Gastroparesis (GP) can be a severe and debilitating disease. Its pathophysiology is complex and not completely understood. Two principal mechanisms are responsible for the development of symptoms - gastric hypomotility and pylorospasm. Pylorus targeted therapies aim to decrease presumably elevated pyloric tone - pylorospasm. There is a growing body of evidence about their role in the treatment algorithm of GP. G-POEM (endoscopic pyloromyotomy) is an extensively studied pylorus targeted therapy. Its efficacy ranges between 56 and 80% and the number of recurrences among those with treatment effect seems low. G-POEM is a safe procedure with very low frequency of severe adverse events. At present, G-POEM should not be considered as an experimental approach and may be offered to all patients with refractory and severe GP. Nevertheless, G-POEM is not a first line treatment. Conservative measures such as diet modification and pharmacotherapy should always be tried before G-POEM is considered. Further research must focus on better patient selection as at present there are no standardized criteria. Functional imaging such as impedance planimetry (EndoFlip) may hold promise in this regard.
- MeSH
- gastroparéza * chirurgie patofyziologie terapie etiologie MeSH
- lidé MeSH
- pyloromyotomie * metody škodlivé účinky MeSH
- pylorus * chirurgie patofyziologie MeSH
- recidiva MeSH
- výběr pacientů MeSH
- vyprazdňování žaludku MeSH
- výsledek terapie MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH
Biologická terapie je v dnešní době léčebným standardem u pacientů se středně těžkou až těžkou ulcerózní kolitidou, kteří nereagují na konvenční terapii, včetně kortikosteroidů a azathioprinu, nebo kteří tuto léčbu netolerují či je kontraindikována. Biosimilární infliximab (IFX) je pro léčbu idiopatických střevních zánětů (inflammatory bowel disease, IBD) v Evropské unii schválen od září 2013, do klinické praxe v České republice se dostal v roce 2015. V roce 2019 European Medicines Agency (EMA) povolila užívání biosimilárního infliximabu CT-P13 ve formě k subkutánnímu podávání ve všech indikacích původního přípravku. Kazuistické sdělení popisuje případ pacienta s těžkým průběhem ulcerózní kolitidy. Vysoká aktivita nemoci, selhání konvenční terapie a kortikodependence si u pacienta vyžádala zahájení biologické terapie biosimilárním IFX. Po počátečním vynikajícím léčebném účinku se po zhruba šesti měsících pacientův stav zhoršil, došlo k významnému snížení údolní koncentrace (trough level, TL) léčiva s významnou tvorbou protilátek. Na základě údajů o dosažení vyšších středních koncentrací IFX a nižší imunogenitě byla u pacienta zahájena léčba subkutánním IFX, která vedla k normalizaci protilátek, navýšení TL IFX a tím k opětovnému klinickému účinku.
Biologic therapy is a standard care for patients with moderate-to-severe ulcerative colitis who do not respond to conventional therapy or who are intolerant or contraindicated to including corticosteroids and azathioprine. Biosimilar infliximab (IFX) has been approved for a treatment of inflammatory bowel disease (IBD) in the European Union since September 2013, and entered clinical practice in the Czech Republic in 2015. In 2019, the European Medicines Agency (EMA) approved a new formula of biosimilar infliximab CT-P13 for subcutaneous application in all indications of the original preparation. The case report describes a patient with a severe course of ulcerative colitis. High disease activity, failure of conventional therapy and corticodependency necessitated initiation of biologic therapy with biosimiLar IFX. After 6 months with an initial excellent therapeutic effect patient's condition worsened, there was a significant decrease in the trough Level (TL) of the drug with a significant formation of antibodies. Based on data on higher middle Levels of IFX and Lower immunogenicity patient was switched on subcutaneous IFX treatment, which Led to the normalization of antibodies, increase in TL IFX and improve of cLinicaL condition.
