A colorimetric, photothermal, and fluorescent triple-mode CRISPR/cas biosensor for drug-resistance bacteria detection.

A multimodal analytical strategy utilizing different modalities to cross-validate each other, can effectively minimize false positives or negatives and ensure the accuracy of detection results. Herein, we establish a colorimetric, photothermal, and fluorescent triple modal CRISPR/Cas12a detection platform (CPF-CRISPR). An MNPs-ssDNA-HRP signal probe is designed to act as a substrate to trigger three signal outputs. In the presence of the DNA target, MNPs-ssDNA-HRP is cleaved by the activated CRISPR/Cas12a, resulting in the release of HRP and generating short DNA strands with 3-terminal hydroxyl on magnetic beads. The released HRP subsequently catalyzed TMB-H2O2 reaction and oxidized TMB is used for colorimetric and photothermal signal detection. Under the catalysis of terminal deoxynucleotidyl transferase (TdT), the remaining short DNA strands are used as primers to form poly-T and function as scaffolds to form copper nanoclusters for fluorescent signal output. To verify the practical application of CPF-CRISPR, we employed MRSA as a model. The results demonstrate the platform's high accuracy and sensitivity, with a limit of detection of 101 CFU/mL when combined with recombinase polymerase amplification. Therefore, by harnessing the programmability of CRISPR/Cas12a, the biosensor has the potential to detect various drug-resistant bacteria, demonstrating significant practical applicability.

Inoculation Age of Bacillus Calmette-Guérin Tokyo-172 Strain and Vaccine-related Adverse Reactions in Taiwan Birth Cohort of 2012-2017.

BACKGROUND: In 2016 in Taiwan, inoculation with the Bacillus Calmette-Guérin (BCG) Tokyo-172 vaccine was postponed from 24 hours after birth to 5-8 months of age. We reviewed BCG-induced adverse reactions reported to the Vaccine Injury Compensation Program (VICP) to identify differences between early and delayed BCG inoculation. METHODS: Clinical presentations of BCG-related adverse reactions reported to VICP for the 2012-2017 birth cohort were reviewed until the end of 2019. The correlations between inoculation age and complications were evaluated. RESULTS: We analyzed 233 BCG adverse reactions, including regional lymphadenitis (33.9%), injection site reactions (35.2%), osteitis/osteomyelitis (27.9%), and distant soft tissue infections (3.0%). The incidence of osteitis/osteomyelitis was lower when vaccination was done after 5 months of age (relative risk [RR], 0.32; 95% confidence interval [CI], .16-.64). Injection site reactions (RR, 8.82; 95% CI, 5.04-15.44) and lymphadenitis (RR, 2.24; 95% CI, 1.44-3.45) were significantly more common in vaccinees older than 5 months. Shorter onset durations of mild adverse reactions (lymphadenitis and injection site reactions) were reported in vaccinees older than 5 months, while no statistical significance was found regarding osteitis/osteomyelitis. CONCLUSIONS: Osteomyelitis and distant soft tissue infection may occur less frequently when BCG inoculation occurs after 5 months of age, although mild adverse reactions can be more frequent, symptom onset times can be shortened. As few severe reactions might occur more than 2 years after BCG inoculation and the policy of delayed BCG inoculation was implemented in 2016, a longer observational period is needed to clarify the exact severe complications decrement.

Clinical Manifestations, Management, and Outcomes of Osteitis/Osteomyelitis Caused by Mycobacterium bovis Bacillus Calmette-Guérin in Children: Comparison by Site(s) of Affected Bones.

