Laboratory diagnostics of emergency conditions associated with inborn errors of metabolism

Inborn errors of metabolism are a growing group of monogenic hereditary diseases whose pathogenesis may be accounted for by biochemical disorders. The great majority of these diseases may occur as a metabolic crisis at any period of life. For their adequate treatment, fast recognition of the cause of the metabolic disorder is necessary, as well as good collaboration of all health professionals involved in immediate patient healthcare. On the path to final diagnosis, it is advisable to consult specialised centres in order to select appropriate diagnostic tests and procedures

Biliary brush cytology for the diagnosis of malignancy: a single center experience [Citološki razmazi brisa četkicom u dijagnostici malignih promjena bilijarnog stabla: naše iskustvo]

Differentiation between benign and malignant biliary strictures is critical to the provision of adequate treatment. Brush cytology during the endoscopic retrograde cholangiopancreatography (ERCP) is the most commonly used method for obtaining tissue confirmation of the nature of biliary strictures. It’s specificity is remarkably high but reported sensitivities for the diagnosis of malignancy are low. Aim of our study was to assess sensitivity and specificity of biliary brush cytology in our institution, to find out main causes of false negative diagnoses and to confirm impression that the team approach has impact on sensitivity. Gold standard for diagnosis was definitive surgical histology or adequate clinical follow up for minimum of six month. Direct smears made by cytotechnician at the endoscopy room, and stained according to Papanicolaou and May-Grünwald Giemsa (MGG) were examined for well-recognized features of malignancy on conventional smears as a part of diagnostic routine. Cytologic diagnoses were benign, atypical/reactive, suspicious for malignancy and malignant. Of 143 brushings with available definitive diagnosis 36 (25%) had malignant cytologic diagnosis and 91(63.6%) were classified as benign, 3 were atypical/reactive and 13 suspicious for malignancy with 20 »false-negative« cases. When specimens with atypical and suspicious cytology were excluded from data analysis sensitivity was 64% and specificity was 100% and when suspicious findings were taken into account as true positives sensitivity rose to 71%. We find that biliary brush cytology, although mainly depending on the skill of endoscopist, as well as the experience of the cytologist, is a valuable method for obtaining accurate tissue diagnosis of biliary strictures, thus solving eternal diagnostic dilemma: benign or malignant

Povezanost upalnog statusa, patohistoloških karakteristika i perioperativne potrebe za transfuzijskim liječenjem u bolesnika s kolorektalnim karcinomom

