Immunogenicity and safety of Sinovac-CoronaVac booster vaccinations in 12-17- year-olds with clinically significant reactions from Pfizer-BNT162b2 vaccination.

Heterologous Sinovac-CoronaVac booster(s) in 12-17-year-olds who had a moderate/severe reaction to Pfizer-BNT162b2 mRNA vaccine was found to safe with no serious adverse events reported. In those primed with 1 dose of Pfizer-BNT162b2 vaccine, subsequent boosters with 2 doses of Sinovac-CoronaVac vaccines achieved neutralizing antibody levels which were comparable to those who had received 2 doses of Pfizer-BNT162b2 vaccines followed by 1 dose of Sinovac-CoronaVac vaccination. Adolescents with 1 Pfizer-BNT162b2 followed by 2 Sinovac-CoronaVac vaccines developed T-cell responses against broad peptides including membrane, nucleoprotein 1 and 2 but levels were highest for Spike protein and lasted until day 150 post-vaccination.

Defining the Clinicoradiologic Syndrome of SARS-CoV-2 Acute Necrotizing Encephalopathy: A Systematic Review and 3 New Pediatric Cases

BACKGROUND AND OBJECTIVES: We characterize clinical and neuroimaging features of SARS-CoV-2-related acute necrotizing encephalopathy (ANE). METHODS: Systematic review of English language publications in PubMed and reference lists between January 1, 2020, and June 30, 2023, in accordance with PRISMA guidelines. Patients with SARS-CoV-2 infection who fulfilled diagnostic criteria for sporadic and genetic ANE were included. RESULTS: From 899 articles, 20 cases (17 single case reports and 3 additional cases) were curated for review (50% female; 8 were children). Associated COVID-19 illnesses were febrile upper respiratory tract infections in children while adults had pneumonia (45.6%) and myocarditis (8.2%). Children had early neurologic deterioration (median day 2 in children vs day 4 in adults), seizures (5 (62.5%) children vs 3 of 9 (33.3%) adults), and motor abnormalities (6 of 7 (85.7%) children vs 3 of 7 (42.9%) adults). Eight of 12 (66.7%) adults and 4 (50.0%) children had high-risk ANE scores. Five (62.5%) children and 12 (66.7%) adults had brain lesions bilaterally and symmetrically in the putamina, external capsules, insula cortex, or medial temporal lobes, in addition to typical thalamic lesions of ANE. Hypotension was only seen in adults (30%). Hematologic derangements were common: lymphopenia (66.7%), coagulopathy (60.0%), or elevated D-dimers (100%), C-reactive protein (91.7%), and ferritin (62.5%). A pathogenic heterozygous c/.1754 C>T variant in RANBP2 was present in 2 children: one known to have this before SARS-CoV-2 infection, and a patient tested because the SARS-CoV-2 infection was the second encephalopathic illness. Three other children with no prior encephalopathy or family history of encephalopathy were negative for this variant. Fifteen (75%) received immunotherapy (with IV methylprednisolone, immunoglobulins, tocilizumab, or plasma exchange): 6 (40.0%) with monotherapy and 9 (60.0%) had combination therapy. Deaths were in 8 of 17 with data (47.1%): a 2-month-old male infant and 7 adults (87.5%) of median age 56 years (33-70 years), 4 of whom did not receive immunotherapy. DISCUSSION: Children and adults with SARS-CoV-2 ANE have similar clinical features and neuroimaging characteristics. Mortality is high, predominantly in patients not receiving immunotherapy and at the extremes of age.

Trimethoprim-sulfamethoxazole-induced lung injury: a case report.

