Necrotizing enterocolitis of infants – new treatment possibilities

Necrotizing enterocolitis (NEC) of infants is a devastating disease that is both difficult to treat and to effectively predict its development. Its occurrence and progression are associated with a plethora of possible causes. That is why, in recent years, many studies were made with the intent of finding efficient new ways of treatment and prevention. Some of those were designed to study and isolate specific factors found in maternal milk and others were more focused on testing synthetic molecules or natural remedies. The etiology of NEC and its epidemiology followed by a characterization of the pathology and pathogenesis, as well as symptomatology, clinical, radiological, and biochemical methods of detection. New possible treatment methods and techniques are briefly described: insulin-like growth factor, human milk oligosaccharides, epidermal growth factor family, transforming growth factor β, an enzyme – alkaline phosphatase, vitamin A, trefoil factor family, branch chain fatty acids, erythropoietin, oxygen, and ozone. Particular emphasis is given to the role of maternal milk as a source of many of biochemical factors in prevention and even treatment of NEC. Further investigations are needed to decrease the incidence and severity as well as to improve the chances of NEC patients

KONCENTRACIJE SRČANOG VISOKOOSJETLJIVOG TROPONINA I U MOKRAĆI ZDRAVIH OSOBA – PRELIMINARNI REFERENTNI INTERVALI

Recent studies have shown the presence of troponin molecules in urine, with kidneys considered the main organs of elimination. Availability of the new generation of high-sensitivity assays has enabled detection of low concentrations of circulating cardiac troponins, but the high-sensitivity troponin assays are not designed for analysis of urine specimens. The aim of this study was to establish preliminary reference intervals for the high-sensitivity cardiac troponin I (hs-cTnI) concentrations in urine of healthy adults in Croatia. A total of 60 reference persons were selected (30 males and 30 females) and the concentrations of hs-cTnI in random urine samples were determined on the Abbott Architect i1000SR (Abbott Laboratories) analytical system with chemiluminescent immunochemical method on microparticles (CMIA, ARCHITECT STAT High Sensitive Troponin-I), accredited according to the HR EN ISO 15189:2012 standard (Medical laboratorieds – requirements for quality and competence. Geneva, International Organization for Standardization, 2012). We determined the limit of detection, total laboratory precision, expanded measurement uncertainty and preliminary estimates of the gender-specifi c 99th percentile of the upper reference limit (URL) using nonparametric analysis (methods). The male and female 99th percentile cut-off values were 39.3 and 35.2 pg/mL, respectively. The results of this pilot study suggest that troponin I is removed from the blood by the kidneys and can be determined in the urine with CMIA, ARCHITECT STAT High Sensitive Troponin-I assays. Further research is focused on detailed studies of biochemistry and determination of troponin I in the urine as a new biological marker.Cilj ovoga istraživanja bio je odrediti preliminarne referentne intervale visokoosjetljivog troponina l u mokraći zdravih osoba. Koncentracije srčanog visokoosjetljivog troponina I u slučajnim uzorcima mokraće određene su na analitičkom sustavu Abbott Architecti1000SR (Abbott Laboratories) kemiluminiscentnom imunokemijskom metodom na mikročesticama (CMIA, ARCHITECT STAT High Sensitive Troponin-I), akreditiranom prema HR EN ISO 15189. Referentni interval izrađen je u Referentnom centru Ministarstva zdravstva Republike Hrvatske za izradu referentnih vrijednosti u području opće medicinske biokemije na uzorku od 30 referentnih osoba po spolu sljedećih karakteristika: nepušač, 25-65 godina, indeks tjelesne mase <30 kg/m2, odsutnost akutne i kronične bolesti, bez noćnog rada tijekom zadnjih 30 dana. Granica kvantifi kacija određena je sukladno smjernicama CLSI EP17-A2 i uz zadovoljavanje kriterija za preciznost za visokoosjetljivi test (KV<10 %). Linearnost metode u deklariranom području potvrđena je multikalibracijskom krivuljom. Ukupna laboratorijska preciznost izračunata je sukladno smjernicama CLSI EP15-A2 i iznosi 2,23 % (KV) u normalnom području i 1,45% (KV) u patološkom području. Proširena mjerna nesigurnost (k=2) izračunata je iz ukupne laboratorijske preciznosti i mjerne nesigurnosti kalibratora i iznosi ±4,5 % za normalno područje i ±2,9 % za patološko područje; 99. percentila gornje granice referentnog intervala izračunata je neparametarskom statističkom analizom, sukladno smjernicama CLSI C28-A3. Određena 99. Percentila gornje granice referentnog intervala za visokoosjetljivi troponin I u mokraći iznosi 39,3 ng/L za muškarce i 35,2 ng/L za žene. Dobiveni preliminarni rezultati ukazuju na to da se troponin I odstranjuje iz krvi putem bubrega i da se može pouzdano mjeriti na analitičkom sustavu Abbott Architecti1000SR (Abbott Laboratories) kemiluminiscentnom imunokemijskom metodom na mikročesticama

