Joško Markić

Neurodevelopmental disabilities and quality of life after intensive care treatment

Aim:  To analyze the quality of life after Pediatric Intensive Care Unit (PICU) treatment and compare the differences between quality of life in children who suffer chronic health conditions, and those who do not, post discharge from PICU.

Life-threatening Valproate Overdose Successfully Treated with Haemodialysis

Life-threatening Valproate Overdose Successfully Treated with Haemodialysis Valproate (VPA) poisoning is an increasing clinical problem. The most common finding in VPA overdose is the depression of the central nervous system, which may progress to coma and death. This type of poisoning is difficult to treat, as no antidote exists. This report describes a case with a 16-year-old girl who poisoned herself with valproate. Initial treatment included naloxone, but she did not respond. She became comatose, with serum VPA concentration of 1320 μg mL-1. Three sessions of haemodialysis were performed, effectively eliminating VPA and decreasing the serum concentration. The patient regained consciousness and fully recovered. To our knowledge, this is the highest serum VPA concentration reported by now in children aged 16 or less. Haemodialysis has proved to be the treatment of choice for life-threatening acute VPA overdose in children. Uspješno liječenje teškog trovanja valproatom s pomoću hemodijalize Trovanje valproatom sve je češći klinički problem. Najčešći simptom nađen kod trovanja je depresija središnjega živčanog sustava koja može dovesti do kome i smrti. Trovanje se teško liječi jer antidot ne postoji. Prikazujemo slučaj 16-godišnje djevojke koja se otrovala valproatom. U početku je liječena naloksonom, ali nije došlo do poboljšanja. Postala je komatozna s koncentracijom valproata u serumu od 1320 μg mL-1. Provođenjem triju ciklusa hemodijalize serumska koncentracija valproata učinkovito je smanjena, nakon čega se razina svijesti vratila na normalu i djevojka se potpuno oporavila. Prema našim saznanjima, ovo je slučaj s najvišom izmjerenom serumskom koncentracijom valproata u djece od 16 godina ili manje. Na osnovi dobivenih rezultata preporučujemo uporabu hemodijalize u liječenju teških trovanja valproatom u djece.

Immune Modulation Therapy in a CRIM-Positive and IgG Antibody-Positive Infant with Pompe Disease Treated with Alglucosidase Alfa: A Case Report

Pompe disease is characterized by deficiency or absence of activity of the lysosomal enzyme acid alpha-glucosidase. As a result of ineffective metabolism, glycogen progressively accumulates in muscle tissues. Patients with an aggressive classic infantile-onset form generally rapidly die of cardiorespiratory failure. A cross-reactive immunological material (CRIM)-negative status is predictive of high anti-alglucosidase alfa antibody titers and usually a poor clinical outcome of enzyme replacement therapy (ERT). CRIM-positive patients can also develop robust antibody titers complicating therapeutic management.We successfully used an immune modulation therapy (IMT) protocol in a CRIM-positive infantile-onset patient with Pompe disease in whom infusions had to be temporarily discontinued because of safety concerns despite administration of pre-infusion medication. Prior to discontinuation, she had shown signs of clinical deterioration and continuous ventilation support through a tracheostomy was required. She was found to be positive for anti-alglucosidase alfa antibodies (1:6,400). IMT (rituximab, methotrexate and intravenous gamma globulin) was started, ERT was safely reintroduced during the IMT induction phase and, subsequently, the enzyme dose was increased, all without any complications. Antibodies disappeared, IMT was tapered and discontinued, and cadiomyopathy steadily improved. During 1 year of follow-up, she remained ventilator dependent and no gains in motor skills were noticed; motor functions will be closely monitored during sustained ERT.Although the reversal of clinical decline in our CRIM-positive and antibody-positive infant with Pompe disease cannot be solely attributed to IMT, our experiences with this protocol may be helpful to other physicians encountering comparable therapeutic dilemmas.

Lab-score is a valuable predictor of serious bacterial infection in infants admitted to hospital

SummaryParents frequently bring their children to the Emergency Department (ED) because of the fever without apparent source (FWAS). To avoid possible complications, it is important to recognize serious bacterial infection (SBI) as early as possible. Various tests, including different clinical scores and scales, are used in the laboratory evaluation of patients. However, it is still impossible to predict the presence of SBI with complete certainty. Galetto-Lacour et al. developed and validated a risk index score, named Lab-score. Lab-score is based on the three predictive variables independently associated with SBI: procalcitonin (PCT), C-reactive protein (CRP), and urinary dipstick. The objective of this study was to assess the performance of the Lab-score in predicting SBI in well-appearing infants ≤ 180 days of age with FWAS, who presented to ED and were hospitalized with suspicion of having SBI. Based on this study findings, white blood cells count (WBC), CRP, PCT, and lab-score ≥ 3 were confirmed as useful biomarkers for differentiation between SBI and non-SBI. Also, receiver operating characteristic curve (ROC) analysis confirmed that all of them were useful for differentiation between SBI and non-SBI patients with the highest area under curve (AUC) calculated for the Lab-score. The results of this research confirmed its value, with calculated sensitivity of 67.7 % and specificity of 98.6 % in prediction of SBI in infants aged ≤ 180 days. Its value was even better in infants aged ≤ 90 days with sensitivity of 75 % and specificity of 97.7 %. In conclusion, we demonstrated the high value of lab-score in detecting SBI in infants under 6 months of age with FWAS.

