Phage display-derived alpaca nanobodies as potential therapeutics for Naja atra snake envenomation.

Naja atra, the Chinese cobra, is a major cause of snake envenomation in Asia, causing hundreds of thousands of clinical incidents annually. The current treatment, horse serum-derived antivenom, has unpredictable side effects and presents manufacturing challenges. This study focused on developing new-generation snake venom antidotes by using microbial phage display technology to derive nanobodies from an alpaca immunized with attenuated N. atra venom. Following confirmation of the immune response in the alpaca, we amplified VHH genes from isolated peripheral blood mononuclear cells and constructed a phage display VHH library of 1.0 × 107 transformants. After four rounds of biopanning, the enriched phages exhibited increased binding activity to N. atra venom. Four nanobody clones with high binding affinities were selected: aNAH1, aNAH6, aNAH7, and aNAH9. Specificity testing against venom from various snake species, including two Southeast Asian cobra species, revealed nanobodies specific to the genus Naja. An in vivo mouse venom neutralization assay demonstrated that all nanobodies prolonged mouse survival and aNAH6 protected 66.6% of the mice from the lethal dosage. These findings highlight the potential of phage display-derived nanobodies as valuable antidotes for N. atra venom, laying the groundwork for future applications in snakebite treatment.IMPORTANCEChinese cobra venom bites present a formidable medical challenge, and current serum treatments face unresolved issues. Our research applied microbial phage display technology to obtain a new, effective, and cost-efficient treatment approach. Despite interest among scientists in utilizing this technology to screen alpaca antibodies against toxins, the available literature is limited. This study makes a significant contribution by introducing neutralizing antibodies that are specifically tailored to Chinese cobra venom. We provide a comprehensive and unbiased account of the antibody construction process, accompanied by thorough testing of various nanobodies and an assessment of cross-reactivity with diverse snake venoms. These nanobodies represent a promising avenue for targeted antivenom development that bridges microbiology and biotechnology to address critical health needs.

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.

Abdominal wound length influences the postoperative serum level of interleukin-6 and recovery of flatus passage among patients with colorectal cancer.

Introduction: A mini-laparotomy for colorectal cancer (CRC) has been reported to shorten postoperative ileus (POI) and hospital stay. Interleukin-6 (IL-6) plays a role in intestinal tissue inflammation, leading to POI. This study investigated the effects of abdominal wounds and IL-6 levels on POI in patients having CRC surgery. Materials and methods: Forty-three patients with CRC underwent bowel resection. Serum samples were collected preoperatively and at 2, 24, and 48 h after surgery for cytokine quantification by ELISA. Clinical data, including time from surgery to first passage of flatus and postoperative hospital stay, demographic and pathological data, and routine blood tests, were compared statistically with abdominal wound length and the postoperative increments of cytokines (designated as Δ). Results: The length of the abdominal wound showed a significant correlation with clinical variables (length of operation time, time of first flatus passage, and length of postoperative hospital stay) and cytokine variables (IL-6(Δ2 h), IL-8(Δ2 h) and IL-10(Δ2 h). Linear regression analysis showed that the abdominal wound length significantly influenced the operation time, time of first flatus passage, and length of postoperative hospital stay (p < 0.001). The length of the abdominal wound showed a significant influence on the IL-6(Δ2 h) and IL-8(Δ2 h) (p < 0.001, respectively) but no influence on IL-10(Δ2 h). IL-6(Δ2 h), but not IL-8(Δ2 h), significantly influenced the time to first flatus passage and length of hospital stay (p = 0.007, p = 0.006, respectively). The mini-laparotomy approach (wound length <7 cm) led to significantly shortened operation time, time of first flatus passage, length of postoperative stay (p = 0.004, p = 0.003, p = 0.006, respectively) as well as reduced postoperative increment of IL-6(Δ2 h) (p = 0.015). The mini-laparotomy for anterior resection surgery significantly influenced operation time, time of first passage of flatus, length of postoperative stay, and IL-6(Δ2 h). Conclusion: Our study is the first to report the complex interaction among the length of the abdominal wound, IL-6 serum level, recovery of the first passage of flatus, and postoperative hospital stay. These results suggest that smaller abdominal wounds and smaller postoperative IL-6 increments were associated with faster recovery of flatus passage and shorter hospital stays.

