Quality of endoscopic screening for colorectal cancer in Italy: A national survey.

BACKGROUND: Colorectal cancer (CRC) is a major healthcare problem all over the world and screening is effective in reducing mortality and increasing survival. Since colonoscopy has a central role in faecal immunochemical test (FIT)-based CRC screening and surveillance, consistent quality measures are essential to ensure quality and outcomes. Nevertheless, screening modalities in clinical practice may differ according to the centers experience and the local availability of instrumentation and devices. AIMS: to assess the quality of endoscopic screening for CRC and adherence to international guidelines across Gastroenterology Departments in Italy. METHODS: All members of the Italian Society of Gastroenterology (SIGE) were invited to answer a web-based survey. RESULTS: Data from 64 hospitals from 17 Italian regions were analyzed. 32/64 (50.0%) were from northern, 12/64 (18.75%) from central and 20/64 (31.25%) from southern Italy. Each center is equipped with a median of 5.0 (3.5-7.0) endoscopists involved in CRC screening, 71.4% of which are gastroenterologists. After a positive FIT, most centers (93.8%) schedule a colonoscopy within 3 months. High-definition video endoscopy is routinely performed in 68.8% and chromoendoscopy in 53.1% of centers. Withdrawal time is ≥6 min in 79.9% and cecal intubation rate is ≥90% in 94.4% of departments. Finally, in 92.7% of centers adenoma detection rate (ADR) overcome the minimum standard of 25%. Analyzing the data by regional areas, a significant higher number of median endoscopic examinations/year (6500 vs 4000 and 3000, respectively, p = 0.024) and of endoscopists per center (6.5 vs 5.0 and 3.5, respectively, p < 0.001) has been registered in the northern compared to central-southern centers. CONCLUSIONS: Data from this survey show adequacy and good quality of endoscopic screening for CRC in Italy, highlighting, at the same time, relevant deficiencies and a discrepancy in procedural attitudes between the different centers. These findings call for a urgent action to overcome the shortcomings, refine and homogenize the behaviour of all screening centers in the national territory and improve the outcomes.

COVID-19 in celiac disease: a multicentric retrospective cohort study.

OBJECTIVE: Celiac disease (CD) is an autoimmune disorder, characterized by increased susceptibility to bacterial and viral infections. Therefore, the CD patients could be exposed to an increased risk of contracting SARS-CoV-2, a virus for which the WHO declared a pandemic status in March 2020. This study aims to investigate the incidence of SARS-CoV-2 infection in CD patients, to assess the impact of CD on the risk of contracting this virus. PATIENTS AND METHODS: This retrospective multicentric cohort study evaluated 542 celiac patients, who answered a questionnaire concerning both the underlying disease (adherence to the gluten-free diet, residual symptoms) and the possible SARS-CoV-2 infection (swab outcome, presence and characteristics of symptoms and type of treatment received), referring to the period between 20th January 2020 and 27th October 2020. RESULTS: Five patients (0.92%) tested positive; of these, 2 were asymptomatic and 3 developed symptoms of COVID-19. The incidence of SARS-CoV-2 infection in CD patients was not significantly different from the general population. The ratio of positive/diagnostic swabs tends to be higher in CD patients than in the general population (IR: 0.15; 0.06; p=0.06), whereas the number of subjects who performed the swab in this group is significantly lower (IR: 0.06; 0.15; p<0.001). CONCLUSIONS: Although CD patients are more susceptible to infections, the incidence of SARS-CoV-2 infection in our sample was not significantly different from the general population. However, the positive/diagnostic swabs ratio seems to be higher, probably also due to the lower number of patients tested.

How to define a quadruple aim framework to assess value in critical pathway of the patients with Clostridioides difficile infection.

