Effects of Inhaled Corticosteroids on the Growth Plates of Infant Rats.

The most significant adverse effect of inhaled steroid administration in children is suppression of hypothalamic-pituitary-adrenal axis responsiveness and suppression of growth. This study evaluates the effects of inhaled corticosteroids on the growth plates in infant rats. Rats aged 10 days were divided into five groups. Low and high doses of budesonide and fluticasone propionate (50-200-250 mcg/day) were applied with a modified spacer for 10 days. The rat's tibias were then removed and the effects of the steroids on the growth plates were compared. Growth cartilage chondrocyte proliferation and apoptosis rates; IGF-1 and glucocorticoid receptor levels; and resting, proliferative, hypertrophic, and total zone (TZ) measurements were compared using immunohistochemical-staining methods. With high doses of fluticasone, growth plates were affected much more than with high doses of budesonide (p = 0.01). Fluticasone, particularly at a dose of 250 mcg, inhibited the growth plate with an intensive negative impact on all parameters.

Predictive value of soluble urokinase plasminogen activator receptor, soluble ST2, and IL-33 in bronchopulmonary dysplasia.

BACKGROUND: Bronchopulmonary dysplasia (BPD) remains an important complication of preterm births. The soluble form of ST2 (sST2), interleukin-33 (IL-33), and soluble form of the urokinase plasminogen activator receptor (suPAR) have attracted increasing attention as biomarkers for different diseases. The aim of the current study was to assess the predictive value of plasma sST2, IL-33, and suPAR levels in patients with risk of BPD development. METHODS: A total of 38 babies were studied prospectively on delivery to the neonatal intensive care unit. Serum levels of IL-33, sST2, and suPAR were measured using enzyme-linked immunosorbent assay. Serum samples were collected from umbilical cord (at the time of delivery, termed CB) and peripheral blood (on day 14, termed PB). RESULTS: Levels of suPAR (PB-suPAR) and sST2 (PB-sST2) in the peripheral blood of the BPD group were significantly higher than the corresponding levels in the non-BPD group (P < 0.001, P = 0.028, respectively. There was a statistically significant correlation between PB-suPAR levels and the severity of BPD (P < 0.001)) when the suPAR results were analyzed using the receiver operating characteristic curve. CONCLUSION: PB-suPAR and PB-sST2 levels are sensitive and specific independent predictive biomarkers in preterm babies with BPD.

High serum 25-hydroxyvitamin D levels are associated with pediatric sepsis.

Despite major advances in intensive care, sepsis continues to be a major cause of morbidity and mortality. Vitamin D is involved in various physiologic functions, including cellular responses during infection and inflammation. The aim of this study was to evaluate diagnostic value of 25-hydroxyvitamin D in childhood sepsis because it can be fatal if diagnosis delayed. The study included 40 children with sepsis and 20 children without sepsis (control group). We included only the patients with high probable sepsis, judged by clinical and laboratory findings, including positive blood culture. Blood samples were collected from patients with sepsis before treatment (pre-treatment group) and 48-72 hours later (post-treatment group). Treatment varied from ampicillin-sulbactam to cephalosporin. Blood samples were collected from control group once on admission. Serum 25-hydroxyvitamin D levels were significantly higher in sepsis (pre-treatment group) than control group (74 ± 8 ng/ml vs. 28 ± 12 ng/ml, p = 0.01) and the serum 25-hydroxyvitamin D levels were decreased to 44 ± 5 ng/ml (p = 0.01) after treatment. Moreover, we found significant positive correlation between 25-hydroxyvitamin D and each of well-know sepsis markers, C-reactive protein, tumor necrosis factor-α and interleukin-6. A cut-off point of 20 ng/mL for serum 25-hydroxyvitamin D showed 84% sensitivity and 76% specificity for sepsis diagnosis. This is the first study evaluating the diagnostic role of vitamin D in pediatric sepsis, thereby suggesting that serum 25-hydroxyvitamin D level can be used as a diagnostic marker for sepsis with high sensitivity and specificity.

Comparison of humoral immune response in heterologous and homologous COVID-19 booster vaccine groups using CoronaVac and mRNA-based BNT162b2 vaccines.

