Background: The expanding therapeutic landscape of ulcerative colitis (UC) introduces uncertainty regarding the optimal positioning of new agents. Objectives: This study aimed to compare the real-world persistence of advanced therapies for UC. Design: This observational cohort study used a population-based national registry of biologic and small-molecule therapies for inflammatory bowel disease, CREdIT, to identify patients treated with advanced therapy for UC. Methods: The primary outcome was treatment persistence – defined as time from therapy initiation to discontinuation or last follow-up, whichever occurred first – and was analysed using mixed-effects Cox models and inverse probability weighting. Persistence was assessed overall, in first-line therapy, and in second-line therapy after adalimumab or infliximab exposure. Results: We included 3718 observations from 2525 patients with UC (48% female). Infliximab (40%), vedolizumab (27%) and adalimumab (17%) were most frequently used. At 5 years, 1852 of 3718 observations (49.8%) remained on the same therapy. The treatment line alone was not associated with treatment persistence after accounting for patient-level clustering using a mixed-effects model. Vedolizumab showed significantly greater persistence than infliximab or adalimumab, including in first-line use. In second-line settings post-anti-tumour necrosis factor (TNF) exposure, upadacitinib had the highest persistence compared to tofacitinib, vedolizumab and ustekinumab, whereas vedolizumab was more persistent than tofacitinib. Conclusion: Vedolizumab demonstrated longer persistence than infliximab or adalimumab, regardless of treatment line. Following anti-TNF failure, upadacitinib showed the highest persistence.

Summary: Introduction: Urinary excretion of magnesium is an important preventive factor against nephrolithiasis by inhibiting several key processes in its pathogenesis. Patients with Crohn’s disease (CD) have an approximately 2-fold higher risk of lithiasis, especially those after ileocolic (IC) resection. The aim is to determine the magnesuria level in these patients and compare it with patients with CD and IC involvement without resection and then both groups with healthy controls. The secondary objective was to assess calciuria and other modifying factors. Methods: CD patients aged 18 years or older with IC resection (group 1) and terminal ileal involvement without resection (group 2) were enrolled in the study, with subjects without known bowel disease as controls (group 3). Exclusion criteria were citrate therapy, severe renal insufficiency (GFR < 30 ml/ min/ 1.73 m2), more than two bowel resections, ileostomy, colectomy, short bowel syndrome, acute urinary tract infection and evidence of CD relapse. Anamnestic data were collected by questionnaire, blood and fresh urine samples were collected, renal and gallbladder ultrasound was performed for the presence of lithiasis, and patients underwent 24-hour urine collection to determine oxaluria, citraturia, magnesuria and calciuria. Results: 107 subjects were included in the study, including 34 patients with IC resection, 42 with CD without resection and 31 healthy controls. 43% were women, mean age was 38 ± 11.5 years. There was a significant difference in magnesuria values between the resection and non-resection group (median 2.28 vs. 3.97 mmol/ l; P = 0.047) and especially between the resection group and healthy controls (median 2.28 vs. 4.31 mmol/ l; P = 0.0003). The group without resection vs. healthy controls did not reach a significant difference (median 3.97 vs. 4.31 mmol/ l; P = 0.455). Calciuria values did not differ significantly between groups (median 3.75 vs. 4.6 vs. 4.3 mmol/ l; P = 0.293). Conclusion: Magnesuria values of CD patients after IC resection were significantly lower compared to the group of CD patients with IC involvement without resection and healthy controls. The group without resection achieved results comparable to controls. Calciuria values were not significantly different between groups in our study. We hypothesize that patients with CD after IC resection at higher risk of urolithiasis might benefit from Mg supplementation to prevent concretion formation. However, confirmation of this thesis will require verification by further research. Key words: inflammatory bowel disease – Crohn’s disease – urolithiasis – magnesium – calcium oxalate

Evidence on serological responses to vaccination in children exposed to ustekinumab (UST) or vedolizumab (VDZ) in utero is lacking. This multicentre prospective study aimed to assess the impact of prenatal exposure to UST or VDZ due to maternal inflammatory bowel disease (IBD) on serological responses to vaccination and other immunological parameters in exposed children. Children aged ≥ 1 year who were exposed in utero to UST or VDZ and completed at least 1-year of mandatory vaccination were included. We assessed the serological response to vaccination (non-live: tetanus, diphtheria, and Haemophilus influenzae B; live: mumps, rubella, and measles), whole blood count, and immunoglobulin levels. The control group comprised unexposed children born to mothers without IBD. A total of 23 children (median age, 25 months) exposed to UST (n = 13) or VDZ (n = 10) and 10 controls (median age, 37 months) were included. The serological response to vaccination was comparable between the UST and VDZ groups and controls, with an adequate serological response rate of ≥ 80

