Diagnostic and prognostic value of fecal, serum and endoscopic markers in inflammatory bowel disease and colorectal cancer

Background. The most important goals of the recent therapies of inflammatory bowel disease (IBD) are to induce and maintain clinical remission and mucosal healing (MH), which can be achieved with anti-TNF-α biological therapy. CT-P13 is the first biosimilar to infliximab (IFX) that has been approved for the same indications as its originator IFX, but no data was available on the effect of IFX biosimilar on mucosal healing. Serum IFX and antibody-to-infliximab (ATI) levels are objective parameters, that may have a great role in the therapeutic decisions during maintenance biological therapy in the use of original and biosimilar agents. The aims of this thesis were, to evaluate (I) the correlation between clinical and endoscopic disease activities of UC defined by activity scores. (II) the efficacy of CT-P13 induction therapy, (III) to assess the correlation between serum IFX and ATI levels, the response to IFX therapy, and to determine the accuracy of serum drug concentration measurement in the prediction of the long-term clinical response. The last part of this thesis evaluates (IV) the diagnostic accuracy of different fecal markers in the detection of colorectal adenomas and cancer. Biomarkers are important in not only studying IBD, but may be important in colorectal cancer (CRC) as well. As CRC is the second deadliest malignancy worldwide, the simple and early detection methods are critical for theeffective management of this disease. Methods Clinical and endoscopic activities were evaluated in 100 consecutive UC patients. Clinical activities were defined by two activity indices: the Rachmilewitz Activity Index (CAI) and the partial Mayo score. They graded the findings both according to the endoscopic part of the Rachmilewitz Endoscopic Activity Index (EI) and the Mayo endoscopic subscore. MH was defined as Mayo endoscopic subscore and EI of 0. Histological activity was scored by the Riley score. Sixty-three UC patients who underwent CT-P13 induction therapy were enrolled in the second study. Sigmoidoscopy was performed after the end of the induction therapy at week 14. Mucosal healing was defined as Mayo endoscopic subscore 0 or 1. Complete mucosal healing was defined as Mayo endoscopic subscore 0. Trough level (TL) of CT-P13 was measured at week 14. Fourty-eight IBD patients receiving maintenance IFX therapy were prospectively enrolled and divided into adequate and inadequate groups. Blood samples were collected just before (trough level) and two (W2aTL) and six weeks (W6aTL) after the administration of IFX. Stool samples of patients referred to colonoscopy were collected, from 95 non-IBD patients, for the analysis of tumor M2 pyruvate kinase (M2PK), human hemoglobin (Hb), hemoglobin/haptoglobin (Hb/Hp) complex, fecal calprotectin (FC), and matrix metalloproteinase-9 (MMP-9). Results Clinical and endoscopic activities showed strong correlations using both scoring systems (p = 0.0029 and p = 0.0001). Endoscopic disease activity also correlated with the histological activity (p 1 cm were 60% and 67.5% and for CRC were 94.7% and 67.5%. Sensitivity and specificity of iFOBT for adenomas sized ≥ 1 cm were 80% and 72.5% and for CRC were 94.7% and 72.5%. Sensitivity and specificity of Hb/Hp complex for adenomas sized≥ 1 cm were 80% and 52.9% and for CRC were 100% and 52.9%. Sensitivity of FC andMMP-9 for CRC was 77.8% and 72.2%. Combined use ofM2PK, iFOBT, and FC resulted in a sensitivity and specificity of 95% and 47.5% for the detection of adenomas sized ≥ 1 cm. Conclusion Assessment of MH is very important for guiding therapy and for the evaluation of remission in patients with UC..

A gyulladásos bélbetegségek kezelése a SARS-CoV-2-járvány idején - gyakorlati javaslatok [The treatment of inflammatory bowel disease during the SARS-CoV-2 epidemic - practical advices]

A gyulladásos bélbetegségben szenvedők kezeléstől függetlenül fogékonyabbak a súlyos, hospitalizációt igénylő ví- rusinfekciókkal szemben. A betegség kezelésére használt immunszuppresszív és/vagy biológiai terápiák sokszorosára növelik az opportunista fertőzések, köztük az alsó légúti infekciók veszélyét, így az új koronavírus (severe acute res- piratory syndrome coronavirus-2) okozta járvány miatt – mely elsősorban tüdőgyulladást okoz – érdemes a megszo- kottól eltérő terápiás megfontolásokat alkalmazni az effektív és biztonságos betegellátás érdekében. A gyulladásos bélbetegek fokozott koronavírus-rizikóját feltételező várakozásokkal ellentétben a járványban legjobban érintett or- szágok közül sem az Észak-Olaszország, sem a Kína területéről származó tanulmány nem közölt fertőzést egyetlen, gyulladásos bélbetegségben szenvedő egyénnél sem. Ennek hátterében számos tényező állhat, mint például a betegek alacsonyabb átlagéletkora, a társbetegségek ritkább előfordulása stb. Ennek ellenére nem szabad megfeledkezni arról, hogy az immunszuppresszív és/vagy biológiai kezelésben részesülő betegek a veszélyeztetett csoportba tartoznak. Bizonyos esetekben szükségessé válhat a terápia módosítása, a gyógyszeres kezelés változtatásakor azonban vegyük figyelembe, hogy a relapsus és az ennek következtében szükségessé váló ambuláns megjelenés, majd esetleges hospi- talizáció növeli a koronavírus-infekció veszélyét. Ennek tükrében a fellángolást mindenképp el kell kerülni, aminek záloga a megkezdett, hatékony kezelés folytatása. Mégis, a nem fertőzött, de a prognosztikai tényezők alapján foko- zott rizikójú csoportban is már ajánlott lehet a módosítás. Közleményünk célja, hogy – a nemzetközi terápiás irány- elvek alapján – hazánkban is alkalmazható gyakorlati ajánlást nyújtson a praktizáló orvosok számára a járvány idejére, megkönnyítve és hatékonyabbá téve ezzel a gyulladásos bélbetegek ellátását

