SARS-CoV-2 infection in patients with inflammatory bowel disease: comparison between the first and second pandemic waves.

BACKGROUND: In Italy, the incidence of SARS-CoV-2 infection peaked in April and November 2020, defining two pandemic waves of coronavirus disease 2019 (COVID-19). This study compared the characteristics and outcomes of patients with inflammatory bowel disease (IBD) and SARS-CoV-2 infections between pandemic waves. METHODS: Observational longitudinal study of IBD patients with SARS-CoV-2 infection. Patients with established diagnoses of IBD and of SARS-CoV-2 infection were consecutively enrolled in two periods: (i) first wave, from 1 March 2020 to 31 May 2020; and (ii) second wave, from 15 September to 15 December 2020. RESULTS: We enrolled 937 IBD patients (219 in the first wave, 718 in the second wave). Patients of the first wave were older (mean ± SD: 46.3 ± 16.2 vs. 44.1 ± 15.4 years, p = 0.06), more likely to have ulcerative colitis (58.0% vs. 44.4%, p < 0.001) and comorbidities (48.9% vs. 38.9%; p < 0.01), and more frequently residing in Northern Italy (73.1% vs. 46.0%, p < 0.001) than patients of the second wave. There were no significant differences between pandemic waves in sex (male: 54.3% vs. 53.3%, p = 0.82) or frequency of active IBD (44.3% vs. 39.0%, p = 0.18). The rates of negative outcomes were significantly higher in the first than second wave: pneumonia (27.8% vs. 11.7%, p < 0.001), hospital admission (27.4% vs. 9.7%, p < 0.001), ventilatory support (11.9% vs. 5.4%, p < 0.003) and death (5.5% vs. 1.8%, p < 0.007). CONCLUSION: Between the first and second SARS-CoV-2 pandemic waves, demographic, clinical and geographical features of IBD patients were different as were the symptoms and outcomes of infection. These differences are likely due to the different epidemiological situations and diagnostic possibilities between the two waves.

Shared microbiological and immunological patterns in periodontitis and IBD: A scoping review.

OBJECTIVES: To extract the microbiological and immunological evidence underpinning the association between periodontitis and inflammatory bowel disease (IBD). METHODS: Relevant articles were sorted through a systematic search on PubMed, Embase, Scopus and Web of Science up to October 2020. Available evidence was grouped in three different clusters: (a) studies that examined oral microbial alterations in IBD patients; (b) studies that investigated intestinal dysbiosis in patients with periodontitis; and (c) evidence for a shared immunological pattern between the two conditions. RESULTS: A total of 15 studies involving 1,171 patients were included. Oral microbiome, either subgingival or salivary, was consistently altered in patients with IBD compared to healthy subjects (a) Additionally, gut dysbiotic microbiota of IBD patients was colonized by pathobionts from oral origin, either via haematogenous or enteric route. Suffering from periodontitis is associated with lower alpha diversity in the gut microbiome (b) Lastly, both IBD and periodontitis are characterized by similar expression patterns of inflammatory cytokines at the gingival and gut levels that are exacerbated when both diseases are present (c). CONCLUSIONS: Periodontitis and IBD share common dysbiotic and immunological traits. Well-designed preclinical models and longitudinal cohort studies are required to better explore the causal pathways between the two conditions (PROSPERO CRD42020194379).

Long-term follow-up of diabetic and non-diabetic patients with chronic hepatitis C successfully treated with direct-acting antiviral agents.

BACKGROUND AND AIMS: Clearance of hepatitis C virus (HCV) is associated with improved glycometabolic control in patients with diabetes mellitus (DM) but whether this effect is maintained over the long term with a reduction in liver-related events (LRE) is still debated. To address these issues, we conducted a long-term prospective study on diabetic and non-diabetic patients with chronic hepatitis C cured by direct antiviral agents (DAAs). METHODS: Among 893 recruited patients, 15.7% were diabetic (Group 1) and 84.3% non-diabetic (Group 2); changes in fasting glucose (FG) and glycated haemoglobin (HbA1c) levels were assessed in Group 1 while the incidence of LRE was established in the whole cohort. Differences between groups were evaluated and independent predictors of unfavourable clinical outcome were established. RESULTS: After a mean follow up of 44.5 months, a significant reduction in FG and HbA1c values was found in Group 1. Death was reported in 5.7% of patients in Group 1 vs 1.6% in Group 2 (P = .003), hepatocellular carcinoma (HCC)-free survival was significantly lower in Group 2 (P = .015) as well as LRE-free survival in Group 1 cirrhotic patients (P = .0006). After adjustment for baseline variables, cirrhosis and albumin levels emerged as independent predictors of LRE; low albumin levels, DM and central obesity were associated with HCC risk in cirrhotic patients while insulin therapy emerged as unfavourable predictor among diabetics. CONCLUSIONS: SVR achieved by DAAs is associated with long-term improvement of glycometabolic control in diabetic patients, but among cirrhotics DM still exerts a detrimental effect on the liver.

