Acute heart failure with mildly reduced ejection fraction and myocardial infarction: a multi-institutional cohort study.

BACKGROUND: Little research has been done on ischemic outcomes related to left ventricular ejection fraction (EF) in acute decompensated heart failure (ADHF). METHODS: A retrospective cohort study was conducted between 2001 and 2021 using the Chang Gung Research Database. ADHF Patients discharged from hospitals between January 1, 2005, and December 31, 2019. Cardiovascular (CV) mortality and heart failure (HF) rehospitalization are the primary outcome components, along with all-cause mortality, acute myocardial infarction (AMI) and stroke. RESULTS: A total of 12,852 ADHF patients were identified, of whom 2,222 (17.3%) had HFmrEF, the mean (SD) age was 68.5 (14.6) years, and 1,327 (59.7%) were males. In comparison with HFrEF and HFpEF patients, HFmrEF patients had a significant phenotype comorbid with diabetes, dyslipidemia, and ischemic heart disease. Patients with HFmrEF were more likely to experience renal failure, dialysis, and replacement. Both HFmrEF and HFrEF had similar rates of cardioversion and coronary interventions. There was an intermediate clinical outcome between HFpEF and HFrEF, but HFmrEF had the highest rate of AMI (HFpEF, 9.3%; HFmrEF, 13.6%; HFrEF, 9.9%). The AMI rates in HFmrEF were higher than those in HFpEF (AHR, 1.15; 95% Confidence Interval, 0.99 to 1.32) but not in HFrEF (AHR, 0.99; 95% Confidence Interval, 0.87 to 1.13). CONCLUSION: Acute decompression in patients with HFmrEF increases the risk of myocardial infarction. The relationship between HFmrEF and ischemic cardiomyopathy, as well as optimal anti-ischemic treatment, requires further research on a large scale.

The Clinical and Genetic Characteristics of Streptococcus agalactiae Meningitis in Neonates.

Streptococcus agalactiae (Group B Streptococcus, GBS) is an important pathogen of bacterial meningitis in neonates. We aimed to investigate the clinical and genetic characteristics of neonatal GBS meningitis. All neonates with GBS meningitis at a tertiary level medical center in Taiwan between 2003 and 2020 were analyzed. Capsule serotyping, multilocus sequence typing, antimicrobial resistance, and whole-genome sequencing (WGS) were performed on the GBS isolates. We identified 48 neonates with GBS meningitis and 140 neonates with GBS sepsis. Neonates with GBS meningitis had significantly more severe clinical symptoms; thirty-seven neonates (77.8%) had neurological complications; seven (14.6%) neonates died; and 17 (41.5%) survivors had neurological sequelae at discharge. The most common serotypes that caused meningitis in neonates were type III (68.8%), Ia (20.8%), and Ib (8.3%). Sequence type (ST) is highly correlated with serotypes, and ST17/III GBS accounted for more than half of GBS meningitis cases (56.3%, n = 27), followed by ST19/Ia, ST23/Ia, and ST12/Ib. All GBS isolates were sensitive to ampicillin, but a high resistance rates of 72.3% and 70.7% to erythromycin and clindamycin, respectively, were noted in the cohort. The virulence and pilus genes varied greatly between different GBS serotypes. WGS analyses showed that the presence of PezT; BspC; and ICESag37 was likely associated with the occurrence of meningitis and was documented in 60.4%, 77.1%, and 52.1% of the GBS isolates that caused neonatal meningitis. We concluded that GBS meningitis can cause serious morbidity in neonates. Further experimental models are warranted to investigate the clinical and genetic relevance of GBS meningitis. Specific GBS strains that likely cause meningitis requires further investigation and clinical attention.

Clinical characteristics and outcomes of neonates with polymicrobial ventilator-associated pneumonia in the intensive care unit.

