Publications by authors named "Chien-Chou Hsiao"

24 Publications

  • Page 1 of 1

Heat Shock Protein-70 Levels Are Associated With a State of Oxidative Damage in the Development of Bronchopulmonary Dysplasia.

Front Pediatr 2021 26;9:616452. Epub 2021 May 26.

Department of Pediatrics, Changhua Christian Children's Hospital, Changhua, Taiwan.

Heat shock protein-70 (Hsp-70) exhibits cytoprotective effects against oxidative stress-induced airway injury. This study aimed to examine Hsp-70 and 8-hydroxy-2'-deoxyguanosine (8-OHdG) from tracheal aspirates (TA) in very low-birth weight (VLBW) preterm infants to predict the development of bronchopulmonary dysplasia (BPD). This birth cohort study enrolled 109 VLBW preterm infants, including 32 infants who developed BPD. Hsp-70 and 8-OHdG concentrations from TA were measured by immunoassay. The apoptosis of TA epithelial cells obtained on Day 28 after birth was measured using annexin-V staining assay. Hsp-70 and 8-OHdG levels in TA fluid were persistently increased from Day 1 to Day 28 of life in the BPD group. Multiple linear regression analysis demonstrated that BPD was significantly associated with gestational age, respiratory distress syndrome, and TA Hsp-70 and 8-OHdG levels on post-natal Day 28. The TA Hsp-70 level positively correlated with TA 8-OHdG level on the Day 1 ( = 0.47) and Day 28 of life ( = 0.68). Incubation of recombinant Hsp-70 with primary epithelial cells derived from TA of patients decreased hydrogen peroxide-induced epithelial cell death. Hsp-70 levels are associated with a state of oxidative injury in the development of BPD.
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http://dx.doi.org/10.3389/fped.2021.616452DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8187579PMC
May 2021

Parenteral nutrition with fish oil-based lipid emulsion reduces the risk of cholestasis in preterm infants.

J Int Med Res 2021 May;49(5):3000605211011805

Division of Neonatology, Department of Pediatrics, Changhua Christian Children's Hospital, Changhua, Taiwan.

Objective: Preterm infants receive long-term parenteral nutrition (PN) for gastrointestinal immaturity. This study aimed to determine if mixed lipid emulsions containing fish oil decrease the incidence of PN-associated cholestasis by reducing oxidative stress and providing an anti-inflammatory effect.

Methods: This retrospective cohort study enrolled 399 very low birth weight premature infants (gestational age ≤32 weeks) between January 2009 and November 2017 at a single neonatal intensive care unit. Preterm infants received total PN with either mixed lipid emulsion including fish oil (SMOFlipid®, n = 195) or soybean oil-based lipid emulsion (Lipovenoes®, n = 204) for at least 7 days. We compared the outcomes of PN-associated cholestasis, comorbidities, and mortality between the groups.

Results: The incidence of PN-associated cholestasis was significantly lower in the SMOFlipid group than in the Lipovenoes group. The duration to full feeding days was significantly shorter in the SMOFlipid group compared with the Lipovenoes group. Relevant complications, such as severe retinopathy of prematurity and bronchopulmonary dysplasia, were also significantly reduced in the SMOFlipid group compared with the Lipovenoes group.

Conclusion: In premature infants, PN with fish oil-based lipid emulsions is associated with a lower incidence of PN-associated cholestasis compared with soybean oil-based lipid emulsions.
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http://dx.doi.org/10.1177/03000605211011805DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8127804PMC
May 2021

Implementation of nutrition practice improves growth velocity and weight gain in premature infants ≤ 1250 grams.

Pediatr Neonatol 2020 10 3;61(5):534-541. Epub 2020 Jun 3.

Department of Nutrition, Chung Shan Medical University, Taichung, 40201, Taiwan; Department of Nutrition, Chung Shan Medical University Hospital, Taichung, 40201, Taiwan. Electronic address:

Background: The concept of parental nutritional care for premature infants has been applied and advanced over the past decade. This study compared the clinical outcomes before and after nutrition practice (NP) implementation and evaluated the effects of implementation on growth velocity and weight gain in premature infants.

Methods: Descriptive data of premature infants (gestational age < 30 weeks; body weight ≤ 1250 g) born 4 years before and after NP implementation were retrospectively reviewed in a neonatal intensive care unit at a hospital in Taiwan. Nutrient intake, growth velocity, weight gain, and nutrition-related biochemical markers were compared at weeks 1, 2, and 4 after delivery.

Results: A total of 77 premature infants were enrolled before NP implementation (non-NP group), whereas 89 were enrolled after implementation (NP group). The non-NP group consumed less fat and energy in week 1, and less protein, fat, and energy in weeks 2 and 4 compared with the NP group. Growth velocity was slower in the non-NP group. Fat intake was significantly positively correlated with body weight at week 4 in the non-NP group. However, protein and fat intake were significantly associated with body weight at week 1, fat and energy intakes were significantly associated with body weight at week 2, and fat intake was significantly associated with body weight at week 4 in the NP group.

Conclusion: These findings indicate that the NP implemented in this study is relatively safe and can improve growth velocity and body weight gain in premature infants.
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http://dx.doi.org/10.1016/j.pedneo.2020.05.013DOI Listing
October 2020

Pomegranate extract inhibits migration and invasion of oral cancer cells by downregulating matrix metalloproteinase-2/9 and epithelial-mesenchymal transition.