A neoadjuváns kezelés mint a rectalis ultrahangvizsgálat korlátozó tényezője

Absztrakt Bevezetés: A rectalis ultrahang a rectumtumorok stagingjének egyik alapmódszere. Előrehaladott tumorok esetén a műtét előtti neoadjuváns kezelés hatására létrejövő szöveti változások hatással vannak a módszer pontosságára. Célkitűzés: A rectalis ultrahang pontosságának felmérése preoperatív kemo-radioterápiát követően, összehasonlítva az iniciális staging során tapasztalt pontossággal. Módszer: Retrospektív módon vetették össze a Szegedi Tudományegyetem I. Belgyógyászati Klinikán 2006 és 2014 között végzett rectalis ultrahangvizsgálatok során meghatározott T-, illetve N-stádiumot a műtéti reszekátum feldolgozásakor megadott patológiai T- és N-stádiummal neoadjuváns kezelést követően és az iniciális staging során (kontrollcsoport). Eredmények: A T-stádium esetén az iniciális staging 70%-ban, a re-staging 61%-ban volt pontos, utóbbinál 31%-ban túlértékelés történt. Az ypT0 stádiumot egy esetben sem sikerült azonosítani. Az N-stádium meghatározásának pontossága 64% volt a kontrollcsoportban és 61% volt re-staging alkalmával. Következtetések: Neoadjuváns kezelést követően a rectalis ultrahang pontossága romlik. Az onkológiai kezelés hatásosságának megítélésében és a műtéti tervezésben a rectalis ultrahanggal történő re-staging szerepe megkérdőjelezhető. Orv. Hetil., 2016, 157(30), 1193–1197

The triggering role of Clostridioides difficile infection in relapsed IBD outpatients

Although the exact aetiology of inflammatory bowel disease (IBD) is unknown, one hypothesis suggests that the inflammation may be the consequence of an altered or pathogenic microbiota in a genetically susceptible host. The aim of this study was to assess the frequency of enteral infections in patients with relapse of IBD, and to evaluate the clinical utility of faecal calprotectin (FC) and faecal matrixmetalloproteinase- 9 (MMP-9) in the differential diagnosis of relapses with different origins, and to determine the recurrence rate of Clostridioides difficile (C. difficile), the hospitalisation and colectomy rate among C. difficile positive IBD patients at the end of 4 years follow-up period. Methods: In this prospective, “real life” study clinical data, serum and stool samples were assessed. Results: Overall, 135 outpatients with IBD were enrolled [91 IBD patients who relapsed and 44 subjects in clinical remission (control group)]. C. difficile A/B toxins were detected in 42.2% of all cases. Candida was presented in 9.9% among the enrolled subjects. We found significant difference between FC and MMP-9 values in patients in relapse and remission, but not in C. difficile positive and negative cases. Our results revealed an association between previous antibiotic use and the rate of toxigenic C. difficile. Toxigenic C. difficile positivity recurrence rate was 4.4%. Hospitalisation during follow-up due to IBD was 45.4% and 35% in C. difficile positive and negative group, respectively. Value of FC and MMP-9 did not predict the need of hospitalisation. Conclusions: The occurrences of toxigenic C. difficile and Candida positivity were excessively high in our patients in an acute relapse, which suggests the importance of intestinal microbiota in IBD. FC and MMP-9 has no diagnostic value to differentiate between infection-induced and natural relapse. In our study was confirmed that hospitalisation rate was higher in C. difficile positive cases, but we did not find any relationship on long-term period

The Radial Acceleration Relation and a Magnetostatic Analogy in Quasilinear MOND

Recently a remarkable relation has been demonstrated between the observed radial acceleration in disk galaxies and the acceleration predicted on the basis of baryonic matter alone. Here we study this relation within the framework of the modified gravity model MOND. The field equations of MOND automatically imply the radial acceleration relation for spherically symmetric galaxies, but for disk galaxies deviations from the relation are expected. Here we investigate whether these deviations are of sufficient magnitude to bring MOND into conflict with the observed relation. In the quasilinear formulation of MOND, to calculate the gravitational field of a given distribution of matter, an intermediate step is to calculate the "pristine field", which is a simple nonlinear function of the Newtonian field corresponding to the same distribution of matter. Hence, to the extent that the quasilinear gravitational field is approximately equal to the pristine field, the radial acceleration relation will be satisfied. We show that the difference between the quasilinear and pristine fields obeys the equations of magnetostatics, the curl of the pristine field serves as the source for the difference in the two fields, much as currents serve as sources for the magnetic field. Using the magnetostatic analogy we numerically study the difference between the pristine and quasilinear fields for simple model galaxies with a Gaussian profile. Our principal finding is that the difference between the fields is small compared to the observational uncertainties and that quasilinear MOND is therefore compatible with the observed radial acceleration relation.Comment: 9 pages, 6 figure