AIMS Sufficient visibility of the mucosa during upper endoscopy is crucial for successful diagnosis, especially for early neoplastic lesions. Data documenting the effect of administration of mucolytic solution prior to gastroscopy in order to improve mucosal visibility are limited in Europe. The aim of the study was to assess the score of mucosal visibility in the upper gastrointestinal tract after administration of the mucolytic solution defined by us. PATIENTS AND METHODS This is a monocentric, double-blind, randomized study involving 134 patients indicated for diagnostic upper endoscopy. Patients were randomly assigned to one of three arms, with mucolytic solution (100 mL water + 400 mg N-acetylcysteine + 20 mg simethicone), without the solution , and with 100 mL pure water. During the examination, 11 photographs were taken in defined areas. The visibility score was given by the sum of the score 0-5 from 5 defined localities evaluated by a blinded endoscopist and subsequently by two blinded endoscopists. Other parameters monitored were examination time and a semiquantitative evaluation of residual gastric fluid. RESULTS The basic characteristics of the group (sex, age, indications for examination) were comparable between arms. The visibility score was similar in all arms - 17.4 ± 1.9 vs. 17.0 ± 2.0 vs. 17.6 ± 1.8 (P=0.32). The examination time and the amount of residual fluid in the stomach were comparable in all arms. CONCLUSIONS Administration of the mucolytic solution in our study did not increase the mucosal visibility score in the esophagus, stomach and duodenum. TRIAL REGISTRATION ClinicalTrials.gov, NCT02967094.

Summary: Signet ring cell carcinoma (SRCC) is a rare type of highly malignant adenocarcinoma that produces mucin and predominantly affects the stomach, ovaries, and the small intestine. Primary localisation in the colon is rare, and the prognosis of this type of adenocarcinoma is very poor. We present a case report of a 44-year-old woman who suffered from Crohn‘s disease beginning in the year 2000. During the last three years of her treatment, she was treated using bio­logical therapy with ustekinumab. The treatment led to clinical, laboratory, and endoscopic remission. In February 2021, she had widely metastatic primary signet ring cell carcinoma of the colon, which mimicked the IBD activity in the case of her colon obstruction. Because of the extensive infiltration of her liver and peritoneum at the time of the dia­gnosis, in addition to the symptoms of the passage disorders she was experiencing, she proceeded with an end ileostomy and palliative treatment was started. The patient‘s prognosis was unfavourable, and she died within 5 months of the dia­gnosis in hospice care. Key words: primary signet ring cell carcinoma – colon cancer – Crohn‘s disease – colonic stenosis

Background: Inflammatory bowel disease (IBD) is mostly diagnosed in young women of fertile age, and a significant number of patients become pregnant while they have the disease. The remission of the illness, which is often achieved by intensive anti inflammatory treatment, has been found to be the most important factor of a successful pregnancy. Vedolizumab (VDZ) and ustekinumab (UST) are newer types of monoclonal antibodies with different mechanisms of effect when compared to anti-TNF treatment. VDZ is a monoclonal antibody against the α4ß7 integrin receptor, and UST against interleukin 12/23; both have expanded the spectrum of the biological treatment of IBD in recent years. Aims: To present the results of a multicentre observational study. The primary aim was to assess the safety of vedolizumab and ustekinumab for pregnancy, foetal development and the neonatal outcome. The secondary aim was to measure the drug concentration in maternal and cord blood at the time of delivery. Methods: It was a multicentre, retrospective-prospective observational study. Data on patients’ demographics, clinical characteristics and pregnancy were collected by the treating physician using a predefined questionnaire, data on newborn outcome were obtained from medical documentation. The ELISA method was used to measure the VDZ and UST concentrations. Results: The study took place in 15 IBD clinical centres in the Czech Republic. 79 women with 85 completed pregnancies were included in the study, and they were exposed to VDZ or UST during pregnancy. 36 women were treated with vedolizumab (median age 32 years) and 49 with ustekinumab (median age 30.5 years). In the group with VDZ, live births occurred with 32 women (88.9%), and there were two early spontaneous abortions up to the eighth week of gestation in addition to two instrumentally aborted pregnancies (4, 11.1%). 31 children (93.9%) in the group with VDZ were born at term with a median birth weight of 3,097.5 grams. In the ustekinumab group, 39 women (79.6%) had live births, there were nine early abortions and one instrumentally aborted pregnancy (10, 20.4%). 38 (97.4%) children were born at term with a median birth weight of 3,265 grams. The drug levels of VDZ and UST at birth were measured in 44 neonate-mother pairs (21 VDZ, 23 UST). The median level of VDZ in maternal venous blood was 7.2 mg/l, and in cord blood it was 4.7 mg/l (infant / maternal ratio 0.66). With UST, the median maternal level was 4.7 mg/l, and in neonates it was 7.9 mg/l (infant / maternal ratio 1.65). Conclusion: The results found in a group of women that were being treated for IBD and were exposed to at least one dose of biologic treatment with UST or VDZ during pregnancy are consistent with previously published evidence showing no adverse events, and they confirm the safety profile of new biologics in pregnancy. Due to the still limited number of enrolled patients, further studies are needed on the outcomes of pregnancies with new biologics drugs. Keywords vedolizumab, ustekinumab, pregnancy, transplacentární přenos