Environ Toxicol 2020 Jun 29;35(6):673-682. Epub 2020 Jan 29.

Department of Biomedical Science and Environmental Biology, Kaohsiung Medical University, Kaohsiung, Taiwan.

Discovering drug candidates for the modulation of metastasis is of great importance in inhibiting oral cancer malignancy. Although most pomegranate extract applications aim at the antiproliferation of cancer cells, its antimetastatic effects remain unclear, especially for oral cancer cells. The aim of this study is to evaluate the change of two main metastasis characters, migration and invasion of oral cancer cells. Further, we want to explore the molecular mechanisms of action of pomegranate extract (POMx) at low cytotoxic concentration. We found that POMx ranged from 0 to 50 μg/mL showing low cytotoxicity to oral cancer cells. In the case of oral cancer HSC-3 and Ca9-22 cells, POMx inhibits wound healing migration, transwell migration, and matrix gel invasion. Mechanistically, POMx downregulates matrix metalloproteinase (MMP)-2 and MMP-9 activities and expressions as well as epithelial-mesenchymal transition (EMT) signaling. POMx upregulates extracellular signal-regulated kinases 1/2 (ERK1/2), but not c-Jun N-terminal kinase (JNK) and p38 expression. Addition of ERK1/2 inhibitor (PD98059) significantly recovered the POMx-suppressed transwell migration and MMP-2/-9 activities in HSC-3 cells. Taken together, these findings suggest to further test low cytotoxic concentrations of POMx as a potential antimetastatic therapy against oral cancer cells.
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http://dx.doi.org/10.1002/tox.22903DOI Listing
June 2020

Effects of fish oil-containing lipid emulsions on retinopathy of prematurity in very low birth weight infants.

Pediatr Neonatol 2020 04 30;61(2):224-230. Epub 2019 Nov 30.

Department of Neonatology, Changhua Christian Children's Hospital, Changhua, Taiwan; Institute of Medicine, Chung Shan Medical University, Taichung, Taiwan; School of Medicine, Kaohsiung Medical University, Taiwan. Electronic address:

Background: The aim of the study was to assess the impact of different types of parenteral emulsions on retinopathy of prematurity (ROP) in very low birth weight (VLBW, birth body weight < 1500 g) infants by comparing fish oil-containing and soy-based parenteral emulsions.

Methods: Data of preterm infants with body weights below 1500 gm at birth and receiving total parenteral nutrition (TPN) for a minimum of 7 days during the period between January 2009 and November 2017 were analyzed in this retrospective study. We compared clinical outcomes in two epochs using different lipid emulsions: epoch 1 (soybean-based lipid emulsions, January 2009-February 2014) versus epoch 2 (fish oil-containing lipid emulsions, January 2015-November 2017). The primary outcomes measured were the incidence of ROP and the number of ROP cases requiring bevacizumab therapy.

Results: A total of 396 infants were enrolled in this study (203 in epoch 1 and 193 in epoch 2). A lower incidence of any stage ROP (24.1 vs. 11.4%, p < 0.001) and lower requirement of bevacizumab therapy (12.8 vs. 5.2%, p = 0.001) were observed in epoch 2. Gestational age, glutamic-pyruvic transaminase, total bilirubin, and alkaline phosphatase levels, and type of lipid emulsion in TPN were associated with higher ROP incidence. Multivariate logistic regression analysis revealed that parenteral nutrition in the form of lipid emulsions containing fish oil was associated with a lower risk of development of ROP [Odds Ratio: 0.178, 95% confidence interval (CI): 0.095-0.330, p < 0.001].

Conclusions: Compared with soybean-based lipid solutions, the use of fish oil-containing lipid solutions may be associated with a lower incidence of ROP and decreased need for bevacizumab treatment in preterm infants.
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http://dx.doi.org/10.1016/j.pedneo.2019.11.010DOI Listing
April 2020

Intravenous immunoglobulin therapy enhances suppressive regulatory T cells and decreases innate lymphoid cells in children with immune thrombocytopenia.

Pediatr Blood Cancer 2020 02 17;67(2):e28075. Epub 2019 Nov 17.

Division of Pediatric Hematology-Oncology, Department of Pediatrics, Changhua Christian Children's Hospital, Changhua City, Taiwan.

Background: This study aimed to investigate the relationship between CD4 regulatory T cells (Tregs) and innate lymphoid cells (ILCs) in children with primary immune thrombocytopenia (ITP) undergoing high-dose intravenous immunoglobulin (IVIG) therapy.

Methods: We enrolled a cohort of 30 children with newly diagnosed ITP and 30 healthy controls and collected blood samples for levels of Tregs, ILCs, relevant cytokines, and Treg suppression assay at the diagnosis, two days, four weeks, and one year (only platelet count) after high-dose IVIG treatment. IVIG partial responders was defined by a platelet count less than 100 × 10 /L at 12 months after IVIG treatment.

Results: Children with newly diagnosed ITP exhibited elevated levels of ILC1, ILC2, ILC3, Th17, myeloid dendritic cells (DCs), plasmacytoid DCs, and serum IFN-γ and IL-17A levels, accompanied by a decrease in IL-10-producing Tregs. High-dose IVIG therapy reversed these aberrations. Platelet counts positively correlated with Tregs (rho = 0.72) and negatively correlated with both ILC1 (rho = -0.49) and ILC3 (rho = -0.60) (P < 0.05). Significantly lower Tregs and higher ILC1, ILC3, DCs, and serum IL-17A levels were noted in the partial responders (n = 8) versus responders (n = 22; P < 0.05). We found that Tregs suppressed proliferation of ILCs and CD4 T cells in CD25-depleted peripheral PBMCs and enhanced the apoptosis of CD4 CD45RO T cells in vitro following IVIG therapy.