BACKGROUND: Heterologous COVID-19 booster vaccination is an alternative strategy to homologous vaccination, especially in developing countries, due to shortages, delays, or unequal distribution of COVID-19 vaccines. We compared cohorts vaccinated with different vaccine combinations to investigate whether a heterologous booster dose of mRNA-based BNT162b2 vaccine boosts the immune response in individuals primed with the CoronaVac vaccine. METHODS: Anti-RBD IgG is generally measured 4 weeks after primary immunization and 4 weeks after booster vaccination. Data on anti-receptor-binding domain (anti-RBD) IgG antibody titers and clinical characteristics were provided by infection control units. RESULTS: The highest median anti-RBD IgG antibody titers (14589 AU/mL) after primary immunization was observed in the group vaccinated with two doses of BNT162b2 vaccine. Antibody titers were lower 4 months or more after the second CoronaVac vaccine dose in CoronaVac recipients with or without previous COVID-19. In the homologous COVID-19 booster vaccine group (primed with two doses of CoronaVac 4 weeks apart and a single booster dose of CoronaVac) the median anti-RBD titers decreased from 1025 to 242 AU/mL before the booster dose. In the heterologous group (primed with two doses of CoronaVac 4 weeks apart and a single booster dose of BNT162b2), the median anti-RBD titer increased to 31624 AU/mL, a 132-fold increase, 16 days after the booster dose. CONCLUSIONS: After the second dose of CoronaVac, protective neutralizing antibody levels decrease over time, and a booster dose is required. Heterologous COVID-19 booster vaccination with BNT162b2 is effective at boosting neutralizing antibody levels.

Low 25-hydroxyvitamin D level and adiponectin is associated with insulin sensitivity in large gestational age infants.

OBJECTIVE: To investigate the relationship between adipokines (visfatin, adiponectin) and 25-hydroxyvitamin D (25(OH)D), and markers of insulin sensitivity in large for gestational age (LGA) infants. PATIENTS AND METHODS: Forty LGA infants (25 LGA born to diabetic mothers and 15 LGA born to non-diabetic mothers) and 34 appropriate for gestational age (AGA) infants were recruited. RESULTS: FGIR, QUICK-I, adiponectin and 25(OH)D levels were significantly lower in LGA with diabetic mother group than AGA and LGA with non-diabetic mother group. HOMA-IR, fasting insulin, visfatin and parathormone (PTH) levels were significantly higher in LGA with diabetic mother group than AGA and LGA with non-diabetic mother group. CONCLUSION: Based on the findings of this study, visfatin, adiponectin and 25(OH)D levels can be used as specific markers for insulin sensitivity and may help advance new therapies for glucose intolerance spectrum.

Increased fecal calprotectin in preterm infants with necrotizing enterocolitis.

BACKGROUND: Necrotizing entrocolitis (NEC) remains a potentially fatal disease in premature infants despite the recent advances in neonatal care. It is a disease with a multifactorial etiology leading to the one common final pathway of necrosis and inflammmation of the neonatal intestine. METHODS: Calprotectin is a calcium and zinc-binding protein in human neutrophils. Its concentration rises in various organic bowel diseases in adults and is resistant to degradation and has been proposed as a useful, simple, and rapid diagnostic method of inflammatory bowel disease that shows gastrointestinal inflammation in children and adults. RESULTS: We found that infants with necrotizing enterocolitis had increased fecal calprotectin concentrations, and there was a correlation between calprotectin concentrations and severity of NEC. CONCLUSIONS: We concluded that fecal calprotectin is a useful marker for diagnosis and severity of NEC in preterm infants.

VACTERL association: a new case with biotinidase deficiency and annular pancreas.

VACTERL (V - Vertebral anomalies, A - Anal atresia, C - Cardiovascular anomalies, T - Tracheoesophageal fistula, E - Esophageal atresia, R - Renal (Kidney) and/or radial anomalies, L - Limb defects) association includes vertebral defects, anal atresia, cardiac defects, tracheo-esophageal fistula, renal dysplasia, and limb anomalies. Less frequent defects seen with VACTERL association are prenatal and postnatal growth deficiency, laryngeal stenosis, ear anomaly, large fontanels, defect of lower limb, rib anomaly, tethered cord, and defects of external genitalia. We report a case of VACTERL association who had concomitant biotinidase deficiency and annular pancreas, which has not been previously reported.

Salmonella typhimurium infections in BALB/c mice: a comparison of tissue bioluminescence, tissue cultures and mice clinical scores.

In response to systemic infection, mice usually present specific behaviors such as reduced activity and feeding, ruffled fur, hunched position, ataxia and tremor. We aimed to compare tissue bioluminescence, tissue cultures and clinical scores of BALB/c mice as potentially complementary outcome measures of Salmonella disease progression In Balb/c mice. The clinical status of the mice was assessed by visual examination for motility, ruffled fur, hunched position, feeding, ataxia and tremor. Patterns of bioluminescent light emission indicated the progression of infection from the abdominal region (initial site) to secondary tissue sites, which was indicative of systemic infection. As the severity and progression of infection increased, the bioluminescence signal became both more prominent and more anatomically disseminated. Bioluminescent Imaging (BLI) of Salmonella that have been genetically engineered to be bioluminescent is a new method that gives the opportunity to track Salmonella dissemination in mice. BLI is a helpful method to estimate tissue Salmonella concentration and may reduce the number of mice used in experiments, providing the opportunity to obtain serial assessments of disease progression in a single mouse subject. Clinical scores helped us to assess the clinical status of BALB/c mice in systemic Salmonella infections.

