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Inflammatory bowel diseases (IBD), comprising Crohn’s disease (CD) and Ulcerative Colitis (UC), are multifactorial disorders characterized by a chronic inflammatory status with the secretion of cytokines and immune mediators. Biologic drugs targeting pro-inflammatory cytokines, such as infliximab, are broadly used in the treatment of IBD patients, but some patients lose responsiveness after an initial success. The research into new biomarkers is crucial for advancing personalized therapies and monitoring the response to biologics. The aim of this single center, observational study is to analyze the relationship between serum levels of 90K/Mac-2 BP and the response to infliximab, in a cohort of 48 IBD patients (30 CD and 18 UC), enrolled from February 2017 to December 2018. In our IBD cohort, high 90K serum levels were found at baseline in patients who then developed anti-infliximab antibodies at the fifth infusion (22 weeks after the first), becoming non-responders (9.76 ± 4.65 µg/mL compared to 6.53 ± 3.29 µg/mL in responder patients, p = 0.005). This difference was significant in the total cohort and in CD, but not significant in UC. We then analyzed the relationship between serum levels of 90K, C-reactive protein (CRP), and Fecal calprotectin. A significant positive correlation was found at baseline between 90K and CRP, the most common serum inflammation marker (R = 0.42, p = 0.0032). We concluded that circulating 90K could be considered a new non-invasive biomarker for monitoring the response to infliximab. Furthermore, 90K serum level determination, before the first infliximab infusion, in association with other inflammatory markers such as CRP, could assist in the choice of biologics for the treatment of IBD patients, thereby obviating the need for a drug switch due to loss of response, and so improving clinical practice and patient care.

Objective Atrophic gastritis may affect circulating ghrelin levels and, indirectly, body mass index. The aim of this study was to investigate the relationship between atrophic gastritis, focusing on autoimmune atrophic gastritis and advanced stages of atrophic gastritis, serum ghrelin levels and BMI. Methods Sixty-three patients, of whom 18 had autoimmune atrophic gastritis, 27 non-autoimmune antrum and corpus atrophic gastritis, and 18 non-atrophic gastritis or antrum-limited atrophic gastritis (control group) were assessed. All participants underwent endoscopy with multiple gastric biopsies. Atrophic gastritis was diagnosed by histology, classified according to the Updated Sydney System and staged by the Operative Link on Gastritis Assessment (OLGA) Classification. Total serum ghrelin, body weight and height were measured. Results Compared with control patients (144.6 ± 111 pg/ml), mean serum level of total ghrelin was higher in patients with autoimmune atrophic gastritis (226.08 ± 243.03 pg/ml, P = 0.65) and lower in those with both antrum and corpus atrophic gastritis (74.51 ± 37.38 pg/ml, P = 0.12), although differences were not statistically significant. Serum ghrelin decreased in patients with advanced OLGA stages of atrophic gastritis. In non-obese patients BMI was significantly lower in those with both antrum and corpus atrophic gastritis than in control patients (23.1 ± 1.8 vs. 24.5 ± 1.6, P = 0.01), also after adjustment for age and sex (P = 0.02); BMI was positively correlated with serum total ghrelin (r = 0.51, P < 0.001). Conclusion Advanced stages of atrophic gastritis, but not autoimmune atrophic gastritis, seem to be associated with lower serum levels of ghrelin and lower BMI. In non-obese patients, BMI was positively correlated with total serum ghrelin.

