Agreement between patients and physicians on scores of inflammatory bowel disease activity and burden assessed on a telemonitoring platform.

BACKGROUND AND AIMS: Telemonitoring is increasingly used in the management of IBD patients. We investigated the agreement between patients and physicians on scores of disease activity and burden. METHODS: Consecutive outpatients at one IBD clinic were recruited between February and December 2021. Enrolled patients completed a questionnaire for disease activity (Harvey-Bradshaw Index [HBI] for Crohn's disease or Simple Clinical Colitis Activity Index [SCCAI] for ulcerative colitis) and a test of disease burden (Pictorial Representation of Illness and Self Measure [PRISM]). They did the tests within 5 days of an outpatient visit, working independently on IBD Tool, a new web-based telemonitoring application. Concomitantly, the senior and junior physicians who examined them completed the same tests. The agreement was tested for every pair of scores. RESULTS: Five hundred and sixty patients (289 Crohn's disease; 271 ulcerative colitis) completed disease questionnaires on IBD Tool (in total, 742 times). By Spearman's correlation, the agreement was substantial both for HBI (rho 0.685-0.837) and SCCAI (rho 0.694-0.888) for comparisons between patients, junior and senior physicians. The agreement was moderate-to-substantial for PRISM (rho 0.406-0.725) for the same comparisons. The correlation between disease activity (HBI/SCCAI) and PRISM scores was substantial for senior (rho 0.757-0.788) or junior (rho 0.746-0.753) physicians and moderate for patients (rho 0.458-0.486). The median PRISM score difference was 2.3-1.6 points lower between patients and senior-junior physicians. CONCLUSION: Agreement between IBD patients and physicians was substantial for disease activity and moderate for disease impact. The inclusion of disease burden scoring in telemonitoring platforms provides important information for the management of IBD patients.Study highlightsWhat IS known•Continuous response to treatments and patient-reported outcomes became an essential goal for IBD patient management.•The use of tele-monitoring and eHealth technologies allows for regular disease assessments and for managing more efficiently IBD patients; disease questionnaires and tests are key to support eHealth tools.What is new here•Agreement between IBD patients and physicians was substantial for disease activity and moderate for disease burden, while agreement among junior and senior physicians was substantial for both.•PRISM performs as well for ulcerative colitis as for Crohn's patients.•The inclusion of disease burden tests might add to eHealth platforms valuable information, complemental to disease activity questionnaires.

Effectiveness of adalimumab for ulcerative colitis: A multicentre, retrospective study of clinical practice in Italy.

BACKGROUND: Adalimumab is used to treat ulcerative colitis, but additional effectiveness and safety data are needed. PATIENTS AND METHODS: This retrospective study considered adults with ulcerative colitis treated with adalimumab at 19 hospitals. Clinical data were collected from the start of treatment, after 2, 6 and 12 months, and at the last visit. Outcome measures of effectiveness were treatment duration, reasons for discontinuation and colectomy. RESULTS: We studied 381 patients treated with adalimumab for a median of 12.1 months. Disease activity at the start of treatment was moderate to severe in 262 cases (68.8%) and endoscopic activity was moderate to severe in 339 cases (89.0%). At week 8, clinical responses were observed in 177 cases (46.5%) and clinical remission in 136 cases (35.7%). At 12 months, remission was observed in 128 cases (33.6%). Overall, 44 patients required colectomy, and 170 patients (44.6%) were still taking adalimumab when data were collected. Variables associated with adalimumab discontinuation were concomitant steroid treatment, severe clinical-endoscopic activity at baseline, need for adalimumab intensification and drug-related adverse events. Variables associated with colectomy were concomitant steroid treatment and high baseline C-reactive protein. CONCLUSION: Adalimumab is safe and effective for the treatment of ulcerative colitis.

A multicenter survey on endoscopic retrograde cholangiopancreatography during the COVID-19 pandemic in northern and central Italy.