Glasgow Prognostic Score (GPS) is such an inflammation-based factor, defined by the combination of the level of serum C-reactive protein (CRP) and albumin, which are indicators of systematic inflammatory response and nutritional status. A higher score is associated with a worse prognosis of different tumor sites. The score is based on the immunomodulatory and inflammatory status found in patients with elevated CRP. We hypothesized that there is a correlation between GPS and histopathological tumor characteristics and GPS and perioperative administration of erythrocyte concentrates in patients undergoing curative tumor resection. We retrospectively revied the data of fifty-one consecutive patient who underwent elective colorectal surgery. We extracted the values of preoperative C-reactive protein(CRP) and albumin and calculated the GPS. We correlated the histopathology of cancer and perioperative transfusion with the outcome. GPS 0 and 2 having a tumor localized in the colon, with GPS 1 in the rectum. T4 tumor stage had patients only in the group of GPS 2 which was statistically significant from the GPS 0 group. The GPS was not associated with the presence of metastases in the lymph nodes, lymphatic and perineural invasions, while a statistically significant difference was present comparing GPS with tumor deposits between GPS 0 and GPS 1 and GPS 0 and GPS 2. Transfusions were statistically significantly higher in GPS 2 group compared to GPS 0 and 1. A higher GPS score is associated with the changes of immune status of the tumor environment which can affect the recurrence of the disease and survival. GPS should be considered when recommending the frequency of follow up and therapy after curative tumor resection. We have shown that there is an increased risk for perioperative blood consumption, which may independently result in a worse prognosis of the underlying disease.Prognostički upalni zbroj (Glasgow prognostic score, GPS) omogućava prognozu ishoda bolesti u osoba s rakom. Baziran je na serumskim biomarkerima C-reactivnom proteinu (CRP) i albuminu. Viši zbroj povezan je s lošijom prognozom bolesti. Mehanizam se temelji na imunomodulaciji i upalnom miljeu bolesnika s povišenim CRP-om. Resekcija debelog crijeva izvršena je u 51 bolesnika. CRP i albumini određeni su prije operacije. GPS je uspoređen s patohistološkim karakteristikama tumora i perioperacijskom transfuzijom koncentrata eritrocita. Utvrđeno je statistički značajna razlika u sijelu tumora analiziranih skupina. Značjano veći broj bolesnika s GPS 0 i 2 imao je tumor lokaliziran u kolonu, a s GPS 1 u rektumu. Tumorski stadij T4 imali su bolesnici samo u skupini GPS 2 što je statistički značajno različito od skupine GPS 0. GPS nije bio povezan s prisutnošću metastaza u limfne čvorove, limfatične i perineuralne invazije, dok je statistički značajna razlika bila u prisutnosti tumorskih depozita između GPS 0 i GPS 1, te GPS 0 i GPS 2. Statistički značajno češće krv je transfudirana bolesnicima GPS 2 skupine u odnosu na GPS 0 i 1. GPS je povezan s patohistološkim karakteristikama, povratom bolesti, preživljenjem i većim rizikom za primjenu krvi

Biliary Brush Cytology for the Diagnosis of Malignancy: A Single Center Experience

Differentiation between benign and malignant biliary strictures is critical to the provision of adequate treatment. Brush cytology during the endoscopic retrograde cholangiopancreatography (ERCP) is the most commonly used method for obtaining tissue confirmation of the nature of biliary strictures. It’s specificity is remarkably high but reported sensitivities for the diagnosis of malignancy are low. Aim of our study was to assess sensitivity and specificity of biliary brush cytology in our institution, to find out main causes of false negative diagnoses and to confirm impression that the team approach has impact on sensitivity. Gold standard for diagnosis was definitive surgical histology or adequate clinical follow up for minimum of six month. Direct smears made by cytotechnician at the endoscopy room, and stained according to Papanicolaou and May-Grünwald Giemsa (MGG) were examined for well-recognized features of malignancy on conventional smears as a part of diagnostic routine. Cytologic diagnoses were benign, atypical/reactive, suspicious for malignancy and malignant. Of 143 brushings with available definitive diagnosis 36 (25%) had malignant cytologic diagnosis and 91(63.6%) were classified as benign, 3 were atypical/reactive and 13 suspicious for malignancy with 20 »false-negative« cases. When specimens with atypical and suspicious cytology were excluded from data analysis sensitivity was 64% and specificity was 100% and when suspicious findings were taken into account as true positives sensitivity rose to 71%. We find that biliary brush cytology, although mainly depending on the skill of endoscopist, as well as the experience of the cytologist, is a valuable method for obtaining accurate tissue diagnosis of biliary strictures, thus solving eternal diagnostic dilemma: benign or malignant

A path towards a cultured skin fi broblast biobank of patients with inherited errors of metabolism in Croatia