BACKGROUND: Ventilator associated pneumonia (VAP) caused by more than one microorganisms is not uncommon and may be potentially challenging, but the relevant data is scarce in ventilated neonates. We aimed to investigate the clinical characteristics and outcomes of polymicrobial VAP in the neonatal intensive care unit (NICU). METHODS: All neonates with definite diagnosis of VAP from a tertiary level neonatal intensive care unit (NICU) in Taiwan between October 2017 and September 2020 were prospectively observed and enrolled for analyses. All clinical features, therapeutic interventions and outcomes were compared between the polymicrobial VAP and monomicrobial VAP episodes. Multivariate regression analyses were used to find the independent risk factors for treatment failure. RESULTS: Among 236 episodes of neonatal VAP, 60 (25.4%) were caused by more than one microorganisms. Polymicrobial VAP episodes were more likely to be associated with multidrug-resistant pathogens (53.3% versus 34.7%, P = 0.014), more often occurred in later days of life and in neonates with prolonged intubation and underlying bronchopulmonary dysplasia. Otherwise most clinical characteristics of polymicrobial VAP were similar to those of monomicrobial VAP. The therapeutic responses and treatment outcomes were also comparable between these two groups, although modification of therapeutic antibiotics were significantly more common in polymicrobial VAP episodes than monomicrobial VAP episodes (63.3% versus 46.2%; P < 0.001). None of any specific pathogens was significantly associated with worse outcomes. Instead, it is the severity of illness, including presence of concurrent bacteremia, septic shock, and requirement of high-frequency oscillatory ventilator and underlying neurological sequelae that are independently associated with treatment failure. CONCLUSIONS: Polymicrobial VAP accounted for 25.4% of all neonatal VAP in the NICU, and frequently occurred in neonates with prolonged intubation and underlying bronchopulmonary dysplasia. In our cohort, most clinical features, therapeutic responses and final outcomes of neonates with monomicrobial and polymicrobial VAP did not differ significantly.

Clustered Regularly Interspaced Short Palindromic Repeat Analysis of Clonal Complex 17 Serotype III Group B Streptococcus Strains Causing Neonatal Invasive Diseases.

Group B Streptococcus (GBS) is an important pathogen of neonatal infections, and the clonal complex (CC)-17/serotype III GBS strain has emerged as the dominant strain. The clinical manifestations of CC17/III GBS sepsis may vary greatly but have not been well-investigated. A total of 103 CC17/III GBS isolates that caused neonatal invasive diseases were studied using a new approach based on clustered regularly interspaced short palindromic repeats (CRISPR) loci and restriction fragment length polymorphism (RFLP) analyses. All spacers of CRISPR loci were sequenced and analyzed with the clinical presentations. After CRISPR-RFLP analyses, a total of 11 different patterns were observed among the 103 CRISPR-positive GBS isolates. GBS isolates with the same RFLP patterns were found to have highly comparable spacer contents. Comparative sequence analysis of the CRISPR1 spacer content revealed that it is highly diverse and consistent with the dynamics of this system. A total of 29 of 43 (67.4%) spacers displayed homology to reported phage and plasmid DNA sequences. In addition, all CC17/III GBS isolates could be categorized into three subgroups based on the CRISPR-RFLP patterns and eBURST analysis. The CC17/III GBS isolates with a specific CRISPR-RFLP pattern were more significantly associated with occurrences of severe sepsis (57.1% vs. 29.3%, p = 0.012) and meningitis (50.0% vs. 20.8%, p = 0.009) than GBS isolates with RFLP lengths between 1000 and 1300 bp. Whole-genome sequencing was also performed to verify the differences between CC17/III GBS isolates with different CRISPR-RFLP patterns. We concluded that the CRISPR-RFLP analysis is potentially applicable to categorizing CC17/III GBS isolates, and a specific CRISPR-RFLP pattern could be used as a new biomarker to predict meningitis and illness severity after further verification.

Emerging serotype III sequence type 17 group B streptococcus invasive infection in infants: the clinical characteristics and impacts on outcomes.

BACKGROUND: Group B Streptococcus (GBS) is an important pathogen that causes high mortality and morbidity in young infants. However, data on clinical manifestations between different GBS serotypes and correlation with molecular epidemiology are largely incomplete. The aim of this study was to determine the serotype distribution, antimicrobial resistance, clinical features and molecular characteristics of invasive GBS isolates recovered from Taiwanese infants. METHODS: From 2003 to 2017, 182 non-duplicate GBS isolates that caused invasive disease in infants less than one year of age underwent serotyping, multilocus sequence typing (MLST) and antibiotic susceptibility testing. The clinical features of these infants with GBS disease were also reviewed. RESULTS: Of the 182 patients with invasive GBS disease, 41 (22.5%) were early-onset disease, 121 (66.5%) were late-onset disease and 20 (11.0%) were late late-onset disease (> 90 days of age). All these patients were treated with effective antibiotics on time. Among them, 51 (28.0%) had meningitis, 29 (16.0%) had neurological complications, 12 (6.6%) died during hospitalization, and 15 (8.8%) out of 170 patients who survived had long-term neurological sequelae at discharge. Serotype III GBS strains accounted for 64.8%, followed by serotype Ia (18.1%) and Ib (8.2%). MLST analysis revealed 11 different sequence types among the 182 isolates and ST-17 was the most dominant sequence type (56.6%). The correlation between serotype III and ST17 was evident, as ST17 accounted for 87.3% of all serotype III isolates. There was an obvious increasing trend of type III/ST-17 GBS that caused invasive disease in infants. All isolates were susceptible to penicillin, cefotaxime, and vancomycin, while 68.1 and 65.9% were resistant to erythromycin and clindamycin, respectively. CONCLUSIONS: Despite timely and appropriate antibiotic treatment, a significant proportion of invasive GBS disease still inevitably causes adverse outcomes. Further study to explore preventive strategies and development of serotype-based vaccines will be necessary in the future.