Comparing beneficial effects of inhaled nitric oxide to L-arginine in necrotizing enterocolitis model in neonatal rats.

OBJECTIVE: Necrotizing enterocolitis (NEC) is a common and devastating gastrointestinal condition of neonatal infants. The pathophysiology of NEC remains poorly understood. We tried to evaluate the effectiveness of inhaled NO compared to L-arginine usage in necrotizing enterocolitis model in rats. MATERIAL-METHODS: 46 newborn pups from 4 time-mated Sprague-Dawley pregnant rats were divided equally into 4 groups as follows: NEC (subjected to NEC), NEC + L-arginine, NEC + inhaled NO and control. RESULTS: SOD, GSH-Px and NOx levels were significantly higher and MDA levels were significantly lower in NEC + inhaled NO group compared to NEC + L-arginine group. There was significantly lower intestinal injury and apoptosis index scoring in NEC + inhaled NO group compared to NEC + L-arginine group. CONCLUSION: We think that inhaled NO can be used as a novel therapeutic agent like L-arginine in NEC, like using in pulmonary hypertention in newborns but much more studies are needed.

A case of Mowat-Wilson syndrome caused by a truncating mutation within exon 8 of the ZEB2 gene.

Mowat-Wilson syndrome (MWS) is characterized by severe mental retardation with seizures, specific facial dysmorphism, Hirschsprung disease, anomalies of the corpus callosum, and genitourinary and cardiac malformations. The cause of MWS is a de novo mutation in the ZEB2 gene. This report describes a Turkish boy who was clinically diagnosed with MWS and had his diagnosis confirmed by molecular analysis of the ZEB2 gene. The investigation identified a heterozygous complex rearrangement in exon 8 of ZEB2, specifically a 48-nucleotide deletion and a 44-nucleotide insertion that caused a frameshift. MWS is a relatively newly identified disorder, and even MWS patients without Hirschsprung disease can be diagnosed easily based on clinical findings alone.

Role of cyclooxygenase 2 and endothelial nitric oxide synthetase in preclinical atherosclerosis.

Cyclooxygenase-2 and endothelial nitric oxide (NO) synthase enzymes may have a role in developing preclinical atherosclerosis. Designed groups were as follows: smoke exposed rats before and during pregnancy, only before pregnancy, and controls. Cross-sectional samples of abdominal aorta were examined immunohistochemically. Cyclooxygenase-2 and eNOS expression was evaluated semi-quantitatively through staining extent (focal, diffuse) and staining intensity. Diffuse COX-2 expression was detected in study groups. Endothelial NO synthase expression was diffuse in study groups. COX-2 and eNOS may contribute to the formation of preatherosclerotic lesions in offspring of rats exposed to cigarette smoke through inflammatory response.

Bilateral renal hypoplasia and cystic dysplasia: a new phenotype of Thomas syndrome or a new syndrome?

Thomas syndrome is a rare syndrome including Potter sequence, renal anomalies, heart defects, cleft palate with other oropharyngeal anomalies. Here, we report a newborn with Potter sequence, bilateral renal hypoplasia and cystic dysplasia, multiple cardiovascular malformations, long large ears, frontal bossing, small lips, partial simple toe syndactyly, and cleft palate. To our best knowledge, this patient may be considered as a new variant of Thomas syndrome or a new syndrome.

Partial rupture of the quadriceps muscle in a child.

BACKGROUND: The quadriceps femoris muscle ruptures usually occur in the middle-aged population. We present a 4-year-old patient with partial rupture of the quadriceps femoris muscle. To our knowledge, this is the youngest patient reported with a quadriceps femoris muscle rupture. CASE PRESENTATION: A 4-year-old girl admitted to our clinic with left knee pain and limitation in knee movements. Her father reported that she felt pain while jumping on sofa. There was no direct trauma to thigh or knee. We located a palpable soft tissue swelling at distal anterolateral side of thigh. The history revealed that 10 days ago the patient was treated for upper tract respiratory infection with intramuscular Clindamycin for 7 days. When we consulted the patient with her previous doctor and nurse, we learnt that multiple daily injections might be injected to same side of left thigh. MRI showed a partial tear of vastus lateralis muscle matching with the injection sites. The patient treated with long leg half-casting for three weeks. Clinical examination and knee flexion had good results with conservative treatment. CONCLUSIONS: Multiple intramuscular injections may contribute to damage muscles and make prone to tears with muscle contractions. Doctors and nurses must be cautious to inject from different parts of both thighs.

