Kako liječiti bolesnike nakon teških neželjenih djelovanja uzrokovanih inhibitorima TNF

Biological agents are widely used in the treatment of autoimmune rheumatic disorders. We report on serious adverse events during treatment with anti-tumor necrosis factor antibody in two of our patients with juvenile idiopathic arthritis. One patient was treated with a biological agent due to juvenile idiopathic arthritis complicated by uveitis, developing miliary tuberculosis during treatment. After treatment with antituberculotics, she recovered completely. Her underlying disease is currently in remission. Another patient was treated for juvenile spondyloarthritis and developed an inflammatory process of the central nervous system with serious neurological deficits. He was treated with high-dose corticosteroids, followed by slowly tapering doses of corticosteroids. His neurological deficits improved, but are still present. Similar cases have been described previously, but there are no recommendations how to treat arthritis afterwards in such patients. We would like to emphasize the need of developing guidelines for further treatment of arthritis after the occurrence of serious adverse effects during treatment with biological agents.Biološki lijekovi se primjenjuju u liječenju brojnih autoimunih reumatskih bolesti. U ovom članku prikazujemo dva slučaja ozbiljnih nuspojava liječenja inhibitorima čimbenika nekroze tumora (tumor necrosis factor, TNF) kod bolesnika s juvenilnim idiopatskim artritisom (JIA): bolesnice liječene zbog JIA kompliciranog razvojem uveitisa, kod koje se javila milijarna tuberkuloza tijekom liječenja. Nakon liječenja antituberkuloticima došlo je do potpunog oporavka. Njena osnovna bolest je u remisiji. Drugi bolesnik je liječen zbog juvenilnog spondiloartritisa te je razvio upalni proces središnjega živčanog sustava s ozbiljnim neurološkim posljedicama. Liječen je visokim dozama kortikosteroida koje su potom postupno snižavane. Neurološki ispadi su se dijelom poboljšali, ali su ipak još uvijek prisutni. Slični slučajevi su opisivani i ranije, ali nema preporuka kako bi trebalo liječiti artritis nakon što nastupe takve nuspojave. Željeli bismo naglasiti potrebu stvaranja smjernica za daljnje liječenje artritisa nakon pojave teških nuspojava prilikom liječenja biološkim lijekom

FUNCTIONAL OUTCOME OF CHILDREN TREATED IN AN INTENSIVE CARE UNIT (ICU)

Uvod: Ishod bolesnika nakon liječenja ne određuje samo težina osnovne bolesti nego i njegovo stanje prije hopsitalizacije. Cilj: Utvrditi ishod bolesnika liječenih u JIL-u, osobito djece s kroničnim bolestima. Ispitanici i metode: Podatci su prikupljani prospektivno. Ishod je procijenjen uporabom ljestvice Pediatric Overall Performance Category (POPC) za 449-ero djece liječene u JIL-u, KBC Split. Procijenjeno je funkcionalno stanje prije hospitalizacije i na otpustu iz bolnice - u bolesnika s neurorazvojnim bolestima, s drugim kroničnim bolestima i bez kronične bolesti. POPC je ljestvica od šest stupnjeva, od zbroja 1 (normalan) do 6 (mrtav), u rasponu koji upućuje na sve veće stupnjeve funkcionalnog oštećenja. Svaki stupanj ljestvice je popraćen definicijama stanja koje su prikladne za dob. Procijenili smo bazalno funkcionalno stanje bolesnika (bPOPC) prije pojave osnovne bolesti, koja je neposredno uzrokovala hospitalizaciju, temeljem razgovora s roditeljima. Ocjena funkcije prije otpusta (dPOPC od engl. discharge functional score) odnosila se na bolesnikovo stanje prije otpusta iz JIL-a. Rezultati: Funkcionalno stanje na otpustu bilo je značajno ovisno o funkcionalnom stanju prije hospitalizacije i o predviđenoj smrtnosti. Djeca s neurorazvojnim bolestima imala su značajno lošiju bazalnu ocjenu i značajno manje pogoršanje funkcionalnog morbiditeta pri otpustu u usporedbi s djecom bez kronične bolesti i onom s drugim kroničnim bolestima. Zaključci: Ljestvica POPC je dokazala svoju primjenjivost u maloj jedinici intenzivnog liječenja i na heterogenoj populaciji bolesnika. Zato je treba uzeti u obzir za redovitu procjenu kakvoće rada u zdravstvu, jer je to jednostavno i pouzdano sredstvo. U suprotnosti s ostalim bolesnicima, funkcionalno stanje djece s neurorazvojnim bolestima značajno je obilježeno utjecajem komorbiditeta. Njihovo stanje prije hospitalizacije bilo je već lošije od stanja ostale djece i stoga se nije moglo značajno promijeniti pri otpustu.Introduction: Patients’ outcome is determined not only by the severity of the index illness, but also the impact of the patients’ pre-admission comorbid status. Aim: We intended to evaluate the outcome of patients treated in a pediatric ICU, with special emphasis on the group of children with chronic diseases. Methods and subjects: The data was obtained prospectively and outcome was assessed according to the Pediatric Overall Performance Category (POPC) scale for 449 sick children in the pediatric ICU of Split University Hospital. Functional performance was assessed as the pre-admission score and the discharge score in patients with neurodevelopmental disabilities, patients with other chronic diesases, and those without a chronic disease. POPC is a six-point scale ranging from the score of 1 (normal) to 6 (dead), with interim points representing progressively greater functional impairment. Each scale category is accompanied by age-appropriate operational definitions. Functional performance of patients was assessed as the baseline, pre-admission score (bPOPC), prior to the index disease, based on an interview with each child\u27s parent. The discharge functional score (dPOPC) was evaluated before transfer of patients from the PICU. Results: The discharge functional status was significantly dependent on the pre-admission functional status and the predicted mortality. Children with neurodevelopmental disabilities had a significantly worse baseline score and significantly smaller deterioration of functional morbidity at discharge compared to children with no chronic disease and children with other chronic diseases. Conclusions: The POPC scale proved its applicability in a small ICU, with a heterogenous population of patients. It should therefore be considered for regular evaluation of the quality of health care, as a simple and accurate tool. As opposed to other patients, the functional status of children with neurodevelopmental disabilities was markedly influenced by their comorbidity. Their pre-admission status was worse than the status of other children, and hence could not deteriorate significantly at discharge

