Clinical characteristics and risk factors of severe human parainfluenza virus infection in hospitalized children.

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.

Seroprevalence of SARS-CoV-2 in self-reported COVID-19-free children.

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 < 0.001). Until January 2024, the overall infection rate was 41.9% (99/236) among children who were negative for anti-N antibodies, irrespective of vaccination status or the presence of chronic disease. CONCLUSION: We discovered previously undisclosed cases of SARS-CoV-2 infection among children. The risk of seropositivity increases substantially with household contact. Regarding children who report no prior exposure to COVID-19, clinicians must remain vigilant, as SARS-CoV-2 remains a concern.

High incidence of cerebrovascular lesions on magnetic resonance imaging in pediatric COVID-19 during omicron outbreak - A retrospective case series.

BACKGROUND: The incidence of pediatric hospitalizations has significantly increased since the spread of the omicron variant of COVID-19. Changes of characteristics in respiratory and neurological symptoms have been reported. We performed a retrospective, cross-sectional study to characterize the MRI change in children with an emphasis on the change of cerebral vasculatures. METHODS: We retrospectively collected clinical and MRI data of 31 pediatric patients with neurological symptoms during the acute infection and abnormalities on MRI during the outbreak of omicron variant from April 2022 to June 2022 in Taiwan. The clinical manifestations and MRI abnormalities were collected and proportion of patients with vascular abnormalities was calculated. RESULTS: Among 31 pediatric patients with post-COVID-19 neurological symptoms, MRI abnormalities were observed in 15 (48.4%), predominantly encephalitis/encephalopathy (73.3%). Notable MRI findings included focal diffusion-weighted imaging (DWI) hyperintensity in cerebral cortex and thalamus, diffuse cortical T2/DWI hyperintensity, and lesions in the medulla, pons, cerebellum, and splenium of corpus callosum. Vascular abnormalities were seen in 12 (80%) patients with MRI abnormalities, mainly affecting the middle cerebral arteries. The spectrum of neurological manifestations ranged from seizures to Alice in Wonderland syndrome, underscoring the diverse impact of COVID-19 on pediatric patients. CONCLUSION: A high proportion of vascular abnormalities was observed in pediatric patients with neurological involvements, suggesting that vascular involvement is an important mechanism of neurological manifestations in omicron variant infection.

Risk Factors for Severe Respiratory Syncytial Virus Infection in Hospitalized Children.

BACKGROUND: Respiratory syncytial virus (RSV) is a common cause of bronchiolitis and pneumonia in infants and young children. Starting in December 2010, RSV monoclonal antibody (RSV mAb) was endorsed by Taiwan National Health Insurance and given to children with prematurity and/or congenital heart diseases, which are considered high-risk factors for severe RSV diseases. Investigating other important contributing risk factors is warranted. METHODS: We conducted a cohort study at National Taiwan University Hospital to determine the rate of severe outcomes among children hospitalized due to RSV infection from 2008 to 2018. Adjusted for age, sex and birth cohorts born before and after RSV mAb endorsement, we identified risk factors for severe RSV infection, defined as the requirement of invasive ventilator support. RESULTS: There were 1985 admissions due to RSV infections. Among them, 66 patients (3.3%) had severe RSV infection. The proportion of severe RSV infections decreased significantly after RSV mAb endorsement. Multivariable analysis revealed that age <1.5 months and cardiovascular and congenital/genetic diseases were high-risk underlying conditions. In addition, bacterial coinfections, elevated creatinine levels and initial abnormal chest radiograph findings posed warning signs for severe RSV infection. CONCLUSIONS: Children younger than 1.5 months of age with cardiovascular or congenital/genetic diseases were predisposed to severe RSV infection and might benefit from RSV mAb prophylaxis.

Clinical manifestations and risk factors of shock in children with multisystem inflammatory syndrome.

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.

Adverse events from HPV vaccination in Taiwan.

The safety of human papillomavirus (HPV) vaccines has been evaluated continuously in pre-licensure clinical trials, post-marketing surveillance systems, and observational studies. Most studies have found no significant association between serious adverse events and HPV vaccination. However, these studies have focused on Western populations; similar studies focusing on Asian populations are insufficient. Our retrospective cohort study used the HPV-vaccination records of junior high-school adolescent girls aged 12-15 years between 2013 and 2018 in Taiwan's National Immunization Information System and linked them to a registry for beneficiaries in Taiwan's National Health Insurance Database (NHID) to establish the vaccinated group. We selected 19 serious diseases as serious adverse events. We compared the incidence rates of these serious adverse events between the vaccinated group and girls in the same age group population, and we calculated the standardized incidence ratio (SIR) to evaluate the risk of serious adverse events after HPV vaccination. Because of the onset of different types of diseases, we set three periods after the subjects received HPV vaccination: within 3 months, within 1 year, and during the study period (2013-2018). The results showed the incidence rates and the SIRs of 19 selected adverse events. Among the 19 selected serious adverse events, the disease with the highest incidence rate during the study period was fibromyalgia (73.23 cases per million population), and the disease with the lowest incidence rate during the study period was Crohn's disease (0.15 cases per million population). The results showed no statistically significant increases in the risk of 19 selected serious adverse events and indicated no association between HPV vaccination and serious adverse events. Given the benefits and safety of HPV vaccination, our research can reduce concerns about vaccine side effects, inform health policies and improve public and clinician's acceptance of HPV vaccine policy.

