Dysfunction of peripheral somatic and autonomic nervous system in patients with severe forms of Crohn's disease on biological therapy with TNFα inhibitors-A single center study.

OBJECTIVE: Crohn's disease (CD) can be associated with a wide range of extraintestinal manifestations (EIMs), including neurological ones. Published studies differ in their conclusions about the epidemiology and etiopathogenesis of neurological EIMs. The aims of this study were to demonstrate the presence and find risk factors of peripheral (somatic and autonomic) neuropathy patients with severe CD on anti-TNFα biological therapy. MATERIAL AND METHODS: A clinical examination focusing on detection of peripheral sensor-motor nervous dysfunction (including Sudoscan) and examination of autonomic nervous system dysfunction (using Ewing´s battery tests and spectral analysis) together with laboratory tests and collection of demographic data followed by administration of questionnaires were performed on a total of 30 neurologically asymptomatic outpatients with severe CD on anti-TNFα biological therapy. RESULTS: Peripheral sensor-motor nervous function via clinical neurological examination was pathological in 36.7% and Sudoscan in 33.3% of cases. Statistically significant associations between vibration perception test and age, CD and biological therapy duration, body mass index and Crohn's Disease Activity Index were proved while statistically significant associations between temperature perception test and age and BMI were proved as well. Additionally, a decrease of total protein in a patient´s serum below the physiological cut-off in the 6 months prior to measurement was associated with a pathological result of a Sudoscan. Cardiovascular autonomic neuropathy based on Ewing´s battery tests was present in 56.7% of patients, no statistically significant risk factors were found. Our peripheral neuropathy questionnaire correlated with the results of the Sudoscan test and some tests of the clinical examination of peripheral sensor-motor nervous function (discriminatory contact perception test, temperature perception test). CONCLUSIONS: This study demonstrated a relatively high prevalence of peripheral (especially autonomic) neuropathy and verified some risk factors for the development of peripheral somatic neuropathy in asymptomatic patients with severe form of CD on anti-TNFα biological therapy.

Factors affecting participation in the colorectal cancer screening program: a cross-sectional population study.

PURPOSE: Fecal immunochemical test (FIT) once a year or colonoscopy once in 10 years is the option approved for colorectal cancer (CRC) screening for asymptomatic individuals aged ≥ 50 years in the Czech Republic. We analyzed participation in the screening program to determine possible improvements. METHODS: In this observational cross-sectional study, data were collected from 4044 randomly chosen individuals from the Czech population (1866 men, 2178 women) aged ≥ 50 years by questionnaires. Individuals who underwent colonoscopy within the last 10 years or/and FIT within the last 2 years were classified as participants in the screening. RESULTS: 1050 individuals underwent FIT, 464 colonoscopy, and 558 underwent both. Adjusted for age, gender, and education, a higher chance of participation in the screening was observed in groups of non-smokers (OR = 1.25; CI 1.05-1.48), ex-smokers (OR = 1.51; CI 1.26-1.83), consuming smoked meat products less than once a week (OR = 1.26; CI 1.09-1.45), practicing physical activity at least once a week (OR = 1.25; CI 1.03-1.51), hospitalized in the past 12 months (OR = 1.73; CI 1.47-2.05), or consulting a general practitioner (GP) in the past 12 months (OR = 2.26; CI 1.87-2.74). The chance of participation of individuals having a risk factor for CRC (obesity, smoking, diabetes, low physical activity, alcohol drinking) was not higher compared to those without the risk factors. CONCLUSION: Individuals with a tendency to a healthy lifestyle or being in recent contact with the healthcare system by various means, mainly visiting a GP, had a higher participation in the screening for CRC. Among groups with an increased risk for CRC, higher participation was not shown.

Efficacy and safety of SARS-CoV-2 vaccination in patients with inflammatory bowel disease on immunosuppressive and biological therapy: Prospective observational study.