In-hospital and post-discharge outcomes of pediatric acute myocarditis underwent after high-dose steroid or intravenous immunoglobulin therapy.

BACKGROUND: High-dose steroids and intravenous immunoglobulin (IVIG) are controversial treatments for pediatric patients with acute myocarditis. This study aimed to investigate their efficacies in the Taiwanese pediatric population. METHODS: This study evaluated 5563 acute myocarditis patients from the Taiwan's National Health Insurance Research Database and identified 1542 pediatric patients hospitalized for acute myocarditis between January 1, 2001 and December 31, 2011. The exclusion criteria were age of > 11 years, associated cardiovascular comorbidities, autoimmune disease, malignancy before the index hospitalization, extracorporeal membrane oxygenation, intra-aortic balloon pumping, and dual therapy using IVIG and high-dose steroids. RESULTS: After 2:1 propensity score matching, we identified 208 subjects without steroid therapy and 104 subjects who received high-dose steroids. The mean age in that cohort was 2.6 ± 2.9 years, and high-dose steroid therapy had no significant effects on major in-hospital complications and post-discharge outcomes. After 2:1 propensity score matching, we identified 178 subjects without IVIG therapy and 89 subjects who received IVIG. The mean age in that cohort was 2.0 ± 2.1 years, and IVIG had no significant effects on the major outcomes. CONCLUSIONS: The present study revealed that high-dose steroid or IVIG therapy had no significant effects on major in-hospital complications, late heart failure hospitalization, and long-term mortality.

Aminotransferase Ratio Is a Useful Index for Hepatosteatosis in Children and Adolescents: A Cross-Sectional Observational Study.

Nonalcoholic fatty liver disease (NAFLD) and childhood obesity are emerging global health issues. The aim of this study was to identify a simple predictor of NAFLD in children and adolescents. This community-based study was conducted from December 2012 to September 2013 in Taiwan and included 1,222 children between 10 and 19 years of age. After excluding alcohol consumption and hepatic-related lesions, NAFLD was diagnosed according to sonographic criteria. Potential confounding factors (including age, gender, and anthropometric and laboratory data) were tested by logistic regression analysis. The cutoff value was determined using receiver operating characteristic (ROC) curve analysis. In addition to older age, heavier weight, and wider waist, subjects with NAFLD had significantly higher blood pressure, lipid disturbances, and alanine aminotransferase/aspartate aminotransferase (ALT/AST) ratios. The correlation between NAFLD and ALT/AST ratio remained significant even after adjusting for confounders (adjusted odds ratio [OR], 2.19; 95% confidence interval [CI], 1.24-3.87; p = .007). The risk score of having a fatty liver, based on ALT/AST ratio, was greater than 0.981 according to ROC curve analysis (sensitivity, 60.5%; specificity, 80.3%; area under the curve, 0.756; CI, 0.71-0.80; p < .001). Therefore, ALT/AST ratio may represent a powerful index of hepatosteatosis in children and adolescents.

Comparison of the incidence, clinical features and outcomes of invasive candidiasis in children and neonates.

