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Background: Human parainfluenza viruses (HPIVs) commonly cause childhood respiratory illness requiring hospitalization in Taiwan. This study aimed to investigate clinical severity and identify risk factors predisposing to severe disease in hospitalized children with HPIV infection. Methods: We included hospitalized patients with lab-confirmed HPIV infection from 2007 to 2018 and collected their demographic and clinical characteristics. Patients with ventilator support, intravenous inotropic agents, and extracorporeal membrane oxygenation were defined as severe cases. Results: There were 554 children hospitalized for HPIV infection. The median age was 1.2 years; 518 patients had non-severe HPIV infection, whereas 36 patients (6.5%) had severe HPIV infection. 266 (48%) patients had underlying diseases, and 190 patients (34.3%) had bacterial co-detection. Children with severe HPIV infection were more likely to have bacterial co-detection than those without (52.8% vs 33.0%, p = 0.02). Patients with lung patch or consolidation had more invasive bacterial co-infection or co-detection than those without patch or consolidation (43% vs 33%, p = 0.06). Patients with neurological disease (adjusted OR 4.77, 95% CI 1.94–11.68), lung consolidation/patch (adjusted OR 6.64, 95% CI 2.80–15.75), and effusion (adjusted OR 11.59, 95% CI 1.52–88.36) had significantly higher risk to have severe HPIV infection. Conclusion: Neurological disease and lung consolidation/patch or effusion were the most significant predictors of severe HPIV infection.

Introduction: COVID-19 poses risks and leads to complications for vulnerable populations, including children. Unreported cases of COVID-19 among children hinder our understanding of the true disease burden. In this study, we aimed to investigate the proportion of children who report no prior infection to SARS-CoV-2 but who nevertheless exhibit serological evidence of prior infection. Methods: Between November 2022 and February 2023, we recruited children and adolescents under 19 years of age who lacked a prior history of SARS-CoV-2 infection. Participants underwent SARS-CoV-2 antibody testing to assess the presence of IgG antibodies specific to nucleocapsid (N) and spike (S) proteins. Demographic and contact information were also collected. Results: Among 260 COVID-19-free children, the overall anti-N antibody positivity rate, which varied across age groups (4%–25%), was 9.2% (24/260). Contact with individuals who were positive for COVID-19, particularly the children's mothers, significantly increased the likelihood of antibody positivity. The median age of the 34 children who remained unvaccinated against COVID-19 was lower than that of the children who were vaccinated (6.5 vs. 9 years; p

Background: Multisystem inflammatory syndrome in children (MIS-C) is a novel disease associated with COVID-19. The COVID-19 epidemic peaked in May 2022 in Taiwan, and we encountered our first case of MIS-C in late May 2022. We aimed to present patients’ clinical manifestations and identify risk factors for shock. Methods: We included patients diagnosed with MIS-C at two medical centers from May 2022 to August 2022. We separated those patients into two groups according to whether they experienced shock. We collected demographic, clinical manifestation, and laboratory data of the patients and performed statistical analysis between the two groups. Results: We enrolled 28 patients, including 13 (46 %) with shock and 15 (54 %) without shock. The median age was 6.4 years (IQR: 1.9–7.5). In single variable analysis, patients with shock tended to be older, had more neurological symptoms, more conjunctivitis and strawberry tongue, lower lymphocyte count, lower platelet counts, and higher C-reactive protein, higher procalcitonin, higher ferritin, and higher D-dimer levels than those without shock. The area under the ROC curve that used procalcitonin to be the risk factor of shock with MIS-C was 0.815 (95 % CI 0.644 to 0.987). The cutoff value obtained by ROC analysis of procalcitonin was 1.68 ng/mL. With this cutoff, the test characteristics of procalcitonin were as follows: sensitivity 77 %, specificity 93 %, positive predictive value 91 %, negative predictive value 82 %. Multivariable analysis revealed that procalcitonin was the only independent risk factor of shock with MIS-C on admission (OR, 26.00, 95 % CI, 1.01–668.89). Conclusions: MIS-C patients with high initial procalcitonin levels have higher risks of experiencing shock and may need ICU admission.