BACKGROUND AND AIMS: SARS-CoV-2 is a worldwide serious health problem and vaccination seems to have a crucial role in managing the COVID-19 pandemic. The aim of this prospective observational study was to monitor the trend of antibodies against SARS-CoV-2 after vaccination with BNT162b2 (COMIRNATY) in patients with inflammatory bowel disease treated by immunosuppressive and/or biological therapy, demonstrate whether any type of this therapy is associated with poorer production of antibodies against COVID-19 and evaluate the safety of vaccination against COVID-19 in these patients. METHODS: Eighty-seven eligible patients from one tertiary gastroenterological center with inflammatory bowel disease (60 with CD, 27 with UC) treated by immunosuppressive and/or biological therapy from the antiTNFα group were indicated to vaccination against SARS-CoV-2. Effectiveness of vaccination was evaluated by the values of antibodies before and 4 weeks after 2nd dose of vaccine. Additional goal was to evaluate adverse events of vaccination. RESULTS: Before the 2nd dose of vaccine, geometric mean of SARS-CoV-2 IgG antibodies were 40.7 U/ml in the biological therapy group, 34.8 U/ml in the azathioprine group and 44.8 U/ml in the combination therapy group of patients. The geometric means were 676.5.7 U/ml in the biological therapy group, 614.4 U/ml in the azathioprine group and 500.1 U/ml in the combination therapy group of patients four weeks after 2nd dose. Statistically significant differences between these groups were not proved. Several non-severe local and general adverse events were present in our patients with a majority of these events on the day of vaccine administration and the day after, no anaphylactic reactions were present. CONCLUSIONS: Our measurements proved the efficacy and safety of vaccination against SARS-CoV-2 in patients with inflammatory bowel disease treated by immunosuppressive and/or biological therapy. Statistically significant differences between our groups of patients were not proved.

Adalimumab biosimilars in the therapy of Crohn´s disease and ulcerative colitis: Prospective multicentric clinical monitoring.

OBJECTIVE: The adalimumab biosimilars FKB327 and GP2017 were approved for the therapy of patients with inflammatory bowel disease (IBD). Relatively few prospective studies with biosimilar adalimumab in patients with IBD have been published. The aim of this prospective observational study was to evaluate the effectiveness and safety of the biosimilar adalimumab. MATERIAL AND METHODS: Adalimumab biosimilars FKB327 (Hulio®) and GP2017 (Hyrimoz®) were indicated to 50 naive patients in terms of biological therapy with Crohn's disease (CD) or ulcerative colitis (UC). Effectiveness of therapy was evaluated via the Crohn's Disease Activity Index [CDAI] or the Mayo Scoring System [MSS] in patients with CD or UC, respectively, before and after 12 weeks. Additional goals were to evaluate weight changes, laboratory tests and complications or adverse events of this therapy. RESULTS: In CD patients, remission (CDAI <150) was achieved in 73.5% of cases, partial response (≥70-point decrease in CDAI score from baseline) in 11.8%, no response in 11.8% and 2.9% patients discontinued therapy. In UC patients, remission (total score on partial Mayo index ≤2 points) was achieved only in 18.8% of cases, partial response (≥2-point decrease in partial Mayo score from baseline) in 43.8%, no response in 25.0% and 12.5% patients discontinued therapy. There were statistically significant improvements in CDAI, MSS, haemoglobin, fecal calprotectin, albumin and CRP serum levels after 12 weeks of therapy. Seven adverse events were identified, three of which resulted in therapy being discontinued. CONCLUSIONS: This prospective observational study proved the effectiveness of the adalimumab biosimilars FKB327 and GP2017 in IBD.

Conjugated Hyperbilirubinemia in Infants: Is There Still a Role for ERCP?