Background and study aims COVID-19 has dramatically impacted endoscopy practice because upper endoscopy procedures can be aerosol-generating. Most elective procedures have been rescheduled. Endoscopic retrograde cholangiopancreatography (ERCP) is frequently performed in emergency or urgent settings in which rescheduling is not possible. We evaluated the impact of the COVID-19 pandemic on ERCP in Italy during the SARS-CoV-2 lockdown, in areas with high incidence of COVID-19. Patients and methods We performed a retrospective survey of centers performing ERCP in high COVID-19 prevalence areas in Italy to collect information regarding clinical data from patients undergoing ERCP, staff, case-volume and organization of endoscopy units from March 8, 2020 to April 30, 2020. Results We collected data from 31 centers and 804 patients. All centers adopted a triage and/or screening protocol for SARS-CoV-2 and performed follow-up of patients 2 weeks after the procedure. ERCP case-volume was reduced by 44.1 % compared to the respective 2019 timeframe. Of the 804 patients undergoing ERCP, 22 (2.7 %) were positive for COVID-19. Adverse events occurred at a similar rate to previously published data. Of the patients, endoscopists, and nurses, 1.6 %, 11.7 %, and 4.9 %, respectively, tested positive for SARS-CoV-2 at follow up. Only 38.7 % of centers had access to a negative-pressure room for ERCP. Conclusion The case-volume reduction for ERCP during lockdown was lower than for other gastrointestinal endoscopy procedures. No definitive conclusions can be drawn about the percentage of SARS-CoV-2-positive patients and healthcare workers observed after ERCP. Appropriate triage and screening of patients and adherence to society recommendations are paramount.

Predictivity of early and late assessment for post-surgical recurrence of Crohn's disease: Data from a single-center retrospective series.

BACKGROUND AND AIMS: Post-surgical recurrence of Crohn's disease (CD) after ileocolonic resection is common. Early identification of features associated with recurrence is a standard procedure of postoperative management, but the prognostic role of such features when detected at later time points is unclear. We compared the predictivity for Crohn's disease recurrence of common clinical-instrumental variables when assessed early (<12 months) or late (>36 months) after surgery. METHODS: This retrospective study considered CD patients who had ileocolonic resection and were followed for a median of 7.6 years. Clinical characteristics, post-surgical therapy, endoscopy recurrence (Rutgeerts' score ≥i2) and ultrasound features were compared between subgroups who had a early or late post-surgical assessment. Univariate and multivariate analyses were done to identify variables associated with recurrence (clinical and surgical). RESULTS: Of 201 patients, 70 (32%) had a early and 39 (19%) had a late post-surgical assessment. The Early and Late subgroups had similar clinical characteristics. Overall, clinical relapse was observed in 131 patients (66%), surgical relapse in 31 (16%), endoscopic recurrence in 149 (75%) and ultrasonographic recurrence in 132 (66%), without significant differences in frequencies between subgroups. By Cox proportional hazard regression, endoscopic recurrence was a significant predictor of clinical recurrence overall (HR=2.31, P = 0.002) and in the Early (HR=3.85, P = 0.002) but not Late subgroup. DISCUSSION: The most informative postoperative CD assessment is the one done within the first year of surgery. Later endoscopic evaluations have no prognostic value and should be done only for clinical needs or for research purposes.

Switching from infliximab originator to a first biosimilar is safe and effective. Results of a case-control study with drug levels and antibodies evaluation.

BACKGROUND: Inflammatory bowel disease is treated with anti-TNF agents such as infliximab and its biosimilars, but use of biosimilars is limited due to perceived risks of adverse events. AIM: To explore safety and effectiveness of switching from the infliximab originator to a first biosimilar. PATIENTS AND METHODS: Clinical and biological outcomes were compared between 53 patients who switched from the infliximab originator to the biosimilar CT-P13 (Switched group) and 13 patients treated with CT-P13 from the beginning (Naïve group). Infliximab trough levels and antidrug antibodies were measured. RESULTS: At enrolment, patients in the Switched group had a longer median duration of infliximab treatment than Naïve (4.0 vs. 0.6 years, p < 0.0001) but similar proportions of patients were in remission (77% and 62%, respectively). Infliximab discontinuation due to adverse events or loss of efficacy was less common in the Switched (26%) than Naïve group (62%, p = 0.017). Variables independently associated with time to discontinuation were disease activity (p < 0.0001) and immunomodulating treatment (p = 0.019) at enrolment. Trough levels and antidrug antibodies were similar between groups during observation. CONCLUSION: This study confirms that switching from infliximab originator to a first biosimilar is safe and effective. Patients at highest risk of losing treatment efficacy are those with active disease, irrespective of the therapeutic switch.

Cytomegalovirus myocarditis in a patient with systemic lupus erythematosus (SLE) successfully treated with ganciclovir.

