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.
- Klíčová slova
- Inflammatory bowel disease, placental transfer, pregnancy, ustekinumab, vedolizumab,
- MeSH
- gastrointestinální látky škodlivé účinky terapeutické užití MeSH
- humanizované monoklonální protilátky * škodlivé účinky terapeutické užití MeSH
- idiopatické střevní záněty * farmakoterapie MeSH
- inhibitory TNF škodlivé účinky terapeutické užití MeSH
- kojenec MeSH
- lidé MeSH
- matka - expozice noxám MeSH
- novorozenec MeSH
- placenta MeSH
- prospektivní studie MeSH
- těhotenství MeSH
- ustekinumab * škodlivé účinky terapeutické užití MeSH
- výsledek těhotenství MeSH
- výsledek terapie MeSH
- Check Tag
- kojenec MeSH
- lidé MeSH
- novorozenec MeSH
- těhotenství MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- multicentrická studie MeSH
- pozorovací studie MeSH
- Názvy látek
- gastrointestinální látky MeSH
- humanizované monoklonální protilátky * MeSH
- inhibitory TNF MeSH
- ustekinumab * MeSH
- vedolizumab MeSH Prohlížeč
Non-canonical forms of nucleic acids represent challenging objects for both structure-determination and investigation of their potential role in living systems. In this work, we uncover a structure adopted by GA repetition locked in a parallel homoduplex by an i-motif. A series of DNA oligonucleotides comprising GAGA segment and C3 clip is analyzed by NMR and CD spectroscopies to understand the sequence-structure-stability relationships. We demonstrate how the relative position of the homopurine GAGA segment and the C3 clip as well as single-base mutations (guanine deamination and cytosine methylation) affect base pairing arrangement of purines, i-motif topology and overall stability. We focus on oligonucleotides C3GAGA and methylated GAGAC3 exhibiting the highest stability and structural uniformity which allowed determination of high-resolution structures further analyzed by unbiased molecular dynamics simulation. We describe sequence-specific supramolecular interactions on the junction between homoduplex and i-motif blocks that contribute to the overall stability of the structures. The results show that the distinct structural motifs can not only coexist in the tight neighborhood within the same molecule but even mutually support their formation. Our findings are expected to have general validity and could serve as guides in future structure and stability investigations of nucleic acids.
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.
- Klíčová slova
- pregnancy, ustekinumab, vedolizumab,
- Publikační typ
- časopisecké články MeSH
BACKGROUND AND AIMS: Ulcerative colitis (UC) is a chronic inflammatory disease. Fecal microbial transplantation (FMT) is a promising alternative treatment. METHODS: This multicenter, open-label, noninferiority trial randomized patients with active left-sided UC (Mayo score 4-10) equally to FMT or 5-aminosalicylic acid (5-ASA) enemas. FMT enemas were administered five times in the first week and then once weekly for 5 weeks. 5-ASA enemas were administered daily for 2 weeks and then every other day. The primary study endpoint was clinical remission, with a total Mayo score ≤2 at week 12 with no subscore >1. RESULTS: Sixty-one patients were screened; 45 were enrolled and randomized to FMT (n = 23) or 5-ASA (n = 22). Twenty-one FMT and 22 5-ASA patients completed at least the week 4 study visit and were included in the mITT analysis. Twelve FMT (57%) and eight 5-ASA patients achieved the primary study endpoint. FMT noninferiority with 10% margin was confirmed (95% CI: -7.6%, 48.9%). Adverse events occurred in 12 FMT (57%) and 13 5-ASA (59%) patients. Increased microbial diversity persisted 3 months after FMT. CONCLUSION: FMT is an effective treatment for left-sided UC and increased recipient microbiome diversity. Targeted microbiome modification may improve FMT efficacy. Further investigation is needed to guide donor and patient selection.
