Rapid genome sequencing for critically ill infants: an inaugural pilot study from Turkey.

Introduction: Rare and ultra-rare genetic conditions significantly contribute to infant morbidity and mortality, often presenting with atypical features and genetic heterogeneity that complicate management. Rapid genome sequencing (RGS) offers a timely and cost-effective approach to diagnosis, aiding in early clinical management and reducing unnecessary interventions. This pilot study represents the inaugural use of next-generation sequencing (NGS) as a diagnostic instrument for critically ill neonatal and pediatric ICU patients in a Turkish hospital setting. Methods: Ten infants were enrolled based on predefined inclusion criteria, and trio RGS was performed. The mean age of the participants was 124 days, with congenital abnormalities being the most common indication for testing. Three patients had consanguineous parents. The mean turnaround time from enrollment to delivery of results was 169 h, with a diagnostic yield of 50%. Results: Three patients received a definitive molecular diagnosis, impacting their clinical management. Two patients benefited from the exclusion of Mendelian conditions, leading to alternative diagnoses. Discussion: This study demonstrates the feasibility and results of RGS in Turkish hospital settings, emphasizing the importance of timely genetic diagnosis in reducing the diagnostic odyssey for families and improving patient care. Further research is needed to evaluate the cost-effectiveness and applicability of RGS in the Turkish healthcare system for children with diseases of uncertain etiology.

The effects of valproate on serum leptin, insulin, and lipid levels in epileptic children.

BACKGROUND: Weight gain is an important adverse effect of valproate (VPA) therapy. A number of mechanisms have been proposed for its pathophysiology. The aim of the present study is the evaluation of insulin, leptin and lipid levels in epileptic children on treatment with VPA. METHODS: Thirty epileptic children treated with VPA, and 20 age-sex-matched healthy children, were enrolled in this study. Blood samples were taken and the body mass index was calculated for all of the subjects. Serum insulin, leptin, and lipid levels were compared between the two groups. RESULTS: Leptin levels were significantly higher in the patient group (P = 0.009) whereas body mass index values were comparable. There was a positive correlation between leptin and body mass index among both patient (r = 0.464, P = 0.01) and control groups (r = 0.734, P = 0.0001). Total cholesterol and low-density lipoprotein (LDL) cholesterol levels were lower in VPA-treated epileptic children than the control group (P = 0.008; P = 0.003, respectively). No significant difference was determined in insulin levels between the two groups. A negative correlation was observed between plasma VPA level and total cholesterol and LDL cholesterol levels in the patient group (r = -0.380, P = 0.03, r = -0.474, P = 0.008, respectively). CONCLUSION: This study demonstrated higher leptin levels in the patient group despite similar BMI values. Hence, it seems likely that VPA causes leptin resistance. Unlike other anti-epileptics, VPA does not produce an increase in serum cholesterol levels. On the contrary, lower levels of total and LDL cholesterol levels in VPA-receiving patients have been observed in our study.

Hidden Toxicity in Neonatal Intensive Care Units: Phthalate Exposure in Very Low Birth Weight Infants.