Background: Trimethoprim-sulfamethoxazole (TMP-SMX) is a commonly used antibiotic. While cutaneous adverse drug reactions associated with TMP-SMX are commonly recognized, lung toxicity induced by TMP-SMX is an unusual condition, with scattered reports of hypersensitivity pneumonitis, acute fibrinous organizing pneumonia, interstitial lung disease and acute respiratory distress syndrome. Reports of TMP-SMX-associated drug-induced lung injury (DLI) are rare in the pediatric population and its pathogenesis is not well understood. Diagnosis of DLI remains a challenge, given the wide range of clinical presentations that overlap with other conditions and the lack of diagnostic tests. In this report, we describe a case of TMP-SMX-induced lung injury in an eight-year-old child. Case Description: An eight-year-old girl presented in respiratory failure with acute symptoms of shortness of breath, fever, maculopapular rash and vomiting. This was associated with pneumonitis, pneumothorax, pneumomediastinum and subcutaneous emphysema on imaging. She had been on 25 days of TMP-SMX for treatment of Group D Salmonella bacteremia and osteomyelitis that was diagnosed prior to this current presentation. TMP-SMX was discontinued on admission due to concerns of possible drug reaction. Extensive infective, autoimmune and immunologic workup did not reveal the cause of the respiratory failure. Considering the absence of an alternative explanation for her clinical presentation and similarities in clinical courses to other reported cases, she was eventually diagnosed with TMP-SMX-associated DLI. She received a course of corticosteroids with subsequent clinical improvement and was weaned off home oxygen therapy a few months after her discharge from the hospital. Conclusions: Diagnosis of DLI can be challenging. The early identification of DLI and discontinuation of culprit drug is essential in its management. Further understanding of the underlying pathophysiology and risk factors for TMP-SMX-associated DLI is required.

Remdesivir therapy for severe pediatric COVID-19 in Singapore: A single-center retrospective observational cohort study.

Background and Aims: There is a paucity of information on remdesivir (RDV) use in severe pediatric coronavirus disease 2019 (COVID-19). We aimed to explore the effectiveness of RDV as the cumulative proportion of pediatric COVID-19 patients deescalated from Day 5 of high dependency or intensive care unit (HD/ICU). Methods: All children ≤18 years admitted to Singapore's largest pediatric hospital from January 1, 2020 to March 18, 2022 were reviewed retrospectively. Patients were included if they were positive for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) on reverse transcriptase polymerase chain reaction, required oxygen, and HD/ICU care. The characteristics and outcomes of those who received RDV or not (no-RDV) were compared. Results: We reviewed 15 children with a median age of 2.5 years (interquartile range [IQR]: 0.8-11.0), of which 7 (46.7%) received RDV. There was no difference in cumulative proportion of children deescalated from Day 5 of HD/ICU care in the RDV versus the no-RDV group (5/7, 70% vs. 7/8, 87.5%, p = 0.57). The RDV versus no-RDV group had higher disease severity, that is, WHO Ordinal Scale scores (median 6, IQR: 5-7 vs. 5, IQR: 4-5, p = 0.03), higher procalcitonin levels (ug/L) (median 4.31, IQR: 0.8-24.2 vs. 0.12, IQR: 0.09-0.26, p = 0.02), and longer HD/ICU care days (median 5, IQR: 4-9, vs. 1, IQR: 1-4, p = 0.01). There was no significant difference in hospitalization days. There were no adverse events directly attributable to RDV. None died from COVID-19 infection. Conclusion: Our observational analysis was unable to detect any clear benefit of RDV in terms of reducing duration in HD/ICU. RDV was well-tolerated in children with severe COVID-19.

BNT162b2 vaccine induced variant-specific immunity, safety and risk of Omicron breakthrough infection in children aged 5 to 11 years: a cohort study.

There is little information on BNT162b2 vaccine-induced variant-specific immunogenicity, safety data and dynamics of breakthrough infections in pediatric populations. We addressed these questions using a prospective two dose BNT162b2 (10 mcg) vaccination cohort study of healthy children 5-11 years in Singapore. Follow up included blood samples at scheduled visits, daily vaccination symptom diary and confirmation of SARS-CoV-2 infection. Surrogate virus neutralization test (sVNT) and spike-specific T cell responses against SARS-CoV-2 variants were performed. The mean age of 127 participants was 8.27 years (SD 1.95) and 51.2% were males. The median sVNT level against original variant after 1 dose and 2 dose vaccination was 61.4% and 95.1% respectively (p < 0.0001). Neutralizing antibodies against the Omicron variant was the lowest, median 22.4% (IQR 16.5-30.8). However, T cell IFN-γ cytokine response against Omicron variant was high and remained so about 4 months after vaccination. Fever rate increased significantly from 4% (dose 1) to 11.5% (dose 2). The risk of Omicron breakthrough infection decreased by 7.8% for every 1% increase in sVNT inhibition level measured after dose 2 vaccination. BNT162b2 vaccines were safe, induced good T cell responses but poor neutralizing antibodies against Omicron in children. Low neutralizing antibody levels post-vaccination was predictive of subsequent breakthrough infection.