BACKGROUND Few studies have examined intestinal motility disorders, which are disabling conditions associated with chronic functional constipation, whose pathogenesis is actually not well-defined. AIM To investigate the relationship between serum 25-hydroxyvitamin D levels and functional chronic constipation associated to intestinal motility disorders. METHODS We performed a prospective case-control study, from May-June to November 2017. Glucose/lactulose breath tests, radiopaque markers (multiple capsule techniques) and wireless motility capsule analysis were used to assess colonic and oro-cecal transit time, after excluding small-intestinal bacterial overgrowth condition. Then, we measured 25-hydroxyvitamin D levels in patients with intestinal motility disorders and we further evaluated the influence of intestinal motility disorders on psychological symptoms/quality of life using validated questionnaires, the Irritable Bowel Syndrome Quality of life (IBS-QOL), the Short Form Health Survey 12, and the Hospital Anxiety and Depression Scale 14 (HADS-14 A and HADS-14 D). RESULTS We enrolled 86 patients with chronic functional constipation associated to intestinal motility disorders and 86 matched healthy subjects. Patients with intestinal motility disorders had lower 25-hydroxyvitamin D levels (P < 0.001), and they showed a significant impairment of all health-related quality of life and psychological tests (IBS-QOL, Short Form Health Survey 12-Physical Component Summary, Short Form Health Survey 12-Mental Component Summary, HADS-14 A and HADS-14 D), as compared to the control group (P < 0.001), which significantly correlated with low vitamin D levels (r = - 0.57, P < 0.001; r = 0.21, P = 0.01; r = - 0.48, P < 0.001; r = - 0.57, P < 0.001; r = - 0.29, P < 0.001, respectively). At multivariate analysis vitamin D low levels remained a significant independent risk factor for the occurrence of intestinal motility disorder (odds ratio = 1.19; 95% confidence interval: 1.14-1.26, P < 0.001). CONCLUSION Vitamin D deficiency, anxiety and depression symptoms are commonly associated with chronic functional constipation induced by intestinal motility disorders. Vitamin D serum levels should be routinely measured in these patients.

Background: Elevated fasting remnant cholesterol (REM-C) levels have been associated with an increased cardiovascular risk in patients with metabolic syndrome (Mets) and Non-Alcoholic Fatty Liver Disease (NAFLD). We aimed to estimate the effect of different diets on REM-C levels in patients with MetS, as well as the association between NAFLD and REM-C. Methods: This is a secondary analysis of the MEDIDIET study, a parallel-arm Randomized Clinical Trial (RCT). We examined 237 people with MetS who underwent Liver Ultrasound (LUS) to assess the NAFLD score at baseline, 3-, and 6-months follow-up. Subjects were randomly assigned to the Mediterranean diet (MD), Low Glycemic Index diet (LGID), or Low Glycemic Index Mediterranean diet (LGIMD). REM-C was calculated as [total cholesterol&ndash, low density lipoprotein cholesterol (LDL-C)&ndash, high density lipoprotein cholesterol (HDL-C)]. Results: REM-C levels were higher in subjects with moderate or severe NAFLD than in mild or absent ones. All diets had a direct effect in lowering the levels of REM-C after 3 and 6 months of intervention. In adherents subjects, this effect was stronger among LGIMD as compared to the control group. There was also a significant increase in REM-C levels among Severe NAFLD subjects at 3 months and a decrease at 6 months. Conclusions: fasting REM-C level is independently associated with the grade of severity of NAFLD. LGIMD adherence directly reduced the fasting REM-C in patients with MetS.

SCOPE The study aims to investigate the effects of fresh table grape consumption in healthy subjects on circulating levels of the most common human microRNAs (miRNAs). The regulatory network governed by these modulated miRNAs is also investigated. METHODS AND RESULTS Autumn Royal table grape, used in this study, is chosen for its high polyphenolic content and antioxidant properties. The study is a randomized controlled trial, in which 40 consecutive subjects are recruited on a voluntary basis and randomly assigned to two groups of the study, the control group, receiving only dietary recommendations and a grape group receiving a daily dose of 5 g of fresh table grape per kg of body weight for 21 days. All analyses are performed at baseline and after 21 days of dietary treatment. Circulating miRNAs levels are detected by Real-Time quantitative PCR (RT-qPCR) followed by bioinformatic functional analysis. The study identifies 20 circulating miRNAs differentially expressed in healthy subjects after grape intake, and in particular, 18 of 20 are down-regulated and 2 are up-regulated. CONCLUSION The dietary intake of table grape affects circulating miRNAs levels in healthy subjects, particularly the miRNAs related to pathways involved in counteracting cancer development, including gastrointestinal cancers.