BACKGROUND: Invasive candidiasis differs greatly between children and neonates. We aimed to investigate the different therapeutic approaches and their effects on treatment outcomes of these two groups. METHODS: Episodes of neonatal invasive candidiasis were compared with non-neonatal pediatric episodes during a 12-year cohort study. Clinical isolates were documented by matrix-assisted laser desorption/ionization-time of flight mass spectrometry and DNA sequencing, and antifungal susceptibility testing was performed. RESULTS: A total of 342 episodes of invasive candidiasis (113 neonatal and 229 non-neonatal pediatric episodes) in 281 pediatric patients (96 neonates and 185 children) were identified. Candida albicans was the most common pathogen causing invasive candidiasis in neonates and children (47.8% vs. 44.1%). The antifungal susceptibility profiles were not significantly different between neonates and children. More neonates received amphotericin B as therapy, whereas more children received fluconazole or caspofungin. Compared with children, neonates had a significantly longer duration of fungemia, higher rates of septic shock (34.5% vs. 21.8%; P = 0.013), sepsis-attributable mortality (28.3% vs. 17.5%; P = 0.024) and in-hospital mortality (42.7% vs. 25.4%; P = 0.004) than children. Independent risk factors for treatment failure of invasive candidiasis were septic shock (odds ration [OR] 16.01; 95% confidence interval [CI] 7.64-33.56; P <  0.001), delayed removal of intravenous catheter (OR 6.78; 95% CI 2.80-17.41; P <  0.001), renal failure (OR 5.38; 95% CI 1.99-14.57; P = 0.001), and breakthrough invasive candidiasis (OR 2.99; 95% CI 1.04-8.67; P = 0.043). CONCLUSIONS: Neonatal invasive candidiasis has worse outcomes than non-neonatal pediatric candidiasis. Neonatologists and pediatricians must consider age-specific differences when developing treatment and prevention guidelines, or when interpreting studies of other age groups.

Incidence, clinical features, and implications on outcomes of neonatal late-onset sepsis with concurrent infectious focus.

BACKGROUND: Neonatal bloodstream infection (BSI) is the most important cause of morbidity and mortality in the neonatal intensive care unit (NICU). Although most neonatal BSIs are primary bacteremia, some are associated with a focus of infection. This distinction is not well characterized. METHODS: All patients with neonatal late-onset sepsis (LOS) between January 2006 and December 2013 were enrolled. LOS was categorized as a BSI with a concurrent focus of infection if LOS occurred before or within 24 h after the diagnosis of a specific infectious entity, and as "primary bacteremia" if no concurrent focus of infection was identified. Data concerning demographics, hospital course, microbiology, and outcomes were compared via univariate and multivariate analyses. RESULTS: Of 948 episodes of neonatal LOS, 781 (82.4%) were primary bacteremia, whereas 167 (17.6%) were associated with a known focus of infection, including meningitis (n = 51, 5.4%), ventilator-associated pneumonia (VAP) (n = 36, 3.8%), catheter-related bloodstream infections (n = 57, 6.0%), and necrotizing enterocolitis (NEC) (n = 21, 2.2%). The majority of NEC-associated BSIs were caused by gram-negative bacilli (85.7%). Group B streptococcus accounted for nearly one-third of all meningitis cases (29.4%). Although sepsis-attributable mortality was comparable between primary bacteremia and neonatal BSIs with a focus of infection, neonatal BSIs with meningitis, VAP, and NEC had significantly higher rates of infectious complications. The independent risk factors of sepsis-attributable mortality were infectious complications (Odds ratio [OR] 6.98; 95% confidence interval [CI] 3.64-13.39, P < 0.001); history of one or more than one previous episode(s) of BSI (OR 2.40 and 7.40; 95% CI 1.21-4.74 and 3.70-14.78, P = 0.012 and <0.001, respectively); and underlying secondary pulmonary hypertension in neonates (OR 4.77; 95% CI 1.91-11.96, P = 0.001). CONCLUSIONS: A considerable proportion of neonatal LOS can be associated with known infectious foci in the NICU. The microbiologic etiology of neonatal LOS with a concurrent focus of infection is significantly different from that of primary bacteremia. Neonatal BSIs with concurrent meningitis, VAP, or NEC are significantly more likely to have infectious complications. This association independently leads to sepsis-attributable mortality.

Waist-to-height ratio is a useful index for nonalcoholic fatty liver disease in children and adolescents: a secondary data analysis.

BACKGROUND: Nonalcoholic fatty liver disease (NAFLD) is a global problem and pediatric obesity has risen dramatically. Early NAFLD might progress to nonalcoholic steatohepatitis (NASH) or liver cirrhosis and significantly increase liver disease-related mortality. We looked for NAFLD predictors in children and adolescents. METHODS: This community-based, cross-sectional study ran from December 2012 to September 2013 in southwestern Taiwan. Children <10 and >19 years old, with detected hepatic diseases, or who drank alcohol were excluded. The diagnosis of NAFLD was based on ultrasound: age, sex, anthropometric measurements, and laboratory data were evaluated for associated risks by using logistic regression analysis. Receiver operating characteristic (ROC) curves were used to determine cutoff values. RESULTS: We enrolled one thousand, two hundred and ten children (594 males; 616 females; mean age: 15.5 ± 2.8 years). Age, anthropometric measurements, and laboratory data were significantly higher in children with NAFLD. The association between NAFLD and the waist-to-height ratio (WHtR) was significant (adjusted odds ratio: 2.6; 95% confidence interval: 1.909-3.549; P < 0.001). It indicated highly suspicion of NAFLD (sensitivity: 70.1%; specificity 76.9%) when the WHtR for children and adolescents is above the cutoff value of 0.469. CONCLUSIONS: The WHtR might be a powerful index of the severity of pediatric NAFLD.

