Pediatric high-altitude pulmonary edema and acute mountain sickness: Clinical features and risk determinants.

OBJECTIVE: This investigation aimed to delineate the clinical manifestations associated with high-altitude pulmonary edema (HAPE) and acute mountain sickness (AMS) in pediatric populations and find the risk factors of HAPE. METHODS: We conducted a retrospective analysis of clinical data from children under 18 years diagnosed with HAPE and AMS at an average altitude of 3000 m. The clinical data between these two groups were compared. RESULTS: The study encompassed 74 pediatric patients, 27 with AMS and 47 with HAPE. HAPE presentations included classic HAPE (55.3%), reentry HAPE (27.7%), and high-altitude resident pulmonary edema (HARPE, 17.0%). Notably, 87.2% of HAPE cases were male, and 68.1% had a high body mass index (BMI). HARPE instances followed viral infections, prominently SARS-CoV-2. HAPE cases exhibited higher BMI, respiratory tract infections within 1 week preceding symptom onset, an increase in white blood cell counts (WBCs), lower peripheral arterial oxygen saturation (SpO2), and higher heart rate compared to the AMS group. Multivariate logistic regression pinpointed high BMI as an independent HAPE risk factor (odds ratio = 19.389, 95% confidence interval: 1.069-351.759, p = .045). CONCLUSION: HAPE occurs predominantly in males, with high BMI identified as a critical independent risk factor. The study underscores the need for heightened awareness and preventive strategies against HAPE in children at high altitudes.

Droplet digital PCR aids in the diagnosis of children with fever of unknown origin --A typical case report.

Many clinical conditions can cause fever of unknown origin (FUO) in children, but the etiological diagnosis remains challenging despite the variety of inspection methods available at present. This study aims to investigate the effectiveness of droplet digital polymerase chain reaction (ddPCR) in identifying pathogens in children with FUO as a novel application. A 7-month-old boy failed to obtain etiology evidence for his disease through various tests. After collecting peripheral blood for ddPCR analysis, Staphylococcus aureus and Escherichia coli were detected, and Sanger sequencing confirmed the pathogens. During the disease, the child developed septic arthritis and osteomyelitis in the femur. Despite the patient's fever being removed, his limb activity improving, and inflammatory biomarkers decreasing, avascular necrosis of the femoral head remained after targeted antibiotic treatment and surgery. If the patient had undergone ddPCR analysis at an early stage, it may be possible to avoid sequelae. ddPCR helps identify pathogens in the diagnosis of children with FUO and could be a promising complementary tool.

High-altitude resident pulmonary edema induced by SARS-CoV-2 infection in children - A case series.

From December 2022 to January 2023, seven children aged ≤14 years and residing in an area at 2999 m without altitude change in the past month developed severe cough, dyspnea, cyanosis, and severe pulmonary lesions within 2-3 days after SARS-CoV-2 infection. They were diagnosed to have high-altitude resident pulmonary edema. They completely recovered following 4-7 days of treatment with oxygen inhalation, vasodilation, diuretics, and glucocorticoids.

Epidemiological and clinical characteristics of pertussis in children and their close contacts in households: A cross-sectional survey in Zhejiang Province, China.

