Is There a Role of Using a Rapid Finger Prick Antibody Test in Screening for Celiac Disease in Children?

Celiac disease (CD) is an autoimmune disease triggered by gluten in genetically predisposed individuals. Despite the increasing prevalence of CD, many patients remain undiagnosed. Standard serology tests are expensive and invasive, so several point-of-care tests (POC) for CD have been developed. We aimed to determine the prevalence of CD in first-grade pupils in Primorje-Gorski Kotar County, Croatia, using a POC test. A Biocard celiac test that detects IgA antibodies to tissue transglutaminase in whole blood was used to screen for celiac disease in healthy first-grade children born in 2011 and 2012 who consumed gluten without restrictions. 1478 children were tested, and none of them were tested positive with a rapid test. In 10 children (0,6%), IgA deficiency has been suspected; only 4 of them agreed to be tested further for total IgA, anti-tTG, and anti-DGP antibodies. IgA deficiency was confirmed in 3 patients, and in all 4 children, CD has been excluded. Our results have not confirmed the usefulness of the POC test in screening the general population of first-grade schoolchildren. Further research is needed to establish the true epidemiology of CD in Primorje-Gorski Kotar County and to confirm the value of the rapid test in comparison with standard antibody CD testing

Mână de mână cu Boala Celiacă (BC)

Proiectul CD SKILLS PP13 a Universității de Stat de Medicină și Farmacie “Nicolae Testemițanu” din Republica Moldova și permisă spre traducere din limba engleză cu suportul tehnic al echipei de implementare: Tatiana Raba, Olesea Nicu, Anton Pivtora

DESIGN OF PAVEMENT STRUCTURE WITH REGARD TO PERMANENT DEFORMATION IN UNBOUND PAVING LAYERS

Diplomsko delo predstavlja splošen opis voziščne konstrukcije, sledi dimenzioniranje voziščne konstrukcije z uporabo tehničnih specifikacij za javne ceste ter izračun napetostno deformacijskega stanja v nevezani nosilni plasti. Izračun napetosti in deformacij izvedemo po metodi končnih elementov z uporabo geotehničnega programa Plaxis. Dobljene rezultate analiziramo in jih primerjamo z izmerjenimi rezultati na terenu. V drugem delu diplomske naloge so na praktičnem primeru uporabe murskih prodov prikazani rezultati laboratorijskih preiskav različnih mešanic murskega proda in s pomočjo matematičnih metod izračunane napetosti in deformacije. Rezultati pokažejo, da se z uporabo drobljenih prodov trajne deformacije v nevezani nosilni plasti bistveno zmanjšajo.Diploma presents general description of pavement structure, then follow design of pavement structure with use of technical specifications for public roads and calculation of stresses and strains in unbound paving layers. Calculation of stresses and strains are made with finite element method with use of geotechnical program Plaxis. The obtained results were analyzed and compared with measured results on the ground. The second part of diploma is a practical example of Mura gravel and shows the results of laboratory tests of different mixtures of Mura gravel. Stresses and strains are calculated using different mathematical methods. The results showed that the crushing of Mura gravel substantially reduced permanent deformation of unbound paving layer

Klinična uporabnost seroloških označevalcev v diagnostiki kronične vnetne črevesne bolezni v pediatriji

