[A multicenter study on respiratory pathogen detection with Mycoplasma pneumoniae pneumonia in children].

Objective: To analyze the status of respiratory pathogen detection and the clinical features in children with Mycoplasma pneumoniae pneumonia (MPP). Methods: A prospective, multicenter study was conducted to collect clinical data, including medical history, laboratory examinations and multiplex PCR tests of children diagnosed with MPP from 4 hospitals in China between November 15th and December 20th, 2023. The multiplex PCR results and clinical characteristics of MPP children in different regions were analyzed. The children were divided into severe and mild groups according to the severity of the disease. Patients in the severe group were further divided into Mycoplasma pneumoniae (MP) alone and Multi-pathogen co-detection groups based on whether other pathogens were detected besides MP, to analyze the influence of respiratory pathogen co-detection rate on the severity of the disease. Mann-Whitney rank sum test and Chi-square test were used to compare data between independent groups. Results: A total of 298 children, 136 males and 162 females, were enrolled in this study, including 204 children in the severe group with an onset age of 7.0 (6.0, 8.0) years, and 94 children in the mild group with an onset age of 6.5 (4.0, 7.8) years. The level of C-reactive protein, D-dimer, lactic dehydrogenase (LDH) were significantly higher (10.0 (5.0, 18.0) vs. 5.0 (5.0, 7.5) mg/L, 0.6 (0.4, 1.1) vs. 0.5 (0.3, 0.6) mg/L, 337 (286, 431) vs. 314 (271, 393) U/L, Z=2.02, 2.50, 3.05, all P<0.05), and the length of hospitalization was significantly longer in the severe group compared with those in mild group (6.0 (6.0, 7.0) vs. 5.0 (4.0, 6.0) d, Z=4.37, P<0.05). The time from onset to admission in severe MPP children was significantly shorter than that in mild MPP children (6.0 (5.0, 9.5) vs. 9.0 (7.0, 13.0) d, Z=2.23, P=0.026). All patients completed the multiplex PCR test, with 142 cases (47.7%) MPP children detected with 21 pathogens including adenovirus 25 cases (8.4%), human coronavirus 23 cases (7.7%), rhinovirus 21 cases (7.0%), Streptococcus pneumoniae 21 cases (7.0%), influenza A virus 18 cases (6.0%). The pathogens with the highest detection rates in Tianjin, Shanghai, Wenzhou and Chengdu were Staphylococcus aureus at 10.7% (8/75), adenovirus at 13.0% (10/77), adenovirus at 15.3% (9/59), and both rhinovirus and Haemophilus influenzae at 11.5% (10/87) each. The multi-pathogen co-detection rate in severe MPP children was significantly higher than that in mild MPP group (52.9% (108/204) vs. 36.2% (34/94), χ²=10.62,P=0.005). Among severe MPP children, there are 89 cases in the multi-pathogen co-detection group and 73 cases in the simple MPP group. The levels of LDH, D-dimer and neutrophil counts in the multi-pathogen co-detection group were significantly higher than those in the simple MPP group (348 (284, 422) vs. 307 (270, 358) U/L, 0.8 (0.5, 1.5) vs. 0.6 (0.4, 1.0) mg/L, 4.99 (3.66, 6.89)×109 vs. 4.06 (2.91, 5.65)×109/L, Z=5.17, 4.99, 6.11, all P<0.05). Conclusions: The co-detection rate of respiratory pathogens, LDH and D-dimer in children with severe MPP were higher than those with mild MPP. Among severe MPP children the stress response of children in co-detection group was more serious than that of children with simple MPP.

[Analysis of the clinical features and the risk factors of severe human metapneu movirus-associated community acquired pneumonia in children].

