Úvod: Přestože je infliximab (IFX) dosud „zlatým standardem“ biologické léčby Crohnovy nemoci (CN), jeho účinnost se může lišit v závislosti na mnoha faktorech. Jedním z nich je individuální reakce pacienta na lék. Významným klinickým problémem je imunogenicita IFX, kdy může až u 60 % léčených pacientů dojít k vývoji protilátek proti léčivu, což vede ke ztrátě odpovědi na léčbu a/nebo k nežádoucím reakcím na terapii. Od roku 2020 je k léčbě nemocných s CN k dispozici infliximab k subkutánnímu podání (IFX-SC), jehož farmakokinetika se vyznačuje stabilní a vysokou údolní koncentrací léčiva (TL – trough level) v krevním oběhu. Je možné, že jedním z důsledků této vlastnosti IFX-SC je jeho nižší míra imunogenicity. Předkládáme prospektivní studii sledování pacientů s diagnózou CN s velmi těžkým až refrakterním průběhem, kteří byli léčeni IFX-SC. Cílem studie bylo sledování imunogenicity IFX-SC včetně sledování dynamiky TL a protilátek proti léčivu (anti-IFX). Je popsána dynamika klinických, zobrazovacích a laboratorních markerů CN v průběhu jednoho roku sledování a léčby. Materiál a metodika: Do studie bylo zařazeno 23 pacientů s diagnózou CN s anamnézou selhání 2–6 předchozích linií biologické léčby, přičemž jednou z proběhlých terapií byl nitrožilní infliximab (IFX-IV). Pacienti byli rozděleni do dvou ramen indukční léčby na základě přítomnosti anti-IFX. Udržovací terapie představovala 120 mg s.c. ? 14 dní, v případě potřeby intenzifikace se jednalo o 240 mg s.c. ? 14 dní. Nemocní byli sledováni v týdnech (W – week) W0, W4, W14, W30 a W52, přičemž byly zaznamenány Harvey-Bradshawův index (HBI), sérová hladina C-reaktivního proteinu (CRP), fekální koncentrace kalprotektinu (FC), hladina léku (TL IFX) a anti-IFX. Dále bylo stanoveno endoskopické a ultrasonografické skóre nemoci (SES-CD a IUS) a u všech pacientů byl vyšetřen haplotyp HLA DQA1*05. Data byla analyzována pomocí softwaru MedCalc® s použitím neparametrických statistických metod a binární logistické regrese. Výsledky: U 13 z 23 pacientů (56,5 %) bylo zaznamenáno 52týdenní setrvání na léčbě IFX-SC se signifikantním poklesem všech sledovaných klinických, zobrazovacích i laboratorních markerů aktivity CN. V průběhu terapie došlo u 8 ze 16 vstupně anti-IFX pozitivních osob k sérokonverzi k negativním anti-IFX (50 %). Žádný z pacientů léčených IFX-SC ve W52 již nepotřeboval konkomitantní léčbu imunomodulátory. Během 52 týdnů terapie nebyla ve sledované kohortě zaznamenána ani jedna nová senzibilizace infliximabem. Závěr: Subkutánní cesta podání infliximabu může být vhodným a úspěšným řešením v situaci, kdy je žádoucí reindukce terapie infliximabem, a to včetně pacientů s přítomností neutralizujících protilátek proti léčivu.