BNT162b2 vaccine protection against omicron and effect of previous infection variant and vaccination sequence among children and adolescents in Singapore: a population-based cohort study.

BACKGROUND: Information on variant-specific vaccine protection and the effect of previous infection variant is scarce in children. We aimed to ascertain the level of protection conferred by BNT162b2 COVID-19 vaccination against omicron variant infection (BA.4 or BA.5, and XBB) in a previously infected national paediatric cohort. We also explored the association between sequence of previous infection (variant) and vaccination on protection. METHODS: We did a retrospective, population-based cohort study using the national databases of all confirmed SARS-CoV-2 infections, vaccines administered, and demographic records maintained by the Ministry of Health, Singapore. The study cohort consisted of children aged 5-11 years and adolescents aged 12-17 years who had a previous SARS-CoV-2 infection from Jan 1, 2020, to Dec 15, 2022. People who were infected during the pre-delta period or were immunocompromised (received three vaccination doses [children 5-11 years old] and four vaccinations doses [adolescents 12-17 years old]) were excluded. Those who had multiple episodes of infection before the study start date, were not vaccinated before infection but completed three doses, received bivalent mRNA vaccine, or received non-mRNA vaccine doses were also excluded. All SARS-CoV-2 infections confirmed by reverse transcriptase polymerase chain reaction or rapid antigen testing were grouped into delta, BA.1, BA.2, BA.4 or BA.5, or XBB variants using a combination of whole-genome sequencing, S-gene target failure results, and imputation. For BA.4 or BA.5, the study outcome period was June 1-Sept 30, 2022, and for XBB variants the outcome period was Oct 18-Dec 15, 2022. Incidence rate ratios between vaccinated and unvaccinated were derived using adjusted Poisson regressions and vaccine effectiveness was estimated as (1-risk ratio) × 100%. FINDINGS: 135 197 people aged 5-17 years (79 332 children and 55 865 adolescents) were included in the cohort for the vaccine effectiveness analysis against omicron BA.4 or BA.5, and 164 704 people aged 5-17 years (97 235 children and 67 469 adolescents) were included for the analysis against omicron XBB. Approximately 47% of participants were female and 53% were male. Among those previously infected, vaccine effectiveness against BA.4 or BA.5 infection in fully vaccinated children (two doses) was 74·0% (95% CI 67·7-79·1) and in adolescents (three doses) was 85·7% (80·2-89·6). Against XBB, protection conferred with full vaccination was lower at 62·8% (95% CI 42·3-76·0) in children and 47·9% (20·2-66·1) in adolescents. In children, receipt of two-dose vaccination before first SARS-CoV-2 infection provided them with the highest protection against subsequent BA.4 or BA.5 infection at 85·3% (95% CI 80·2-89·1); however, this was not shown to be the case for adolescents. First infection variant had an effect on vaccine effectiveness against omicron BA.4 or BA.5 reinfection in the following descending order: BA.2 conferred the highest protection (92·3% [95% CI 88·9-94·7] in children and 96·4% [93·5-98·0] in adolescents) followed by BA.1 (81·9% [75·9-86·4] in children and 95·0% [91·6-97·0] in adolescents), and delta which conferred the lowest protection (51·9% [5·3-75·6] in children and 77·5% [63·9-86·0] in adolescents). INTERPRETATION: In previously infected children and adolescents, BNT162b2 vaccination provided additional protection against omicron BA.4 or BA.5 and XBB variants compared with those who remained unvaccinated. Hybrid immunity against XBB was lower than against BA.4 or BA.5, especially in adolescents. Early vaccination of previously uninfected children before their first SARS-CoV-2 exposure could potentially strengthen population immunity resilience against future variants. FUNDING: None.

Paediatric actinomycosis: A 16-year, single-institution retrospective review of cases.

