these findings strengthen the health-promoting potential of yeast-derived ingredients

Comparison of the therapeutic effect of treatment with antibiotics or nutraceuticals on clinical activity and the fecal microbiome of dogs with acute diarrhea

Dogs with acute diarrhea are often presented to clinical practice and, although this generally represents a self-limiting condition, antibiotics are still frequently used as treatment. The aim of this study was to evaluate the effects in dogs with acute non-hemorrhagic diarrhea of the administration of an antibiotic combination in comparison to a nutraceutical product. Thirty dogs were enrolled and randomly assigned to two groups: 15 dogs (group A) received a nutraceutical commercial product while 15 dogs (group B) received an antimicrobial combination of metronidazole and spiramycin. For each dog, the Canine Acute Diarrhea Severity Index, the fecal microbiota and the Dysbiosis Index were assessed. Both stool consistency and frequency decreased on day 2 in the dogs of group A compared to baseline, while in group B, these parameters significantly decreased at days 3 and 4. The global concern for rising antibiotic resistance associated with indiscriminate use of antimicrobials, in both humans and animals, suggests the necessity of avoiding empirical and injudicious use of these molecules in diarrheic dogs. These results suggest that the nutraceutical treatment had a similar clinical effect compared to the antibiotic formulation, representing a valid antibiotic-sparing therapeutic approach in canine acute diarrhea

Fecal microbiota in client-owned obese dogs changes after weight loss with a high-fiber-high-protein diet

Background. The fecal microbiota from obese individuals can induce obesity in animal models. In addition, studies in humans, animal models and dogs have revealed that the fecal microbiota of subjects with obesity is different from that of lean subjects and changes after weight loss. However, the impact of weight loss on the fecal microbiota in dogs with obesity has not been fully characterized. Methods. In this study, we used 16S rRNA gene sequencing to investigate the differences in the fecal microbiota of 20 pet dogs with obesity that underwent a weight loss program. The endpoint of the weight loss program was individually tailored to the ideal body weight of each dog. In addition, we evaluated the qPCR based Dysbiosis Index before and after weight loss. Results. After weight loss, the fecal microbiota structure of dogs with obesity changed significantly (weighted ANOSIM; p = 0.016, R = 0.073), showing an increase in bacterial richness (p = 0.007), evenness (p = 0.007) and the number of bacterial species (p = 0.007). The fecal microbiota composition of obese dogs after weight loss was characterized by a decrease in Firmicutes (92.3% to 78.2%, q = 0.001), and increase in Bacteroidetes (1.4% to 10.1%, q = 0.002) and Fusobacteria (1.6% to 6.2%, q = 0.040). The qPCR results revealed an overall decrease in the Dysbiosis Index, driven mostly due to a significant decrease in E. coli (p = 0.030), and increase in Fusobacterium spp. (p = 0.017). Conclusion. The changes observed in the fecal microbiota of dogs with obesity after weight loss with a weight loss diet rich in fiber and protein were in agreement with previous studies in humans, that reported an increase of bacterial biodiversity and a decrease of the ratio Firmicutes/Bacteroidetes

Years of life that could be saved from prevention of hepatocellular carcinoma

BACKGROUND: Hepatocellular carcinoma (HCC) causes premature death and loss of life expectancy worldwide. Its primary and secondary prevention can result in a significant number of years of life saved. AIM: To assess how many years of life are lost after HCC diagnosis. METHODS: Data from 5346 patients with first HCC diagnosis were used to estimate lifespan and number of years of life lost after tumour onset, using a semi-parametric extrapolation having as reference an age-, sex- and year-of-onset-matched population derived from national life tables. RESULTS: Between 1986 and 2014, HCC lead to an average of 11.5 years-of-life lost for each patient. The youngest age-quartile group (18-61 years) had the highest number of years-of-life lost, representing approximately 41% of the overall benefit obtainable from prevention. Advancements in HCC management have progressively reduced the number of years-of-life lost from 12.6 years in 1986-1999, to 10.7 in 2000-2006 and 7.4 years in 2007-2014. Currently, an HCC diagnosis when a single tumour <2 cm results in 3.7 years-of-life lost while the diagnosis when a single tumour 65 2 cm or 2/3 nodules still within the Milan criteria, results in 5.0 years-of-life lost, representing the loss of only approximately 5.5% and 7.2%, respectively, of the entire lifespan from birth. CONCLUSIONS: Hepatocellular carcinoma occurrence results in the loss of a considerable number of years-of-life, especially for younger patients. In recent years, the increased possibility of effectively treating this tumour has improved life expectancy, thus reducing years-of-life lost

Trans-arterial radioembolization for intermediate-advanced hepatocellular carcinoma: a budget impact analysis