Background: Despite the expanded immunization programs, the "re-emergence of pertussis" has become a global concern in recent years. At present, the prevalence of pertussis in China is seriously underestimated, and the role of close contact on the disease spreading in children remains unclear. Objectives: Our study aimed to investigate pertussis's epidemiological and clinical characteristics in children and their close contacts in households, as well as the antimicrobial resistance of Bordetella pertussis (B. pertussis) in Zhejiang Province, China. Methods: We have collected the retrospective and prospective data of children who were suspected of pertussis and their close contacts in households from January 1, 2018, to December 31, 2020, in the Children's Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China. Nasopharyngeal swabs were collected and cultured for B. pertussis. Antibiotics susceptibility test was determined by using E-test methods. Clinical information was collected from the medical records systems. Results: A total of 350 index patients and their 946 family members (close contacts in households) from 350 families were recruited. B. pertussis strains were isolated from 130 (37.1%) index patients and 116 (12.3%) close contacts. 37 index patients had negative culture results for B. pertussis while their close contacts were positive. A higher positive rate was found in female adults than that in male adults (16.3% vs. 5.1%, P < 0.01). The positive rate in index patients from multi-child families was significantly higher than that from one-child families (51.7% vs. 37.7%, P < 0.05). 53.3% of the pertussis patients were under 6 months of age. 98 (75.4%) isolates had MICs ≥ 256 mg/L to erythromycin, azithromycin, and clindamycin, and 127 (97.7%) had MICs < 0.016 mg/L to piperacillin. Conclusion: Infants under 6 months of age are at high risk of pertussis, and close contacts in households are prone to cluster infection. Culture for B. pertussis both in children and their close contacts contributes to improving the diagnosis rate of pertussis in children. Isolates of B. pertussis in China are highly resistant to macrolides.

Clinical features and epidemiological analysis of respiratory human adenovirus infection in hospitalized children: a cross-sectional study in Zhejiang.

BACKGROUND: HAdV is one of the common pathogens in hospitalized children with acute respiratory infections (ARIs). We aim to describe the clinical and laboratory features, epidemiological characteristics, and HAdV species and/or types of inpatients with HAdV respiratory infections. METHODS: Respiratory samples were gathered from inpatients diagnosed ARIs in Children's Hospital, Zhejiang University School of Medicine, and were detected by using Direct Immunofluorescence Assay from 2018 to 2019. PCR amplification and sequencing of the hypervariable zone of hexon gene were used for genotyping. The clinical and laboratory features, and HAdV genotyping, and epidemiological characteristic analysis were retrospectively performed. RESULTS: Of 7072 samples collected, 488 were identified as HAdV-positive. The overall detection rate was 6.9%. The peaked detection rate was 14.1% in January 2019. HAdV-positive cases with ARIs mainly appeared in winter. The detection rate was highest among children between 6 months and 2 years (8.7%, 123/1408). Clinical diagnosis included pneumonia (70.3%, 343/488), bronchitis (7.0%, 34/488) and acute upper respiratory tract infection (22.7%, 111/488). The common clinical manifestations were fever (93.4%, 456/488), cough (94.7%, 462/488), wheezing (26.2%, 128/488), and shortness of breath (14.8%, 72/488). 213 (43.6%) cases had co-infection and 138 (28.3%) cases had extrapulmonary symptoms. 96(19.7%) cases had intrapulmonary and intrathoracic complications.78 (16.0%) had an underlying condition, most of which were congenital heart diseases (20.5%, 16/78). The proportions of hyperpyrexia, duration of fever > 10 days, severe pneumonia, and wheezing in the co-infection group were remarkably higher than those in HAdV single-infection group (all p < 0.05). The proportions of duration of hospitalization, duration of fever > 10 days, wheezing, shortness of breath, change in level of consciousness, serosal fluids, extrapulmonary symptoms, co-infections and underlying diseases were significantly higher in severe pneumonia group than those in the mild pneumonia group (all p < 0.05). Four HAdV species were successfully identified in 155 cases and presented by 8 genotypes. HAdV-B3 (56.1%, 87/155) and HAdV -B7 (31.0%, 48/155) were the most predominant detected types and occurred commonly in different severity groups (p = 0.000), while, HAdV-B55 was detected only in the severe group. HAdV-B7's detection rate in the severe pneumonia group was significantly higher than the non-severe pneumonia group. CONCLUSION: HAdV detection rate is related to age and season. Bronchopneumonia accounts for about 70% HAdV-positive inpatients. The common clinical manifestations include hyperpyrexia, cough, wheezing, and shortness of breath. HAdV-B3 and HAdV-B7 are the most common types in children diagnosed with respiration infections.

Effect of Macrolides and ß-lactams on Clearance of Bordetella pertussis in the Nasopharynx in Children With Whooping Cough.