Cudraflavone C Induces Apoptosis of A375.S2 Melanoma Cells through Mitochondrial ROS Production and MAPK Activation.

Melanoma is the most malignant form of skin cancer and is associated with a very poor prognosis. The aim of this study was to evaluate the apoptotic effects of cudraflavone C on A375.S2 melanoma cells and to determine the underlying mechanisms involved in apoptosis. Cell viability was determined using the MTT and real-time cytotoxicity assays. Flow cytometric evaluation of apoptosis was performed after staining the cells with Annexin V-FITC and propidium iodide. The mitochondrial membrane potential was evaluated using the JC-1 assay. Cellular ROS production was measured using the CellROX assay, while mitochondrial ROS production was evaluated using the MitoSOX assay. It was observed that cudraflavone C inhibited growth in A375.S2 melanoma cells, and promoted apoptosis via the mitochondrial pathway mediated by increased mitochondrial ROS production. In addition, cudraflavone C induced phosphorylation of MAPKs (p38, ERK, and JNK) and up-regulated the expression of apoptotic proteins (Puma, Bax, Bad, Bid, Apaf-1, cytochrome C, caspase-9, and caspase-3/7) in A375.S2 cells. Pretreatment of A375.S2 cells with MitoTEMPOL (a mitochondria-targeted antioxidant) attenuated the phosphorylation of MAPKs, expression of apoptotic proteins, and the overall progression of apoptosis. In summary, cudraflavone C induced apoptosis in A375.S2 melanoma cells by increasing mitochondrial ROS production; thus, activating p38, ERK, and JNK; and increasing the expression of apoptotic proteins. Therefore, cudraflavone C may be regarded as a potential form of treatment for malignant melanoma.

Sleep Problems in Children with Attention Deficit/Hyperactivity Disorder: Current Status of Knowledge and Appropriate Management.

Attention deficit hyperactivity disorder (ADHD) affects approximately 5 % of children and adolescents, and sleep problems are common in these patients. There is growing evidence informing the significant importance of sleep problems in youth with ADHD. The sleep problems in children with ADHD include specific sleep disorders and sleep disturbances due to comorbid psychiatric disorders or ADHD medications. The specific sleep disorders of ADHD children include behaviorally based insomnia, sleep-disordered breathing, and restless legs syndrome/periodic limb movement disorder. Current practices on the management of sleep problems for ADHD children are based mostly on expert consensus, whereas more evidence-based literature can be found only recently. Assessment of the sleep conditions in ADHD children before initiation of pharmacotherapy is the currently recommended guideline, and good sleep hygiene can be considered as the first-line treatment option. In addition to modifying the dose regimens, formulation, or alternative stimulants when sleep problems are encountered in ADHD children, atomoxetine, once daily guanfacine extended release, and melatonin are potential choices for ADHD children with more severe sleep problems. In this review, we aimed to provide the most updated information, preferably based on meta-analyses, systemic review, and randomized controlled trials published in the latest 3 years, in order to be clinically useful for practitioners and clinicians.

Characteristics of neonates with culture-proven bloodstream infection who have low levels of C-reactive protein (≦10 mg/L).

