Main factors influencing long-term outcomes of liver transplantation in 2022.

Liver transplant (LT) outcomes have markedly improved in the recent decades, even if long-term morbidity and mortality are still considerable. Most of late deaths are independent from graft function and different comorbidities, including complications of metabolic syndrome and de novo neoplasms, seem to play a key role in determining long-term outcomes in LT recipients. This review discusses the main factors associated with late mortality and suggests possible strategies to improve long-term management and follow-up after liver transplantation. In particular, the reduction of drug toxicity, the use of tools to identify high-risk patients, and setting up a multidisciplinary team also for long-term management of LT recipients may further improve survival after liver transplantation.

Correlation of Ultrasound Scores with Endoscopic Activity in Crohn's Disease: A Prospective Exploratory Study.

BACKGROUND AND AIMS: Intestinal ultrasound [IUS] is widely accepted as a reliable tool to monitor Crohn's disease [CD]. Several IUS scores have been proposed, but none has been formally accepted by international organizations. Our aim here was to compare the available scores regarding their correlation with endoscopic activity. METHODS: Consenting CD patients undergoing ileocolonoscopy at our Unit between September 2021 and February 2023 were included. Endoscopic activity was defined as SES-CD ≥ 3 or Rutgeerts score ≥ i2b for operated patients. IUS was performed within 6 weeks of endoscopy and scored with IBUS-SAS, BUSS, Simple-US and SUS-CD scores. All correlations were performed using Spearman's rank coefficient [rho = ρ]. Receiver operating characteristic [ROC] curves were compared with the Hanley and McNeil method. RESULTS: Of 73 CD patients, 45 [61.6%] presented endoscopic activity, of whom 22 were severe [30.1%]. All IUS scores showed a significant positive correlation with endoscopy [p < 0.0001], with IBUS-SAS ranking the highest [ρ = 0.87]. Similarly, IBUS-SAS was the most highly correlated with clinical activity [ρ = 0.58]. ROC analysis of IBUS-SAS for any endoscopic activity showed the highest area under the curve (0.95 [95% confidence interval 0.87-0.99]), with sensitivity of 82.2% and specificity of 100% for a cut-off value of 25.2. IBUS-SAS was statistically superior to all the other scores in detecting severe endoscopic activity [SES-CD ≥ 9 or Rutgeerts i4]. CONCLUSIONS: All IUS scores provided solid correlation with endoscopy and clinical symptoms. IBUS-SAS outperformed the others due to a more granular description that might help in stratifying different levels of disease activity. Therefore, the use of IBUS-SAS in centres with well-founded expertise in IUS can be suggested.

Ingestible light source for intragastric antibacterial phototherapy: a device safety study on a minipig model.

Helicobacter pylori gastric infections are among the most diffused worldwide, suffering from a rising rate of antibiotic resistance. In this context, some of the authors have previously designed an ingestible device in the form of a luminous capsule to perform antibacterial photodynamic inactivation in the stomach. In this study, the light-emitting capsules were tested to verify the safety of use prior to perform clinical efficacy studies. First, laboratory tests measured the capsule temperature while in function and verified its chemical resistance in conditions mimicking the gastric and gut environments. Second, safety tests in a healthy minipig model were designed and completed, to verify both the capsule integrity and the absence of side effects, associated with its illumination and transit throughout the gastrointestinal tract. To this aim, a capsule administration protocol was defined considering a total of 6 animals with n = 2 treated with 8 capsules, n = 2 treated with 16 capsules and n = 2 controls with no capsule administration. Endoscopies were performed in sedated conditions before-after every capsule administration. Biopsies were taken from the corpus and antrum regions, while the gastric cavity temperature was monitored during illumination. The bench tests confirmed a very good chemical resistance and a moderate (about 3 °C) heating of the capsules. The animal trials showed no significant effects on the gastric wall tissues, both visually and histologically, accompanied with overall good animal tolerance to the treatment. The integrity of the administered capsules was verified as well. These encouraging results pose the basis for the definition of successive trials at the clinical level.

