1.Programmed death-ligand 1 tumor proportion score in predicting the safety and efficacy of PD-1/PD-L1 antibody-based therapy in patients with advanced non-small cell lung cancer: A retrospective, multicenter, observational study.
Yuequan SHI ; Xiaoyan LIU ; Anwen LIU ; Jian FANG ; Qingwei MENG ; Cuimin DING ; Bin AI ; Yangchun GU ; Cuiying ZHANG ; Chengzhi ZHOU ; Yan WANG ; Yongjie SHUI ; Siyuan YU ; Dongming ZHANG ; Jia LIU ; Haoran ZHANG ; Qing ZHOU ; Xiaoxing GAO ; Minjiang CHEN ; Jing ZHAO ; Wei ZHONG ; Yan XU ; Mengzhao WANG
Chinese Medical Journal 2025;138(14):1730-1740
BACKGROUND:
This study aimed to investigate programmed death-ligand 1 tumor proportion score in predicting the safety and efficacy of PD-1/PD-L1 antibody-based therapy in treating patients with advanced non-small cell lung cancer (NSCLC) in a real-world setting.
METHODS:
This retrospective, multicenter, observational study enrolled adult patients who received PD-1/PD-L1 antibody-based therapy in China and met the following criteria: (1) had pathologically confirmed, unresectable stage III-IV NSCLC; (2) had a baseline PD-L1 tumor proportion score (TPS); and (3) had confirmed efficacy evaluation results after PD-1/PD-L1 treatment. Logistic regression, Kaplan-Meier analysis, and Cox regression were used to assess the progression-free survival (PFS), overall survival (OS), and immune-related adverse events (irAEs) as appropriate.
RESULTS:
A total of 409 patients, 65.0% ( n = 266) with a positive PD-L1 TPS (≥1%) and 32.8% ( n = 134) with PD-L1 TPS ≥50%, were included in this study. Cox regression confirmed that patients with a PD-L1 TPS ≥1% had significantly improved PFS (hazard ratio [HR] 0.747, 95% confidence interval [CI] 0.573-0.975, P = 0.032). A total of 160 (39.1%) patients experienced 206 irAEs, and 27 (6.6%) patients experienced 31 grade 3-5 irAEs. The organs most frequently associated with irAEs were the skin (52/409, 12.7%), thyroid (40/409, 9.8%), and lung (34/409, 8.3%). Multivariate logistic regression revealed that a PD-L1 TPS ≥1% (odds ratio [OR] 1.713, 95% CI 1.054-2.784, P = 0.030) was an independent risk factor for irAEs. Other risk factors for irAEs included pretreatment absolute lymphocyte count >2.5 × 10 9 /L (OR 3.772, 95% CI 1.377-10.329, P = 0.010) and pretreatment absolute eosinophil count >0.2 × 10 9 /L (OR 2.006, 95% CI 1.219-3.302, P = 0.006). Moreover, patients who developed irAEs demonstrated improved PFS (13.7 months vs. 8.4 months, P <0.001) and OS (28.0 months vs. 18.0 months, P = 0.007) compared with patients without irAEs.
CONCLUSIONS
A positive PD-L1 TPS (≥1%) was associated with improved PFS and an increased risk of irAEs in a real-world setting. The onset of irAEs was associated with improved PFS and OS in patients with advanced NSCLC receiving PD-1/PD-L1-based therapy.
Humans
;
Carcinoma, Non-Small-Cell Lung/metabolism*
;
Male
;
Female
;
Retrospective Studies
;
Middle Aged
;
Lung Neoplasms/metabolism*
;
Aged
;
B7-H1 Antigen/metabolism*
;
Programmed Cell Death 1 Receptor/metabolism*
;
Adult
;
Aged, 80 and over
;
Immune Checkpoint Inhibitors/therapeutic use*
2.P4HA1 mediates YAP hydroxylation and accelerates collagen synthesis in temozolomide-resistant glioblastoma.