Immune-Mediated Inflammatory Diseases Awareness and Management among Physicians Treating Patients with Inflammatory Bowel Disease: An IG-IBD Survey.

(1) Background: Inflammatory bowel disease (IBD) is frequently associated to other immune-mediated inflammatory diseases (IMIDs). This study aims at assessing physicians' awareness of the issue and the current status of IMID management. (2) Methods: A web-based survey was distributed to all 567 physicians affiliated to IG-IBD. (3) Results: A total of 249 (43.9%) physicians completed the survey. Over 90% of the responding physicians were gastroenterology specialists, primarily working in public hospitals. About 51.0% of the physicians had access to an integrated outpatient clinic, where gastroenterologists collaborated with rheumatologists and 28.5% with dermatologists. However, for 36.5% of physicians, integrated ambulatory care was not feasible. Designated appointment slots for rheumatologists and dermatologists were accessible to 72.2% and 58.2% of physicians, respectively, while 20.1% had no access to designated slots. About 5.2% of physicians report investigating signs or symptoms of IMIDs only during the initial patient assessment. However, 87.9% inquired about the presence of concomitant IMIDs at the initial assessment and actively investigated any signs or symptoms during subsequent clinical examination. (4) Conclusions: While Italian physicians recognize the importance of IMIDs associated with IBD, organizational challenges impede the attainment of optimal multidisciplinary collaboration. Efforts should be directed toward enhancing practical frameworks to improve the overall management of these complex conditions.

COVID-19 and the enteric system: rapidly propagating issues.

The newly described SARS-CoV-2 respiratory virus is now righteously presenting as an ominous threat, based on the speed with which it originated a zoonosis from bats; advancing at a similar rate, the virus has placed mankind before a pandemic, with an infection toll of some 431 million, and a lethality of 5,9 million (as of February 25, 2022). The size of the harm that this agent can unleash against us is appallingly wide, from brain ischemia to foot chilblain, passing by heart massive infarction. Designing a possible response, we reappraised the well-known equation depression-inflammation, and tested the hypothesis that an upgraded ease-of-mind might help reduce the host's hospitality towards SARS-CoV-2. With time passing, it becomes increasingly evident that the virus shall tend to progressively occupy spaces, replacing pandemics with an apparently calm endemicity. This will have to be avoided, and surveillance of society on psychological terms will be one tenet. Needless to say, the role of the enteric tract in these issues is growing higher, and it will be narrated to seal the matters with the last (not the least) touch of glue.

Modulation of the gut microbiota: opportunities and regulatory aspects.

The human gut is an intensively colonized organ containing microorganisms that can be health-promoting or pathogenic. This feature led to the development of functional foods aiming to fortify the former category at the expense of the latter. Since long, cultured products, including probiotics fortification, have been used for humans as live microbial feed additions. This review presents some of the microbes used as probiotics and discusses how supplementation with probiotics may help initiate and/or restore eubiotic composition of gut microbiota. Additionally, it considers safety and regulatory aspects of probiotics.

Efficacy and Safety of Adalimumab Biosimilar GP2017 in Patients with Inflammatory Bowel Disease.

(1) Background: GP2017 is one of the biosimilar drugs of adalimumab, one of the anti-TNF agents used for inflammatory bowel disease (IBD). To date, there is little real-world data about the use of GP2017 in IBD patients. The aim of our study was to evaluate the effectiveness and safety of this biosimilar in an IBD population. (2) Methods: This is an observational retrospective study including patients that were all treated with GP2017 as a first step or as a switch from the originator or other biosimilars. The clinical activity was evaluated at baseline and after 6 and 12 months of therapy. The therapy discontinuation and side effects were also evaluated. (3) Results: a total of 72 patients were included (65 with Crohn's disease and 7 with ulcerative colitis). Of the 29 patients starting GP2017 as a first adalimumab therapy, clinical remission was achieved in 58.6%. Of the patients starting GP2017 as a switch from the originator (33 patients) or other biosimilars (10 patients), clinical remission was maintained in 78.8% and in 70%, respectively. Regarding the safety, only 11 patients experienced non-serious side effects. During the follow-up, nine patients suspended treatment mainly due to side effects or secondary failure. (4) Conclusions: GP2017 is an effective and safe therapy for IBD patients.

