Ceftriaxone-induced severe hemolytic anemia, renal calculi, and cholecystolithiasis in a 3-year-old child: a case report and literature review.

Ceftriaxone is widely used in pediatric outpatient care for its efficacy against respiratory and digestive system infections, yet its increasing association with severe immune hemolytic reactions requires heightened vigilance from pediatricians. This report details a rare and severe case of ceftriaxone-induced severe immune hemolytic anemia (IHA), hemolytic crisis, myocardial injury, liver injury, renal calculi, and cholecystolithiasis in a previously healthy 3-year-old child. The child, treated for bronchitis, experienced sudden pallor, limb stiffness, and altered consciousness following the fifth day of ceftriaxone infusion, with hemoglobin (Hb) levels precipitously dropping to 21 g/L. Immediate cessation of ceftriaxone and the administration of oxygen therapy, blood transfusion, intravenous immunoglobulin (IVIG), and corticosteroids led to a gradual recovery. Despite initial improvements, the patient's condition necessitated extensive hospital care due to complications including myocardial injury, liver injury, renal calculi, and cholecystolithiasis. After a 12-day hospital stay and a 3-month follow-up, the child showed complete normalization of Hb and liver function and resolution of calculi. In children, ceftriaxone infusion may trigger severe, potentially fatal, hemolytic reactions. Pediatricians must promptly recognize symptoms such as pallor, limb stiffness, and unresponsiveness, indicative of ceftriaxone-induced severe IHA, and immediately discontinue the drug. Effective management includes timely blood transfusion, respiratory support, IVIG administration, and corticosteroids when necessary, along with rigorous vital signs monitoring. Continued vigilance is imperative, even after cessation of ceftriaxone, to promptly address any residual adverse effects.

Pyroptosis, inflammasome, and gasdermins in tumor immunity.

The gasdermins (GSDM), a family of pore-forming proteins, consist of gasdermin A (GSDMA), gasdermin B (GSDMB), gasdermin C (GSDMC), gasdermin D (GSDMD), gasdermin E (GSDME) and DFNB59 (Pejvakin (PJVK)) in humans. These proteins play an important role in pyroptosis. Among them, GSDMD is the most extensively studied protein and is identified as the executioner of pyroptosis. Other family members have also been implicated in certain cancers. As a unique form of programmed cell death, pyroptosis is closely related to tumor progression, and the inflammasome, an innate immune mechanism that induces inflammation and pyroptosis. In this review, we explore the current developments of pyroptosis, the inflammasome, and especially we review the gasdermin family members and their role in inducing pyroptosis and the possible therapeutic values in antitumor effects.

Intestinal Microbes-based Analysis of Immune Mechanism of Childhood Asthma.

This work was developed to explore the relationship between intestinal microflora composition and immune function changes in children with asthma and to provide theoretical references for clinical diagnosis and treatment. Forty-eight children with asthma who received standardized treatment in the outpatient department of pediatric respiratory asthma in Children's Hospital were selected as the research objects, which were rolled into 24 cases of S0 group (complete control) and 24 cases of S1 group (incomplete control group). In addition, ten healthy children with general data matching the research objects were selected as a blank control (D0 group). The intestinal microbial composition and immune function indexes of each group were detected. The results showed that there were differences in the intestinal microbes of the three groups of children with Bifidobacterium, Megasphaera, Oscillibacter, Bilophila, and f_Ruminococcaceae. Among them, the proportions of Bifidobacterium, Megasphaera, and f_Ruminococcaceae in the intestinal microbes of the children in the S1 group were notably less than those in the S0 and D0 groups. The proportion of these three bacterial genera in the S0 group was also considerably smaller than that in the D0 group (P<0.05). In addition, the CD3+ levels of children in the S1 group were notably lower than those in the S0 and D0 groups, while the CD4+ and CD4+/CD3+ were higher than the S0 and D0 groups (P<0.05). The differences between CD3+, CD4+, and CD4+/CD3+ in the S0 and D0 groups were not considerable (P<0.05). The proportions of Bifidobacterium, Megasphaera, f_Ruminococcaceae, and Parasutterella in children with intestinal microbes were significantly positively correlated with CD3+ levels (P<0.05), and significantly negatively correlated with CD4+ and CD4+/CD3+ levels (P<0.05). In short, children with different levels of asthma control had a certain degree of flora disorder and decreased immune function in the intestinal flora. The decrease in the relative abundance of Bifidobacterium, f_Ruminococcaceae of Firmicutes, and Parasutterella of Riken Bacteria, and the increase in the relative abundance of Oscillatoria meant the decline of the immune function of the children.