Pregnancy outcomes in inflammatory bowel disease: Data from a large cohort survey.

OBJECTIVES: Inflammatory bowel disease (IBD) can affect young and reproductively active patients. Our aim was to analyze pregnancy outcomes in a large cohort of women with IBD. METHODS: All women with at least one pregnancy were given a questionnaire regarding the outcome of their pregnancy. They were divided into IBD pregnancies and controls depending on whether pregnancy occurred within or over 10 years prior to the diagnosis of IBD. RESULTS: Three hundred questionnaires were analyzed for a total of 478 pregnancies that led to live-born babies. Age at conception was older in IBD women than in the controls. Active smoking was more frequent in the control group. The risk of intrauterine growth restriction (IUGR) was higher in IBD pregnancies (odds ratio [OR] 3.028, 95% confidence interval [CI] 1.245-7.370, P = 0.013). The week of gestation at delivery was lower in the IBD population. And the risk of cesarean section was higher in IBD pregnancies (OR 1.963, 95% CI 1.274-3.028, P = 0.002). Among women with IBD pregnancy, the risk of preterm birth was higher in patients with active disease at the time of conception (OR 4.088, 95% CI 1.112-15.025, P = 0.030), but lower in patients who continued regular therapy during pregnancy. Similarly, the risk of urgent cesarean section was reduced in the case of disease remission, while the risk of a planned cesarean delivery was higher in patients with perianal disease (OR 11.314, 95% CI 3.550-36.058, P < 0.01). CONCLUSIONS: Our study shows a higher risk of IUGR, cesarean section, and poor blood pressure control in IBD pregnancies. We emphasize the importance of achieving disease remission before considering pregnancy.

Single CT colonography versus three rounds of faecal immunochemical test for population-based screening of colorectal cancer (SAVE): a randomised controlled trial.

BACKGROUND: Colorectal cancer screening is recommended for people aged 50-75 years, but the optimal screening test and strategy are not established. We aimed to compare single CT colonography versus three faecal immunochemical test (FIT) rounds for population-based screening of colorectal cancer. METHODS: This randomised controlled trial was done in Florence, Italy. Adults aged 54-65 years, never screened for colorectal cancer, were randomly assigned (1:2) by simple randomisation and invited by post to either a single CT colonography (CT colonography group) or three FIT rounds (FIT group; each round was done 2 years apart). Exclusion criteria included previous colorectal cancer, advanced adenoma, or inflammatory bowel disease, colonoscopy within the last 5 years or FIT within the last 2 years, and severe medical conditions. Participants who had a colonic mass or at least one polyp of 6 mm or more in diameter in the CT colonography group and those who had at least 20 µg haemoglobin per g faeces in the FIT group were referred for work-up optical colonoscopy. The primary outcome was detection rate for advanced neoplasia. Outcomes were assessed in the modified intention-to-screen and per-protocol populations. The trial is registered with ClinicalTrials.gov, NCT01651624. FINDINGS: From Dec 12, 2012, to March 5, 2018, 14 981 adults were randomised and invited to screening interventions. 5242 (35·0%) individuals (2809 [53·6%] women and 2433 [46·4%] men) were assigned to the CT colonography group and 9739 (65·0%) individuals (5208 [53·5%] women and 4531 [46·5%] men) were assigned to the FIT group. Participation in the screening intervention was lower in the CT colonography group (1286 [26·7%] of the 4825 eligible invitees) than it was for the FIT group (6027 [64·9%] of the 9288 eligible invitees took part in at least one screening round, 4573 [49·2%] in at least two rounds, and 3105 [33·4%] in all three rounds). The detection rate for advanced neoplasia of CT colonography was significantly lower than the detection rate after three FIT rounds (1·4% [95% CI 1·1-1·8] vs 2·0% [1·7-2·3]; p=0·0094) in the modified intention-to-screen analysis, but the detection rate was significantly higher in the CT colonography group than in the FIT group (5·2% [95% CI 4·1-6·6] vs 3·1% [2·7-3·6]; p=0·0002]) in the per-protocol analysis. Referral rate to work-up optical colonoscopy (the secondary outcome of the trial) was significantly lower for the CT colonography group than for the FIT group after three FIT rounds (2·7% [95% CI 2·2-3·1] vs 7·5% [7·0-8·1]; p<0·0001) in the modified intention-to-screen analysis, whereas no significant difference was observed in the per-protocol analysis (10·0% [8·4-11·8] vs 11·6% [10·8-12·4]). No major complications were observed in the CT colonography group after screening and work-up optical colonoscopy, whereas three cases of bleeding were reported in the FIT group after work-up optical colonoscopy (two after the first FIT and one after the second FIT). INTERPRETATION: Greater participation makes FIT more efficient than single CT colonography for detection of advanced neoplasia in population screening for colorectal cancer. Nonetheless, higher detection rate in participants and fewer work-up colonoscopies are possible advantages of CT colonography as a screening tool, which might deserve consideration in future trials. FUNDING: Government of Tuscany and Cassa di Risparmio di Firenze Foundation. TRANSLATION: For the Italian translation of the abstract see Supplementary Materials section.