AIM: Actinomycosis is a rare subacute to chronic granulomatous infection which can mimic other infectious or malignant diseases. This study examined the epidemiology and treatment outcome of actinomycosis in children. METHODS: A retrospective study on children admitted for actinomycosis in a tertiary paediatric hospital in Singapore, from January 2004 to December 2020. Clinical profile, therapeutic interventions and outcomes were examined. RESULTS: A total of 10 patients were identified; 7 were female. The median age at first presentation was 9.8 years (range 4.7-15.7). The most common presenting symptom was fever (n = 6, 60%), followed by facial or neck swelling (n = 3, 30%) and ear pain (n = 3, 30%). Actinomycosis occurred predominantly in the orocervicofacial region (n = 6, 60%). Four patients (40%) had preceding dental infections in the form of dental caries or gingivitis. One patient had poorly controlled insulin-dependent diabetes mellitus. Actinomycosis was confirmed via culture in four patients, histopathology in four patients and both methods in two patients. All except one patient (n = 9, 90%) underwent surgical procedures. All patients received ampicillin or amoxicillin/clavulanate or other beta-lactams, for a median duration of 6.5 months (range 1.5-14). Complications included osteomyelitis (n = 4, 40%), mastoiditis (n = 2, 20%), brain abscess (n = 1, 10%) and recurrent neck abscess (n = 1, 10%). There was no mortality and all patients achieved complete resolution. CONCLUSIONS: Paediatric actinomycosis was rare in our 16-year review, but had a high complication rate. It can occur in immunocompetent patients, and dental infection was the predominant risk factor identified. Prognosis was excellent after surgical intervention and appropriate antimicrobial therapy.

Synthetic miR-26a mimics delivered by tumor exosomes repress hepatocellular carcinoma through downregulating lymphoid enhancer factor 1.

BACKGROUND: The dysregulation of exosomal microRNAs plays an important role in the progression of hepatocarcinogenesis. In this study, we investigated the therapeutic potential of synthetic exosomal miR-26a against HCC cells and explored the feasibility of tumor-derived exosomes as drug delivery vehicles. METHODS: Proliferation and migration assays were performed to examine the effects of miR-26a on HCC in vitro. The direct target gene of miR-26a was identified through miRecords analysis and target validation. The transferring efficiency and anti-HCC effect of exosomes with different origin were studied and the optimal miR-26a delivery method was established and verified in vitro and in vivo. In addition, the relationships between prognosis of HCC patients and miR-26a expression in HCC serum and exosomes were retrospectively analyzed. RESULTS: Here, we found that tumor cell-derived exosomes were taken in preferentially by HCC cells and promoted HCC progression through Wnt pathway by low-density lipoprotein receptor-related protein 6 (LRP6). HCC cells with vacuolar protein sorting-associated protein 35 knocked down were adopted to generate engineered LRP6-exosomes. The engineered HCC-derived exosomes loading miR-26a inhibited HCC progression in vitro and in vivo effectively. Overexpression of miR-26a impaired the growth and migration of HCC by targeting lymphoid enhancer factor 1 (LEF1). Moreover, low expression of exosomal miR-26a was an independent prognostic factor for recurrence and survival in HCC patients. CONCLUSIONS: Our findings suggested the exosomal miR-26a could serve as a non-invasive prognostic marker for HCC patients. Genetically modified tumor-derived exosomes showed preferable transfection efficiency but reduced Wnt activity, which provides a novel therapeutic strategy for HCC.

Combating a resurgence of poliomyelitis through public health surveillance and vaccination.

Poliomyelitis, or polio, is a highly infectious disease and can result in permanent flaccid paralysis of the limbs. Singapore was certified polio-free by the World Health Organization (WHO) on 29 October 2000, together with 36 other countries in the Western Pacific Region. The last imported case of polio in Singapore was in 2006. Fortunately, polio is vaccine-preventable-the world saw the global eradication of wild poliovirus types 2 and 3 achieved in 2015 and 2019, respectively. However, in late 2022, a resurgence of paralytic polio cases from vaccine-derived poliovirus (VDPV) was detected in countries like Israel and the US (specifically, New York); VDPV was also detected during routine sewage water surveillance with no paralysis cases in London, UK. Without global eradication, there is a risk of re-infection from importation and spread of wild poliovirus or VDPV, or new emergence and circulation of VDPV. During the COVID-19 pandemic, worldwide routine childhood vaccination coverage fell by 5% to 81% in 2020-2021. Fortunately, Singapore has maintained a constantly high vaccination coverage of 96% among 1-year-old children as recorded in 2021. All countries must ensure high poliovirus vaccination coverage in their population to eradicate poliovirus globally, and appropriate interventions must be taken to rectify this if the coverage falters. In 2020, WHO approved the emergency use listing of a novel oral polio vaccine type 2 for countries experiencing circulating VDPV type 2 outbreaks. Environmental and wastewater surveillance should be implemented to allow early detection of "silent" poliovirus transmission in the population, instead of relying on clinical surveillance of acute flaccid paralysis based on case definition alone.