- MeSH
- biosimilární léčivé přípravky farmakologie klasifikace terapeutické užití MeSH
- humanizované monoklonální protilátky farmakologie klasifikace terapeutické užití MeSH
- infliximab * aplikace a dávkování farmakologie terapeutické užití MeSH
- injekce subkutánní metody MeSH
- lidé středního věku MeSH
- lidé MeSH
- ulcerózní kolitida * diagnóza farmakoterapie MeSH
- Check Tag
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- Publikační typ
- kazuistiky MeSH
Chronická postfundoplikační dysfagie (PFD) není častá, ale představuje závažnou komplikaci antirefluxní operace. Standardním řešením je v současnosti pouze reoperace, neboť endoskopická pneumatická nebo hydraulická dilatace nejsou v této indikaci účinné. Perorální endoskopická myotomie (POEM) dnes představuje zlatý standard v léčbě pacientů s achalázií jícnu, u pacientů s PFD se však jedná o metodu experimentální a její klinická účinnost není známá. Naše kazuistika popisuje případ pacientky po fundoplikaci a následné reoperaci, u které došlo v průběhu let k rozvoji těžké dysfagie s progresivním váhovým úbytkem, bez adekvátní odpovědi na několik absolvovaných etap endoskopické dilatace. Jako ultimum refugium byla v tomto případě zvažovaná ezofagektomie. Případ byl diskutován na multioborovém semináři a po provedení doplňujících vyšetření (EndoFLIP) byl u pacientky nekomplikovaně proveden POEM s výborným efektem. Výkon proběhl bez jakýchkoli komplikací.
Although uncommon, chronic postfundoplication dysphagia (PFD) is a serious complication of antireflux surgery. Currently, reoperation is the only possible solution as endoscopic pneumatic or hydraulic dilation are not effective. At present, POEM represents a standard method for the treatment of esophageal achalasia; however, in patients with PFD it is an experimental approach whose clinical effectiveness is unknown. Our case report describes a female patient who suffered from severe PFD after two surgeries (fundoplication and subsequent reoperation). Dysphagia and progressive weight loss had developed over the years and all treatment attempts (several sessions of dilation) were unsuccessful. Subsequently, esophageal resection was considered as the last resort. After a discussion in a multidisciplinary team and additional examinations (EndoFLIP), POEM was performed without any complications, and the procedure had an excellent effect without any adverse events.
- Klíčová slova
- pneumatická dilatace,
- MeSH
- dilatace metody MeSH
- fundoplikace metody MeSH
- laparoskopie metody MeSH
- lidé MeSH
- poruchy polykání * chirurgie etiologie MeSH
- pyloromyotomie * metody MeSH
- senioři MeSH
- výsledek terapie MeSH
- Check Tag
- lidé MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- kazuistiky MeSH
BACKGROUND: Tumor necrosis factor-alpha (TNF-α) agonists revolutionized therapeutic algorithms in inflammatory bowel disease (IBD) management. However, approximately every third IBD patient does not respond to this therapy in the long term, which delays efficient control of the intestinal inflammation. METHODS: We analyzed the power of serum biomarkers to predict the failure of anti-TNF-α. We collected serum of 38 IBD patients at therapy prescription and 38 weeks later and analyzed them with relation to therapy response (no-, partial-, and full response). We used enzyme-linked immunosorbent assay to quantify 16 biomarkers related to gut barrier (intestinal fatty acid-binding protein, liver fatty acid-binding protein, trefoil factor 3, and interleukin (IL)-33), microbial translocation, immune system regulation (TNF-α, CD14, lipopolysaccharide-binding protein, mannan-binding lectin, IL-18, transforming growth factor-β1 (TGF-β1), osteoprotegerin (OPG), insulin-like growth factor 2 (IGF-2), endocrine-gland-derived vascular endothelial growth factor), and matrix metalloproteinase system (MMP-9, MMP-14, and tissue inhibitors of metalloproteinase-1). RESULTS: We found that future full-responders have different biomarker profiles than non-responders, while partial-responders cannot be distinguished from either group. When future non-responders were compared to responders, their baseline contained significantly more TGF-β1, less CD14, and increased level of MMP-9, and concentration of these factors could predict non-responders with high accuracy (AUC = 0.938). Interestingly, during the 38 weeks, levels of MMP-9 decreased in all patients, irrespective of the outcome, while OPG, IGF-2, and TGF-β1 were higher in non-responders compared to full-responders both at the beginning and the end of the treatment. CONCLUSIONS: The TGF-β1 and CD14 can distinguish non-responders from responders. The changes in biomarker dynamics during the therapy suggest that growth factors (such as OPG, IGF-2, and TGF-β) are not markedly influenced by the treatment and that anti-TNF-α therapy decreases MMP-9 without influencing the treatment outcome.