Objective: To investigate the clinical characteristics and the risk factors of severe human metapneumovirus (hMPV)-associated community acquired pneumonia (CAP) in children. Methods: A retrospective case summary was conducted. From December 2020 to March 2022, 721 children who were diagnosed with CAP and tested positive for hMPV nucleic acid by PCR-capillary electrophoresis fragment analysis of nasopharyngeal secretions at the Yuying Children's Hospital, the Second Affiliated Hospital of Wenzhou Medical University were selected as the research objects. The clinical characteristics, epidemiological characteristics and mixed pathogens of the two groups were analyzed. According to CAP diagnostic criteria, the children were divided into the severe group and the mild group. Chi-square test or Mann-Whitney rank and contrast analysis was used for comparison between groups, while multivariate Logistic regression was applied to analyze the risk factors of the severe hMPV-associated CAP. Results: A total of 721 children who were diagnosed with hMPV-associated CAP were included in this study, with 397 males and 324 females. There were 154 cases in the severe group. The age of onset was 1.0 (0.9, 3.0) years, <3 years old 104 cases (67.5%), and the length of hospital stay was 7 (6, 9) days. In the severe group, 67 children (43.5%) were complicated with underlying diseases. In the severe group, 154 cases (100.0%) had cough, 148 cases (96.1%) had shortness of breath and pulmonary moist rales, and 132 cases (85.7%) had fever, 23 cases (14.9%) were complicated with respiratory failure. C-reactive protein (CRP) was elevated in 86 children (55.8%), including CRP≥50 mg/L in 33 children (21.4%). Co-infection was detected in 77 cases (50.0%) and 102 strains of pathogen were detected, 25 strains of rhinovirus, 17 strains of Mycoplasma pneumoniae, 15 strains of Streptococcus pneumoniae, 12 strains of Haemophilus influenzae and 10 strains of respiratory syncytial virus were detected. Six cases (3.9%) received heated and humidified high flow nasal cannula oxygen therapy, 15 cases (9.7%) were admitted to intensive care unit, and 2 cases (1.3%) received mechanical ventilation. In the severe group, 108 children were cured, 42 children were improved, 4 chlidren were discharged automatically without recovery and no death occurred. There were 567 cases in the mild group. The age of onset was 2.7 (1.0, 4.0) years, and the length of hospital stay was 4 (4, 6) days.Compared with the mild group, the proportion of children who age of disease onset <6 months, CRP≥50 mg/L, the proportions of preterm birth, congenital heart disease, malnutrition, congenital airway malformation, neuromuscular disease, mixed respiratory syncytial viruses infection were higher (20 cases (13.0%) vs. 31 cases (5.5%), 32 cases (20.8%) vs. 64 cases (11.3%), 23 cases (14.9%) vs. 44 cases (7.8%), 11 cases (7.1%) vs. 18 cases (3.2%), 9 cases (5.8%) vs. 6 cases (1.1%), 11 cases (7.1%) vs. 12 cases (2.1%), 8 cases (5.2%) vs. 4 cases (0.7%), 10 cases (6.5%) vs. 13 cases (2.3%), χ2=0.42, 9.45, 7.40, 4.94, 11.40, 8.35, 3.52, 6.92, all P<0.05). Multivariate Logistic regression analysis showed that age<6 months (OR=2.51, 95%CI 1.29-4.89), CRP≥50 mg/L (OR=2.20, 95%CI 1.36-3.57), prematurity (OR=2.19, 95%CI 1.26-3.81), malnutrition (OR=6.05, 95%CI 1.89-19.39) were the independent risk factors for severe hMPV-associated CAP. Conclusions: Severe hMPV-associated CAP is most likely to occur in infants under 3 years old and has a higher proportion of underlying diseases and co-infection. The main clinical manifestations are cough, shortness of breath and pulmonary moist rales, fever. The overall prognosis is good. Age<6 months, CRP≥50 mg/L, preterm birth, malnutrition are the independent risk factors for severe hMPV-associated CAP.

[A cross-sectional study of renal dysfunction in chronic hepatitis B outpatients treated with nucleos(t)ide drugs in China].