BACKGROUND: Elevated C-reactive protein (CRP) level is widely used in clinical practice as a marker to distinguish between neonates with or without sepsis. However, some neonates with bacteremia have a CRP level within the normal range and they are not well characterized. METHODS: All episodes of neonatal culture-proven bloodstream infections (BSIs) between July 2004 and June 2012 were enrolled. Patients characteristics were compared for three CRP groups (low, ≤ 10 mg/L; intermediate, 11-100 mg/L; and high, > 100 mg/L) using the Chi-square test and one-way ANOVA. The sepsis-attributable mortality rates were compared using logistic regression analyses. RESULTS: Of 986 episodes of neonatal BSI, 247 (25.1 %) had CRP ≤10 mg/L at the onset of clinical sepsis. In the low CRP group, patients had lower gestational age and birth weight, and an earlier occurrence of BSI. Patients with underlying gastrointestinal pathology, renal disorders, cholestasis, and pulmonary hypertension had a non-significant elevated CRP level at the onset of sepsis. In the blood culture of the low CRP group, coagulase-negative staphylococci (CoNS) were relatively more common (55.9 %, p < 0.001) than the other two groups, although one-fourth were infected with gram-negative bacilli (19.0 %), fungi (2.8 %), or polymicrobial pathogens (3.6 %). Of the BSIs with initial low CRP, 29.1 % were treated with inadequate antibiotics, 13.0 % progressed to septic shock, and 5.3 % had infectious complications. The sepsis-attributable mortality rate was lower in the low CRP group (4.9 %) than in the high CRP group (13.6 %). CONCLUSIONS: A considerable proportion of neonatal BSIs had a normal or low initial CRP level (≤10 mg/L), which was more likely to occur in low birth weight or extremely preterm infants, those with earlier onset of sepsis, and those infected with CoNS. Plasma CRP level should not be used to rule out severe culture-proven sepsis or guide the empirical choice of antibiotics.

Eupafolin inhibits PGE2 production and COX2 expression in LPS-stimulated human dermal fibroblasts by blocking JNK/AP-1 and Nox2/p47(phox) pathway.

Eupafolin, a major active component found in the methanol extracts of Phyla nodiflora, has been used to treat inflammation of skin. We examined its effects on cyclooxygenase-2 (COX-2) expression in LPS-treated human dermal fibroblasts. Lipopolysaccharide (LPS) significantly increased prostaglandin-E2 (PGE2) production associated with increased COX-2 expression in Hs68 cells. This effect was blocked by eupafolin, TLR-4 antibody, antioxidants (APO and NAC), as well as inhibitors, including U0126 (ERK1/2), SB202190 (p38), SP600125 (JNK1/2), and Tanshinone IIA (AP-1). In gene regulation level, qPCR and promoter assays revealed that COX-2 expression was attenuated by eupafolin. In addition, eupafolin also ameliorated LPS-induced p47 phox activation and decreased reactive oxygen species (ROS) generation and NADPH oxidase (Nox) activity. Moreover, pretreatment with eupafolin and APO led to reduced LPS-induced phosphorylation of ERK1/2, JNK, and p38. Further, eupafolin attenuated LPS-induced increase in AP-1 transcription factor binding activity as well as the increase in the phosphorylation of c-Jun and c-Fos. In vivo studies have shown that in dermal fibroblasts of LPS treated mice, eupafolin exerted anti-inflammation effects by decreasing COX-2 protein levels. Our results reveal a novel mechanism for anti-inflammatory and anti-oxidative effects of eupafolin that involved inhibition of LPS-induced ROS generation, suppression of MAPK phosphorylation, diminished DNA binding activity of AP-1 and attenuated COX-2 expression leading to reduced production of prostaglandin E2 (PGE2). Our results demonstrate that eupafolin may be used to treat inflammatory responses associated with dermatologic diseases.

The impact of fetuin-A on predicting aortic arch calcification: secondary analysis of a community-based survey.

Introduction: Atherosclerotic cardiovascular disease is associated with a high mortality rate due to vascular calcification. The role of fetuin-A in aortic arch calcification (AAC) is less well understood. Methods: An analysis of secondary biomarkers was performed on 800 individuals from the biobank using the community database. AAC was defined by radiologists based on imaging. Multiple variables logical analysis was used for risk analysis. Results: A total of 736 individual samples were collected based on age and gender. The average age is 65 ± 10 years, and half the population comprises men. In spite of similar body weight, renal function, and hepatic function, the AAC group had higher blood pressure and fetuin-A levels independently: systolic blood pressure (SBP) index ≥130 mmHg [adjusted odds ratio (aOR) 1.85, 95% confidence interval (CI) 1.34-2.57, p = 0.002] and fetuin-A (aOR 0.62, 95% CI 0.50-0.76, p < 0.001). Moreover, it is evident that AAC can be predicted more accurately when combined with SBP ≥130 mmHg and a low fetuin-A level (<358 µg/ml: aOR 5.39, 95% CI 3.21-9.08) compared with the reference. Conclusion: Low fetuin-A levels are significantly correlated with AAC while there is an increased association between vascular calcification and coexisting hypertension.

The Epidemiology, Management and Therapeutic Outcomes of Subdural Empyema in Neonates with Acute Bacterial Meningitis.