Improving the catalytic activity of ß-glucosidase from Coniophora puteana via semi-rational design for efficient biomass cellulose degradation.

In order to improve the degradation activity of ß-glucosidase (CpBgl) from Coniophora puteana, the structural modification was conducted. The enzyme activity of mutants CpBgl-Q20C and CpBgl-A240S was increased by 65.75% and 58.58%, respectively. These mutants exhibited maximum activity under the same conditions as wild-type CpBgl (65 â„ƒ and pH 5.0), slightly improved stabilities compared that of the wild-type, and remarkably enhanced activities in the presence of Mn2+ or Fe2+. The Vmax of CpBgl-Q20C and CpBgl-A240S was increased to 138.18 and 125.14 µmol/mg/min, respectively, from 81.34 µmol/mg/min of the wild-type, and the catalysis efficiency (kcat/Km) of CpBgl-Q20C (335.79 min-1/mM) and CpBgl-A240S (281.51 min-1/mM) was significantly improved compared with that of the wild-type (149.12 min-1/mM). When the mutant CpBgl-Q20C were used in the practical degradation of different biomasses, the glucose yields of filter paper, corncob residue, and fungi mycelia residue were increased by 17.68%, 25.10%, and 20.37%, respectively. The spatial locations of the mutation residues in the architecture of CpBgl and their unique roles in the enzyme-substrate binding and catalytic efficiency were probed in this work. These results laid a foundation for evolution of other glycoside hydrolases and the industrial bio-degradation of cellulosic biomass in nature.

SARS-CoV-2 antigen rapid tests and universal screening for COVID-19 Omicron variant among hospitalized children.

BACKGROUND: Clinical utility of universal antigen rapid test (ART) in the pediatric setting is unknown. We aimed to assess the performance and utility of universal ART in hospitalized children (≥5-year-old) to prevent nosocomial COVID-19 transmission. METHODS: Cross-sectional study involving all hospitalized pediatric patients aged ≥5-year-old from 2 periods during Omicron wave. Clinical data, ART and polymerase chain reaction test results were collected. RESULTS: A total of 444 patients were included from the 2 study periods, and 416 patients (93.7%) had concordant results between ART and polymerase chain reaction. The overall sensitivity and specificity of ART were 83.3% (95% CI: 75.2-89.3) and 97.5% (95% CI: 95.0-98.8), respectively. Negative predictive values of ART between the Omicron emergence and Omicron peak periods for a probable case group were 71.4% and 66.7%, respectively, and for a suspect case group 91.4% and 75.0%, respectively. Negative predictive values for an unlikely case group was >95% in both periods. Positive predictive value of ART was >85% for probable and suspect case groups in both periods. Seventy-five percent of patients (n = 15) who were incorrectly classified as SARS-CoV-2 negative by ART had potentially viable virus. No large nosocomial transmission clusters were detected. CONCLUSIONS: Universal ART screening may limit nosocomial outbreaks in hospitalized children. The performance can be optimized by considering clinical symptoms, exposure and periods within COVID waves.

Efficient biosynthesis of γ-aminobutyric acid by rationally engineering the catalytic pH range of a glutamate decarboxylase from Lactobacillus plantarum / 生物工程学报