Background: Since April 2022, a notable increase in COVID-19 cases with the rapid spread of the SARS-CoV-2 Omicron variant has been reported in Taiwan. In the epidemic, children were one of the most vulnerable groups, so we analyzed their clinical presentations and factors associated with severe complications of COVID-19 in children. Methods: We included hospitalized patients under 18 years old with lab-confirmed SARS-CoV-2 infection from March 1, 2022, to July 31, 2022. We collected the demographic and clinical characteristics of the patients. Patients requiring intensive care were defined as severe cases. Results: Among the 339 enrolled patients, the median age was 31 months (interquartile range (IQR), 8–79.0 months); and 96 patients (28.3%) had underlying diseases. Fever was noted in 319 patients (94.1%) with a median duration of two days (IQR 2–3 days). Twenty-two patients (6.5%) were severe cases, including 10 patients (2.9%) with encephalopathy with abnormal neuroimaging and ten patients (2.9%) with shock. Two patients (0.6%) died. Patients with congenital cardiovascular disease (aOR: 21.689), duration of fever up to four days or more (aOR: 6.466), desaturation (aOR: 16.081), seizure (aOR: 20.92), and procalcitonin >0.5 ng/mL (aOR: 7.886) had a higher risk of severe COVID-19. Conclusions: Vital signs need close monitoring, early management and/or intensive care may be applied in COVID-19 patients with congenital cardiovascular diseases, fever lasting ≥4 days, seizures, desaturation and/or elevated procalcition since they are at higher risks of severe diseases.

Background: In Taiwan, the prevalence of COVID-19 was low before April 2022. The low SARS-CoV-2 seroprevalence in the population of Taiwan provides an opportunity for comparison with fewer confounding factors than other populations globally. Cycle threshold (Ct) value is an easily accessible method for modeling SARS-CoV-2 dynamics. In this study, we used clinical samples collected from hospitalized patients to explore the Ct value dynamics of the Omicron variant infection. Methods: From Jan 2022 to May 2022, we retrospectively included hospitalized patients tested positive by nasopharyngeal SARS-CoV-2 PCR. We categorized the test-positive subjects into different groups according to age, vaccination status, and use of antiviral agents. To investigate the nonlinear relationship between symptom onset days and Ct value, a fractional polynomial model was applied to draw a regression line. Results: We collected 1718 SARS-CoV-2 viral samples from 812 individuals. The Ct values of unvaccinated individuals were lower than those of vaccinated persons from Day 4 to Day 10 after symptom onset. The Ct value increased more rapidly in those individuals with antiviral drug treatment from Day 2 to Day 7. In elderly individuals, the Ct values increased slowly from Day 5 to Day 10, and the increasing trend was unique compared with that in children and adults. Conclusion: Our study demonstrated the primary viral infection dynamics of the Omicron variant in hospitalized patients. Vaccination significantly affected viral dynamics, and antiviral agents modified viral dynamics irrespective of vaccination status. In elderly individuals, viral clearance is slower than that in adults and children.

Objectives: The SARS-CoV-2 Omicron variant pandemic struck Taiwan in April 2022. Rapid antigen tests (RATs) play an important role in providing rapid results during a pandemic. However, self-collected samples by the children's caregivers without the supervision of medical personnel raise some concerns. Methods: This study was performed to investigate household transmission, clinical characteristics, and antigen performance in a special COVID-19 family clinic in a children's hospital. The performance of at-home RATs was evaluated based on reverse transcription-polymerase chain reaction. Results: We included 627 patients in our study between May 11 and June 10, 2022. The COVID-19 full vaccination rate was significantly higher in adults (98.5%) than in children (5.9%, P

