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Tzu-Hao Liu,1,2 Hsiao-Ping Wang,1,3 Fu-Nang Cho,3,4 Jiun-Ling Wang,5,6 Chih-Hsin Hung,7 Yee-Hsuan Chiou,1,3 Yao-Shen Chen,3,8 Susan Shin-Jung Lee,3,8 Ming-Fang Cheng1,3,7,91Department of Pediatrics, Kaohsiung Veterans General Hospital, Kaohsiung 81362, Taiwan; 2Department of Pediatrics, Zuoying Branch of Kaohsiung Armed Forces General Hospital, Kaohsiung 81342, Taiwan; 3School of Medicine, National Yang-Ming University, Taipei 11221, Taiwan; 4Department of Obstetrics and Gynecology, Kaohsiung Veterans General Hospital, Kaohsiung 81362, Taiwan; 5Department of Internal Medicine, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan 70101, Taiwan; 6Department of Medicine, College of Medicine, National Cheng Kung University, Tainan 70101, Taiwan; 7Department of Chemical Engineering and Institute of Biotechnology and Chemical Engineering, I-Shou University, Kaohsiung 84001, Taiwan; 8Department of Internal Medicine, Kaohsiung Veterans General Hospital, Kaohsiung 81362, Taiwan; 9School of Nursing, Fooyin University, Kaohsiung 83102, TaiwanCorrespondence: Ming-Fang ChengDepartment of Pediatrics, No. 386, Dazhong 1st Road, Zuoying District, Kaohsiung 813, TaiwanTel +886-7342-2121Fax +886-7346-8207Email mfcheng@vghks.gov.twPurpose: The role of pathogenic Escherichia coli colonization in asymptomatic pregnant women is not well understood. The purpose of this work was to determine the prevalence, antimicrobial susceptibility, and neonatal outcomes of pathogenic E. coli colonization in pregnant women.Patients and methods: A total of 137 women from southern Taiwan with singleton pregnancies were enrolled between March 2016 and June 2017. The women were prospectively screened for E. coli colonization in the rectovaginal region during prenatal examination. The exclusion criteria are twin pregnancy of the mother and major anomaly of the neonate. All E. coli isolates were identified as either pathogenic or commensal strains, and their susceptibility to various antimicrobials was investigated. Clinical data of the infants were retrieved from their medical records.Results: Results showed that 35.8% of asymptomatic pregnant women had pathogenic E. coli colonization in the rectovaginal region. Neonates born to such mothers showed significant morbidities, including hospitalization (OR= 3.74, 95% CI= 1.18∼11.87), hyperbilirubinemia (OR= 2.81, 95% CI= 1.24∼6.38), and gastrointestinal symptoms (OR= 5.53, 95% CI= 1.39∼21.94). Maternal colonization with pathogenic E. coli at rectoanal site was a risk factor for neonatal hyperbilirubinemia after Benjamini–Hochberg (BH) adjustment (52% vs 24%, adjusted P= 0.048).Conclusion: The prevalence of pathogenic E. coli colonization in Taiwanese asymptomatic pregnant women was high, and the neonates born to colonized mothers exhibited potential neonatal morbidities. Larger studies are necessary to confirm these findings.Keywords: maternal-neonatal transmission, respiratory distress, hyperbilirubinemia, gastrointestinal symptoms

Background: Previous research has indicated a negative correlation between exclusive breastfeeding and the incidence of Kawasaki disease (KD). However, the validation of this discovery through meta-analytical studies has been lacking. Furthermore, uncertainties persist regarding whether breastfeeding reduces the risk of coronary artery lesions (CAL) or resistance to intravenous immunoglobulin (IVIG)., Methods: A systematic exploration of the MEDLINE, Cochrane Central Register of Controlled Trials (CENTRAL), PubMed, EMBASE, and ClinicalTrials.gov databases was conducted to identify longitudinal or randomized controlled trials investigating the efficacy of breastfeeding in preventing KD. The primary focus was on the incidence of KD, with secondary emphasis placed on the incidence of CAL and IVIG resistance. Data were pooled using a frequentist-restricted maximum-likelihood random-effects model., Results: Of the 179 potentially eligible studies identified, five (n = 1,982,634) were included. The analysis revealed a significantly lower risk of KD (expressed as odds ratio, with 95% confidence intervals and p-values) in comparisons between exclusive breastfeeding and formula feeding (0.62, 0.43-0.91, p = 0.014), exclusive breastfeeding/partial breastfeeding and formula feeding (0.66, 0.46- 0.96, p = 0.03), and exclusive breastfeeding and partial breastfeeding/formula feeding (0.81, 0.74- 0.90, p < 0.01). However, no significant difference was observed in the risk of developing KD when comparing partial breastfeeding to formula feeding exclusively. Regarding secondary outcomes, no statistically significant difference was found in the risk of CAL or IVIG resistance across any comparison formats., Conclusions: Our study suggests that breastfeeding correlated with a reduced risk of KD but not with a reduced risk of CAL or IVIG resistance. These findings advocate for the implementation of breastfeeding policies in clinical practice., Competing Interests: Declaration of competing interest No conflict of interest., (Copyright © 2024 Taiwan Pediatric Association. Published by Elsevier B.V. All rights reserved.)

Vaccine-induced immune thrombotic thrombocytopenia (VITT), also known as thrombosis with thrombocytopenia syndrome, is a rare complication of ChAdOx1 nCoV-19 (AZD1222) vaccine administration. The overall incidence of VITT worldwide is one case per 100 000 exposures. Because of the high mortality rate from VITT, thorough monitoring is crucial to predict the risk of occurrence. The underlying risk factors for VITT are not fully understood. Potential risk factors include sex (female) and young age (less than 50 years), but further research must be conducted to confirm these assumptions. We report the case of a woman with obesity, which is a risk factor for deep vein thrombosis in the legs and for pulmonary embolism, who experienced fulminant VITT after AZD1222 vaccine administration. Keywords: Vaccine-induced immune thrombotic thrombocytopenia, AZ vaccine, Obesity, Risk factor.

Background: This study aimed to compare the efficacy of mycophenolic acid (MPA) and cyclophosphamide (CYC) for treating pediatric lupus nephritis (pLN)., Methods: Data on patients with pLN class III, IV, and V, diagnosed by renal biopsy, were collected from the Databank of Kaohsiung Veterans General Hospital between February 2005 and December 2020. The study included 31 pLN patients. Of these, 15 received MPA (MPA group) and 16 received CYC (CYC group). Systemic lupus erythematosus disease activity index score, laboratory findings, complete remission (CR), and partial remission (PR) were assessed at 6, 12, and 24 months., Results: In the MPA group, CR occurred in 7/15 (47%) patients at month 6 and in 11/15 (73%) at months 12 and 24. In the CYC group, CR was reached in 5/16 (31%) patients at month 6, in 8/16 (50%) at month 12, and in 9/16 (56%) at month 24. PR was seen in 3/15 (20%) patients in the MPA group and in 3/16 (19%) in the CYC group at month 24. The cumulative probability of CR and PR showed no statistically significant difference between the two groups. However, the estimated glomerular filtration rate (eGFR) improved significantly in the MPA group at months 6, 12 and 24 compared to that in the CYC group (p < 0.05)., Conclusion: The efficacy of MPA is similar to that of CYC for pLN treatment, with MPA providing a significant improvement in eGFR after pLN induction therapy at months 6,12 and 24., Competing Interests: Declaration of competing interest The authors had no competing interests., (Copyright © 2023. Published by Elsevier B.V.)