BACKGROUND: Ustekinumab, is a new therapy for patients with IBD, especially for patients suffering from Crohn's disease (CD) who did not respond to anti-TNF treatment. To shed light on the longitudinal effect of ustekinumab on the immune system, we investigated the effect on skin and gut microbiota composition, specific immune response to commensals, and various serum biomarkers. METHODOLOGY/PRINCIPAL FINDINGS: We recruited 11 patients with IBD who were monitored over 40 weeks of ustekinumab therapy and 39 healthy controls (HC). We found differences in the concentrations of serum levels of osteoprotegerin, TGF-β1, IL-33, and serum IgM antibodies against Lactobacillus plantarum between patients with IBD and HC. The levels of these biomarkers did not change in response to ustekinumab treatment or with disease improvement during the 40 weeks of observation. Additionally, we identified differences in stool abundance of uncultured Subdoligranulum, Faecalibacterium, and Bacteroides between patients with IBD and HC. CONCLUSION/SIGNIFICANCE: In this preliminary study, we provide a unique overview of the longitudinal monitoring of fecal and skin microbial profiles as well as various serum biomarkers and humoral and cellular response to gut commensals in a small cohort of patients with IBD on ustekinumab therapy.
- MeSH
- biologické markery MeSH
- Crohnova nemoc * terapie MeSH
- inhibitory TNF MeSH
- lidé MeSH
- mikrobiota * MeSH
- pilotní projekty MeSH
- ustekinumab terapeutické užití MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem 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
BACKGROUND: Patients with inflammatory bowel disease (IBD) on immune-modifying treatment could be at an increased risk for severe coronavirus disease 2019 (COVID-19); thus, data on the efficacy and safety of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) vaccines are essential. We conducted a prospective study of IBD patients vaccinated with BNT162b2, CX-024414, and ChAdOx1 nCoV-19 vaccines. The aim was to evaluate the rate and magnitude of seroconversion, assess the effect of different immune-modifying treatment modalities on the magnitude of anti-SARS-CoV-2 IgG antibody levels, and analyze the impact of anti-SARS-CoV-2 vaccination on the inflammatory biomarkers of IBD. METHODS: The study included 602 IBD patients and 168 immunocompetent health care workers serving as controls. Serum anti-SARS-CoV-2 IgG antibodies were measured by chemiluminescent microparticle immunoassay before the vaccination and 8 weeks after the vaccination. RESULTS: Of IBD patients, 82.2% were receiving biological treatment: most of them were treated with antitumor necrosis factor (TNF)-α inhibitors (48.5%), and just under half of them were treated with concomitant thiopurines or methotrexate, followed by vedolizumab (18.6%) and ustekinumab (15.1%). Only 8.1% of patients were on 5-aminosalicylates, and a minority (2.2%) were treatment-free. The postvaccine seropositivity rate among IBD patients and controls was 97.8% vs 100%. Median anti-SARS-CoV-2 IgG levels were lower among IBD recipients of ChAdOx1 nCoV-19 compared with 2 other vaccines (P < .0001) and control ChAdOx1 nCoV-19 recipients (P = .01). No correlation was found between serum trough levels and anti-SARS-CoV-2 IgG concentrations for any of the biological drugs used. The TNF-α inhibitors with concomitant immunosuppressive treatment but no other treatment modalities were associated with a lower postvaccination antibody response (P < .0001). When evaluating the laboratory activity of IBD by C-reactive protein and fecal calprotectin levels, no significant differences were found before the vaccination and 8 weeks after its completion. CONCLUSIONS: Our findings warrant particular attention to the anti-SARS-CoV-2 vaccination of IBD patients treated with TNF-α inhibitors with concomitant immunomodulators and show the priority of mRNA vaccines in this specific group of patients.