OBJECTIVE: To determine exposure to endocrine-disrupting phthalates in preterm infants in neonatal intensive care units (NICU). METHODS: Urine samples (n=151) from 36 preterm infants (<32 weeks of gestation and/or <1500 g of birth weight) were collected on the first 3 days of admission to the NICU and biweekly thereafter. Diethylhexyl phthalate contents of indwelling medical devices used in various procedures and the concentrations of phthalate metabolites in the urine samples were analyzed. The relationships between urinary excretion, exposure intensity, postnatal age and birth weight were examined. RESULTS: The mean gestational age and mean birth weight of the study infants were 28.9±1.5 weeks and 1024±262 g, respectively. Diethylhexyl phthalate was detected in umbilical catheters, endotracheal tubes, nasogastric tubes, and nasal cannula. Monoethylhydroxyhexyl phthalate (MEHHP) was the most frequently detected metabolite (81.4%); its concentration increased during the first 4 weeks and then started to decrease but never disappeared. Patients who did not need indwelling catheters (except nasogastric tubes) after 2 weeks were classified as group 1 and those who continued to have indwelling catheters as group 2. Although not of statistical significance, MEHHP levels decreased in group 1 but continued to stay high in group 2 (in the 4th week, group 1: 65.9 ng/mL and group 2: 255.3 ng/mL). Levels of MEHHP in the first urinary samples were significantly higher in infants with a birth weight <1000 g (<1000 g: 63.2±93.8 ng/mL, ≥1000 g: 10.9±22.9 ng/mL, p=0.001). CONCLUSION: Phthalate metabolites were detected even in the first urine samples of very low birth weight newborns. Phthalate levels were higher in the first weeks of intensive invasive procedures and in preterm infants with a birth weight less than 1000 g. MEHHP was the most frequently detected metabolite and could be a suitable biomarker for the detection of phthalate exposure in preterm infants.

Successful percutaneous removal of broken umbilical vein catheter in a very low-birth-weight preterm infant.

A 28-week-old preterm infant with a birth weight of 1250 g had a broken segment of umbilical vein catheter (UVC) lodged in the right atrium. It was observed that a 7-cm fragment of catheter had migrated to the right atrium through the inferior vena cava. The catheter was successfully retrieved by fluoroscopically guided percutaneous cardiac catheterization, using a cobra catheter and snare wire, without complication. Fracture and embolization of UVC is a rare but serious complication. Presently described was a case of fractured and embolized UVC in a very low-birth-weight preterm infant, and its successful retrieval via percutaneous endovascular approach.

Preliminary anatomical and neurodevelopmental outcomes of intravitreal bevacizumab as adjunctive treatment for retinopathy of prematurity.

PURPOSE: To evaluate the two-year follow-up of patients with type 1 retinopathy of prematurity (ROP) who received intravitreal bevacizumab (IVB) as adjunctive treatment. MATERIALS AND METHODS: We conducted a longitudinal follow-up study of premature infants who received 0.625 mg IVB therapy in addition to standard laser photocoagulation therapy. For comparison of the ophthalmological and neurological assessment outcomes of these infants, a control group was formed with 13 birth weight- and gestational age-matched infants who were treated with laser therapy alone for type 1 ROP. The neurological status of the study group and the control group was examined systematically, and neurodevelopmental evaluation was assessed by the Bayley Scales of Infant Development (BSID-III). RESULTS: A total of 18 eyes of 13 infants were included in the study. Anatomical success was obtained in 14 eyes (78%) and retinal detachment was observed in 4 eyes (22%). At two years of age, no significant difference was found in terms of spherical or cylindrical refractive errors compared to the control group. In control group, 2/13 patients' and in study group, 3/13 patients' neurological examinations were abnormal. No significant difference was found in the mean cognitive, language or motor BSID-III test scores of the groups. CONCLUSIONS: IVB appears to be useful for advanced ROP when laser treatment is precluded or not sufficient for preventing the progression of ROP. This pilot study indicates that IVB seems to contribute no further complications to the complications already present due to prematurity.

Malignant epignathus including a nephroblastoma component and successful management.

A male infant was born to a 24-year-old mother (gravida 1 para 1) by cesarean delivery at 33 1/7 weeks of gestation. The physical examination revealed a large mass protruding from the baby's mouth, which appeared to be attached to the palate. Tracheostomy was performed immediately in the delivery room. A partial surgical excision was performed on the second postnatal day, removing most of the teratoma (epignathus), which was attached to the back of the pharynx and protruding from the baby's mouth measuring 13×11×9 cm and weighing 545 g. The final pathological diagnosis was "malignant epignathus with nephroblastoma component." According to our knowledge, this is the first case that have malignant epignathus including nephroblastoma component in the literature.