Introduction: Despite infliximab (IFX) still being the “gold standard” of biological therapy for Crohn’s disease (CD), its effectiveness may vary depending on many factors. One of these factors is the individual patient’s reaction to the drug. A significant clinical problem is the immunogenicity of IFX, where up to 60% of treated patients may develop antibodies against the drug, leading to a loss of response to treatment and/or adverse reactions to therapy. Since 2020, subcutaneous infliximab (IFX-SC) has been available for treating CD patients, characterized by its stable and high trough level (TL) concentration in blood. It is possible that one consequence of this property of IFX-SC is its lower rate of immunogenicity. We present a prospective study of patients diagnosed with CD with severe to refractory courses, treated with IFX-SC. The aim of the study was to monitor the immunogenicity of IFX-SC, including the dynamics of TL and anti-drug antibodies (anti-IFX). The dynamics of clinical, imaging, and laboratory markers of CD over one year of monitoring and treatment are described. Materials and methods: The study included 23 patients diagnosed with CD who had failed 2 to 6 previous lines of biological therapy, one of which was intravenous infliximab (IFX-IV). Patients were divided into two arms of induction therapy based on the presence of anti-IFX. Maintenance therapy consisted of 120 mg s.c. every 14 days, and intensification was 240 mg s.c. every 14 days if necessary. Patients were monitored at weeks W0, W4, W14, W30, and W52, recording Harvey-Bradshaw Index (HBI), serum C-reactive protein (CRP), fecal calprotectin (FC) concentrations, drug trough levels (TL IFX) and serum anti-drug antibodies (anti-IFX). Endoscopic and ultrasonographic disease scores (SES-CD and IUS) were determined, and HLA DQA1*05 haplotype was examined in all patients. Data were analyzed using MedCalc® Statistical Software with non-parametric statistical methods and binary logistic regression. Results: 52-week persistence on IFX-SC treatment was recorded in 13 out of 23 patients (56.5%), with a significant decrease in all monitored clinical, imaging, and laboratory markers of CD activity. During the therapy, 8 out of 16 initially anti-IFX positive individuals seroconverted to negative anti-IFX (50%). None of the patients treated with IFX-SC in W52 needed concomitant immunomodulator treatment. No new sensitization to infliximab was recorded in the cohort during the 52-week therapy. Conclusion: The subcutaneous route of infliximab administration may be a suitable and successful solution in situations where reinduction of infliximab therapy is desired, including patients with the presence of neutralizing antibodies against the drug.
BACKGROUND: A subcutaneous formulation of infliximab (IFX-SC) approved to treat patients with inflammatory bowel disease may offer improved efficacy versus intravenous infliximab. METHODS: Patients with refractory Crohn's disease (CD, n = 32) previously treated unsuccessfully with at least 2 biologics were treated with IFX-SC and followed from baseline at Week 0 (W0) to Week 30 (W30). The study's primary endpoint was the treatment's persistence at W30, while secondary goals included the analysis of serum infliximab trough levels (TL IFX), dynamics of anti-IFX antibodies (ATIs), and clinical, serum and fecal markers of CD activity during IFX-SC treatment. RESULTS: Midterm treatment persistence with the continuation of treatment after W30 was 53%. TL IFX median values showed rapid, significant upward dynamics and exceeded 15.5 μg/mL at W30, whereas median ATI levels significantly declined. Among ATI-negative patients at W0 (n = 15), only one showed IFX immunogenicity with newly developed ATIs at W30. Among ATI-positive patients at W0, ATI seroconversion from ATI-positive to ATI-negative status was observed in 10 of 17 patients (58.8%). Patients who had continued IFX-SC treatment at W30 showed significant decreases in C-reactive protein (P = .0341), fecal calprotectin (P = .0002), and Harvey-Bradshaw index (P = .0029) since W0. CONCLUSIONS: Patients with refractory CD previously treated with at least 2 biologics exhibited clinically relevant improvement with IFX-SC, which showed less immunogenic potential than IFX-IV and highly stable TL IFX.