Xueru LI ; Gangfeng YU ; Xiao ZHONG ; Jiacheng ZHONG ; Xiangyu CHEN ; Qinglong CHEN ; Jinjiang XUE ; Xi YANG ; Xinchun ZHANG ; Yao LING ; Yun XIU ; Yaqi DENG ; Hongda LI ; Wei MO ; Yong ZHU ; Ting ZHANG ; Liangjun QIAO ; Song CHEN ; Fanghui LU
Chinese Medical Journal 2025;138(16):1991-2005
BACKGROUND:
Temozolomide (TMZ) resistance is a significant challenge in treating glioblastoma (GBM). Collagen remodeling has been shown to be a critical factor for therapy resistance in other cancers. This study aimed to investigate the mechanism of TMZ chemoresistance by GBM cells reprogramming collagens.
METHODS:
Key extracellular matrix components, including collagens, were examined in paired primary and recurrent GBM samples as well as in TMZ-treated spontaneous and grafted GBM murine models. Human GBM cell lines (U251, TS667) and mouse primary GBM cells were used for in vitro studies. RNA-sequencing analysis, chromatin immunoprecipitation, immunoprecipitation-mass spectrometry, and co-immunoprecipitation assays were conducted to explore the mechanisms involved in collagen accumulation. A series of in vitro and in vivo experiments were designed to assess the role of the collagen regulators prolyl 4-hydroxylase subunit alpha 1 (P4HA1) and yes-associated protein (YAP) in sensitizing GBM cells to TMZ.
RESULTS:
This study revealed that TMZ exposure significantly elevated collagen type I (COL I) expression in both GBM patients and murine models. Collagen accumulation sustained GBM cell survival under TMZ-induced stress, contributing to enhanced TMZ resistance. Mechanistically, P4HA1 directly binded to and hydroxylated YAP, preventing ubiquitination-mediated YAP degradation. Stabilized YAP robustly drove collagen type I alpha 1 ( COL1A1) transcription, leading to increased collagen deposition. Disruption of the P4HA1-YAP axis effectively reduced COL I deposition, sensitized GBM cells to TMZ, and significantly improved mouse survival.
CONCLUSION
P4HA1 maintained YAP-mediated COL1A1 transcription, leading to collagen accumulation and promoting chemoresistance in GBM.
Temozolomide
;
Humans
;
Glioblastoma/drug therapy*
;
Animals
;
Mice
;
Cell Line, Tumor
;
Drug Resistance, Neoplasm/genetics*
;
YAP-Signaling Proteins
;
Hydroxylation
;
Dacarbazine/pharmacology*
;
Adaptor Proteins, Signal Transducing/metabolism*
;
Transcription Factors/metabolism*
;
Collagen/biosynthesis*
;
Collagen Type I/metabolism*
;
Prolyl Hydroxylases/metabolism*
;
Antineoplastic Agents, Alkylating/therapeutic use*
3.Randomized, double-blind, parallel-controlled, multicenter, equivalence clinical trial of Jiuwei Xifeng Granules(Os Draconis replaced by Ostreae Concha) for treating tic disorder in children.
Qiu-Han CAI ; Cheng-Liang ZHONG ; Si-Yuan HU ; Xin-Min LI ; Zhi-Chun XU ; Hui CHEN ; Ying HUA ; Jun-Hong WANG ; Ji-Hong TANG ; Bing-Xiang MA ; Xiu-Xia WANG ; Ai-Zhen WANG ; Meng-Qing WANG ; Wei ZHANG ; Chun WANG ; Yi-Qun TENG ; Yi-Hui SHAN ; Sheng-Xuan GUO
China Journal of Chinese Materia Medica 2025;50(6):1699-1705
Jiuwei Xifeng Granules have become a Chinese patent medicine in the market. Because the formula contains Os Draconis, a top-level protected fossil of ancient organisms, the formula was to be improved by replacing Os Draconis with Ostreae Concha. To evaluate whether the improved formula has the same effectiveness and safety as the original formula, a randomized, double-blind, parallel-controlled, equivalence clinical trial was conducted. This study enrolled 288 tic disorder(TD) of children and assigned them into two groups in 1∶1. The treatment group and control group took the modified formula and original formula, respectively. The treatment lasted for 6 weeks, and follow-up visits were conducted at weeks 2, 4, and 6. The primary efficacy endpoint was the difference in Yale global tic severity scale(YGTSS)-total tic severity(TTS) score from baseline after 6 weeks of treatment. The results showed that after 6 weeks of treatment, the declines in YGTSS-TSS score showed no statistically significant difference between the two groups. The difference in YGTSS-TSS score(treatment group-control group) and the 95%CI of the full analysis set(FAS) were-0.17[-1.42, 1.08] and those of per-protocol set(PPS) were 0.29[-0.97, 1.56], which were within the equivalence boundary [-3, 3]. The equivalence test was therefore concluded. The two groups showed no significant differences in the secondary efficacy endpoints of effective rate for TD, total score and factor scores of YGTSS, clinical global impressions-severity(CGI-S) score, traditional Chinese medicine(TCM) response rate, or symptom disappearance rate, and thus a complete evidence chain with the primary outcome was formed. A total of 6 adverse reactions were reported, including 4(2.82%) cases in the treatment group and 2(1.41%) cases in the control group, which showed no statistically significant difference between the two groups. No serious suspected unexpected adverse reactions were reported, and no laboratory test results indicated serious clinically significant abnormalities. The results support the replacement of Os Draconis by Ostreae Concha in the original formula, and the efficacy and safety of the modified formula are consistent with those of the original formula.