Background and Aims Evidence on the safety of newer biologics during pregnancy is limited. We aimed to assess the safety of ustekinumab and vedolizumab treatment during gestation on pregnancy and infant outcome. Furthermore, we evaluated the placental transfer of these agents. Methods We performed a prospective, multicentre, observational study in consecutive women with inflammatory bowel disease exposed to ustekinumab or vedolizumab 2 months prior to conception or during pregnancy. Pregnancy, neonatal, and infant outcomes were evaluated and compared with the anti-tumour necrosis factor [TNF]-exposed control group. Drug levels were assessed in maternal and cord blood at delivery. Results We included 54 and 39 pregnancies exposed to ustekinumab and vedolizumab, respectively. In the ustekinumab group, 43 [79.9%] resulted in live births, and 11 [20.4%] led to spontaneous abortion. Thirty-five [89.7%] pregnancies on vedolizumab ended in a live birth, two [5.1%] in spontaneous, and two [5.1%] in therapeutic abortion. No significant difference in pregnancy outcome between either the vedolizumab or the ustekinumab group and controls was observed [p >0.05]. Similarly, there was no negative safety signal in the postnatal outcome of exposed children regarding growth, psychomotor development, and risk of allergy/atopy or infectious complications. The median infant-to-maternal ratio of ustekinumab levels was 1.67 and it was 0.59 in vedolizumab. Conclusions Use of ustekinumab and vedolizumab in pregnancy seems to be safe, with favuorable pregnancy and postnatal infant outcomes. Placental transfer differed between these two drugs, with ustekinumab having similar and vedolizumab having inverse infant-to-maternal ratio of drug levels compared with anti-TNF preparations.

Clostridioides difficile (Clostridium difficile in older taxonomy) is a gram-positive anaerobic and bacteria enabled by endospores. Clostridioides difficile is currently the main cause of nosocomial infections in developed countries. Due to the high probability of developing bacterial resistance to treatment and the numerous recurrences in multiple chronic conditions in older adults of our society it causes a widespread medical problem. Faecal microbiota transplantation (FMT) is a highly effective method for treating recurrent intestinal Clostridioides difficile infections (CDI). With this method the potential mechanism of effect is the transmission of a complex intestinal ecosystem, including vital microorganisms, from the donor to the recipient. Presenting the results of monocentric prospective monitoring: Primary aim of the study was to evaluate long-term remission (the continued absence of clinical manifestations of CDI 3 months after FMT administration). The secondary aim of the study was to monitor the short-term remission in the 7 days after FMT administration. Demographic data, information about CDI and the details of therapy were obtained and completed by the treating physician of each patient or by targeted questioning of the patient or their family. We used clinical monitoring to determine the effect of the treatment. The examinations of stool donors and the preparation for a faecal microbiota transplantation were performed according to the currently valid guidelines of the Czech Society of Infectious Diseases for the treatment of the recurrent bacterial infection Clostridioides difficile with faecal microbiota transplantation. The follow-ups took place from February 2011 to July 2021 in the gastroenterology department at the AGEL Ostrava-Vítkovice Hospital and included 116 patients with their first and subsequent recurrence of CDI that were treated with faecal bacteriotherapy. The median age of our patients was 71 years old (the youngest was 19 years old, the oldest 103 years old). 69 women and 47 men took part in the study. 56 patients had their first recurrence of CDI, 41 had a second attack, and 20 patients had a third and subsequent recurrences. In 62 patients (53.4 %), the route of FMT administration was a local enema into the left colon. With 37 patients (31.9 %) we used a colonoscopy after standard anterograde bowel preparation. With 12 patients (10.3 %) gastroscopy administration (deep into the duodenum) was used. 4 patients (3.5 %) were given a nasoenteral tube and one patient (0.9 %) was administered FMT per percutaneous endoscopic gastrostomy (PEG). We applied a frozen universal donor FMT in 81 patients (69.8 %), and a freshly prepared FMT from a person living in the same household was used in 35 patients (30.1 %). The secondary endpoint (the absence of clinical manifestations of CDI within 7 days of FMT administration) was achieved with 102 patients (87.9 %) in our study. The fulfilment of the primary endpoint (the development of long-term remission) was observed with 93 patients (80.2 %). An early administration of FMT appears to be a significant predictor of treatment effect (p = 0.05; OR 5.11; 95% CI 1.65-15.8). Faecal microbiota transplantation is an effective and safe therapy for recurrent intestinal Clostridioides difficile infection, and it respects the up-to-date guidelines for treatment. Of the 116 patients included in our study with first and subsequent CDI, we achieved long-term remission in 80.2 % of them. An early administration of FMT appears to be a significant predictor of treatment effect.