Background: Among children and adolescents, the diagnosis of inflammatory bowel disease (IBD) is often missed or delayed because of the nonspecific nature of the clinical symptoms. In such instances noninvasive and accurate diagnostic tests that would accurately distinguish IBD from functional disorders would be most valuable to clinicians. Several serological markers have been used as non-invasive diagnostic tools in IBD pediatric patients. The aim of our study was to determine the prevalence and diagnostic accuracy of perinuclear antineutrophil cytoplasmic antibodies (p-ANCA), anti-Saccharomyces cerevisiae antibodies (ASCA), anti-exocrine pancreatic antibodies (PAB) and anti-goblet cells antibodies (GAB) alone and in combination in children and adolescents with IBD. Patients and methods: Serum specimens were analyzed for p-ANCA, ASCA IgG, ASCA IgA, PAB and GAB antibodies in 49 children and adolescents with confirmed IBD and 53 non-IBD controls. P-ANCA, PAB and GAB antibodies were determined by indirect immunofluorescent test and ASCA by enzyme-linked immunosorbent assay. All patients with Crohn\u27s disease (CD) had genotyping performed using a sequence specific PCR directed against the wild type and the three principal mutations of NOD2/CARD15 gene. Disease location, body mass index (BMI) and disease activity by pediatric Crohn\u27s disease activity index (PCDAI) at the time of diagnosis were determined in CD patients. Results: The prevalence of p-ANCA in patients with UC and ASCA in CD patients was high (82.3 % and 67.9 %, respectively). Positivity for PAB antibodies in CD and GAB in UC was lower (35.7 % and 23.5 %, respectively). Accuracy data (sensitivity, specificity, PPV, NPV, respectively) for differentiating IBD from non-IBD controls were as follows: p-ANCA: 82 %, 100 %, 100 %, 94 %ASCA IgG: 68 %, 94 %, 86 %, 84 %ASCA IgA: 54 %, 100 %, 100 %, 80 %PAB: 36 %, 98 %, 91 %, 74 %GAB: 23 %, 100 %, 100 %, 80 %. In distinguishing CD from UC we found out the following accuracy data (sensitivity, specificity, PPV, NPV, respectively): p-ANCA: 82 %, 82 %, 74 %, 88 %ASCA IgG: 68 %, 100 %, 100 %, 65 %ASCA IgA: 54 %, 100 %, 100 %, 57 %PAB: 36 %, 100 %, 100 %, 49 %GAB: 23 %, 100 %, 100 %, 68 %. There were no significant association between ASCA positivity and the three major mutations of NOD2/CARD15 gene, disesase location and family history in CD patients, however an association between BMI and disease activity at the time of diagnosis was found out. Conclusions: Specificity and positive predictive value of serological markers p-ANCA, ASCA IgG, ASCA IgA, PAB and GAB for IBD alone and in combination are high and which make them useful in diagnosis of inflammatory bowel disease in day-to-day clinical practice, particulary in making decision about performing invasive diagnostic procedures. Because of low sensitivity they are less useful as screening tests for inflammatory bowel disease in pediatric population.Izhodišča: Kronična vnetna črevesna bolezen (KVČB) pri otrocih in mladostnikih pogosto poteka z nespecifičnimi kliničnimi znaki, ki so lahko podobni funkcionalnim motnjam, zato je diagnoza KVČB pogosto postavljena pozno ali pa celo spregledana. V pediatriji so v klinični praksi še posebno zaželjeni zanesljivi neinvazivni diagnostični testi, ki ločijo KVČB od funkcionalnih motenj. Številni serološki označevalci se že uporabljajo kot neinvazivni diagnostični testi v diagnostiki KVČB v pediatriji. Namen naše raziskave je bil določiti prevalenco ter diagnostično uporabnost seroloških označevalcev - protiteles proti citoplazemskim antigenom nevtrofilcev (Antineutrophil Cytoplasmic Antibodies - ANCA), protiteles proti kvasovki Saccharomyces cerevisiae (Anti-Saccharomyces Cerevisiae Antibodies - ASCA), protiteles proti eksokrinemu delu pankreasa (Pancreas Antibodies - PAB) in protiteles proti čašastim celicam (Goblet cells Antibodies - GAB) posamezno in v kombinaciji pri otrocih in mladostnikih s KVČB. Bolniki in metode: V vzorcih serumov 49 otrok in mladostnikov s KVČB in 53 otrok in mladostnikov kontrolne skupine, ki niso imeli KVČB, smo ugotavljali prisotnost protiteles p-ANCA, ASCA IgG, ASCA IgA, PAB and GAB. Protitelesa p-ANCA, PAB in GAB smo določali z metodo indirektne imunofluorescence, protitelesa ASCA IgG in IgA pa z encimsko-imunsko metodo ELISA. Dodatno smo vsem bolnikom s Crohnovo boleznijo določali morebitno prisotnost treh najpomembnejsih mutacij v genu NOD2/CARD15 z metodo polimerazne verižne reakcije (PCR), opredelili umestitev vnetja, določili indeks telesne mase in stopnjo aktivnosti vnetja s pediatričnim indeksom aktivnosti bolezni (PCDAI) ob postavitvi diagnoze. Rezultati: Ugotovili smo visoko prevalenco p-ANCA protiteles pri bolnikih z ulceroznim kolitisom (UK) (82,3 %), medtem ko je bila prevalenca ASCA protiteles pri bolnikih s Crohnovo boleznijo (CB) nekoliko nižja (67,9 %). Prevalenca PAB protiteles pri CB in GAB pri bolnikih z UK je bila še nižja (35,7 % za PAB pri CB in 23,5 % za GAB protitelesa pri UK). Občutljivost, specifičnost, pozitivna napovedna vrednost (PPV) in negativna napovedna vrednost (NPV) omenjenih seroloških označevalcev v diagnostičnem razlikovanju KVČB od zdravih preiskovancev so bile sledeče: za p-ANCA: 82 %, 100 %, 100 %, 94 %za ASCA IgG: 68 %, 94 %, 86 %, 84 %za ASCA IgA: 54 %, 100 %, 100 %, 80%za PAB: 36 %, 98 %, 91 %, 74 % in za GAB: 23 %, 100 %, 100 %, 80 %. V razlikovanju med CB in UK pa so občutljivost, specifičnost, pozitivna napovedna vrednost (PPV) in negativna napovedna vrednost (NPV) znašale: za p-ANCA: 82 %, 82 %, 74 %, 88 %za ASCA IgG: 68 %, 100 %, 100 %, 65 %za ASCAIgA: 54 %, 100 %, 100 %, 57 %za PAB: 36 %, 100 %, 100 %, 49 % in za GAB:23 %, 100 %, 100 %, 68 %. V naši študiji nismo potrdili statistično pomembne povezave med prisotnostjo ASCA protiteles in treh najpogostejših mutacij v genu NOD2/CARD15 pri bolnikih s CB. Prav tako nismo potrdili povezave med ASCA pozitivnim serološkim statusom in ilealno umestitvijo vnetja ter pozitivno družinsko anamnezo. Ugotovili pa smo statistično pomembno povezavo med prisotnostjo ASCA protiteles z večjo aktivnostjo CB in nižjim indeksom telesne mase pri bolnikih s CB. Zaključki: Zaradi visoke specifičnosti ter pozitivne napovedne vrednosti so serološki označevalci p-ANCA, ASCA IgG, ASCA IgA, PAB in GAB tako samostojno kot v kombinaciji pomembni neinvazivni diagnostični testi. V vsakodnevni klinični praksi nam koristijo predvsem v diagnostični razmejitvi med kronično vnetno črevesno boleznijo in funkcionalnimi motnjami ter pri odločitvi za invazivne diagnostične metode. Zaradi prenizke občutljivosti pa niso primerni za uporabo kot presejalni testi za kronično vnetno črevesno bolezen v pediatrični populaciji