Background: Congenital anomalies of the kidney and urinary tract (CAKUT) are the primary cause of pediatric chronic kidney disease. Maternal body mass index (BMI) before pregnancy, pregestational diabetic mellitus (DM), and gestational diabetic mellitus (GDM) are potential modifiable risk factors for CAKUT in offspring., Methods: In this case control study, 4619 neonates were enrolled during 2012-2020 from Kaohsiung Veterans General Hospital in Taiwan. Maternal risk factors before and during pregnancy were compared in children with and without CAKUT. The yearly incidence of CAKUT in offspring and maternal overweight were recorded., Results: In total, 73 (1.6%) cases of CAKUT in offspring were identified. Maternal overweight before pregnancy (BMI ≥ 24 kg/m 2 ) was an independent risk factor for CAKUT in offspring. No associations of pregestational DM and GDM with CAKUT in offspring were observed. The incidence rates of CAKUT and maternal obesity have increased in the past 10 years., Conclusions: Maternal obesity before pregnancy is associated with CAKUT in offspring and should be addressed to ensure better outcomes. A higher resolution version of the Graphical abstract is available as Supplementary information., (© 2023. The Author(s), under exclusive licence to International Pediatric Nephrology Association.)

Background: Children with febrile urinary tract infections (UTIs) are prone to kidney scarring if they are not treated promptly; however, ambiguous symptoms before fever onset makes the early detection of UTIs difficult. Our study aimed to identify urethral discharge as an early manifestation in children with UTI., Methods: This study enrolled 678 children younger than 24 months with paired urinalysis and culture performed between 2015 and 2021; 544 children were diagnosed with UTIs. Clinical symptoms, urinalysis, and paired urine culture results were compared., Results: Urethral discharge was observed in 5.1% of children with UTI and yielded a specificity of 92.5% for diagnosing UTI. Children with urethral discharge had a less severe UTI course, furthermore, nine of them received antibiotics before fever occurred and seven of them were free of fever during UTI course. Urethral discharge was associated with alkalotic urine and Klebsiella pneumonia infection., Conclusions: Urethral discharge is an early symptom in children with UTI; it may present before fever onset and help ensure prompt antibiotic intervention., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (© 2023 Fang, Ou, Huang and Chiou.)

Background: The geographic distribution of the major clone of sequence type 131 (ST131) in extended-spectrum beta-lactamase (ESBL)-producing Escherichia coli (E. coli) infections is not known. We analyzed the clinical features, resistance mechanisms, and geographic distribution of ESBL-producing E. coli clones in 120 children., Methods: We studied the 120 ESBL-producing E. coli strains from children younger than 18 years. A VITEK 2 automated system was used to determine bacterial identification and ESBL production. Sequence type was determined by multi-locus sequence typing (MLST). The genetic relationship of the ESBL-producing strains was studied using pulsed-field gel electrophoresis (PFGE). Phylogenetic group and blaCTX-M group was performed using polymerase chain reaction (PCR). Multiplex PCR for detecting the common group 9 variant, CTX-M-14, and group 1 variant, CTX-M-15, was also performed. The addresses of the 120 children were collected, and plotted on the Taiwan map., Results: The groups in the center of Kaohsiung City lived mainly in urban areas with a population density of over 10,000 people per square kilometer, and the majority of the Kaohsiung groups on the outskirts of the city center lived in suburban areas with a population density of under 6000 people per square kilometer. There was no statistically significant difference between the city center and outskirt groups in terms of clinical presentation, laboratory, and imaging data. However, more ST131 clones, major pulsotype groups, and phylogenetic group B2 strains were found in the center of Kaohsiung than on the outskirts., Conclusion: ESBL-producing E. coli clones may be more challenging to treat clinically. Most infections were community-acquired, and there appeared to be major pulsotype clones, mainly in urban areas. This reinforces the necessity of environmental surveillance and sanitary procedures for ESBL-producing E. coli., Competing Interests: Declaration of Competing Interest The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: Aminophylline use and the association between clinical outcomes and therapy timing have been less investigated. The objective of this study was to determine the efficacy of early aminophylline use (within the first two days of life) in premature infants., Method: A retrospective observational cohort of infants weighing <1500 g and <30 weeks of gestational age at Kaohsiung Veterans General Hospital received aminophylline either within the first two days of life (EA, early aminophylline group), after the third day of life (LA, late aminophylline group), or without aminophylline during the first month of life (WA, without aminophylline group). Demographic data and neonatal clinical outcomes were compared among the three groups., Results: This study included 89 preterm infants (EA = 33, LA = 38, WA = 18). The EA group had a lower incidence of bronchopulmonary dysplasia (BPD) than the WA group (adjusted odds ratio [aOR] = 8.86(1.56-59.32); P = 0.024). Although there was no significant difference in BPD incidence between the EA and LA groups (aOR = 2.66(0.51-13.81), P = 0.244), a trend remained. Birth body weight less than 1000 g was also a significant risk factor for BPD (aOR = 8.86(1.32-47.41), P = 0.014). The duration of mechanical ventilation was shorter in the infants in the EA group compared to the WA group (estimated beta = -11.344(-19.57-3.12); P = 0.008)., Conclusion: Early aminophylline administration may be associated with a decreased incidence of BPD in preterm infants. However, the clinical benefits of aminophylline treatment require further investigation. In addition, a birth body weight of less than 1000 g was a crucial risk factor for BPD., Competing Interests: Declaration of competing interest The authors declare that they have no potential conflicts of interest., (Copyright © 2022 Taiwan Pediatric Association. Published by Elsevier B.V. All rights reserved.)

Atypical hemolytic uremic syndrome (aHUS), characterized by microangiopathic hemolytic anemia, thrombocytopenia, and acute kidney injury, is a rare but life-threatening systemic disorder caused by the dysregulation of the complement pathway. Current advances in molecular analysis and pathogenesis have facilitated the establishment of diagnosis and development of effective complement blockade. Based on this recent consensus, we provide suggestions regarding the diagnosis and management of aHUS in Taiwan. The diagnosis of aHUS is made by the presence of TMA with normal ADAMTS13 activity without known secondary causes. Although only 60% of patients with aHUS have mutations in genes involving the compliment and coagulation systems, molecular analysis is suggestive for helping establish diagnosis, clarifying the underlying pathophysiology, guiding the treatment decision-making, predicting the prognosis, and deciding renal transplantation. Complement blockade, anti-C5 monoclonal antibody, is the first-line therapy for patients with aHUS. Plasma therapy should be considered for removing autoantibody in patients with atypical HUS caused by anti-CFH or complement inhibitor is unavailable., Competing Interests: Declaration of competing interest The authors have no conflicts of interest relevant to this article., (Copyright © 2022 Formosan Medical Association. Published by Elsevier B.V. All rights reserved.)