Higher volume growth rate is associated with development of worrisome features in patients with branch duct-intraductal papillary mucinous neoplasms.

BACKGROUND: Branch duct-intraductal papillary mucinous neoplasms (BD-IPMNs) are the most common pancreatic cystic tumours and have a low risk of malignant transformation. Current guidelines only evaluate cyst diameter as an important risk factor but it is not always easy to measure, especially when comparing different methods. On the other side, cyst volume is a new parameter with low inter-observer variability and is highly reproducible over time. AIM: To assess both diameter and volume growth rate of BD-IPMNs and evaluate their correlation with the development of malignant characteristics. METHODS: Computed tomography scans and magnetic resonance imaging exams were retrospectively reviewed. The diameter was measured on three planes, while the volume was calculated by segmentation: The volume of the entire cyst was determined by manually drawing a region of interest along the edge of the neoplasm on each consecutive slice covering the whole lesion; therefore, a three-dimensional volume of interest was finally obtained with the calculated value expressed in cm3. Changes in size over time were measured. The development of worrisome features was evaluated. RESULTS: We evaluated exams of 98 patients across a 40.5-mo median follow-up time. Ten patients developed worrisome features. Cysts at baseline were significantly larger in patients who developed worrisome features (diameters P = 0.0035, P = 0.00652, P = 0.00424; volume P = 0.00222). Volume growth rate was significantly higher in patients who developed worrisome features (1.12 cm3/year vs 0 cm3/year, P = 0.0001); diameter growth rate was higher as well, but the difference did not always reach statistical significance. Volume but not diameter growth rate in the first year of follow-up was higher in patients who developed worrisome features (0.46 cm3/year vs 0 cm3/year, P = 0.00634). CONCLUSION: The measurement of baseline volume and its variation over time is a reliable tool for the follow-up of BD-IPMNs. Volume measurement could be a better tool than diameter measurement to predict the development of worrisome features.

Isoforms of the orphan nuclear receptor COUP­TFII differentially modulate pancreatic cancer progression.

The expression of the nuclear receptor transcription factor (TF) COUP­TFII is broadly associated with cell differentiation and cancer development, including of pancreatic ductal adenocarcinoma (PDAC), a devastating disease with one of the poorest prognoses among cancers worldwide. Recent studies have started to investigate the pathological and physiological roles of a novel COUP­TFII isoform (COUP­TFII_V2) that lacks the DNA­binding domain. As the role of the canonical COUP­TFII in PDAC was previously demonstrated, the present study evaluated whether COUP­TFII_V2 may have a functional role in PDAC. It was demonstrated that COUP­TFII_V2 naturally occurs in PDAC cells and in primary samples, where its expression is consistent with shorter overall survival and peripheral invasion. Of note, COUP­TFII_V2, exhibiting nuclear and cytosolic expression, is linked to epithelial to mesenchymal transition (EMT) and cancer progression, as confirmed by nude mouse experiments. The present results demonstrated that COUP­TFII_V2 distinctively regulates the EMT of PDAC and, similarly to its sibling, it is associated with tumor aggressiveness. The two isoforms have both overlapping and exclusive functions that cooperate with cancer growth and dissemination. By studying how PDAC cells switch from one isoform to the other, novel insight into cancer biology was gained, indicating that this receptor may serve as a novel possible target for PDAC management.