OBJECTIVE: The study aims to define the set of Key Performance Indicators (KPIs) required to assess the Value delivered by managing patients with Clostridioides difficile infection through a Critical Pathway. We used the quadruple aim Value-Based approach, and we validated the set of KPIs with the Delphi method. MATERIALS AND METHODS: The study focuses on patients on board a Critical Pathway on Clostridioides difficile Infection and targeted towards a Fecal Microbiota Transplantation (FMT). FMT has been used to successfully treat recurrent Clostridium difficile infection. A two-round e-Delphi survey collecting data was conducted in 2019-2020 to validate the Value-Based evaluation tool. The Value-Based criteria taken into account are Clinical Outcomes, Experience of Care, Per-capita cost, Physician's burnout. RESULTS: The two rounds led to the validation of 50 items, and four primary clinical outcomes (Mortality rate, length of stay, readmission and complications related to the illness). CONCLUSIONS: The evaluation tool included is validated in its totality and can provide a comprehensive overview of the Value created by the Critical pathway for patients with Clostridioides difficile. We can extend the approach illustrated in this study can also to evaluate other Critical pathways.

A potential risk assessment tool to monitor pathogens circulation in coastal waters.

The present study reports data on a 20 months campaign monitoring enteric viruses (hepatitis A, norovirus, rotavirus, astrovirus, sapovirus, and aichivirus) and bacteria (Salmonella spp.) in seawater. The aim of this work was to assess the potential correlation among the presence of viruses/bacteria and different environmental factors like seasonality, water discharge sources (treated and untreated wastewater, mixed waters and raw water) as well as influence of the Italian lockdown measure against COVID-19 pandemic. Results showed different prevalence of the investigated viruses with values equal to 16 % for norovirus GI, 15.1 % for norovirus GII, followed by 13.8 % for astrovirus, and 13.3 % for sapovirus. Rotavirus was detected in the 8.4 % of samples and aichivirus was detected with the lowest prevalence of 3.5 %. Hepatitis A virus was never identified in the monitoring campaign. Salmonella spp. was detected with a prevalence of 36.6 %. Statistical analysis displayed a high correlation for the two noroviruses simultaneous detection (NGI and NGII) while a lower correlation was found for co-presence of noroviruses with astrovirus, sapovirus or Salmonella spp. A significant decrease of enteric pathogens in seawater was observed during the restrictions period. Results on seasonality highlighted a higher viral prevalence correlated to the wet season for all the pathogens but rotavirus and aichivirus, which instead showed an opposite trend and a higher incidence in the dry season. With respect to discharge typology, some viruses displayed a higher prevalence in treated waters (astrovirus, rotavirus, sapovirus and aichivirus) while the other investigated pathogens (noroviruses and Salmonella spp.) showed a higher prevalence in mixed waters. The main observations of this work were used to define a potential monitoring strategy that could be useful for sanitary Authorities to implement surveillance plans aimed at preventing possible sanitary outbreaks and/or environmental quality deterioration.

Prevalence of liver injury and correlation with clinical outcomes in patients with COVID-19: systematic review with meta-analysis.

OBJECTIVE: Liver involvement of SARS-CoV-2 infection has been reported in several papers, but without homogeneous findings. We aimed to systematically review the prevalence of liver involvement in patients with SARS-CoV-2 infection at their hospital admission, and its correlation with disease severity and clinical outcomes in patients with or without pre-existing chronic liver disease. MATERIALS AND METHODS: We systematically searched PubMed, Embase, Web of Science, Medline, PMC, clinical trial registries, and other Coronavirus family publications for studies reporting data on SARS-CoV-2 infection or COVID-19 and liver function tests (LFTs) alterations, as well as clinical course of patients with chronic liver disease or cirrhosis. Case reports, preprints, editorials, reviews were excluded. We also revised literature to describe the background of liver involvement during SARS-CoV-2 infection. RESULTS: 36 studies, including 20724 patients with SARS-CoV-2 infection, were included. The pooled prevalence of LFTs abnormalities at admission was 46.9% (AST 26.5%, ALT 22.8%, GGT 22.5%, ALP 5.7%, tBIL 8.0%). ALT, AST, tBIL were independent predictors of disease severity (ALT OR 1.54, 95% CI 1.17-2.03; AST OR 3.17, 95% CI 2.10-4.77; tBIL OR 2.32, 95% CI 1.18-4.58) and in-hospital mortality (ALT OR 1.48, 95% CI 1.12-1.96; AST OR 4.39, 95% CI 2.68-7.18; tBIL OR 7.75, 95% CI 2.28-26.40). Heterogeneity among studies was high. The few available data also reported that COVID-19 was associated with increased risk of liver decompensation and mortality in patients with liver cirrhosis. CONCLUSIONS: LFTs alterations were reported in up to 47% of unselected patients with COVID-19 and were associated with severe disease or in-hospital mortality. In cirrhotic patients, COVID-19 was associated with high risk of liver decompensation or mortality.