Background: Serious bacterial infections (SBIs) could lead to mortality or severe long-term sequelae in neonates and infants aged <3 months. Accordingly, the aim of this study was to develop a quantitative and accurate assessment tool for predicting the risk of SBIs in febrile neonates., Methods: This retrospective study enrolled 131 febrile term neonates (aged <30 days) who were hospitalized at Kaohsiung Veterans General Hospital between January 2005 and December 2020. These neonates were classified into SBI and nonbacterial infection (NBI) groups on the basis of microbiological laboratory reports. The clinical characteristics and routine blood tests of both groups at the time of admission were analyzed. Stepwise logistic regression was applied to create and validate the nomogram for SBI prediction., Results: Among the 131 febrile neonates, 38 and 93 developed SBIs and NBIs, respectively. At the time of admission, ill clinical appearance, serum myelocyte/metamyelocyte presence, C-reactive protein (CRP) > 2.5 mg/dL, and pyuria were associated with an increased risk of SBIs. Accordingly, these four factors were used to develop a nomogram for SBI prediction, which exhibited significantly high performance (area under curve = 0.848, p < 0.001) in predicting SBI risk., Conclusion: We developed a nomogram combining clinical appearance, serum myelocyte/metamyelocyte presence, CRP, and pyuria for predicting SBI risk in febrile neonates. This tool can assist clinicians in making early diagnoses and delivering the appropriate treatment., Competing Interests: Declaration of competing interest The authors declare that they have no potential conflicts of interest., (Copyright © 2022 Taiwan Pediatric Association. Published by Elsevier B.V. All rights reserved.)

Background: For risk stratification and individualized treatment for children with urinary tract infection (UTI), they must be assessed for the presence of acute pyelonephritis (APN). Our study aimed to combine variables that can predict APN and establish a nomogram for clinical use., Methods: In total, 111 children <5 years old hospitalized at Kaohsiung Veterans General Hospital for UTI were classified into APN and simple UTI groups based on a technetium-99 m dimercaptosuccinic acid scan. Their demographic, laboratory test, and renal and urinary bladder sonography (RUBS) data were compared., Results: Fever peak of >39 °C, serum procalcitonin (PCT) ≥ 0.52 pg/mL, C-reactive protein (CRP) ≥ 2.86 mg/dL, and abnormal RUBS findings were independent variables for predicting APN in children. The nomogram established using the aforementioned variables had an area under the receiver operating characteristic curve (AUC) of 0.89, which was higher than those of PCT and CRP alone (0.776 and 0.774, respectively)., Conclusion: The combination of four variables had the highest power in predicting APN in children with UTI. The established nomogram is practical for clinical use., Competing Interests: Declaration of competing interest The authors declare that they have no conflicts of interest., (Copyright © 2022 Taiwan Pediatric Association. Published by Elsevier B.V. All rights reserved.)

Neutrophil extracellular traps (NETs) are chromatin-based structures that are released from neutrophils during infections and prevent microbes from spreading in the body through efficient degradation of their composition. Based on this chromatin-driven strategy of capturing and killing bacteria, we designed NET-like structures using DNA and ZnO nanoparticles (NPs). DNA was first purified from kiwifruit and treated with HCl to increase hydroxyl groups in the opened-deoxylribose form. The carboxyl groups of citric acid were then thermally crosslinked with said hydroxyl and primary amine groups in DNA, forming DNA-HCl nanogels (NGs). ZnO NPs were then used as positively charged granule enzymes, adsorbed onto the DNA-HCl NG, obtaining ZnO/DNA-HCl NGs (with NET biomimicry). In an anti-inflammatory assay, ZnO/DNA-HCl NGs significantly inhibited TNF-α, IL-6, iNOS and COX-2 expression in LPS-stimulated Raw264.7 cells. Moreover, the ZnO/DNA-HCl NGs markedly alleviated clinical symptoms in LPS-induced mouse peritonitis. Finally, ZnO/DNA-HCl NGs suppressed E. coli from entering circulation in septic mice while prolonging their survival. Our results suggest that the ZnO/DNA-HCl NGs, which mimic NET-like structures in the blocking of bacteria-inducted inflammation, may be a potential therapeutic strategy for bacterial infections., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Backgrounds: Chronic kidney disease (CKD) is underdiagnosed in children with congenital heart disease (CHD). Our aim was to study the incidence of CKD in CHD children and identify risk factors for CKD., Methods: CHD patients were enrolled from the Kaohsiung Veterans General Hospital database between 2010 and 2019. Patient age at enrollment was age at first visit to the hospital. The end of follow-up was marked by the last measurement of serum creatinine, urine protein-to-creatinine ratio (UPCR), or urine microalbumin-to-creatinine ratio (UACR) after enrollment, and only patients who underwent the aforementioned tests in 2 different years were included. Patients with an estimated glomerular filtration rate (eGFR) < 90 mL/min/1.73m 2 were diagnosed as having CKD and were further classified into clinically recognized CKD (CR-CKD, defined as eGFR <60 mL/min/1.73m 2 , UPCR >0.5, or UACR >30 mg/g) and non-clinically recognized CKD (NCR-CKD). Their demographic data, CHD category, heart surgery types, medications, and contrast-related examinations during follow-up were collected., Results: The study included 359 CHD patients, of whom 167 (46.5%) developed CKD (18 patients with CR-CKD and 341 with NCR-CKD). Patients with CR-CKD were significantly older at enrollment than patients with NCR-CKD. Corrective heart surgery may be a protective factor for CKD. Furthermore, cyanotic heart disease, two or more image-related contrast exposures, and diuretic use may be associated with CKD., Conclusion: CHD patients have a high incidence of CKD. The early detection of CKD and prompt corrective heart surgery for CHD may be beneficial for kidney function., (© 2021. The Author(s).)

Nocturnal enuresis (NE) is a common problem among 10% school-aged children. The etiologies underlying childhood NE is complex and not fully understood nowadays. Nevertheless, increasing evidence suggests a potential link between neurobehavioral disorders and enuresis in children. In this study, we aimed to explore novel metabolomic insights into the pathophysiology of NE and also, its association with pediatric psychiatric problems. Urine collected from 41 bedwetting children and 27 healthy control children was analyzed by using 1 H-nuclear magnetic resonance spectroscopy from August 2017 to December 2018. At regular follow-up, there were 14 children with refractory NE having a diagnosis of attention deficient hyperactivity disorder (ADHD) or anxiety. Eventually, we identified eight significantly differential urinary metabolites and particularly increased urinary excretion of betaine, creatine and guanidinoacetate linked to glycine, serine and threonine metabolism were associated with a comorbidity of neurobehavioral disorders in refractory bedwetting children. Notably, based on physiological functions of betaine acting as a renal osmolyte and methyl group donor, we speculated its potential role in modulation of renal and/or central circadian clock systems, becoming a useful urinary metabolic marker in diagnosis of treatment-resistant NE in children affected by these two disorders., (© 2021. The Author(s).)

Competing Interests: Declaration of competing interest The authors have no conflicts of interest relevant to this article.

Abstract: Thrombotic microangiopathy (TMA) syndromes are extraordinarily diverse in clinical presentations and etiologies. However, there are still a limited number of large cohort studies focusing on the underlying causes, outcomes, and response to plasmapheresis.A retrospective study was designed to understand trigger etiologies, organ dysfunctions, clinical outcomes, and efficacy of plasmapheresis in patients with TMA. The whole population of Taiwan was set up into 2 cohorts: 875 patients with TMA in the 2006 cohort (2006-2010) and 1352 patients with TMA in the 2011 cohort (2011-2015). One hundred ninety-five patients in the 2006 cohort and 272 patients in the 2011 cohort were under plasmapheresis treatment.The common underlying etiologies were pregnancy, followed by systemic lupus erythematosus, rheumatoid arthritis, transplantation and drugs, which were significantly higher than the control group. Stroke, seizure, arterial thrombosis, vascular stenosis, hypertension, myocardial infarction, and pancreatitis were the main clinical signs and extra-renal involvements. In the multivariate regression analysis, stroke, arterial thrombosis, peripheral arterial disease, and uremia were significantly higher compared with the control group. The mortality rate in TMA under plasmapheresis was significantly higher than all TMA cases (39.33% vs 15.39% in the 2006 cohort and 39.27% vs 15.06% in the 2011 cohort).This study indicated the spectrum of underlying causes, extra-renal characteristics, and the response to plasmapheresis of patients with TMA in Taiwan. Of note, the poor clinical outcomes of plasmapheresis in patients with TMA might highlight the masked underlying etiology or worse disease condition that should be noticed., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2021 the Author(s). Published by Wolters Kluwer Health, Inc.)