Infliximab is more effective than cyclosporine as a rescue therapy for acute severe ulcerative colitis: a retrospective single-center study.

BACKGROUND: Acute severe ulcerative colitis (ASUC) is a potentially life-threatening disease, and the best option in cases of steroid-refractory disease is still debated. We compared the early- and long-term efficacy and safety of the 2 available "rescue therapies", infliximab (IFX) and cyclosporine (CYS), in this setting. METHODS: We retrospectively evaluated patients admitted for ASUC and treated with "rescue therapy". The primary endpoint was early colectomy-free survival (30 days) and colectomy-free survival until the end of follow up. The secondary endpoints were predictors of colectomy and long-term maintenance of the treatment strategy over time. RESULTS: Of 129 patients admitted, 68 received rescue therapy (47 with IFX), whereas 7 underwent early colectomy (10.3%). At 30 days, fewer patients treated with IFX showed a need for colectomy (8.5% vs. 14.3%) compared to those in the CYS group, though the difference was non-significant (odds ratio [OR] 0.69, 95% confidence interval [CI] 0.10-4.69; P=0.47). No severe side effects due to IFX and CYS were observed. During a mean follow up of 40 months, 23 additional patients (37.7%) underwent colectomy, and the rate was significantly lower in the IFX group (25.6%) than in the CYS group (66.7%) (hazard ratio 0.25, 95%CI 0.10-0.61; P=0.003). Colectomy-free survival was significantly higher in the IFX group than in the CYS group (P=0.018) at 12 months. CONCLUSIONS: In our setting, the early outcomes of IFX and CYS for ASUC were comparable. IFX was associated with significantly lower colectomy rates during the observation period and had a similar safety profile to CYS.

Non-small-bowel lesions identification by capsule endoscopy: A single centre retrospective study.

BACKGROUND: Capsule endoscopy has been considered the first-line approach for the investigation of obscure gastro-intestinal bleeding since its approval in 2001. Our study aims to evaluate the diagnostic yield of capsule endoscopy in the investigation of this condition. We also analyse the incidence of non-small-bowel lesions missed after conventional endoscopy and later detected by capsule endoscopy in patients with suspected obscure bleeding. METHODS: A total of 290 patients with negative conventional endoscopy referred to our centre to undergo a capsule endoscopy examination for the investigation of obscure gastro-intestinal bleeding. We considered as non-small-bowel lesions those outside the tract between the second duodenal portion and the ileocecal valve. We also looked for actively bleeding lesions at the time of the exam. RESULTS: Intestinal preparation was good, adequate or poor in 74.1%, 8.4%, and 17.5% of the tests, respectively. Caecum was reached in 92.4%. Capsule retention occurred in 0.7%. Mean small bowel transit time was 5hours and 13minutes. Diagnostic yield was 73.8%. An actively bleeding lesion was noticed in 39.3% of positive tests. Capsule endoscopy revealed clinically significant non-small-bowel lesions missed at gastroscopy or colonoscopy in 30.3% of patients, 43.2% of which were bleeding. CONCLUSIONS: Capsule endoscopy has high diagnostic yield and safety in the investigation of obscure gastro-intestinal bleedings. Given the high percentage of non-small-bowel lesions detected, it may be appropriate to consider an endoscopic second look before performing a capsule endoscopy study.

Infectious risk of vedolizumab compared with other biological agents in the treatment of inflammatory bowel disease.

