Heui Seung Jo

Increase in cord blood soluble E-selectin and tracheal aspirate neutrophils at birth and the development of new bronchopulmonary dysplasia.

Abstract Aim: To test the hypothesis that preterm infants who develop new type of bronchopulmonary dysplasia BPD have higher cord blood sE-selectin levels and neutrophil counts in the tracheal aspirate at birth than those who do not. Methods: The relationship between cord blood sE-selectin levels and neutrophil counts in the tracheal aspirate at birth and the development of BPD was examined in 30 preterm infants. Levels of sE-selectin and neutrophil counts were measured by specific immunoassay and by cytospin analysis. Results: Median cord blood levels of sE-selectin and neutrophil counts in the tracheal aspirate at birth were higher in preterm infants who developed BPD than in those who did not (P<0.01 for each). These differences persisted significantly after adjusting for the effects of gestational age and the presence of histologic chorioamnionitis and patent ductus arteriosus PDA (P<0.01 for each). Conclusion: Fetal pulmonary inflammation, as measured by increased cord blood levels of sE-selectin and neutrophil counts in the tracheal aspirate at birth, may be a risk factor for the development of new BPD in preterm infants. These results support the hypothesis that the lung injury responsible for new BPD in preterm infants can begin in the prenatal period and could be associated with a fetal pulmonary inflammation.

Recent Changes in the Incidence of Bronchopulmonary Dysplasia among Very-Low-Birth-Weight Infants in Korea.

We investigated the incidence of bronchopulmonary dysplasia (BPD) in very-low-birth-weight (VLBW) infants in Korea using the Korean Neonatal Network (KNN) data. In total, 2,386 VLBW infants born from January 2013 to June 2014 were prospectively registered. BPD was defined as supplemental oxygen or positive pressure support at 36 weeks postmenstrual age (PMA). The overall incidence of BPD was 28.9%, and the overall mortality rate in the neonatal intensive care units (NICUs) was 11.9%. To investigate recent changes in the incidence of BPD among VLBW infants, we compared the BPD rate in the present study with the latest nationwide retrospective survey conducted between 2007 and 2008. For comparison, we selected infants (23-31 weeks of gestation) (n=1,990) to adjust for the same conditions with the previous survey in 2007-2008 (n=3,841). Among the limited data on VLBW infants (23-31 weeks of gestation), the incidence of BPD increased by 85% (from 17.8% to 33.0%) and the mortality rate in the NICU decreased by 31.4% (from 18.8% to 12.9%) compared to those in the study conducted in 2007-2008. The current trend of increase in the incidence of BPD among infants can be attributed to the increase in the survival rate of VLBW infants.

Surfactant Protein A Associated with Respiratory Distress Syndrome in Korean Preterm Infants: Evidence of Ethnic Difference

Background: Insufficiency of the pulmonary surfactant system is the primary cause of respiratory distress syndrome (RDS) in preterm infants. Genetic factors, including specific single-nucleotide polymorphisms in the genetic components of surfactant protein A (SP-A1 and SP-A2), affect protein structure and function, as well as risk of RDS. Objective: We investigated the association between variations in SP-A genotypes and RDS within the genetically homogeneous Korean population. Methods: We used TaqMan® real-time polymerase chain reaction technology to assess nine single-nucleotide polymorphisms of SP-A in 261 full-term and 152 preterm infants. Among the preterm infants, 76 infants with RDS were matched with 76 control infants with respect to gestation, use of antenatal steroids and gender. Results: The SP-A2 1A⁰ variant and the homozygous 1A⁰/1A⁰ genotype were associated with protection from RDS (OR 0.31, 95% CI 0.13–0.78). In addition, the 1A1 carrier genotype (containing one copy of the 1A1 variant) was associated with increased risk of RDS (OR 2.42, 95% CI 1.06–5.52). The significance of these results is that the association of patterns with RDS was opposite to the findings of previous research with Finnish and North American study populations. Conclusions: We have identified associations between specific variants of the SP-A genes and RDS risk in the Korean preterm study population. Our data strongly support SP-A as a candidate gene for susceptibility to RDS, and reveal the dissimilarity of the associated risk/protective genetic variants between different ethnic study populations.

Double exposure to intra-amniotic lipopolysaccharide and maternal betamethasone induces sustained increase of neutrophils in the lungs and disrupts alveolarization in newborn rats.