Primary effusion lymphoma (PEL) is an aggressive neoplasm correlated with human herpesvirus 8 (HHV8). Metabolic reprogramming is a hallmark of cancers. The alterations in cellular metabolism are important to the survival of HHV8 latently infected cells. Pyruvate dehydrogenase (PDH) controls the flux of metabolites between glycolysis and the tricarboxylic acid cycle (TCA cycle) and is a key enzyme in cancer metabolic reprogramming. Glutaminolysis is required for the survival of PEL cells. Glutamate dehydrogenase 1 (GDH1) converts glutamate into α-ketoglutarate supplying the TCA cycle with intermediates to support anaplerosis. Previously we have observed that epigallocatechin-3-gallate (EGCG) can induce PEL cell death and N-acetyl cysteine (NAC) attenuates EGCG induced PEL cell death. In this study, results showed that EGCG upregulated the expression of glucose transporter GLUT3, and reduced the expression of pyruvate dehydrogenase E1-alpha (PDHA1), the major regulator of PDH, and GDH1. NAC could partially reverse the effects of EGCG in PEL cells. Overexpression of PDHA1 in PEL cells or supplement of α-ketoglutarate attenuated EGCG induced cell death. EGCG also reduced the levels of oncometabolite D-2-hydroxyglutarate (D2HG). These results suggest that EGCG may modulate the metabolism of PEL cells leading to cell death., Competing Interests: Declaration of Competing Interest The authors declare no conflict of interest., (Copyright © 2019. Published by Elsevier Ltd.)

Nocturnal enuresis causes significant psychological distress to affected children and their family and requires appropriate management. A 12-member expert committee of pediatric urologists and pediatric nephrologists in Taiwan with extensive experience in treating enuresis was established to develop consensus statements and a recommended treatment algorithm for the management of patients with nocturnal enuresis in Taiwan after careful consideration of current evidence, existing guidelines, and expert opinion as well as local practice and culture. The finalized consensus statements were reviewed by and have received endorsement from the Taiwan Urological Association and the Taiwan Pediatric Association. Patients with suspected enuresis should undergo a thorough initial assessment to fully evaluate urinary signs and symptoms and to rule out underlying causes of diurnal and nocturnal incontinence. Behavioral therapy is recommended throughout the course of management. Desmopressin in the fast-melting formulation is the recommended first-line pharmacological treatment. Combination therapy may be effective in patients who have failed first-line treatment. These consensus statements and a recommended treatment algorithm were created by the expert committee to provide practical support for clinical decision making by physicians in Taiwan., (Copyright © 2018. Published by Elsevier B.V.)

Background: To investigate the clinical features of Kikuchi-Fujimoto disease (KFD) in children, and place an emphasis on the therapeutic effects of hydroxychloroquine as monotherapy., Methods: We retrospectively reviewed the medical records of all children diagnosed with KFD during the period January 1992 to September 2016 at a tertiary medical center in Taiwan., Results: 40 patients were histopathologically confirmed as KFD, and the mean age of the patients was 13.9 ± 3.1 years. The male to female ratio was 1:1. The lymph node involvements were often cervical (95%) with features of unilateral predisposition (75%), polyadenopathy (84.4%) and tenderness (56.3%). Fever, cough, rhinorrhea, and tonsillitis were other common presentations. Laboratory findings included leukopenia (56.5%), monocytosis (63.6%), with positive results of EB-VCA IgG (88.9%), EB-VCA IgM (22.2%), EBEA IgG (22.2%) and EBNA IgG (88.9%). The univariate analyses of prolonged fever with lymphopenia, monocytosis, thrombocytopenia and necrotizing type in histopathology were disclosed as statistically significant (P < 0.05). Corticosteroids and hydroxychloroquine were administered in 15.6% of patients respectively, along with symptomatic treatments for the rest. Recurrence occurred in 13.0% of patients without corticosteroids or hydroxychloroquine treatment. There were neither recurrences nor relevant major adverse effects in all the five KFD cases treated with hydroxychloroquine., Conclusion: KFD should be suspected in children with febrile cervical lymphadenopathy, especially when concomitant with leukopenia and monocytosis. Lymphopenia, monocytosis, thrombocytopenia and necrotizing type in histopathology are reliable predictors for prolonged fever. Hydroxychloroquine may be an alternative choice to corticosteroids for its favorable effects and safety., (Copyright © 2017. Published by Elsevier B.V.)

Background/purpose: The prevalence of extended-spectrum β-lactamase (ESBL)-producing Escherichia coli is increasing worldwide. This study investigated the clinical features and bacteriology of pediatric patients with ESBL-producing E. coli bacteremia and compared their characteristics with those of adult patients., Methods: Clinical and laboratory data from all of the 41 patients aged ≤18 years diagnosed with E. coli bacteremia were collected over 5 years. Patients aged >18 years diagnosed with E. coli bacteremia, matched 1:1 for calendar time, were enrolled as the adult group. All E. coli isolates were tested for their blaCTX-M group and sequence type 131 (ST131). A novel seven-single nucleotide polymorphism-based clonotyping test was applied to detect the septatypes of each isolate., Results: In the adult group, patients with ESBL-producing E. coli bacteremia had more previous hospitalizations and antimicrobial agent use than did those with non-ESBL-producing E. coli bacteremia, but these differences were not found in pediatric group. In the pediatric group, the proportion of isolates producing CTX-M group 9 was higher than that in the adult group (85.7% vs. 42.9%; p < 0.05). Among both groups, there were more E. coli ST131 in ESBL isolates in than there were non-ESBL isolates. The distribution of septatypes was more homogenous in ESBL-producing E. coli among the pediatric patients than among the adult patients., Conclusion: ST131 was the major clone causing E. coli bacteremia in both pediatric and adult populations. The pediatric population demonstrated a higher number of isolates producing CTX-M group 9 with more homogenous septatypes compared with the adult population., (Copyright © 2017. Published by Elsevier B.V.)

There is little information available on the association between primary renal disease (PRD) and long-term mortality in the pediatric dialysis population. The objective of this study was to explore mortality risks in children and adolescents on chronic dialysis, specifically focused on the risk of various PRDs. The study cohort included children and adolescents with end-stage renal disease (ESRD) (aged < 20 years) who had received dialysis for at least 90 days between 2000 and 2014 and were identified from Taiwan's National Health Insurance medical claims. A total of 530 children and adolescents were included in the study. The median age of the included patients was 13.6 years and 305 (57.5%) patients were males. One hundred and seven patients died during the follow-up period and the median survival time was 6.0 years. Mortality was highest in the youngest patients. For patients with the following PRDs, mortality was significantly higher than that in patients with primary glomerulonephritis: secondary glomerulonephritis (adjusted hazard ratio (aHR): 2.50; 95% confidence interval (CI): 1.03⁻6.08), urologic disorder (aHR: 4.77; 95% CI: 1.69⁻13.46), and metabolic diseases (aHR: 5.57; 95% CI: 1.84⁻16.85). Several kinds of PRDs appear to have high mortality risks in the pediatric dialysis population. These differences in mortality risk highlight the importance of the focused clinical management of these high-risk subgroups.