BACKGROUND AND AIMS: Vedolizumab is a gut-selective anti-integrin (α4ß7) antibody for the treatment of inflammatory bowel disease with a well-known optimal safety profile. We aimed to compare its risk of infections with that of anti-TNF drugs and ustekinumab in patients with both ulcerative colitis and Crohn's disease. METHODS: All Crohn's disease and ulcerative colitis patients undergoing biological treatment at our centre between 2013 and 2019 were retrospectively included. All infectious complications were registered, considering both inpatient and outpatient events. A comparison of the exposure-adjusted infection rates of vedolizumab, anti-TNF drugs and ustekinumab was carried out, with a specific focus on the rate of gut infections. All infection rates were expressed in events per patient-years (PYs). RESULTS: The overall exposure-adjusted infection rate was 11.5/100 PYs. The most common infections were respiratory tract infections, cutaneous infections, HSV infections/reactivations and gut infections. The rate of serious infections was 1.3/100 PYs. The infection rate of vedolizumab was 17.5/100 PYs, with Crohn's disease patients having a lower infection risk compared with ulcerative colitis patients (P = 0.035). Gut infections were observed in 3.0% of the whole patient population (1.5/100 PYs) and were more common in the vedolizumab group (P = 0.0001). CONCLUSIONS: Our study confirms the good safety profile of vedolizumab. Among patients treated with vedolizumab, those with ulcerative colitis have a higher risk of developing infectious complications. Patients treated with vedolizumab have a higher risk of gut infections compared with patients treated with anti-TNF drugs or ustekinumab. Presumably, this is due to the gut-selective mechanism of action of vedolizumab.

Resection of NAFLD-Associated HCC: Patient Selection and Reported Outcomes.

Global prevalence of non-alcoholic fatty liver disease (NAFLD) has been growing in the last decades, especially in western countries, due to increased prevalence of diabetes, obesity or other components of metabolic syndrome. NAFLD recently became an important cause of hepatocellular carcinoma (HCC), even in non-cirrhotic patients. Patients with HCC-NAFLD are usually older, with more morbidities (especially cardiovascular diseases and metabolic disorders) and have advanced disease at the diagnosis due to the absence of surveillance, which is considered not cost-effective in patients without advanced fibrosis/cirrhosis, given the large prevalence of NAFLD in the general population. For these reasons, patients with HCC-NAFLD unlikely underwent curative treatments, and have been reported to have lower overall survival (OS) compared to individuals with HCC related to other aetiologies. However, this difference is not confirmed by data of patient subgroups who received curative treatment. In our review, we selected studies published over the past 8 years that analyse characteristics and outcomes of HCC-NAFLD patients who underwent surgery with the aim of identifying features that could predict outcomes and potential selection criteria. All the studies confirm that patients with HCC-NAFLD are older, with many comorbidities and that HCC occurs frequently even in non-cirrhotic livers. There is no agreement about intraoperative and perioperative complications. Regarding outcomes, all papers agree that patients with HCC in NAFLD who undergo surgery have a better OS compared to other aetiologies. Summarizing, surgery is a good curative option for patients with HCC-NAFLD, perhaps even better than transplantation in terms of OS. In this group of patients, it seems to be essential to evaluate cardio-pulmonary and general operative risk, in addition to the normal risk assessment related to liver function to avoid an underestimation, especially for patients without severe underlying fibrosis.

Stevens-Johnson Syndrome and Herpes Simplex Type 1 Infection during Adalimumab Therapy for Crohn's Disease.

Stevens-Johnson syndrome (SJS) is a severe mucocutaneous adverse drug reaction with a relatively high mortality rate. SJS is described during herpes simplex virus type 1 (HSV1) infection and, rarely, even during adalimumab therapy. We report the case of a patient with Crohn's disease who developed SJS during an HSV1 infection and a contemporaneous anti-TNFα therapy with adalimumab. Remission was achieved with suspension of adalimumab and high doses of intravenous steroids and antivirals. Patients with HSV1 infection and on adalimumab therapy have a combined risk of SJS and should be monitored closely.

Increased Risk of Liver Cirrhosis during Azathioprine Therapy for Crohn's Disease.