Anti-neutrophil Cytoplasmic Antibody Positivity in Five Children with Systemic Lupus Erythematosus - What is the Importance of this Finding?

Juvenile systemic lupus erythematosus (JSLE) is a systemic autoimmune chronic disease that can affect any part of the body. It is characterized by the formation of antibodies against nuclear antigens. Vasculitis may be found in SLE, but it scarcely complies with anti-neutrophil cytoplasmic antibodies (ANCA)-associated vasculitis (AAV) criteria. We report five cases of severe JSLE associated with AAV diagnosed between 1991 and 2013 in three university-based tertiary care centers. The patients (3 girls and 2 boys, aged 12 to 17) presented with a severe clinical picture and the following features: cytopenia (n=5), autoimmune hepatitis (n=3), lupus nephritis (n=1), pancreatitis (n=1), secondary antiphospholipid syndrome (n=2), impending respiratory failure (n=2), and gastrointestinal bleeding (n=1).All patients were proteinase 3 (PR3) ANCA positive, while two of them were myeloperoxidase (MPO) and PR3 ANCAs positive at the same time. They were treated with corticosteroids and immunosuppressive drugs. Remission of the disease was achieved in three patients. The course of the disease was worsening in two patients and we included rituximab (anti-CD20) in therapy. All of our patients presented as the most severe SLE patients, who must be diagnosed as soon as possible and treated very intensively. Since the comorbidity of JSLE and AAV occurs very rarely in children, presentation of such patients, their clinical pictures, treatment, and the course of the diseases are experiences that can be of great help.</p

Cholestasis in infants

Kolestaza je poremećaj stvaranja i/ili protoka žuči koji dovodi do zadržavanja žuči u jetri. Javlja se kod 1 : 2500 terminske dojenčadi, najčešće u prva tri mjeseca života. Konjugirana hiperbilirubinemija je biokemijska manifestacija kolestaze o kojoj govorimo kada je konjugirani bilirubin veći od 17 umol/L i/ili na njega otpada više od 20% ukupnog bilirubina. Kolestaza je uvijek patološka i zahtijeva opsežnu obradu. Najčešći pojedinačni uzroci su atrezija žučnih vodova, infekcija, kolestaza uzrokovana parenteralnom prehranom i manjak alfa-1 antitripsina, dok u četvrtine bolesnika etiologija ostaje nerazjašnjena pa govorimo o idiopatskom neonatalnom hepatitisu. Kliničke su manifestacije kolestaze žutica, pruritus i pojava svijetlih (hipokoličnih ili akoličnih) stolica i tamnijeg urina. Otežana apsorpcija masti i vitamina topivih u masti, pothranjenost i pruritus izazovni su klinički problemi koje susrećemo u ovih bolesnika. Zaključak: Kolestaza u dojenačkoj dobi rijetko je stanje koje je često uzrokovano teškim bolestima, te je stoga temeljna zadaća svakog pedijatra pravovremeno prepoznati ove bolesnike i uputiti ih na daljnju obradu.Cholestasis is a disorder of bile production and/or flow that leads to the retention of bile in the liver. It is found in 1:2500 term infants, typically during the first three months of life. Conjugated hyperbilirubinemia is a biochemical manifestation of cholestasis defined as a conjugated bilirubin > 17 umol/L and/or > 20% of the total bilirubin. Cholestasis is always pathological and requires extensive workup. The most common individual causes of cholestasis are biliary atresia, infection, parenteral nutrition-associated liver disease, and alpha-1 antitrypsin deficiency. A quarter of patients in whom the etiology of cholestasis remains unexplained are diagnosed with idiopathic neonatal hepatitis. Clinical manifestations of cholestasis are jaundice, pruritus, light-colored stools, and dark urine. Impaired absorption of fat and fat-soluble vitamins, malnutrition, and pruritus are challenging clinical problems encountered in these patients. Conclusion: Cholestasis in infancy is a rare condition that is often caused by life-treatening diseases, and therefore the main task of every pediatrician is to recognize these patients in time and refer them for further workup