The small intestine: barrier, permeability and microbiota.

In recent years, there has been growing interest in the comprehension of the physiology of intestinal permeability and microbiota; and how these elements could influence the pathogenesis of diseases. The term intestinal permeability describes all the processes that allow the passage of molecules as water, electrolytes and nutrients through the intestinal barrier by the paracellular or the transcellular transport systems with several implications for self-tolerance and not-self immunity. An increased permeability might induce a more significant interaction of the immune system with unknown external antigens. This might favor the onset of several immune-related extra-intestinal diseases including coeliac disease, diabetes mellitus type 1, bronchial asthma and inflammatory bowel diseases. Furthermore, the intestinal permeability interacts every day with microbiota, the complex system of mutualistic inhabitants and commensal microorganisms living in the healthy gut. Microbiota is implicated in physiological functions by actively participating in digestion, absorption, synthesis of vitamins and protection from external aggressions. The critical site where these processes occur is the small intestine to which this updated review is dedicated. Understanding its anatomy, its barrier structure and permeability modulation and its microbiota composition is the essential skill to comprehend the complex pathogenesis of several - not only gastroenterological - diseases.

Serum glypican-3 for the prediction of survival in patients with hepatocellular carcinoma.

BACKGROUND: Glypican-3 (GPC-3) is a heparan sulfate proteoglycan overexpressed by hepatocellular carcinoma (HCC) cells. Several studies highlighted the diagnostic and prognostic value of GPC-3 expression in liver tissue, while data on the reliability of serum GPC-3 are limited and conflicting. We aimed to evaluate the prognostic value of serum GPC-3 in patients with HCC. METHODS: A total of 449 patients (91 F and 358 M; median age 65 [38-86] years) with a new diagnosis of HCC and available serum samples collected at tumor diagnosis were retrospectively analyzed. All patients had cirrhosis and the main underlying etiology was viral (N.=323, 72%). Barcelona Clinic Liver Cancer (BCLC) staging system was adopted for patients' classification (BCLC 0/A, N.=293, 65% vs. B/C/D, N.=156, 35%) and treatment allocation. Response to therapy was assessed by modified Response Evaluation Criteria in Solid Tumors (mRECIST). RESULTS: Median overall survival (OS) after HCC diagnosis was 30 months (95% confidence interval [CI]: 27-34). Patients with serum GPC-3>150 pg/mL showed lower overall survival (16; 95%CI: 13-24 months) compared to those with GPC-3≤150 pg/mL (36; 95%CI: 30-56 months) (Log-rank test, P<0.001). At multivariate Cox proportional-hazard regression analysis, presence of ascites (adjusted Hazard Ratio [aHR]=1.84; 95%CI: 1.23-2.74, P=0.003), BCLC stage (aHR=1.65; 95%CI: 1.39-1.97, P<0.001), mRECIST (aHR=0.33; 95%CI: 0.21-0.51, P<0.001) and GPC-3>150 pg/mL (aHR=2.02; 95%CI: 1.47-2.78, P<0.001) resulted significantly associated to overall survival. CONCLUSIONS: Serum GPC-3 resulted an independent prognostic factor for patients with HCC irrespectively from tumor stage and response to therapy.

Moving towards core antigen for the management of patients with overt and occult HBV infection.

Chronic Hepatitis B virus (HBV) infection encompasses a wide virologic and clinical spectrum with heterogeneous outcomes. The natural history of chronic HBV infection ranges from an inactive carrier state (hepatitis B e antigen-negative chronic infection) to progressive chronic hepatitis that may evolve in end-stage liver disease and hepatocellular carcinoma. The issue becomes even more complicated when we consider the unique biology of the virus; the HBV covalently-closed-circular DNA, that acts as virus transcription template, is the key factor responsible of the persistence of the infection even after hepatitis B surface antigen loss. In the last decade, novel serological and immunological biomarkers associated to the core protein of HBV have been approached in different clinical conditions. Remarkable results have been obtained both in the setting of overt and occult HBV infection. Here, we reviewed the meaning and the potential clinical applications of the measurement of core antigen and antibodies.

COVID-19: a user's guide, status of the art and an original proposal to terminate viral recurrence.