Myocarditis is an inflammatory disease of the myocardium. Viruses, such as enterovirus, adenovirus, parvovirus B19, HHV6 or cytomegalovirus (CMV) and autoimmune diseases are recognized causes of myocarditis. We describe the clinical case of a young Indian woman with SLE and a concomitant acute CMV related myocarditis with favourable outcome after ganciclovir therapy. CMV myocarditis may range from being a subclinical infection with incidental findings on ECG to a life threating presentation. There are no trials demonstrating the efficacy of antiviral therapy in myocarditis. Case series of patients with CMV myocarditis have reported an excellent clinical outcome after antiviral agents. Lupus Myocarditis (LM) is more prevalent in young females. There are no specific ECG or echocardiographic signs. Treatment strategies of LM are based on corticosteroids, immunosuppressive agents and cardiovascular support, usually with a favorable prognosis, but LM often lead to a severe clinical picture, with mortality of 10.3%. Endomyocardial biopsy (EBM) is recommended as the gold standard but it is very underused in clinical practice, It should be performed in a specialized center but there are concerns on lack of specificity, low negative predictive value, risk of complication, and sampling errors due to the focal nature of myocarditis. Both SLE and CMV are potentially responsible of acute myocarditis. In our knowledge, CMV myocarditis with SLE was described in only one other patient. The initiation of antiviral therapy improved the clinical picture and, in our opinion, it is mandatory when CMV related life threating conditions develop.

Management of Helicobacter pylori in Piedmont, Italy.

Helicobacter pylori (H. pylori) is a Gram-negative bacterium, usually acquired during childhood, whose natural habitat is the gastric lumen. H. pylori is accepted as the most important cause of gastritis and peptic ulcer in humans. Nevertheless, its important role in the pathogenesis of gastric cancer as well as in several extra-gastroduodenal diseases has been confirmed. The aim of this work is to discuss, for the first time in a single article, all publications concerning H. pylori infection arising from Piedmont region, Italy, where in 1893 Giulio Bizzozero was the first who observed and described spiral organisms in the stomach of animal models. A systematic review of all publications on the management of H. pylori in adults in Piedmont, based on a PubMed and a Scopus research from 1965 to 2017 was performed. The discussed aspects are the epidemiology, the study on gastric and extragastric diseases related to H. pylori, the diagnostic methods, the treatment of H. pylori infection, and the possibility of reinfection. In conclusions, with almost 70 publications, Piedmont has proudly maintained the tradition of the father of the H. pylori.

Clinical relevance and inter-test reliability of anti-infliximab antibodies and infliximab trough levels in patients with inflammatory bowel disease.

BACKGROUND: Treatment with infliximab is a common option for inflammatory bowel disease (IBD) patients. Therapeutic drug monitoring could improve treatment management. AIMS: To test inter-test reliability of two commercially available diagnostic kits for infliximab trough levels and infliximab antibodies, and their association with treatment outcomes. METHODS: 86 IBD outpatients on infliximab maintenance treatment were enrolled in a prospective cross-sectional study, 115 samples were available for inter-test reliability. RESULTS: Inter-test agreement was good both for trough levels (concordance correlation coefficient 0.78, weighted κ 0.60, Sperman's ρ 0.937) and for infliximab antibodies (weighted κ 0.79) measurement, when comparing Promonitor and ImmunDiagnostik kits. According to manufacturers' cut-off values, trough levels were classified as undetectable (17%), low (21%) or in range (63%). The only significant associations were: mucosal healing (p=0.026; OR 6.50), infliximab antibody status (p=0.0015; OR 0.031) and adverse events (p=0.009; OR 0.115). Higher trough levels were observed among patients on concomitant steroid/immunosuppressive therapy and among patients with dose-intensification. Infliximab antibodies were significantly associated to treatment-related adverse events (p=0.0003, OR 30.42), and to lower trough levels, but not to other clinical variables. CONCLUSION: The two tests performed equally well. Infliximab antibodies were associated to adverse events, while trough levels were not associated to treatment outcomes.

Application of multiple laboratory tests for Mycobacterium avium ssp. paratuberculosis detection in Crohn's disease patient specimens.