Over a twenty-year period, we performed 255 ERCP procedures in infants aged up to 1 year. ERCP was indicated in cholestatic infants with suspicion of biliary obstruction. The most common diagnosis was biliary atresia (48%), choledochal cysts (13%), and choledocholithiasis (4%). The procedure complication rate was 13.7%. Hyperamylasemia occurred in 12.9%. More severe complications were rare-0.8% of ERCP procedure. There were no cases of postprocedural pancreatitis or death. Our study has proved that ERCP is a safe and reliable method in this age group. Its high specificity and negative predictive value for extrahepatic biliary atresia can prevent unnecessary surgeries in patients with normal bile ducts or endoscopically treatable pathologies.

Commonly available but highly effective protection against SARS-CoV-2 during gastrointestinal endoscopies.

BACKGROUND AND AIMS: SARS-CoV-2 is a worldwide serious health problem. The aim of this study was to demonstrate the number of potentially infectious particles present during endoscopic procedures and find effective tools to eliminate the risks of SARS-CoV-2 infection while performing them. METHODS: An experimental model which focused on aerosol problematics was made in a specialized laboratory. This model simulated conditions present during endoscopic procedures and monitored the formation of potentially infectious fluid particles from the patient's body, which pass through the endoscope and are then released into the environment. For this reason, we designed and tested a prototype of a protective cover for the endoscope's control body to prevent the release and spread of these fluid particles from its working channel. We performed measurements with and without the protective cover of the endoscope's control body. RESULTS: It was found that liquid coming through the working channel of the endoscope with forceps or other instruments inside generates droplets with a diameter in the range of 0.1-1.1 mm and an initial velocity of up to 0.9 m/s. The average number of particles per measurement per whole measured area without a protective cover on the endoscope control body was 51.1; with this protective cover on, the measurement was 0.0, p<0.0001. CONCLUSIONS: Our measurements proved that fluid particles are released from the working channel of an endoscope when forceps are inserted. A special protective cover for the endoscope control body, made out of breathable material (surgical cap) and designed by our team, was found to eliminate this release of potentially infectious fluid particles.

Acute portal vein thrombosis in noncirrhotic patients - different prognoses based on presence of inflammatory markers: a long-term multicenter retrospective analysis.

Background: Portal vein thrombosis (PVT) is a partial or complete thrombotic occlusion of the portal vein and is rare in noncirrhotic patients.Patients and methods: 78 adult patients with noncirrhotic acute PVT without known malignity were evaluated. Patients with initial CRP level 61-149 mg/l were excluded.Results: Patients were divided into two groups - the first one (33 patients) was characterized with signs of inflammation and CRP over 149 mg/l. The second group (45 patients) was without signs of inflammation and CRP level less than 61 mg/l. The frequency of prothrombotic hematologic factors was statistically significantly different in levels of factor VIII and MTHFR 677 C mutation. All patients from both groups underwent the same oncologic and hemato-oncologic screening which was positive in 23 patients (51.1%) in the group without signs of inflammation. In the group of patients with clinical and laboratory signs of inflammation oncologic and hemato-oncologic screening was positive only in 1 patient (3.0%). Complete portal vein recanalization was achieved in 19.2%, partial recanalization in 26.9%.Conclusions: Patients with clinical signs of inflammation and acute PVT have a low risk of malignancy in contrast to patients without signs of inflammation and acute PVT, which have a high risk of oncologic or hemato-oncologic disease. Patients with negative hemato-oncologic screening should be carefully observed over time because we expect they are at higher risk for the development of hemato-oncologic disease, independent from the presence and number of procoagulation risk factors.

ERCP in infants, children, and adolescents-Different roles of the methods in different age groups.