OBJECTIVE: To evaluate the clinical manifestations, management, and outcomes of Mycobacterium bovis Bacillus Calmette-Guérin (BCG) osteitis/osteomyelitis. STUDY DESIGN: We reviewed 71 cases of BCG osteitis/osteomyelitis registered in Taiwan's vaccine injury compensation program (VICP) in 1998-2014. Demographic, clinical, laboratory, treatment, and outcome data were compared according to site(s) of infection. RESULTS: Involvement of a long bone of the lower extremity was present in 36.6% of the children, followed by foot bone (23.9%), rib or sternum (15.5%), upper extremity long bone (9.9%), hand bone (7%), multiple bones (4.2%), and vertebrae (2.8%). Children with lower extremity long bone involvement had a longer interval from receipt of BCG vaccine to presentation (median, 16.0 months; P = .02), and those with foot bone infection had higher rates of swelling (94.1%; P = .02) and local tenderness (76.5%; P = .004). Surgical intervention was performed in 70 children, with no significant difference in the number of procedures by site (median, 1.0 procedure per patient). Among the 70 children who received antimicrobial therapy, those with vertebral and multifocal infections had a longer duration of treatment (P < .001) and/or second-line antituberculosis medications (P = .002). Three children with vertebral and multifocal infections had major sequelae with kyphosis or leg length discrepancy. Outcomes were good for children with involvement of the ribs, sternum, and peripheral bones without multifocal involvement. The average time for functional recovery was 6.2 ± 3.9 months. CONCLUSION: Children with BCG osteitis/osteomyelitis in different bones had distinct presentations and outcomes. Pediatricians should consider BCG bone infection in young vaccinated children with insidious onset of signs and symptoms, and consider affected site(s) in the management plan.

Preliminary Report of Nationwide COVID-19 Vaccine Compensation in Taiwan.

The potential adverse effects of coronavirus disease 2019 (COVID-19) vaccinations raise public concerns. Data from Taiwan's Vaccine Injury Compensation Program (VICP) can provide valuable insights. This study analyzed the preliminary application data for COVID-19 vaccine compensation in Taiwan's VICP, focusing on applicants receiving vaccines between March 2021 and June 2022. Among the 2941 adverse events, 113 cases (3.8%) were deemed causally associated with vaccination, 313 (10.6%) were indeterminate, and 2515 (85.5%) had no causal association. Nearly half (47.6%) of the applicants were over 60 years old, and 76.6% had a history of pre-existing chronic diseases. Among the 426 vaccine-associated or indeterminate cases, the most common causes were hematological diseases and thrombosis. There were 920 mortality cases reported, and 97.4% were unassociated with vaccination. Only five deaths were judged to be associated with the COVID-19 vaccination, all involving the adenovirus vector vaccine and thrombosis with thrombocytopenia syndrome. In conclusion, most compensation applications were not causally linked to vaccination. Compared to other countries, the number of applications in Taiwan's VICP is relatively high. These findings may indicate a need to adjust the application requirements for compensation in Taiwan's program.

Neonatal orbital abscess.

Orbital abscess is life-threatening and rare in children. Reported herein is a term male neonate who had methicillin-resistant Staphylococcus aureus orbital abscess, and a literature review of this disease. A total of 16 neonates diagnosed with neonatal orbital abscess are reported in the literature. There is a mild male predilection and two neonates were delivered prematurely. Leukocytosis, fever, ethmoiditis and associated upper respiratory tract infection were found in approximately half of them. Eight neonates had sepsis and 14 patients underwent surgical intervention. One patient died. Staphylococcus aureus was identified in 14 out of 17 patients. Neonatal orbital abscess is rarely encountered but may be fatal. Although streptococci are prevalent in childhood orbital infection, S. aureus was predominant in neonatal orbital abscess in the present series. Appropriate antimicrobial therapy against S. aureus is essential in treating neonatal orbital abs ess. This case suggests that a higher initial dose of vancomycin may be an effective and safe strategy for severe S. aureus infection in neonates.

An Ultrasensitive Colorimetric Foodborne Pathogenic Detection Method Using a CRISPR/Cas12a Mediated Strand Displacement/Hybridization Chain Reaction.

Accurate, rapid, and sensitive pathogenic detections play an important role in food safety. Herein, we developed a novel CRISPR/Cas12a mediated strand displacement/hybridization chain reaction (CSDHCR) nucleic acid assay for foodborne pathogenic colorimetric detection. A biotinylated DNA toehold is coupled on avidin magnetic beads and acts as an initiator strand to trigger the SDHCR. The SDHCR amplification allowed the formation of long hemin/G-quadruplex-based DNAzyme products to catalyze the TMB-H2O2 reaction. In the presence of the DNA targets, the trans-cleavage activity of CRISPR/Cas12a was activated to cleave the initiator DNA, resulting in the failure of SDHCR and no color change. Under optimal conditions, the CSDHCR has a satisfactory linear detection of DNA targets with a regression equation Y = 0.0531*X - 0.0091 (R2 = 0.9903) in the range of 10 fM to 1 nM, and the limit of detection was determined as 4.54 fM. In addition, Vibrio vulnificus, one foodborne pathogen, was used to verify the practical application of the method, and it showed satisfactory specificity and sensitivity with a limit of detection at 1.0 × 100 CFU/mL coupling with recombinase polymerase amplification. Our proposed CSDHCR biosensor could be a promising alternative method for ultrasensitive and visual detection of nucleic acids and the practical application of foodborne pathogens.