Abstract Aim: We investigated the combined effects of intra-amniotic lipopolysaccharide (LPS) and maternal betamethasone (BMZ) on alveolarization using a newborn rat model. Methods: LPS (1.0 μg/sac) or vehicle was injected into the amniotic sacs of pregnant rats and BMZ (170 μg/kg) or vehicle was injected intramuscularly into the pregnant rats twice at 8-h intervals on gestation day 20. The rat pups were delivered spontaneously after 2–2.5 days and raised until the measurements were taken. Bronchoalveolar lavage was performed on days 2 and 5, and morphometric analyses of the lungs were performed on days 5 and 14. Results: Intra-amniotic LPS significantly increased the neutrophils in the bronchoalveolar lavage fluid (BALF) on day 2, but double exposure to LPS and BMZ significantly alleviated the neutrophil increase in the BALF. On day 5, while the neutrophils in the BALF decreased in the animals exposed to LPS alone, the neutrophil numbers in the BALF were steady in the animals exposed to both LPS and BMZ. Morphometric analyses on days 5 and 14 revealed a significant disruption of alveolarization only in the animals exposed to both LPS and BMZ. Conclusions: Our results suggested that double exposure to maternal BMZ and intra-amniotic LPS induces sustained increase of neutrophils in the lungs and disrupts alveolarization.

22q11.2 Microduplication with thyroid hemiagenesis.

Background: Chromosome 22q11.2 microduplications are extremely rarely detected; in comparison, the deletion of same region, known as the DiGeorge/velocardiofacial syndrome, occurs more frequently. Thyroid anomalies commonly occur in patients with 22q11.2 deletion syndrome, however few reports of thyroid anomalies associated with 22q11.2 microduplication have been published thus far. Case Report: We present a case of a male infant who was prenatally diagnosed with 22q11.2 microduplication and was found to have congenital hypothyroidism due to thyroid hemiagenesis after birth. Moreover, the baby had bilateral hearing impairment, bilateral cryptorchidism, and a rotated penis. At the age of 2 years, the infant was euthyroid with levothyroxine replacement, but he showed significant developmental delay. Conclusions: To our knowledge, this is the first case of congenital hypothyroidism with thyroid hemiagenesis in a patient showing 22q11.2 microduplication. Thyroid dysgenesis could be an additional clinical feature shared by the 22q11.2 microduplication and deletion syndrome, suggesting that the duplication and deletion of a gene may result in a common phenotype. Thyroid dysgenesis should be considered in the evaluation and management of patients with this genomic disorder.

A Rare Case of Pediatric T Lymphoblastic Leukemia With t(11;17)(q23;q21) Involving Mixed-Lineage Leukemia Gene Rearrangement