Abstracts: Background/purpose: Clinical data on carbapenem-resistant Enterobacterales (CRE) bacteremia in the pediatric population are limited. This study investigated the clinical characteristics and outcomes of pediatric CRE bacteremia. Methods: Clinical data on bacteremia caused by carbapenem-susceptible and carbapenem-resistant Enterobacterales, including Escherichia coli, Klebsiella spp., Enterobacter spp., Serratia marcescens, Proteus mirabilis, Citrobacter spp., and Morganella spp., in pediatric patients from a children's hospital in Taiwan were retrospectively retrieved and analyzed. Results: From January 2013 to December 2021, 471 clinical isolates of Enterobacterales bacteremia were identified in 451 episodes from 379 pediatric patients. Among all the isolates, the predominant species were E. coli (199/471, 42.2%), Klebsiella spp. (168/471, 35.6%), and Enterobacter spp. (59/471, 12.5%), with carbapenem-resistance rates of 1.5%, 11.9%, and 25.0%, respectively. Overall, 40 (8.4%) showed a carbapenem resistance phenotype. Patients’ all-cause mortality rate at 14 days was significantly higher in CRE bacteremia episodes than non-CRE ones (12.5% vs. 3.6%, p

As an increasing number of robotic manipulators possess seven or more degrees-of-freedom (DoF), solving inverse kinematic (IK) for kinematically redundant manipulators is becoming critical. Numerical optimizations are commonly used to solve the problem due to their generality and accuracy. Unfortunately, they typically only generate one joint solution at a time, despite the multiple joint configurations that redundant manipulators can provide to move the end-effector to a target position. The long iterative optimization process is also a concern, particularly if extra constraints such as obstacle avoidance have to be evaluated. In this paper, we show that numerical methods may be complemented by deep learning to overcome these limitations. Through deep learning, the solution space of redundant IK may be learned with neural networks (NNs), which allows multiple distinct joint solutions corresponding to a given target position to be obtained by navigating the solution space. The main challenge is to overcome the one-to-one functional mapping of NNs. This paper solves this problem with a novel probabilistic encoding of manipulator poses and their corresponding infinite number of joint solutions. Two examples are presented to demonstrate the application of the proposed method to facilitate numerical IK computations: (1) finding a good initial joint solution to bootstrap the numerical IK calculation, and (2) evaluating extra constraints, such as obstacle avoidance, off the optimization iterations. Experiments show that the proposed method can accelerate the execution of different numerical IK modules in the popular IKpy package up to 50% for a 7-DoF manipulator, depending on the accuracy required.

Background: Mycoplasma pneumoniae is a pathogen that causes respiratory diseases in children. Infections caused by M. pneumoniae are usually self-limited but occasionally can be severe. We observed emerging cases of severe mycoplasma infection requiring extracorporeal membrane oxygenation (ECMO). Thus, we investigated chronological changes in the molecular features of the M. pneumoniae and its clinical impacts among the pediatric population. Methods: From 2011 to 2019, respiratory samples were collected from patients younger than 18 years old with pneumonia in a tertiary children's hospital. Focused multiple-locus variable number of tandem repeats analysis (MLVA) typing was performed on samples positive for M. pneumoniae in 2016 and 2019. Clinical data from the patients' electronic medical records were collected. We described the annual trend of macrolide resistance and MLVA type and analyzed the associations between clinical manifestations and MLVA types. Results: The percentage of macrolide-resistant (MLR) M. pneumoniae gradually increased from 22% (27/122) in 2015 to 70% (82/117) in 2019. Among the MLR M. pneumoniae, the predominant strain shifted from type P (31% [13/42]) to type A (40% [19/46]). The demographics, initial presentations, and clinical courses of the subjects with MLR M. pneumoniae did not differ significantly between 2011 and 2019. However, in 2019, two fulminant cases requiring venovenous ECMO were observed, which indicates that more attention to the clinical severity of MLR M. pneumoniae infections is warranted. Conclusion: Obtaining accurate information on macrolide susceptibility is crucial for physicians to initiate appropriate antibiotic treatment in a timely fashion. Although we could not identify significant differences among mycoplasma pneumonias caused by different MLVAs over a span of 9 years, the emergence of severe mycoplasma infections requiring ECMO was clinically significant, and further monitoring was required.