Conclusions: Effective high-dose IVIG therapy for children with newly diagnosed ITP appears to result in the induction of Tregs, which suppresses ILC proliferation in vitro and is associated with platelet response.
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http://dx.doi.org/10.1002/pbc.28075DOI Listing
February 2020

Intravenous fish oil containing lipid emulsion attenuates inflammatory cytokines and the development of bronchopulmonary dysplasia in very premature infants: A double-blind, randomized controlled trial.

Clin Nutr 2019 06 18;38(3):1045-1052. Epub 2018 Jun 18.

Institute of Medicine, Chung Shan Medical University, Taichung, Taiwan; Department of Pediatrics, Changhua Christian Children's Hospital, Changhua, Taiwan; School of Medicine, Kaohsiung Medical University, Taiwan. Electronic address:

Background & Aims: Preterm infants have lower levels of long-chain polyunsaturated fatty acids (LCPUFAs). Supplementing very premature infants with intravenous lipid emulsions that fish oil, which is rich in n-3 LC-PUFAs, may decrease bronchopulmonary dysplasia (BPD) by modulating inflammation and neonatal immune function.

Methods: Sixty very low birth weight (VLBW) premature infants requiring ventilator support were randomized in a double-blind manner to 2 groups and received total parenteral nutrition with fish oil containing LE (intervention group, n = 30) or soybean oil containing LE (control group, n = 30) for 7 days. Blood samples and bronchoalveolar lavage fluid (BALF) were obtained for assay on day 1 and 7 days after LE. The primary outcome was to compare the levels of interleukin (IL)-1β and IL-6 in serum and BALF. Secondary outcomes were to compare mortality and co-morbidities.

Results: The levels of IL-1β and IL-6 in serum and BALF were significantly lower in the intervention group at day 8 (p < 0.05). The incidence of BPD in the intervention group compared to the control group was 13.3% versus 36.7% (p = 0.04; odds ratio [OR], 0.36; 95% confidence interval [CI], 0.21-0.86). The duration of ventilator support and oxygen use was significantly less in the intervention group than in the control group (p < 0.05). The level of alanine aminotransferase was significantly lower in the intervention group on day 8 (p = 0.031).

Conclusions: In very premature infants, early administration of fish oil containing LE significantly decreased IL-1β and IL-6 levels in serum and BALF and was associated with shorter duration of ventilator support and less bronchopulmonary dysplasia (BPD).

Trial Registration Number: ISRCTN 11427103.
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http://dx.doi.org/10.1016/j.clnu.2018.06.929DOI Listing
June 2019

Correlates of Elevated Interleukin-6 and 8-Hydroxy-2'-Deoxyguanosine Levels in Tracheal Aspirates from Very Low Birth Weight Infants Who Develop Bronchopulmonary Dysplasia.

Pediatr Neonatol 2017 02 30;58(1):63-69. Epub 2016 May 30.

Department of Pediatrics, Changhua Christian Children's Hospital, Changhua City, Taiwan; School of Medicine, Kaohsiung Medical University, Kaohsiung City, Taiwan; School of Medicine, Chung Shan Medical University, Taichung City, Taiwan. Electronic address:

Background: Bronchopulmonary dysplasia (BPD) remains the most common complication of very low birth weight (VLBW) preterm infants, and inflammatory regulation plays a role in the development of the BPD. Interleukin-6 (IL-6) has an important role in airway inflammation and therefore can be used as a marker of airway injury. The study aimed to compare the changes between IL-6 and oxidative stress marker with 8-hydroxy-2'-deoxyguanosine (8-OHdG) from serum and tracheal aspiration (TA) in VLBW preterm infants following development of BPD.

Methods: This birth cohort study enrolled 80 VLBW preterm infants, including 26 who developed BPD. All infants completed the study and survived at 36 weeks postmenstrual age. IL-6 and 8-OHdG concentrations from serum and TA on Day 1 and Day 28 after birth were measured using immunoassay.

Results: IL-6 and 8-OHdG in serum and TA were higher in the BPD group than in the non-BPD group on the 1 day after birth (p < 0.05). The IL-6 and 8-OHdG levels in TA fluid were persistently increased on the 28 day of life in the BPD group (p < 0.05). The TA IL-6 was positively correlated with 8-OHdG levels on the 1 day (r = 0.64, p < 0.05) and 28 day of life (r = 0.76, p < 0.05). Based on receiver operating characteristic curves as a predictor of BPD development, TA IL-6 (cutoff, 456.8 pg/mg) had 81.5% sensitivity and 77.8% specificity, whereas TA 8-OHdG (cutoff, 4.4 ng/mg) had a sensitivity of 81.5% and a specificity of 64.4%.

Conclusion: Persistent inflammation with oxidative DNA damage in the respiratory tract may be a crucial mechanism in BPD.
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http://dx.doi.org/10.1016/j.pedneo.2016.01.004DOI Listing
February 2017

Comparison of the Educational Needs of Neonatologists and Neonatal Nurses Regarding Palliative Care in Taiwan.