Modern diagnostic aproach to celiac disease

Izhodišča: Celiakija je imunsko pogojena bolezen tankega črevesa, ki nastane kot posledica uživanja glutena pri genetsko predisponiranih osebah. Bolezen prizadene okoli 1 % prebivalstva in ni le bolezen otroške dobe, saj v različnih kliničnih oblikah prizadene ljudi vseh starosti. Diagnostika bolezni temelji na merilih, ki jih je sprejelo in nato revidiralo Evropsko združenje za pediatrično gastroenterologijo, hepatologijo in prehrano (ESPGHAN). Kot zlati standard predvidevajo dokaz reverzibilne okvare sluznice tankega črevesa. Revidirana merila predvidevajo manjše število biopsij za postavitev dokončne diagnoze, kar je predvsem posledica uporabe seroloških testov. V diagnostiki celiakije igrajo pomembno vlogo tudi genetske preiskave, predvsem določanje prisotnosti zapisa za HLA-DQ2 in HLA-DQ8. Najnovejši testi, ki omogočajo določanje prisotnosti protiteles proti tkivni transglutaminazi v kapilarni krvi ob obisku bolnika v ambulanti, bodo verjetno zelo olajšali diagnostiko bolezni. Nova dognanja, ki kažejo, da gre pri celiakiji za sistemski patološki imunski odgovor na gluten pri genetsko predisponiranih osebah, pa že kažejo na to, da v prihodnje biopsija sluznice tankega črevesa morda ne bo več imela primarne vloge. Zaključki: Sodobna diagnostika celiakije temelji na uporabi bolezensko specifičnih seroloških testov in dokazu povratne okvare sluznice tankega črevesa. V diagnostiki se v zadnjem času uspešno uporabljajo tudi genetski testi in novi hitri serološki testi. Intenzivne raziskave patogeneze in klinične slike celiakije pa bodo pokazale, ali bo v prihodnje moč postaviti zanesljivo diagnozo bolezni tudi brez biopsije sluznice tankega črevesa.Background: Celiac disease, also known as genetic gluten intolerance is a chronic disease that affects genetically predisposed individuals after the gluten ingestion. It affects about 1 % of population regardless of the age, and can manifest with diverse clinical picture. Diagnosis of celiac disease is based on criteria adopted and later revised by European Society for Paediatric Gastroenterology, Hepatology and Nutrition (ESPGHAN). These criteria consider intestinal biopsy as a gold standard. The number of biopsies has decreased after the introduction of serological tests, which are considered in revised criteria. Genetic tests have also proven to be very valuable in diagnostic procedure, especially HLA-DQ2 and HLA-DQ8 determination. Bedside or point-of-care tests, which enable quick determination of anti tissue transglutaminase antibodies in capillary blood, are a promising new tool. Many reports have shown that adverse immunological response to gluten in genetically predisposed individuals is systemic, which can lead to a decreased importance of intestinal biopsy in future. Conclusions: Diagnosis of celiac disease is based on specific serological markes and reversible mucosal changes of small intestine. Lately developed genetic tests and new quick serological tests are also used. Intensive research focused on pathogenesis and manifestations of celiac disease will show whether definite diagnosis could be confirmed without the use of intestinal biopsy in future