Blood pressure (BP) is a crucial indicator of cardiac health and vascular status. This study explores the relationship between radial artery BP and wrist skin strain. A BP estimation method based on the physical model of wrist skin tissues and pulse wave velocity (PWV) is proposed. A photoplethysmography (PPG) sensor and strain gauge are used in this method. The developed strain-based pulse wave sensor consists of a pressing force sensor, which ensures consistent pressing force, and a strain gauge, which measures the cardiac pulsation on the wrist skin. These features enable long-term BP monitoring without incurring the limb compression caused by a cuff. Thus, this method is useful for individuals requiring continuous BP monitoring. In this study, the BP of each participant was measured in three modes (before, during, and after exercise), and the data were compared using a clinically validated sphygmomanometer. The percentage errors of diastolic and systolic BP readings were, respectively, 4.74% and 4.49% before exercise, 6.38% and 6.10% during exercise, and 5.98% and 4.81% after a rest. The errors were compared with a clinically validated sphygmomanometer.

Background: Henoch-Schönlein purpura (HSP) is a common vasculitis in childhood characterized by purpura, arthritis, abdominal pain and renal involvement. However, bullous HSP is a rare cutaneous manifestation, and a few cases have been reported., Case Presentation: Herein, we report a 15-year-old male with bullous HSP who presented with severe abdominal pain and hemorrhagic bullous lesions over his lower extremities. He was treated with corticosteroid, after which the symptoms improved dramatically. No recurrence was noted after follow-up, though scarring was present. We also reviewed the literature related to bullous HSP and identified 39 cases, most of whom were treated with corticosteroids., Conclusion: Clinicians should be aware of the atypical types of HSP, including bullous HSP. Most patients with bullous HSP have a good prognosis.

Introduction: Immune thrombocytopenia (ITP) is an immune-mediated disease; it has been reported to be associated with several diseases. The data on ITP in patients with hepatitis B, tuberculosis, or thyroid diseases are relatively scarce. In addition, these diseases are not rare in Taiwan, together with hepatitis C and Helicobacter pylori which are also related to ITP., Methods and Materials: We identified 1223 ITP patients and characterized these patients between 2000 and 2013 from the National Health Insurance Research Database. The adult ITP patients were matched with non-ITP patients., Results: The overall incidence of ITP was 2.59/100,000 person-years. The frequencies of hepatitis B and C in adult ITP patients were much higher than those indicated in previous studies. The frequencies of non-traumatic intracerebral hemorrhage and gastrointestinal bleeding during hospitalization among ITP patients were low. The diseases associated with increased risks of ITP included hepatitis B (OR = 18.70, 95% CI = 9.71-36.03), hepatitis C (OR = 54.43, 95% CI = 15.94-185.88), hepatitis B and hepatitis C (OR = 7.02, 95% CI = 1.47-33.56), tuberculosis (OR = 5.37, 95% CI = 2.72-10.61), Helicobacter pylori infection (OR = 5.93, 95% CI = 3.16-11.10), hyperthyroidism (OR = 3.43, 95% CI = 2.09-5.64), hypothyroidism (OR = 6.70, 95% CI = 2.35-19.13), and simple and unspecified goiter (OR = 2.68, 95% CI = 1.43-5.03)., Conclusions: Surveying for the diseases which are frequent and related to increased risks of ITP among patients with newly diagnosed ITP should be considered., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Epigallocatechin-3-gallate (EGCG), the major constituent of green tea, has been shown to induce cell death in cancer cells. Primary effusion lymphoma (PEL) is an aggressive neoplasm caused by human herpesvirus 8 (HHV8). In this study, we examined the role of EGCG on PEL cells in cell death and HHV8 replication. We performed trypan blue exclusion assay to assess the cell viability of PEL cells, flow cytometry analysis to examine the cell cycle distribution and reactive oxygen species (ROS) generation, caspase-3 activity to assay apoptosis, acridine orange staining to determine autophagy, and immunoblotting to detect the protein levels involved in apoptosis and autophagy as well as mitogen activated protein kinases (MAPKs) activation upon EGCG treatment. The expression of the HHV8 lytic gene was determined by luciferase reporter assay and reverse transcription-PCR, and viral progeny production was determined by PCR. Results revealed that EGCG induced cell death and ROS generation in PEL cells in a dose-dependent manner. N -acetylcysteine (NAC) inhibited the EGCG-induced ROS and rescued the cell from EGCG-induced cell death. Even though EGCG induced ROS generation in PEL cells, it reduced the production of progeny virus from PEL cells without causing HHV8 reactivation. These results suggest that EGCG may represent a novel strategy for the treatment of HHV8 infection and HHV8-associated lymphomas., Competing Interests: The authors declare no conflict of interest.

High-dose methotrexate (HDMTX) is important for children with acute lymphoblastic leukemia (ALL). There is no effective treatment for patients with oral mucositis, which is a major side effect associated with HDMTX. Here, we reviewed the medical records of patients younger than 18 yr with newly diagnosed ALL in our hospitals from 2002 to 2013. According to the nationwide protocol (TPOG-ALL-2002), each patient received four courses of HDMTX (2.5 or 5 g/m 2 ) during consolidation therapy. HDMTX courses with glutamine therapy were as the glutamine group, and intravenous glutamine (0.4 g/kg/day) was started within 48 h after the initiation of HDMTX for 3 consecutive days. HDMTX courses without glutamine were as the control group. A total of 347 HDMTX courses were administrated in the 96 children with ALL during the study period. The incidence of oral mucositis was significantly lower in the glutamine group than in the control group (3.8% vs. 17.6%; P = 0.004). In the glutamine group, no patients suffered from severe oral mucositis. No severe adverse effects associated with glutamine administration were noted. Accordingly, parenteral glutamine appears to be feasible and safe to prevent oral mucositis in patients receiving HDMTX.

Background/purpose: This study aims to examine the characteristics of Taiwanese children with chronic kidney disease (CKD) and delineate the factors that lead to disease progression in this population., Methods: We reviewed the records of the Taiwan Pediatric Renal Collaborative Study, a multicenter database of Taiwanese children with CKD. Multivariate regression analysis was used to identify the main factors associated with disease progression., Results: A total of 382 children aged 1-18 years were included in the study (median age was 10.6 years; interquartile range: 6.4-13.8). There were 197 males (51.6%) and 185 females. CKD Stage 1 was diagnosed in 159 children (41.6%), Stage 2 in 160 (41.9%), Stage 3 in 51 (13.4%), and Stage 4 in 12 (3.1%). Fifty-six children (14.7%) experienced CKD progression. A multivariate analysis for all patients indicated that the risk for disease progression was increased in children with CKD secondary to a structural abnormality, genetic disease, anemia, elevated diastolic blood pressure, or elevated blood urea nitrogen. Compared with children with Stage 1 CKD, those with Stage 2 and Stage 4 CKD had decreased risk for CKD progression in this short-term cohort follow-up., Conclusion: CKD etiology affects disease progression. Careful monitoring and treatment of anemia and elevated blood pressure in children with CKD may slow disease progression., (Copyright © 2015. Published by Elsevier B.V.)