Effects of immune modulation therapy in the first Croatian infant diagnosed with Pompe disease: a 3-year follow-up study

SummaryPompe disease is a storage disorder characterized by deficient or absent activity of the enzyme acid alpha-glucosidase. As a result of ineffective metabolism, glycogen accumulates in muscle tissues. Patients with a classic infantile-onset form present by the first few months of life with hypertrophic cardiomyopathy and muscle weakness. If left untreated, these patients rapidly die of cardiorespiratory failure. A cross-reactive immunological material (CRIM)-negative status is predictive of high anti-alglucosidase alpha antibody titers. However, CRIM-positive patients also sometimes develop robust antibody titers. High antibody titers complicate therapeutic management, and those patients have a worse clinical outcome of enzyme replacement therapy (ERT).Four years ago, we successfully used an immune modulation therapy (IMT) protocol in a CRIM-positive infantile-onset patient with Pompe disease in whom ERT had to be discontinued because of severe infusion-associated reactions. She was found to be positive for anti-alglucosidase alpha antibodies. IMT (rituximab, methotrexate, and intravenous gammaglobulin) was started, and ERT was safely reintroduced during the IMT induction phase without any complications. Antibodies disappeared; IMT was tapered and discontinued; and cardiomyopathy steadily improved. During more than 3 years of follow-up, she remained ventilator dependent, and no gains in motor skills were noticed. The antibodies are still undetectable, and no adverse reactions associated with IMT had occurred. The cardiomyopathy is gradually increasing, but there is still ~ 50 % reduction as compared with the highest value measured. Although the reversal of clinical decline in our CRIM-positive and antibody-positive infant cannot be solely attributed to IMT, this protocol proved itself efficient and safe.ZusammenfassungDie Pompe’sche Krankheit ist eine Speicherkrankheit, die durch eine gestörte oder fehlende Aktivität des Enzyms saure alpha-Glucosidase gekennzeichnet ist. Als Folge des ineffizienten Stoffwechsels reichert sich Glykogen im Muskelgewebe an. Patienten mit der klassischen Form des Ausbruchs der Erkrankung im Kindesalter präsentieren sich bereits in den ersten Lebensmonaten mit einer hypertrophen Kardiomyopathie und Muskelschwäche. Unbehandelt sterben diese Patienten rasch am kardiorespiratorischen Versagen.Ein kreuzreaktiv immunologisches Material (CRIM) negativer Status sagt hohe anti-alpha Glucosidase Antikörper voraus. CRIM positive Patienten haben allerdings auch manchmal deutlich erhöhte Antikörper Titer. Hohe Antikörper Titer machen das therapeutische Management kompliziert: diese Patienten sprechen klinisch schlechter auf eine Enzymersatz Therapie an.Vor 4 Jahren verwendeten wir ein Protokoll einer immumodulatorischen Therapie (IMT) erfolgreich bei einer CRIM positiven Patientin mit Ausbruch der Pompe’schen Krankheit im Kindesalter, bei der die Enzymersatz-Therapie wegen schwerer infusions-assoziierter Reaktionen abgesetzt werden musste. Sie hatte anti-alpha Glucosidase Antikörper. Eine IMT bestehend aus Rituximab, Methotrexat, und intravenösem Gammaglobulin wurde begonnen. Während der IMT konnte die Enzymersatz Therapie wieder sicher ohne irgendwelche Komplikationen begonnen werden. Die Antikörper verschwanden und die IMT konnte ausgeschlichen beziehungsweise abgesetzt werden. Die Kardiomyopathie wurde kontinuierlich besser.Während mehr als 3 Jahren follow-up blieb die Patientin Respirator abhängig – es wurde keine Besserung der motorischen Fähigkeiten beobachtet. Die Antikörper sind weiterhin unter dem Detektionslimit. Die Kardiomyopathie wird nun langsam schlechter – ist aber noch immer 50 % besser im Vergleich zum schlechtesten im Verlauf gemessenen Wert.Obwohl die klinische Besserung unseres CRIM- und Antikörper-positiven Kindes nicht nur der IMT zugeschrieben werden kann, zeigte sich das Protokoll jedenfalls als wirksam und sicher.