Azathioprine is a cornerstone of the therapy of Crohn's disease. Unfortunately, infections and malignancies are relatively common adverse effects related to this drug; however, cirrhosis is exceptionally reported as a side effect. We report the case of a 49-year-old male patient with ileocolonic steno-penetrating Crohn's disease who developed hepatic cirrhosis while treated with azathioprine. After taking azathioprine for 3 years with regular follow-up, he developed pancytopenia, and liver cirrhosis was diagnosed with ultrasound, abdomen computed tomography scan, transient elastography, and liver biopsy. As all other causes of liver damage were excluded, azathioprine was believed to be the cause of liver injury and therefore was interrupted.

The Relationship Between the Serotonin Metabolism, Gut-Microbiota and the Gut-Brain Axis.

BACKGROUND: Serotonin (5-HT) has a pleiotropic function in gastrointestinal, neurological/psychiatric and liver diseases. The aim of this review was to elucidate whether the gut-microbiota played a critical role in regulating peripheral serotonin levels. METHODS: We searched for relevant studies published in English using the PubMed database from 1993 to the present. RESULTS: Several studies suggested that alterations in the gut-microbiota may contribute to a modulation of serotonin signalling. The first indication regarded the changes in the composition of the commensal bacteria and the intestinal transit time caused by antibiotic treatment. The second indication regarded the changes in serotonin levels correlated to specific bacteria. The third indication regarded the fact that decreased serotonin transporter expression was associated with a shift in gut-microbiota from homeostasis to inflammatory type microbiota. Serotonin plays a key role in the regulation of visceral pain, secretion, and initiation of the peristaltic reflex; however, its altered levels are also detected in many different psychiatric disorders. Symptoms of some gastrointestinal functional disorders may be due to deregulation in central nervous system activity, dysregulation at the peripheral level (intestine), or a combination of both (brain-gut axis) by means of neuro-endocrine-immune stimuli. Moreover, several studies have demonstrated the profibrogenic role of 5-HT in the liver, showing that it works synergistically with platelet-derived growth factor in stimulating hepatic stellate cell proliferation. CONCLUSION: Although the specific interaction mechanisms are still unclear, some studies have suggested that there is a correlation between the gut-microbiota, some gastrointestinal and liver diseases and the serotonin metabolism.

Comparison and correlation of fibrosis stage assessment by collagen proportionate area (CPA) and the ELF panel in patients with chronic liver disease.

BACKGROUND: Fibrosis progression is the common consequence of most chronic liver diseases. AIMS: To evaluate the performance of Collagen Proportionate Area (CPA) and ELF using Ishak's score in patients with chronic liver diseases. METHODS: Retrospective analysis of medical data from patients on whom a liver biopsy was performed as part of the diagnostic assessment. CPA was calculated by using digital image analysis and then compared with Ishak and ELF scores. RESULTS: 143 patients (84 men (59%); mean age 48.8 ±â€¯12.8 years) were evaluated. Patients were mainly affected by viral hepatitis (92 HCV and 8 HBV). CPA and ELF values increased with worsening Ishak stage (P < 0.001) and their median values were significantly different among Ishak stages (P < 0.001). There was a significant correlation between CPA and ELF (r = 0.5). In AUROC analysis, CPA and ELF had similar diagnostic accuracy in identifying cirrhosis, but CPA had higher diagnostic accuracy than ELF in identifying significant or absent fibrosis. High ELF scores were observed in non-cirrhotic patients who suffered non-liver related deaths. CONCLUSIONS: This study demonstrated that CPA and ELF values successfully identified patients with advanced fibrosis or cirrhosis, thus confirming the role of ELF as a clinical method for non-invasive assessment of fibrosis stage in chronic hepatitis.

Epidemiological, demographic and clinical data on chronic viral hepatitis C in Tuscany.