Impact of the COVID-19 pandemic on Gastroenterology Divisions in Italy: A national survey.

BACKGROUND: In Italy, the spread of the COVID-19 pandemic has stressed the entire healthcare system and required a huge re-organization of many Divisions, including those of Gastroenterology. AIMS: to assess the impact of COVID-19 pandemic on Gastroenterology Divisions across Italy. METHODS: All members of the Italian Society of Gastroenterology (SIGE) were invited to answer a web-based survey. RESULTS: Data of 121 hospitals from all 20 Italian regions were analyzed. Overall, 10.7% Gastroenterology Divisions have been converted to Covid Units. Outpatients consultations, endoscopic and ultrasound procedures were limited to urgencies and oncology indications in 85.1%, 96.2% and 72.2% of Units, respectively, and 46.7% of them suspended the screening for colorectal cancer. Moreover, 72.2% of the staff received a training for use of personal protective equipment, although 45.5% did not have sufficient devices for adequate replacement. Overall, 132 healthcare workers in 41 Gastroenterology Divisions were found to be infected. CONCLUSION: This is the first study to evaluate, at a country level, the impact of COVID-19 outbreak on Gastroenterology Divisions. Substantial changes of practice and reduction of procedures have been recorded in the entire country. The long-term impact of such modifications is difficult to estimate but potentially very risky for many digestive diseases.

Biliary tract microbiota: a new kid on the block of liver diseases?

The microbiome plays a crucial role in maintaining the homeostasis of the organism. Recent evidence has provided novel insights for understanding the interaction between the microbiota and the host. However, the vast majority of such studies have analyzed the interactions taking place in the intestinal tract. The biliary tree has traditionally been considered sterile under normal conditions. However, the advent of metagenomic techniques has revealed an unexpectedly rich bacterial community in the biliary tract. Associations between specific microbiological patterns and inflammatory biliary diseases and cancer have been recently described. Hence, biliary dysbiosis may be a primary trigger in the pathogenesis of biliary diseases. In particular, recent studies have suggested that microorganisms could play a significant role in the development of gallstones, pathogenesis of autoimmune cholangiopathies and biliary carcinogenesis. Moreover, the intimate connection between the biliary tract, liver and pancreas, could reveal hidden influences on the development of diseases of these organs. Further studies are needed to deepen the comprehension of the influence of the biliary microbiota in human pathology. This knowledge could lead to the formulation of strategies for modulating the biliary microbiota in order to treat and prevent these pathological conditions.

Laboratory handling practice for faecal microbiota transplantation.

AIMS: Faecal microbiota transplantation (FMT) consists of the infusion of faeces from a healthy donor to the gastrointestinal tract of a recipient patient to treat disease associated with alterations in gut microbiota. The objective of this article was to describe laboratory workflow of an FMT laboratory to provide tips for preparing the faecal suspensions to be infused. METHODS AND RESULTS: Twenty-stool solutions obtained from ten donors were prepared using two different protocols: magnet plate emulsion (MPE) and Seward StomacherTM Emulsion (SSE). We evaluated parameters such as preparation time, handiness, and aerobic and anaerobic microbial count. For three donors, we monitored bacterial counts after defrosting at different time-points. MPE requires more time than SSE. In terms of microbial load, both methods showed similar values, with small and statistically differences (P ≤ 0·05) regarding anaerobes in favour of SSE. Frozen aliquots showed the same bacterial load values after defrosting. CONCLUSION: Although both methods allow an easy and available preparation of a stool suspension, SSE seems more suitable, particularly for stool banking. Aerobic and anaerobic species are preserved with both protocols; and safety for laboratory operators is guaranteed. SIGNIFICANCE AND IMPACT OF THE STUDY: In recent years, FMT has become a fascinating and interesting subject. Nevertheless, there are no real guidelines describing laboratory facilities and procedures. This paper aims to be a useful and simple guide to increase the number FMT centres as much possible.