Building nomogram plots for predicting urinary tract infections in children less than three years of age.

BACKGROUND AND PURPOSE: Urinary tract infections (UTIs) are the most common bacterial infection in young children. This study aimed to formulate nomogram plots for clinicians to predict UTIs in children aged <3 years by evaluating the risk factors for UTIs in these children. METHODS: This retrospective study was conducted at a tertiary medical center from December 2017 to November 2020. Children less than three years of age were eligible for the study if they had undergone both urine culture and urinalysis during the study period. Mixed-effects logistic regression models with a stepwise procedure were used to determine the relationship between outcome (positive/negative UTI) and covariates of interest (e.g., weight percentile, laboratory) for each patient. Nomogram plots were constructed on the basis of significant factors. We repeated the analysis thrice to adapt it to three different medical settings: medical centers, regional hospitals, and local clinics. RESULTS: In the medical center setting, the two most significant factors were urine leukocyte count ≥100 (OR =8.87; 95% CI (Confidence Interval), 4.135-19.027) and urine nitrite level (OR =8.809; 95% CI, 5.009-15.489). The two factors showed similar significance at the regional hospital and local clinic settings. Abnormal renal echo findings were positively correlated with UTI in the medical center setting (OR =2.534; 95% CI 1.757-3.655). Three nomogram plots for the prediction of UTIs were drawn for medical centers, regional hospitals, and local clinics. CONCLUSION: Using the three nomogram plots, frontline doctors can formulate the probabilities of pediatric UTIs for better decision-making.

ITPKC gene SNP rs28493229 and Kawasaki disease in Taiwanese children.

Kawasaki disease (KD) is a systemic vasculitis caused by unknown infectious agents, host immune dysregulation and genetic susceptibility in children. Coronary artery lesions (CALs) complicate 15-25% of cases of untreated KD. The aim of this study was to investigate if the single-nucleotide polymorphism (SNP) rs28493229 of the ITPKC gene is associated with susceptibility to KD or with CALs in Taiwanese children. A total of 385 unrelated Taiwanese children (222 boys and 163 girls) with KD were included, 140 of whom had CALs. Mean age at diagnosis was 1.9 +/- 1.7 (0.1-10.2) years. Rs28493229 was genotyped in children with KD and 1158 ethnically matched healthy controls using the TaqMan Allelic Discrimination Assay. In 184 families with KD, both biological parents were available, constituting 184 trios with their children. They were assessed in a family-based study by means of a transmission/disequilibrium test (TDT). No significant differences in genotype (P = 0.29 and P = 0.29, respectively), allele (P = 0.14 and P = 0.22, respectively) and carrier (P = 0.22 and P = 0.25, respectively) frequencies of the SNP were found between healthy controls and children with KD or those with CALs. TDT in the 184 family trios and in 69 trios where the child had CALs did not reveal significant overtransmittion of the C allele. In conclusion, we did not find a statistically significant association between the ITPKC gene SNP rs28493229 and KD or CALs in Taiwanese children.

Screening high-grade vesicoureteral reflux in young infants with a febrile urinary tract infection.