Adolescent
;
Child
;
Child, Preschool
;
Female
;
Humans
;
Male
;
Double-Blind Method
;
Drugs, Chinese Herbal/therapeutic use*
;
Tic Disorders/drug therapy*
;
Treatment Outcome
4.Comparative study on clinical effect of bone cement-strengthened screw fixation in the correction of Kümmell's disease with kyphosis.
Hai-Feng HANG ; Hong-Wei WANG ; Li-Xin CHEN ; Xin-Bing TANG ; Ai-Bing HUANG
China Journal of Orthopaedics and Traumatology 2025;38(3):280-286
OBJECTIVE:
To explore clinical effect of bone cement-strengthened pedicle screw technique in the correction of stage Ⅲ asymptomatic Kümmell disease with kyphosis.
METHODS:
A retrospective analysis was conducted on clinical data of 40 asymptomatic stage Ⅲ Kümmell disease patients admitted between March 2019 and December 2021, including 15 males and 25 females, aged from 61 to 81 years old with an average of (67.4±5.2) years old;according to different surgical methods, they were divided into percutaneous kyphoplasty group (PKP) and reinforced screw group. There were 18 patients in PKP group, including 7 males and 11 females, aged from 61 to 78 years old with an average of (66.2±5.5) years old;the courses of disease ranged from 5 to 12 months with an average of (7.33±1.78) months;bone mineral density(BMD) T values ranged from -2.45 to -4.00 with an average of (-3.08±0.46);2 patients with T8-T9, 10 patients with T10-T12, and 6 patients with L1-L2;treated with PKP. There were 22 patients in reinforced screw group, including 8 males and 14 females, aged from 65 to 81 years old with an average of (68.5±3.8) years old;the courses of disease ranged from 4 to 15 months with an average of (7.86±2.73)months;bone mineral density(BMD) T values ranged from -2.40 to -4.50 with an average of (-3.18±0.54);3 patients with T8-T9, 12 patients with T10-T12, and 7 patients with L1-L2;treated with bone cement reinforced pedicle screw internal fixation combined with kyphoplasty. Cobb angle and anterior margin height of the injured vertebra were compared before operation, 3 d and 12 months after operation. Visual analogue scale (VAS) and Oswestry disability index (ODI) were compared between two groups before operation and 12 months after operation. The incidence of postoperative complications was compared between two groups.
RESULTS:
All patients were followed up, PKP group followed up for 11 to 14 months with an average of (11.97±0.96) months and 10 to 14 months with an average of (12.05±1.09) months in reinforced screw group;there was no significant difference between two groups (P>0.05). Postoperative Cobb angle at 3 days and 12 months in reinforced screw group were (7.34±2.26) ° and (18.86±1.96) °, while in PKP group were (18.88±1.89) ° and (23.28±1.90) °;there were statistical difference between two groups (P<0.05). The anterior margin height of the injured vertebra in reinforced screw group were (25.28±1.33) mm and (19.62±2.22) mm at 3 days and 12 months after operation, while in PKP group were (18.61±2.16) mm and(15.93±1.34) mm;there were statistical difference between two groups (P<0.05). Cobb angle and the anterior margin height of the injured vertebra were significantly improved at 3 days and 12 months after operation between two groups (P<0.05). Postoperative VAS and ODI at 12 months in PKP group were (2.00±0.69) score and (13.44±4.02)%, while in reinforced screw group were(1.91±0.61) score and (10.18±4.26)%;which were significantly lower than (6.89±0.76) score and (36.33±3.40)% in PKP group, (7.23±0.75) score and (37.09±3.73) % in reinforced screw group before operation. There were no difference in postoperative VAS between two groups at 12 months (P>0.05);postoperative ODI in reinforced screw group at 12 months was lower than that in PKP group(P<0.05). There was no significant difference in complications between two groups (χ2=0.071, P>0.05).