Am J Hosp Palliat Care 2016 Apr 28;33(3):264-71. Epub 2014 Nov 28.

College of Nursing, National Yang-Ming University, Taiwan (ROC)

Background: Education and training are very critical to development of high-quality neonatal palliative care. However, little investigation has been done into Taiwanese neonatal clinicians' educational needs regarding neonatal palliative care.

Purposes: The purposes of this study were to characterize and identify neonatal clinicians' educational needs regarding neonatal palliative care.

Methods: A cross-sectional descriptive surveyed method via a self administered questionnaire was used in this research. Thirty neonatologists were recruited by a convenience sampling and 30 nurses were recruited by a randomized sampling.

Results: Out of sixty neonatal clinicians' survey, few had received the education in neonatal palliative care. Most reported minimal training in, experience with, and knowledge of neonatal palliative care. For neonatologists, two of twelve most strongly-felt educational needs were "discussing palliative care and ethical decision-making with parents" (70%) and "informing parents the poor progress in neonates" (63.3%). In contrast, neonatal nurses wanted more training regarding pain control (50%). Communication skills, including the discussing poor prognosis, bad news, and code status and talking with neonates about end-of-life care, were the educational need most commonly felt by both neonatologists and nurses.

Conclusions: Survey data from neonatologists and neonatal nurses in Taiwan indicate a need for further training on a range of neonatal palliative care competencies.
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http://dx.doi.org/10.1177/1049909114559068DOI Listing
April 2016

Early optimal nutrition improves neurodevelopmental outcomes for very preterm infants.

Nutr Rev 2014 Aug 17;72(8):532-40. Epub 2014 Jun 17.

Department of Neonatology, Changhua Christian Hospital, Changhua, Taiwan; School of Medicine, Chung Shan Medical University, Taichung, Taiwan.

Recent advances in perinatal and neonatal intensive care have resulted in significant improvements in the survival of preterm extremely low-birthweight (PELBW) infants; however, extrauterine growth restriction (EUGR) and undernutrition occur frequently during hospitalization and are associated with adverse outcomes, including bronchopulmonary dysplasia, sepsis, and neurodevelopmental impairment. Early optimal parenteral nutrition with adequate amino acids and lipids, especially long-chain polyunsaturated fatty acids, has been shown to decrease the incidence of EUGR, bronchopulmonary dysplasia, necrotizing enterocolitis, sepsis, and retinopathy of prematurity in animal models and clinical trials. In PELBW infants, breast milk and probiotics have been shown to reduce the incidence of necrotizing enterocolitis, and lactoferrin has been demonstrated to prevent late-onset sepsis. Thus, early administration of optimal postnatal parenteral and enteral nutrients can help prevent neurodevelopmental impairment caused by EUGR, necrotizing enterocolitis, sepsis, bronchopulmonary dysplasia, and retinopathy of prematurity, and recent evidence indicates such treatment is feasible.
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http://dx.doi.org/10.1111/nure.12110DOI Listing
August 2014

Pigtail catheters versus traditional chest tubes for pneumothoraces in premature infants treated in a neonatal intensive care unit.

Pediatr Neonatol 2014 Oct 19;55(5):376-80. Epub 2014 Mar 19.

Division of Neonatology, Department of Pediatric, Changhua Christian Hospital, Changhua, Taiwan; Medical College of Chung Shan Medical University, Taichung, Taiwan. Electronic address:

Background: Pneumothorax is more frequent in the neonatal period, especially among premature infants. Pigtail catheters have been shown to be as effective as and less invasive than traditional chest tubes in adults; however, data regarding premature infants are limited. We aimed to compare the efficacy, safety, and complications associated with the placement of traditional chest tubes versus pigtail catheters in premature infants with pneumothoraces.

Methods: We retrospectively reviewed the medical records of premature infants with pneumothorax seen in the neonatal intensive care unit of a single medical center over a period of 11 years, who were treated with either traditional chest tubes or pigtail catheters. Changes in the vital signs before and after the procedures were recorded in both groups. Data on age, sex, clinical presentation, procedure time, subsequent therapies, hospital days to discharge, success rate, and complications of the procedures were collected from medical records and compared between the two methods of intervention.

Results: Eighty-six thoracostomies, including 60 pigtail catheters and 26 traditional chest tubes, were performed in 66 premature infants. The success rate, demographics, days of tube insertion, length of hospital stay, days of mechanical ventilation, type of oxygen supply, and insertion-related complications were not significantly different between the two groups. Pigtail catheter insertion required a shorter procedure time than the traditional chest tube insertion (14.92 minutes vs. 25.31 minutes, respectively, p < 0.001).

Conclusion: Pigtail catheters are a safe and effective alternative to traditional chest tubes for premature infants receiving treatment for pneumothoraces in a neonatal intensive care unit. Placement of pigtail catheters is an easy and quick bedside procedure and is particularly useful for premature infants who require immediate air drainage.
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http://dx.doi.org/10.1016/j.pedneo.2014.01.002DOI Listing
October 2014

Diverse effects of parenteral arginine on systemic and local oxidant-antioxidant homeostasis and nitrosative stress in rats with subacute peritonitis.

J Surg Res 2014 Mar 9;187(1):134-41. Epub 2013 Oct 9.

