[Long-term Follow-up After Cryocoagulation in Preterm Newborns from Northern Greece with Retinopathy of Prematurity: Three Year Results]. / Langzeit-Follow-up nach Exokryokoagulation bei Frühgeborenenretinopathie in Nordgriechenland: 3-Jahres-Ergebnisse.

BACKGROUND: This is a retrospective study of the efficacy of treatment of neonates (NN) with exocryocoagulation retinopathy of prematurity (ROP) with respect to morphology of the retina and visual function. MATERIALS AND METHODS: Out of a total of 3103 neonates, 304 (9.8%) had a ROP. 66 of these were treated. All neonates were observed for 3 years after this treatment. When the patients suffered retinal ablation or dragging of the macula, the treatment was rated as unsuccessful. Best corrected grid visual acuity and best corrected visual acuity were assessed with Lea symbols and Kay pictures. RESULTS: The 66 treated neonates (132 eyes) had a gestation age of less than 28 weeks and weight at birth of < 1280 g. 28 neonates exhibited ROP and the rest in zone 2. Among these 66 neonates, 64 (128 eyes) exhibited improved vision. 37 neonates (74 eyes) also exhibited morphological improvement. Only one neonate developed retinal detachment. CONCLUSION: Early treatment with cryopexia of neonates with ROP can improve vision and stabilise the retina.

Use of Tigecycline in Pediatric Patients With Infections Predominantly Due to Extensively Drug-Resistant Gram-Negative Bacteria.

BACKGROUND.: Emergence of extensively drug-resistant (XDR) bacteria has forced clinicians to use off-label antimicrobial agents such as tigecycline. We present our experience on salvage use of tigecycline for the treatment of infections caused by XDR Gram-negative bacteria in critically ill children and review published cases. METHODS.: We conducted a retrospective chart review in pediatric departments of a tertiary level hospital from January 2009 to May 2014. Patients were identified using pharmacy database. For the literature review, relevant articles were identified from PubMed. RESULTS.: In our case series, 13 children (7 males) with a median age of 8 years (range, 2.5 months-14 years) received tigecycline for ≥2 days as treatment for healthcare-associated infections including 5 bacteremias, 6 lower respiratory tract infections, and 3 other infections. Isolated pathogens were XDR Gram-negative bacteria except 1. A loading dose (range, 1.8-6.5 mg/kg) was given in all except 2 cases. Maintenance dose was given at 1-3.2 mg/kg q12 h. Other antimicrobials including colistin and aminoglycosides (85% and 62%, respectively) were coadministered to all patients. No serious adverse events were detected in these very ill children. Twenty cases of children treated with tigecycline were previously published, mostly for multidrug-resistant/XDR bacteria. An episode of acute pancreatitis and neutrophil engraftment delay in 2 cases were reported during tigecycline treatment. Analyzing reported and all our cases together, mortality in bloodstream infections was 86%, whereas in nonbacteremic cases it was 24% (P = .009). CONCLUSIONS.: Tigecycline, given at the range of administered doses as salvage therapy and in combination with other antimicrobial agents, seemed to be well tolerated in a series of mainly critically ill pediatric patients and demonstrated relatively good clinical response in nonbacteremic patients.

Successful management of an outbreak due to carbapenem-resistant Acinetobacter baumannii in a neonatal intensive care unit.

UNLABELLED: The investigation and successful management of a monoclonal Acinetobacter baumannii outbreak in a neonatal intensive care unit are described. Upon the first clustered carbapenem-resistant A. baumannii (CRAB) infections, a bundle of actions were taken, including enhanced infection control, active surveillance (weekly stool samples), case-control study, staff education, daily audits and discontinuation of new admissions. Between September and December 2011, eight neonates developed 10 CRAB infections (five blood, four respiratory and one eye). A total of 216 active surveillance cultures were obtained from 96 neonates (43 % had ≥2 samples). During weeks 12, 16 and 17, active surveillance detected 3, 1 and 2 new CRAB acquisitions, respectively. Prevalence of infections/colonizations decreased, and no event occurred after 20th week. A colonized neonate developed CRAB sepsis and died. All CRAB isolates harboured bla OXA-58 and the intrinsic chromosomal bla OXA-51 carbapenemase genes. CONCLUSION: Active surveillance and enhanced infection control measures effectively contained spread of CRAB clone in the neonatal intensive care unit.