CONCLUSION
PKP and bone cement reinforced nail combined with PKP could improve kyphotic deformity and postoperative function, and relieve pain. The application of bone cement-reinforced nail fixation technology could provide a more stable support, more obvious functional recovery, lower the risk of re-collapse of the injured vertebra, and maintain the long-term stability of spine.
Humans
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Male
;
Female
;
Aged, 80 and over
;
Kyphosis/surgery*
;
Aged
;
Bone Cements
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Middle Aged
;
Retrospective Studies
;
Pedicle Screws
;
Spinal Fractures/surgery*
;
Fracture Fixation, Internal/methods*
;
Bone Screws
;
Kyphoplasty
5.Association of Body Mass Index with All-Cause Mortality and Cause-Specific Mortality in Rural China: 10-Year Follow-up of a Population-Based Multicenter Prospective Study.
Juan Juan HUANG ; Yuan Zhi DI ; Ling Yu SHEN ; Jian Guo LIANG ; Jiang DU ; Xue Fang CAO ; Wei Tao DUAN ; Ai Wei HE ; Jun LIANG ; Li Mei ZHU ; Zi Sen LIU ; Fang LIU ; Shu Min YANG ; Zu Hui XU ; Cheng CHEN ; Bin ZHANG ; Jiao Xia YAN ; Yan Chun LIANG ; Rong LIU ; Tao ZHU ; Hong Zhi LI ; Fei SHEN ; Bo Xuan FENG ; Yi Jun HE ; Zi Han LI ; Ya Qi ZHAO ; Tong Lei GUO ; Li Qiong BAI ; Wei LU ; Qi JIN ; Lei GAO ; He Nan XIN
Biomedical and Environmental Sciences 2025;38(10):1179-1193
OBJECTIVE:
This study aimed to explore the association between body mass index (BMI) and mortality based on the 10-year population-based multicenter prospective study.
METHODS:
A general population-based multicenter prospective study was conducted at four sites in rural China between 2013 and 2023. Multivariate Cox proportional hazards models and restricted cubic spline analyses were used to assess the association between BMI and mortality. Stratified analyses were performed based on the individual characteristics of the participants.
RESULTS:
Overall, 19,107 participants with a sum of 163,095 person-years were included and 1,910 participants died. The underweight (< 18.5 kg/m 2) presented an increase in all-cause mortality (adjusted hazards ratio [ aHR] = 2.00, 95% confidence interval [ CI]: 1.66-2.41), while overweight (≥ 24.0 to < 28.0 kg/m 2) and obesity (≥ 28.0 kg/m 2) presented a decrease with an aHR of 0.61 (95% CI: 0.52-0.73) and 0.51 (95% CI: 0.37-0.70), respectively. Overweight ( aHR = 0.76, 95% CI: 0.67-0.86) and mild obesity ( aHR = 0.72, 95% CI: 0.59-0.87) had a positive impact on mortality in people older than 60 years. All-cause mortality decreased rapidly until reaching a BMI of 25.7 kg/m 2 ( aHR = 0.95, 95% CI: 0.92-0.98) and increased slightly above that value, indicating a U-shaped association. The beneficial impact of being overweight on mortality was robust in most subgroups and sensitivity analyses.
CONCLUSION
This study provides additional evidence that overweight and mild obesity may be inversely related to the risk of death in individuals older than 60 years. Therefore, it is essential to consider age differences when formulating health and weight management strategies.