Background: Community-acquired urinary tract infection (UTI) caused by extended-spectrum beta-lactamase (ESBL)-producing Escherichia coli is an emerging problem. Compared with urban infants, rural infants may encounter different distributions of community-acquired resistant strains and various barriers to efficient management., Methods: A retrospective survey and comparison was conducted for infants with UTI caused by ESBL-producing E. coli admitted to an urban hospital (n = 111) and a rural hospital (n = 48) in southern Taiwan from 2009 to 2012., Results: Compared with 2009 and 2010, the total number of cases at both hospitals significantly increased in 2011 and 2012 (p < 0.001). Compared with the rural patients, the urban patients were significantly younger, and they had fewer days of fever before and after admission, fewer presentations of poor activity and poor appetite, and a lower serum creatinine level. Most of the patients had no prior history of illness, and we could not identify any significant different risk factors for acquiring ESBL-producing E. coli, such as past antimicrobial use, hospitalization, UTI, and underlying renal diseases, between the urban and rural populations., Conclusions: The increase in community-acquired UTI in infants caused by ESBL-producing E. coli was similar between the urban and rural populations. Our preliminary data suggest that the rural-urban disparities were probably related to easy access to health care by the urban population. ESBL complicates disease management, and the increase in the prevalence of ESBL producers is a major health concern and requires further healthy carrier and environmental surveillance.

Background: Little information is available regarding the clinical characteristics and prevalence of complications in children with chronic kidney disease (CKD), especially in early disease stages. The objective of this study was to determine the clinical characteristics and prevalence of complications in children with predialytic CKD., Methods: This multicenter, cross-sectional study enrolled children at all stages of predialytic CKD. Children who were between the ages of 1 year and 18 years and who fulfilled the clinical criteria of CKD were included in the study. Baseline demographic data, previous history, clinical characteristics, and laboratory data were collected., Results: A total of 757 children were included in the study. The median age at the time of enrollment was 10.6 years; 397 patients (52.4 %) were males. A total of 39.0 % of the patients were in CKD stage 1, 37.6 % were in stage 2, 14.8 % were in stage 3, 3.0 % were in stage 4, and 5.5 % were in stage 5. Nonglomerular renal diseases were the primary cause of CKD, comprising 51.9 % of the patients with CKD. The age at disease onset, gender, CKD stage distribution, and proportion of co-morbidities varied between the glomerular and nonglomerular CKD cases. Anemia, hyperlipidemia, hypocalcemia, and hyperphosphatemia were more prevalent in patients with glomerular CKD. The overall prevalence of complications was as follows: uncontrolled blood pressure, 44.1 %; anemia, 34.2 %; hyperlipidemia, 44.9 %; short stature, 10.3 %; and failure to thrive, 8.2 %. Uncontrolled blood pressure (BP), anemia, and hyperlipidemia were common, even in the early CKD stages. The prevalence of CKD complications generally increased with the worsening stage of CKD., Conclusions: This study reveals differences in CKD etiology and prevalence of specific complications according to the stage of CKD. Early recognition and awareness of complications are mandatory for clinicians during the follow-up visits of children with CKD.

STEAP1 (six transmembrane epithelial antigen of the prostate 1) is a transmembrane protein that functions as a potential channel or transporter protein. It is overexpressed in certain cancers and is viewed as a promising therapeutic target. However, the prognostic role of STEAP1 is still controversial, and no role for STEAP1 has yet been indicated in colorectal cancer. The aim of this study was to investigate the possible association of STEAP1 expression with colorectal cancer prognosis. STEAP1 expression was analyzed by immunohistochemical staining of a tissue array of 165 cancer specimens from primary colorectal cancer patients. The mean and medium follow-up times after surgery were 5.1 and 3.9 years, respectively. A total of 139 patients died during the 13 years of follow-up in the survey period. The prognostic value of STEAP1 with respect to overall survival was analyzed by Kaplan-Meier analysis and Cox proportional hazard models. In total, 164 samples displayed detectable STEAP1 expression in the cytoplasm and membrane. Low STEAP1 expression was correlated with poor overall survival (five-year survival: 33.7% vs. 57.0%, low expression vs. high expression, p = 0.020). Accordingly, multivariate analysis identified low STEAP1 expression as an independent risk factor (hazard ratio = 1.500, p = 0.018), especially in elderly patients or those with late stage cancers, late T values, and early N values. We suggest that analysis of STEAP1 expression by immunohistochemical staining could serve as an independent prognostic marker for colorectal patients. This finding should be validated by other investigative groups.

Extended-spectrum β-lactamase (ESBL)-producing Escherichia coli sequence type ST131 has emerged as the leading cause of community-acquired urinary tract infections and bacteremia worldwide. Whether environmental water is a potential reservoir of these strains remains unclear. River water samples were collected from 40 stations in southern Taiwan from February to August 2014. PCR assay and multilocus sequence typing (MLST) analysis were conducted to determine the CTX-M group and sequence type, respectively. In addition, we identified the seasonal frequency of ESBL-producing E. coli strains and their geographical relationship with runoffs from livestock and poultry farms between February and August 2014. ESBL-producing E. coli accounted for 30% of the 621 E. coli strains isolated from river water in southern Taiwan. ESBL-producing E. coli ST131 was not detected among the isolates. The most commonly detected strain was E. coli CTX-M group 9. Among the 92 isolates selected for MLST analysis, the most common ESBL-producing clonal complexes were ST10 and ST58. The proportion of ESBL-producing E. coli was significantly higher in areas with a lower river pollution index (P = 0.025) and regions with a large number of chickens being raised (P = 0.013). ESBL-producing E. coli strains were commonly isolated from river waters in southern Taiwan. The most commonly isolated ESBL-producing clonal complexes were ST10 and ST58, which were geographically related to chicken farms. ESBL-producing E. coli ST131, the major clone causing community-acquired infections in Taiwan and worldwide, was not detected in river waters., (Copyright © 2016, American Society for Microbiology. All Rights Reserved.)

Resveratrol (3,4',5-trihydroxy-trans-stilbene) has been reported to inhibit proliferation of various cancer cells. However, the effects of resveratrol on the human herpesvirus 8 (HHV8) harboring primary effusion lymphoma (PEL) cells remains unclear. The anti-proliferation effects and possible mechanisms of resveratrol in the HHV8 harboring PEL cells were examined in this study. Results showed that resveratrol induced caspase-3 activation and the formation of acidic vacuoles in the HHV8 harboring PEL cells, indicating resveratrol treatment could cause apoptosis and autophagy in PEL cells. In addition, resveratrol treatment increased ROS generation but did not lead to HHV8 reactivation. ROS scavenger (N-acetyl cysteine, NAC) could attenuate both the resveratrol induced caspase-3 activity and the formation of acidic vacuoles, but failed to attenuate resveratrol induced PEL cell death. Caspase inhibitor, autophagy inhibitors and necroptosis inhibitor could not block resveratrol induced PEL cell death. Moreover, resveratrol disrupted HHV8 latent infection, inhibited HHV8 lytic gene expression and decreased virus progeny production. Overexpression of HHV8-encoded viral FLICE inhibitory protein (vFLIP) could partially block resveratrol induced cell death in PEL cells. These data suggest that resveratrol-induced cell death in PEL cells may be mediated by disruption of HHV8 replication. Resveratrol may be a potential anti-HHV8 drug and an effective treatment for HHV8-related tumors., (Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.)