Epidemiological analysis of retinopathy of prematurity in a referral centre in Turkey.

PURPOSE: To collect data towards the establishment of a guideline to predict the population under risk for the development of retinopathy of prematurity (ROP) in Turkey. METHODS: Medical reports of 2950 preterm infants who underwent screening examinations for ROP between 1996 and 2010 at Istanbul Faculty of Medicine, Department of Ophthalmology were reviewed. The study population was classified as inpatient infants and referred infants. A risk factor analysis was performed limited to the 788 inpatient infants. The demographical variables regarding birth weight (BW), gestational age (GA) and postnatal age at the time of treatment were compared independently between 403 referred and 64 inpatient infants who were treated for severe ROP. RESULTS: The mean GA of the infants with severe ROP was 31.2±2.7 weeks, mean BW was 1543.4±508.3 g. The risk factor analysis of inpatient infants revealed BW<1500 g, GA<32 weeks; intraventricular haemorrhage, respiratory distress syndrome, sepsis, apnoea and phototherapy were associated with a higher incidence of ROP. In addition, sepsis, male gender, multiple gestations, BW<1500 g were associated with a higher incidence of progression to severe ROP, whereas maternal pre-eclampsia was associated with a lower incidence. On the other hand, comparison of demographic features revealed that the referred infants with ROP were born at a significantly higher BW and needed significantly earlier treatment than inpatient infants with ROP. CONCLUSIONS: The high BW and GA of infants with severe ROP indicate wider screening criteria should be used in our country. BW might be a more important criterion than GA for ROP screening.

Left ventricular non-compaction in children and adolescents: clinical features, treatment and follow-up.

BACKGROUND: Left ventricular non-compaction (LVNC) is a specific cardiomyopathy that occurs following a disruption of endomyocardial morphogenesis. This study presents clinical findings, diagnostic features, treatment and follow-up of pediatric patients diagnosed with LVNC. METHODS: Patients with LVNC who were followed from January 2006 to March 2010 were included in this study. Diagnosis was made with the use of characteristic findings of magnetic resonance imaging and echocardiography. Holter electrocardiography and metabolic screening tests were also performed in all patients. RESULTS: A total of 24 patients were studied (18 male, six female). Patient age at diagnosis was 50 ± 60 months (eight days to 15 years). Average follow-up period was 22 ± 12 months (four months to four years). Findings at diagnosis were as follows: eight (33%) patients had heart failure, five (20%) had rhythm abnormalities, five (20%) had cardiomegaly, two had murmurs, two had cyanosis, and two presented with fatigue. Ten (41%) patients had been followed previously with other diagnoses. In 21 (87.5%) patients, electrocardiographic abnormalities were noted, especially left ventricular hypertrophy and ST-T changes. Patients had an average ejection fraction of 46% (18-73%) and three of them had additional congenital heart disease (patent ductus arteriosus, aortopulmonary window and complex cyanotic heart disease). Scanning for metabolic diseases revealed fatty acid oxidation disorder in one patient, and mitochondrial disease in another. During follow-up, a permanent pacemaker was implanted in a patient with severe bradycardia and ventricular dysfunction, and three patients died. CONCLUSION: LVNC can be diagnosed at any age from newborn to adolescent and has a variable clinical course. Closer study of patients with cardiomegaly and heart failure can reduce delays in diagnosis of LVNC.

Recombinant human erythropoietin beta therapy: an effective strategy to reduce transfusion requirement in children receiving anticancer treatment.