Case report: Duplication of gallbladder in a newborn with gastroschisis

Gastroshiza je defekt trbušne stijenke kroz koji protrudiraju trbušni organi i često je udružena s drugim malformacijama. Najčešće se radi o crijevnim (tri četvrtine), rjeđe ju prate urološke, srčane i malformacije ekstrahepatičkog bilijarnog stabla. Duplikature žučnog mjehura u općoj populaciji su relativno rijetke i javljaju se 1 na 3000–4000. U ovom prikazu slučaja prezentirat ćemo slučaj novorođenčeta s gastroshizom udruženom s duplikaturom žučnog mjehura. Kod novorođenčeta je pronađena kompletna duplikatura žučnog mjehura s dva odvojena duktusa cistikusa (tip 2 po Boydenu). Smjernica za postupak kod duplikature žučnog mjehura u novorođenčadi s gastroshizom nema, mi smo postupili po smjernicama za duplikaturu žučnog mjehura u općoj populaciji. Duplikature žučnog mjehura udružene s gastroshizom ne zahtijevaju aktivno kirurško liječenje ako nisu simptomatske ili ako ne postoji druga malformacija bilijarnog sustava.Gastroschisis is a defect of the anterior abdominal wall through which viscera can protrude, and can be followed by additional malformations. Three quarters of the gastroschisis malformations are confined to the midgut. Other malformations are urologic and cardiac malformations and malformations of extrahepatic biliary tract. Duplication of gallbladder in general population is relatively rare, occurring once in every 3,000 to 4,000.In this case report we will present a case of an infant with gastroschisis accompanied with the duplication of gallbladder. In the newborn a complete duplication of gallbladder was found with two separate cystic ducts, i.e. type 2 by Boyden. Since the guidelines for duplication of the gallbladder associated with gastroschisis do not exist, we acted according to the guidelines for duplication of the gallbladder in the general population, i.e. nonsurgical intervention was performed on the biliary tree. Duplications of the gallbladder associated with gastroschisis do not require active surgical treatment, unless they are symptomatic or if there is other malformation of the biliary system

Survival prediction of high-risk outborn neonates with congenital diaphragmatic hernia from capillary blood gases

BACKGROUND: The extent of lung hypoplasia in neonates with congenital diaphragmatic hernia (CDH) can be assessed from gas exchange. We examined the role of preductal capillary blood gases in prognosticating outcome in patients with CDH. ----- METHODS: We retrospectively reviewed demographic data, disease characteristics, and preductal capillary blood gases on admission and within 24 h following admission for 44 high-risk outborn neonates. All neonates were intubated after delivery due to acute respiratory distress, and were emergently transferred via ground ambulance to our unit between 1/2000 and 12/2014. The main outcome measure was survival to hospital discharge and explanatory variables of interest were preductal capillary blood gases obtained on admission and during the first 24 h following admission. ----- RESULTS: Higher ratio of preductal partial pressure of oxygen to fraction of inspired oxygen (PcO2/FIO2) on admission predicted survival (AUC = 0.69, P = 0.04). However, some neonates substantially improve PcO2/FIO2 following initiation of treatment. Among neonates who survived at least 24 h, the highest preductal PcO2/FIO2 achieved in the initial 24 h was the strongest predictor of survival (AUC = 0.87, P = 0.002). Nonsurvivors had a mean admission preductal PcCO2 higher than survivors (91 ± 31 vs. 70 ± 25 mmHg, P = 0.02), and their PcCO2 remained high during the first 24 h of treatment. ----- CONCLUSION: The inability to achieve adequate gas exchange within 24 h of initiation of intensive care treatment is an ominous sign in high-risk outborn neonates with CDH. We suggest that improvement of oxygenation during the first 24 h, along with other relevant clinical signs, should be used when making decisions regarding treatment options in these critically ill neonates

