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| 2. |
- Block, Keith I., et al.
(författare)
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Designing a broad-spectrum integrative approach for cancer prevention and treatment
- 2015
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Ingår i: Seminars in Cancer Biology. - : Academic Press. - 1044-579X .- 1096-3650. ; 35, s. S276-S304
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Forskningsöversikt (refereegranskat)abstract
- Targeted therapies and the consequent adoption of "personalized" oncology have achieved notable successes in some cancers; however, significant problems remain with this approach. Many targeted therapies are highly toxic, costs are extremely high, and most patients experience relapse after a few disease-free months. Relapses arise from genetic heterogeneity in tumors, which harbor therapy-resistant immortalized cells that have adopted alternate and compensatory pathways (i.e., pathways that are not reliant upon the same mechanisms as those which have been targeted). To address these limitations, an international task force of 180 scientists was assembled to explore the concept of a low-toxicity "broadspectrum" therapeutic approach that could simultaneously target many key pathways and mechanisms. Using cancer hallmark phenotypes and the tumor microenvironment to account for the various aspects of relevant cancer biology, interdisciplinary teams reviewed each hallmark area and nominated a wide range of high-priority targets (74 in total) that could be modified to improve patient outcomes. For these targets, corresponding low-toxicity therapeutic approaches were then suggested, many of which were phytochemicals. Proposed actions on each target and all of the approaches were further reviewed for known effects on other hallmark areas and the tumor microenvironment Potential contrary or procarcinogenic effects were found for 3.9% of the relationships between targets and hallmarks, and mixed evidence of complementary and contrary relationships was found for 7.1%. Approximately 67% of the relationships revealed potentially complementary effects, and the remainder had no known relationship. Among the approaches, 1.1% had contrary, 2.8% had mixed and 62.1% had complementary relationships. These results suggest that a broad-spectrum approach should be feasible from a safety standpoint. This novel approach has potential to be relatively inexpensive, it should help us address stages and types of cancer that lack conventional treatment, and it may reduce relapse risks. A proposed agenda for future research is offered. (C) 2015 The Authors. Published by Elsevier Ltd.
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| 3. |
- Spagnuolo, R., et al.
(författare)
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Deregulation of SGK1 in Ulcerative Colitis: A Paradoxical Relationship Between Immune Cells and Colonic Epithelial Cells
- 2018
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Ingår i: Inflammatory Bowel Diseases. - : Oxford University Press (OUP). - 1078-0998 .- 1536-4844. ; 24:9, s. 1967-1977
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Tidskriftsartikel (refereegranskat)abstract
- Background: Inflammatory bowel disease (IBD) is due to the interaction of genetic and environmental factors that trigger an unbalanced immune response ultimately resulting in the peculiar inflammatory reaction. Experimental models of IBD point to a role of T-cell-derived cytokines (Th17) and to SGK1 as mediator of the Th17 switch. We hypothesize that SGK1, a salt inducible kinase, directs lymphocytic behavior and tissue damage. Methods: Eleven controls and 32 ulcerative colitis (UC) patients were randomized according to endoscopic Mayo score. Mucosal biopsies from different intestinal tracts were analyzed by immunohistochemistry and quantitative real-time polymerase chain reaction to check the expression of disease markers including SGK1. Peripheral blood mononuclear cells (PBMCs) from patients and controls were analyzed by fluorescence-activated cell sorting. Finally, an in vitro cell model was developed to test the hypothesis. Results: SGK1 mRNA and protein expression in lesional areas of UC patients were lower than in normal peri-lesional areas of the same patients and in normal tissues of healthy controls. SGK1 expression was increased in PBMCs from UC patients, particularly in the CD4+ cell population, enriched in Th17 cells. IL17/IL13 was increased in patients and correlated with SGK1 expression. Genetically engineered Jurkat cells confirmed the effect of SGK1 overexpression on viability of RKO cells. Conclusions: These observations suggest a pathogenic mechanism whereby SGK1 overexpression in CD4+ T cells induces the secretion of the inflammatory cytokines IL17 and IL13, which downregulate the expression of SGK1 in target tissues. Our data suggest a novel hypothesis in the pathogenesis of UC, integrating colonic epithelial cells and lymphocytes.
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| 4. |
- De Vincentis, A., et al.