Developing an entrustable professional activity for providing health education and consultation in occupational therapy and examining its validity.

BACKGROUND: Entrustable Professional Activities (EPA)-based assessment is easily and intuitively used in evaluating the learning outcomes of competency-based medical education (CBME). This study aimed to develop an EPA for occupational therapy focused on providing health education and consultation (TP-EPA3) and examine its validity. METHODS: Nineteen occupational therapists who had completed online training on the EQual rubric evaluation participated in this study. An expert committee identified six core EPAs for pediatric occupational therapy. TP-EPA3 was developed following the EPA template and refined through consensus meetings. The EQual rubric, a 14-item, five-point criterion-based anchor system, encompassing discrete units of work (DU), entrustable, essential, and important tasks of the profession (EEIT), and curricular role (CR), was used to evaluate the quality of TP-EPA3. Overall scores below 4.07, or scores for DU, EEIT, and CR domains below 4.17. 4.00, and 4.00, respectively, indicate the need for modifications. RESULTS: The TP-EPA3 demonstrated good validity, surpassing the required cut-off score with an average overall EQual score of 4.21 (SD = 0.41). Specific domain scores for DU, EEIT, and CR were 3.90 (SD = 0.69), 4.46 (SD = 0.44), and 4.42 (SD = 0.45), respectively. Subsequent revisions clarified observation contexts, enhancing specificity and focus. Further validation of the revised TP-EPA3 and a thorough examination of its reliability and validity are needed. CONCLUSION: The successful validation of TP-EPA3 suggests its potential as a valid assessment tool in occupational therapy education, offering a structured approach for developing competency in providing health education and consultation. This process model for EPA development and validation can guide occupational therapists in creating tailored EPAs for diverse specialties and settings.

Chief complaints and computed tomography results in the emergency department: a three-year retrospective cohort study.

BACKGROUND: Computed tomography (CT) is frequently performed in the patients who admitted to the emergency department (ED), discharged but returned to ED within 72 h. It is unknown whether the main complaints of patients assist physicians to use CT effectively. This study aimed to find the association between chief complaints and the CT results. METHODS: This three-year retrospective cohort study was conducted in the ED of a tertiary medical center. Adult patients who returned to the ED after the index visit were included from 2019 to 2021. Demographics, pre-existing diseases, chief complaints, and CT region were recorded by independent ED physicians. A logistic regression model with an odds ratio (OR) and 95% confidence interval (CI) was used to determine the relationship between chief complaints and positive CT results. RESULTS: In total, 7,699 patients revisited ED after the index visit; 1,202 (15.6%) received CT. The top chief complaints in patients who received CT were abdominal pain, dizziness, and muscle weakness. Patients with abdominal pain or gastrointestinal symptoms had a significantly higher rate of positive abdominopelvic CT than those without it (OR 2.83, 95% CI 1.98-4.05, p < 0.001), while the central nervous system and cardiopulmonary chief complaints were not associated (or negatively associated) with new positive CT findings. CONCLUSION: Chief complaints of patients on revisit to the ED are associated with different yields of new findings when CT scans of the chest, abdomen and head are performed. Physicians should consider these differential likelihoods of new positive findings based on these data.

The genomic evolutionary dynamics and global circulation patterns of respiratory syncytial virus.