- Klíčová slova
- 5-aminosalicylic acid, fecal microbial transplantation, ulcerative colitis,
- Publikační typ
- časopisecké články MeSH
This article reports a case of a female patient who presented with epigastric pain. Further investigations confirmed CMV infection as a cause of stenosing gastric ulcer. In this case treatment with a proton pump inhibitor and antivirotic treatment led to a full recovery. Orgain manifestation of CMV infection if often in immunocompromitant hosts and it is, on the contratry, relatively rare in immunocompetent adults.
- Klíčová slova
- Gastritis, cytomegalovirus, immunocompetent.,
- MeSH
- bolesti břicha MeSH
- cytomegalovirové infekce * komplikace MeSH
- dospělí MeSH
- lidé MeSH
- stenóza MeSH
- žaludeční vředy * komplikace MeSH
- Check Tag
- dospělí MeSH
- lidé MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- kazuistiky MeSH
PURPOSE: We aimed to evaluate the diagnostic performance of computed tomography colonography (CTC) in the detection of internal hemorrhoids. METHODS: Three gastroenterologists systematically reported on the presence of internal hemorrhoids in patients with incomplete colonoscopy, for whom they considered a subsequent CTC. For 44 patients with internal hemorrhoids revealed by optical colonoscopy, an age- and gender-matched cohort of 66 patients with normal findings in the rectum was selected. Endoluminal and transaxial CTC views of the rectum were evaluated for the presence of internal hemorrhoids, the anal verge prominence, asymmetry, and cushion-like appearance on a Likert scale by two experienced radiologists and two gastroenterologists. RESULTS: The sensitivity, specificity, and AUC for identification of internal hemorrhoids were 0.61 (95% CI, 0.53-0.68), 0.69 (95% CI, 0.63-0.75) and 0.66 (95% CI, 0.62-0.70), respectively. The radiologists showed a better specificity, the gastroenterologists a slightly better sensitivity. When only the rating "very likely" was considered as positive, the specificity rose to 0.89 (95% CI, 0.81-0.94) with a sensitivity of 0.50 (95% CI, 0.38-0.62). The interobserver agreement was fair. The best predictor of the presence of hemorrhoids was a prominent anal verge in the supine position (OR=1.789, 95% CI, 1.267-2.525). The difference between supine and prone positions in the evaluated features in patients with internal hemorrhoids was not significant. CONCLUSION: CTC has low sensitivity but high specificity in the detection of internal hemorrhoids, if the rater is confident in detecting them. Internal hemorrhoids do not substantially change their shape between prone and supine positions.
- MeSH
- hemoroidy diagnostické zobrazování MeSH
- kolonografie počítačovou tomografií metody MeSH
- lidé MeSH
- prospektivní studie MeSH
- rektum diagnostické zobrazování MeSH
- reprodukovatelnost výsledků MeSH
- senioři MeSH
- senzitivita a specificita MeSH
- sexuální faktory MeSH
- věkové faktory MeSH
- Check Tag
- lidé MeSH
- mužské pohlaví MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
Crohns disease and ulcerative colitis has affected people for many centuries however its incidence most likely used to be very low. The knowledge of the idiopathic intestinal inflammation at that time was also very limited - an interest about the disease has emerged since the second half of 19th century. Despite all the progress in medicine its etiology still remains unclear.Diagnosis had for a long been based only on clinical investigation and later radiography, endoscopy came in to use in the 1970s. First significant advances in therapy came during the 1940s and 1950s with the invention of aminosalicylates, antibiotics and corticoids. The most advanced conservative therapy today is biological treatment although the importance of gastrointestinal surgery should not be overlooked.The aim of this article is to briefly review the development of knowledge of the idiopathic intestinal inflammation with an emphasis on the 20th century.
- Klíčová slova
- Crohns disease., inflammatory bowel diseases, ulcerative colitis,
- MeSH
- gastrointestinální endoskopie metody MeSH
- idiopatické střevní záněty diagnóza terapie MeSH
- kyselina aminosalicylová terapeutické užití MeSH
- lidé MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH
- Názvy látek
- kyselina aminosalicylová MeSH
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.