BACKGROUND: Recent introduction of direct antiviral agents (DAAs) has completely changed the scenario regarding hepatitis C virus (HCV) treatment. Certain countries' economic health programs prioritize DAAs according to specific clinical features of HCV-infected patients. The aim of this study was to define epidemiological, demographic and clinical characteristics of HCV-infected patients in the Tuscany region of central Italy. METHODS: We enrolled HCV patients with chronic viral hepatitis who were referred to the outpatient services of 16 hospitals in Tuscany from 1 January 2015 to 31 December 2015. Case report forms contained patient information including main demographic data, blood chemistry data, viral hepatitis markers, instrumental evaluations (liver biopsy or transient elastometry, liver ultrasound), eligibility for DAAs, and liver transplantation or therapy already in progress. RESULTS: Of all patients considered, 2919 HCV patients were enrolled (mean age: 57.44 ± 15.15; 54% males, 46% females). All routes of transmission were well represented (intravenous drug use in 20.7%; nosocomial/dental care in 20.6%; and coagulation factors/blood transfusions in 13.3%). Diabetes was the highest represented comorbidity (20.8%), followed by metabolic syndrome (15.5%) and ischemic heart disease (6.2%). The most prevalent HCV genotypes were 1b (47.4%) and 2 (16.5%). In the whole cohort of patients, 32.8% were cirrhotic (40 patients were listed for liver transplantation). Signs of portal hypertension were present mostly in the group older than 45 years (92.3%). Extrahepatic HCV-related diseases were present in 13.3% of cases (cryoglobulinemic syndrome in 58.3% and B-cell non-Hodgkin's lymphoma in 10.5%). CONCLUSIONS: Our study provides evidence of a high prevalence of epidemiological changes in HCV infection with a major prevalence of advanced liver disease, such as portal hypertension, in this elderly cohort of patients.

COUP-TFII in Health and Disease.

The nuclear receptors (NRs) belong to a vast family of evolutionary conserved proteins acting as ligand-activated transcription factors. Functionally, NRs are essential in embryogenesis and organogenesis and in adulthood they are involved in almost every physiological and pathological process. Our knowledge of NRs action has greatly improved in recent years, demonstrating that both their expression and activity are tightly regulated by a network of signaling pathways, miRNA and reciprocal interactions. The Chicken Ovalbumin Upstream Promoter Transcription Factor II (COUP-TFII, NR2F2) is a NR classified as an orphan due to the lack of a known natural ligand. Although its expression peaks during development, and then decreases considerably, in adult tissues, COUP-TFII is an important regulator of differentiation and it is variably implicated in tissues homeostasis. As such, alterations of its expression or its transcriptional activity have been studied and linked to a spectrum of diseases in organs and tissues of different origins. Indeed, an altered COUP-TFII expression and activity may cause infertility, abnormality in the vascular system and metabolic diseases like diabetes. Moreover, COUP-TFII is actively investigated in cancer research but its role in tumor progression is yet to be fully understood. In this review, we summarize the current understanding of COUP-TFII in healthy and pathological conditions, proposing an updated and critical view of the many functions of this NR.

Patients' experience of screening CT colonography with reduced and full bowel preparation in a randomised trial.

OBJECTIVES: To assess patients' experience of bowel preparation and procedure for screening CT colonography with reduced (r-CTC) and full cathartic preparation (f-CTC) that showed similar detection rate for advanced neoplasia in a randomised trial. METHODS: Six hundred seventy-four subjects undergoing r-CTC and 612 undergoing f-CTC in the SAVE trial were asked to complete two pre-examination questionnaires-(1) Life Orientation Test - Revised (LOT-R) assessing optimism and (2) bowel preparation questionnaire-and a post-examination questionnaire evaluating overall experience of CTC screening test. Items were analysed with chi-square and t test separately and pooled. RESULTS: LOT-R was completed by 529 (78%) of r-CTC and by 462 (75%) of f-CTC participants and bowel preparation questionnaire by 531 (79%) subjects in the r-CTC group and by 465 (76%) in the f-CTC group. Post-examination questionnaire was completed by 525 (78%) subjects in the r-CTC group and by 453 (74%) in the f-CTC group. LOT-R average score was not different between r-CTC (14.27 ± 3.66) and f-CTC (14.54 ± 3.35) (p = 0.22). In bowel preparation questionnaire, 88% of r-CTC subjects reported no preparation-related symptoms as compared to 70% of f-CTC subjects (p < 0.001). No interference of bowel preparation with daily activities was reported in 80% of subjects in the r-CTC group as compared to 53% of subjects in the f-CTC group (p < 0.001). In post-examination questionnaire, average scores for discomfort of the procedure were not significantly different between r-CTC (3.53 ± 0.04) and f-CTC (3.59 ± 0.04) groups (p = 0.84). CONCLUSIONS: Reduced bowel preparation is better tolerated than full preparation for screening CT colonography. KEY POINTS: • Reduced bowel preparation is better tolerated than full preparation for screening CT colonography. • Procedure-related discomfort of screening CT colonography is not influenced by bowel preparation. • Males tolerate bowel preparation and CT colonography screening procedure better than females.