Background/Purpose: Invasive candidiasis is a severe infectious disease that could lead to mortality in critically ill children. Methods: We collected data regarding demographics, underlying diseases, predisposing factors, outcomes for pediatric patients with candidemia at a medical centre in Taiwan from 2011 to 2017. Results: Fifty-eight patients with 60 candidemia episodes were diagnosed. The 3 most common species were Candida albicans (42%), Candida parapsilosis (25%) and Candida tropicalis (23%). C. parapsilosis predominantly infected infants and neonates (median age: 0.8 years, range: 0.1–14.5). Cases with C. tropicalis had significantly higher rates of multidrug resistance (p = 0.011) and disseminated candidiasis (p = 0.025) compared with other cases. The all-cause mortality rate was 43%, and the candidemia-related mortality rate was 29%. Pediatric sequential organ failure assessment score >8 [adjusted odds ratio (aOR) 66.2, 95% CI 4.03–1088.5] and posaconazole resistance (aOR 33.57, 95% CI 1.61–700.3) were the most significant risk factors associated with candidemia-related mortality, whereas treatment with effective antifungal agents within 48 h (aOR 0.07, 95% CI 0.01–0.9) was the only significant protective factor. Conclusion: Candidemia-related mortality was related to azole resistance; therefore, empirical therapy with echinocandin or amphotericin B is recommended pending species and susceptibility results.

Background: Recurrent pneumonia is uncommon in children and few studies investigate the clinical impact of underlying diseases on this issue. This study aimed to explore the difference in clinical manifestations, pathogens, and prognosis of recurrent pneumonia in children with or without underlying diseases. Methods: We conducted a retrospective study of pediatric recurrent pneumonia from 2007 to 2019 in National Taiwan University Hospital. Patients under the age of 18 who had two or more episodes of pneumonia in a year were included, and the minimum interval of two pneumonia episodes was more than one month. Aspiration pneumonia was excluded. Demographic and clinical characteristics of patients were collected and compared. Results: Among 8508 children with pneumonia, 802 (9.4%) of them had recurrent pneumonia. Among these 802 patients, 655 (81.7%) had underlying diseases including neurological disorders (N = 252, 38.5%), allergy (N = 211, 32.2%), and cardiovascular diseases (N = 193, 29.5%). Children without underlying diseases had more viral bronchopneumonia (p < 0.001). Children with underlying diseases were more likely to acquire Staphylococcus aureus (p = 0.001), and gram-negative bacteriae, more pneumonia episodes (3 vs 2, p < 0.001), a longer hospital stay (median: 7 vs. 4 days, p < 0.001), a higher ICU rate (28.8% vs 3.59%, p < 0.001), and a higher case-fatality rate (5.19% vs 0%, p < 0.001) than those without underlying diseases. Conclusion: Children with underlying diseases, prone to have recurrent pneumonia and more susceptible to resistant microorganisms, had more severe diseases and poorer clinical outcomes. Therefore, more attention may be paid on clinical severity and the therapeutic plan.

Background/purpose: Influenza is frequently complicated with bacterial co-infection. This study aimed to disclose the significance of Streptococcus pneumoniae co-infection in children with influenza. Methods: We retrospectively reviewed medical records of pediatric patients hospitalized for influenza with or without pneumococcal co-infection at the National Taiwan University Hospital from 2007 to 2019. Clinical characteristics and outcomes were compared between patients with and without S. pneumoniae co-infection. Results: There were 558 children hospitalized for influenza: 494 had influenza alone whereas 64 had S. pneumoniae co-infection. Patients with S. pneumoniae co-infection had older ages, lower SpO2, higher C-Reactive Protein (CRP), lower serum sodium, lower platelet counts, more chest radiograph findings of patch and consolidation on admission, longer hospitalization, more intensive care, longer intensive care unit (ICU) stay, more mechanical ventilation, more inotropes/vasopressors use, more surgical interventions including video-assisted thoracoscopic surgery (VATS) and extracorporeal membrane oxygenation (ECMO), and higher case-fatality rate. Conclusion: Compared to influenza alone, patients with S. pneumoniae co-infection had more morbidities and mortalities. Pneumococcal co-infection is considered when influenza patients have lower SpO2, lower platelet counts, higher CRP, lower serum sodium, and more radiographic patches and consolidations on admission.