Department of Nutritional Science, Fu Jen Catholic University, New Taipei City, Taiwan, Republic of China. Electronic address:

Background: The beneficial effects of arginine on oxidative stress have been previously reported; however, excess production of nitric oxide, an arginine metabolite, may cause hemodynamic instability and inflammatory response. Previous studies have demonstrated that parenteral arginine levels at 2%-4% of total calories may alleviate inflammation and enhance immunity, whereas greater than 6% of total calories may have adverse effects in rats with subacute peritonitis. Herein, we investigated the effects of parenteral arginine dose on lipid peroxidation (thiobarbituric acid reactive substances, TBARS) and antioxidant enzyme activities in the plasma and organs.

Materials And Methods: Male Wistar rats with cecal puncture-induced subacute peritonitis were infused with parenteral nutrition solutions containing 1.61% (CP group), 2.85% (LA group), 4.08% (MA group), and 6.54% (HA group) of total calories as arginine for 7 d. Healthy, orally fed rats (NC group) were used as references.

Results: Subacute peritonitis significantly elevated the levels of nitrate, nitrite and TBARS in the plasma and decreased glutathione peroxidase activity in the kidneys. These changes were significantly reversed in the MA and HA groups. The MA and HA groups had significantly increased nitrotyrosine levels in the plasma. The LA, MA, and HA groups had significantly increased glutathione peroxidase activity in the plasma, cytochrome P450 levels in the liver, and nitrotyrosine levels in the heart and had significantly decreased TBARS levels in the kidneys compared with the CP group.

Conclusions: Our results suggest that parenteral arginine at a dose less than 4% of total calories may attenuate lipid peroxidation and increase antioxidant enzyme activities without leading to nitrosative stress in subacute peritonitis.
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http://dx.doi.org/10.1016/j.jss.2013.10.002DOI Listing
March 2014

The accuracy of a glucose-oxidase-based point-of-care glucometer in premature infants.

Arch Dis Child Fetal Neonatal Ed 2013 Nov 9;98(6):F545-8. Epub 2013 Jul 9.

Department of Neonatology, Changhua Christian Hospital, , Changhua, Taiwan.

Objective: The purpose of this study was to evaluate the accuracy of a novel commercial glucose-oxidase (GO)-based glucometer in measuring glucose concentrations in arterial blood samples collected from premature infants.

Patients And Methods: A commercial glucometer, which is a plasma separation GO-based glucometer, was employed to compare the accuracy of the commercial blood glucometer with that of a standard glucose analyser for monitoring blood glucose levels in premature infants. Arterial blood samples were collected and analysed, including samples adjusted for specific glucose (3.6 mmol/L, 8.3 mmol/L and 16.7 mmol/L) and PaO2 levels (range, 40-400 mm Hg).

Results: In total, 159 samples were collected. Bland-Altman analysis showed good correlation between the commercial glucometer and standard glucose analyser. Error-grid analysis revealed that all of the results were within zone A (ie, the clinically accurate estimate zone). The biases between the two systems were low at different PaO2 levels and haematocrits. Finally, the influence of different PaO2 levels was within acceptable ranges.

Conclusions: The GO-based glucometer evaluated in this study provides accurate results even when measured at high PaO2 and different haematocrits and is suitable for measuring arterial glucose levels in premature infants.
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http://dx.doi.org/10.1136/archdischild-2012-303613DOI Listing
November 2013

Nationwide population-based epidemiologic study of childhood and adulthood intussusception in Taiwan.

Pediatr Neonatol 2013 Jun 27;54(3):188-93. Epub 2013 Feb 27.

Department of Pediatrics, Changhua Christian Hospital, Changhua, Taiwan.

Background: Most studies have evaluated the epidemiology of intussusception only in children. This was the first nationwide population-based study conducted to investigate the epidemiology and associated medical expenses of intussusception for all age groups in Taiwan.

Methods: Cases of intussusception were identified from the annual hospitalization discharge claims of the National Health Insurance Research Database with corresponding International Classification of Diseases, Ninth Revision (ICD-9) code 560.0, from January 2000 to December 2007.

Results: In total, 7255 incident cases of intussusception were detected. The majority of cases were children younger than 4 years of age. Significant male predominance was observed in the under-10-, 55-59-, and older-than-80-year age groups. The incidence peaked in the 1-2-year age group, reaching as high as 112.84 and 81.96 per 100,000 person-years for males and females, respectively. The incidence of intussusception was very low in adults. However, the medical expenses, number of coexisting neoplasms and malignancies, and hospitalization days were substantially higher in adults than in children. Although coexisting neoplasms developed in 40.8% of adult patients with intussusception, it occurred in only 0.4% of those younger than 3 years.

Conclusion: This study is the first to describe detailed age- and sex-specific incidence rates and medical expenses of intussusception for both pediatric and adult groups in Taiwan. There were significant differences between the two groups, with a much higher incidence in young children, but more coexisting neoplasms and malignancies and average medical expenses in adult patients.
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http://dx.doi.org/10.1016/j.pedneo.2013.01.004DOI Listing
June 2013

Oral ibuprofen versus intravenous indomethacin for closure of patent ductus arteriosus in very low birth weight infants.

Pediatr Neonatol 2012 Dec 29;53(6):346-53. Epub 2012 Sep 29.

Division of Neonatal Medicine and Pediatric Cardiology, Department of Pediatrics, Changhua Christian Hospital, Changhua, Taiwan.

Background: The purpose of this study is to compare the effects and complications of pharmacologic closure of patent ductus arteriosus (PDA) by intravenous indomethacin or oral ibuprofen in neonates weighing <1500 g at birth [very low birth weight (VLBW) infants].