Rijetke bolesti etiološki su heterogena skupina najčešće nasljednih, kroničnih i degenerativnih bolesti s pojavnošću manjom od 5 na 10 000 osoba. Poznato je više od 7000 rijetkih bolesti od kojih više od 600 ima osobitosti nasljednih metaboličkih poremećaja. Zbog velike kliničke heterogenosti i zahtjevnih dijagnostičkih testova put do konačne dijagnoze je često dug te uključuje i obradu u ino zemnim laboratorijima. Unatoč tome, dio bolesnika ostaje bez konačne dijagnoze. U situacijama kad je bolesnik vitalno ugrožen uz mogućnost letalnog ishoda i pri sumnji na nasljednu metaboličku bolest, biopsija kože je dio standardnog postupka. Posljednjih godina sve je više dostupnih mogućnosti liječenja za širok spektar nasljednih metaboličkih bolesti. Osnovni preduvjet za njihovu djelotvornost je pravodobna dijagnoza. Kultivirani kožni fi broblasti pohranjeni u biobanke vrijedan su biološki materijal. Osim za postavljanje dijagnoze, mogu se primijeniti i za provjeru djelotvornosti novih pristupa liječenju kao što su male molekule pratitelji. Sve navedeno upućuje na značenje organiziranja biobanke fi broblasta prema međunarodno prihvaćenim standardima.Rare diseases are an etiologically heterogeneous group of hereditary, chronic and degenerative disorders with the incidence lower than 5 per 10,000 individuals. More than 7,000 rare diseases have been identifi ed so far, and more than 600 of them have the characteristics of hereditary metabolic disorders. Due to the high clinical heterogeneity and demanding diagnostic tests, the path to fi nal diagnosis is often long and may also involve tests performed in laboratories abroad. Despite this, a number of patients remain without fi nal diagnosis. In life-threatening situations for the patient and in case of suspected hereditary metabolic disease, skin biopsy is part of the routinely performed standard procedure. Recent years have seen an increasing availability of treatment options for a broad range of hereditary metabolic diseases. The basic precondition for therapy effi cacy is timely diagnosis. Cultured skin fi broblasts that are stored in biobanks are a valuable biological material. Except for making diagnosis, they may be used to verify the effi cacy of novel approaches to treatment, e.g., small chaperon molecules. All of the above indicates the signifi cance of establishing a fi broblast biobank according to the internationally accepted standards

LYSOSOMAL ACID LIPASE DEFICIENCY IN CHILDREN: OUR EXPERIENCE AND A NOVEL POSSIBILITY OF ENZYME REPLACEMENT THERAPY

Manjak lizosomske kisele lipaze autosomno je recesivno nasljedna bolest s dva klinička fenotipa. Wolmanova bolest počinje u ranoj dojenačkoj dobi i brzo je progresivna. Zbog masivnog nakupljanja kolesterolskih estera i triglicerida u crijevima, jetri, slezeni i drugim stanicama monocitno-makrofagnog reda dolazi do malapsorpcije, hepatosplenomegalije, zatajenja jetre i smrti u prvoj godini života. Bolest nakupljanja kolesterolskih estera može se očitovati od rane dječje do kasne odrasle dobi, varijabilna je tijeka i progresije. Glavna su obilježja različito izražena jetrena bolest, uključujući cirozu i zatajenje jetre, hiperkolesterolemija i rana ateroskleroza. Karakterističan je patohistološki nalaz mikrovezikularne steatoze i fibroze, a patognomoničan je ultrastrukturni nalaz kristala kolesterolskih estera. Dijagnozu potvrđuju mjerenje enzimske aktivnosti i/ili analiza gena. Liječenje je donedavno bilo suportivno i simptomatsko. Klinička istraživanja enzimskoga nadomjesnog liječenja pokazuju vrlo ohrabrujuće rezultate. Prikazujemo dojenče s Wolmanovom bolešću i dvoje djece s bolešću nakupljanja kolesterolskih estera s ciljem skretanja pozornosti na bolesti zbog manjka lizosomske kisele lipaze i što ranijeg početka optimalne skrbi.Lysosomal acid lipase deficiency is an autosomal recessive disorder with two distinct clinical phenotypes. Wolman disease is rapidly progressive with onset in early infancy. Complete enzyme deficiency results in massive accumulation of cholesterol esters and triglycerides in intestines, liver, spleen and other monocyte-macrophage system cells causing malabsorption, hepatosplenomegaly, liver failure and death in early infancy. Cholesterol ester storage disease may be diagnosed in childhood or later in life. It is characterized by chronic course and variable progression. Main features are variously expressed hepatopathy, including cirrhosis and liver failure, hypercholesterolemia and premature atherosclerosis. Characteristic is pathohistological finding of microvesicular steatosis and fibrosis and patognomonic are typical cholesterol ester crystals. Diagnosis is confirmed by enzyme assay and/or gene analysis. Until recently treatment was symptomatic. Ongoing clinical trials of enzyme replacement therapy have shown very promising results. We are presenting an infant with Wolman disease and two children with cholesterol ester storage disease with the aim to raise awareness about this disease and to start optimal care early