γ-aminobutyric acid can be produced by a one-step enzymatic reaction catalyzed by glutamic acid decarboxylase. The reaction system is simple and environmentally friendly. However, the majority of GAD enzymes catalyze the reaction under acidic pH at a relatively narrow range. Thus, inorganic salts are usually needed to maintain the optimal catalytic environment, which adds additional components to the reaction system. In addition, the pH of solution will gradually rise along with the production of γ-aminobutyric acid, which is not conducive for GAD to function continuously. In this study, we cloned the glutamate decarboxylase LpGAD from a Lactobacillus plantarum capable of efficiently producing γ-aminobutyric acid, and rationally engineered the catalytic pH range of LpGAD based on surface charge. A triple point mutant LpGADS24R/D88R/Y309K was obtained from different combinations of 9 point mutations. The enzyme activity at pH 6.0 was 1.68 times of that of the wild type, suggesting the catalytic pH range of the mutant was widened, and the possible mechanism underpinning this increase was discussed through kinetic simulation. Furthermore, we overexpressed the Lpgad and LpgadS24R/D88R/Y309K genes in Corynebacterium glutamicum E01 and optimized the transformation conditions. An optimized whole cell transformation process was conducted under 40 ℃, cell mass (OD600) 20, 100 g/L l-glutamic acid substrate and 100 μmol/L pyridoxal 5-phosphate. The γ-aminobutyric acid titer of the recombinant strain reached 402.8 g/L in a fed-batch reaction carried out in a 5 L fermenter without adjusting pH, which was 1.63 times higher than that of the control. This study expanded the catalytic pH range of and increased the enzyme activity of LpGAD. The improved production efficiency of γ-aminobutyric acid may facilitate its large-scale production.

Etiological diagnostic value of metagenomic next-generation sequencing in peritoneal dialysis-related peritonitis / 中华肾脏病杂志

Objective:To explore the etiological diagnostic value of metagenomic next-generation sequencing (mNGS) in peritoneal dialysis (PD)-related peritonitis.Methods:The study was a retrospective cohort study. The clinical data of patients with PD-related peritonitis who were treated and underwent microbial cultivation and mNGS test at the same time from June 2020 to July 2021 in the Affiliated Drum Tower Hospital, Medical School of Nanjing University were analyzed. The positive rate, detection time and consistency between mNGS test and traditional microbial culture were compared.Results:A total of 18 patients with age of (50.4±15.4) years old and median dialysis time of 34.0 (12.4, 62.0) months were enrolled in the study, including 11 males and 7 females. Pathogenic microorganisms were isolated in 17 patients by mNGS test, with a positive rate of 17/18, which was higher than 13/18 of microbial culture, but the difference was not statistically significant ( P=0.219). Both mNGS test and microbial culture isolated positive pathogenic bacteria in 12 patients, and mNGS test isolated the same types of pathogenic bacteria as microbial cultivation did in 11 patients. In five patients with negative microbial culture, mNGS test also isolated pathogenic microorganisms, including 3 cases of Staphylococcus epidermidis, 1 case of Mycobacterium tuberculosis and 1 case of Ureaplasma urealyticum. In 1 patient, microbial culture isolated pathogenic bacteria ( Escherichia coli) whereas mNGS test did not. The detection time of mNGS was 25.0 (24.0, 27.0) h, which was significantly shorter than 89.0 (72.8, 122.0) h of microbial culture ( Z=3.726, P<0.001). Conclusions:mNGS test can improve the detection rate of pathogenic microorganisms in PD-related peritonitis and greatly shorten the detection time, and has good consistency with microbial culture. mNGS may provide a new approach for pathogen identification of PD-related peritonitis, especially refractory peritonitis.

Combating a resurgence of poliomyelitis through public health surveillance and vaccination

Poliomyelitis, or polio, is a highly infectious disease and can result in permanent flaccid paralysis of the limbs. Singapore was certified polio-free by the World Health Organization (WHO) on 29 October 2000, together with 36 other countries in the Western Pacific Region. The last imported case of polio in Singapore was in 2006. Fortunately, polio is vaccine-preventable-the world saw the global eradication of wild poliovirus types 2 and 3 achieved in 2015 and 2019, respectively. However, in late 2022, a resurgence of paralytic polio cases from vaccine-derived poliovirus (VDPV) was detected in countries like Israel and the US (specifically, New York); VDPV was also detected during routine sewage water surveillance with no paralysis cases in London, UK. Without global eradication, there is a risk of re-infection from importation and spread of wild poliovirus or VDPV, or new emergence and circulation of VDPV. During the COVID-19 pandemic, worldwide routine childhood vaccination coverage fell by 5% to 81% in 2020-2021. Fortunately, Singapore has maintained a constantly high vaccination coverage of 96% among 1-year-old children as recorded in 2021. All countries must ensure high poliovirus vaccination coverage in their population to eradicate poliovirus globally, and appropriate interventions must be taken to rectify this if the coverage falters. In 2020, WHO approved the emergency use listing of a novel oral polio vaccine type 2 for countries experiencing circulating VDPV type 2 outbreaks. Environmental and wastewater surveillance should be implemented to allow early detection of "silent" poliovirus transmission in the population, instead of relying on clinical surveillance of acute flaccid paralysis based on case definition alone.