Background: Respiratory syncytial virus (RSV) is a common cause of childhood pneumonia, but there is limited understanding of whether bacterial co-infections affect clinical severity. Methods: We conducted a retrospective cohort study at National Taiwan University Hospital from 2010 to 2019 to compare clinical characteristics and outcomes between RSV with and without bacterial co-infection in children without underlying diseases, including length of hospital stay, intensive care unit (ICU) admission, ventilator use, and death. Results: Among 620 inpatients with RSV pneumonia, the median age was 1.33 months (interquartile range, 0.67–2 years); 239 (38.6%) under 1 year old; 366 (59.0%) males; 201 (32.4%) co-infected with bacteria. The three most common bacteria are Streptococcus pneumoniae, Staphylococcus aureus and Haemophilus influenzae. The annually seasonal analysis showed that spring and autumn were peak seasons, and September was the peak month. Compared with single RSV infection, children with bacterial co-infection were younger (p = 0.021), had longer hospital stay (p

Background/purpose(s): This study aimed to investigate clinical features and antimicrobial susceptibility of inpatient children with nontyphoidal salmonellosis from 2010 to 2018. Methods: We retrospectively collected pediatric patients with nontyphoidal Salmonella infection confirmed by positive cultures in a tertiary medical center in Taiwan from 2010 to 2018. Patients' characteristics, clinical manifestations, and laboratory data were collected. Serogroup category and antimicrobial susceptibility were also analyzed. Results: Of total 569 isolates, ampicillin resistant rate was 53% in average, third-generation cephalosporin resistant rate was 6.7%, ciprofloxacin resistant rate was 9% and trimethoprim–sulfamethoxazole resistant rate was 30%. Compared to the resistant rates in 2010, the resistance rate of third generation cephalosporin was significantly higher (3.4% vs. 11%, p = 0.003) but that of ciprofloxacin was significantly lower (20% vs. 11%, p

Background/Purpose: Despite the high prevalence of Mycoplasma pneumoniae infections, reports on severe life-threatening M. pneumoniae pneumonia (MPP) in children are limited. Methods: We retrospectively enrolled pediatric patients with PCR-positive MPP requiring ICU admission in a children's hospital in Taipei, Taiwan from Jun 2010 to October 2019. Clinical manifestations and laboratory data of severe MPP were analyzed. Macrolide susceptibility was determined by genotyping, and its relationship with clinical manifestations was also analyzed. Results: Approximately 5% (34/658) children hospitalized for MPP required ICU admission. Compared with non-ICU cases (n = 291), ICU cases (n = 34) were associated with more underlying conditions, more pleural effusion, longer fever duration, longer hospital stay, the requirement of second-line antibiotic treatment, and delayed effective and second-line antibiotic treatment. Macrolide resistance was similar in ICU and non-ICU groups (53% vs 53%; p = 0.986). In severe MPP, patients requiring endotracheal intubation were associated with more septic shock, empyema, ARDS, prolonged fever after effective antibiotic treatment, delayed second-line and effective antibiotic treatment. In 18 of the 22 patients with pleural fluid analysis, the pleural effusion was alkaline (pH > 7.7) and lymphocyte-predominant. Conclusion: M. pneumoniae infection can cause severe life-threatening pneumonia in children. Delayed effective and second-line antibiotic treatments are associated with severe life-threatening MPP.

Purpose: To investigate the clinical feature of tuberculosis and BCG adverse effects in children and to examine whether delayed BCG vaccination changes the incidence of BCG osteomyelitis. Methods: We analyzed patients younger than 18 years with tuberculosis or BCG-associated adverse effects from 2008 to 2019. We compared their clinical features, laboratory tests and outcomes. Results: Totally 137 patients were collected, with 27% of pulmonary tuberculosis (PTB), 31% of extrapulmonary tuberculosis (EPTB) and 42% of BCG-associated adverse effects. The median age was older in PTB than EPTB group (17.1 vs 15.4 years; p = 0.015). More patients in EPTB group had fever than PTB group (55% vs 25%; p = 0.008). Compared with exclusively EPTB, more patients in EPTB plus PTB group had fever (78% vs 38%; p = 0.009), and had more systemic symptoms (67% vs 25%; p = 0.007), lower absolute lymphocyte count (1230 vs 1850/μL; p = 0.033), higher CRP level (5.62 vs 2.21 mg/dL; p = 0.024) and longer hospital stay (20 vs 11 days; p = 0.031). In BCG osteomyelitis group, the median time interval from vaccination to diagnosis was 16.4 months (IQR 15.0–20.2). Age at vaccination, either at birth or 5-8 month-old, did not affect the proportion of BCG osteomyelitis among children with BCG-associated adverse effects. Conclusion: Children with EPTB plus PTB had more fever, lower lymphocyte count and higher CRP. The median time interval from vaccination to diagnosis of BCG osteomyelitis was 16.4 months and the proportion of BCG osteomyelitis among children with BCG-associated adverse effects was not affected by delayed vaccination in this study.