Objective: To compare the proportion of abnormal renal function indexes in outpatients with chronic hepatitis B (CHB), and to further explore the correlation between the history of nucleos(t)ide analogues (NA) antiviral therapy and abnormal renal function indexes. Methods: A cross-sectional design was adopted for renal function screening. Baseline characteristics, history of antiviral treatment, and renal function indexes were collected, including glomerular filtration rate (eGFR), blood urea nitrogen, blood creatinine, blood uric acid, and urine ß2- microglobulin α 1-microglobulin and urinary protein. According to the definition and standard of abnormal renal function indexes, the correlation between chronic kidney disease (CKD) - 1/2 and related risk factors, renal tubular indicators and risk factors, and the correlation between antiviral treatment duration and renal tubular risk were analyzed. The data were analyzed by single and multi-factor regression. Results: 2703 outpatients from 47 hospitals across the country were enrolled. 70.7% were males with an average age of 47.5 years. 15.5% of cases had hypertension, 14.6% cases had chronic kidney disease, 11.3% cases had diabetes, and 15.4% had CKD 1/2. Retinol-binding protein, urinary ß2-microglobulin or urinary α1-microglobulin showed renal tubular damage rates of 10.4%, 27.1% and 18.4%, respectively. Renal tubular damage risk was related to the antiviral treatment duration (OR = 1.06, 95% CI = 1.028 ~ 1.093). Multivariate analysis results showed that the risk factors related to eGFR < 90 ml/min in male were 40-60 or > 60 years old, high viral load, poorly controlled hypertension, use of nephrotoxic drugs, liver fibrosis status, family history of hepatitis B; while the risk factors related to eGFR < 60 ml/min in female were decompensated cirrhosis, poorly controlled diabetes, and family history of hepatitis B. Conclusion: CHB outpatients have a high proportion of chronic kidney damage, including early renal tubular damage, which suggests that baseline renal function should be assessed before NA use and closely monitored during the treatment. Regular monitoring of the renal tubular damage index can detect the risk of kidney damage earlier than the estimated eGFR.

[A phase â dose-escalating trial of pegylated liposomal doxorubicin in combination with cyclophosphamide, vincristine and prednisone for aggressive non-Hodgkin lymphoma].

Objective: To explore the maximum tolerated dose of pegylated liposomal doxorubicin (PLD) in combination with cyclophosphamide, vincristine and prednisone as a modified CHOP regimen for aggressive non-Hodgkin lymphoma. Methods: Patients with newly diagnosed aggressive non-Hodgkin lymphoma were eligible for this trial. PLD was administered in cycle 1 and categorized into 4 dose level (30 mg/m2, 35 mg/m2, 40 mg/m2, 45 mg/m2 D1) according to a 3 + 3 approach for dose-escalation. Doxorubin was used in cycles 2-6. In this combination regimen, the doses of cyclophosphamide (750 mg/m2 D1), vincristine (1.4 mg/m2 D1, maximum dose of 2 mg) and prednisone (100 mg D1-5) were fixed. Toxicities of cycle 1 were documented. Results: Totally, 21 patients were enrolled in this trial. Among them, 15 patients had T-cell lymphoma and 6 had B-cell lymphoma. When the dose of PLD was escalated to the level of 45 mg/m2, 2 of 3 patients developed grade 3 mucositis, which met the criteria of dose-limiting toxicity. Therefore, the dose was de-escalated for one level. At the level of 40 mg/m2, only one among 12 patients had pneumonia and grade 4 neutropenia. In all dose levels, the grade 3/4 toxicities observed were neutropenia (13 cases, 61.9% ), mucositis (2 cases, 9.5% ), thrombocytopenia (1 case, 4.8%) and pneumonia (1 case, 4.8%). Conclusion: When combined with cyclophosphamide, vincristine and prednisone as a combination regimen, the maximum tolerated dose of PLD was 40 mg/m2.