Plasma citrulline levels in preterm neonates with necrotizing enterocolitis.

BACKGROUND AND AIM: Citrulline is a non-protein amino acid synthesized in the small intestine. In children with short-bowel syndrome, citrulline has served as a reliable marker of the residual bowel length and parenteral nutrition (PN) independence. In the present study we aim to assess the value of citrulline measurement in preterm neonates developing necrotizing enterocolitis (NEC). METHODS: Plasma citrulline levels were measured prospectively in 17 preterm neonates with NEC stage II during the entire course of the disease. Serial citrulline determinations in 24 healthy preterm neonates on 2, 7, 14, 21 and 28 days of life (DOL), served as reference values. RESULTS: In healthy preterm neonates plasma citrulline levels showed a progressive increase in relation to age. In neonates presenting with NEC, mean citrulline levels were significantly lower as compared to controls' citrulline levels of the most approximate day of life (DOL 7: 16.85±4.2 vs 20.5±4.5 µmol/L, p<0.05; DOL 14: 18±4.2 vs 23.5±4.3 µmol/L, p<0.01; DOL 21: 17±2.5 vs 30±5.7 µmol/L, p<0.01). The optimal citrulline cut-off distinguishing NEC patient from controls was 17.75 µmol/L (sensitivity 76%, specificity 87%). Plasma citrulline at presentation correlated inversely with the duration of parenteral nutrition (r=-0.49, p<0.05). Consecutive citrulline determinations revealed that plasma citrulline increased during reintroduction and gradual increase of enteral nutrition. CONCLUSIONS: Our findings provide preliminary evidence that citrulline levels that are reduced in preterm neonates with NEC in comparison to age-matched controls and serial citrulline determinations could help to monitor improvement of functional enterocyte mass during the course and resolution of NEC.

Short-term and long-term mortality following pediatric intensive care.

BACKGROUND: The aim of the present study was to examine short-term and long-term mortality following discharge from the pediatric intensive care unit (PICU). METHODS: This was a prospective observational study. Data collected consisted of demographics, severity scores, procedures, treatment, need for and duration of mechanical ventilation (MV), length of PICU and hospital stay, and mortality at PICU and hospital discharge, at 3 and 6 months and at 1 and 2 years. RESULTS: A total of 300 patients (196 boys and 104 girls), aged 54.26 ± 49.93 months, were included in the study. Median (interquartile range) Pediatric Risk of Mortality (PRISM III-24) score was 7 (3-11) and predicted mortality rate was 11.16%. MV rate was 67.3% (58.3% at admission) for 6.54 ± 14.15 days, and length of PICU and hospital stay was 8.85 ± 23.28 days and 20.69 ± 28.64 days, respectively. Mortality rate at discharge was 9.7% and cumulative mortality rate thereafter was 12.7%, 15.0%, 16.7%, 19.0%, and 19.0% at hospital discharge, 3 months, 6 months, 1 year and 2 years, respectively. Significant risk factors of PICU mortality were inotrope use, PRISM III-24 score >8, MV, arterial and central venous catheterization, nosocomial infection, complications, and cancer. Independent predictors of mortality at discharge were inotrope use and PRISM III-24 score, whereas predictors of mortality at 2 years were comorbidity and cancer. CONCLUSIONS: A 2 year follow-up period seems sufficient for a comprehensive mortality analysis of PICU patients. Severity of critical illness is the key factor of short-term mortality, whereas comorbidity is the major determinant of long-term mortality.

Diagnostic utility of elevated serum soluble triggering receptor expressed on myeloid cells (sTREM)-1 in infected neonates.