Infliximab in the treatment of severe steroid-refractory ulcerative colitis - a case report

Izhodišča: Ulcerozni kolitis (UK) lahko poteka kot akutni zagon s hudo stopnjo vnetne dejavnosti, ki predstavlja življenje ogrožajoče stanje. Kortikosteroidi (KS) v intravenski obliki so zdravilo prve izbire za indukcijo klinične remisije pri akutnem hudem zagonu UK. Pri hudi obliki ulceroznega kolitisa, neodzivni na kortikosteroide, je potrebno kirurško zdravljenje. Bolniki in metode: Prikazan je primer desetletne deklice s hudo obliko na KS neodzivnega ulceroznega kolitisa. Da bi se izognili kirurškemu posegu, smo uvedli zdravljenje z infliximabom. Že po enkratni infuziji infliximaba je prišlo do hitrega izboljšanja kliničnega stanja in remisije bolezni, ki smo jo nato vzdrževali z azatioprinom. Zaključki: Zdravljenje z infliximabom je lahko uspešno pri hudo potekajočem, na KS neodzivnem UK. S tovrstnim zdravljenjem se lahko izognemo kirurškemu zdravljenju (kolektomiji), ki za bolnike predstavlja doživljenjsko invalidnost. Doseženo remisijo vzdržujemo z uveljavljenimi imunosupresivi (azatioprinom ali 6-merkaptopurinom).Background: The natural course of ulcerative colitis (UC) can be complicated with an acute severe attack of high degree of activity of inflammation which represents a life-threatening condition. High-dose intravenous steroids have been the treatment of choice for induction of clinical remission of acute severe attack. In corticosteroid refractory ulcerative colitis a surgical therapy is required. Patients and methods: A case of a ten year-old girl with severe steroid-refractory UC is presented. The treatment with infliximab was introduced with intention to avoid colectomy. After the first infusion of infliximab her condition improved and clinical remission was achieved which was maintained with azathioprine. Conclusions: Therapy with infliximab can be successful for a severe steroid-refractory UC. The patients treated with infliximab can avoid surgical therapy (colectomy) which can represent a life-long disablement. The achieved remission is best maintained with conventional immunosuppressive therapy (azathioprine or 6-mercaptopurin)

Odpornost glioblastoma na radioterapijo : vpliv rakavih matičnih celic in mikroo[ko]lja tumorja

Glioblastom je najpogostejši možganski tumor pri odraslih z zelo slabo prognozo preživetja bolnikov. Ta je posledica odpornosti glioblastoma na standardno zdravljenje, ki vključuje radioterapijo in kemoterapijo. Z namenom načrtovanja učinkovitejših pristopov zdravljenja preučujemo biološke mehanizme odpornosti glioblastoma na radioterapijo s poudarkom na mikrookolju tumorja in rakavih matičnih celicah. V predkliničnih raziskavah uporabljamo napredne in personalizirane celične modele, ki posnemajo mikrookolje tumorja v bolnikih in z večjo natančnostjo napovedo odziv bolnika na zdravljenje. Hkrati so takšni modeli pomembni za testiranje novih pristopov za zdravljenje kot je imunoterapija