Impact of the 13-valent pneumococcal conjugate vaccine on the incidences of community-acquired pneumonia and pneumonia-related hospitalizations in children ≤5 years after its implementation into the national immunization program of Turkey.

The aim of the study was to investigate changes in the incidences of community-acquired pneumonia (CAP) and CAP-related hospitalizations following introduction of 13-valent pneumococcal conjugate vaccine (PCV13) in children ≤5 years of age into the national immunization programme (NIP) of Turkey. PCV7 was included in the NIP of Turkey in November 2008 and was replaced by PCV13 in late 2011. Changes in the incidences of CAP and CAP-related hospitalizations per 100,000 children admissions were investigated from 2011 to 2017. A total of 225,963 children visits were recorded; CAP was diagnosed in 4863 (2.15%) children and 1086 (22%) of them hospitalized between 2011 and 2017. The incidence of CAP declined from 5448 to 1144/100,000 from 2011 to 2017 (p = .001, r = -0.965). When the mean annual incidence of CAP between the transition period of PCV13 (2011/2012) was compared with a post-PCV13 period (2016/2017), CAP incidence was found to be 22% lower (p = .009). Also, the incidence of CAP-related hospitalization decreased significantly from 943 to 335/100,000 from 2011 to 2017 (p = .004 r = -0.91). Moreover, the mean incidence of CAP hospitalization declined 35% (p = .01) between the transition period of PCV13 and a post-PCV13 period. Thus, our study showed a significant reductions in the incidences of CAP and CAP-related hospitalization in children ≤5 years-old after the implementation of PCV13 into the NIP of Turkey.

Response to "Letter to the Editor: Vaccine Failures in Pediatric Cases Caused by Streptococcus pneumoniae Serotype 19A".

We are happy to answer to the Letter from Ozkaya-Parlakay et al. to the Editor commenting on our recent paper, 1  investigated impact of the 13-valent pneumococcal conjugate vaccine (PCV13)  on the incidences of community-acquired pneumonia and pneumonia-related hospitalizations in children ≤5 years after its implementation into the national immunization program (NIP) of Turkey.   Ozkaya-Parlakay et al. draw attention to vaccine failure and importance of continuous  surveillance of relevant disease especially in the perspective of  Streptococcus pneumoniae  serotype 19A. They supported their opinion by their clinical observation of seven children who were vaccinated with PCV13 developed empyema and meningitidis caused by Streptococcus pneumoniae  serotype 19A 
 in Turkey.

Impact of the 13-valent pneumococcal conjugate vaccine on the incidences of acute otitis media, recurrent otitis media and tympanostomy tube insertion in children after its implementation into the national immunization program in Turkey.

The aim of this study was to investigate changes in the incidences of acute otitis media (AOM), recurrent AOM (rAOM) and tympanostomy tube (TT) insertion in children following the introduction of 13-valent pneumococcal conjugate vaccine (PCV13) into the national immunization program (NIP) of Turkey in April 2011. National coverage for the PCV7 was 97% in 2009, 93% in 2010, 96% in 2011 and for the PVC13 was 97% in 2012, 97% in 2013, 96% in 2014, 97% in 2015, 98% in 2016, and 96% in 2017 for Turkish children younger than 12 months of age. A total of 499932 pediatric visits were recorded, and AOM was diagnosed in 23005 (4.6%) children. The incidence of AOM in children ≤5 years of age decreased from 10700/100000 (2011) to 4712/100000 (2017), with a significant decreasing trend (p < .001, r = -0.965). When the mean annual incidences of AOM between the transition period of PCV13 (years 2011/2012) were compared with those of a post-PCV13 period (years 2016/2017) for children ≤5 years of age, the incidence of AOM was found to be decreased by 54% (p = 0.013). The mean incidence of TT insertion was found to be decreased by 65% (p = 0.003) between the transition period of PCV13 and a post-PCV13 period for children ≤5 years of age. On the other hand, rAOM incidence was found to be increased in whole pediatric age groups. Our study showed a significant decrease in the incidences of AOM and TT insertion in children ≤5 years old after implementation of PCV13 in the NIP in Turkey.

