- MeSH
- gastroenterologie * dějiny MeSH
- lidé MeSH
- významné osobnosti * MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- biografie MeSH
- O autorovi
- Lukáš, Karel, 1942-2024 Autorita
- MeSH
- Crohnova nemoc * diagnóza MeSH
- diagnostické zobrazování metody MeSH
- kolonoskopie metody MeSH
- lidé MeSH
- magnetická rezonanční tomografie metody MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- směrnice pro lékařskou praxi MeSH
- MeSH
- diferenciální diagnóza MeSH
- lidé MeSH
- těhotenství MeSH
- ulcerózní kolitida * diagnóza klasifikace terapie MeSH
- vakcinace MeSH
- Check Tag
- lidé MeSH
- těhotenství MeSH
- Publikační typ
- směrnice pro lékařskou praxi MeSH
Úvod: Idiopatické střevní záněty (IBD – inflammatory bowel disease) jsou onemocněním převážně mladého a fertilního věku, kdy i značná část pacientek otěhotní v průběhu nemoci. Jako nejdůležitější faktor zdárného průběhu těhotenství je klidová fáze nemoci, které dosáhneme často intenzivní protizánětlivou léčbou. Vedolizumab (VDZ) a ustekinumab (UST) jsou nové monoklonální protilátky s rozdílným mechanizmem účinku. VDZ je protilátka proti a4ß7 integrinovému receptoru, UST proti interleukinu 12/23 a obě v posledních letech rozšířily spektrum biologické léčby IBD. Cíle: Prezentace výsledků multicentrické observační studie. Primárním cílem našeho sledování bylo posoudit bezpečnost VDZ a UST na průběh gravidity, vývoj plodu a novorozence. Sekundárním cílem bylo zhodnocení transplacentárního přenosu léků prostřednictvím analýzy hladin léků v pupečníkové krvi a žilní krvi matky. Metodika: Multicentrická retrospektivně-prospektivní observační studie. Demografické údaje, informace o charakteru IBD v průběhu těhotenství a detaily terapie byly získávány z preformovaného dotazníku, údaje o porodu a stavu novorozence byly doplněny z porodnické dokumentace. Ke stanovení míry transplacentárního přenosu byly měřeny hladiny VDZ a UST z odběrů pupečníkové krve a žilní krve matky v době porodu pomocí metody ELISA. Výsledky: Od března 2019 do září 2021 bylo do studie zařazeno celkem 85 dokončených gravidit u 79 pacientek z 15 center biologické léčby IBD v České republice, z nichž 36 bylo léčeno VDZ (s mediánem věku žen 32 let) a 49 UST (s mediánem věku žen 30,5 let). Ve skupině s VDZ došlo k porodům živých dětí u 32 gravidit (88,9 %), zaznamenány byly dva časné spontánní aborty a dvě instrumentálně přerušená těhotenství (4; 11,1 %). Celkem 31 dětí (93,9 %) bylo porozeno v termínu, medián porodních hmotností byl 3 097,5 g. V linii s UST bylo porozeno 39 živých dětí (79,6 %), devět těhotenství skončilo časným spontánním abortem a jedno bylo instrumentálně přerušeno (10; 20,4 %). Celkem 38 dětí (97,4 %) bylo narozeno v termínu s mediánem porodních hmotností 3 265 g. Farmakokinetické parametry byly sledovány u 44 párů novorozenec-matka (21 VDZ, 23 UST). Medián hladin VDZ v žilní krvi matky byl 7,2 mg/l, v pupečníkové krvi novorozence 4,7 mg/l (poměr hladin v pupečníku / u matky 0,66), u UST byl medián hladin u matky 4,7 mg/l a novorozence 7,9 mg/l (poměr hladin v pupečníku / u matky 1,65). Závěr: Námi prezentované výsledky pacientek léčených pro IBD a exponovaných v průběhu gravidity minimálně jedné dávce biologické léčby UST nebo VDZ jsou v souladu s dříve publikovanými údaji a potvrzují příznivý bezpečností profil nových biologik v graviditě. Vzhledem ke stále limitovaným počtům zařazených pacientek bude potřeba do budoucna ještě dalšího sledování.
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 a4b7 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.
- Klíčová slova
- vedolizumab,
- MeSH
- biologická terapie MeSH
- dospělí MeSH
- humanizované monoklonální protilátky farmakokinetika terapeutické užití MeSH
- idiopatické střevní záněty * farmakoterapie MeSH
- klinické zkoušky jako téma MeSH
- komplikace těhotenství MeSH
- lidé MeSH
- maternofetální výměna látek MeSH
- mladý dospělý MeSH
- těhotenství * účinky léků MeSH
- ustekinumab farmakokinetika terapeutické užití MeSH
- výsledek těhotenství MeSH
- Check Tag
- dospělí MeSH
- lidé MeSH
- mladý dospělý MeSH
- těhotenství * účinky léků MeSH
- ženské pohlaví MeSH
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.
- 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
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.
- 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.
- Publikační typ
- časopisecké články MeSH
V tomto článku popisujeme případ pacientky s bolestmi v epigastriu, u níž byl diagnostikován cirkulární stenózující vřed žaludku. Dalším vyšetřením byla zjištěna CMV etiologie. Po zahájení terapie inhibitory protonové pumpy a antivirové terapie došlo k úzdravě. Orgánová manifestace CMV infekce je poměrně častou komplikací u imunokompromitovaných pacientů. U imunokompetentních pacientů bývá orgánové postižení relativně vzácné. Přesto je však nutno i na tuto etiologii pomýšlet.
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.
- MeSH
- cytomegalovirové infekce * diagnóza farmakoterapie komplikace MeSH
- Cytomegalovirus izolace a purifikace MeSH
- dospělí MeSH
- gastritida * diagnóza etiologie terapie MeSH
- lidé MeSH
- slez patologie MeSH
- stenóza patologie MeSH
- výsledek terapie MeSH
- Check Tag
- dospělí MeSH
- lidé MeSH
- ženské pohlaví MeSH
- Publikační typ
- kazuistiky MeSH
- práce podpořená grantem MeSH