Respiratory syncytial virus (RSV) is a leading cause of acute lower respiratory tract infection in young children and the second leading cause of infant death worldwide. While global circulation has been extensively studied for respiratory viruses such as seasonal influenza, and more recently also in great detail for SARS-CoV-2, a lack of global multi-annual sampling of complete RSV genomes limits our understanding of RSV molecular epidemiology. Here, we capitalise on the genomic surveillance by the INFORM-RSV study and apply phylodynamic approaches to uncover how selection and neutral epidemiological processes shape RSV diversity. Using complete viral genome sequences, we show similar patterns of site-specific diversifying selection among RSVA and RSVB and recover the imprint of non-neutral epidemic processes on their genealogies. Using a phylogeographic approach, we provide evidence for air travel governing the global patterns of RSVA and RSVB spread, which results in a considerable degree of phylogenetic mixing across countries. Our findings highlight the potential of systematic global RSV genomic surveillance for transforming our understanding of global RSV spread.

Prediction of high-risk emergency department revisits from a machine-learning algorithm: a proof-of-concept study.

BACKGROUND: High-risk emergency department (ED) revisit is considered an important quality indicator that may reflect an increase in complications and medical burden. However, because of its multidimensional and highly complex nature, this factor has not been comprehensively investigated. This study aimed to predict high-risk ED revisit with a machine-learning (ML) approach. METHODS: This 3-year retrospective cohort study assessed adult patients between January 2019 and December 2021 from National Taiwan University Hospital Hsin-Chu Branch with high-risk ED revisit, defined as hospital or intensive care unit admission after ED return within 72 hours. A total of 150 features were preliminarily screened, and 79 were used in the prediction model. Deep learning, random forest, extreme gradient boosting (XGBoost) and stacked ensemble algorithm were used. The stacked ensemble model combined multiple ML models and performed model stacking as a meta-level algorithm. Confusion matrix, accuracy, sensitivity, specificity and area under the receiver operating characteristic curve (AUROC) were used to evaluate performance. RESULTS: Analysis was performed for 6282 eligible adult patients: 5025 (80.0%) in the training set and 1257 (20.0%) in the testing set. High-risk ED revisit occurred for 971 (19.3%) of training set patients vs 252 (20.1%) in the testing set. Leading predictors of high-risk ED revisit were age, systolic blood pressure and heart rate. The stacked ensemble model showed more favourable prediction performance (AUROC 0.82) than the other models: deep learning (0.69), random forest (0.78) and XGBoost (0.79). Also, the stacked ensemble model achieved favourable accuracy and specificity. CONCLUSION: The stacked ensemble algorithm exhibited better prediction performance in which the predictions were generated from different ML algorithms to optimally maximise the final set of results. Patients with older age and abnormal systolic blood pressure and heart rate at the index ED visit were vulnerable to high-risk ED revisit. Further studies should be conducted to externally validate the model.

Exploring the Barriers and Facilitators of Mask-Wearing Behavior During the COVID-19 Pandemic in Taiwan, the United States, the Netherlands, and Haiti: A Qualitative Study.

OBJECTIVE: This study explored the barriers and facilitators of mask-wearing behaviors during the pandemic in Taiwan, the United States, the Netherlands, and Haiti. METHODS: Face-to-face interviews were conducted in Taiwan and online interviews were conducted with participants in the United States, the Netherlands, and Haiti. RESULTS: In general, the habit of wearing a mask before coronavirus disease 2019 (COVID-19) was reported by Taiwanese participants. Additionally, Taiwanese participants perceived that wearing a mask was a social responsibility during the pandemic, suggesting that the collectivistic context might influence mask-wearing behavior. Unlike the Taiwanese population, some people in the United States and the Netherlands were reluctant to wear masks due to perceived restrictions on their freedom. Participants from Haiti mentioned that people who wore masks encountered violence, bullying, and discrimination. The results of this study suggest that political leadership and mask mandates have a strong impact on people's mask-wearing behavior. CONCLUSIONS: These findings have valuable implications for the design of diverse behavioral interventions to enhance mask-wearing as part of infectious disease preparedness. Additionally, the findings from these countries offer valuable insights for the development of effective public health interventions to enhance society's resilience during the current pandemic and future infectious disease outbreaks.

Characterization of chicken-derived antibody against Alpha-Enolase of Streptococcus pneumoniae.