BACKGROUND: The lack of good evidence for improved outcomes in children and young infants with febrile urinary tract infection (UTI) after aggressive treatment for vesicoureteral reflux (VUR) has raised doubts regarding the need for routine voiding cystourethrography (VCUG), and the appropriate imaging evaluation in these children remains controversial. OBJECTIVES: This prospective study aimed to determine whether abnormalities found on acute dimercaptosuccinic acid (DMSA) scan and ultrasound (US) can help indicate the necessity of voiding cystourethrography (VCUG) in young infants. METHODS: For 3.5 years, all infants younger than 3 months presenting with first febrile UTI were prospectively studied. All infants were hospitalized and investigated using US (<3 days after admission), DMSA scan (<5 days after admission), and VCUG (7-10 days after antibiotic treatment) after diagnosis. The association among findings of US, DMSA scan, and VCUG were evaluated. RESULTS: From 220 infants, there were abnormal results in 136 (61.8%) US and in 111 (50.5%) DMSA scans. By US, ten infants (4.5%) with abscess or structural abnormalities other than VUR were diagnosed. High-grade (III-V) VUR was present in 39 patients (17.7%). The sensitivities for high-grade VUR of renal US alone (76.9%) or DMSA scan alone (82.1%) were not as good as that of the "OR rule" strategy, which had 92.3% sensitivity and 94.3% negative predictive value. CONCLUSIONS: To screen high-grade VUR in young infants with febrile UTI, US and acute DMSA scan could be performed first. VCUG is only indicated when abnormalities are apparent on either US or DMSA scan or both.

Epidemiological and microbiological characteristics of culture-proven acute otitis media in Taiwanese children.

BACKGROUND/PURPOSE: Acute otitis media (AOM) is one of the most common diseases in children. Here, we describe the epidemiological and microbiological characteristics of AOM in Taiwanese children over a 10-year period. METHODS: We retrospectively enrolled pediatric patients with culture-proven AOM who were treated at Mackay Memorial Hospital, Taipei between 1999-2008. The data include demographic characteristics, clinical history, and microbiological characteristics. RESULTS: Six hundred and fourteen patients were included. The male:female ratio was 1.4 (p<0.001). Greater than three-fourths of the patients (476 [77.5%]) were < 5 years of age, and most patients were 1-2 years of age. The most common isolated pathogen was Streptococcus pneumoniae (419 patients [68.2%]), followed by nontypeable Haemophilus influenzae (NTHi; 118 patients [19.2%]). The distributions of age, gender, use of tympanocentesis, history of previous AOM, and use of antibiotic between patients infected with the two pathogens were not significantly different. However, the number of patients with AOM caused by S. pneumoniae, but not NTHi, decreased during the study period (p=0.004). Three hundred and eighty-seven children (63.0%) with AOM developed spontaneous otorrhea. Compared with patients who underwent tympanocentesis, those with spontaneous otorrhea were younger (27.0±16.4 vs. 31.1±15.2 months of age, p=0.004), more likely to have a previous history of AOM (p=0.019), and more likely to receive more antibiotics (p=0.012). The third most common pathogen was S. pyogenes (25 patients [4.1%]). S. pyogenes occurred more often in children > 5 years of age and was associated with spontaneous otorrhea (p<0.001). CONCLUSION: S. pneumoniae and NTHi are common causes of culture-confirmed AOM in Taiwanese children. Although S. pyogenes is not as common, it usually causes AOM in children > 5 years of age and is associated with spontaneous otorrhea.

Etiology, clinical features, management, and outcomes of skin and soft tissue infections in hospitalized children: A 10-year review.

PURPOSE: This study aimed to describe the etiology, clinical features, hospital course, and outcomes of hospitalized children with skin and soft tissue infections (SSTIs) and to test if clinical and laboratory variables at admission could differentiate between community-acquired methicillin-resistant Staphylococcus aureus (CA-MRSA) and community-acquired methicillin-sensitive S. aureus (CA-MSSA). METHODS: We reviewed the clinical, laboratory, treatment, and outcome data for children hospitalized with SSTIs, aged 0-18 years at MacKay Children's Hospital between 2010 and 2019. Multivariable logistic regression was used to identify independent predictors of CA-MRSA and CA-MSSA SSTIs. RESULTS: A total of 1631 patients were enrolled. Erysipelas/cellulitis (73.8%) was the most common pediatric SSTI type, followed by acute lymphadenitis (13.6%) and abscess/furuncle/carbuncle (8.6%). Among the 639 culture-positive isolates (purulent SSTIs), 142 (22.2%) were CA-MSSA and 363 (56.8%) were CA-MRSA. The age group 0-1 month (OR, 6.52; 95% CI 1.09-38.92; P = 0.04) and local lymph node reaction (OR, 2.47; 95% CI 1.004-6.08; P = 0.049) were independent factors for differentiating children with CA-MSSA from those with CA-MRSA SSTIs. MRSA isolates in our cohort were highly susceptible to glycopeptides (100%), linezolid (100%), daptomycin (100%), and sulfamethoxazole/trimethoprim (98.6%) but were significantly less susceptible to clindamycin compared with MSSA (34.2% vs. 78.2%, P < 0.001). CONCLUSION: S. aureus is the leading pathogen of culture-proven SSTIs in hospitalized children with MRSA accounting for more than half. Determining the optimal empirical antibiotics in CA-SSTIs may rely on the patient's age, disease severity, and local epidemiologic data.