Akkermansia muciniphila: key player in metabolic and gastrointestinal disorders.

OBJECTIVE: Gut microbiota has a key role in host metabolic regulation and immune response, and its dysbiosis represents one of the main causes of gastrointestinal diseases. In this scenario, Akkermansia muciniphila is a crucial player in keeping the integrity of the gastrointestinal tract. MATERIALS AND METHODS: This review focuses on the correlation between gut microbiota and intestinal homeostasis, primarily exploring A. muciniphila and its involvement in the development of metabolic disorders and gastrointestinal diseases. RESULTS: Akkermansia muciniphila belongs to the Verrucomicrobia phylum, and it colonizes the mucus layer in the gastrointestinal tract, representing 1 to 4% of the fecal microbiota. It stimulates mucosal microbial networks, and it improves intestinal barrier function, providing crucial host immunological responses. Several studies have demonstrated the possible involvement of A. muciniphila in the development of intestinal and metabolic disorders. Indeed, adipose and glucose metabolisms are influenced by A. muciniphila, and its levels inversely correlate to inflammatory conditions, such as inflammatory bowel disease, obesity, and diabetes. Conversely, its therapeutic administration decreases their development. CONCLUSIONS: A. muciniphila exerts a key role in the maintenance of intestinal health and in host metabolic modulation. Future studies could open new horizons towards its potential therapeutic applications in gastrointestinal and extra-intestinal diseases.

Serum trefoil factor 3 predicts disease activity in patients with ulcerative colitis.

OBJECTIVE: In this study, we aimed to evaluate the role of serum trefoil factor 3 (TFF3) as a biomarker of disease activity in patients with inflammatory bowel disease (IBD) and to compare TFF3 values with those of fecal calprotectin (FC). PATIENTS AND METHODS: 128 patients with IBD were divided into four groups: 1) active ulcerative colitis (UC); 2) quiescent UC; 3) active Crohn's disease (CD); 4) quiescent CD. The serum levels of TFF3 and FC levels were assessed in all patients and 16 controls. RESULTS: Patients with active UC had higher TFF3 levels than those with quiescent UC (p<0.001), those with active (p<0.001) or quiescent CD (p<0.001) and controls (p <0.001). We found a correlation between TFF3 and FC values in patients with active (r = 0.478, p = 0.006) and quiescent UC (r=0.528, p=0.002). TFF3 levels correlated with endoscopic activity in UC (evaluated by UC Endoscopic Index of Severity - UCEIS) (r=0.662, p<0.001). CONCLUSIONS: Serum TFF3 is able to identify patients with active UC. It could be used as a marker to predict disease activity in patients with UC.

Randomised clinical trial: faecal microbiota transplantation by colonoscopy plus vancomycin for the treatment of severe refractory Clostridium difficile infection-single versus multiple infusions.

BACKGROUND: Faecal microbiota transplantation (FMT) is a highly effective treatment against recurrent Clostridium difficile infection. Far less evidence exists on the efficacy of FMT in treating severe Clostridium difficile infection refractory to antibiotics. AIM: To compare the efficacy of two FMT-based protocols associated with vancomycin in curing subjects with severe Clostridium difficile infection refractory to antibiotics. METHODS: Subjects with severe Clostridium difficile infection refractory to antibiotics were randomly assigned to one of the two following treatment arms: (1) FMT-S, including a single faecal infusion via colonoscopy followed by a 14-day vancomycin course, (2) FMT-M, including multiple faecal infusions plus a 14-day vancomycin course. In the FMT-M group, all subjects received at least two infusions, while those with pseudomembranous colitis underwent further infusions until the disappearance of pseudomembranes. The primary outcome was the cure of refractory severe Clostridium difficile infection. RESULTS: Fifty six subjects, 28 in each treatment arm, were enrolled. Twenty one patients in the FMT-S group and 28 patients in the FMT-M group were cured (75% vs 100%, respectively, both in per protocol and intention-to-treat analyses; P = 0.01). No serious adverse events associated with any of the two treatment protocols were observed. CONCLUSIONS: A pseudomembrane-driven FMT protocol consisting of multiple faecal infusions and concomitant vancomycin was significantly more effective than a single faecal transplant followed by vancomycin in curing severe Clostridium difficile infection refractory to antibiotics. Clinical-Trials.gov registration number: NCT03427229.