Streptococcus pneumoniae is a clinically relevant pathogen notorious for causing pneumonia, meningitis, and otitis media in immunocompromised patients. Currently, antibiotic therapy is the most efficient treatment for fighting pneumococcal infections. However, an arise in antimicrobial resistance in S. pneumoniae has become a serious health issue globally. To resolve the problem, alternative and cost-effective strategies, such as monoclonal antibody-based targeted therapy, are needed for combating bacterial infection. S. pneumoniae alpha-enolase (spEno1), which is thought to be a great target, is a surface protein that binds and converts human plasminogen to plasmin, leading to accelerated bacterial infections. We first purified recombinant spEno1 protein for chicken immunization to generate specific IgY antibodies. We next constructed two single-chain variable fragments (scFv) antibody libraries by phage display technology, containing 7.2 × 107 and 4.8 × 107 transformants. After bio-panning, ten scFv antibodies were obtained, and their binding activities to spEno1 were evaluated on ELISA, Western blot and IFA. The epitopes of spEno1 were identified by these scFv antibodies, which binding affinities were determined by competitive ELISA. Moreover, inhibition assay displayed that the scFv antibodies effectively inhibit the binding between spEno1 and human plasminogen. Overall, the results suggested that these scFv antibodies have the potential to serve as an immunotherapeutic drug against S. pneumoniae infections.

Trypanosoma cruzi infection reduces the population fitness of Mepraia spinolai, a Chagas disease vector.

The hematophagous insect Mepraia spinolai (Hemiptera: Reduviidae: Triatominae) is naturally infected with the protozoan parasite Trypanosoma cruzi, the agent of Chagas disease in humans. In this study, we compared the demographic parameters of M. spinolai with and without T. cruzi infection. We collected the immature life table data of 479 M. spinolai individuals of control cohort (reared on mice without T. cruzi infection) and 563 M. spinolai individuals of treatment cohort (reared on mice with T. cruzi infection). Nymphs were maintained in individual compartments inside a growth chamber (26°C; 65-75%) until adult emergence; moulting and survival were recorded daily. For the adult life table study of the control, we used 24 pairs of adults from the control cohort. For the adult life table study of T. cruzi-infected cohort, 25 infected females were paired with 25 males from the control cohort. Life table data were analysed using bootstrap-match technique based on the age-stage, two-sex life table. The preadult survival rate (0.5282) of the control cohort was significantly higher than that of the infected cohort (0.2913). However, the mean fecundity of reproductive females (Fr = 22.29 eggs/♀) and net reproductive rate of population (R0 = 5.07 offspring/individual) of the 0.5th percentile bootstrap-match control cohort were not significantly different from those of the infected cohort (Fr = 23.35 eggs/♀, R0 = 3.77 offspring/individual). Due to the shorter total preoviposition period and higher proportion of reproductive female, the intrinsic rate of increase (r = 0.0053 d-1 ) and finite rate of increase (λ = 1.0053 d-1 ) of control cohort of M. spinolai were significantly higher than those of the T. cruzi-infected cohort (r = 0.0035 d-1 , λ = 1.0035 d-1 ). These results suggest that T. cruzi infection reduces the population fitness of the Chagas disease vector M. spinolai.

A lissencephaly-associated BAIAP2 variant causes defects in neuronal migration during brain development.

Lissencephaly is a neurodevelopmental disorder characterized by a loss of brain surface convolutions caused by genetic variants that disrupt neuronal migration. However, the genetic origins of the disorder remain unidentified in nearly one-fifth of people with lissencephaly. Using whole-exome sequencing, we identified a de novo BAIAP2 variant, p.Arg29Trp, in an individual with lissencephaly with a posterior more severe than anterior (P>A) gradient, implicating BAIAP2 as a potential lissencephaly gene. Spatial transcriptome analysis in the developing mouse cortex revealed that Baiap2 is expressed in the cortical plate and intermediate zone in an anterior low to posterior high gradient. We next used in utero electroporation to explore the effects of the Baiap2 variant in the developing mouse cortex. We found that Baiap2 knockdown caused abnormalities in neuronal migration, morphogenesis and differentiation. Expression of the p.Arg29Trp variant failed to rescue the migration defect, suggesting a loss-of-function effect. Mechanistically, the variant interfered with the ability of BAIAP2 to localize to the cell membrane. These results suggest that the functions of BAIAP2 in the cytoskeleton, cell morphogenesis and migration are important for cortical development and for the pathogenesis of lissencephaly in humans.