- Publikační typ
- časopisecké články MeSH
- MeSH
- diagnostické techniky gastrointestinální klasifikace MeSH
- diferenciální diagnóza MeSH
- gastrointestinální endoskopie klasifikace metody MeSH
- kolorektální nádory * chirurgie diagnóza epidemiologie klasifikace patofyziologie prevence a kontrola terapie MeSH
- lidé MeSH
- nádory rekta terapie MeSH
- nádory tračníku chirurgie diagnostické zobrazování farmakoterapie terapie MeSH
- screeningové diagnostické programy MeSH
- staging nádorů klasifikace metody MeSH
- terciární prevence klasifikace MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- přehledy MeSH
BACKGROUND AND AIMS: Adequate bowel preparation is essential for successful and effective colonoscopy. Several types of cleansing agents are currently available including low-volume solutions. The aim of this study was to compare the efficacy of four different bowel cleansing agents. METHODS: A single-center, prospective, randomized, and single-blind study was performed. Consecutive patients referred for colonoscopy were enrolled and randomized into one of the following types of laxatives: polyethylenglycol 4L (PEG), oral sulfate solution (OSS), 2L polyethylenglycol + ascorbate (2L-PEG/Asc), or magnesium citrate + sodium picosulfate (MCSP). The primary outcome was quality of bowel cleansing evaluated according to the Boston Bowel Preparation Scale (BBPS). Secondary outcomes were polyp detection rate (PDR) and tolerability. RESULTS: Final analysis was performed on 431 patients. The number of patients with adequate bowel preparation (BBPS total scores ≥6 and sub scores ≥2 in each segment) was not significantly different throughout all groups (95.4% PEG; 94.6% OSS; 96.3% 2L-PEG/Asc; 96.2% MCSP; p=0.955). Excellent bowel preparation (BBPS total scores ≥ 8) was associated with younger age (p=0.007). The groups did not have significantly different PDRs (49.5% PEG; 49.1% OSS; 38% 2L-PEG/Asc; 40.4% MCSP; p=0.201). The strongest predictors of pathology identification were age and male gender. The best-tolerated solution was MCSP (palatability: p<0.001; nausea: p=0.024).
BACKGROUND AND AIMS: Adequate bowel preparation is essential for successful and effective colonoscopy. Several types of cleansing agents are currently available including low-volume solutions. The aim of this study was to compare the efficacy of four different bowel cleansing agents. METHODS: A single-center, prospective, randomized, and single-blind study was performed. Consecutive patients referred for colonoscopy were enrolled and randomized into one of the following types of laxatives: polyethylenglycol 4L (PEG), oral sulfate solution (OSS), 2L polyethylenglycol + ascorbate (2L-PEG/Asc), or magnesium citrate + sodium picosulfate (MCSP). The primary outcome was quality of bowel cleansing evaluated according to the Boston Bowel Preparation Scale (BBPS). Secondary outcomes were polyp detection rate (PDR) and tolerability. RESULTS: Final analysis was performed on 431 patients. The number of patients with adequate bowel preparation (BBPS total scores ≥6 and sub scores ≥2 in each segment) was not significantly different throughout all groups (95.4% PEG; 94.6% OSS; 96.3% 2L-PEG/Asc; 96.2% MCSP; p=0.955). Excellent bowel preparation (BBPS total scores ≥ 8) was associated with younger age (p=0.007). The groups did not have significantly different PDRs (49.5% PEG; 49.1% OSS; 38% 2L-PEG/Asc; 40.4% MCSP; p=0.201). The strongest predictors of pathology identification were age and male gender. The best-tolerated solution was MCSP (palatability: p<0.001; nausea: p=0.024).
A substantial body of literature has provided evidence that type 2 diabetes mellitus (T2DM) and colorectal neoplasia share several common factors. Both diseases are among the leading causes of death worldwide and have an increasing incidence. In addition to usual risk factors such as sedentary lifestyle, obesity, and family history, common pathophysiological mechanisms involved in the development of these diseases have been identified. These include changes in glucose metabolism associated with adipose tissue dysfunction including insulin resistance resulting to hyperinsulinemia and chronic hyperglycemia. In addition to altered glucose metabolism, abdominal obesity has been associated with accented carcinogenesis with chronic subclinical inflammation. An increasing number of studies have recently described the role of the gut microbiota in metabolic diseases including T2DM and the development of colorectal cancer (CRC). Due to the interconnectedness of different pathophysiological processes, it is not entirely clear which factor is crucial in the development of carcinogenesis in patients with T2DM. The aim of this work is to review the current knowledge on the pathophysiological mechanisms of colorectal neoplasia development in individuals with T2DM. Here, we review the potential pathophysiological processes involved in the onset and progression of colorectal neoplasia in patients with T2DM. Uncovering common pathophysiological characteristics is essential for understanding the nature of these diseases and may lead to effective treatment and prevention.