Crohnova choroba (CN) a ulcerózní kolitida (UC) patří do skupiny onemocnění s názvem idiopatické střevní záněty (IB - inflammatory bowel disease). IBD mají dosud ne zcela jasnou etiologii, bývají diagnostikovány převážně v mladším věku a v průměru u více než třetiny těchto pacientů se v průběhu let vyvinou mimostřevní projevy nemoci. K těm nejčastějším patří artropatie, oční a kožní manifestace zánětu, metabolická kostní choroba a hepatobiliární či urologické postižení. Terapie je obdobná jako léčba základního onemocnění a spočívá převážně v systémové imunosupresi.

BACKGROUND:Vedolizumab demonstrated different placental pharmacokinetics than other immunoglobulin G1 antibodies, leading to lower drug levels in cord blood in contrast to maternal blood at the time of delivery. The placental transfer of ustekinumab seems to have a pattern similar to anti-tumour necrosis factor agents. Current evidence on the placental pharmacokinetics of vedolizumab and ustekinumab is limited. We aimed to assess the placental transfer of ustekinumab and vedolizumab in pregnant patients with inflammatory bowel disease.METHODS:Consecutive women from a prospective observational study who were exposed to ustekinumab or vedolizumab within 2 months prior to conception or during pregnancy were included. Ustekinumab and vedolizumab levels were measured in maternal and cord blood at the time of delivery.RESULTS:Drug levels were available in 31 infant-mother pairs (15 exposed to ustekinumab and 16 to vedolizumab). The median maternal and newborn ustekinumab levels were 5.3 mg/l and 10.3 mg/l, respectively (the median infant-to-maternal ratio was 1.7), while the median maternal and cord vedolizumab levels were 7.3 mg/l and 4.5 mg/l (the median infant-to-maternal ratio was 0.66). The ustekinumab levels in cord blood positively correlated with the maternal levels at delivery (ρ = 0.751, p = 0.001). However, no correlation with the timing of the last drug administration was found. In contrast, the vedolizumab levels in cord blood demonstrated significant positive correlation with the maternal levels (ρ = 0.831, p < 0.001) along with the gestational week of the last infusion (ρ = 0.736, p = 0.001).CONCLUSION:Vedolizumab demonstrated different placental pharmacokinetics, leading to lower drug levels in cord blood compared to maternal blood at delivery; in contrast, the placental transfer of ustekinumab seems to have a pattern similar to anti-tumour necrosis factor (TNF) agents.

Inflammatory bowel disease (IBD) includes Crohns disease (CD) and ulcerative colitis (UC). Those are chronic gastrointestinal disorders of inflammatory nature and not fully known etiology. As a result of their immune-mediated mechanism and complex impact on the whole organism other organs than gastrointestinal system may be affected in many ways. These extraintestinal manifestations (EIM) and complications may severely deteriorate prognosis of the patient, cause his morbidity and worsen the quality of life. While classical extraintestinal manifestations, such as enteropathic arthropathy, skin or eye involvement or primary sclerosing cholangitis, share common immunopathological mechanism with IBD, whole range of other disorders may result from various anatomical or metabolic abnormalities caused by IBD or its treatment. This review focus on the most common extraintestinal complications, such as anaemia, metabolic bone disease, biliary and urolithiasis, which we meet in our daily clinical practice.