(författare)
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Metabolic and genetic determinants for progression to severe liver disease in subjects with obesity from the UK Biobank
- 2022
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Ingår i: International Journal of Obesity. - : Springer Science and Business Media LLC. - 0307-0565 .- 1476-5497. ; 46, s. 486-493
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Tidskriftsartikel (refereegranskat)abstract
- Background Obesity is among the main determinants of nonalcoholic fatty liver disease progression towards severe liver disease (SLD). However, risk factors for SLD in individuals with obesity have not been examined. Objectives To identify the independent risk factors for SLD among participants with obesity from the UK Biobank. Methods A total of 80,224 UK Biobank participants with obesity (body mass index[BMI] > 30 kg/m(2)) and 242,822 without obesity, of European descent without clinical history of liver disease and liver cancer were prospectively followed for the onset of SLD, defined as a composite diagnosis of cirrhosis, decompensated liver disease, hepatocellular carcinoma and/or liver transplantation. Risk factors for incident SLD were assessed by Cox proportional hazards models. Different clinical phenotypes were derived by latent class analysis (LCA). Results Obesity conferred a 2.6-fold increased risk for SLD that was abolished after the inclusion of waist circumference (WC) in the model. Among individuals with obesity, age (adjusted hazard ratio [aHR] 1.05, 95%CI 1.03-1.07, p = 3.9 * 10(-7)), type 2 diabetes (aHR 2.18, 95%CI 1.55-3.05, p = 6.2 * 10(-6)), PNPLA3 rs738409 (aHR 1.59, 95%CI 1.33-1.9, p = 3.1 * 10(-7)) and WC (aHR 1.04, 95%CI 1.02-1.06, p = 8.5 * 10(-6)) were independent predictors of SLD. BMI category-specific WC thresholds allowed a better risk stratification compared to traditional ones. By LCA, the clinical phenotype at highest risk for SLD was that with BMI < 35 kg/m(2) and WC above BMI-category specific thresholds. Conclusions Age, WC, type 2 diabetes, and the PNPLA3 variant are the main risk factors for SLD in individuals with obesity. WC is the principal mediator of SLD risk conveyed by increased BMI. BMI category-specific WC-thresholds may refine the SLD risk more accurately than traditional thresholds.
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| 5. |
- Mancina, Rosellina Margherita, et al.
(författare)
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Gastrointestinal Symptoms of and Psychosocial Changes in Inflammatory Bowel Disease: A Nursing-Led Cross-Sectional Study of Patients in Clinical Remission
- 2020
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Ingår i: Medicina-Lithuania. - : MDPI AG. - 1010-660X. ; 56:1
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Tidskriftsartikel (refereegranskat)abstract
- Background and Objectives: Nursing management in Inflammatory Bowel Disease (IBD) is focused on global patient care. Starting from basic knowledge of diagnostic and therapeutic management, nurses can assess the impact of IBD on patients' quality of life not only at the physical level, but also at the psychological, social, and emotional levels. The aim of this study was to evaluate the impact of gastrointestinal symptoms on psychosocial changes in IBD patients in remission through nursing-led Patient-Reported Outcomes. Materials and Methods: We performed a cross-sectional study of 109 IBD patients in clinical and endoscopic remission. Specialist nurses invited patients to complete questionnaires on gastrointestinal symptoms and quality of life through the Patient-Reported Outcomes Measurement Information System (PROMIS). Results: We found that the gastrointestinal symptoms that the patients reported had a significant impact on the analyzed aspects of health. More specifically, belly pain, diarrhea, and bloating were associated with depressive symptoms (p < 0.001), anxiety (p < 0.001), fatigue (p < 0.001), and sleep disturbances (p < 0.001). Moreover, these symptoms also significantly affected patients' social dimension in terms of satisfaction with participation in social roles (p < 0.001, p < 0.05, and p < 0.001 for belly pain, diarrhea, and bloating, respectively) and physical functions (p < 0.001). The results were virtually the same in a multivariable analysis adjusted by age, gender, body mass index (BMI), and disease duration. Conclusions: Even during remission, gastrointestinal symptoms are the main factors that influence quality of life in IBD patients. This exploratory study highlights the need to adopt validated questionnaires in clinical practice, and demonstrates that PROMIS is a valid, objective, and standardized instrument that can help nursing staff to better define the consequences of the disease in a patient's daily life.
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| 6. |
- Mancina, Rosellina Margherita, et al.