OBJECTIVE: To assess the value of serum levels of soluble triggering receptor expressed on myeloid cells-1 (sTREM-1) for early diagnosis of late-onset sepsis (LOS) in neonates, compared with interleukin-6 (IL-6). DESIGN AND SETTING: Prospective, observational study in a single, level III neonatal intensive care unit of a university hospital. PATIENTS: Fifty-two preterm and term neonates evaluated for suspected LOS were studied. Neonates were classified into two groups: infected [confirmed sepsis (n = 22) and possible sepsis (n = 9)] and noninfected neonates (n = 21). MEASUREMENTS AND RESULTS: Serum sTREM-1 and IL-6 were measured (enzyme-linked immunosorbent assays) when signs suggestive of sepsis emerged. Infected neonates had significantly higher sTREM-1 (p = 0.004) and IL-6 (p < 0.0001) than noninfected neonates. Receiver operating characteristic (ROC) curve analysis resulted in significant areas under the curve (AUC) for both sTREM-1 (AUC = 0.733, p = 0.005) and IL-6 (AUC = 0.892, p = 0.001) for identification of infected neonates, with the difference between the two AUC not being significant. Further analysis documented acceptable diagnostic performance of sTREM-1 and IL-6, which was not improved, however, when the two markers were combined. CONCLUSIONS: Serum sTREM-1 increases in infected neonates. Diagnostic accuracy of sTREM-1 either alone or in combination with IL-6 is not better than that of IL-6.

Plasma RANTES increase during the first month of life independently of the feeding mode.

The chemokine RANTES (regulated upon activation, normal T cell expressed and secreted) plays a significant role in the innate immunity, which is particularly important in the neonatal period. In this study, we aimed to investigate the ability of the neonate to increase plasma levels of RANTES in the first month of life, and the possible impact of breast feeding on this ability. The study population consisted of 125 healthy term neonates that were exclusively breast-fed (n = 62) or formula-fed (n = 63) for at least 1 month after birth. Plasma RANTES concentrations (ELISA) as well as circulating leukocytes and platelets were measured on days 1 and 30 of life. Median RANTES concentrations of the total group showed a significant increase between day 1 [1000 (448-2100) pg/mL] and day 30 [3688 (1488-5400) pg/mL, p < 0.0001], as did median total lymphocyte, T-cell, B-cell, NK-cell and eosinophil counts (all p values <0.0001). Monocyte and platelet counts did not change significantly over the neonatal period. Further analysis according to the mode of feeding showed that RANTES levels as well as leukocyte populations and platelet counts did not differ significantly between breast-fed and formula-fed neonates on either day 1 or 30. Healthy term neonates are capable of increasing plasma RANTES levels during the 1st month after birth independently of the mode of feeding.

Rare manifestations of sirenomelia syndrome: a report of five cases.

Five cases of sirenomelia presented with rare manifestations are discussed. Three neonates were born alive and died within 2 to 12 hours after birth. One case was the offspring of a triple in vitro fertilization pregnancy with history of early intrauterine death of one of the triplets. The main features included fusion of lower extremities (five of five), renal agenesis (three of five), polycystic renal dysplasia (two of five), anal atresia with large bowel hypoplasia (three of five), pulmonary hypoplasia (four of five), and single umbilical artery (five of five). Other features that have only rarely been associated with sirenomelia included concurrence of congenital heart disease and neuroblastoma, gallbladder agenesis, and upper extremity defects.

Intracellular and plasma cytokine profile in neonates born to non-atopic parents: the impact of breast feeding.

UNLABELLED: The aim of this study was to profile the changes in intracellular and plasma cytokines during the neonatal period and evaluate the impact of breast feeding on these parameters. For this purpose, we measured the interleukin (IL)-2 and IL-4 producing CD3+/CD69+ T-cells using flow cytometry and plasma concentrations of interferon (IFN)-gamma and IL-4 using ELISA, in 122 healthy term neonates, aged 6-12 h, born to non-atopic parents, and 25 healthy children aged 1-12 years. A total of 42/122 neonates exclusively breast-fed (BF) and 39/122 formula fed (FF) were studied again on the 30th day of life for the above parameters. Finally, a clinical evaluation for the presence of atopic disease was conducted at 2 years of age. We found that at birth, the percentage of CD3+/CD69+/IL-4+ T-cells (median = 15.8%, range = 4.4%-49%) and plasma concentrations of IL-4 (median = 0.22 pg/ml, range = 0.18-0.25 pg/ml) were significantly higher (P < 0.0001) compared to those of children (median = 1.6%, range = 0.16%-2.7% for CD3+/CD69+/IL-4+ and median = 0.17 pg/ml, range = 0.13-0.26 pg/ml for IL-4), whereas plasma concentrations of IFN-gamma were significantly lower in neonates (median = 0.42 pg/ml, range = 0.3-1.5 pg/ml) than in children (median = 1.2 pg/ml, range = 0.3-2.6 pg/ml, P < 0.0001). During the neonatal period, only the CD3+/CD69+/IL-4+ T-cells increased significantly in both BF and FF groups. Comparison between BF and FF groups revealed no significant difference in any of the parameters measured. Moreover, no difference in the development of atopy during the first 2 years of life was found between BF and FF infants. CONCLUSION: our findings demonstrate that during the entire neonatal period type 2 immunity dominates, regardless of the mode of feeding, whereas type 1 immunity dominates during childhood. Moreover, in the absence of family history of atopy, the mode of feeding per se does not play a crucial role in the development of atopy within the first 2 years of life.