Comparison of on-scene Glasgow Coma Scale with GCS-motor for prediction of 30-day mortality and functional outcomes of patients with trauma in Asia.

BACKGROUND AND IMPORTANCE: This study compared the on-scene Glasgow Coma Scale (GCS) and the GCS-motor (GCS-M) for predictive accuracy of mortality and severe disability using a large, multicenter population of trauma patients in Asian countries. OBJECTIVE: To compare the ability of the prehospital GCS and GCS-M to predict 30-day mortality and severe disability in trauma patients. DESIGN: We used the Pan-Asia Trauma Outcomes Study registry to enroll all trauma patients >18 years of age who presented to hospitals via emergency medical services from 1 January 2016 to November 30, 2018. SETTINGS AND PARTICIPANTS: A total of 16,218 patients were included in the analysis of 30-day mortality and 11 653 patients in the analysis of functional outcomes. OUTCOME MEASURES AND ANALYSIS: The primary outcome was 30-day mortality after injury, and the secondary outcome was severe disability at discharge defined as a Modified Rankin Scale (MRS) score ≥4. Areas under the receiver operating characteristic curve (AUROCs) were compared between GCS and GCS-M for these outcomes. Patients with and without traumatic brain injury (TBI) were analyzed separately. The predictive discrimination ability of logistic regression models for outcomes (30-day mortality and MRS) between GCS and GCS-M is illustrated using AUROCs. MAIN RESULTS: The primary outcome for 30-day mortality was 1.04% and the AUROCs and 95% confidence intervals for prediction were GCS: 0.917 (0.887-0.946) vs. GCS-M:0.907 (0.875-0.938), P  = 0.155. The secondary outcome for poor functional outcome (MRS ≥ 4) was 12.4% and the AUROCs and 95% confidence intervals for prediction were GCS: 0.617 (0.597-0.637) vs. GCS-M: 0.613 (0.593-0.633), P  = 0.616. The subgroup analyses of patients with and without TBI demonstrated consistent discrimination ability between the GCS and GCS-M. The AUROC values of the GCS vs. GCS-M models for 30-day mortality and poor functional outcome were 0.92 (0.821-1.0) vs. 0.92 (0.824-1.0) ( P  = 0.64) and 0.75 (0.72-0.78) vs. 0.74 (0.717-0.758) ( P  = 0.21), respectively. CONCLUSION: In the prehospital setting, on-scene GCS-M was comparable to GCS in predicting 30-day mortality and poor functional outcomes among patients with trauma, whether or not there was a TBI.

Genomic analysis of penicillin-binding proteins and recombination events in an emerging amoxicillin- and meropenem-resistant PMEN3 (Spain9V-3, ST156) variant in Taiwan and comparison with global descendants of this lineage.