Clinical significance of multigene assay in papillary thyroid carcinoma / 临床耳鼻咽喉头颈外科杂志

Objective:To analyze the clinical significance of multigene assay in papillary thyroid carcinoma（PTC）. Methods:Patients who underwent thyroidectomy in a tertiary hospital from August 2021 to May 2022 were enrolled. The eight-gene panel was used to detect the tumor tissue of patients, and the correlation between gene mutations and clinical features was analyzed. Results:Among 161 patients, mutation rate of BRAF V600E, RET/PTC1 and TERT promotor were 82.0%, 6.8% and 4.3%, respectively. BRAF V600E mutation was more common in male patients（P=0.023）. TERT promotor-mutated tumors had a large diameter（P=0.019）, a high proportion of multifocal lesions（P=0.050）, and a large number of lymph node metastases（P=0.031）. Among 89 patients who completed preoperative BRAF detection, there was a strong consistency between the preoperative aspiration test and postoperative panel（Cohen κ=0.694, 95%CI: 0.482-0.906, P<0.01）. In the hematoxylin-eosin sections obtained from 80 patients, BRAF V600E was still the main type of gene mutation, and the classical/follicular type was more distributed. TERT promotor and RET/PTC1 mutation were the main genetic events for tall-cell/columnar/hobnail type and diffuse sclerosing type, respectively. One-way ANOVA showed that there were differences in diagnosis age（P=0.029） and tumor size（P<0.01） among different pathological types. Conclusion:As a simple and feasible clinical detection method for PTC, the multigene assay can supplement the identification of important genetic events other than BRAF V600E, and provide more prognostic information and follow-up hints for postoperative patients.

Etiological diagnostic value of metagenomic next-generation sequencing in peritoneal dialysis-related peritonitis / 中华肝脏病杂志

Objective: To explore the etiological diagnostic value of metagenomic next-generation sequencing (mNGS) in peritoneal dialysis (PD)-related peritonitis. Methods: The study was a retrospective cohort study. The clinical data of patients with PD-related peritonitis who were treated and underwent microbial cultivation and mNGS test at the same time from June 2020 to July 2021 in the Affiliated Drum Tower Hospital, Medical School of Nanjing University were analyzed. The positive rate, detection time and consistency between mNGS test and traditional microbial culture were compared. Results: A total of 18 patients with age of (50.4±15.4) years old and median dialysis time of 34.0 (12.4, 62.0) months were enrolled in the study, including 11 males and 7 females. Pathogenic microorganisms were isolated in 17 patients by mNGS test, with a positive rate of 17/18, which was higher than 13/18 of microbial culture, but the difference was not statistically significant (P=0.219). Both mNGS test and microbial culture isolated positive pathogenic bacteria in 12 patients, and mNGS test isolated the same types of pathogenic bacteria as microbial cultivation did in 11 patients. In five patients with negative microbial culture, mNGS test also isolated pathogenic microorganisms, including 3 cases of Staphylococcus epidermidis, 1 case of Mycobacterium tuberculosis and 1 case of Ureaplasma urealyticum. In 1 patient, microbial culture isolated pathogenic bacteria (Escherichia coli) whereas mNGS test did not. The detection time of mNGS was 25.0 (24.0, 27.0) h, which was significantly shorter than 89.0 (72.8, 122.0) h of microbial culture (Z=3.726, P<0.001). Conclusions: mNGS test can improve the detection rate of pathogenic microorganisms in PD-related peritonitis and greatly shorten the detection time, and has good consistency with microbial culture. mNGS may provide a new approach for pathogen identification of PD-related peritonitis, especially refractory peritonitis.

Multisystem inflammatory syndrome in children in Singapore.