Several new multikinase inhibitors have recently been introduced into clinical practice for hepatocellular carcinoma (HCC) therapy. Small increases in survival were reported as well as considerable toxicity. There is thus a need for effective therapies with lower toxicities. We examined whether a combination of sorafenib and regorafenib might also be effective at very low concentrations, with resulting potential for lessened clinical toxicity. MTT test, clonogenic assay, Ki67 staining and cell cycle analysis were assessed for cell proliferation and Annexin V and western blotting analysis relative to the expression of cleaved Caspase-3 and BID for cell apoptosis. In these experimental conditions cell growth and migration were potently inhibited and apoptosis induced even in HCC cells producing high alpha fetoprotein (AFP) levels (clinically worse prognosis). The combination also inhibited levels of the two HCC biomarkers, AFP and des gamma carboxy prothrombin (DCP). Additional inhibition of Vascular Endothelial Growth Factor Receptor (VEGFR) or Insulin-like Growth Factor 1 Receptor (IGF1R) enhanced effects on AFP and DCP levels, cell growth inhibition and MAPK and PI3K/Akt signaling inhibition due to sorafenib/regorafenib combination. These combinations have the potential for decreased toxicity while simultaneously enhancing therapeutic effects. This potential decrease in toxicity is being explored in ongoing studies.

Objective:In the postmenopausal period, most women suffer vasomotor symptoms (VMS). It is well-known that VMS can worsen the quality of life. Diet seems to play a relevant role in the development of VMS, but the effect of diet on VMS is mainly limited to observational studies, and analyses of nutritional supplements. The aim of this study was thus to determine the efficacy of a lactoovo- vegetarian (LOVe) diet rich in omega-3 fatty acids vs. a lacto-ovo-vegetarian diet rich in EVO (extra-virgin olive oil) in reducing VMS frequency in postmenopausal women.Methods:A two-arms (lacto-ovo-vegetarian diet with EVO vs. lacto-ovo-vegetarian diet rich in omega-3) randomized-controlled trial with a follow-up period of 16 weeks. We considered as primary outcome the change in the Kupperman index (follow-up vs. baseline evaluation, reported as delta, D) and in its subscales. Secondary outcomes included changes in common anthropometric and biohumoral measurements.Results:Among 54 women randomly assigned to a study group, 40 (mean age 55.1±5.4 years) completed the study and complied with their assigned diet. Women randomized to the omega-3 group (n=18) showed significant improvements, compared to the EVO group (n=22), in Kupperman index (Δ=-11.4±9.8 vs. -5.9±8.2; p=0.045), hot flashes (Δ=-3.3±3.4 vs. -1.3±2.6; p=0.04), and a marginally significant improvement in nervousness (Δ=-1.7±1.7 vs. -0.8±1.5; p=0.07). No significant differences were observed for the secondary outcomes. No relevant side effects were reported.Conclusion:After 16 weeks, a lacto-ovo-vegetarian diet rich in omega-3 reduced VMS frequency in postmenopausal women more than the lacto-ovo-vegetarian diet rich in EVO.

Background:Systematic difference between thyroid-stimulating hormone (TSH) immunoassays may produce misleading interpretation when samples of the same patients are measured with different methods. The study aims were to evaluate whether systematic differences are present among TSH immunoassays, and whether it is possible to obtain a better harmonization among TSH methods using results obtained in external quality assessment (EQA) schemes.Methods:Seven Italian clinical laboratories measured TSH in 745 serum samples of healthy subjects and patients with thyroid disorders. These samples were also re-measured by two reference laboratories of the study with the six TSH immunoassays most popular in Italy after 2 months of storage at −80 °C. Moreover, these data were compared to 53,823 TSH measurements, obtained by laboratories participant to 2012–2015 EQA annual cycles in 72 quality control samples (TSH concentrations from about 0.1 mIU/L to 18.0 mIU/L). TSH concentrations were recalibrated using a mathematical approach based on the principal component analysis (PCA).Results:Systematic differences were found between the most popular commercially available TSH immunoassays. TSH concentrations measured by the clinical laboratories were very closely correlated to those measured with the same method by reference laboratories after 2 months of storage at −80 °C. After recalibration using the PCA approach the variation of TSH values significantly decreased from a median pre-calibration value of 13.53% (10.79%–16.53%) to 9.63% (6.90%–13.21%) after recalibration.Conclusions:Our data suggest that EQA schemes are useful to improve harmonization among TSH immunoassays and also to produce some mathematical formulas, which can be used by clinicians to better compare TSH values measured with different methods.