Dear Editor, T lymphoblastic leukemia (T-ALL) comprises 10-15% of pediatric ALL cases and is known to be a clinically and genetically heterogeneous disease [1]. Recent studies have presented various cytogenetic abnormalities in T-ALL. The alterations often present as reciprocal translocations implicated in several transcriptional factor genes and lead to arrest during T-cell differentiation [1,2]. Although cytogenetic aberrations are known to be critical in leukemogenesis of many hematologic malignancies, the relationships between these aberrations and the prognosis are not well understood in T-ALL except for t(11;19), a mixed-lineage leukemia gene (MLL)-ENL fusion related to favorable prognosis [3]. Here, we report a very rare case of pediatric T-ALL with t(11;17)(q23;q21) involving MLL rearrangement, which has not been previously reported in Korea. A 16-month-old boy was admitted to our hospital because of fever, cough, rhinorrhea, and poor oral intake. Physical examination revealed anemic conjunctiva, cervical lymph node enlargement, and splenomegaly. Chest radiography showed no abnormal findings. The complete blood count (CBC) results were as follows: hemoglobin, 8.2 g/dL; leukocytes, 41.3×109/L; platelets, 177×109/L; and reticulocyte count, 3.4%. The blood smear showed increased blasts (66%). The bone marrow (BM) specimen contained 65% blasts and showed a hypercellular pattern. Small-to-medium sized blasts were observed with condensed nuclear chromatin and an irregular nuclei margin. Immunophenotyping using the BM aspirate was brightly positive for CD2 (86%), cCD3 (91%), CD5 (91%), CD7 (92%), and CD34 (76%). Serum lactate dehydrogenase was increased to 638 IU/L. Cytogenetic studies on the BM revealed the karyotype of 46,XY,t(11;17)(q23;q21)[17]/46,XY[3] (Fig. 1A). The patient was diagnosed with T-ALL according to the 2008 WHO classification [4]. Fig. 1 Bone marrow karyogram at diagnosis and interphase FISH analysis after induction chemotherapy. (A) G-banded karyogram showing t(11;17)(q23;q21). The arrows denote the rearranged chromosomes. (B) FISH analysis using 11q23 break-apart probe revealed MLL ... The patient began receiving induction chemotherapy comprised of prednisolone, vincristine, L-asparaginase, intrathecal cytosine arabinoside, and methotrexate. He seemed to respond to chemotherapy, with decreasing leukocyte counts and spleen size. However, the BM aspirate performed on the 7th day showed increased blasts to 69%. Moreover, interphase FISH analysis using an 11q23 break-apart probe revealed MLL rearrangement (158 of 200, 79%) (Fig. 1B). He was switched to more intensive induction chemotherapy including doxorubicin and cyclophosphamide. The patient achieved complete remission after 28 days of re-induction chemotherapy. Because of his high-risk features, the patient received cord blood stem cell transplantation. At the time of writing, he is alive and has been in a continuous complete remission state for 26 months. MLL/11q23 rearrangement is intricate in many hematologic malignancies such as ALL, AML, and MDS. The 11q23 translocation, which is rarely identified in T-ALL, is a distinct subtype characterized by differentiation arrest at an early stage of thymocyte differentiation [5]. Since MLL fusion partners are also known to have an important role in leukemogenesis, recent efforts to unravel MLL fusion partners using long-distance inverse-PCR (LDI-PCR) as compensatory diagnostic method have been implemented by using current molecular diagnostic tools [6,7]. Not only scarce MLL rearrangement but also few fusion genes are involved in T-ALL, despite that 79 different MLL fusion partner genes have been identified in other hematologic malignancies [6,8]. When balanced t(11;17)(q23;q21) involving MLL rearrangement was searched on the molecular level, three different fusions with MLL at 11q23 were generated by proximally clustered genes at the same chromosomal loci: MLLT6/AF17, ACACA, and LASP1 at 17q21 [8]. Thus far, MLL with each of the other three fusion partner genes at 17q21 has been identified mainly in AML and rarely in ALL [8]. Unfortunately, the fusion partner gene in this case could not be confirmed by using LDI-PCR because of specimen problems. A literature search revealed only two cases regarding t(11;17)(q23;q21) in adults with T-ALL [9,10] (Table 1). Table 1 Reported cases of T-ALL with t(11;17)(q23;q21) Prior studies have suggested that immunophenotypic markers are correlated with genetic alterations in pediatric acute leukemia [2]. The immunophenotype of leukemic cells in our patient could be classified into the pre-T stage and immature stage according to the European Group for the Immunological Characterization of Leukaemias and T-cell receptor classification system [2]. The immature stage of T-ALL was reported with respect to poor outcome and the lack of a common genetic lesion [1,2]. In several studies, MLL-rearranged T-ALL overexpressed multiple HOX, which are transcription factors that initiate T-cell differentiation [5]. Additional cases involving genetic profiling of t(11;17)(q23; q21) involving MLL rearrangement will help assess whether this rare fusion impacts the disease progression and reveals prognostic information.

Is the Routine Insertion of a Gastric Tube Necessary for Full Term or LatePreterm Infants Admitted with Mild Respiratory Distress in NICU

Objectives: Gastric tubes are routinely in infants with transient tachypnea of newborn and mild respiratory distress. This study was conducted to investigate the need for routine insertion of gastric tube in full term and late preterm infants with mild respiratory distress admitted to the neonatal intensive care unit. Methods: This study was conducted on full term and late preterm infants who were admitted with mild respiratory distress to the Gangnam Cha Hospital NICU. From January to June 2014, a retrospective chart review was done 62 infants in the control group for whom an orogastric or nasogastric tube was routinely inserted and whose feedings were increased before gastric tubes were removed. In the experimental group infants, from July to September 2014, no gastric tube was inserted or was inserted for the identification of choanal atresia and for gastric contents aspiration and then removed rapidly. Results: The mean gestational age and birth weight of the infants in the experimental group were 37.2 ± 3.6 weeks and 2866 ± 337 gm, respectively, and those in the control group, 37.2 ± 3.2 weeks and 2849 ± 677 gm. There were no infants who needed intubation and CPAP or mandatory ventilator support. Most of the subjects in the experimental and control group were diagnosed with transient tachypnea of the newborn. The mean achieving age at full enteral feeding of experimental group infants was 4.76 days that for the control group infants, 4.67 day. The duration of hospital stay was 7.15 days for the experimental group infants and 7.23 days control group infants. Conclusion: We concluded that the routine use of a gastric tube for term and late preterm infants admitted with mild respiratory distress in NICU may be unnecessary, and that either a gastric tube should not be used at all for such infants or the period of its use should be minimized.