Humans
;
Body Mass Index
;
China/epidemiology*
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Male
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Female
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Middle Aged
;
Prospective Studies
;
Rural Population/statistics & numerical data*
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Aged
;
Follow-Up Studies
;
Adult
;
Mortality
;
Cause of Death
;
Obesity/mortality*
;
Overweight/mortality*
6.Validity and Cost-Consequence Analysis of the Brief Version of the Montreal Cognitive Assessment for Discriminating Cognitive Impairment in a Community-Based Middle-Aged and Elderly Population.
Ting PANG ; Ya-Ping ZHANG ; Ren-Wei CHEN ; Ai-Ju MA ; Xiao-Yi YU ; Yi-Wen HUANG ; Yi-Chun LU ; Xin XU
Acta Academiae Medicinae Sinicae 2025;47(3):382-389
Objective To evaluate the reliability and validity and perform cost-consequence analysis of the brief version of the Montreal cognitive assessment(MoCA)for identifying cognitive impairment in a community-based population ≥50 years of age.Methods The internal consistency and retest reliability of the brief version of the MoCA were analyzed,and the area under the curve(AUC),sensitivity,and specificity were determined to discriminate mild cognitive impairment(MCI)and dementia with the clinical dementia rating(CDR)as the diagnostic criterion.The consistency between the brief version and the full version was analyzed by the Kappa test and the Bland-Altman method,and the number of individuals entering the diagnostic assessment and the overall assessment time were estimated and compared between the two versions.Results A total of 303 individuals were included in this study,of whom 192,94,and 17 had normal cognitive function,MCI,and dementia,respectively.The Cronbach's α and re-test coefficients of the brief version of MoCA were 0.754 and 0.711(P<0.001),respectively.The brief version showed the AUC,sensitivity,and specificity of 0.889,74.5%,and 93.8% for identifying MCI,and 0.994,100%,and 93.8% for identifying dementia,respectively.When the brief version of MoCA was used to identify 94 patients with MCI in 303 individuals,107 individuals required additional diagnostic assessment,with an overall assessment time of 142.4 h,which represented decreases of 21.3% and 32.7%,respectively,compared with those of the full version.When the brief version of MoCA was used to identify 17 patients with dementia in 303 individuals,35 individuals required additional diagnostic assessment,with an overall assessment time of 70.4 h,a decrease of 29.5% in the time cost compared with the full version.Conclusions The brief version of MoCA can identify cognitively impaired individuals in a community-based middle-aged and elderly population,with diagnostic validity comparable to that of the full version but less time cost and fewer individuals needing additional diagnostic assessment to detect true-positive cases.It could be expanded for use in the community-based primary screening setting.
Humans
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Aged
;
Middle Aged
;
Cognitive Dysfunction/diagnosis*
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Male
;
Female
;
Mental Status and Dementia Tests
;
Reproducibility of Results
;
Dementia/diagnosis*
;
Sensitivity and Specificity
;
Aged, 80 and over
;
Cost-Benefit Analysis
7.Phenotypic and molecular characterizations of 46, XY disorders of sex development due to variants of NR5A1 gene
Dongxia FU ; Yongxing CHEN ; Ai HUANG ; Xue WU ; Huizhen WANG ; Haiyan WEI
Chinese Journal of Medical Genetics 2024;41(8):909-915
Objective:The clinical and molecular genetic characteristics of 46, XY disorders of sex development caused by NR5A1 gene variants in 15 cases were analyzed to improve the understanding of this disease. Methods:The clinical data of children with NR5A1 gene variants diagnosed at the Children′s Hospital Affiliated to Zhengzhou University from March 2016 to December 2021 were retrospectively analyzed. Whole exome sequencing was performed to confirm the candidate sites, and Sanger sequencing was performed for validation. The patients were treated and followed up according to their disease characteristics. Results:At the initial diagnosis, 5 of the 15 cases were raised as females and 10 as males. The gonadal tissue was testis without residual Müllerian or ooticular structure, and all had various degrees of genital abnormalities. The average EMS masculinity score was 4.8 (1~9), including micropenis (100.0%), hypospadia (86.7%), unfused scrotum (46.7%), and abnormal testicular position (60.0%), in which the hypospadias was Ⅱ°~Ⅳ°. There was no skin pigmentation in 5 patients with growth retardation. Chromosomol karyotypes were 46, XY, adrenocorticotropin and cortisol levels were normal, electrolyte levels were normal, HCG stimulation test in 5 cases had normal response, 9 cases had low response. Anti-Müllerian hormone and statin B had decreased abnormally with age. A total of 14 NR5A1 variants were detected in the 15 children, most of which occurred in exon 4, of which 9 variant loci were not included in the HGMD database as of December 2022. Conclusion:The clinical phenotype of 46, XY abnormal sexual development caused by NR5A1 gene variants is extensive, with the external genitals showing varying degrees of insufficient masculinization. Adrenal involvement is rare.