Methods: This is a retrospective study of infants treated with intravenous indomethacin (0.2 mg/kg initially followed by two doses at 24-hour intervals) or oral ibuprofen (10 mg/kg initially followed an interval of 24 hours by two doses of 5 mg/kg) for symptomatic PDA in a neonatal intensive care unit at a medical center in Taiwan during the period of January 2005 to December 2010.

Results: A total of 88 infants received indomethacin and 52 received oral ibuprofen. Among the survivors, the closure rate without surgical ductal ligation was 70.5% (62/88) in the indomethacin group and 61.5% (32/52) in the ibuprofen group (p = 0.342). The incidence rates of oliguria and elevated serum creatinine were significantly lower in the ibuprofen group (p =0.002 and p =0.022, respectively). There was no significant difference in incidence of upper gastrointestinal hemorrhage or necrotizing enterocolitis between the ibuprofen and indomethacin groups (17.3% versus 23.9%; 3.8% versus 11.3%).

Conclusion: In infants with VLBW, oral ibuprofen is as effective as intravenous indomethacin for closure of PDA and is associated with significantly fewer cases of necrotizing enterocolitis among infants with birth body weights <1250 g and significantly lower rates of elevated creatinine levels among neonates with birth body weights ranging from 1000 to 1500 g.
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http://dx.doi.org/10.1016/j.pedneo.2012.08.011DOI Listing
December 2012

The dose-dependent immunoregulatory effects of the nitric oxide synthase inhibitor N(G)-nitro-L-arginine methyl ester in rats with sub-acute peritonitis.

PLoS One 2012 3;7(8):e42467. Epub 2012 Aug 3.

Department of Pediatrics, Clinical Nutrition Support Service Team, Changhua Christian Hospital, Changhau, Taiwan.

Background: Chronic inflammation accompanied by arginine deficiency, immune dysfunction, and excess nitric oxide (NO) production is a clinical condition found in patients with peritonitis. A previous study showed that the nonselective NOS inhibitor N(G)-nitro-L-arginine methyl ester (L-NAME) may facilitate the metabolism of the immune nutrient arginine without altering NO homeostasis in rats with sub-acute peritonitis. Here, we investigated the effects of L-NAME on the immunocytic subpopulation distribution and response.

Materials And Methods: Male Wistar rats with cecal puncture-induced peritonitis were administered parenteral nutrition solutions supplemented with 0 (CPP group), 5 (LNA group), 25 (MNA group) or 50 (HNA group) mg · kg(-1) · day(-1) of L-NAME for 7 days. Parenteral-fed sham-operated rats (TPN group) and orally-fed healthy rats (R group) were included as controls.

Results: The TPN group had significantly increased spleen weights and levels of plasma nitrite/nitrate (NOx), circulating white blood cells (WBC), and splenocytic T cells, as well as significantly decreased levels of cytotoxic T- and B-leukocytes and B-splenocytes compared to the R group. The CPP group had significantly decreased levels of plasma NOx and concanavalin (Con) A-stimulated interferon (IFN)-γ and interleukin (IL)-2 production by leukocytes and significantly increased production of Con A-stimulated tumor necrosis factor (TNF)-α and lipopolysaccharide (LPS)-stimulated IFN-γ in the leukocytes. In addition, the LNA and MNA groups had significantly decreased spontaneous IL-6 and Con A-stimulated TNF-α and IFN-γ production by the leukocytes while the HNA group had significantly increased LPS-stimulated TNF-α and Con A-stimulated IFN-γ and IL-2 production by the splenocytes compared to the CPP group.

Conclusions: Low-dose L-NAME infusion may suppress proinflammatory and T-helper-1 (Th1) response in leukocytes, and high-dose infusion may activate the proinflammatory response in splenic macrophages and Th1 response in T-splenocytes in rats with sub-acute peritonitis.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0042467PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3411778PMC
January 2013

Combination treatment of parenteral arginine and nitric oxide inhibitor N(G)-nitro-L-arginine methyl ester in rats with peritonitis.

J Surg Res 2013 May 18;181(1):99-105. Epub 2012 Jun 18.

Division of Pediatric Surgery, Department of Surgery, Changhua Christian Hospital, Changhua, Taiwan.

Purpose: It has been shown that parenteral arginine may facilitate ureagenesis and improve leukocytic and splenocytic immunity and that the infusion of nitric oxide synthase inhibitor N(G)-nitro-L-arginine methyl ester (L-NAME) may facilitate the production of arginine-associated amino acids in rats with subacute peritonitis. Herein, we investigated the effects of the combined treatment of parenteral arginine and L-NAME on arginine metabolism and inflammatory response.

Methods And Materials: Male Wistar rats underwent cecal puncture for induction of subacute peritonitis and were infused with conventional parenteral nutrition (arginine 0.95 g/kg/d) or parenteral nutrition supplemented with arginine (1.88 g/kg/d), L-NAME (25 mg/kg/d), or arginine plus L-NAME. Sham-operated and nonperitonitic rats with oral feeding (R group) or conventional parenteral nutrition (TPN group) were also included.