Fecal microbiota transplantation for the treatment of patients with ulcerative colitis and other gastrointestinal conditions beyond Clostridium difficile infection: an update.

Fecal microbiota transplantation (FMT) is the transplantation of microbial gut contents from a healthy individual into the gastrointestinal tract of a person with a disease, with a view to increasing the recipient's gut microbial diversity and bacterial richness and restoring microbial homeostasis. FMT has been proven to be a safe and effective treatment for Clostridium difficile infection (CDI) and it is now a recommended treatment for recurrent or refractory infection. FMT is not currently recommended for use outside of CDI due to concerns regarding outcome and safety; however, several case series and randomized controlled trials have described its use in a research environment for a few gastrointestinal conditions related to intestinal dysbiosis including ulcerative colitis (UC), Crohn's disease (CD) and irritable bowel syndrome (IBS). The most successful reports of the clinical efficacy of FMT in gastrointestinal conditions outside of CDI have been in treating UC. We summarize the current literature regarding the use of FMT in UC, including methodology, clinical efficacy and safety concerns, and identify pitfalls and areas for future development. We also describe the available evidence to date on the use of FMT in CD, IBS and other conditions related to intestinal dysbiosi.

Review article: the gut microbiome in inflammatory bowel disease-avenues for microbial management.

BACKGROUND: The concept of an altered collective gut microbiota rather than identification of a single culprit is possibly the most significant development in inflammatory bowel disease research. We have entered the "omics" era, which now allows us to undertake large-scale/high-throughput microbiota analysis which may well define how we approach diagnosis and treatment of inflammatory bowel disease (IBD) in the future, with a strong steer towards personalised therapeutics. AIM: To assess current epidemiological, experimental and clinical evidence of the current status of knowledge relating to the gut microbiome, and its role in IBD, with emphasis on reviewing the evidence relating to microbial therapeutics and future microbiome modulating therapeutics. METHODS: A Medline search including items 'intestinal microbiota/microbiome', 'inflammatory bowel disease', 'ulcerative colitis', 'Crohn's disease', 'faecal microbial transplantation', 'dietary manipulation' was performed. RESULTS: Disease remission and relapse are associated with microbial changes in both mucosal and luminal samples. In particular, a loss of species richness in Crohn's disease has been widely observed. Existing therapeutic approaches broadly fall into 3 categories, namely: accession, reduction or indirect modulation of the microbiome. In terms of microbial therapeutics, faecal microbial transplantation appears to hold the most promise; however, differences in study design/methodology mean it is currently challenging to elegantly translate results into clinical practice. CONCLUSIONS: Existing approaches to modulate the gut microbiome are relatively unrefined. Looking forward, the future of microbiome-modulating therapeutics looks bright with several novel strategies/technologies on the horizon. Taken collectively, it is clear that ignoring the microbiome in IBD is not an option.

Group A rotavirus genotypes in hospital-acquired gastroenteritis in Italy, 2012-14.