From 2008 to 2020, the Taiwan National Notifiable Disease Surveillance System database demonstrated that the incidence of non-vaccine serotype 23A invasive pneumococcal disease (IPD) approximately doubled. In this study, 276 non-repetitive pneumococcal clinical isolates were collected from two medical centers in Taiwan between 2019 and 2021. Of these 267 pneumococci, 60 were serotype 23A. Among them, 50 (83%) of serotype 23A isolates belonged to the sequence type (ST) 166 variant of the Spain9V-3 clone. Pneumococcal 23A-ST166 isolates were collected to assess their evolutionary relationships using whole-genome sequencing. All 23A-ST166 isolates were resistant to amoxicillin and meropenem, and 96% harbored a novel combination of penicillin-binding proteins (PBPs) (1a:2b:2x):15:11:299, the newly identified PBP2x-299 in Taiwan. Transformation of the pbp1a, pbp2b, and pbp2x alleles into the ß-lactam-susceptible R6 strain revealed that PBP2x-299 and PBP2b-11 increased the MIC of ceftriaxone and meropenem by 16-fold, respectively. Prediction analysis of recombination sites in PMEN3 descendants (23A-ST166 in Taiwan, 35B-ST156 in the United States, and 11A-ST838/ST6521 in Europe) showed that adaptive evolution involved repeated, selectively favored convergent recombination in the capsular polysaccharide synthesis region, PBPs, murM, and folP genome sites. In the late 13-valent pneumococcal conjugate vaccine era, PMEN3 continuously displayed an evolutionary capacity for global dissemination and persistence, increasing IPD incidence, leading to an offset in the decrease of pneumococcal conjugate vaccine serotype-related diseases, and contributing to high antibiotic resistance. A clonal shift with a highly ß-lactam-resistant non-vaccine serotype 23A, from ST338 to ST166, increased in Taiwan. ST166 is a single-locus variant of the Spain9V-3 clone, which is also called the PMEN3 lineage. All 23A-ST166 isolates, in this study, were resistant to amoxicillin and meropenem, and 96% harbored a novel combination of penicillin-binding proteins (PBPs) (1a:2b:2x):15:11:299. PBP2x-299 and PBP2b-11 contributed to the increasing MIC of ceftriaxone and meropenem, respectively. Prediction analysis of recombination sites in PMEN3 descendants showed that adaptive evolution involved repeated, selectively favored convergent recombination in the capsular polysaccharide synthesis region, PBPs, murM, and folP genome sites. In the late 13-valent pneumococcal conjugate vaccine era, PMEN3 continuously displays the evolutionary capacity for dissemination, leading to an offset in the decrease of pneumococcal conjugate vaccine serotype-related diseases and contributing to high antibiotic resistance.

Updated trends in the outcomes of out-of-hospital cardiac arrest from 2017-2021: Prior to and during the coronavirus disease (COVID-19) pandemic.

Objective: This study aims to describe out-of-hospital cardiac arrest (OHCA) characteristics and trends before and during the coronavirus disease-2019 (COVID-19) pandemic in Taiwan. Methods: We conducted a retrospective cohort study using a 5-year interrupted time series analysis. Eligible adults with non-traumatic OHCAs from January 2017 to December 2021 in 3 hospitals (university medical center, urban second-tier hospital, and rural second-tier hospital) were retrospectively enrolled. Variables were extracted from the emergency medical service reports and medical records. The years 2020 and 2021 were defined as the COVID-19 pandemic period. Outcomes included survival to admission after a sustained return of spontaneous circulation, survival to hospital discharge, and good neurological outcomes (cerebral performance category score 1 or 2). Results: We analyzed 2819 OHCA, including 1227 from a university medical center, 617 from an urban second-tier hospital, and 975 from a rural second-tier hospital. The mean age was 71 years old, and 60% of patients were males. During the COVID-19 pandemic period, video-assisted endotracheal tube intubation replaced the traditional direct laryngoscopy intubation. The trends of outcomes in the pre-pandemic and pandemic periods varied among different hospitals. Compared with the pre-pandemic period, the outcomes at the university medical center during the COVID-19 pandemic were significantly poorer in several respects. The survival rate on admission dropped from 44.6% to 39.4% (P = 0.037), and the survival rate to hospital discharge fell from 17.5% to 14.9% (P = 0.042). Additionally, there was a notable decrease in patients' good neurological outcomes, declining from 13.2% to 9.7% (P = 0.048). In contrast, the outcomes in urban and rural second-tier hospitals during the COVID-19 pandemic did not significantly differ from those in the pre-pandemic period. Conclusions: COVID-19 may alter some resuscitation management in OHCAs. There were no overall significant differences in outcomes before and during COVID-19 pandemic, but there were significant differences in outcomes when stratified by hospital types.