The difficulties involved in detecting and enumerating Mycobacterium avium subsp. paratuberculosis (MAP) as a pathogen potentially involved in Crohn's disease (CD) are well known. This study aimed to improve this situation through the application of multiple laboratory diagnostic tests to detect and isolate this bacterium from different specimens collected from CD-patients and non-CD subjects as controls. A total of 120 samples (terminal ileum and colon biopsies, blood and stool) were obtained from 19 CD-patients and from 11 individuals who did not have a clinicopathological diagnosis of CD (non-CD controls) attending for ileocolonoscopy. All samples were processed by staining techniques, culture on both solid and liquid media, and Insertion Sequence 900/F57 real-time PCR. The MAP frequency in CD-patients was found in a significantly greater proportion than in non-CD subjects; the most positive samples were biopsies from CD-patients tested by real-time PCR. MAP detection in biopsies, and in the other samples, by applying multiple and validated laboratory diagnostic tests, could be a marker of active infection, supporting MAP involvement in CD.

Infliximab three-dose induction regimen in severe corticosteroid-refractory ulcerative colitis: early and late outcome and predictors of colectomy.

BACKGROUND: Infliximab is effective as rescue therapy in severe corticosteroid-refractory ulcerative colitis. The optimal dose regimen and the long term benefits are not well defined. The aim of the present study was to evaluate short- and long-term colectomy rate in a cohort of patients with severe corticosteroid-refractory ulcerative colitis who received a three-dose infliximab induction regimen. METHODS: One hundred and thirteen patients admitted to 11 Italian IBD referral centres and treated with infliximab according to an intention to treat three-dose regimen were included. The co-primary endpoints were 3- and 12-month colectomy rate. The secondary end-points were the overall colectomy-free survival and the identification of predictors of colectomy. RESULTS: The 3- and 12-month colectomy rates were 18.6% (95%CI 11.8%-26.9%) and 25.6% (95%CI 17.9%-34.7%) respectively. High CRP values and severe endoscopic lesions were associated with the risk of colectomy: Risk Ratio (RR)=2.15 (95%CI 1.05-4.36), and RR=5.13 (95%CI 1.55-16.96), respectively. In patients escaping early colectomy, the probability of a colectomy-free course at 12, 24, 36 and 60months was 91%, 85%, 81% and 73%, respectively. Endoscopic severity was the only predictor of long term colectomy (RR=7.0; 95%CI 1.09-44.7). Adverse events occurred in 16 patients (14%); there was one death (0.88%) due to pulmonary abscess. CONCLUSIONS: Infliximab is an effective and safe rescue therapy for severe corticosteroid-refractory ulcerative colitis. A three-dose induction regimen seems to be the treatment of choice for preventing early colectomy. Severe endoscopic lesions appear to be predictor of short- and long-term colectomy.

Abdominal bowel ultrasound can predict the risk of surgery in Crohn's disease: proposal of an ultrasonographic score.

OBJECTIVE: Abdominal bowel ultrasound (US) is widely used in the management of Crohn's disease (CD). The aim of this study was to evaluate the prognostic role of bowel-wall US morphology on the short-term risk of surgery. MATERIAL AND METHODS: The 147 CD patients recruited in a case-control study comprised 49 cases operated on within 30 days after US examination and 98 matched non-operated controls. Clinical and US characteristics were analysed. Bowel-wall thickness was recorded, bowel-wall patterns were grouped into five types, but for final analysis they were grouped as "preserved" or "disrupted stratification". RESULTS: Wall thickness and US patterns were significantly different between cases and controls (p<0.0001). A wall thickness >4.5 mm was observed in 45/49 cases and 47/98 controls (OR = 12.21), while "disrupted stratification" was observed in 34/49 cases and 12/98 controls (OR = 16.24). Among the clinical and US characteristics recorded, only 4 US variables were independently associated with surgery (pattern, thickness, presence of fistulae/abscesses and stenoses) and considered for the US score=(2.5*US pattern)+(1.5*Bowel thickness)+(3*Presence of fistulae/abscesses)+(1.5*Presence of stenoses). Based on this score, up to 84% of patients were correctly classified according to actual status (operated/non-operated). CONCLUSIONS: Although it needs further prospective validation, the score we propose seems to be a reliable prognostic marker for the short-term risk of surgery in CD. In particular, the score points out those patients with an impending risk of surgery who need careful and frequent control in order to decide on the right time for surgery.

Infliximab and the risk of latent viruses reactivation in active Crohn's disease.