8.A multi-center epidemiological study on pneumococcal meningitis in children from 2019 to 2020
Cai-Yun WANG ; Hong-Mei XU ; Gang LIU ; Jing LIU ; Hui YU ; Bi-Quan CHEN ; Guo ZHENG ; Min SHU ; Li-Jun DU ; Zhi-Wei XU ; Li-Su HUANG ; Hai-Bo LI ; Dong WANG ; Song-Ting BAI ; Qing-Wen SHAN ; Chun-Hui ZHU ; Jian-Mei TIAN ; Jian-Hua HAO ; Ai-Wei LIN ; Dao-Jiong LIN ; Jin-Zhun WU ; Xin-Hua ZHANG ; Qing CAO ; Zhong-Bin TAO ; Yuan CHEN ; Guo-Long ZHU ; Ping XUE ; Zheng-Zhen TANG ; Xue-Wen SU ; Zheng-Hai QU ; Shi-Yong ZHAO ; Lin PANG ; Hui-Ling DENG ; Sai-Nan SHU ; Ying-Hu CHEN
Chinese Journal of Contemporary Pediatrics 2024;26(2):131-138
Objective To investigate the clinical characteristics and prognosis of pneumococcal meningitis(PM),and drug sensitivity of Streptococcus pneumoniae(SP)isolates in Chinese children.Methods A retrospective analysis was conducted on clinical information,laboratory data,and microbiological data of 160 hospitalized children under 15 years old with PM from January 2019 to December 2020 in 33 tertiary hospitals across the country.Results Among the 160 children with PM,there were 103 males and 57 females.The age ranged from 15 days to 15 years,with 109 cases(68.1% )aged 3 months to under 3 years.SP strains were isolated from 95 cases(59.4% )in cerebrospinal fluid cultures and from 57 cases(35.6% )in blood cultures.The positive rates of SP detection by cerebrospinal fluid metagenomic next-generation sequencing and cerebrospinal fluid SP antigen testing were 40% (35/87)and 27% (21/78),respectively.Fifty-five cases(34.4% )had one or more risk factors for purulent meningitis,113 cases(70.6% )had one or more extra-cranial infectious foci,and 18 cases(11.3% )had underlying diseases.The most common clinical symptoms were fever(147 cases,91.9% ),followed by lethargy(98 cases,61.3% )and vomiting(61 cases,38.1% ).Sixty-nine cases(43.1% )experienced intracranial complications during hospitalization,with subdural effusion and/or empyema being the most common complication[43 cases(26.9% )],followed by hydrocephalus in 24 cases(15.0% ),brain abscess in 23 cases(14.4% ),and cerebral hemorrhage in 8 cases(5.0% ).Subdural effusion and/or empyema and hydrocephalus mainly occurred in children under 1 year old,with rates of 91% (39/43)and 83% (20/24),respectively.SP strains exhibited complete sensitivity to vancomycin(100% ,75/75),linezolid(100% ,56/56),and meropenem(100% ,6/6).High sensitivity rates were also observed for levofloxacin(81% ,22/27),moxifloxacin(82% ,14/17),rifampicin(96% ,25/26),and chloramphenicol(91% ,21/23).However,low sensitivity rates were found for penicillin(16% ,11/68)and clindamycin(6% ,1/17),and SP strains were completely resistant to erythromycin(100% ,31/31).The rates of discharge with cure and improvement were 22.5% (36/160)and 66.2% (106/160),respectively,while 18 cases(11.3% )had adverse outcomes.Conclusions Pediatric PM is more common in children aged 3 months to under 3 years.Intracranial complications are more frequently observed in children under 1 year old.Fever is the most common clinical manifestation of PM,and subdural effusion/emphysema and hydrocephalus are the most frequent complications.Non-culture detection methods for cerebrospinal fluid can improve pathogen detection rates.Adverse outcomes can be noted in more than 10% of PM cases.SP strains are high sensitivity to vancomycin,linezolid,meropenem,levofloxacin,moxifloxacin,rifampicin,and chloramphenicol.[Chinese Journal of Contemporary Pediatrics,2024,26(2):131-138]
9.Respiratory virus infection and its influence on outcome in children with septic shock