Pulse Wave Velocity as a Method of Outcome Monitoring after Renal Denervation

Rezistentna hipertenzija definirana je nemogućnošću uspostavljanja ciljnih vrijednosti arterijskoga tlaka (AT) unatoč terapiji koja uključuje tri i više antihipertenzivnih lijekova različitih skupina (od kojih je jedan diuretik) u kombinacijama i optimalnim tolerabilnim dozama. Osim farmakološkog liječenja, bolesnike s refraktornom rezistentnom hipertenzijom upućuje se na postupak denervacije renalnog pleksusa ukoliko ne postoji zapreka. Mjerenjem krutosti žila brzinom pulsnog vala dokazan je marker povišenoga kardiovaskularnog rizika. Cilj istraživanja bio je prikazati vrijednosti mjerenja krutosti krvnih žila kao metodu praćenja ishoda denervacije renalnog pleksusa. Obuhvaćeno je 10 bolesnika koji su bili praćeni nakon denervacije renalnoga pleksusa u vremenu od jedne do četiri godine. Krutost žila mjerena je oscilometrijskim uređajem „Agedio B900“. Istraživanje je pokazalo da denervacija renalnoga pleksusa, kao dodatna metoda kontrole AT-a, ima dugoročne pozitivne učinke povrh sniženja AT-a u smislu sniženja krutosti žila tijekom više godina, čime se snizuje kardiovaskularni rizik. Krutost žila mogući je novi marker praćenja ishoda denervacije renalnog pleksusa.Resistant hypertension is defined as failure to achieve target blood pressure (BP) in spite of using a minimum of 3 antihypertensive drugs of different classes, one of which must be a diuretic, at optimal tolerated doses. Device-based therapies like renal denervation are indicated in patients in whom pharmacological agents failed to control BP and patients with refractory resistant hypertension have no contraindications for the procedure. Pulse wave velocity is the measure of arterial stiffness which is directly connected to cardiovascular risk and hypertension-mediated organ damage. The aim of this study was to present measurement of arterial stiffness as a noninvasive method of assessing cardiovascular risk in patients with resistant hypertension after renal denervation. This study included 10 patients over the course of 1 to 4 years after renal denervation. Arterial stiffness was measured for patients with a noninvasive method using the Agedio B900 device operating on the principle of oscillometry. This study demonstrates that renal denervation as an additional method of controlling BP has long term positive effects in addition to lowering BP and vascular stiffness over several years, thus lowering cardiovascular risk. Noninvasive measurement of arterial stiffness could be a novel prognostic marker of the impact of renal denervation on arterial stiffness