Next-Generation Sequencing and Proteomics of Cerebrospinal Fluid From COVID-19 Patients With Neurological Manifestations.

The SARS-CoV-2 and its variants are still hitting the world. Ever since the outbreak, neurological involvements as headache, ageusia, and anosmia in COVID-19 patients have been emphasized and reported. But the pathogenesis of these new-onset neurological manifestations in COVID-19 patients is still obscure and controversial. As difficulty always lay in the diagnosis of neurological infection, current reports to validate the presence of SARS-CoV-2 in cerebrospinal fluid (CSF) almost relied on the basic methods and warranted improvement. Here we reported a case series of 8 patients with prominent new-onset neurological manifestations, who were screened out from a patch of 304 COVID-19 confirmed patients. Next-generation sequencing (NGS) and proteomics were conducted in the simultaneously obtained CSF and serum samples of the selected patients, with three non-COVID-19 patients with matched demographic features used as the controls for proteomic analysis. SARS-CoV-2 RNA was detected in the CSF of four COVID-19 patients and was suspicious in the rest four remaining patients by NGS, but was negative in all serum samples. Proteomic analysis revealed that 185 and 59 proteins were differentially expressed in CSF and serum samples, respectively, and that only 20 proteins were shared, indicating that the proteomic changes in CSF were highly specific. Further proteomic annotation highlighted the involvement of complement system, PI3K-Akt signaling pathway, enhanced cellular interaction, and macrophages in the CSF proteomic alterations. This study, equipped with NGS and proteomics, reported a high detection rate of SARS-CoV-2 in the CSF of COVID-19 patients and the proteomic alteration of CSF, which would provide insights into understanding the pathological mechanism of SARS-CoV-2 CNS infection.

Cardiopulmonary bypass as a bridge for bronchial foreign body removal in a child with pulmonary artery sling: A case report.

RATIONALE: Successful removal of an airway foreign body (FB) in some intractable cases can be very challenging, because of tracheal anomalies, unstable respiratory status of the patients, and the location of FB. The use of cardiopulmonary bypass (CPB) support for the treatment of a FB is extremely rare. PATIENT CONCERNS: We present a case of a 39-month-old previously healthy girl who was admitted to our hospital for suspected FB aspiration (FBA). Initially, the attempt for removal of the FB by conventional bronchoscopy failed because of hypoxic intolerance. DIAGNOSES: Bronchoscopy revealed tracheal anomalies and subsequent computed tomography angiography demonstrated the presence of a pulmonary artery sling (PAS), which confirmed the diagnosis of PAS accompanied with FBA. INTERVENTIONS: With the assistance of CPB, multidisciplinary treatment involving the respiratory, cardiothoracic and anesthetic teams were involved and the bronchial FB was removed by flexible bronchoscopy successfully and then PAS was corrected by surgical intervention. OUTCOMES: The patient remained asymptomatic, without shortness of breath or wheezing during the 15 months follow-up. LESSONS: This case highlights that in a complicated case of FBA, bronchoscopy and computed tomography imaging are of great importance to achieve an accurate diagnosis, and a multidisciplinary treatment approach is essential for a satisfactory outcome. If the patient is unstable for bronchoscopy, CPB can be temporarily used in the stabilization of the patient to allow safe removal of the FB.

Interventional therapy via flexible bronchoscopy in the management of foreign body-related occlusive endobronchial granulation tissue formation in children.