LATE VENTRICULOPERITONEAL SHUNT INFECTION CAUSED BY SHEWANELLA ALGAE

We present a case of ventriculitis and peritonitis in a child with ventriculoperitoneal shunt, which occurred 5 years after the surgery. The infection developed after contact with seawater and began as otitis. For the first time, Shewanella algae, a marine microorganism, was identified as the cause of ventriculoperitoneal shunt infection.

Late preterm birth is a strong predictor of maternal stress later in life: Retrospective cohort study in school-aged children.

The aim of this study was to compare the level of stress in mothers of school‐aged children born late preterm and admitted to the intensive care unit (ICU) with the level of maternal stress if a child was born late preterm and not admitted to the ICU as well as if a full‐term child was admitted to the ICU.

Serum vitamin D levels in children with newly diagnosed and chronic immune thrombocytopenia

The primary objective of the study was to assess the vitamin D (VD) status of patients suffering from ITP. Children from the case cohort (total 21) were recruited from chronic ITP patients (followed as outpatients) and newly diagnosed ITP (prospective study) patients. VD deficiency (values <75 nmol/L) was detected in 11 patients with newly diagnosed ITP, and seven patients with chronic ITP. Only three patients with newly diagnosed, and none with chronic ITP had normal VD values. Newly diagnosed ITP patients had statistically significantly higher values (P <.044) of VD than the patients with chronic type of ITP. Platelets values did not follow VD level. VD deficiency is very common in children with either newly diagnosed or chronic ITP form. Therefore there is a utility supplementing VD in these patients. To investigate the role of VD as an immune modulating drug for patients with ITP, a prospective randomized placebo-controlled trial needs to be performed.

Evaluation of Neonatal Hemolytic Jaundice: Clinical and Laboratory Parameters

BACKGROUND: Neonatal jaundice that occurs in ABO or Rhesus issoimunisation has been recognized as one of the major risk factors for development of severe hyperbilirubinemia and bilirubin neurotoxicity. AIM: Aim of our study was to investigate clinical and laboratory parameters associated with hemolytic jaundice due to Rh and ABO incompatibility and compare results with the group of unspecific jaundice. MATERIAL AND METHODS: One hundred sixty seven (167) neonatal hyperbilirubinemia cases were included in the study, 24.6% of which presented with ABO/Rhesus type hemolytic jaundice, and the rest with unspecific jaundice. Evaluation included: blood count, reticulocites, serum bilirubin, aminotransferases, blood grouping, and Coombs test, also the day of bilirubin peak, duration of the hyperbilirubinemia, and additional bilirubin measurements. RESULTS: We showed significantly lower mean values of hemoglobin, erythrocytes and hematocrit and significantly higher values of reticulocytes in the group of ABO/Rh incompatibility compared to the group of jaundice of unspecific etiology; also an earlier presentation and a higher-grade jaundice in this group. CONCLUSIONS: The laboratory profile in ABO/Rh isoimmunisation cases depicts hemolytic mechanism of jaundice. These cases carry a significant risk for early and severe hyperbilirubinemia and are eligible for neurodevelopmental follow-up. Hematological parameters and blood grouping are simple diagnostic methods that assist the etiological diagnosis of neonatal hyperbilirubinemia.

Emotional and behavioral outcomes and quality of life in school-age children born as late preterm: retrospective cohort study

Aim To determine the effect of late preterm birth and treatment at the intensive care unit (ICU) on school-age children’s emotional and behavioral problems and quality of life (QoL). Methods Emotional and behavioral problems and QoL were investigated in 6-12-year-olds who were born late preterm at the University Hospital Center Split in the period from January 2002 to March 2008. The study included 126 late preterm children treated in ICU (LP-ICU group), 127 late preterm children not treated in ICU (LP-non-ICU group), and 131 full-term children treated in ICU (FT-ICU group). Emotional and behavioral difficulties were assessed using the Child Behavior Checklist. QoL was evaluated with the Royal Alexandra Hospital for Children Measure of Function questionnaire. The data was collected via telephone interview with mothers during 2014. Results Late preterm children had a nearly 5-fold risk for internalizing problems in comparison with FT-ICU children (OR 4.76, 95% confidence interval [CI] 2.37-9.56 and OR 4.82, 95% CI 2.25-10.37 in LP-ICU and LP-non-ICU children, respectively). They also had a greater risk for externalizing problems (OR 3.08, 95% CI 1.44-6.61 and OR 2.68, 95% CI 1.14-6.28, respectively) and total problems (OR 6.29, 95% CI 2.86-13.83 and OR 7.38, 95% CI 3.08-17.69, respectively) and a considerably increased risk for lower QoL (OR 12.79, 95% CI 5.56-29.41 and OR 5.05, 95% CI 2.04-12.48, respectively). Conclusion Children born late preterm had a greater risk for emotional and behavioral problems and lower QoL during childhood than their full-term born peers and they experienced serious health problems upon birth.