(författare)
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Ulcerative Colitis as an Independent Risk Factor for Hepatic Steatosis
- 2020
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Ingår i: Gastroenterology Nursing. - : Ovid Technologies (Wolters Kluwer Health). - 1042-895X. ; 43:4, s. 292-297
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Tidskriftsartikel (refereegranskat)abstract
- Inflammatory bowel disease (IBD) is an inflammatory condition of the gastrointestinal tract encompassing Crohn disease and ulcerative colitis, often associated with extraintestinal manifestations. Nonalcoholic fatty liver disease represents one of the described inflammatory bowel disease-related liver diseases. To understand the IBD contribution to nonalcoholic fatty liver disease onset, we compared liver fat content and fibrosis between IBD patients and healthy controls integrating medical and nursing expertise (integrated nursing approach). A total of 95 patients and 53 healthy volunteers were recruited. Only nondiabetic and nonobese individuals were included in the study. Liver evaluation was performed by an experienced nurse using transient elastography. We found that IBD patients had higher liver fat content than the control group (p= .003). Bonferroni post hoc analyses revealed that patients with Crohn disease or ulcerative colitis had higher liver fat than the control group. We also found that ulcerative colitis was associated with more than a 4-fold increased risk for mild steatosis and 7-fold increased risk for moderate/severe steatosis independently from other risk factors such as glucose and body mass index. In conclusion, we showed for the first time that ulcerative colitis is an independent risk factor for hepatic steatosis measured by transient elastography.
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| 7. |
- Pironi, L., et al.
(författare)
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COVID-19 infection in patients on long-term home parenteral nutrition for chronic intestinal failure
- 2023
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Ingår i: Clinical Nutrition Espen. - : Elsevier BV. - 2405-4577. ; 55, s. 212-220
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Tidskriftsartikel (refereegranskat)abstract
- Background and aims: To investigate the incidence and the severity of COVID-19 infection in patients enrolled in the database for home parenteral nutrition (HPN) for chronic intestinal failure (CIF) of the European Society for Clinical Nutrition and Metabolism (ESPEN). Methods: Period of observation: March 1st, 2020 March 1st, 2021. Inclusion criteria: patients included in the database since 2015 and still receiving HPN on March 1st, 2020 as well as new patients included in the database during the period of observation. Data related to the previous 12 months and recorded on March 1st 2021: 1) occurrence of COVID-19 infection since the beginning of the pandemic (yes, no, unknown); 2) infection severity (asymptomatic; mild, no-hospitalization; moderate, hospitalization no -ICU; severe, hospitalization in ICU); 3) vaccinated against COVID-19 (yes, no, unknown); 4) patient outcome on March 1st 2021: still on HPN, weaned off HPN, deceased, lost to follow up.Results: Sixty-eight centres from 23 countries included 4680 patients. Data on COVID-19 were available for 55.1% of patients. The cumulative incidence of infection was 9.6% in the total group and ranged from 0% to 21.9% in the cohorts of individual countries. Infection severity was reported as: asymptomatic 26.7%, mild 32.0%, moderate 36.0%, severe 5.3%. Vaccination status was unknown in 62.0% of patients, non-vaccinated 25.2%, vaccinated 12.8%. Patient outcome was reported as: still on HPN 78.6%, weaned off HPN 10.6%, deceased 9.7%, lost to follow up 1.1%. A higher incidence of infection (p = 0.04), greater severity of infection (p < 0.001) and a lower vaccination percentage (p = 0.01) were observed in deceased patients. In COVID-19 infected patients, deaths due to infection accounted for 42.8% of total deaths.Conclusions: In patients on HPN for CIF, the incidence of COVID-19 infection differed greatly among countries. Although the majority of cases were reported to be asymptomatic or have mild symptoms only, COVID-19 was reported to be fatal in a significant proportion of infected patients. Lack of vacci-nation was associated with a higher risk of death.(c) 2023 European Society for Clinical Nutrition and Metabolism. Published by Elsevier Ltd. All rights reserved.
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| 8. |
- Spagnuolo, R., et al.