Background: Subdural empyema is one of the more serious complications of bacterial meningitis and therapeutic challenges to clinicians. We aimed to evaluate the clinical characteristics, treatment, and outcome of subdural empyema in neonates with bacterial meningitis. Methods: A retrospective cohort study was conducted in two medical centers in Taiwan that enrolled all cases of neonates with subdural empyema after bacterial meningitis between 2003 and 2020. Results: Subdural empyema was diagnosed in 27 of 153 (17.6%) neonates with acute bacterial meningitis compared with cases of meningitis without subdural empyema. The demographics and pathogen distributions were comparable between the study group and the controls, but neonates with subdural empyema were significantly more likely to have clinical manifestations of fever (85.2%) and seizure (81.5%) (both p values < 0.05). The cerebrospinal fluid results of neonates with subdural empyema showed significantly higher white blood cell counts, lower glucose levels and higher protein levels (p = 0.011, 0.003 and 0.006, respectively). Neonates with subdural empyema had a significantly higher rate of neurological complications, especially subdural effusions and periventricular leukomalacia. Although the final mortality rate was not increased in neonates with subdural empyema when compared with the controls, they were often treated much longer and had a high rate of long-term neurological sequelae. Conclusions: Subdural empyema is not uncommon in neonates with acute bacterial meningitis and was associated with a high risk of neurological complications, although it does not significantly increase the final mortality rate. Close monitoring of the occurrence of subdural empyema is required, and appropriate long-term antibiotic treatment after surgical intervention may lead to optimized outcomes.

Psychosocial and emotional adjustment for children with pediatric cancer and their primary caregivers and the impact on their health-related quality of life during the first 6 months.

PURPOSE: To evaluate caregiver-reported psychosocial adjustment and health-related quality of life (HrQoL) of Taiwanese children with newly diagnosed cancer and their caregivers during the first 6 months of treatment. METHODS: Caregivers of 89 newly diagnosed children completed the child behavior checklist, the pediatric quality of life inventory (PedsQL(™) 4.0), the Parenting Stress Index, and the SF-36 questionnaire at diagnosis, and again 3 and 6 months into treatment. They were compared with a group of age- and sex-matched controls from general community. RESULTS: Significantly worse HrQoL in both children and their caregivers and greater parenting stress were noted in the cancer group than the controls during the first 6 months. Children with cancer were found to have significantly more internalizing behavioral problems and somatic complaints, especially those younger than 12 years old. After starting chemotherapy, significant decrease in parenting stress and improvements of both caregivers and children's HrQoL were noted within the first 6 months, although not to the level comparable with normal controls. CONCLUSIONS: Although children and their caregivers can adjust themselves gradually during the first 6 months after diagnosis of cancer, intervention and efforts aimed at reducing their distress and promoting adjustments are still required during this period.

Long-term effects of stimulants on neurocognitive performance of Taiwanese children with attention-deficit/hyperactivity disorder.

BACKGROUND: Attention-deficit/hyperactivity disorder (ADHD) is a common behavioral and neurocognitive disorder in school-age children. Methylphenidate (MPH) is the most frequently prescribed CNS stimulant for ADHD. The aim of this study is to evaluate the changes in intelligence quotient and domains of neurocognitive function after long-term MPH treatment of Taiwanese children with ADHD. METHODS: The Wechsler Intelligence Scale (WISC-III) was administrated twice at an interval of at least one year for all 171 subjects (6-12 years) and 47 age- and gender-matched children without ADHD. The ADHD-Rating scale and Clinical Global Impression-Severity (CGI-S) were also used at the time of enrolment, and at 6 months and one year later. RESULTS: Taiwanese children with ADHD had lower Verbal IQ (VIQ) and Full IQ (FIQ) and performed poorly on several subtests of the WISC-III, including Similarities, Vocabulary, and Coding, compared to healthy children without ADHD. After one year of MPH treatment, significant decrements in all scores of the ADHD-Rating scale and CGI-S and increments in several domains of the WISC-III, including FIQ, VIQ, PIQ, Perceptual Organization Index (POI), Picture Completion, Picture Arrangement, Object Assembly, and Digit Span were observed. When the ADHD children under MPH treatment were subdivided into two age groups (6-8 years and 9-12 years), significantly better performance in some subtests and subscales of the WISC-III (such as Similarities, Comprehension, and Object assembly) was found in the 6-8 years age group. CONCLUSIONS: Long-term MPH treatment may improve the neurocognitive profiles of the ADHD children, as seen in their performance in several subtests and in the IQ scores on the WISC-III. And this improvement had no correlation with the decrement of ADHD symptoms. Starting stimulant treatment at as young an age as possible is advised due to the greater benefits in the 6-8 years age group, as seen in this study. More research in this area is also needed to confirm these results.