OBJECTIVE: The purpose of the current study is to investigate the bactericidal effect of macrolides and ß-lactams on Bordetella pertussis (B. pertussis) in the nasopharynx and provide guidance for treating macrolides-resistant B. pertussis infections. METHODS: Patients with whooping cough was diagnosed by culture of nasopharynx swabs between January 2016 to December 2018. B. pertussis was identified using specific antisera against pertussis and parapertussis. Drug susceptibility test was carried out using the E-test method. The clearance of B. pertussis in nasopharynx at 7 and 14 days into and posttreatment with macrolides, and ß-lactams was compared. RESULTS: A total of 125 B. pertussis samples were collected from patients who received single antibiotic treatment. Among those isolates, 62.4% (78/125) had high resistance with minimum inhibitory concentrations greater than 256 mg/L for erythromycin and azithromycin. The MIC90 of piperacillin, cefoperazone-sulbactam, meropenem, ampicillin, ceftriaxone, ceftazidime and trimethoprim-sulfamethoxazole for these isolates was <0.016, 0.094, 0.094, 0.19, 0.19, 0.25 and 0.75 mg/L, respectively. The clearance rate with ß-lactams treatment (68.8%, 44/64) was significantly higher than that with macrolides treatment at 14 days posttreatment (50.8%, 31/61) (χ2 = 4.18, P = 0.04). Macrolides had a better clearance rate at 7 days posttreatment than ß-lactams (χ2 = 4.49, P = 0.03) for macrolides-sensitive isolates and a worse clearance rate for macrolides-resistant isolates. CONCLUSION: B. pertussis isolates had a high-resistant rate for macrolides in our study. Macrolides are the first choice for treating pertussis caused by macrolides-sensitive strains, and some ß-lactams such as piperacillin should be considered as alternative antibiotics for treatment of macrolides-resistant B. pertussis infection.

Assessment of serum sialic acid correlated with C3 in children with Mycoplasma pneumoniae pneumonia.

BACKGROUND: Different from the diagnosis of bacterial infections, Mycoplasma pneumoniae pneumonia (MPP) is still lacking of convenient non-specific laboratory parameters. METHOD: A total of 125 children with MPP were included in the MPP group and 89 children with Mycoplasma-negative pneumonia were included in the control group, and the sera were collected from the children at both the acute and recovery stages in the two groups. RESULTS: The sialic acid and C3 in the MPP group were significantly higher than those in the control group both at the acute and at the recovery stage. On the other hand, the sialic acid and C3 at the acute stage were significantly higher than those at the recovery stage in the MPP group. However, in the control group, the sialic acid and C3 demonstrated IgG exhibited no significant change between the acute stage and the recovery stage. Lastly, positive correlations between sialic acid level and C3 level were identified in the MPP group at both acute and recovery stages. CONCLUSION: Our study demonstrated that the serum sialic acid correlated with C3 specifically increased in children with MPP, indicating that it might be the important non-specific parameters in the diagnosis of MPP.

[Effects of respiratory syncytial virus infection on epidermal growth factor receptor, tight junction association proteins and mucin in airway epithelial cells].

OBJECTIVE: To study the effects of respiratory syncytial virus (RSV) infection on epidermal growth factor receptor (EGFR), tight junction association proteins and mucin in the human airway epithelial cells. METHODS: Human airway epithelial cells NCI-H292 were randomly treated by ultraviolet light-inactivated RSV (control group) or thawed RSV (RSV infection group). After 48 hours of treatment, the protein levels of occludin, E-cadherin, phosphorylated EGFR and EGFR in NCI-H292 cells were measured by Western blot. The distribution and expression levels of occludin and E-cadherin in NCI-H292 cells were examined by immunofluorescence technique. The expression levels of MUC5AC mRNA in NCI-H292 cells were assessed by RT-PCR. RESULTS: The protein levels of occludin and E-cadherin were significantly reduced in the RSV infection group compared with the control group (P<0.05). The protein levels of phosphorylated EGFR and EGFR increased significantly in the RSV infection group compared with the control group (P<0.05). The MUC5AC mRNA levels also increased significantly in the RSV infection group compared with the control group (P<0.05). CONCLUSIONS: RSV may down-regulate the tight junction association proteins and up-regulate the expression of MUC5AC in airway epithelial cells, which contributes to epithelial barrier dysfunction. EGFR phosphorylation may play an important role in regulation of airway barrier.