BACKGROUND: Endoscopic retrograde cholangiopancreatography (ERCP) is seldom used in children, and published series have limited numbers of pediatric patients. The aim of this retrospective observational study was to assess the efficacy and safety of pediatric ERCP in a large group of children. METHODS: Data were evaluated from 626 children with biliopancreatic disorders admitted to University Hospital Motol, Prague, between January 1999 and January 2018. Clinical data were obtained by retrospective evaluation of our database of pediatric ERCP procedures and from clinical records. RESULTS: We performed 856 ERCPs on 626 pediatric patients; of these procedures, 59% were therapeutic and 41% were diagnostic. We achieved 96% technical success. Indications for ERCP and pathological findings differed in different age groups. The main role of ERCP was in excluding biliary atresia in those aged less than one year. In children aged 1 to 6 years, the most frequent diagnoses were choledochal cyst followed by choledocholithiasis. In children aged 7 to 12 years and 13 to 19 years, the most frequent diagnoses were choledocholithiasis followed by pancreatic pathology. The overall complication rate found in this study was similar to rates observed in adult populations. CONCLUSIONS: Our study shows the efficacy and safety of diagnostic and therapeutic ERCP in a large series of infants and children with technical success and complication rates comparable to those in adults. Our data show that ERCP had different roles in different age groups of children.

Adherence, risk factors of non-adherence and patient's preferred treatment strategy of mesalazine in ulcerative colitis: multicentric observational study.

OBJECTIVES: Compliance to therapy is a key factor in the efficacy of treatment in clinical practice. The aim of our study was to evaluate the rate of compliance with mesalazine in patients with ulcerative colitis (UC), to examine risk factors of noncompliance and especially find ways on how adherence can be improved. MATERIALS AND METHODS: A total of 198 outpatients with UC completed two anonymous questionnaires including information on basic demographics, details of patient´s disease and the use of mesalazine medication and quality of life. RESULTS: We found noncompliance (percentage of used medication per day less than 80%) with 5-ASA in 21.2% patients. Our study proved that the education level of patients significantly influenced the compliance of patients using mesalazine. A significant difference (p = .014) was found between the compliance of patients with secondary school education (84.1 ± 16.73) and those with university education (94.1 ± 9.9). The majority of patients preferred mesalazine once daily and are less likely to forget to take medication in the morning. Better quality of life was observed based on our data from WHOQOL-BREF questionnaire in statistically significant way in patients using concomitant therapy of immuosuppressive or biological therapy, lower daily doses and using sachets not tablets. CONCLUSIONS: Our study proved that compliance with mesalazine in patients with UC was related only to education level. If we target mesalazine therapy based on patient's preferences, we can improve the adherence with mesalazine. Our data could be beneficial for the treatment strategy in clinical practice.

Clinical monitoring: infliximab biosimilar CT-P13 in the treatment of Crohn's disease and ulcerative colitis.

OBJECTIVE: The infliximab biosimilar CT-P13 (Remsima(®), Inflectra(®)) was approved in Europe for the treatment of inflammatory bowel disease (IBD) based on extrapolation of data from patients with rheumatic disease. Because there are limited published reports on clinical outcomes for IBD patients treated with CT-P13, we monitored responses to induction treatment with this biosimilar in patients with Crohn's disease (CD) or ulcerative colitis (UC) in centres across the Czech Republic. MATERIAL AND METHODS: Fifty-two patients with CD (n = 30) or UC (n = 22) were treated with 5 mg/kg CT-P13 for up to 14 weeks. Effectiveness of therapy was evaluated with the Crohn's Disease Activity Index (CDAI) or the Mayo Scoring System (MSS) in patients with CD or UC, respectively, before and after 14 weeks. Additional goals were to evaluate weight changes, serum C-reactive protein (CRP) levels, and complications/adverse events. RESULTS: In patients with CD, remission (CDAI <150) was achieved in 50.0% of cases, and partial response (≥70-point decrease in CDAI score from baseline) in the remaining 50.0%. In patients with UC, remission (total score on partial Mayo index ≤2 points) was achieved in 40.9% of cases, partial response (≥2-point decrease in partial Mayo score from baseline) in 54.5%, and no response in 4.5%. There were statistically significant improvements in CDAI, MSS and CRP serum levels after 14 weeks of therapy, and body weight increased. Four adverse events were identified (n = 1 each): lower-extremity phlebothrombosis, herpes labialis, pneumonia and allergic reaction. CONCLUSIONS: This prospective observational study provides evidence of the effectiveness of CT-P13 in IBD.