One-step synthesized antimicrobial peptide-functionalized gold nanoclusters for selective imaging and killing of pathogenic bacteria.

The development of multifunctional nanomaterials with bacterial imaging and killing activities is of great importance for the rapid diagnosis and timely treatment of bacterial infections. Herein, peptide-functionalized gold nanoclusters (CWR11-AuNCs) with high-intensity red fluorescence were successfully synthesized via a one-step method using CWR11 as a template and by optimizing the ratio of CWR11 to HAuCl4, reaction time, pH, and temperature. The CWR11-AuNCs bound to bacteria and exhibited selective fluorescence microscopy imaging properties, which is expected to provide a feasible method for locating and imaging bacteria in complex in vivo environments. In addition, CWR11-AuNCs not only retained the antibacterial and bactericidal activities of CWR11 but also exhibited certain inhibitory or killing effects on gram-negative and gram-positive bacteria and biofilms. The MICs of CWR11-AuNCs against Escherichia coli and Staphylococcus aureus were 178 and 89 µg/ml, respectively. Surprisingly, cell viability in the CWR11-AuNC-treated group was greater than that in the CWR11-treated group, and the low cytotoxicity exhibited by the CWR11-AuNCs make them more promising for clinical applications.

Reducing catheter related bloodstream infection risk of infant with a prophylactic antibiotic therapy before removing peripherally inserted central catheter: A retrospective study.

PURPOSE: This study examined the efficacy of prescribing antibiotics, specifically a single dose of vancomycin, in reducing the incidence of culture-positive and culture-negative sepsis prior to the removal of peripherally inserted central catheters (PICCs). MATERIALS AND METHODS: We retrospectively reviewed charts of infants who had PICCs in a tertiary level hospital during the period from 2010 to 2019. The incidence of post-catheter removal clinical sepsis between the groups with or without antibiotics was compared. The antibiotic group was defined by receiving a single dose of vancomycin or any other antibiotic prior to line removal. RESULTS: We enrolled 585 PICC removal episodes in 546 infants for analysis. Antibiotics were given prior to removal in 257 cases (43.9%) and not given prior to removal in 328 cases (56.1%). There were 13 episodes of post-catheter removal clinical sepsis detected within 72 h (2.2%), 2 of which were culture-positive (0.3%). A 9.3-fold decrease in the odds for clinical sepsis was observed in the antibiotic group (p = 0.01). The incidence of post-catheter removal sepsis was decreased by a single prophylactic dose of vancomycin (p = 0.02), whereas the use of other antibiotics showed no effect (p = 0.35). Logistic regression analysis demonstrated that comorbidities with gastrointestinal diseases (p = 0.01), PICC insertion sites in the scalp and neck (p = 0.04), and no vancomycin administration prior to line removal (p = 0.02) were independent risk factors for subsequent clinical sepsis. CONCLUSION: A single prophylactic dose of vancomycin prior to PICC line removal might reduce clinical sepsis events in infants.

Why is hypercalciuria absent at diagnosis in some children with ATP6V1B1 mutation?