The technology for detecting forged images is good at detecting known forgery methods. It trains neural networks using many original and corresponding forged images created with known methods. However, when encountering unseen forgery methods, the technology performs poorly. Recently, one suggested approach to tackle this problem is to use a hand-crafted generator of forged images to create a range of fake images, which can then be used to train the neural network. However, the aforementioned method has limited detection performance when encountering unseen forging techniques that the hand-craft generator has not accounted for. To overcome the limitations of existing methods, in this paper, we adopt a meta-learning approach to develop a highly adaptive detector for identifying new forging techniques. The proposed method trains a forged image detector using meta-learning techniques, making it possible to fine-tune the detector with only a few new forged samples. The proposed method inputs a small number of the forged images to the detector and enables the detector to adjust its weights based on the statistical features of the input forged images, allowing the detection of forged images with similar characteristics. The proposed method achieves significant improvement in detecting forgery methods, with IoU improvements ranging from 35.4% to 127.2% and AUC improvements ranging from 2.0% to 48.9%, depending on the forgery method. These results show that the proposed method significantly improves detection performance with only a small number of samples and demonstrates better performance compared to current state-of-the-art methods in most scenarios.

Background/purpose: To date, molecular typing studies on Mycoplasma pneumoniae are limited. We evaluated the molecular types of Mycoplasma pneumoniae in pediatric patients in Taiwan in 2016. Methods: We used real-time quantitative PCR on respiratory specimens to identify M. pneumoniae in children with community-acquired pneumonia. The domain V of their 23S rRNA were sequenced for detection of macrolide-resistant point mutations. Molecular typing with multiple locus variable-number tandem repeat analysis (MLVA) was done for both macrolide-susceptible and -resistance M. pneumoniae samples. Results: M. pneumoniae was detected in 22% (180/826) respiratory samples during the study period. Among all M. pneumoniae-positive samples, 24% (43/180) had harbored macrolide-resistant genotypes, and 86% (37/43) of them were A2063G mutation. Forty-two macrolide-resistant strains and 20 randomly selected macrolide-susceptible strains underwent MLVA profiling. MLVA 4-5-7-2 was the most frequent type (32/62, 52%), followed by 4-5-7-3 (17/62, 27%) and 1-5-6-2 (9/62, 15%). There was a strong association between MLVA 4-5-7-2 and macrolide resistance (p < 0.001). In contrast, M 4-5-7-3 and 1-5-6-2 were related to macrolide susceptibility (p < 0.001, and p = 0.025, respectively). Conclusion: Macrolide resistance was relatively low (24%) in this age group in 2016 in Taiwan, and A2063G was the dominant point mutation. MLVA 4-5-7-2 was associated with macrolide resistance.