Manjak lizosomske kisele lipaze u djece: vlastita iskustva i nova mogućnost enzimskoga nadomjesnog liječenja [Lysosomal acid lipase deficiency in children: our experience and a novel possibility of enzyme replacement therapy]

Lysosomal acid lipase deficiency is an autosomal recessive disorder with two distinct clinical phenotypes. Wolman disease is rapidly progressive with onset in early infancy. Complete enzyme deficiency results in massive accumulation of cholesterol esters and triglycerides in intestines, liver, spleen and other monocyte-macrophage system cells causing malabsorption, hepatosplenomegaly, liver failure and death in early infancy. Cholesterol ester storage disease may be diagnosed in childhood or later in life. It is characterized by chronic course and variable progression. Main features are variously expressed hepatopathy, including cirrhosis and liver failure, hypercholesterolemia and premature atherosclerosis. Characteristic is pathohistological finding of microvesicular steatosis and fibrosis and patognomonic are typical cholesterol ester crystals. Diagnosis is confirmed by enzyme assay and/or gene analysis. Until recently treatment was symptomatic. Ongoing clinical trials of enzyme replacement therapy have shown very promising results. We are presenting an infant with Wolman disease and two children with cholesterol ester storage disease with the aim to raise awareness about this disease and to start optimal care early

VITAMIN B12 DEFICIENCY IN CHILDREN – UNDERESTIMATED DANGER IN THE LIGHT OF NEW KNOWLEDGE

Vitamin B12 (kobalamin) ima dva aktivna oblika, adenozilkobalamin i metilkobalamin, koji imaju ključnu ulogu u dvama važnim metaboličkim putovima u ljudi i njihov je manjak odgovoran za kliničke teškoće u bolesnika. Kobalamin je nuždan tijekom cijelog života, no njegova dovoljna količina posebno je bitna u fetalno i dojenačko doba, kada je iznimno važan za normalan rast i razvoj djeteta, kao i za normalan razvoj središnjega živčanog sustava. Zbog vrlo složenog prometa i metabolizma njegov se manjak može očitovati pri raznim prirođenim i stečenim poremećajima. Klinička slika kojom se očituje manjak vitamina B12 obično je nespecifična, nosi velik rizik od trajnih posljedica za bolesnika, a najčešće se vrlo jednostavno liječi ako se na vrijeme prepozna. U Republici Hrvatskoj poremećaji metabolizma kobalamina u djece prerijetko se otkrivaju. Zato je cilj ovog rada skrenuti pozornost na nove spoznaje o metabolizmu kobalamina, prikazati bolesnike s tipičnim kliničkim tijekom i laboratorijskim nalazima te dati smjernice za brzo dijagnosticiranje i liječenje poremećaja vitamina B12 u djece.Vitamin B12 (cobalamin) has two active forms, adenosylcobalamin and methylcobalamin which have a key role in two important metabolic pathways in humans and their deficiency is responsible for clinical problems. Cobalamin is essential during whole life, but its sufficient amount is extra important in fetal and neonatal period, when it is essential for normal child growth and development as well as for normal development of the central nervous system. Because of very complex transport and metabolism, its deficiency can be manifested in numerous congenital and acquired disorders. Vitamin B12 deficiency mostly has non-specific clinical features, it carries a great risk of permanent consequences, but most frequently it is easily curable if diagnosed on time. In Croatia cobalamin deficiency in children has been diagnosed too rarely. Accordingly, the aim of this paper is to point to the recently gained knowledge on cobalamin metabolism, present typical case reports and to provide guidelines for rapid and proper diagnostic and therapeutic approach