Comparison of humoral immune response in heterologous and homologous COVID-19 booster vaccine groups using CoronaVac and mRNA-based BNT162b2 vaccines

ABSTRACT Background: Heterologous COVID-19 booster vaccination is an alternative strategy to homologous vaccination, especially in developing countries, due to shortages, delays, or unequal distribution of COVID-19 vaccines. We compared cohorts vaccinated with different vaccine combinations to investigate whether a heterologous booster dose of mRNA-based BNT162b2 vaccine boosts the immune response in individuals primed with the CoronaVac vaccine. Methods: Anti-RBD IgG is generally measured 4 weeks after primary immunization and 4 weeks after booster vaccination. Data on anti-receptor-binding domain (anti-RBD) IgG antibody titers and clinical characteristics were provided by infection control units. Results: The highest median anti-RBD IgG antibody titers (14589 AU/mL) after primary immunization was observed in the group vaccinated with two doses of BNT162b2 vaccine. Antibody titers were lower 4 months or more after the second CoronaVac vaccine dose in CoronaVac recipients with or without previous COVID-19. In the homologous COVID-19 booster vaccine group (primed with two doses of CoronaVac 4 weeks apart and a single booster dose of CoronaVac) the median anti-RBD titers decreased from 1025 to 242 AU/mL before the booster dose. In the heterologous group (primed with two doses of CoronaVac 4 weeks apart and a single booster dose of BNT162b2), the median anti-RBD titer increased to 31624 AU/mL, a 132-fold increase, 16 days after the booster dose. Conclusions: After the second dose of CoronaVac, protective neutralizing antibody levels decrease over time, and a booster dose is required. Heterologous COVID-19 booster vaccination with BNT162b2 is effective at boosting neutralizing antibody levels.

The effect of the pre-pregnancy weight of the mother and the gestational weight gain on the bilirubin level of term newborn.

OBJECTIVE: Jaundice is a problem in newborns. There are many maternal and infant-related factors affecting neonatal jaundice. The maternal pre-pregnancy weight, maternal body mass index (BMI) and gestational weight gain may have an effect on the newborn bilirubin levels. We research the effect of the maternal pre-pregnancy weight and gestational weight gain on the bilirubin levels of the newborn infants in the first 2 weeks prospectively. METHODS: Term and healthy infants who were born between 38 and 42 weeks in our clinic were included in the study. Maternal pre-pregnancy BMIs were calculated. Babies were divided into three groups according to their mothers' advised amount of gestational weight gain. Total serum bilirubin (TSB) values of the newborns were measured in the 2nd, 5th and 15th postnatal days. RESULTS: In our study, the 5th and 15th day capillary bilirubin level of the babies with mothers who gained more weight than the advised amount during pregnancy were found statistically significant higher compared to the other two groups (p < 0.05). Similarly, the hematocrit level of the babies with mothers who gained more weight than the advised amount were found statistically significant higher compared to the other two groups (p < 0.05). CONCLUSIONS: We conclude that the babies with mothers who gained more weight than the advised amount were under risk for newborn jaundice. Therefore, these babies should be monitored more closely for neonatal jaundice and prolonged jaundice.

The Association between Serum 25-Hydroxy Vitamin D Level and Urine Cathelicidin in Children with a Urinary Tract Infection.

OBJECTIVE: Cathelicidin is an important antimicrobial peptide in the urinary tract. Cathelicidin expression is strongly stimulated by 1,25-dihydroxy vitamin D in epithelial cells, macrophages/monocytes, and neutrophils. Vitamin D and cathelicidin status in children with urinary tract infection (UTI) caused by Escherichia coli is unknown. To establish the relationship between serum vitamin D and urine cathelicidin levels in children with a UTI caused by Escherichia coli. METHODS: Serum 25-hydroxy vitamin D and urine cathelicidin levels were measured in 36 patients with UTI (mean age 6.8±3.6 years, range: 0.25-12.6 years) and 38 controls (mean age 6.3±2.8 years, range: 0.42-13 years). RESULTS: There were no significant differences in urine cathelicidin levels between the study and control groups (p>0.05). Eight (22.2%) patients in the study group and 21 (58.3%) children in the control group were found to have sufficient vitamin D (≥20 ng/mL). Patients with sufficient vitamin D had higher urine cathelicidin levels than the controls with sufficient vitamin D (respectively 262.5±41.1 vs. 168±31.6 ng/mL, p=0.001). There were no significant differences between the patients and controls with insufficient vitamin D (p>0.05). CONCLUSION: The children with vitamin D insufficiency may not be able to increase their urine cathelicidin level during UTI caused by Escherichia coli. There is a need of prospective studies in order to prove a beneficial effect of vitamin D supplementation for the restoration of cathelicidin stimulation and consequently for prevention of UTI recurrence.