INTRODUCTION: Multisystem inflammatory syndrome in children (MIS-C) is a rare inflammatory syndrome with multisystem involvement affecting children exposed to COVID-19. This condition is rarely reported in East Asia and was not detected in Singapore until 2021. We present 12 cases of MIS-C diagnosed in KK Women's and Children's Hospital (KKH) from October 2021 to December 2021. METHOD: We conducted an observational study on cases fulfilling the Singapore Ministry of Health criteria for MIS-C from January 2020 to December 2021 in KKH. Medical records were reviewed to obtain information on clinical presentation, disease course, treatment received and outcomes. RESULTS: In the 12 cases detected, the median age was 7.50 years (interquartile range 4.00-9.25); 8 were male. All patients had mucocutaneous symptoms similar to Kawasaki disease. Other commonly involved systems were: haematological (coagulopathy 100%, lymphopaenia 91.70% and thrombocytopaenia 75.00%), gastrointestinal (75.00%) and cardiovascular (83.30%). Six patients (50.00%) had shock and were admitted to the intensive care unit. The majority of patients received treatment within 2 days of hospitalisation with intravenous immunoglobulin (IVIg) and steroids. All survived; the majority had normal echocardiograms and no long-term organ sequelae at 6 months post-discharge. CONCLUSION: MIS-C emerged in Singapore as the incidence of COVID-19 in the community increased in 2021. The clinical presentation of our patients is similar to earlier reports, with some significant differences from Kawasaki disease. Multidisciplinary management, timely diagnosis, and early initiation of treatment with IVIg and steroids likely contributed to comparatively good outcomes. Our cases highlight the need for continued awareness of MIS-C among physicians, and surveillance of its incidence, short- and long-term outcomes.

National surgical antibiotic prophylaxis guideline in Singapore.

INTRODUCTION: Institutional surgical antibiotic prophylaxis (SAP) guidelines are in place at all public hospitals in Singapore, but variations exist and adherence to guidelines is not tracked consistently. A national point prevalence survey carried out in 2020 showed that about 60% of surgical prophylactic antibiotics were administered for more than 24 hours. This guideline aims to align best practices nationally and provides a framework for audit and surveillance. METHOD: This guideline was developed by the National Antimicrobial Stewardship Expert Panel's National Surgical Antibiotic Prophylaxis Guideline Development Workgroup Panel, which comprises infectious diseases physicians, pharmacists, surgeons and anaesthesiologists. The Workgroup adopted the ADAPTE methodology framework with modifications for the development of the guideline. The recommended duration of antibiotic prophylaxis was graded according to the strength of consolidated evidence based on the scoring system of the Singapore Ministry of Health Clinical Practice Guidelines. RESULTS: This National SAP Guideline provides evidence-based recommendations for the rational use of antibiotic prophylaxis. These include recommended agents, dose, timing and duration for patients undergoing common surgeries based on surgical disciplines. The Workgroup also provides antibiotic recommendations for special patient population groups (such as patients with ß-lactam allergy and patients colonised with methicillin-resistant Staphylococcus aureus), as well as for monitoring and surveillance of SAP. CONCLUSION: This evidence-based National SAP Guideline for hospitals in Singapore aims to align practices and optimise the use of antibiotics for surgical prophylaxis for the prevention of surgical site infections while reducing adverse events from prolonged durations of SAP.

Effectiveness of maternal pertussis vaccination in Singapore: A test-negative case-control study.

Pertussis vaccination (Tdap -Tetanus-diphtheria-acellular pertussis) for pregnant women has been recommended since November 2017 in Singapore. In this prospective test-negative case-control study from 2018 to 2019, we aimed to evaluate vaccine effectiveness (VE) against pertussis infection and pertussis-related intensive care unit (ICU) admission according to Tdap (Tetanus-diphtheria-acellular pertussis) during pregnancy and/or infant pertussis vaccination. A total of 58 children (26 cases, 32 controls) were recruited with 4 ICU admissions. The median age was 3 months (interquartile range [IQR] 1.50-4.56 months). Overall, 25.9 % of mothers had received antenatal Tdap vaccination and 43.1 % of infants received pertussis vaccination, majority only 1 dose. Tdap in pregnancy alone without infant vaccine or with 0-1 infant dose had a VE of 97.62 % (95 % confidence interval [CI] 53.25-99.88 %), 98.17 % (95 %CI 66.61-99.9 %) respectively, against pertussis infection and 71.9 % (95 %CI 0.0-98.64), 75.86 % (95 % CI 0.0-98.78) respectively, against ICU admissions. Conclusion: Maternal Tdap vaccination was highly protective against infant pertussis and should be routinely recommended for all pregnant women.