Background: Trans-arterial radio-embolization (TARE) is an emerging treatment for the management of hepatocellular carcinoma (HCC). TARE may compete with systemic chemotherapy, sorafenib, in intermediate stage patients with prior chemoembolization failure or advanced patients with tumoral macrovascular invasion with no extra-hepatic spread and good liver function. We performed a budget impact analysis (BIA) evaluating the expected changes in the expenditure for the Italian Healthcare Service within scenarios of increased utilization of TARE in place of sorafenib over the next five years. Methods: Starting from patient level data from three oncology centres in Italy, a Markov model was developed to project on a lifetime horizon survivals and costs associated to matched cohorts of intermediate-advanced HCC patients treated with TARE or sorafenib. The initial model has been integrated with epidemiological data to perform a BIA comparing the current scenario with 20 and 80% utilization rates for TARE and sorafenib, respectively, with increasing utilization rates of TARE of 30, 40 and 50% over the next 1, 3 and 5 years. Results: Compared to the current scenario, progressively increasing utilization rates of TARE over sorafenib in the next 5 years is expected to save globally about 7 million Euros. Conclusions: Radioembolization can be considered a valuable treatment option for patients with intermediate-advanced HCC. These findings enrich the evidence about the economic sustainability of TARE in comparison to standard systemic chemotherapy within the context of a national healthcare servic

Material deprivation affects the management and clinical outcome of hepatocellular carcinoma in a high-resource environment

none94Aim: This study investigated how material deprivation in Italy influences the stage of hepatocellular carcinoma (HCC) at diagnosis and the chance of cure. Methods: 4114 patients from the Italian Liver Cancer database consecutively diagnosed with HCC between January 2008 and December 2018 were analysed about severe material deprivation (SMD) rate tertiles of the region of birth and region of managing hospitals, according to the European Statistics on Income and Living Conditions. The main outcomes were HCC diagnosis modalities (during or outside surveillance), treatment adoption and overall survival. Results: In more deprived regions, HCC was more frequently diagnosed during surveillance, while the incidental diagnosis was prevalent in the least deprived. Tumour characteristics did not differ among regions. The proportion of patients undergoing potentially curative treatments progressively decreased as the SMD worsened. Consequently, overall survival was better in less deprived regions. Patients who moved from most deprived to less deprived regions increased their probability of receiving potentially curative treatments by 1.11 times (95% CI 1.03 to 1.19), decreasing their mortality likelihood (hazard ratio 0.78 95% CI 0.67 to 0.90). Conclusions: Socioeconomic status measured through SMD does not seem to influence HCC features at diagnosis but brings a negative effect on the chance of receiving potentially curative treatments. Patient mobility from the most deprived to the less deprived regions increased the access to curative therapies, with the ultimate result of improving survival.openCucchetti A.; Gramenzi A.; Johnson P.; Giannini E.G.; Tovoli F.; Rapaccini G.L.; Marra F.; Cabibbo G.; Caturelli E.; Gasbarrini A.; Svegliati-Baroni G.; Sacco R.; Zoli M.; Morisco F.; Di Marco M.; Mega A.; Foschi F.G.; Biasini E.; Masotto A.; Nardone G.; Raimondo G.; Azzaroli F.; Vidili G.; Brunetto M.R.; Farinati F.; Trevisani F.; Avanzato F.; Biselli M.; Caraceni P.; Garuti F.; Neri A.; Santi V.; Pellizzaro F.; Imondi A.; Sartori A.; Penzo B.; Sanmarco A.; Granito A.; Muratori L.; Piscaglia F.; Sansone V.; Forgione A.; Dajti E.; Marasco G.; Ravaioli F.; Cappelli A.; Golfieri R.; Mosconi C.; Renzulli M.; Cela E.M.; Facciorusso A.; Cacciato V.; Casagrande E.; Moscatelli A.; Pellegatta G.; de Matthaeis N.; Allegrini G.; Lauria V.; Ghittoni G.; Pelecca G.; Chegai F.; Coratella F.; Ortenzi M.; Missale G.; Olivani A.; Inno A.; Marchetti F.; Busacca A.; Camma C.; Di Martino V.; Maria Rizzo G.E.; Franze M.S.; Saitta C.; Sauchella A.; Berardinelli D.; Bevilacqua V.; Borghi A.; Gardini A.C.; Conti F.; Dall'Aglio A.C.; Ercolani G.; Adotti V.; Arena U.; Di Bonaventura C.; Campani C.; Dragoni G.; Gitto S.; Laffi G.; Coccoli P.; Malerba A.; Guarino M.; Capasso M.; Oliveri F.; Romagnoli V.Cucchetti, A.; Gramenzi, A.; Johnson, P.; Giannini, E. G.; Tovoli, F.; Rapaccini, G. L.; Marra, F.; Cabibbo, G.; Caturelli, E.; Gasbarrini, A.; Svegliati-Baroni, G.; Sacco, R.; Zoli, M.; Morisco, F.; Di Marco, M.; Mega, A.; Foschi, F. G.; Biasini, E.; Masotto, A.; Nardone, G.; Raimondo, G.; Azzaroli, F.; Vidili, G.; Brunetto, M. R.; Farinati, F.; Trevisani, F.; Avanzato, F.; Biselli, M.; Caraceni, P.; Garuti, F.; Neri, A.; Santi, V.; Pellizzaro, F.; Imondi, A.; Sartori, A.; Penzo, B.; Sanmarco, A.; Granito, A.; Muratori, L.; Piscaglia, F.; Sansone, V.; Forgione, A.; Dajti, E.; Marasco, G.; Ravaioli, F.; Cappelli, A.; Golfieri, R.; Mosconi, C.; Renzulli, M.; Cela, E. M.; Facciorusso, A.; Cacciato, V.; Casagrande, E.; Moscatelli, A.; Pellegatta, G.; de Matthaeis, N.; Allegrini, G.; Lauria, V.; Ghittoni, G.; Pelecca, G.; Chegai, F.; Coratella, F.; Ortenzi, M.; Missale, G.; Olivani, A.; Inno, A.; Marchetti, F.; Busacca, A.; Camma, C.; Di Martino, V.; Maria Rizzo, G. E.; Franze, M. S.; Saitta, C.; Sauchella, A.; Berardinelli, D.; Bevilacqua, V.; Borghi, A.; Gardini, A. C.; Conti, F.; Dall'Aglio, A. C.; Ercolani, G.; Adotti, V.; Arena, U.; Di Bonaventura, C.; Campani, C.; Dragoni, G.; Gitto, S.; Laffi, G.; Coccoli, P.; Malerba, A.; Guarino, M.; Capasso, M.; Oliveri, F.; Romagnoli, V