BACKGROUND: Occlusive granulation tissue formation, as one of the most common sequelae of chronic foreign body aspiration, can cause tracheobronchial obstruction and delayed fixed airway stenosis necessitating interventions. The aim of this study was to explore the clinical efficacy and safety of interventional therapy via flexible bronchoscopy for treatment of granulation tissue related airway obstruction secondary to foreign body aspiration in children. METHOD: Patients with long-term foreign body related granulation tissue were treated with flexible bronchoscopy therapeutic modalities, including forceps, cryotherapy, holmium laser, and balloon dilatation. Clinical efficacy was evaluated by clinical symptoms and endoscopic manifestations. RESULTS: A total of eight patients with granulation tissue hyperplasia caused by foreign body in bronchus, with a median age of 29.5 (range, 18-54) months, underwent interventional therapy between January 2016 and December 2019. Four patients received forceps and CO2 cryotherapy and one patient required forceps only. The remaining three patients received holmium laser combined with CO2 cryotherapy, and one of them required additional balloon dilatation. Four cases required a second cryotherapy procedure, and one case received three cryotherapy procedures for extensive granulation tissue. The treatment efficacy was 100% without complications. CONCLUSION: Interventional procedure via flexible bronchoscopy is a safe, reliable, and effective method in the management of tracheobronchial obstruction and stenosis caused by foreign body-related granulation tissue hyperplasia. It is worthy of clinical application.

Urinary Metabolomic Profiling Reveals Biological Pathways and Predictive Signatures Associated with Childhood Asthma.

BACKGROUND: Despite considerable efforts, the pathogenic mechanisms of asthma are still incompletely understood, due to its heterogeneous nature. However, metabolomics can offer a global view of a biological system, making it a valuable tool for further elucidation of mechanisms and biomarker discovery in asthma. METHODS: GC-MS-based metabolomic analysis was conducted for comparison of urine metabolic profiles between asthmatic children (n=30) and healthy controls (n=30). RESULTS: An orthogonal projections to latent structures discriminant-analysis model revealed a clear separation of the asthma and control groups (R 2 x =0.137, R 2 y =0.947, Q 2=0.82). A total of 20 differential metabolites were identified as discriminant factors, of which eleven were significantly increased and nine decreased in the asthma group compared to the control group. Pathway-enrichment analysis based on these differential metabolites indicated that sphingolipid metabolism, protein biosynthesis, and citric acid cycle were strongly associated with asthma. Among the identified metabolites, 2-hydroxybutanoic acid showed excellent discriminatory performance for distinguishing asthma from healthy controls, with an AUC of 0.969. CONCLUSION: Our study revealed significant changes in the urine metabolome of asthma patients. Several perturbed pathways (eg, sphingolipid metabolism and citric acid cycle) may be related to asthma pathogenesis, and 2-hydroxybutanoic acid could serve as a potential biomarker for asthma diagnosis.

Clinical characteristics of Kawasaki disease complicated with Mycoplasma pneumoniae pneumonia: A retrospective study.

This study aimed to investigate the inner linkage and mechanism of Mycoplasma pneumoniae (MP) infection and Kawasaki disease (KD), as well as the risk factors of outcome in this cohort of patients.A retrospective study was performed in 210 patients diagnosed with KD complicated with community acquired pneumonia (CAP) in Children's Hospital, Zhejiang University School of Medicine from January 2014 to December 2017. They were divided into two groups based on MP infection: MP infection group (n = 97) and non-MP infection group (n = 113). We compared the variables of these two groups based on medical records.The MP infection group had higher ESR than the non-MP infection group. During hospitalization, the non-MP infection group had higher levels of WBC during hospital, LDH, PCT, and lower HB when compared to the MP infection group. No differences were found in the hs-CRP level, N%, PLT, ALT, CKMB, and cytokine levels (IL-2, IL-4, IL-6, IL-10, TNF-α, and IFN-γ) between MP and non-MP infection group. Likewise, no difference was found in fever duration or hospital stays between them. Totally 19 patients in the infection group had CAA with a rate of 19.59%; and 27 (23.89%) patients had CAA in the non-MP infection group. Unfortunately, no difference was found in CAA rate between the two groups.MP infection may occur simultaneously in children with Kawasaki disease. KD patients with MP infection tended to occur in older population. MP infection may not increase the risk of CAA, which still needs further large-scaled studies to confirm. Clinicians should be alert to KD patients with high level of ESR. MP should be screened and early treatment with macrolides should be given timely.

Impact of Epstein-Barr virus coinfection in Mycoplasma pneumoniae pneumonia.