(författare)
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Effects of listening to music in digestive endoscopy: A prospective intervention study led by nursing
- 2020
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Ingår i: Journal of Advanced Nursing. - : Wiley. - 0309-2402 .- 1365-2648. ; 76:11, s. 2993-3002
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Tidskriftsartikel (refereegranskat)abstract
- Aims To explore whether music can reduce anxiety and pain in patients who underwent diagnostic endoscopic examinations in conscious and deep sedation and to assess degree of satisfaction and willingness to repeat the procedure. Design Prospective study led by nursing. Methods Between March 2019-June 2019, consecutive outpatients undergoing endoscopic examinations were simple matched into four groups: Group 1: conscious sedation with music; Group 2: conscious sedation without music; Group 3: deep sedation with music and Group 4: deep sedation without music. Ten minutes before the procedure, two trainee nurses applied music.State-Trait Anxiety Inventorywas used to evaluate anxiety. Results Before and at the end of the procedure, patients who listened to music had a lower level anxiety than those who did not listen and, also, reported lower pain intensity during procedure. Only within Group 1 median anxiety, measured after the procedure, is lower than that measured before. In the bivariate logistic regression model, pain and listening to music were independent factors for satisfaction and willingness to repeat procedure. Conclusion music in digestive endoscopy reduce pain and anxiety in conscious sedation, thus could be used to reduce anxiety in support to conscious sedation leading to lower usage of deep sedation and consequently reduction of costs and adverse events. Impact Anxiety in digestive endoscopy limits patients' satisfaction. Music in digestive endoscopy as a specific nursing intervention could reduce anxiety of patients. This nursing intervention study confirms positive effect of music in digestive endoscopy. As part of nursing management, the addition of music to daily care practice in digestive endoscopy may reduce anxiety and increase the patient's degree of satisfaction. Use of music could limit deep sedation use in digestive endoscopy with consequent reduction of risks for patients, execution times, and costs of procedures.
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| 9. |
- Spagnuolo, R., et al.
(författare)
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Satisfaction with Social Roles and Physical Function in Immune-mediated Inflammatory Diseases: A Cross-Sectional Study
- 2022
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Ingår i: Reviews on Recent Clinical Trials. - : Bentham Science Publishers Ltd.. - 1574-8871. ; 17:3, s. 177-186
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Tidskriftsartikel (refereegranskat)abstract
- Background: Although mood disorders have been well characterized by immune-mediated inflammatory diseases, physical function and satisfaction with social roles have not yet been defined as independent domains. Objective: The study aims to assess satisfaction with social roles and physical function alterations in a population with immune-mediated inflammatory diseases and identify associated characteristics. Methods: Physical function and social role satisfaction were evaluated through the Patient-reported Outcomes Measurement System. Besides comparison between groups, univariate and multivariable logistic regression analyses were performed to identify independent predictors. Results: Two hundred sixty-five patients with immune-mediated inflammatory diseases and 206 controls were recruited. Compared to controls, patients with inflammatory bowel diseases had impaired physical function (p<0.001), while patients with inflammatory arthritis reported impairment in both domains (p<0.001, each). In the univariate logistic regression, gender, high school educational level, physical activity, and occupation were positively associated with physical function and social role satisfaction (pp=0.001; pp=0.001 and pp=0.012; p=0.008; p=0.004, respectively). Active disease and steroids were inversely associated with physical function and social roles satisfaction (p=0.033; p=0.022 and p=0.002; p=0.038, respectively). Further associations were found between age and physical function (p=0.002) and biological treatment and ESR with social roles satisfaction (pp=0.043; respectively). In the multivariable regression, gender was found to be associated with physical function (p<0.001) and social roles satisfaction (p=0.003). Negatively associated factors were biological treatment for satisfaction with social roles (p<0.001) and steroids for physical function (p=0.021), and social roles satisfaction (p=0.018). Conclusion: Immune-mediated inflammatory diseases determine alterations in physical function and social life satisfaction. Gender and treatment are independently associated factors. Patient-reported outcomes should be considered in clinical management to define patients' real needs.
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| 10. |
- Burza, Maria Antonella, 1980, et al.
(författare)
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Effect of Excess Body Weight on the Genetic Susceptibility to Cancer
- 2014
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Ingår i: Journal of Clinical Gastroenterology. - 0192-0790. ; 48
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Tidskriftsartikel (refereegranskat)abstract
- Excess body weight and genetics play important roles in cancer susceptibility. Although several studies have reported on obesity and genetic variants as separate risk factors for cancer, very few studies have investigated the interaction between excess body weight and genetic variants in cancer susceptibility. In this review, we focus on the interplay between these 2 risk factors, which are a major determinant of the individual risk of cancer onset.
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