Outcomes of pediatric community-acquired pneumonia before and after national pneumococcal immunization in Taiwan.

OBJECTIVE: In Taiwan, the incidence of invasive pneumococcal disease (IPD) in children declined after the catch-up primary vaccination programs and the full national immunization program (NIP) with PCV13. The objective of the study was to investigate the clinical outcomes of pediatric community-acquired pneumonia (CAP) before and after the NIP. METHODS: The study included patients aged 3 months to 17 years who were diagnosed with CAP and treated at the National Taiwan University Hospital between 2007 and 2019. Patients were assigned to three birth cohorts according to their birth years and vaccination eligibility: non-NIP, catch-up, and full NIP. We compared the rates of severe outcomes, including case fatality and pathogens. RESULTS: A total of 6557 patients who met the CAP criteria were enrolled during the study period. The case-fatality rate decreased from 3.2% (94/2984) in the non-NIP cohort to 0.3% (7/2176) in the catch-up cohort and 0.8% (11/1397) in the full NIP cohort (p < 0.001). Furthermore, there was a significant decrease in invasive ventilation from the non-NIP (17.9%) to both catch-up (6.8%) and full NIP cohorts (9.1%). The rate of IPD declined from the non-NIP cohort to the catch-up cohort (1.8% vs. 0.6%, p < 0.001) and from the catch-up to the full NIP cohort (0.6% vs. 0.07%, p = 0.014). In contrast, the rates of infections with other pathogens increased after NIP. CONCLUSION: The introduction of PCV13 showed significant reduction in case-fatality and IPD rates. The increasing rates of other pathogens warrant further surveillance for their clinical significance.

Clinical characteristics and factors associated with severe COVID-19 in hospitalized children during the SARS-CoV-2 Omicron pandemic in Taiwan.

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.

Genetic Underpinnings and Audiological Characteristics in Children With Unilateral Sensorineural Hearing Loss.

OBJECTIVE: Unilateral sensorineural hearing loss (USNHL) is a condition commonly encountered in otolaryngology clinics. However, its molecular pathogenesis remains unclear. This study aimed to investigate the genetic underpinnings of childhood USNHL and analyze the associated audiological features. STUDY DESIGN: Retrospective analysis of a prospectively recruited cohort. SETTING: Tertiary referral center. METHODS: We enrolled 38 children with USNHL between January 1, 2018, and December 31, 2021, and performed physical, audiological, imaging, and congenital cytomegalovirus (cCMV) examinations as well as genetic testing using next-generation sequencing (NGS) targeting 30 deafness genes. The audiological results were compared across different etiologies. RESULTS: Causative genetic variants were identified in 8 (21.1%) patients, including 5 with GJB2 variants, 2 with PAX3 variants, and 1 with the EDNRB variant. GJB2 variants were found to be associated with mild-to-moderate USNHL in various audiogram configurations, whereas PAX3 and EDNRB variants were associated with profound USNHL in flat audiogram configurations. In addition, whole-genome sequencing and extended NGS targeting 213 deafness genes were performed in 2 multiplex families compatible with autosomal recessive inheritance; yet no definite causative variants were identified. Cochlear nerve deficiency and cCMV infection were observed in 9 and 2, respectively, patients without definite genetic diagnoses. CONCLUSION: Genetic underpinnings can contribute to approximately 20% of childhood USNHL, and different genotypes are associated with various audiological features. These findings highlight the utility of genetic examinations in guiding the diagnosis, counseling, and treatment of USNHL in children.

Viral dynamics of SARS-CoV-2 Omicron infections in a previously low COVID-19 prevalence region: Effects of vaccination status, antiviral agents, and age.

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.

Clinical manifestations and risk factors of campylobacter gastroenteritis in children in Taiwan.