We recently reported that nickel accumulation in lung tissues may be associated with an increased in p53 mutation risk via reduced DNA repair activity. Here, we hypothesized that nickel accumulation in lung tissues could contribute to EGFR mutations in never-smokers with lung cancer. We enrolled 76 never-smoking patients to evaluate nickel level in adjacent normal lung tissues by ICP-MS. The prevalence of EGFR mutations was significantly higher in the high-nickel subgroup than in the low-nickel subgroup. Intriguingly, the OR for the occurrence of EGFR mutations in female, adenocarcinoma, and female adenocarcinoma patients was higher than that of all patients. Mechanistically, SPRY2 and RECK expressions were decreased by nickel-induced miR-21 via activation of the EGFR/NF-κB signaling pathway, which promoted invasiveness in lung cancer cells, and particularly in the cells with EGFR L858R expression vector transfection. The patients' nickel levels were associated with miR-21 expression levels. Kaplan-Meier analysis revealed poorer overall survival (OS) and shorter relapse free survival (RFS) in the high-nickel subgroup than in low-nickel subgroup. The high-nickel/high-miR-21 subgroup had shorter OS and RFS periods when compared to the low-nickel/low-miR-21 subgroup. Our findings support previous epidemiological studies indicating that nickel exposure may not only contribute to cancer incidence but also promote tumor invasion in lung cancer., (Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.)

Background: Patients with acute lobar nephronia (ALN) require a longer duration of antimicrobial treatment than those with acute pyelonephritis (APN), and ALN is associated with renal scarring. The aim of this study was to provide an understanding of ALN by comparing the clinical features of pediatric patients with ALN and APN., Methods: We enrolled all of the patients with ALN (confirmed by computed tomography) admitted to our hospital from 1999 to 2012 in the ALN group. In addition, each patient diagnosed with APN who was matched for sex, age, and admission date to each ALN patient was enrolled in the APN group. The medical charts of patients in these two groups were retrospectively reviewed and analyzed for comparison., Results: The fever duration after hospitalization in the ALN group and the APN group were 4.85 ± 2.33 days and 2.30 ± 1.47 days respectively. The microbiological distributions and the majority of susceptibilities were similar in the ALN and APN groups. The majority of clinical manifestations are nonspecific and unreliable for the differentiation of ALN and APN. The patients with ALN were febrile for longer after antimicrobial treatment, had more nausea/vomiting symptoms, higher neutrophil count, bandemia, and C-reactive protein (CRP) levels, and lower platelet count (all p < 0.05). In multivariate analysis, initial CRP levels, nausea/vomiting symptoms, and fever duration after admission were independent variables with statistical significance to predict ALN. Severe nephromegaly occurred significantly more in the ALN group than in the APN group (p = 0.022)., Conclusion: The majority of clinical manifestations, laboratory findings, and microbiological features are similar between patients with ALN and APN. Clinicians should keep a high index of suspicion regarding ALN, particularly for those with ultrasonographic nephromegaly, initial higher CRP, nausea/vomiting, and fever for > 5 days after antimicrobial treatment., (Copyright © 2014. Published by Elsevier B.V.)

Background: Escherichia coli sero-group O25b-sequence type 131 (O25b-ST131), a multidrug-resistant clonal group, is a significant pathogen in adults and children. This study investigated the genotyping and role of extended spectrum β-lactamase (ESBL)-producing E. coli O25b-ST131 and non-O25b-ST131 in urinary tract infections in infants., Methods: Clinical and laboratory data from 111 infants less than 1 year of age, who were hospitalized for urinary tract infections caused by ESBL-producing E. coli between 2009 and 2012 were collected. Polymerase chain reactions and multi-locus sequence typing were used to identify E. coli O25-ST131 clones. The gene blaCTX-M groups 1, 2 and 9, a specific polymerase chain reaction of CTX-M 14 and 15, were also determined in ESBL-producing E. coli isolates., Results: O25b-ST131 accounted for 65% of the 111 isolates, although 92 isolates belonged to the blaCTX-M group 9, of which most were CTX-M-14. Those with O25b-ST131 clones had similar risk factors, clinical features and outcomes as those with non-O25b-ST131. The E. coli O25b-ST131 isolates were more resistant to ciprofloxacin and gentamicin, but more susceptible to cefoxitin, minocycline and trimethoprim/sulfamethoxazole than the non-O25b-ST131 isolates. Most of the infants (78%) were previously healthy with no apparent risk factors., Conclusions: E. coli O25b-ST131 is a major community-acquired uropathogen in the infant population. Regardless of O25b-ST131 or non-O25b-ST131 clones, CTX-M-14 accounts for majority of the ESBL genotype. The O25b-ST131 clone is not associated with more severe clinical disease, but it may make the diagnosis and selection of antimicrobials for treatment more challenging.

Occupational exposure to nickel compounds has been associated with lung cancer. The correlation between high nickel levels and increased risk of lung cancer has been previously reported in a case-control study. This study assessed whether nickel exposure increased the occurrence of p53 mutations due to DNA repair inhibition by nickel. A total of 189 lung cancer patients were enrolled to determine nickel levels in tumor-adjacent normal lung tissues and p53 mutation status in lung tumors through atomic absorption spectrometry and direct sequencing, respectively. Nickel levels in p53 mutant patients were significantly higher than those in p53 wild-type patients. When patients were divided into high- and low-nickel subgroups by median nickel level, the high-nickel subgroup of patients had an odds ratio (OR) of 3.25 for p53 mutation risk relative to the low-nickel subgroup patients. The OR for p53 mutation risk of lifetime non-smokers, particularly females, in the high-nickel subgroup was greater than that in the low-nickel subgroup. To determine whether nickel affected DNA repair capacity, we conducted the host cell reactivation assay in A549 and H1975 lung cancer cells and showed that the DNA repair activity was reduced by nickel chloride in a dose-dependent manner. This was associated with elevated production of hydrogen peroxide-induced 8-oxo-deoxyguanosine. Therefore, increased risk of p53 mutation due to defective DNA repair caused by high nickel levels in lung tissues may be one mechanism by which nickel exposure contributes to lung cancer development, especially in lifetime female non-smokers., (© 2014 Wiley Periodicals, Inc.)

Background: The relationship between hemoglobin and patent ductus arteriosus (PDA) has not been discussed before. The aim of this study was to assess the influence of hemoglobin and perinatal factors on PDA in very low-birthweight (VLBW) infants., Methods: Using data from the Premature Baby Foundation of Taiwan (PBFA), the characteristics, perinatal factors, and hemoglobin of VLBW infants with and without PDA and treatment were compared., Results: Between January 2008 and December 2010, 89 VLBW infants were admitted to hospital. The overall survival rate was 87.6%. Twelve infants were excluded. Compared to those without PDA, the 34 infants with PDA received oral indomethacin or surgery, had smaller mean gestational age (GA; 27.93 ± 1.818 weeks, P = 0.000003), lower mean birthweight (BW; 1031 ± 259 g, P = 0.0001), significantly lower Apgar score at 5 min, more severe respiratory distress syndrome (RDS; grade 3 or 4), greater use of surfactants, and lower mean hemoglobin (P = 0.018) after birth than those without PDA. Compared to those with indomethacin, the seven infants with surgery had lower mean GA (26.43 ± 1.718 weeks, P = 0.011), significantly lower Apgar scores at 1 min, but higher platelet count (P = 0.002) after birth, and more red blood cell transfusions (P = 0.039)., Conclusions: Smaller GA, lower BW, lower Apgar score at 5 min, more severe RDS, greater use of surfactants, and lower hemoglobin after birth place VLBW infants at greater risk of PDA. Proper prenatal care, and prevention of premature labor and delivery may be the most important preventative factors. The appropriate hemoglobin level for PDA closure requires further investigation., (© 2013 The Authors. Pediatrics International © 2013 Japan Pediatric Society.)