In recent years erythropoietic agents have become important tools in the management of anemia in cancer patients, improving hemoglobin (Hb) concentrations, reducing the need for transfusion, and enhancing quality of life. In this prospective and historically controlled study, the effects of epoetin beta on Hb concentrations and red blood cell transfusion needs in children with cancer receiving chemotherapy or radiotherapy have been investigated. Epoetin beta (150 U/kg/day, 3 days a week) was given subcutaneously to 22 children with cancer when Hb concentration < or = 10 g/dL. Data from these patients were compared with those from 20 historical control patients. Hb concentrations were studied weekly in the first 9 weeks, then weekly or fortnightly thereafter. Minimum, maximum, and mean Hb concentrations, frequency of red blood cell transfusion, and the number of red cell packs given were noted. Hb concentrations in weeks 6, 8, and 11 were clearly higher in the study group than the controls. The minimum Hb concentration of the study group was significantly higher than than the control group (7.98 +/- 0.73 [6.70-9.68] g/dL and 7.24 +/- 1.40 [5.50-11.20] g/dL, respectively [p = .038]). A total of 8 units of erythrocyte suspension was given to 4 of the 22 patients in the epoetin group (0.36 unit per patient), while 16 of the 20 patients in the control group received 37 units of erythrocyte suspension in total (1.85 units per patient). The red cell transfusion requirement and the units of transfused erythrocytes per patient were clearly lower in the epoetin group (p < .001 for both of the parameters). No drug-related side effects were noted during epoetin therapy. Epoetin beta therapy provides significant increase in Hb concentrations in children with cancer under anticancer treatment, especially after the sixth week of therapy. Administration of epoetin beta prevents profound decreases in Hb concentrations in the course of therapy and effectively reduces the need for red blood cell transfusions. Epoetin beta was found to be safe and effective in the dosage and the scheme it was used in our study.

Granulomatous reaction in mediastinal B-cell non-Hodgkin lymphoma and intracardiac thrombosis.

Epithelioid cell granulomas may be associated with several neoplasms. Lymphomas may mimic or are associated with epithelioid granulomas. In this article the authors report a child with granulomatous reaction in B cell non-Hodgkin lymphoma and intracardiac thrombosis. Although cancer alone is a risk factor for thromboembolism, thrombosis is a multifactorial disorder with both hereditary and acquired risk factors. This is the first reported case of intracardiac thrombosis with MTHFR A1298C and factor XIII V34L mutations together with granulomatous reaction in non-Hodgkin lymphoma.

Is Familial Mediterranean Fever a thrombotic disease or not?

The aim of our study was to show how the progression and severity of Familial Mediterranean Fever (FMF) is affected by procoagulant activity and alterations in the markers of thrombosis and fibrinolysis. The study cohort comprised 64 FMF patients who were classified as attack-free patients (Group 1; n = 34 patients, aged 3-19 years) and attack patients (Group 2; n = 30 patients, aged 3-21 years). All patients were on colchicine treatment with the exception the newly diagnosed patients in Group 2. A total of 14 healthy subjects between 5-12 years of age were enrolled as controls (Group 3). Laboratory tests, including leukocyte and thrombocyte counts, erythrocyte sedimentation rate, CRP, fibrinogen, PT, aPTT, Factor VIII, vW factor, D-dimer, P-selectin, tPA and PAI-1, were carried out on all patients. Inflammation continued both during the attack and attack-free period in FMF. The prolongation of PT was observed during attacks (PT = 13.6 s in Group 2, and PT = 12.6 s in Group 3; p = 0.002). tPA levels increased in FMF patients (tPA levels of group 1, 2 and 3 were 12.6, 13.2 and 9.7 ng/ml, respectively; p = 0.01). P-selectin was lower in both patient groups than in the control group. During attack periods PAI-1 levels increased (PAI-1 level of Group 1: 89.6 ng/ml and PAI-1 level of Group 2: 335.7 ng/ml, p = 0.000). Inflammation with increased acute phase reactants continued during both attack and attack-free periods in FMF patients. Prolongation of PT and differences in tPA and P-selectin levels suggest that hypercoagulability may have a role in the etiopathogenesis of FMF. It may be possible to use PAI-1 as a marker for the attacks of FMF.