Lista prihvaćenih znanstvenih projekata - 1. ciklus (2. dio)

Lista prihvaćenih znanstvenih projekata - 1. ciklus (2. dio

High Incidence of Glucose-6-phosphate Dehydrogenase Deficiency in Croatian Island Isolate: Example from Vis Island, Croatia

Aim: To determine the prevalence of glucose-6-phosphate dehydrogenase (G6PD) deficiency in the population of the town of Komiža on the island of Vis, which has previously been reported as a place with several cases of favism. Methods: We screened 302 randomly selected men, using the fluorescent spot test. Fluorescence readings were performed at the beginning and 5, 10, and 20 minutes after incubation, and were classified into three groups: bright fluorescence, weak fluorescence, and no fluorescence. All men found to be G6PD deficient were tested with a quantitative spectrophotometric UV method. Results: Of the 302 tested blood samples, 36 (11.9%) samples showed weak fluorescence or no fluorescence spots. Spectrophotometric UV test showed that 18 (5.96%) men were G6PD deficient. The prevalence of G6PD deficiency in the population of Komiža is significantly higher (P<0.001) than the prevalence in the whole population of Dalmatia in the south of Croatia (0.75% in men). Conclusion: On the basis of these findings, we recommend including the newborns from the island of Vis into a screening program for G6PD deficiency. Our results indicate that G6PD deficiency should be determined for all the island isolates in the Mediterranean basin and they warrant further studies

Association of Appendicitis, Helicobacter Pylori Positive Gastritis and Thrombotic Thrombocytopenic Purpura in an Adolescent

BACKGROUND Thrombotic thrombocytopenic purpura (TTP) in children is a rare life-threatening syndrome, characterized by microangiopathic hemolytic anemia, thrombocytopenia with renal dysfunction, neurologic symptoms, and fever. TTP is usually caused by deficient activity of von Willebrand factor cleaving protease (ADAMTS13), due to either gene mutations or acquired via anti-ADAMTS13 autoantibodies. It can be triggered by bone marrow or solid organ transplantation, cardiothoracic-, abdominal-, and orthopedic surgeries, infections including very rarely Helicobacter pylori infection. CASE REPORT Here we report a case of a 16-year-old male with TTP, who presented with thrombocytopenia before an appendectomy. Seven days after surgery, our patient started to vomit, developed melena, and was admitted to our pediatric intensive care unit (PICU) with clinical presentation of shock. Gastroscopy revealed H. pylori positive hemorrhagic gastritis. The patient was treated by erythrocyte transfusions, fresh frozen plasma, human albumin, glucose-electrolyte solutions, vitamin K, platelet transfusion before implantation of central venous catheter, and antibiotics. After 36 hours, we started plasma exchange (PEX). Blood tests showed deficiency of ADAMTS13. Due to the presence of anti-ADAMTS13 autoantibodies, rituximab was administered. Due to generalized tonic-clonic seizures, he was artificially ventilated. Brain MR angiography showed small ischemic cerebro-vascular insult in the arteria cerebri media region. Despite immunosuppressive therapy and PEX, the patient did not improve completely until the H. pylori infection was eradicated. After which, he recovered completely. CONCLUSIONS We present a rare case of TTP accompanied with appendicitis and gastritis caused by H. pylori, where TTP improvement was dependent on H. pylori infection eradication

Abnormal concentrations of acetylated amino acids in cerebrospinal fluid in acetyl‐CoA transporter deficiency

Acetyl-CoA transporter 1 (AT-1) is a transmembrane protein which regulates influx of acetyl-CoA from the cytosol to the lumen of the endoplasmic reticulum and is therefore important for the posttranslational modification of numerous proteins. Pathological variants in the SLC33A1 gene coding for AT-1 have been linked to a disorder called Huppke-Brendel syndrome, which is characterized by congenital cataracts, hearing loss, severe developmental delay and early death. It has been described in eight patients so far, who all had the abovementioned symptoms together with low serum copper and ceruloplasmin concentrations. The link between AT-1 and low ceruloplasmin concentrations is not clear, nor is the complex pathogenesis of the disease. Here we describe a further case of Huppke-Brendel syndrome with a novel and truncating homozygous gene variant and provide novel biochemical data on N-acetylated amino acids in cerebrospinal fluid (CSF) and plasma. Our results indicate that decreased levels of many N-acetylated amino acids in CSF are a typical metabolic fingerprint for AT-1 deficiency and are potential biomarkers for the defect. As acetyl-CoA is an important substrate for protein acetylation, we performed N-terminal proteomics, but found only minor effects on this particular protein modification. The acetyl-CoA content in patient's fibroblasts was insignificantly decreased. Our data may help to better understand the mechanisms underlying the metabolic disturbances, the pathophysiology and the clinical phenotype of the disease