Gang LIU ; Chenmei ZHANG ; Ying LI ; Junyi SUN ; Yibing CHENG ; Yuping CHEN ; Zhihua WANG ; Hong REN ; Chunfeng LIU ; Youpeng JIN ; Sen CHEN ; Xiaomin WANG ; Feng XU ; Xiangzhi XU ; Qiujiao ZHU ; Xiangdie WANG ; Xinhui LIU ; Yue LIU ; Yang HU ; Wei WANG ; Qi AI ; Hongxing DANG ; Hengmiao GAO ; Chaonan FAN ; Suyun QIAN
Chinese Journal of Pediatrics 2024;62(3):211-217
Objective:To investigate respiratory virus infection in children with septic shock in pediatric care units (PICU) in China and its influence on clinical outcomes.Methods:The clinical data of children with septic shock in children′s PICU from January 2018 to December 2019 in 10 Chinese hospitals were retrospectively collected. They were divided into the pre-COVID-19 and post-COVID-19 groups according to the onset of disease, and the characteristics and composition of respiratory virus in the 2 groups were compared. Matching age, malignant underlying diseases, bacteria, fungi and other viruses, a new database was generated using 1∶1 propensity score matching method. The children were divided into the respiratory virus group and non-respiratory virus group according to the presence or absence of respiratory virus infection; their clinical characteristics, diagnosis, and treatment were compared by t-test, rank sum test and Chi-square test. The correlation between respiratory virus infection and the clinical outcomes was analyzed by logistic regression. Results:A total of 1 247 children with septic shock were included in the study, of them 748 were male; the age was 37 (11, 105) months. In the pre-and post-COVID-19 groups, there were 530 and 717 cases of septic shock, respectively; the positive rate of respiratory virus was 14.9% (79 cases) and 9.8% (70 cases); the seasonal distribution of septic shock was 28.9% (153/530) and 25.9% (185/717) in autumn, and 30.3% (161/530) and 28.3% (203/717) in winter, respectively, and the corresponding positive rates of respiratory viruses were 19.6% (30/153) and 15.7% (29/185) in autumn, and 21.1% (34/161) and 15.3% (31/203) in winter, respectively. The positive rates of influenza virus and adenovirus in the post-COVID-19 group were lower than those in the pre-COVID-19 group (2.1% (15/717) vs. 7.5% (40/530), and 0.7% (5/717) vs. 3.2% (17/530), χ2=21.51 and 11.08, respectively; all P<0.05). Rhinovirus virus were higher than those in the pre-Covid-19 group (1.7% (12/717) vs. 0.2% (1/530), χ2=6.51, P=0.011). After propensity score matching, there were 147 cases in both the respiratory virus group and the non-respiratory virus group. Rate of respiratory failure, acute respiratory distress, rate of disseminated coagulation dysfunction, and immunoglobulin usage of the respiratory virus group were higher than those of non-respiratory virus group (77.6% (114/147) vs. 59.2% (87/147), 17.7% (26/147) vs. 4.1% (6/147), 15.6% (25/147) vs. 4.1% (7/147), and 35.4% (52/147) vs. 21.4% (32/147); χ2=11.07, 14.02, 11.06 and 6.67, all P<0.05); and PICU hospitalization of the former was longer than that of the later (7 (3, 16) vs. 3 (1, 7)d, Z=5.01, P<0.001). Univariate logistic regression analysis showed that the presence of respiratory viral infection was associated with respiratory failure, disseminated coagulation dysfunction, the use of mechanical ventilation, and the use of immunoglobulin and anti-respiratory viral drugs ( OR=2.42, 0.22, 0.25, 0.56 and 1.12, all P<0.05). Conclusions:The composition of respiratory virus infection in children with septic shock is different between pre and post-COVID-19. Respiratory viral infection is associated with organ dysfunction in children with septic shock. Decreasing respiratory viral infection through respiratory protection may improve the clinical outcome of these children.