BACKGROUND: Infliximab is used for refractory Crohn's disease but there are concerns regarding long-term safety. Recently, JC-polyomavirus (JCV) was studied after 3 cases of progressive multifocal leukoencephalopathy (PML) were found after treatment with natalizumab. The aim of this study was to investigate the short-term effect of infliximab on reactivation of several harmful latent viruses. METHODS: Sixty consecutive patients scheduled for infliximab induction course were prospectively enrolled. Blood samples were taken before each infliximab infusion at 0, 2, 6, and 14 weeks. Specific polymerase chain reaction (PCR) analyses were performed to detect JCV, Epstein-Barr virus (EBV), human herpes virus-6, (HHV-6), -7, -8, and cytomegalovirus (CMV). RESULTS: Indications to infliximab were luminal and fistulizing disease in 49 and 15 cases, respectively. Clinical improvement and remission were achieved in 54 (90%) and 39 (65%) of patients, respectively, at 6 weeks. No patient was JCV-positive at any timepoint. EBV serology was positive for 59/60 patients (98%); EBV-PCR tests were transiently positive (>40 copies/10(5) Peripheral blood mononuclear cells, PBMC) in 4 (7%) patients after infliximab, but in each case were negative at subsequent timepoints. All patients were negative for HHV-6, -7, and -8 at all timepoints. CMV serology was positive in 42 patients (70%), but no CMV-PCR-positive patient was observed. There was no association between concomitant treatments or clinical characteristics and viral status. CONCLUSIONS: Our results support the safety of short-term infliximab treatment with respect to latent virus reactivation. The long-term effects of infliximab, particularly for the issue of lymphoproliferative disorders, warrants further studies with larger populations, but so far data are reassuring.

EUS diagnosis and simultaneous endoscopic retrograde cholangiography treatment of common bile duct stones by using an oblique-viewing echoendoscope.

BACKGROUND: MRCP and EUS have replaced ERCP in the diagnosis of biliary diseases, but the latter is needed for treatment. This study evaluates a new approach in the management of common bile duct stones, by using an oblique-viewing echoendoscope. METHODS: Nineteen patients with acute abdominal pain associated with increased liver tests entered the study. Evaluation of the biliary tree was performed by using an oblique-viewing echoendoscope (JF-UM20; Olympus Europe GmbH, Hamburg, Germany). When biliary stones or sludge were found, bile duct cannulation and sphincterotomy were performed in the same session. RESULTS: Bile duct stones were diagnosed by EUS in 4 patients and biliary sludge in 12; the subsequent cholangiography and sphincterotomy with stone extraction confirmed the diagnosis in all patients. Bile duct cannulation failed in 1 patient. EUS showed features of chronic pancreatitis in 3 cases. The mean time for the whole procedure (EUS plus endoscopic retrograde cholangiography with biliary treatment) was 27 minutes. No procedure-related complications were observed. CONCLUSION: This new approach appears to be feasible and safe, providing an accurate diagnosis and, at the same time, an appropriate treatment of common bile duct stones when needed. With technical improvements, this extended EUS technique could be used as the first-line procedure in patients with biliopancreatic diseases.

An outbreak of hepatitis A virus infection with a high case-fatality rate among injecting drug users.

BACKGROUND/AIMS: In 2002, the first reported outbreak of hepatitis A virus (HAV) infection involving mostly intravenous drug users (IDU) occurred in Italy. We attempted a thorough evaluation of the outbreak, including epidemiological, clinical and virological analyses. METHODS: We conducted an epidemiological investigation, including a case-control study, to identify the source and the modes of HAV transmission. Hepatitis B and C (HCV) viruses and human immunodeficiency virus (HIV) coinfections were clinically analysed. Sequence analysis of the VP1/2A junction of the HAV isolates was also performed. RESULTS: Of the 47 symptomatic cases, 35 were IDUs. The only associated risk factor was contact (not related to injecting practices) with a jaundiced person (odds ratio: 5.8; 95% confidence interval: 1.3-29.9). Of the cases, 58% were anti-HCV positive and 4.7% anti-HIV positive. Three individuals died of acute liver failure: 2 were HCV-coinfected alcohol abusers, with underlying liver cirrhosis; 1 was HCV/HIV-coinfected. HAV-RNA was found in 15 of the 24 tested patients: genotype IB (8 cases) and IIIA (7 cases) were detected. CONCLUSIONS: HAV was probably transmitted through the fecal-oral route, although parenteral transmission cannot be excluded. The high fatality rate was probably due to severe underlying liver damage. The occurrence of this outbreak highlights the need for routine HAV vaccination for IDUs.