Metabolic disorders across hepatocellular carcinoma in Italy

BACKGROUND: Metabolic disorders are well-known risk factors for HCC. Conversely, their impact on the natural history of HCC is not established. This study aimed at evaluating the impact of metabolic disorders on clinical features, treatment and survival of HCC patients regardless of its aetiology. METHODS: We analysed the ITA.LI.CA database regarding 839 HCC patients prospectively collected. The following metabolic features were analysed: BMI, diabetes, arterial hypertension, hypercholesterolaemia and hypertriglyceridaemia. According to these features, patients were divided into 3 groups: 0-1, 2 and 3-5 metabolic features. RESULTS: As compared with patients with 0-1 metabolic features, patients with 3-5 features showed lower percentage of HCC diagnosis on surveillance (P = .021), larger tumours (P = .038), better liver function (higher percentage of Child-Pugh class A [P = .007] and MELD &lt; 10 [P = .003]), higher percentage of metastasis (P = .024) and lower percentage of portal vein thrombosis (P = .010). The BCLC stage and treatment options were similar among the 3 groups, with the exception of a less frequent access to loco-regional therapies for BCLC stage B patients with 3-5 features (P = .012). Overall survival and survival according to BCLC stage and/or treatment did not significantly differ among the 3 groups. Only using a probabilistic sensitivity analysis, diabetic patients showed a lower survival (P = .046). MELD score, HCC morphology, nodule size, BCLC stage, portal vein thrombosis and metastasis were independent predictors of lead-time adjusted survival. CONCLUSIONS: Our "real world" study suggests that metabolic disorders shape the clinical presentation of HCC but do not seem to play a major role in setting patient survival.Background: Metabolic disorders are well-known risk factors for HCC. Conversely, their impact on the natural history of HCC is not established. This study aimed at evaluating the impact of metabolic disorders on clinical features, treatment and survival of HCC patients regardless of its aetiology. Methods: We analysed the ITA.LI.CA database regarding 839 HCC patients prospectively collected. The following metabolic features were analysed: BMI, diabetes, arterial hypertension, hypercholesterolaemia and hypertriglyceridaemia. According to these features, patients were divided into 3 groups: 0-1, 2 and 3-5 metabolic features. Results: As compared with patients with 0-1 metabolic features, patients with 3-5 features showed lower percentage of HCC diagnosis on surveillance (P&nbsp;=.021), larger tumours (P&nbsp;=.038), better liver function (higher percentage of Child-Pugh class A [P&nbsp;=.007] and MELD&nbsp;&lt;&nbsp;10 [P&nbsp;=.003]), higher percentage of metastasis (P&nbsp;=.024) and lower percentage of portal vein thrombosis (P&nbsp;=.010). The BCLC stage and treatment options were similar among the 3 groups, with the exception of a less frequent access to loco-regional therapies for BCLC stage B patients with 3-5 features (P&nbsp;=.012). Overall survival and survival according to BCLC stage and/or treatment did not significantly differ among the 3 groups. Only using a probabilistic sensitivity analysis, diabetic patients showed a lower survival (P&nbsp;=.046). MELD score, HCC morphology, nodule size, BCLC stage, portal vein thrombosis and metastasis were independent predictors of lead-time adjusted survival. Conclusions: Our \u201creal world\u201d study suggests that metabolic disorders shape the clinical presentation of HCC but do not seem to play a major role in setting patient survival