BACKGROUND: Campylobacteriosis is a common cause of bacterial gastroenteritis worldwide. This study aimed to investigate the potential risk factors, clinical and laboratory manifestations of children with campylobacteriosis under five years old in Taiwan. METHODS: This retrospective case-control study was conducted in ten major hospitals in Taiwan from 2014 to 2017. Laboratory tests and stool specimen were collected and analyzed together with questionnaire survey. Multivariate stepwise logistic regression model was used for identification of risk factors. RESULTS: A total of 64 campylobacteriosis cases were included with a median age of 25 months. We observed a less prolonged vomiting (p = 0.047), more bloody (p < 0.001) and mucoid (p = 0.005) stools, and lower AST levels (p = 0.020) in patients with campylobacteriosis. Lower parental educational attainment (p < 0.001), direct contact with acute gastroenteritis patients (p < 0.001), as well as diarrhea in the mutually cared children (p = 0.007) were linked to campylobacteriosis. Consumption of municipal water (p < 0.001), milk (OR 0.34, 95% CI 0.118-0.979), and soft beverages (OR 0.41, 95% CI 0.192-0.888) were identified as protective factors, while consuming takeout food (p = 0.032) and seafood (p = 0.019) increased risk of campylobacteriosis. CONCLUSIONS: Shorter vomiting duration, bloody and mucoid stool, and less elevated AST levels are manifestations suggestive of campylobacteriosis. Risk factors of campylobacteriosis were low parental educational attainment, direct contact with acute gastroenteritis patients, diarrhea in mutually cared children, takeout food and seafood intake. Potential protective factors include municipal water, milk, and soft beverage intake.

An Elastic Organic Crystal Enables Macroscopic Photoinduced Crystal Elongation.

Among the various types of photomechanical deformations of organic crystals, photoinduced elongation of millimeter-scale crystals has yet to be demonstrated. Here we report that the millimeter-sized crystalline rods of an anthracene-pentiptycene hybrid organic π-system (1) are highly elastic and able to elongate up to 21.6% or 0.40 mm without fragmentation upon undergoing [4 + 4] photodimerization reactions. Both the mechanical and photomechanical effects reveal a strong cohesion of the system, even at the interface of 1 and its photodimer 2 and under the conditions of randomized molecular packing, representing a new class of mechanically adaptive organic crystals.

Differential clinical characteristics and performance of home antigen tests between parents and children after household transmission of SARS-CoV-2 during the Omicron variant pandemic.

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 <0.001). The transmission rate was significantly higher in children (91.3%) than in adults (76.6%, P <0.001). Infected children had more incidents of fever (82.4% vs 22.4%, P <0.001) and a higher peak fever than adults. Based on the reverse transcription-polymerase chain reaction, the negative predictive rate of the home RAT was only 38.7% (95% confidence interval: 31.9-46.0%) in children. The cycle threshold value of those with false-negative antigen tests was significantly lower in children. CONCLUSION: Children had a higher transmission rate, more fever, and higher peak fever than adults. Home RAT has a suboptimal negative predictive rate in children.

Application of nested multiplex polymerase chain reaction respiratory and pneumonia panels in children with severe community-acquired pneumonia.

Community-acquired pneumonia (CAP) is a serious clinical concern. A lack of accurate diagnosis could hinder pathogen-directed therapeutic strategies. To solve this problem, we evaluated clinical application of nested multiplex polymerase chain reaction (PCR) in children with severe CAP. We prospectively enrolled 60 children with severe CAP requiring intensive care between December 2019 and November 2021 at a tertiary medical center. Nested multiplex PCR respiratory panel (RP) and pneumonia panel (PP) were performed on upper and lower respiratory tract specimens. We integrated standard-of-care tests and quantitative PCR for validation. The combination of RP, PP, and standard-of-care tests could detect at least one pathogen in 98% of cases and the mixed viral-bacterial detection rate was 65%. The positive percent agreement (PPA), and negative percent agreement (NPA) for RP were 94% and 99%; the PPA and NPA for PP were 89% and 98%. The distribution of pathogens was similar in the upper and lower respiratory tracts, and the DNA or RNA copies of pathogens in the lower respiratory tract were equal to or higher than those in the upper respiratory tract. PP detected bacterial pathogens in 40 (67%) cases, and clinicians tended to increase bacterial diagnosis and escalate antimicrobial therapy for them. RP and PP had satisfactory performance to help pediatricians make pathogenic diagnoses and establish therapy earlier. The pathogens in the upper respiratory tract had predictive diagnostic values for lower respiratory tract infections in children with severe CAP.

Clinical characteristics and outcomes of carbapenem-resistant Enterobacterales bacteremia in pediatric patients.