Marvellous and Fairy Tale Elements Sunčana Škrinjarić 's Tales

Razvitak svjetske bajke i fantastične priče doveo je do razvoja hrvatske. Iako su uvjeti bili nepovoljni, a razvoj isprekidan, postojali su autori koji su, ne mareći za društvo i okolinu, pisali na tragu svjetske bajke. Sunčana Škrinjarić bila je jedna od glavnih karika za razvoj moderne bajke i fantastične priče u Hrvatskoj. Ta čuvena dječja spisateljica svojim je djelima obogatila hrvatsku suvremenu bajku, dala joj vlastiti pečat i donijela pravo osvježenje. U ovom će se diplomskom radu dotaknuti njezino stvaralaštvo koje je nastalo na podlozi bajke i fantastične priče, a iza koje se krije stvarnost i suvremeni svijet. U djela Kaktus bajke, Plesna haljina žutog maslačka, Pisac i vrijeme, Pisac i princeza te Čudesna šuma utkani su bajkovitost i fantastičnost koji prikazuju vječno čovjekovo utočište i izvor autoričine mašte - prirodu.The development of the world's fairy tale and fantastic story led to the development of the Croatian. Although the conditions were unfavorable and the development was intermittent, there were authors that, not caring for society and the environment, wrote in the wake of the world's fairy tales. Sunčana Škrinjarić was one of the main writers of a modern fairy tale and a fantastic story in Croatia. This famous children's writer enriched the Croatian contemporary fairy tale with her works, gave her own seal and brought true refreshment. In this project I will write about her creativity, which was created on the basis of a fairy tale and a fantastic story, and behind which lies reality and modern world. Kaktus bajke, Plesna haljina žutog maslačka, Pisac i vrijeme, Pisac i princeza and Čudesna šuma are woven with fairytale and fantasy that depict the eternal refuge of man and the source of the author's imagination - nature

Marvellous and Fairy Tale Elements Sunčana Škrinjarić 's Tales

Razvitak svjetske bajke i fantastične priče doveo je do razvoja hrvatske. Iako su uvjeti bili nepovoljni, a razvoj isprekidan, postojali su autori koji su, ne mareći za društvo i okolinu, pisali na tragu svjetske bajke. Sunčana Škrinjarić bila je jedna od glavnih karika za razvoj moderne bajke i fantastične priče u Hrvatskoj. Ta čuvena dječja spisateljica svojim je djelima obogatila hrvatsku suvremenu bajku, dala joj vlastiti pečat i donijela pravo osvježenje. U ovom će se diplomskom radu dotaknuti njezino stvaralaštvo koje je nastalo na podlozi bajke i fantastične priče, a iza koje se krije stvarnost i suvremeni svijet. U djela Kaktus bajke, Plesna haljina žutog maslačka, Pisac i vrijeme, Pisac i princeza te Čudesna šuma utkani su bajkovitost i fantastičnost koji prikazuju vječno čovjekovo utočište i izvor autoričine mašte - prirodu.The development of the world's fairy tale and fantastic story led to the development of the Croatian. Although the conditions were unfavorable and the development was intermittent, there were authors that, not caring for society and the environment, wrote in the wake of the world's fairy tales. Sunčana Škrinjarić was one of the main writers of a modern fairy tale and a fantastic story in Croatia. This famous children's writer enriched the Croatian contemporary fairy tale with her works, gave her own seal and brought true refreshment. In this project I will write about her creativity, which was created on the basis of a fairy tale and a fantastic story, and behind which lies reality and modern world. Kaktus bajke, Plesna haljina žutog maslačka, Pisac i vrijeme, Pisac i princeza and Čudesna šuma are woven with fairytale and fantasy that depict the eternal refuge of man and the source of the author's imagination - nature