Volume 48, Issue 3

Infectious diseases seriously threaten the lives of children. Timely and accurate detection of pathogenic microorganisms and targeted medication are the keys to the diagnosing and treatment of infectious diseases in children. The next-generation metagenomic sequencing technology has attracted great attention in infectious diseases because of its characteristics such as no culture, high throughput, short detection cycle, wide coverage, and a good application prospect. In this paper, we review the studies of metagenomic next-generation sequencing in pediatric infectious diseases and analyze the challenges of its application in pediatric diseases.

Objectives Liquid biopsy (LBx) provides diagnostic, prognostic and predictive insights for malignant diseases and offers promising applications regarding tumor burden, tumor heterogeneity and clonal evolution. Methods The Augsburg Longitudinal Plasma Study (ALPS) is a prospective trial for patients with metastatic cancer that comprises sequential collection of LBx samples, tumor tissue, radiological imaging data, clinical information and patient-reported outcomes. Peripheral blood plasma is collected based on the individual patient’s staging intervals and LBx-derived ctDNA analyses are performed using CAncer Personalized Profiling sequencing (CAPP-seq). Results From April 2021 to October 2023, 419 patients have been enrolled. A total of 1,293 LBx samples were collected, 419 samples (100 %) at the beginning of the study and an average of 3 (range 1–12) during the 30-month follow-up period of the current interim analysis. 380 tissue biopsy (TBx) samples (90.7 %) were available at baseline and 39.6 % had ≥1 TBx samples at follow-up. Lung cancer patients are most prevalent in ALPS (n=147), followed by colorectal (n=38), prostate (n=31) and gastroesophageal cancer (n=28). On average, 12.0 ng/mL plasma cell-free DNA (cfDNA) could be isolated. First CAPP-seq analyses in 60 patients comprised 110 samples and demonstrated a detection sensitivity of 0.1 %. Conclusions The first interim analysis of ALPS confirms feasibility for comprehensive longitudinal evaluation of LBx and demonstrates suitability for ctDNA evaluation.

Objectives Mycoplasma pneumoniae (MP) is known to be a common pathogen causing human respiratory infections. On December 7, 2022, the Chinese government announced 10 new measures of Prevention and Control of COVID-19, marking the onset of the post-COVID-19 era. This study aimed to investigate the epidemiological characteristics of MP infections among children from January 2021 to June 2023. Methods Children with respiratory tract infection were enrolled in the study with fever and one or more respiratory symptoms. A serological diagnosis was confirmed with MP IgM antibodies. Results A total of 18,763 patients were enrolled, of whom 4,867 cases were MP-positive, resulting in a positivity rate of 25.9 %. The MP positivity rate increased annually, with 18.6 , 26.7, and 33.2 % in 2021, 2022, and 2023, respectively. The main disease type of MP infection was Mycoplasma pneumoniae pneumonia (MPP), with 74.0 , 87.8, and 86.4 % in 2021, 2022, and 2023, respectively. Higher positivity rates were concentrated in children aged 6 years and older, and the positivity rate in children under 1 year of age in 2023 is the largest increase among all age groups. Conclusions The positivity rate of MP increased significantly after the adjustment of COVID-19 prevention and control in China, and the most significant increase was seen in the infant group. Effective prevention and control measures should be implemented to reduce the prevalence of MP infection among children aged 6 years older and the infant group (<1 year).

Objectives Anti-mitochondrial antibody (AMA) is not always present in patients with primary biliary cholangitis (PBC). We aimed to determine the additional value of anti-hexokinase 1 (anti-HK1) and anti-kelch-like 12 (anti-KLHL12) antibody in PBC and analyzed the biochemical and immunological parameters of 212 subjects, including PBC patients and healthy controls. Methods Serum anti-gp210 and sp100 antibodies were determined by an immunoblotting test (IBT). Enzyme-linked immunosorbent assay (ELISA) was employed to evaluate anti-HK1 and anti-KLHL12. The diagnostic value of anti-HK1 and anti-KLHL12 to PBC was analyzed by constructing a receiver operating characteristic (ROC) curve. Results ROC analyses didn’t show a very good performance of serum anti-HK1 for PBC diagnosis; the AUC was 0.664 with a sensitivity of 53.3 % and a specificity of 79.2 %. Regarding anti-KLHL12, ROC analysis yielded an AUC of 0.626, with a sensitivity of 45.7 % and a specificity of 93.8 %. For AMA-negative PBC patients, the AUC increased to 0.790 for KLHL12, and 0.708 for HK1. AMA combined with anti-HK1 or anti-KLHL12 antibody significantly improved the diagnostic sensitivity of PBC from 82 to about 95 %, respectively. In AMA-negative PBC patients, the sensitivities for anti-HK1 (62.50 %) and anti-KLHL12 (75 %) antibodies were higher than for anti-gp210 (37.5 %) and anti-sp100 antibody (43.75 %). When these four antibodies were combined, the overall sensitivity increased to 87.5 %. Conclusions The determination of anti-HK1 and anti-KLHL12 facilitates the diagnosis of PBC, particularly in AMA-negative patients. Adding anti-HK1 and anti-KLHL12 antibodies to clinical detection enables early diagnosis and timely treatment, potentially improving patient prognosis.

Objectives In recent years, chemiluminescent microparticle immunoassay (CMIA) has been widely used for determination of high-sensitivity troponin I (hs-cTnI). However, a CMIA analysis is usually affected by the presence of some endogenous or exogenous substances. This case-report aims to unveil the essence of the reoccurrence of false-positive results due to heterophilic antibodies interference with Abbott high-sensitivity cardiac troponin I assay, although the assay method applied a chimeric antibody. Case presentation A 28-year-old female misdiagnosed with myocarditis due to falsely elevated hs-cTnI with an initial test result of 595.0 ng/L considered as critical value was reported. And the false critical value of hs-cTnI reoccurred five times after admission. The heterophilic blocking tube (HBT) procedure caused a decrease in troponin concentrations within the reference values, which suggests the presence of interference from heterophilic antibodies. Conclusions It requires a close and strong collaboration between clinicians and laboratorians to manage the similar case on the interference from heterophilic antibodies. To prevent false-positive results caused by interferences from being used in clinical practice, the clinicians are suggested to contact the laboratorians whenever the clinical picture, historical data and laboratory values are not conclusive.