- Klíčová slova
- Biosimilar, CT-P13, inflammatory bowel disease, infliximab,
- MeSH
- biosimilární léčivé přípravky aplikace a dávkování škodlivé účinky terapeutické užití MeSH
- C-reaktivní protein analýza MeSH
- Crohnova nemoc farmakoterapie MeSH
- dospělí MeSH
- gastrointestinální látky aplikace a dávkování škodlivé účinky MeSH
- indukce remise MeSH
- infliximab aplikace a dávkování škodlivé účinky MeSH
- lidé středního věku MeSH
- lidé MeSH
- mladiství MeSH
- mladý dospělý MeSH
- monoklonální protilátky aplikace a dávkování škodlivé účinky MeSH
- prospektivní studie MeSH
- senioři MeSH
- sexuální faktory MeSH
- ulcerózní kolitida farmakoterapie MeSH
- výsledek terapie MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mladiství MeSH
- mladý dospělý MeSH
- mužské pohlaví MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- multicentrická studie MeSH
- pozorovací studie MeSH
- Geografické názvy
- Česká republika MeSH
- Názvy látek
- biosimilární léčivé přípravky MeSH
- C-reaktivní protein MeSH
- CT-P13 MeSH Prohlížeč
- gastrointestinální látky MeSH
- infliximab MeSH
- monoklonální protilátky MeSH
Familial adenomatous polyposis (FAP) is an autosomal dominant syndrome with almost 100 % risk of colorectal cancer. The typical FAP is characterized by hundreds to thousands of colorectal adenomatous polyps and by extracolonic manifestations, later onset and lower number of polyps in colon is characteristic of an attenuated form (AFAP). We analyzed the APC gene for germline mutations in 90 FAP/AFAP patients. Mutation screening was performed using Denaturing Gradient Gel Electrophoresis. DNA fragments showing an aberrant electrophoretic banding pattern were sequenced. APC-mutation-negative probands were screened for large deletions of the APC gene using multiplex ligation dependent probe amplification. Analysis of mRNA variants followed in probands with possible splicing mutation by PCR amplification of target site flanking exons and sequencing the normal and aberrant products. We identified 30 germline variants among 36 unrelated probands including large deletions. Eleven APC variants detected last two years have not been reported yet. At all, fifteen of them are expected to cause errors in mRNA splicing. Analysis of mRNA in ten of these patients revealed exon skipping in seven cases, exonisation of intron in one of these as well, change of the amount of alternatively spliced product in one case, and no effect was found in three cases. In two of the patients, the biopsy of colon mucosa and polyp enabled us to examine the effect of the mutation on splicing pattern in colon cells directly. The comparison of alternative and standard transcript amount showed similar transcription pattern of exon 14 in control colon mucosa tissue (9 samples) as in 51 blood control samples.
- MeSH
- alternativní sestřih * MeSH
- familiární adenomatózní polypóza genetika MeSH
- genetická predispozice k nemoci MeSH
- geny APC * MeSH
- kolorektální nádory genetika MeSH
- lidé MeSH
- mutace MeSH
- Check Tag
- lidé MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Geografické názvy
- Česká republika MeSH
Inflammation of the ileum - ileitis - is classically connected with Crohn's disease. But a wide variety of diseases is associated with inflammation of the ileum. These include inflammatory bowel disease, infections, spondyloarthropathies, vascular diseases, drug-related enteritis, infiltration (e.g. sarcoidosis, amyloidosis), postirradiation enteritis, tumors, endometriosis, celiac disease and collagenosis.
- MeSH
- diferenciální diagnóza MeSH
- lidé MeSH
- nemoci ilea diagnóza MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- anglický abstrakt MeSH
- časopisecké články MeSH
- přehledy MeSH