BACKGROUND: Group A rotaviruses (RVA) are the leading cause of acute gastroenteritis (AGE) in young (aged <5 years) children, causing ∼250,000 deaths worldwide, mostly in developing countries. Differences on nucleotide sequences of VP7 (G-type) and VP4 (P-type) genes are the basis for the binary RVA nomenclature. Although at least 32 G-types and 47 P-types of rotavirus are presently known, most RVA infections in humans worldwide are related to five major G/P combinations: G1P[8], G2P[4], G3P[8], G4P[8], and G9P[8]. AIM: To provide the hospitals of the Italian surveillance network with update information on RVA AGE. METHODS: During RVA gastroenteritis surveillance in Italy in 2012-14, a total of 2341 RVA-positive faecal samples were collected from children hospitalized with AGE, and RVA strains were genotyped following standard EuroRotaNet protocols. FINDINGS: Most strains analysed belonged to the five major human genotypes and 118 out of 2341 (5.0%) were reported to be hospital-acquired. Comparison of the distributions of the RVA genotypes circulating in the community or associated with nosocomial infections showed a different distribution of genotypes circulating inside the hospital wards, with respect to those observed in the community. G1P[8] and G9P[8] RVA strains were detected frequently, whereas G12P[8] caused a single large nosocomial outbreak. CONCLUSION: The information from this study will be useful to implement guidelines for preventing RVA AGE and optimizing the management of patients in hospital wards.

Defining the biology of intrahepatic cholangiocarcinoma: molecular pathways and early detection of precursor lesions.

Intrahepatic cholangiocarcinoma (ICC) is a rare malignant tumor of the biliary tract with growing incidence and dismal prognosis. It is responsible for 10-20% of primary liver cancer worldwide, but early diagnosis is still a challenge and few treatment options are available. Aim of this review is to summarize the current knowledge about biological features and arising molecular patterns of this disease. The identification of emerging biomarkers and early detection of precursor lesions shall play a key role in the perspective of future tailored targeted therapies.

Predictors of failure after single faecal microbiota transplantation in patients with recurrent Clostridium difficile infection: results from a 3-year, single-centre cohort study.

OBJECTIVES: Faecal microbiota transplantation (FMT) is an effective treatment for recurrent Clostridium difficile infection (CDI). Although a single faecal infusion is usually sufficient to eradicate CDI, a considerable number of patients need multiple infusions to be cured. The aim of this study was to identify predictors of failure after single faecal infusion in patients with recurrent CDI. METHODS: We included patients with recurrent CDI prospectively treated with FMT by colonoscopy. By means of univariate and multivariate analysis, variables including female gender, age, number of CDI recurrences, severity of CDI, hospitalization, inadequate bowel preparation, unrelated donor, and use of frozen faeces, were assessed to predict failure after single faecal infusion. RESULTS: Sixty-four patients (39 women; mean age 74 years) were included. Of them, 44 (69%) were cured by a single faecal infusion, whereas 20 (31%) needed repeat infusions. Overall, FMT cured 62 of 64 (97%) patients. In the subgroup of patients with severe CDI, only eight of 26 (30%) were cured with a single infusion. At multivariate analysis, severe CDI (OR 24.66; 95% CI 4.44-242.08; p 0.001) and inadequate bowel preparation (OR 11.53; 95% CI 1.71-115.51; p 0.019) were found to be independent predictors of failure after single faecal infusion. CONCLUSIONS: Severe CDI and inadequate bowel preparation appear to be independent predictors of failure after single faecal infusion in patients treated with FMT by colonoscopy for recurrent CDI. Our results may help to optimize protocols and outcomes of FMT in patients with recurrent CDI.

The role of diet on gut microbiota composition.

Gut microbiota is characterized by an inter-individual variability due to genetic and environmental factors. Among the environmental ones, dietary habits play a key role in the modulation of gut microbiota composition. There are main differences between the intestinal microbiota of subjects fed with prevalent Western diet and that of subjects with a diet rich in fibers. Specific changes in the composition of gut microbiota have been demonstrated among subjects according to a different dietary intake. A particular diet may promote the growth of specific bacterial strains, driving hosts to a consequent alteration of fermentative metabolism, with a direct effect on intestinal pH, which can be responsible for the development of a pathogenic flora. Moreover, a high-fat diet can promote the development of a pro-inflammatory gut microbiota, with a consequent increase of intestinal permeability and, consequently, of circulating levels of lipopolysaccharides. In this review, we discuss the direct role of the diet in the composition of gut microbiota and about the possible clinical consequences.