Results: After 7 d of parenteral feeding, the L-NAME treatment significantly attenuated the peritonitis-induced reduction in body weight gain (1-way ANOVA, P < 0.05) and had a significant impact on decreasing body water percentage and on increasing body fat percentage and serum insulin concentrations (2-way ANOVA, P < 0.05). Parenteral arginine had a significant impact on increasing plasma arginine and ornithine and on decreasing serum glutamate oxaloacetate transaminase and plasma nitrite/nitrate in peritonitic rats. In addition, plasma interleukin-6 was significantly decreased by arginine and/or L-NAME treatment, and plasma prostaglandin E2 was significantly decreased by arginine plus L-NAME treatment.

Conclusion: These results suggest that the combination treatment of parenteral arginine and L-NAME may improve liver function and alleviate inflammatory response in rats with subacute peritonitis; however, it seems that parenteral arginine treatment is more beneficial than L-NAME.
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http://dx.doi.org/10.1016/j.jss.2012.05.089DOI Listing
May 2013

Appropriate dose of parenteral arginine enhances immunity of peripheral blood cells and splenocytes in rats with subacute peritonitis.

JPEN J Parenter Enteral Nutr 2012 Nov 23;36(6):741-9. Epub 2012 Jan 23.

Department of Medical Education and Research, Changhua Christian Hospital, Changhua, Taiwan.

Background: Arginine deficiency and chronic inflammation may cause immune dysfunction. The authors previously showed that a pharmacological dose of parenteral arginine facilitates ornithine rather than nitric oxide production in subacute peritonitis. Herein, they investigated the effects of different doses of parenteral arginine supplementation on immunocytic subpopulation distribution and function.

Materials: Male Wistar rats that underwent cecal punctures for induction of subacute peritonitis were infused with conventional parenteral nutrition solution (1.61% of total calories as arginine) or solutions supplemented with low-, medium-, or high-dose arginine (2.85%, 4.08%, and 6.54% of total calories, respectively) for 7 days. Distributions of T cells, B cells, and monocytes/macrophages and cytokine productions of peripheral blood lymphocytes (PBLs) and splenocytes were analyzed.

Results: There were no significant differences in circulating white blood cell numbers and serum tumor necrosis factor (TNF)-α and interferon (IFN)-γ concentrations among groups. Serum nitrate/nitrite (NOx) and interleukin (IL)-2 levels were significantly decreased by arginine in a dose-dependent manner. Animals supplemented with parenteral arginine had significantly decreased productions of concanavalin (Con) A- and lipopolysaccharide (LPS)-stimulated TNF-α in PBLs and splenocytes, spontaneous IL-6 and LPS-stimulated IFN-γ in PBLs, and LPS-stimulated IL-6 in splenocytes. In addition, low-dose arginine significantly increased production of spontaneous IFN-γ in PBLs and splenocytes. High-dose arginine significantly increased spontaneous TNF-α, and Con A stimulated IL-4 and IL-6 in PBLs.

Conclusion: Parenteral arginine administration at approximately 4% of total calories may alter PBLs and splenocytic immunity, and >6% of total calories might not be of benefit in rats with subacute peritonitis.
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http://dx.doi.org/10.1177/0148607111429793DOI Listing
November 2012

Long-term enteral arginine supplementation in rats with intestinal ischemia and reperfusion.

J Surg Res 2012 Jun 6;175(1):67-75. Epub 2011 Mar 6.

Department of Surgery, Division of Pediatric Surgery, Changhua Christian Hospital, Changhua, Taiwan.

Background: The effects of short-term enteral arginine supplementation on intestinal ischemia-reperfusion (IR) injury have been widely studied, especially the ischemic preconditioning supplementation. The aim of this study was to investigate the effects of long-term intra-duodenal supplementation of arginine on intestinal morphology, arginine-associated amino acid metabolism, and inflammatory responses in rats with intestinal IR.

Materials And Methods: Male Wistar rats with or without three hours of ileal ischemia underwent duodenal cannulation for continuous infusion of formula with 2% arginine or commercial protein powder for 7 d. The serological examinations, plasma amino acid and cytokine profiles, and intestinal morphology were assessed.

Results: Intestinal IR injury had significant impacts on the decreases in circulating red blood cells, hemoglobin, ileum mass, and villus height and crypt depth of the distal jejunum. In addition, arginine supplementation decreased serum cholesterol and increased plasma arginine concentrations. In rats with intestinal IR injury, arginine supplementation significantly decreased serum nitric oxide, plasma citrulline and ornithine, and the mucosal protein content of the ileum.

Conclusions: These results suggest that long-term intra-duodenal arginine administration may not have observable benefits on intestinal morphology or inflammatory response in rats with intestinal ischemia and reperfusion injury. Therefore, the necessity of long-term arginine supplementation for patients with intestinal ischemia and reperfusion injury remains questionable and requires further investigation.
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http://dx.doi.org/10.1016/j.jss.2011.02.003DOI Listing
June 2012

Dose effects of chronically infused nitric oxide synthase inhibitor N(G)-nitro-L-arginine methyl ester on anabolic response and arginine metabolism in rats with subacute peritonitis.

Biol Pharm Bull 2011 ;34(2):177-82

Department of Pediatrics, Clinical Nutrition Support Service Team, Changhua Christian Hospital, Changhau 50094, Taiwan.