We try to explain why hypercalciuria is absent at diagnosis in some children with an ATP6V1B1 mutation. A 5-month-old girl presented with distal renal tubular acidosis (dRTA) and sensorineural hearing loss. Direct sequencing of the ATP6V1B1 genes disclosed a new homozygous mutation (452 delT) in exon 13. In particular, an absence of hypercalciuria and a normal level of parathyroid hormones were noted. After alkaline therapy, the signs of nephrocalcinosis improved on ultrasound during follow-up. After a review of the literature regarding patients with ATP6V1B1 gene mutations, a young age seemed to be an important factor for normocalciuria. The probable mechanism of normocalciuria and a dynamic mode of calcium excretion in patients with dRTA is proposed. The determinant factors include the degree of systemic acidosis, urine pH, genetic polymorphisms, age, dietary factors, and volume status. Low sodium intake may be a major determinant of normocalciuria in these patients. It is suggested that hypercalciuria is usually absent at diagnosis of dRTA in young infants. Blood pH, plasma bicarbonate concentration, urinary citrate levels, and growth catch-up may be better indicators of adequate alkali therapy in normocalciuric children. Volume contraction, low salt content in infant formula, and alkaline urine in young infants are likely to account for the increased calcium reabsorption.

Rasburicase improves hyperuricemia in patients with acute kidney injury secondary to rhabdomyolysis caused by ecstasy intoxication and exertional heat stroke.

OBJECTIVE: To report the successful use of rasburicase in two children with hyperuricemia secondary to severe rhabdomyolysis. DESIGN: : Case report. SETTING: Pediatric intensive care unit in a freestanding quaternary hospital. PATIENTS: Two pediatric patients with severe rhabdomyolysis and hyperuricemia caused by ecstasy intoxication and exertional heat stroke. INTERVENTION: Use of a single low dose (6 mg) of rasburicase, a urate oxidase enzyme. MEASUREMENTS AND MAIN RESULTS: Rasburicase was administered on the first and second hospital days with a single low dose of 6 mg (0.086 mg/kg in patient A and 0.092 mg/kg in patient B). Within 24 hrs, the levels of serum uric acid in both patients decreased dramatically, and their creatinine levels decreased and urine output increased concurrently. Continuous improvements in the uric acid levels, creatinine levels, and urine output were noted during hospitalization. CONCLUSION: Rasburicase seems to be a safe and effective drug for improving hyperuricemia in patients with rhabdomyolysis and renal failure.

Epidemiological study of hospitalization associated with respiratory syncytial virus infection in Taiwanese children between 2004 and 2007.

BACKGROUND/PURPOSE: Respiratory Syncytial Virus (RSV) is the leading cause of hospitalization in young children. The population-based burden of RSV hospitalization and the effect of potential risk factors on the severity of illness were evaluated in Taiwanese children. METHODS: We analyzed the annual population-based incidence, underlying diseases and characteristics of hospitalizations due to RSV in Taiwanese children under 5 years of age from 2004 to 2007 by using Taiwan's National Health Insurance database. RESULTS: A total of 11,081 children with RSV-associated hospitalization were studied. Average annual population-based hospitalization incidence was 1,077 and 232 per 100,000 children-year in children under 6 months and under 5 years of age, respectively. The peak incidence occurred between 1 and 2 months of age. The male-to-female incidence risk ratio was 1.4:1 (p < 0.001). There was a significant seasonal distribution with consistent peaks in the spring and autumn every year (p < 0.001). A total of 373 patients (3.3%) had repeated RSV infection. The 943 children (8.5%) with underlying diseases were older (p = 0.001), required longer intensive care unit (ICU) stays (p < 0.001), had a higher rate of endotracheal intubation (p < 0.05), and incurred higher medical costs (p < 0.001). A total of 888 patients (8%) required ICU care. Younger age (p < 0.001), prematurity (p < 0.001), cerebral palsy (p < 0.001) and congenital heart disease (p < 0.001) were independent predictors of requiring ICU care. CONCLUSION: RSV infection occurs biennially with peaks in spring and fall in Taiwan. Patients with underlying diseases need longer hospital and ICU stays and incur higher medical costs. Younger age, prematurity, congenital heart disease and cerebral palsy are predictors of ICU care.

Prediction of Coronary Artery Aneurysms in Children With Kawasaki Disease Before Starting Initial Treatment.