The CDED diet (Crohn‘s disease exclusion diet) is the first elimination diet that induces and maintains remission in adult patients with mild to moderate Crohn‘s disease. It is based on mandatory, recommended and prohibited foods. In our article we present our workplace experience, that is still limited, as well as the case report of a patient with a long history of Crohn‘s disease in ileocecal localization on immunosuppressive therapy with azathioprine. He has benefited significantly from the CDED diet, his abdominal symptomatology and laboratory parameters have improved. There has also been a significant improvement in the quality of his life. Key words: CDED – Crohn’s disease – diet – alternative nutrition – relapse of the disease

Idiopatické střevní záněty (IBD ‐inflammatory bowel disease) jsou skupinou onemocnění, které zahrnují Crohnovu chorobu (CN) a ulcerózní kolitidu (UC) a postihují především mladé dospělé v produktivním věku. Anti ‐TNF látky představují první typ biologické léčby IBD a jejich podávání v průběhu těhotenství je již doloženo četnými observačními studiemi. V posledních několika letech se však spektrum biologické léčby IBD rozšířilo o dvě nové monoklonální protilátky s odlišným mechanismem účinku: protilátku proti α4ß7 integrinovému receptoru – vedolizumab a protilátku proti interleukinu 12/23 – ustekinumab. I když dosavadně publikované údaje neprokazují jednoznačně negativní vliv těchto nových léčiv na průběh těhotenství a vývoj plodu, vzhledem k celkovému malému počtu doposud studovaných pacientek chybí spolehlivé důkazy o bezpečnosti této léčby v průběhu gravidity. Klíčová slova: idiopatické střevní záněty, těhotenství, monoklonální protilátky, adalimumab, infliximab, vedolizumab, ustekinumab.

Abstract Background Ileocolonic resection is the most common surgery in Crohn’s disease (CD). However, stricture formation in the anastomosis is considered to be a frequent cause of significant morbidity in CD and a reason for reoperation. Endoscopic balloon dilatation (EBD) is an established modality for non-surgical treatment of strictures in CD, however, summary data from the Czech Republic are lacking. Methods All EBDs of CD anastomotic strictures performed in the 7 centres from the Czech Republic between January 1, 2013, and May 30, 2019, were included. Demographics, disease characteristics, concomitant medication and procedure outcomes were analysed. Technical success was defined as an ability to pass the endoscope through the site of the stricture following the procedure. Complications included perforation and bleeding with the need for intervention or hospitalisation. Kaplan–Meier and logistic regression analysis were performed. Results In total, 615 procedures performed in 282 patients, 52.1% males, were included. Mean age at the time of the first procedure was 41.9 ± 12.7 years and mean disease duration was 14.5 ± 8.4 years. Single dilatation was performed in 47.9% of patients, 52.1% requested repeated interventions (2–10, median 2). Cumulative probability of redilatation at 6 months, 1 year and 3 years was 20.2% (95% CI 14.8–26.2%), 31.8% (95% CI 26.5–37.2%) and 59.4% (95% CI 55.5–63.0%) respectively. Cumulative probability of a need for reoperation at 6 months, 1 year and 3 years was 4.4% (95% CI 0.5–16.9%), 8.2% (95% CI 2.3–19.3%) and 14.8% (95% CI 7.1–25.2%) respectively. Technical success was reached in 81.1% of procedures and relief of symptoms in 86.7%. The success of the procedure was dependent on the age of the patient (OR 0.98; 95% CI 0.96–0.99), smoking (OR 0.57; 95% CI 0.32–0.98) and concomitant immunosuppression use (OR 1.99; 95% CI 1.31–3.02). Complications occurred in 2.6% of the procedures. Reintervention until 6 months after the procedure was needed in 26.7% of cases, out of which repeated dilatation in 21.3% of cases and early surgery took place in 5.4% of cases. The technical success (OR 0.44; 95% CI 0.29–0.67) and repeated dilatation (OR 1.57; 95% CI 1.09–2.27) were significantly associated with the need for reintervention until 6 months. Conclusion In a large multicentric Czech cohort, the EBD in Crohn’s disease anastomotic strictures was proven to be safe and effective with results comparable to the available international data.