- MeSH
- adipozita MeSH
- diabetes mellitus 2. typu epidemiologie mikrobiologie patofyziologie MeSH
- dysbióza MeSH
- energetický metabolismus MeSH
- hodnocení rizik MeSH
- hyperglykemie epidemiologie patofyziologie MeSH
- hyperinzulinismus epidemiologie patofyziologie MeSH
- incidence MeSH
- inzulinová rezistence MeSH
- kolorektální nádory epidemiologie mikrobiologie patofyziologie MeSH
- lidé MeSH
- obezita epidemiologie patofyziologie MeSH
- rizikové faktory MeSH
- střevní mikroflóra MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH
Mezi funkční anorektální poruchy řadíme fekální inkontinenci, funkční defekační poruchy a funkční anorektální bolest. Vykazují vysokou prevalenci a znamenají vysokou socioekonomickou zátěž. Anorektální manometrie je považována za zlatý standard v diagnostice. 3D high‑resolution anorektální manometrie představuje nejmodernější diagnostickou techniku a pomáhá pochopit patofyziologické mechanismy v celém análním kanálu a rektoanální koordinaci. Díky správné diagnostice je pro pacienta stanoven individuálně přizpůsobený léčebný plán s cílem zmírnění symptomatiky a zlepšení kvality života.
Functional anorectal disorders include fecal incontinence, functional defecation disorders and functional anorectal pain. They show a high prevalence and represent a high socio‑economic burden. Anorectal manometry is considered the gold standard in diagnosis. 3D high‑resolution anorectal manometry is a modern diagnostic technique and helps to understand pathophysiological mechanisms throughout the anal canal and anorectal coordination. Thanks to the correct diagnosis, an individually tailored treatment plan is set for the patient in order to relieve from symptoms and improve the quality of life.
The adenoma detection rate (ADR) is the primary quality indicator for colonoscopies. The polyp detection rate (PDR) is available from administrative data and does not depend on histology verification. The correlation between PDR and ADR and the ADR/PDR conversion factor in preventive colonoscopies were evaluated. In the prospective study, asymptomatic individuals aged 45-75 years with preventive colonoscopy in 2012-2016 were included. Spearman's correlation coefficient was used to assess PDR/ADR for each endoscopist. Conversion factor predicting ADR from PDR was obtained by linear regression and subsequently compared with adenoma to polyp detection rate quotient. One thousand six hundred fourteen preventive colonoscopies performed by 16 endoscopists in 8 screening colonoscopy centres in the Czech Republic were analysed. Correlation between PDR and ADR in all preventive colonoscopies was high and statistically significant (Rs 0.82; P < 0.001). There was a strong correlation between PDR and ADR in men (Rs 0.74; P = 0.002) and in screening colonoscopies (Rs 0.85; P < 0.001). The conversion factor to convert ADR from PDR was 0.72 in all preventive colonoscopies, 0.76 in FOBT+ colonoscopies and 0.67 in screening colonoscopies. ADR may be replaced by PDR in the assessment of colonoscopy quality. The value of the conversion factor varies according to colonoscopy indication and gender of examined individuals; in this Czech study, it was 0.72 in all preventive colonoscopies. The minimum requested ADR of 25 % corresponds to a PDR of 35 %, when converted with the appropriate conversion factor.
- MeSH
- adenom diagnóza epidemiologie patologie prevence a kontrola MeSH
- administrativní požadavky na zdravotní péči statistika a číselné údaje MeSH
- časná detekce nádoru metody statistika a číselné údaje MeSH
- hodnocení rizik metody statistika a číselné údaje MeSH
- kolon diagnostické zobrazování MeSH
- kolonoskopie statistika a číselné údaje MeSH
- kolorektální nádory diagnóza epidemiologie patologie prevence a kontrola MeSH
- lidé středního věku MeSH
- lidé MeSH
- plošný screening metody statistika a číselné údaje MeSH
- polypy tlustého střeva diagnóza epidemiologie patologie MeSH
- prospektivní studie MeSH
- retrospektivní studie MeSH
- senioři MeSH
- sexuální faktory MeSH
- střevní sliznice diagnostické zobrazování patologie MeSH
- Check Tag
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- srovnávací studie MeSH
- Geografické názvy
- Česká republika MeSH