10.A multicenter retrospective study on clinical features and pathogenic composition of septic shock in children
Gang LIU ; Feng XU ; Hong REN ; Chenmei ZHANG ; Ying LI ; Yibing CHENG ; Yuping CHEN ; Hongnian DUAN ; Chunfeng LIU ; Youpeng JIN ; Sen CHEN ; Xiaomin WANG ; Junyi SUN ; Hongxing DANG ; Xiangzhi XU ; Qiujiao ZHU ; Xiangdie WANG ; Xinhui LIU ; Yue LIU ; Yang HU ; Wei WANG ; Qi AI ; Hengmiao GAO ; Chaonan FAN ; Suyun QIAN
Chinese Journal of Pediatrics 2024;62(11):1083-1089
Objective:To investigate the clinical features, pathogen composition, and prognosis of septic shock in pediatric intensive care units (PICU) in China.Methods:A multicenter retrospective cohort study. A retrospective analysis was conducted on the clinical data of children with septic shock from 10 hospitals in China between January 2018 and December 2021. The clinical features, pathogen composition, and outcomes were collected. Patients were categorized into malignant tumor and non-malignant tumor groups, as well as survival and mortality groups. T test, Mann Whitney U test or Chi square test were used respectively for comparing clinical characteristics and prognosis between 2 groups. Multiple Logistic regression was used to identify risk factors for mortality. Results:A total of 1 247 children with septic shock were included, with 748 males (59.9%) and the age of 3.1 (0.9, 8.8) years. The in-patient mortality rate was 23.2% (289 cases). The overall pathogen positive rate was 68.2% (851 cases), with 1 229 pathogens identified. Bacterial accounted for 61.4% (754 strains) and virus for 24.8% (305 strains). Among all bacterium, Gram negative bacteria constituted 64.2% (484 strains), with Pseudomonas aeruginosa and Enterobacter being the most common; Gram positive bacteria comprised 35.8% (270 strains), primarily Streptococcus and Staphylococcus species. Influenza virus (86 strains (28.2%)), Epstein-Barr virus (53 strains (17.4%)), and respiratory syncytial virus (46 strains (17.1%)) were the top three viruses. Children with malignant tumors were older and had higher pediatric risk of mortality (PRISM) Ⅲ score, paediatric sequential organ failure assessment (pSOFA) score (7.9 (4.3, 11.8) vs. 2.3 (0.8, 7.5) years old, 22 (16, 26) vs. 16 (10, 24) points, 10 (5, 14) vs. 8 (4, 12) points, Z=11.32, 0.87, 4.00, all P<0.05), and higher pathogen positive rate, and in-hospital mortality (77.7% (240/309) vs. 65.1% (611/938), 29.7% (92/309) vs. 21.0% (197/938), χ2=16.84, 10.04, both P<0.05) compared to the non-tumor group. In the death group, the score of PRISM Ⅲ, pSOFA (16 (22, 29) vs. 14 (10, 20) points, 8 (12, 15) vs. 6 (3, 9) points, Z=4.92, 11.88, both P<0.05) were all higher, and presence of neoplastic disease, positive rate of pathogen and proportion of invasive mechanical ventilation in death group were also all higher than those in survival group (29.7% (87/289) vs. 23.2% (222/958), 77.8% (225/289) vs. 65.4% (626/958), 73.7% (213/289) vs. 50.6% (485/958), χ2=5.72, 16.03, 49.98, all P<0.05). Multiple Logistic regression showed that PRISM Ⅲ, pSOFA, and malignant tumor were the independent risk factors for mortality ( OR=1.04, 1.09, 0.67, 95% CI 1.01-1.05, 1.04-1.12, 0.47-0.94, all P<0.05). Conclusions:Bacterial infection are predominant in pediatric septic shock, but viral infection are also significant. Children with malignancies are more severe and resource consumptive. The overall mortality rate for pediatric septic shock remains high, and mortality are associated with malignant tumor, PRISM Ⅲ and pSOFA scores.

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