Background: Precisely predicting coronary artery aneurysms (CAAs) remains a clinical challenge. We aimed to investigate whether coronary dimensions adjusted for body surface area (Z scores) on baseline echocardiography and clinical variables before primary treatment could predict the presence of late CAAs. Methods: We conducted a retrospective study including children hospitalized for Kawasaki disease and received intravenous immunoglobulin within 10 days of illness. We defined late CAAs as a maximum Z score (Zmax) ≥2.5 of the left main, right, or left anterior descending coronary artery at 11-60 days of illness. Associations between late CAAs and clinical parameters and baseline maximum Z scores were analyzed. Results: Among the 314 included children, 31 (9.9%) had late CAAs. Male, higher C-reactive protein, and higher baseline Zmax were risk factors of late CAAs. Late CAAs were significantly associated with baseline Zmax ≥2.0 vs. <2.0 (25 [32.5%] vs. 6 [2.5%], P < 0.001). The odds ratio for late CAAs among the patients with baseline Zmax ≥2.0 vs. <2.0 was 18.5 (95% confidence interval, 7.23 to 47.41, P < 0.001). The sensitivity, specificity, positive predictive value, and negative predictive value of baseline Zmax ≥2.0 for the presence of later CAAs were 80.6, 81.6, 32.5, and 97.5%, respectively. Conclusions: Findings from this study suggest that Zmax ≥2.0 of coronary arteries on baseline echocardiography may be used to predict children at a high risk of late CAAs and allow for targeted early intensification therapy.

To mix or not to mix? A rapid systematic review of heterologous prime-boost covid-19 vaccination.

INTRODUCTION: Coronavirus disease 2019 (COVID-19) has had an enormous impact worldwide, and vaccination is believed to be the method that will control the pandemic. Several types of vaccines developed using different platforms have been authorized, but the immunogenicity and reactogenicity of heterologous prime-boost vaccination with different vaccines remain largely unclear. AREAS COVERED: Electronic databases including PubMed, Embase, medRxiv, Research Square, and SSRN were searched to investigate the immunogenicity and reactogenicity associated with heterologous vaccination.As of 30 June 2021, four trials including 1,862 participants were identified. Heterologous administration of BNT162b2 (BNT) in ChAdOx1 (ChAd)-primed participants (ChAd/BNT) showed noninferior immunogenicity to homologous BNT administration (both prime and booster were BNT vaccines, BNT/BNT) with tolerable reactogenicity and higher T cell responses. Compared with homologous ChAdOX1 vaccination (ChAd/ChAd), heterologous ChAd/BNT was found to elicit higher immunogenicity (ChAd/BNT vs. ChAd/ChAd, antibody titer ratio: 9.2). EXPERT OPINION: Our systematic review found robust immunogenicity and tolerable reactogenicity of heterologous administration of a BNT162b2 boost in ChAdOx1-primed participants. An additional benefit of stronger T cellular immunity was also observed. Heterologous vaccination is a reasonable and feasible strategy to combat COVID-19. Further studies are warranted to confirm the benefits and identify the optimal combinations, doses, and intervals.

Efficacy of clarithromycin-naproxen-oseltamivir combination therapy versus oseltamivir alone in hospitalized pediatric influenza patients.

PURPOSE: This study aimed to compare the safety and efficacy of clarithromycin-naproxen-oseltamivir combination therapy to that of oseltamivir therapy alone in hospitalized pediatric influenza patients. METHODS: This prospective, single-blind study included children aged 1-18 years hospitalized with influenza, in MacKay Children's Hospital, Taiwan, between December 2017 and December 2019. The primary outcomes were the time to defervescence and decrease of the Pediatric Respiratory Severity Score (PRESS) during hospitalization. The secondary outcomes were serial changes in virus titers, measured using real-time polymerase chain reaction. RESULTS: Fifty-four patients were enrolled (28 in the control group and 26 in the combination group) in total. There were no differences in the patients' baseline characteristics between the groups. The time to defervescence was significantly shorter in the combination group than the oseltamivir group (13.2 h vs. 32.1 h, p = 0.002). The decrease in the virus titer from days 1-3 (log Δ13) was more pronounced in the combination group than the oseltamivir group. (39% vs. 19%, p = 0.001). There were no differences in adverse effects such as vomiting, diarrhea, and abdominal pain during the study or within 30 days after antiviral therapy. CONCLUSION: The clarithromycin-naproxen-oseltamivir combination group experienced a more rapid defervescence and a more rapid decline of influenza virus titer than the group treated with oseltamivir alone. Further consideration should be given to whether the overall benefits of combination therapy in hospitalized pediatric influenza patients outweigh the risks.