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 < 0.05). The predicting factor of a CRE bacteremia episode was the causative agent of Enterobacter spp. (adjusted OR of 2.551, CI 1.073-6.066, p < 0.05) and ESBL-producing phenotype (adjusted OR 14.268, CI 5.120-39.762, p < 0.001). CONCLUSION: Bloodstream infections caused by CRE are associated with a higher mortality rate in the pediatric population. Attention must be paid to preventing and managing pediatric patients with CRE infections.

The impact of the coronavirus disease 2019 epidemic and national public restrictions on Pediatric Intensive Care Units in Taiwan.

BACKGROUND/PURPOSE: Coronavirus disease 2019 (COVID-19) pandemic challenges pediatric health globally by limited medical accessibility. In response to COVID-19 epidemic in Taiwan, public restrictions were applied and the Level 3 alert was announced from May to July in 2021 for local outbreak. This study aims to analyze patients' clinical features and outcomes in the pediatric intensive care unit (PICU) during the COVID-19 epidemic with the Level 3 alert in Taiwan. METHODS: Medical records were retrospectively collected in patients admitted to the PICU of National Taiwan University Children's Hospital from May to July 2021 (Level 3 alert) and May to July 2019 and 2020 (control periods). Clinical characteristics and outcomes were compared between patients in the period with the Level 3 alert and control periods. RESULTS: During the study period, PICU monthly admissions significantly decreased in the Level 3 alert period and were negatively correlated with monthly newly confirmed COVID-19 cases. Patients admitted during the Level 3 alert were older, had higher disease severity, lower proportion of cardiovascular disease, and higher proportion of hematology-oncology diseases than those in the control group. After adjusting for the above factors, admission during Level 3 alert was an independent factor for higher mortality rate and prolonged length of stay (>14 days) in the PICU. CONCLUSION: During the COVID-19 epidemic with strict public restrictions, critically ill patients admitted to the PICU decreased but had increased disease severity, prolonged length of stay in the PICU, and higher mortality, reflecting the impact of quarantine and limited medical access.

Children with Mycoplasma pneumoniae infection in Taiwan: Changes in molecular characteristics and clinical outcomes.

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 MLRM. 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 MLRM. 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 MLRM. 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.

Prognostic determinants of hearing outcomes in children with congenital cytomegalovirus infection.

Congenital cytomegalovirus (cCMV) infection is the most prevalent cause of non-genetic sensorineural hearing loss (SNHL) in children. However, the prognostic determinants of SNHL remain unclear. Children with cCMV infection in a tertiary hospital were enrolled. The presence of cCMV-related symptoms at birth, the newborn hearing screening (NHS) results, and the blood viral loads were ascertained. Audiologic outcomes and initial blood viral loads were compared between different groups. Of the 39 children enrolled, 16 developed SNHL. SNHL developed in 60% of children who were initially symptomatic, and in 34.5% of those who were initially asymptomatic with normal hearing or isolated hearing loss, respectively. Failuire in NHS was a reliable tool for early detection of SNHL. The initial viral loads were higher in children who were symptomatic at birth, those who failed NHS, and those who developed SNHL. We observed SNHL deterioration in a patient after CMV DNAemia clearance was achieved, and in another patient with the flare-up of viral load. The presence of cCMV-related symptoms at birth, failure in NHS, and blood viral load might be the prognostic factors for hearing outcomes. Regular audiologic examinations are necessary in all children with cCMV infection even after CMV DNAemia clearance.

Genome Wide Identification of Respiratory Burst Oxidase Homolog (Rboh) Genes in Citrus sinensis and Functional Analysis of CsRbohD in Cold Tolerance.

Respiratory burst oxidase homologs (Rbohs) are critical enzymes involved in the generation of reactive oxygen species (ROS) that play an important role in plant growth and development as well as various biotic and abiotic stresses in plants. Thus far, there have been few reports on the characterization of the Rboh gene family in Citrus. In this study, seven Rboh genes (CsRbohA~CsRbohG) were identified in the Citrus sinensis genome. The CsRboh proteins were predicted to localize to the cell membrane. Most CsRbohs contained four conserved domains, an EF-hand domain, and a transmembrane region. Phylogenetic analysis demonstrated that the CsRbohs were divided into five groups, suggesting potential distinct functions and evolution. The expression profiles revealed that these seven CsRboh genes displayed tissue-specific expression patterns, and five CsRboh genes were responsive to cold stress. Fourteen putative cis-acting elements related to stress response, hormone response, and development regulation were present within the promoters of CsRboh genes. The in-silico microRNA target transcript analyses indicated that CsRbohE might be targeted by csi-miR164. Further functional and physiological analyses showed that the knockdown of CsRbohD in trifoliate orange impaired resistance to cold stress. As a whole, our results provide valuable information for further functional studies of the CsRboh genes in response to cold stress.