The world is now entering its 9th month of combat against a pandemic of deadly pneumonia. Started out from China in December 2019, the disease has been declared as caused by infection with a so far unknown RNA Coronavirus of the respiratory family, then named severe acute respiratory syndrome coronavirus SARS-CoV-2. In the absence of a vaccine, and with scientists still struggling for an effective therapy, COVID-19 (the SARS-dependent syndrome) carries up to now, a death toll of more than 590,000 (July 18,2020) undermining jobs and finance of contemporary society in all continents. Social distancing, the only measure hitherto shown to restrain virus spread, has been progressively loosened from May 2020 in some countries, leaving us in the fear of repeat attacks from the unchecked virus. We discuss the problem and propose to tentatively boost the antivirus cell machinery by using lab-made viral mimics to engage cell receptors.

Long-term outcomes of acute severe ulcerative colitis in the rescue therapy era: A multicentre cohort study.

BACKGROUND: The long-term course of ulcerative colitis after a severe attack is poorly understood. Second-line rescue therapy with cyclosporine or infliximab is effective for reducing short-term colectomy but the impact in the long-term is controversial. OBJECTIVE: The purpose of this study was to evaluate the long-term course of acute severe ulcerative colitis patients who avoid early colectomy either because of response to steroids or rescue therapy. METHODS: This was a multicentre retrospective cohort study of adult patients with acute severe ulcerative colitis admitted to Italian inflammatory bowel disease referral centres from 2005 to 2017. All patients received intravenous steroids, and those who did not respond received either rescue therapy or colectomy. For patients who avoided early colectomy (within 3 months from the index attack), we recorded the date of colectomy, last follow-up visit or death. The primary end-point was long-term colectomy rate in patients avoiding early colectomy. RESULTS: From the included 372 patients with acute severe ulcerative colitis, 337 (90.6%) avoided early colectomy. From those, 60.5% were responsive to steroids and 39.5% to the rescue therapy. Median follow-up was 44 months (interquartile range, 21-85). Colectomy-free survival probability was 93.5%, 81.5% and 79.4% at 1, 3 and 5 years, respectively. Colectomy risk was higher among rescue therapy users than in steroid-responders (log-rank test, p = 0.02). At multivariate analysis response to steroids was independently associated with a lower risk of long-term colectomy (adjusted odds ratio = 0.5; 95% confidence interval, 0.2-0.8), while previous exposure to antitumour necrosis factor-α agents was associated with an increased risk (adjusted odds ratio = 3.0; 95% confidence interval, 1.5-5.7). Approximately 50% of patients required additional therapy or new hospitalisation within 5 years due to a recurrent flare. Death occurred in three patients (0.9%). CONCLUSIONS: Patients with acute severe ulcerative colitis avoiding early colectomy are at risk of long-term colectomy, especially if previously exposed to antitumour necrosis factor-α agents or if rescue therapy during the acute attack was required because of steroid refractoriness.

Effectiveness of Third-Class Biologic Treatment in Crohn's Disease: A Multi-Center Retrospective Cohort Study.

BACKGROUND: Multiple studies have described the effectiveness of ustekinumab (UST) and vedolizumab (VDZ) in patients with Crohn's disease (CD) failing anti- Tumor necrosis factors (TNFs); however, the effectiveness of VDZ or UST as a third-class biologic has not yet been described. AIMS AND METHODS: In this retrospective multicenter cohort study, we aimed to investigate the effectiveness of VDZ and UST as a third-class biologic in patients with CD. RESULTS: Two-hundred and four patients were included; 156/204 (76%) patients received VDZ as a second- and UST as a third-class therapy (group A); the remaining 48/204 (24%) patients received UST as a second- and VDZ as a third-class therapy (group B). At week 16-22, 87/156 (55.5%) patients and 27/48 (56.2%) in groups A and B, respectively, responded to treatment (p = 0.9); 41/156 (26.2%) and 15/48 (31.2%) were in clinical remission (p = 0.5). At week 52; 89/103 (86%) patients and 25/29 (86.2%) of the patients with available data had responded to third-class treatment in groups A and B, respectively (p = 0.9); 31/103 (30%) and 47/29 (24.1%) were in clinical remission (p = 0.5). CONCLUSION: Third-class biological therapy was effective in more than half of the patients with CD. No differences in effectiveness were detected between the use of VDZ and UST as a third-class agent.

Eosinophilic colitis: clinical review and 2020 update.