Case report: Presentations and cytokine profiles of inflammatory non-pulmonary COVID-19 and related diseases in children.

The coronavirus disease 2019 (COVID-19) pandemic has evolved to dynamic waves of different SARS-CoV-2 variants. Initially, children diagnosed with COVID-19 presented pulmonary involvement characterized by mild diseases. In the later waves of the COVID-19 pandemic, life-threatening non-pulmonary inflammatory diseases such as (1) aseptic meningoencephalitis (ME), (2) acute necrotizing encephalopathies (ANE), and (3) multisystem inflammatory syndrome in children (MIS-C) have been reported, affecting the pediatric population. To alert timely identification and prevention of the life-threatening non-pulmonary COVID-19, we present the cases of ME, ANE, and MIS-C in terms of clinical manifestation, cytokine profile, and follow-up consequences. Based on the immunopathogenesis and risk factors associated with non-pulmonary COVID-19, we delineate strategies for an early diagnosis and treatment to reduce morbidity and mortality in children.

The Effectiveness of Bivalent COVID-19 Vaccination: A Preliminary Report.

Vaccination has been a game-changer in the long battle against COVID-19. However, waning vaccine-induced immunity and the immune evasion of emerging variants create challenges. The rapid-fire development of bivalent vaccines (BVs), comprising ancestral strains and a new variant, was authorized to prevent COVID-19, but the effectiveness of the updated vaccines remains largely unclear. Electronic databases were searched to investigate the immunogenicity and reactogenicity of BVs in humans. As of March 2023, 20 trials were identified. Compared with monovalent vaccination, the induced immunogenicity against ancestral strains was similar. The BVs demonstrated approximately 33-50% higher immunogenicity values against additional variant strains. An observational cohort study showed the additional clinical effectiveness of the BVs. The adverse events were similar. In conclusion, our systematic review found that the BVs had equal immunogenicity against ancestral strains without safety concerns. Approximately 33-50% increased additional antibody titers and clinical effectiveness against additional variant strains were observed in subjects with a BV vaccine with moderate heterogeneity, especially for BA.1-containing BVs.

Assessing the utilization of antimicrobial agents in pediatric pneumonia during the era of the 13-valent pneumococcal conjugate vaccine: A retrospective, single-center study.

BACKGROUND AND PURPOSE: Pneumonia and bronchopneumonia are the most common infectious diseases in children. This study aimed to analyze changes in causative pathogens and antibiotic use for bronchopneumonia or pneumonia after the introduction of the 13-valent pneumococcal conjugate vaccine (PCV13) in children. METHODS: This retrospective study was conducted from 2009 to 2019. Hospitalized children aged 6 months-3 years with a discharge diagnosis of bronchopneumonia or pneumonia were included to analyze changes in the potential mismatch between the diagnosed pathogen and antibiotic use. RESULTS: The cohort comprised 1100 patients, including 648 (59%) and 452 (41%) with a discharge diagnosis of bronchopneumonia and pneumonia, respectively. The trend of viral pneumonia increased every year (rs = 0.101, p < 0.05) Antibiotics were administered in 97% patients, with an increasing annual trend in macrolide use (rs = 0.031, p = 0.009). Regarding antibiotic utilization, no significant variations were observed in the days of therapy (DOT) (rs = 0.076, p = 0.208) or length of therapy (LOT) (rs = -0.027, p = 0.534) per patient-year throughout the study duration. Interestingly, the LOT for combined therapy with macrolides and first-line beta-lactams was high (rs = 0.333, p = 0.028). In viral pneumonia treatment, neither the DOT nor LOT exhibited significant variations (rs = -0.006, p = 0.787 and rs = -0.156, p = 0.398). CONCLUSION: After the introduction of PCV13 in Taiwan, no decrease in antibiotic use has been observed among children aged 6 months-3 years with a discharge diagnosis of bronchopneumonia and pneumonia.