KONCENTRACIJE SRČANOG VISOKOOSJETLJIVOG TROPONINA I U MOKRAĆI ZDRAVIH OSOBA – PRELIMINARNI REFERENTNI INTERVALI

Recent studies have shown the presence of troponin molecules in urine, with kidneys considered the main organs of elimination. Availability of the new generation of high-sensitivity assays has enabled detection of low concentrations of circulating cardiac troponins, but the high-sensitivity troponin assays are not designed for analysis of urine specimens. The aim of this study was to establish preliminary reference intervals for the high-sensitivity cardiac troponin I (hs-cTnI) concentrations in urine of healthy adults in Croatia. A total of 60 reference persons were selected (30 males and 30 females) and the concentrations of hs-cTnI in random urine samples were determined on the Abbott Architect i1000SR (Abbott Laboratories) analytical system with chemiluminescent immunochemical method on microparticles (CMIA, ARCHITECT STAT High Sensitive Troponin-I), accredited according to the HR EN ISO 15189:2012 standard (Medical laboratorieds – requirements for quality and competence. Geneva, International Organization for Standardization, 2012). We determined the limit of detection, total laboratory precision, expanded measurement uncertainty and preliminary estimates of the gender-specifi c 99th percentile of the upper reference limit (URL) using nonparametric analysis (methods). The male and female 99th percentile cut-off values were 39.3 and 35.2 pg/mL, respectively. The results of this pilot study suggest that troponin I is removed from the blood by the kidneys and can be determined in the urine with CMIA, ARCHITECT STAT High Sensitive Troponin-I assays. Further research is focused on detailed studies of biochemistry and determination of troponin I in the urine as a new biological marker.Cilj ovoga istraživanja bio je odrediti preliminarne referentne intervale visokoosjetljivog troponina l u mokraći zdravih osoba. Koncentracije srčanog visokoosjetljivog troponina I u slučajnim uzorcima mokraće određene su na analitičkom sustavu Abbott Architecti1000SR (Abbott Laboratories) kemiluminiscentnom imunokemijskom metodom na mikročesticama (CMIA, ARCHITECT STAT High Sensitive Troponin-I), akreditiranom prema HR EN ISO 15189. Referentni interval izrađen je u Referentnom centru Ministarstva zdravstva Republike Hrvatske za izradu referentnih vrijednosti u području opće medicinske biokemije na uzorku od 30 referentnih osoba po spolu sljedećih karakteristika: nepušač, 25-65 godina, indeks tjelesne mase <30 kg/m2, odsutnost akutne i kronične bolesti, bez noćnog rada tijekom zadnjih 30 dana. Granica kvantifi kacija određena je sukladno smjernicama CLSI EP17-A2 i uz zadovoljavanje kriterija za preciznost za visokoosjetljivi test (KV<10 %). Linearnost metode u deklariranom području potvrđena je multikalibracijskom krivuljom. Ukupna laboratorijska preciznost izračunata je sukladno smjernicama CLSI EP15-A2 i iznosi 2,23 % (KV) u normalnom području i 1,45% (KV) u patološkom području. Proširena mjerna nesigurnost (k=2) izračunata je iz ukupne laboratorijske preciznosti i mjerne nesigurnosti kalibratora i iznosi ±4,5 % za normalno područje i ±2,9 % za patološko područje; 99. percentila gornje granice referentnog intervala izračunata je neparametarskom statističkom analizom, sukladno smjernicama CLSI C28-A3. Određena 99. Percentila gornje granice referentnog intervala za visokoosjetljivi troponin I u mokraći iznosi 39,3 ng/L za muškarce i 35,2 ng/L za žene. Dobiveni preliminarni rezultati ukazuju na to da se troponin I odstranjuje iz krvi putem bubrega i da se može pouzdano mjeriti na analitičkom sustavu Abbott Architecti1000SR (Abbott Laboratories) kemiluminiscentnom imunokemijskom metodom na mikročesticama

Survival of outborns with congenital diaphragmatic hernia: the role of protective ventilation, early presentation and transport distance: a retrospective cohort study

BACKGROUND: Congenital diaphragmatic hernia (CDH) is a congenital malformation associated with life-threatening pulmonary dysfunction and high neonatal mortality. Outcomes are improved with protective ventilation, less severe pulmonary pathology, and the proximity of the treating center to the site of delivery. The major CDH treatment center in Croatia lacks a maternity ward, thus all CDH patients are transferred from local Zagreb hospitals or remote areas (outborns). In 2000 this center adopted protective ventilation for CDH management. In the present study we assess the roles of protective ventilation, transport distance, and severity of pulmonary pathology on survival of neonates with CDH. ----- METHODS: The study was divided into Epoch I, (1990-1999, traditional ventilation to achieve normocapnia), and Epoch II, (2000-2014, protective ventilation with permissive hypercapnia). Patients were categorized by transfer distance (local hospital or remote locations) and by acuity of respiratory distress after delivery (early presentation-occurring at birth, or late presentation, ≥ 6 h after delivery). Survival between epochs, types of transfers, and acuity of presentation were assessed. An additional analysis was assessed for the potential association between survival and end-capillary blood CO2 (PcCO2), an indirect measure of pulmonary pathology. ----- RESULTS: There were 83 neonates, 26 in Epoch I, and 57 in Epoch II. In Epoch I 11 patients (42%) survived, and in Epoch II 38 (67%) (P = 0.039). Survival with early presentation (N = 63) was 48 % and with late presentation 95% (P <0.001). Among early presentation, survival was higher in Epoch II vs. Epoch I (57% vs. 26%, P = 0.031). From multiple logistic regression analysis restricted to neonates with early presentation and adjusting for severity of disease, survival was improved in Epoch II (OR 4.8, 95%CI 1.3-18.0, P = 0.019). Survival was unrelated to distance of transfer but improved with lower partial pressure of PcCO2 on admission (OR 1.16, 95%CI 1.01-1.33 per 5 mmHg decrease, P = 0.031). ----- CONCLUSIONS: The introduction of protective ventilation was associated with improved survival in neonates with early presentation. Survival did not differ between local and remote transfers, but primarily depended on severity of pulmonary pathology as inferred from admission capillary PcCO2