- MeSH
- C-reaktivní protein metabolismus MeSH
- ChAdOx1 nCoV-19 MeSH
- COVID-19 * prevence a kontrola MeSH
- idiopatické střevní záněty * farmakoterapie MeSH
- imunoglobulin G MeSH
- leukocytární L1-antigenní komplex MeSH
- lidé MeSH
- methotrexát MeSH
- prospektivní studie MeSH
- protilátky virové MeSH
- SARS-CoV-2 MeSH
- TNF-alfa metabolismus MeSH
- tvorba protilátek MeSH
- ustekinumab MeSH
- vakcína BNT162 MeSH
- vakcinace MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
Crohn's disease (CD) and ulcerative colitis (UC) are two forms of inflammatory bowel disease (IBD), where the role of gut but not skin dysbiosis is well recognized. Inhibitors of TNF have been successful in IBD treatment, but up to a quarter of patients suffer from unpredictable skin adverse events (SkAE). For this purpose, we analyzed temporal dynamics of skin microbiota and serum markers of inflammation and epithelial barrier integrity during anti-TNF therapy and SkAE manifestation in IBD patients. We observed that the skin microbiota signature of IBD patients differs markedly from healthy subjects. In particular, the skin microbiota of CD patients differs significantly from that of UC patients and healthy subjects, mainly in the retroauricular crease. In addition, we showed that anti-TNF-related SkAE are associated with specific shifts in skin microbiota profile and with a decrease in serum levels of L-FABP and I-FABP in IBD patients. For the first time, we showed that shifts in microbial composition in IBD patients are not limited to the gut and that skin microbiota and serum markers of the epithelium barrier may be suitable markers of SkAE during anti-TNF therapy.
Inflammatory bowel diseases (IBD) are chronic disorders of the gastrointestinal tract that have been linked to microbiome dysbiosis and immune system dysregulation. We investigated the longitudinal effect of anti-TNF therapy on gut microbiota composition and specific immune response to commensals in IBD patients. The study included 52 patients tracked over 38 weeks of therapy and 37 healthy controls (HC). To characterize the diversity and composition of the gut microbiota, we used amplicon sequencing of the V3V4 region of 16S rRNA for the bacterial community and of the ITS1 region for the fungal community. We measured total antibody levels as well as specific antibodies against assorted gut commensals by ELISA. We found diversity differences between HC, Crohn's disease, and ulcerative colitis patients. The bacterial community of patients with IBD was more similar to HC at the study endpoint, suggesting a beneficial shift in the microbiome in response to treatment. We identified factors such as disease severity, localization, and surgical intervention that significantly contribute to the observed changes in the gut bacteriome. Furthermore, we revealed increased IgM levels against specific gut commensals after anti-TNF treatment. In summary, this study, with its longitudinal design, brings insights into the course of anti-TNF therapy in patients with IBD and correlates the bacterial diversity with disease severity in patients with ulcerative colitis (UC).
- MeSH
- biodiverzita MeSH
- dospělí MeSH
- feces mikrobiologie MeSH
- houby genetika MeSH
- idiopatické střevní záněty krev farmakoterapie mikrobiologie chirurgie MeSH
- inhibitory TNF terapeutické užití MeSH
- interleukin-17 metabolismus MeSH
- leukocyty mononukleární metabolismus MeSH
- lidé MeSH
- metagenomika MeSH
- protilátky krev MeSH
- RNA ribozomální 16S genetika MeSH
- střevní mikroflóra * genetika MeSH
- studie případů a kontrol MeSH
- stupeň závažnosti nemoci MeSH
- Check Tag
- dospělí MeSH
- lidé MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
Kazuistické sdělení popisuje případ pacienta s komplikovaným průběhem idiopatického střevního zánětu, konkrétně Crohnovy nemoci. Vysoká aktivita nemoci a agresivní průběh si u pacienta i přes intenzivní medikamentózní terapii vyžádaly chirurgické řešení. Vzhledem k brzké endoskopické rekurenci a mnoha rizikovým faktorům byla u pacienta zahájena biologická léčba v rámci prevence pooperační rekurence. Na základě potvrzené účinnosti a bezpečnosti biosimilárních přípravků byla u pacienta zahájena léčba biosimilárním adalimumabem s dobrý klinickým účinkem bez nežádoucích účinků.
This case report describes a case of a patient with a complicated course of inflammatory bowel disease, specifically Crohn's disease. The severe activity and aggressive course required a surgery, despite intesive drug therapy. Due to early endoscopic recurrence and many risk factors, the patient was started on biological treatment in the prophylaxis of postoperative recurrence. Based on the proven efficacy and safety of the biosimilar agents, the patient was started on biosimilar adalimumab with good clinical response and no side effects.