CYP2A13, a human pulmonary specific cytochrome P450 enzyme, plays an important role in susceptibility to tobacco-specific nitrosamines (TSNAs)-induced lung cancer in humans. The pattern of CYP2A13 distribution in respiratory tract affects the susceptibility of the lung to carcinogens. CYP2A13 is expressed in the epithelium of trachea and bronchi; however its pattern of expression in human lung cancer remains largely unknown. This study aimed to determine the CYP2A13 expression in specimens from human non-small cell lung carcinomas (NSCLCs), i.e., adenocarcinoma and squamous carcinoma, by immunohistochemical (IHC) analysis and to identify the potential linkage between tumor CYP2A13 levels and some clinicopathological characteristics of NSCLC patients in Taiwan. The tumor CYP2A13 IHC staining signal was strong in 76% of the 112 study subjects. Study subjects (especially non-smoking or lung adenocarcinoma patients) with higher tumor CYP2A13 levels were younger. Multiple logistic regression analysis revealed that in younger subjects (age ≤ 66) and heavy smokers (pack-years ≥ 40), the odds ratio (OR) for positive tumor CYP2A13 staining was significantly higher than that for negative tumor CYP2A13 staining. Moreover, the association of EGFR gene mutations and positive tumor CYP2A13 staining was also revealed. In conclusion, these findings suggest the potential involvement of pulmonary CYP2A13 in the early occurrence of NSCLC as well as in the development of EGFR gene mutations., (Copyright © 2013 Elsevier Ltd. All rights reserved.)

Backgrounds: The circle of Willis (CoW) is a primary collateral pathway that compensates quickly for a drop in cerebral blood flow. Using the complete CoW as a surrogate marker for good collateral circulation, its prognostic value after intravenous thrombolysis was examined., Methods: We prospectively studied 64 consecutive patients with acute ischemic stroke treated with tissue plasminogen activator within 3 hours of stroke onset between October 2005 and June 2012 in our hospital. The study protocol was based on standard guidelines for intravenous thrombolysis. On computed tomographic angiography 24 hours after thrombolysis, the CoW was complete in 21 (32.8%) cases and incomplete in 43 (67.2%)., Results: Patients with complete CoW were more likely to have early improvement in National Institute of Health Stroke Scale (NIHSS) score (median improvement 2 vs 0 at 2 hours; 4 vs 1 at 24 hours), be independent at 3 months (42% vs 19%). In the incomplete CoW group, the rate of symptomatic intracerebral haemorrhage (SICH) according to the Safe Implementation of Thrombolysis in Stroke-Monitoring Study (SITS-MOST) definition was almost 3 times higher. Complete CoW was one of the strongest predictors of good functional outcome at 3 months (odds ratio 2.32; P = .01)., Conclusions: Complete CoW independently predicted functional independence and survival., (Copyright © 2013 Elsevier Inc. All rights reserved.)

Objectives: To evaluate the prognostic value of initial direct radionuclide cystography (DRC) for spontaneous resolution of vesicoureteral reflux (VUR)., Methods: Fifty-one children with initial diagnosis and 1-6 years' follow-up of VUR by DRC were enrolled in this study. VUR was graded according to the anatomic grading as (1) mild reflux corresponding to tracer just in ureter, (2) moderate reflux with accumulation of activity in a non-dilated collecting system and ureter, and (3) severe reflux equated with a dilated ureter and collecting system. The severity of VUR was also expressed according to the functional classification as (1) transient reflux, which occurred at filling or voiding phase only and (2) persistent reflux, present in both filling and voiding phases., Results: Twenty-nine of the 51 children had unilateral VUR, and the other 22 had bilateral VUR. In the total of 73 refluxing ureters, there were 12 mild, 49 moderate and 12 severe VUR according to anatomic grading, and 30 transient and 43 persistent VUR according to the functional grading. After follow-up, resolution of VUR was found in 92% (11/12) of mild, 59% (29/49) of moderate and 25% (3/12) of severe VUR (P=.04, mild vs. moderate; P=.003, mild vs. severe). Eighty percent (24/30) of transient and 44% (19/43) of persistent reflux showed spontaneous resolution (P=.003)., Conclusions: DRC allows anatomic and functional classification of VUR. It is an ideal method for the diagnosis, staging and follow-up of VUR, and provides valuable information to predict the patient's outcome., (Copyright © 2011 Elsevier España, S.L. and SEMNIM. All rights reserved.)

Parkinsonism with myoclonus is rarely associated with infectious disease in adults. We present a 55-year-old man experiencing acute onset bilateral limb tremor, rigidity, and myoclonus with small-stepped gait, and skin rash involving the trunk and limbs, after a fever. Serum was positive for anti-Orientia tsutsugamushi immunoglobulin M antibody. Brain MRI revealed no abnormalities. The fever improved with oral doxycycline, and the parkinsonism and myoclonus improved with amantadine and clonazepam. This is a rare case of parkinsonism with myolonus associated with scrub typhus infection., (Copyright © 2012 Elsevier Ltd. All rights reserved.)

Background: Beginning 2007, the intratracheal route of epinephrine to end massive pulmonary hemorrhage (MPH) in very low-birthweight (VLBW) infants was modified at Kaohsiung Veterans General Hospital. The aim of the present study was to assess the change in outcomes for these infants, and to evaluate the risk factors of MPH., Methods: Using the database of the Premature Baby Foundation of Taiwan, the mortality, risk factors and characteristics of VLBW infants with or without MPH were compared between 2000-2006 and 2007-2010., Results: Between January 2000 and December 2010, 399 VLBW infants were admitted to Kaohsiung Veterans General Hospital. Mean birthweight (BW) was 1099.6 ± 272.7 g, and mean gestational age (GA) was 28.7 ± 2.9 weeks. The overall survival rate was 84.2%. Sixteen (4%) had MPH: 11 in the first group (2000-2006; 18.2% survival rate), and five in the second group (2007-2010; 80% survival rate; P= 0.0000002). Infants with MPH had lower mean BW (864.9 ± 301.4 g, P= 0.0004), smaller mean GA (26.1 ± 2.0 weeks, P= 0.0002), significantly lower Apgar scores at 1 and 5 min, higher severity of respiratory distress syndrome (RDS; grades 3 or 4), and greater use of surfactant than infants without MPH. They also had more intraventricular hemorrhage and higher mortality., Conclusions: Smaller GA, lower BW, lower Apgar scores at 1 and 5 min, severe RDS (grades 3 or 4), and use of surfactant place VLBW infants at greater risk of MPH. Proper prenatal care and preventing premature labor and delivery were the most important preventative factors. A quick, deep thrust of intratracheal epinephrine with a catheter may improve survival., (© 2012 The Authors. Pediatrics International © 2012 Japan Pediatric Society.)