Eosinophilic colitis (EC) is a rare inflammatory disease included in the chapter of eosinophilic gastrointestinal disorders (EGIDs), diagnosed by the presence of primary eosinophilic infiltrate in the colon wall in symptomatic patients. While the etiology of primary colonic eosinophilia is unknown, several conditions are involved in the pathogenesis of secondary eosinophilic colonic infiltrate (food allergens, parasitic infections, drugs), which have to be excluded in order to correctly diagnose the primary form of the disease. Up to now, EC is lacking of codified guidelines regarding diagnostic criteria (especially eosinophil threshold values) and treatment, thus a correct approach to EC remains very challenging. Imaging, laboratory tests and endoscopy might be helpful in ruling out other mimic conditions, but EC is still a diagnosis of exclusion. Several treatment options are feasible, but most of the evidences are drawn from case reports and small case series, thus limiting their value. We carried out a review of the current literature to evaluate the more appropriate and modern clinical strategy for diagnosis and management of EC.

Proctitis: a glance beyond inflammatory bowel diseases.

Proctitis is an inflammation involving the anus and the distal part of the rectum, frequently diagnosed in the context of inflammatory bowel diseases (IBD). Nevertheless, when the standard therapy for IBD is ineffective, it becomes necessary for the clinician to review alternative etiologies, beginning from the broad chapter of infectious causes up to rare causes such as radiation, ischemia, diversion and traumatisms. While it is possible to find infectious proctitides caused by pathogens generally inducing extensive colitis, the growing incidence of both sexually transmitted infections and isolated proctitis reported in the recent years require a lot of attention. The risk appears to be higher in individuals participating in anal intercourse, especially men having sex with men (MSM) or subjects who use sex toys and participate to sex parties, dark rooms and so on. The commonest implicated pathogens are Neysseria gonorrhoeae, Chlamydia trachomatis, Herpes Simplex virus and Treponema pallidum. Herpes and Chlamydia infections mainly occur in HIV-positive MSM patients. Since symptoms and signs are common independently from etiology, performing a differential diagnosis based on clinical manifestations is complicated. Therefore, the diagnosis is supported by the combination of clinical history and physical examination and, secondly, by endoscopic, serologic and microbiologic findings. Particular emphasis should be given to simultaneous infections by multiple organisms. The involvement of experts in infectious diseases and in sexual health is crucial for the diagnostic and therapeutic management. The available therapies, empirically initiated or specific, in many cases are able to guarantee a good prognosis and to prevent relapses.

Predictors of risk of fracture in inflammatory bowel diseases: a prospective study using FRAX score.

BACKGROUND: Despite the well-known risk of osteoporosis and bone fractures among patients with inflammatory bowel diseases, the WHO FRAX tool has been used in a limited number of studies in this specific population. The purpose of this study was to search for predictors of risk of fractures assessed by FRAX score. METHODS: We prospectively calculated FRAX score for hip and major osteoporotic fractures in inflammatory bowel disease patients consecutively recruited. RESULTS: The mean risk of hip fractures at 10 years, for the 80 recruited patients, resulted 1.4%, while the mean risk of major osteoporotic fractures was 7.8%. The risk of hip fractures was 1.3% among the 30 Crohn's disease patients versus 1.4% (P=0.82) among 50 ulcerative colitis patients. A prolonged use of corticosteroids correlated with a tendency to a greater risk of hip fracture (r=0.38, P=0.08). Patients with normal erythrocyte sedimentation rate (ESR) values had a risk of osteoporotic hip fractures of 0.75%, while those with high ESR values had a risk of 1.86% (P=0.04). Regarding the risk of major bone fractures, patients with normal ESR values had a risk of 5.9%, versus a risk of 18% in those with elevated ESR (P=0.03). CONCLUSIONS: The correlation between increase of inflammatory markers and increased risk of osteoporotic fractures and the lack of difference between Crohn's disease and ulcerative colitis suggest a central role of inflammation over malabsorption in this population.

Management of functional dyspepsia in 2020: a clinical point of view.

Dyspepsia is a disorder that refers mainly to central upper abdominal pain or discomfort. When a cause of this symptom is not identified the condition is termed functional dyspepsia (FD), that affects a large part of the general population. The relevance of FD is due to its high prevalence, but also to its chronic or intermittent course. This induces a significant burden for each national healthcare system. The pathogenesis of FD is complex and multifactorial, depending on cultural, environmental, and biological factors. Although considered of main importance in the pathophysiology of several gastroduodenal diseases, in the context of FD Helicobacter pylori (H. pylori) infection plays a limited role. The diagnosis of FD requires the exclusion of organic gastroduodenal diseases as well as H. pylori infection. Thus, the diagnostic workup includes a complete anamnesis, biochemical tests, and endoscopy with biopsy (when requested), and the satisfaction of clinic criteria recommended by the Rome IV consensus. The treatment of FD is also challenging, in fact more and more studies focused on a wide range of different therapies, with a multitude of results. The aim of this literature review is to provide an update of the new evidences useful for diagnosis and management of FD.