Mycoplasma pneumoniae (MP) is one of the most common pathogens of respiratory infection in children, while Epstein-Barr virus (EBV) infection is usually subclinical in immunocompetent children. Although single MP infection is common enough, MP and EBV coinfection have received little attention. Especially, the pathogenic role of EBV in lung when coinfection with MP, has not been clarified. The purpose of this study was to investigate the impact of EBV on MP pneumonia (MPP) in hospitalized children. We retrospectively reviewed the clinical data of MPP children who underwent screening for EBV by polymerase chain reaction in bronchoalveolar lavage fluid during hospitalization in 2014. Of total 147 patients, 68 patients were in the MP group and 79 were in the MP/EBV coinfection group. We found longer fever duration and higher CRP, IgA, IgG, interleukin-2 (IL-2), percentage of peripheral neutrophils levels, higher incidence of pulmonary consolidation and percentage of refractory MPP in coinfection group, when compared to those in MP group. In ROC curve analysis, IL-2 was useful for differentiating patients with coinfection from those with MP infection. Logistic regression analysis showed that the IL-2 ≥ 3.35 pg/ml (OR = 3.677) was a significant predictor regarding to MP/EBV coinfection. In conclusion, coinfection of EBV and MP poses a higher risk for prolonged symptoms. IL-2 could be used as a good predictor of coinfection.

Lobar location of lesions in computed tomography-guided lung biopsy is correlated with major pneumothorax: A STROBE-compliant retrospective study with 1452 cases.

Pneumothorax is a common complication in computed tomography (CT)-guided percutaneous lung biopsy (CPLB). Whether the lobar location of lesions contributes to the incidence of pneumothorax should be further clarified.A total of 1452 consecutive patients who underwent CPLB between January 2010 and March 2018 were retrospectively analyzed. The incidence of pneumothorax was compared among 5 different lobe biopsies. Minor pneumothorax was defined as pneumothorax without chest tube placement and major pneumothorax was defined as pneumothorax with chest tube placement.The positive diagnosis rate of pathology for this cohort was approximately 84%, with 22.5% (326/1452) of the patients experiencing pneumothorax. The rates of pneumothorax were 19.5%, 24.5%, 33.9%, 21.4%, and 23.9% for the right upper lobe, right lower lobe, right middle lobe, left upper lobe, and left lower lobe, respectively (P = .09). Chest tube placement was necessary in 19.0% (62/326) of the patients with pneumothorax. The rates of major pneumothorax were 5.3%, 2.6%, 10.2%, 4.7%, and 2.6% for the right upper lobe, right lower lobe, right middle lobe, left upper lobe, and left lower lobe biopsies, respectively (P = .02). This result was further confirmed by the propensity score-matching method. Moreover, 8.7% (127/1452) of the patients experienced puncture of fissure, the rates of which were 13.5%, 5%, 10.2%, 9.1%, and 4.3% for the right upper lobe, right lower lobe, right middle lobe, left upper lobe, and left lower lobe, respectively (P < .001). Within the pneumothorax patient group, the rate of lobe fissure puncture (15.2%) was significantly lower in patients with minor pneumothorax than (51.6%) in those with major pneumothorax (P < .001).Upper and middle lobe lesion biopsies show a significantly high rate of major pneumothorax, which may be due to more puncture of fissure. It is crucial to carefully distinguish the fissure around lesions and bypass it to avoid major pneumothorax.

Single-Chain Variable Fragment Antibody of Vascular Cell Adhesion Molecule 1 as a Molecular Imaging Probe for Colitis Model Rabbit Investigation.

Vascular cell adhesion molecule-1 (VCAM-1) can be a promising target for colitis study because of its critical role in inflammation development. Single-chain variable fragment (scFv) antibody presents fast blood clearance when served as an imaging probe. We applied the probe of 99mTc-scFv-VCAM-1 to colitis rabbit to examine its imaging performance. The colitis model rabbit was prepared, and a typical inflammatory lesion was confirmed in the colon. The probe of 99mTc-scFv-VCAM-1 was synthesized and injected into the model animal before imaging examination. Scintigraphy detected colitis lesions in both SPECT planar and SPECT/CT fused images, with higher target-to-nontarget ratios in the model group (2.71 ± 0.31) than those in the control group (1.12 ± 0.10). Biodistribution study determined tracer uptake in different organs, and autoradiography (ARG) confirmed probe accumulation in colon lesions. The uptake ratio of the model colon to the control colon was 4.71 ± 0.61 in quantitative analysis of the ARG regions of interest. Stronger VCAM-1 expression in the model colon than that in the control colon was confirmed by western blotting and immunohistochemistry. Our imaging study indicates molecular imaging with scFv-VCAM-1 as a promising way for inflammatory bowel disease diagnosis and evaluation.