In vitro activity and clinical efficacy of macrolides, cefoperazone-sulbactam and piperacillin/piperacillin-tazobactam against Bordetella pertussis and the clinical manifestations in pertussis patients due to these isolates: A single-centre study in Zhejiang Province, China.

BACKGROUND AND OBJECTIVE: Macrolides are the recommended antibiotics for treating pertussis and preventing transmission. The causative bacterium, Bordetella pertussis, has high macrolide resistance and has recently circulated in China. The objective of this study was to find effective alternative antibiotics for treatment by assessing the in vitro activity and clinical efficacy of antibiotics against Bordetella pertussis. METHODS: Bordetella pertussis was confirmed by agglutination with specific antisera and mass spectrometry. The MICs of antibiotics against isolates were determined using the Etest method. Treatment outcomes were clinically and microbiologically evaluated. RESULTS: A total of 126 pertussis patients were diagnosed based on culture, 69.8% of whom were aged ≤6 months and 72.1% were treated with previous macrolides. Leucocytosis and lymphocytosis were observed in 29.4% and 54.8% of all patients, respectively. Both MIC50 and MIC90 of erythromycin, azithromycin, and clindamycin were >256mg/L, and 75.4% were highly macrolide resistant. The MIC90 of trimethoprim-sulfamethoxazole, ampicillin, ampicillin-sulbactam, cefuroxime, ceftriaxone and cefoperazone-sulbactam were 0.38mg/L, 0.25mg/L, 0.19mg/L, 12mg/L, 0.19mg/L and 0.047mg/L, respectively. The MICs of piperacillin in all of the isolations were <0.016mg/L. Of the patients treated with single cefoperazone-sulbactam or piperacillin-tazobactam, 30 of 32 (93.8%) had significantly improved clinical symptoms and 24 of 25 (96%) had negative culture results after 2 weeks of therapy. CONCLUSION: Macrolide resistance in Bordetella pertussis is a serious problem in Zhejiang Province, China. Piperacillin/piperacillin-tazobactam and cefoperazone-sulbactam have potent antibacterial activity in vitro and in vivo, and may become the alternative choice for treating pertussis caused by macrolide-resistant isolates.

Up-regulation of TGF-ß via the activation of extracellular signal-regulated kinase 1 and 2 induced by prorenin in human renal mesangial cells.

Prorenin is thought to be an inactive precursor of renin. This study investigated whether human prorenin was capable of activating the (pro)renin receptors [(P)RRs], leading to the phosphorylation of extracellular signal-regulated kinase 1 and 2 (ERK1/2) in cultured human renal mesangial cells (HRMCs). HRMCs cultured in vitro were pretreated with an AT1 and AT2 blocker prior to stimulation by prorenin, PD98059 (an inhibitor of ERK1/2) and handle-region peptide (HRP). Phosphorylated ERK1/2 was evaluated using Western blot analysis, and the concentration of TGF-ß was measured by ELISA. The mRNA of TGF-ß was evaluated by RT-PCR. It was found that prorenin activated the (P)RR in cultured HRMCs, which in turn increased p-ERK1/2. Prorenin induced rapid phosphorylation of ERK1/2 and increased p-ERK1/2 in a time- and dose-dependent manner. The protein levels of TGF-ß increased significantly with the stimulation of prorenin. PD98059 significantly decreased p-ERK1/2 and then downregulated TGF-ß. HRP did not inhibit either ERK1/2 phosphorylation or the increase in TGF-ß. ERK1/2 phosphorylation induced by prorenin led to a marked increase in TGF-ß. The regulation of TGF-ß was highly dependent on ERK1/2. Thus, ERK1/2 may play a key role in the development of kidney disease. HRP neither affects the ERK1/2 signaling nor the level of TGF-ß in HRMCs.