Metabolic Signature of Primary Biliary Cholangitis and Its Comparison with Celiac Disease.

Primary biliary cholangitis (PBC) is a chronic autoimmune liver disease characterized by ongoing inflammatory destruction of the interlobular bile ducts, eventually leading to chronic cholestasis and biliary cirrhosis. This study primarily aims to define the metabolomic signature of PBC after comparison with healthy controls (HC). Second, it aims to evaluate the possible metabolic association between PBC and celiac disease (CD), an immune-mediated disorder frequently associated with PBC. Serum and urine samples from 20 PBC, 21 CD, and 19 sex-matched HC subjects were collected. 1H nuclear magnetic resonance (NMR) spectra for all samples were acquired, and multivariate statistics were used to evaluate the differences among the three groups and to provide information about the involved metabolites. The classification accuracies to discriminate PBC and HC groups were 78.9-84.6% for serum and 76.9% for urine. In comparison to HC, PBC patient sera were characterized by altered levels ( p value <0.05) of pyruvate, citrate, glutamate, glutamine, serine, tyrosine, phenylalanine, and lactate. PBC patient urine showed lower levels ( p value <0.05) of trigonelline and hippurate with respect to HC. Furthermore, the NMR metabolomic fingerprint was able to cluster PBC with respect to CD patients, and the classification accuracies in the discriminations between these groups were 81.9-91.7% for serum and 77.7% for urine. Our results show that PBC displays a unique metabolomic fingerprint, which led to speculation about an impaired energy metabolism, probably associated with an altered gut microbiota. PBC and CD showed two distinct metabolic fingerprints. These data could provide clues for the comprehension of the PBC pathogenetic mechanisms and the detection of novel therapeutic targets.

Clinical epidemiology of chronic viral hepatitis B: A Tuscany real-word large-scale cohort study.

AIM: To build a regional database of chronic patients to define the clinical epidemiology of hepatitis B virus (HBV)-infected patients in the Tuscan public health care system. METHODS: This study used a cross-sectional cohort design. We evaluated chronic viral hepatitis patients with HBV referred to the outpatient services of 16 hospital units. Information in the case report forms included main demographic data, blood chemistry data, viral hepatitis markers, instrumental evaluations, and eligibility for treatment or ongoing therapy and liver transplantation. RESULTS: Of 4015 chronic viral hepatitis patients, 1096 (27.3%) were HBV infected. The case report form was correctly completed for only 833 patients (64% males, 36% females; mean age 50.1 ± 15.4). Of these HBV-infected patients, 73% were Caucasian, 21% Asian, 4% Central African, 1% North African and 1% American. Stratifying patients by age and nationality, we found that 21.7% of HBV-infected patients were aged < 34 years (only 2.8% were Italian). The most represented routes of transmission were nosocomial/dental procedures (23%), mother-to-child (17%) and sexual transmission (12%). The most represented HBV genotypes were D (72%) and A (14%). Of the patients, 24.7% of patients were HBeAg positive, and 75.3% were HBeAg negative. Of the HBV patients 7% were anti-HDV positive. In the whole cohort, 26.9% were cirrhotic (35.8% aged < 45 years), and 47% were eligible for or currently undergoing treatment, of whom 41.9 % were cirrhotic. CONCLUSION: Only 27.3% of chronic viral hepatitis patients were HBV infected. Our results provide evidence of HBV infection in people aged < 34 years, especially in the foreign population not protected by vaccination. In our cohort of patients, liver cirrhosis was also found in young adults.