Use of ciprofloxacin in neonatal sepsis: lack of adverse effects up to one year.

AIM: To investigate the adverse effects of ciprofloxacin administered to neonates with sepsis on the hematologic indices, the hepatic and renal function and the joints and growth at 1 year follow-up. METHODS: In this observational prospective study, 2 groups of septic neonates were studied, 116 neonates who received ciprofloxacin and 100 neonates matched for gestational age and birth weight who did not receive ciprofloxacin. In all neonates the leukocyte and platelet counts as well as the serum concentrations of transaminases, bilirubin, albumin, urea and creatinine were measured before initiation of treatment and on the 10th and 15th to 20th days after treatment initiation. In 77 and 83 infants of the ciprofloxacin and control groups, respectively, the growth at the end of the first year of life was evaluated. RESULTS: No significant differences between the two groups were found in the hematologic and biochemical indices as well as growth at the end of the first year of life. Also no clinical evidence of arthropathy was observed. CONCLUSIONS: Treatment of neonatal sepsis with ciprofloxacin resulted in no short term hematologic, renal or hepatic adverse effects and did not appear to be associated with clinical arthropathy or growth impairment at 1 year follow-up evaluation.

In vivo effect of rhGM-CSF And rhG-CSF on monocyte HLA-DR expression of septic neonates.

OBJECTIVE: To investigate the effect of rhGM-CSF and rhG-CSF on the monocyte HLA-DR expression of septic neonates. SUBJECTS: 60 septic neonates and 41 healthy ones. Septic neonates were randomly assigned into three treatment groups, the GM-CSF group [n=20, rhGM-CSF 5 mcg/kg/d for 4 days, intravenously over 2h (IV)], the G-CSF group (n=20, rhG-CSF 10 mcg/kg/d for 4 days, IV) and the placebo group (n=20, normal saline for 4 days, IV). MEASUREMENTS: Serial (days 0,1, 3 and 5 after the onset of sepsis) measurements of the percentage of HLA-DR positive monocytes (%HLA-DR+ monocytes) and mean fluorescence intensity (MFI) by flow-cytometry as well as the absolute monocyte counts (AMC). MAIN RESULTS: On day 0, the HLA-DR expression of the septic neonates (%HLA-DR+ monocytes: 38%+/-1.8% (mean+/-SEM) and MFI: 73+/-3.4) was significantly lower than the healthy control values (%HLA-DR+ monocytes: 68%+/-2% and MFI: 123+/-4.6) (P<0.0001, for both parameters). On follow up (days 1, 3 and 5), a significant increase of HLA-DR expression was observed in all the groups of septic neonates. Healthy control values of %HLA-DR+ monocytes were reached by day 1 in the GM-CSF group and by day 3 in the G-CSF and placebo groups. Healthy control values of MFI were reached by day 3 in all groups of septic neonates. The AMC showed a significant increase in the GM-CSF group (during the whole follow up period) and in the G-CSF group (for the first 3 days of follow up). CONCLUSIONS: The monocyte HLA-DR expression is depressed on the onset of neonatal sepsis and is progressively restored during the following days. Treatment with rhGM-CSF results in an earlier increase of the number of monocytes expressing the HLA-DR.