BackgroundTimely decision-making regarding intensive care unit (ICU) admission for children with pneumonia is crucial for a better prognosis. Despite attempts to establish a guideline or triage system for evaluating ICU care needs, no clinically applicable paradigm is available. ObjectiveThe aim of this study was to develop machine learning (ML) algorithms to predict ICU care needs for pediatric pneumonia patients within 24 hours of admission, evaluate their performance, and identify clinical indices for making decisions for pediatric pneumonia patients. MethodsPneumonia patients admitted to National Taiwan University Hospital from January 2010 to December 2019 aged under 18 years were enrolled. Their underlying diseases, clinical manifestations, and laboratory data at admission were collected. The outcome of interest was ICU transfer within 24 hours of hospitalization. We compared clinically relevant features between early ICU transfer patients and patients without ICU care. ML algorithms were developed to predict ICU admission. The performance of the algorithms was evaluated using sensitivity, specificity, area under the receiver operating characteristic curve (AUC), and average precision. The relative feature importance of the best-performing algorithm was compared with physician-rated feature importance for explainability. ResultsA total of 8464 pediatric hospitalizations due to pneumonia were recorded, and 1166 (1166/8464, 13.8%) hospitalized patients were transferred to the ICU within 24 hours. Early ICU transfer patients were younger (P

Clostridioides difficile infection (CDI) is a major enteric disease associated with antibiotic use and a leading cause of hospital-acquired infections worldwide. This is the first guideline for treatment of CDI in Taiwan, aiming to optimize medical care for patients with CDI. The target audience of this document includes all healthcare personnel who are involved in the medical care of patients with CDI. The 2018 Guidelines Recommendations for Evidence-based Antimicrobial agents use in Taiwan (GREAT) working group was formed, comprising of infectious disease specialists from 13 medical centers in Taiwan, to review the evidence and draft recommendations using the grading of recommendations assessment, development, and evaluation (GRADE) methodology. A nationwide expert panel reviewed the recommendations during a consensus meeting in March 2019. The recommendation is endorsed by the Infectious Diseases Society of Taiwan (IDST). This guideline describes the epidemiology and risk factors of CDI, and provides recommendations for treatment of CDI in both adults and children. Recommendations for treatment of the first episode of CDI, first recurrence, second and subsequent recurrences of CDI, severe CDI, fulminant CDI, and pediatric CDI are provided. Keywords: Clostridium difficile, Diarrhea, CDI, Infectious diarrhea

In fabricating advanced silicon (Si)-based metal–oxide semiconductors, the ability to inspect dopant distribution in Si ultrathin films (tens of nm) is crucial for monitoring the amount of dopant diffusion. Here, we perform an anisotropic reflective second harmonic generation (SHG) measurement to demonstrate the sensitivity of SHG to phosphorus (P) concentration within the range of 2.5×1017 to 1.6×1020 atoms/cm3. In addition, we propose an analysis method based on a simplified bond-hyperpolarizability model to interpret the results. The bond vector model that corresponds to the P vacancy clusters is built to calculate the SHG contribution from substitutionally incorporated P atoms. The effect of incorporating P into the Si lattice is reflected in the effective hyperpolarizability, lattice tilt, and deformation of this model. The fitting results of the intuitively defined coefficients exhibit a high correlation to the P concentration, indicating the potential of this model to resolve the properties in complex material compositions. Finally, a comparison with Fourier analysis is made to evaluate the advantages and disadvantages of this model. Combined anisotropic reflective SHG (Ani-RSHG) and the simplified bond-hyperpolarizability model (SBHM) can analyze the crystal structure of doped ultrathin films and provide a non-destructive nanophotonic way for in-line inspection.

BACKGROUND:Enterovirus D68 (EV-D68) was discovered in 1962 and has unique characteristics compared to the characteristics of other enteroviruses. There were few documented cases before the epidemic in the United States in 2014. The Taiwan Centers for Diseases Control also confirmed that EV-D68 has been endemic, and some cases of acute flaccid myelitis were reported in Taiwan. To understand the current EV-D68 serostatus, we performed an EV-D68 seroepidemiology study in Taiwan in 2017. METHODS:After informed consent was obtained, we enrolled preschool children, 6- to 15-year-old students and 16- to 49-year-old people. The participants underwent a questionnaire investigation and blood sampling to measure the EV-D68 neutralization antibody. RESULTS:In total, 920 subjects were enrolled from the northern, central, southern and eastern parts of Taiwan with a male-to-female ratio of 1.03. The EV-D68 seropositive rate was 32% (26/82) in infants, 18% (27/153) in 1-year-old children, 43% (36/83) in 2-year-old children, 60% (94/156) in 3- to 5-year-old children, 89% (108/122) in 6- to 11-year-old primary school students, 98% (118/121) in 12- to 15-year-old high school students, 100% (122/122) in 16- to 49-year-old women and 100% (81/81) in 16- to 49-year-old males in 2017. Among preschool children, EV-D68 seropositivity was related to age (p for trend