Association between viral hepatitis and metabolic syndrome in lung function impairment: A Taiwan community-based study.

OBJECTIVES: Metabolic syndrome (MetS) and hepatitis C virus (HCV) are associated with a higher risk of impaired pulmonary function (iPF). This study aimed to investigate the relationships among MetS, iPF, and viral hepatitis. METHODS: This community-based study enrolled participants undergoing annual health check-ups in southern Taiwan between March and December 2019. We performed multivariable logistic regression analyses adjusted for demographics and characteristics to identify the factors associated with iPF. RESULTS: A total of 2337 participants completed examinations, of whom 928 (39.7%) had iPF. The participants with iPF were elderly (68.8 ± 12.8 years old) and predominately female (63%). MetS increased the risk of iPF (odds ratio (OR) 1.51, 95% confidence interval (CI) 1.27-1.81, p < 0.001). Beyond age (OR 1.03, 95% CI 1.02-1.04) and smoking (OR 1.309, 95% CI 1.004-1.705), female sex (OR 0.74, 95% CI 0.59-0.93) and high education level (OR 0.96, 95% CI 0.94-0.98, p < 0.001) protected against iPF. HCV was not significantly associated with iPF (OR 1.17, 95% CI 0.90-1.52, p = 0.235) in multivariable analysis. MetS was associated with a higher risk of iPF in the non-HBV/HCV group (OR 1.86, 95% CI 1.54-2.26) and HBV alone group (OR 3.44, 95% CI 1.89-6.28), but not in the HCV alone group (OR 1.02, 95% CI 0.64-1.62). DISCUSSION: MetS was an independent predictor of iPF, especially the restrictive type, and had different effects in the HBV/non-viral hepatitis and HCV groups. Female sex and education were inversely associated with iPF.

Clonal Complex 12 Serotype Ib Streptococcus agalactiae Strain Causing Complicated Sepsis in Neonates: Clinical Features and Genetic Characteristics.

Streptococcus agalactiae (group B Streptococcus [GBS]) is well known to cause serious diseases in infants. A serotype Ib GBS strain has recently emerged and become prevalent in Southeast Asia. We aimed to investigate the clinical and genetic characteristics of this strain. All neonates with invasive GBS diseases from a tertiary-level medical center in Taiwan between 2003 and 2020 were analyzed. The capsule serotyping, multilocus sequence typing, and antimicrobial resistance analyses were performed on all the invasive GBS isolates, and whole-genome sequencing (WGS) was performed specifically on the type Ib GBS strain. A total of 188 neonates with invasive GBS disease during the study period were identified. The type Ib GBS strain accounted for 7.4% (n = 14) of neonatal GBS invasive diseases. Almost all type Ib GBS isolates belonged to sequence type 12 (13/14, 92.9%) and clonal complex 12. Neonates with type Ib GBS disease had a significantly higher rate of complicated sepsis (10/14, 71.4%; P < 0.05) and sepsis-attributable mortality (6/14, 42.9%; P < 0.05). Additionally, type Ib GBS isolates had significantly higher rates of resistance to erythromycin and clindamycin (both 100%; P < 0.05) than other GBS serotypes. WGS revealed the presence of an ~75-kb integrative and conjugative element, ICESag37, comprising multiple antibiotic resistance and virulence genes, and PI-1 plus PI-2a were noted in all type Ib serotype 12 (ST12) GBS isolates; these isolates may be responsible for its high invasiveness and antimicrobial resistance rates. The genomic characteristics of the type Ib clonal complex 12 (CC12) GBS strain may account for the high illness severity associated with this strain and its antibiotic resistance. Continuous monitoring and advanced strategies to control the spread of type Ib CC12 GBS should be considered. IMPORTANCE A type Ib ST12 GBS strain is not a common isolate in neonatal invasive diseases and has been ignored for a long time. However, the recent literature and our data showed that such a GBS strain is associated with a significantly higher risk of severe sepsis, higher illness severity, and a significantly higher rate of sepsis-attributable mortality. This study found a novel gene cluster, including the presence of ICESag37 and specific pilus genes, carrying multiple antimicrobial resistance and virulence genes, which may be responsible for the clinical characteristics. Because of the higher mortality and severity of illness, we concluded that continuous monitoring of the type Ib ST12 GBS strain is warranted in the future.