Nitric oxide synthase (NOS) inhibitors alleviate the adverse effects of nitric oxide (NO) overproduction that occurs during peritonitis, a clinical condition that is accompanied by arginine deficiency. However, the variations in the disease severity and the dosage, route, and period of NOS inhibitor administration are debatable. Therefore, we investigated the dose effects of chronically infused NOS inhibitor, N(G)-nitro-L-arginine methyl ester (L-NAME) on the anabolism, inflammatory responses, and arginine metabolism in parenterally fed rats with cecal puncture-induced subacute peritonitis. Male Wistar rats were divided into 4 groups and were administered total parenteral nutrition solutions with 0, 5 (low dose), 25 (medium dose), or 50 (high dose) mg·kg(-1)·d(-1) of L-NAME for 7 d. Sham-operated rats administered total parenteral nutrition solution and normal healthy rats fed chow diet were also included. Our results showed that parenteral infusion significantly decreased body weight gain and plasma citrulline concentrations. In rats with subacute peritonitis, the parenteral infusion-induced increases in circulating white blood cells and NO were significantly decreased, whereas the decrease in serum albumin levels was significantly increased. Rats with subacute peritonitis that were administered chronic infusion of L-NAME had a significantly reduced nitrogen balance. In addition, rats administered the medium dose of L-NAME had significantly increased plasma arginine, ornithine, glutamate, and proline. In conclusion, chronic infusion of NOS inhibitors may not alter systemic NO homeostasis and inflammatory response but may facilitate the production of arginine-associated amino acids and nitrogen excretion in cases of subacute peritonitis.
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http://dx.doi.org/10.1248/bpb.34.177DOI Listing
November 2011

Changing clinical presentations and survival pattern in trisomy 18.

Pediatr Neonatol 2009 Aug;50(4):147-51

Department of Pediatrics, Children's Hospital, Changhua Christian Hospital, Taiwan.

Background: The clinical presentations and survival patterns of infants with trisomy 18 have changed with increasing utilization of prenatal ultrasound and amniocentesis, and improvements in neonatal intensive care.

Methods: We obtained data on duration of survival, male to female ratio, and clinical details for patients with trisomy 18, and calculated the prevalence rate.

Results: We studied 31 consecutive trisomy 18 infants. The estimated prevalence was 1/4, 144. Eleven (35%) were premature infants, and 20 (65%) were full term. Mean birth weight was 1896 g. Median life expectancy was 12 days; 11 days for males and 14 days for females (p = 0.87). The short-term survival rates of 1 week, 4 weeks, and 6 months were 58%, 32%, and 10%, respectively. The long-term survival rates of 1 year, 2 years, and 3 years were 6%, 6%, and 3%, respectively. Families signed do-not-resuscitate consent forms for five male (50%) and 19 female infants (90%) (p = 0.043).

Conclusion: All trisomy 18 infants in this study were preterm or full-term deliveries. Mean birth weight was lower than previously reported, and a high percentage of families signed do-not-resuscitate consent forms. Females did not survive longer than males, due to more females not being resuscitated. Most infants died in the first few weeks of life, but 3-6% of infants lived for 21 year. The possibility of long-term survival should be considered when counseling parents regarding trisomy 18.
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http://dx.doi.org/10.1016/S1875-9572(09)60053-XDOI Listing
August 2009

Early or late surgical ligation of medical refractory patent ductus arteriosus in premature infants.

J Formos Med Assoc 2009 Jan;108(1):72-7

Department of Pediatrics, Children's Hospital, Changhua Christian Hospital, Changhua, College of Health Sciences, Chang Jung Christian University, Tainan, Taiwan.

Optimal time to surgical ligation of patent ductus arteriosus (PDA) in very-low-birth-weight (< 1500 g) premature infants remains an area of controversy. We compared the outcomes of early or late ligation of medical refractory PDA in very-low-birth-weight premature infants. Fifty-six infants underwent surgical closure of PDA after failure of or having contraindications to medical treatment. Thirteen infants were in the early ligation (< or = 14 days) and 43 in the late ligation (> 14 days) groups. Basic clinical features, major morbidity of prematurity and mortality were compared. Clinical features and major outcomes were similar. The early ligation group had earlier onset of symptomatic PDA (5.7 +/- 1.6 days vs. 8.1 +/- 3.6 days, p = 0.024), and fewer days of total parenteral nutrition (TPN) (39.6 +/- 13.9 days vs. 60.4 +/- 31.4 days, p = 0.025) and ventilator use (11.1 +/- 6.7 days vs. 18.6 +/- 10.5 days, p = 0.019). Early ligation of medical refractory PDA in very-low-birth-weight premature infants improves enteral feeding tolerance and reduces TPN and ventilator use, but long-term benefits need further investigation.
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http://dx.doi.org/10.1016/S0929-6646(09)60035-8DOI Listing
January 2009

Echovirus 11 sepsis in a neonate: report of one case.

Acta Paediatr Taiwan 2003 Mar-Apr;44(2):104-5

Department of Pediatrics, Changhua Christian Hospital, No. 135, Nan-Siau Street, Changhua 500, Taiwan.

Neonates infected with nonpolio enteroviruses are at high risk for developing significant illness, including sepsis-like illness, meningoencephalitis, myocarditis and/or hepatitis. Echoviruses and group B coxsackieviruses account for the majority of neonatal enterovirus infections. We reported a case of echovirus 11 infection in newborn associated with maternal infection. To our knowledge, this is the first reported fatal case of neonatal echovirus infection in Taiwan. Eventually, the baby expired because of severe sepsis-like illness, fulminant hepatitis, disseminated intravascular coagulation, and extensive hemorrhagic manifestations in spite of intensive care, intravenous immunoglobulin infusion and exchange transfusion.
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October 2003
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