Background: Sepsis remains a common but fatal complication among patients with immune suppression. We aimed to investigate the performance of metagenomic next-generation sequencing (mNGS) compared with standard microbiological diagnostics in patients with hematologic malignancies. Methods: We performed a prospective study from June 2019 to December 2019. Adult patients with hematologic malignancies and a clinical diagnosis of sepsis were enrolled. Conventional diagnostic methods included blood cultures, serum galactomannan for Aspergillus, cryptococcal antigen and cytomegalovirus (CMV) viral loads. Blood samples for mNGS were collected within 24 h after hypotension developed. Results: Of 24 patients enrolled, mNGS and conventional diagnostic methods (blood cultures, serology testing and virus RT-PCR) reached comparable positive results in 9 cases. Of ten patients, mNGS was able to identify additional pathogens compared with conventional methods; most of the pathogens were virus. Conclusion: Our results show that mNGS may serve as adjunctive diagnostic tool for the identification of pathogens of hematologic patients with clinically sepsis.

BACKGROUND:During recent 20 years, enterovirus 71 (EV71) has emerged as a major concern among children, particularly in the Asia-Pacific region. To understand current EV71 serostatus, to find risk factors associated with EV71 infection and to establish future EV71 vaccine policy, we performed a seroepidemiology study in Taiwan in 2017. METHODS:After informed consent was obtained, we enrolled preschool children, 6-15-year-old students, 16-50-year-old people. They received a questionnaire and a blood sample was collected to measure the EV71 neutralization antibody. RESULTS:Altogether, 920 subjects were enrolled with a male-to-female ratio of 1.03. The EV71 seropositive rate was 10% (8/82) in infants, 4% (6/153) in 1-year-old children, 8% (7/83) in 2-year-old children, 8% (13/156) in 3-5-year-old children, 31% (38/122) in 6-11-year-old primary school students, 45% (54/121) in 12-15-year-old high school students and 75% (152/203) in 16-50-year-old people. Risk factors associated with EV71 seropositivity in preschool children were female gender, having siblings, more siblings, and contact with herpangina or hand-foot-and-mouth disease. The risk factor with EV71 seropositivity in 16-50-year-old people was having children in their families in addition to older age (p

OBJECTIVE:To evaluate the association of enterovirus 71 (EV71) susceptibility and clinical severity with polymorphisms in EV71 receptors, including human scavenger receptor class B member 2 (SCARB2), P-selectin glycoprotein ligand-1 (PSGL-1), and annexin II (ANXA2). METHODS:We enrolled laboratory-confirmed EV71 cases and healthy age- and gender-matched controls in Taiwan from 2000 to 2012. We detected genetic polymorphisms in SCARB2, PSGL-1, and ANXA2 and correlated the results with EV71 susceptibility and severity. RESULTS:We collected 599 EV71 cases and 98 controls. Among EV71 patients, the male to female ratio was 1.61, and the mean age was 2.99±2.47 years. For clinical severity, 117 (19.6%) had severe central nervous system involvement with or without cardiopulmonary failure. For outcomes, 46 (7.7%) had sequelae, and 14 (2.3%) died. SCARB2 polymorphisms (rs6824953 and rs11097262) were associated with susceptibility to EV71 infection (OR 1.60, 95% CI 1.07-2.39; and OR 1.64, 95% CI 1.09-2.47, respectively). PSGL-1 polymorphisms (rs7137098 and rs8179137) were significantly associated with severe EV71 infection (OR 1.46, 95% CI 1.1-1.96; and OR 1.47, 95% CI 1.07-2.03, respectively). CONCLUSIONS:SCARB2 polymorphisms (rs6824953 and rs11097262) might be associated with EV71 susceptibility. PSGL-1 polymorphisms (rs7137098 and rs8179137) were associated with severe EV71 infection.