Multicenter Study In China Research Articles

Chinese advanced fusion-dependent lung cancer patients: Molecular spectrum and treatment options using next generation sequencing—A multicenter study (Yangtze River Delta Lung Cancer Cooperation Group-001).

e21036 Background: Lung cancer with drug receptor protein kinase fusion is regarded as a large class of molecular event, which is called fusion-dependent lung cancer. Fusion-dependent lung cancer accounts for about 10%-15% of non-small cell lung cancer. Therefore, the identification and detection of fusion-dependent lung cancer patients are very important in China. Here we reported a total of 4111 patients with Chinese fusion-dependent lung cancer. Methods: A multicenter study in China was initiated from Dec. 2019, and lung patients have been enrolled as of Dec. 2020. A total of 4111 patients with fusion-dependent were analyzed based on medical records and detailed patient questionnaires. Results: Of this entire cohort, 4111 patients were identified with fusion-dependent, including ALK fusions (2190, 53.27%), ROS1 fusions (894, 21.75%), RET fusions (521, 12.67%), NTRK fusions (128, 3.11%), FGFR fusions (84, 2.04%), NRG1 fusions (41, 1.00%), ERBB2 fusions (55, 1.34%), BRAF fusions (44, 1.07%), MET fusions (34, 0.83%), EGFR fusions (74, 1.80%), Other fusions (46, 1.12%). In ALK fusions, there were 1856 cases (84.75%) of EML4-, including A20(94.64%) and non-A20(5.36%), and other partners STRN-, KIF5B-, HIP1-, KLCl-, successively; In ROS1 fusions, there were 461 cases (51.57%) of CD74-, and other partners EZR-, SDC4-, SLC34A2-, TPM3-, GOPC-, successively; In RET fusions, there were 329 cases (63.15%) of KIF5B-, and other partners CCDC6-, NCOA4-, ERC1-, successively; In NTRK fusions, there were 22 cases (17.19%) of TPM3-NTRK1, and other types ETV6-NTRK3, LMNA-NTRK1, AGTPBP1-NTRK2 successively; In FGFR fusions, there were 40 cases (47.61%) of FGFR3-TACC3, and other types FGFR2-TACC2, ATE1-FGFR2, BAG4-FGFR1, successively; In NRG1 fusions, there were 11 cases (26.83%) of CD74-, and other partners SDC4-, RBPMS-, successively; In MET fusions, there were 9 cases (26.47%) of CD74-, and other partners HLA-DRB1-, KIF5B-, successively; In ERBB2, BRAF and EGFR fusions, the partners were scattered. And 3643 patiens (88.68%) of the detection were used DNA-based NGS, and Others were used RNA-based NGS. Patients with ALK and ROS1 fusions were routinely treated with targeted therapy. Patients with RET, NTRK, FGFR and NRG1 fusions were actively enrolled in the clinical trial. Patients with ERBB2, BRAF, MET and EGFR fusions were only treated with end-line trial target therapy, and they were eager to be included in the corresponding clinical trials. Conclusions: The common fusions of ALK, ROS1, RET are routine standardized treatment is very important. Although fusions are rare, it can not be ignored. Morever, these patients are eager to receive active targeted therapy. DNA+RNA based NGS is not widely used in China, but it is of great value to detect fusions, especially rare fusions, which is the future development trend.

Serum Folate Status Is Primarily Associated With Neurodevelopment in Children With Autism Spectrum Disorders Aged Three and Under-A Multi-Center Study in China.

Background: Autism spectrum disorder (ASD) is a complex neurodevelopmental disorder. Folate has been demonstrated to be associated with ASD. However, current studies on the correlation between folate and symptoms of children with ASD have inconsistent conclusions, use mainly small samples, and lack age-stratified analysis. This study aimed to explore the association between serum folate and symptoms of autistic children at different age groups from a multi-center perspective.Methods: We enrolled 1,300 children with ASD and 1,246 typically developing (TD) children under 7 years old from 13 cities in China. The Autism Behavior Checklist (ABC), Social Responsiveness Scale (SRS), and Childhood autism rating scale (CARS) were used to evaluate the symptoms of children with ASD. China neuropsychological and Behavior Scale-Revision 2016 (CNBS-R2016) scale was used to evaluate the neurodevelopment of children with ASD. Serum folate was measured by chemiluminescence assay in the two groups.Results: The serum folate levels of children with ASD were lower than that of TD children. In terms of core symptoms of ASD, we found that the serum folate levels were not associated with ABC, SRS, and CARS scores in ASD children of all ages but negatively associated with communication warning behavior scores of CNBS-R2016 in ASD children aged three and under. Concerning development quotients, it was at the age of three and under that serum folate levels were positively associated with gross motor, fine motor, language, and general quotient of ASD children. These ASD children aged three and under were further divided into two groups according to the median of serum folate (14.33 ng/mL); we found that compared to ASD children with folate ≤ 14.33 ng/mL, those with folate >14.33 ng/mL had lower communication warning behavior score and higher gross motor, fine motor, adaptive behavior, language, person-social, and general development quotients.Conclusion: We found that serum folate status was primarily associated with the neurodevelopment of children with ASD aged three and under. Furthermore, relatively higher serum folate levels may be more beneficial for children with ASD. Our results suggest that folate level should be paid more attention in ASD children, especially in early life, to better promote the intervention of ASD children.

Age-stratified and gender-specific reference intervals of six tumor markers panel of lung cancer: A geographic-based multicenter study in China.

BackgroundSerum biomarkers have been widely adopted in clinical practice for assisting lung cancer diagnoses, therapeutic monitoring, and prognostication. The function of a well‐performing tumor biomarker depends on a reliable reference interval (RI) with consideration of the study subjects’ age, gender, and geographical location. This study aimed to establish a RI for each of 6 lung cancer biomarkers for use in the whole country of China on Mindray platform.MethodsThe levels of serum 6 lung cancer biomarkers—namely progastrin‐releasing peptide (ProGRP), neuron‐specific enolase (NSE), squamous cell carcinoma antigen (SCC), carcinoembryonic antigen (CEA), cytokeratin‐19 fragment (CYFRA21‐1), and human epididymis protein 4 (HE4)—were measured utilizing the chemiluminescence immunoassay on the Mindray CL‐6000i platform following the laboratory standard operating procedures in apparently healthy Chinese individuals on large cohort, multicenter, and geographical consideration bases. The CLSI EP28‐A3C guideline was followed for the enrollment of study subjects.ResultsThe age‐stratified, gender‐specific RIs for ProGRP, NSE, SCC, CEA, CYFRA21‐1, and HE4 lung cancer biomarkers in the Chinese population have been established as described in the results and discussion in this work. In addition, various levels of the six lung cancer biomarkers among nine geographical locations in China have been observed.ConclusionsThe sample volume of study cohort, age, and geographical location should be considered upon establishing a reliable biomarker RI. A RI for each of six lung cancer biomarkers has been established. The results from this study would be helpful for clinical laboratories in interpreting the analytical results and for clinicians in patient management.

Prognostic Nomogram for Patients with Hepatitis E Virus-related Acute Liver Failure: A Multicenter Study in China.

Background and AimsTimely and effective assessment scoring systems for predicting the mortality of patients with hepatitis E virus-related acute liver failure (HEV-ALF) are urgently needed. The present study aimed to establish an effective nomogram for predicting the mortality of HEV-ALF patients.MethodsThe nomogram was based on a cross-sectional set of 404 HEV-ALF patients who were identified and enrolled from a cohort of 650 patients with liver failure. To compare the performance with that of the model for end-stage liver disease (MELD) scoring and CLIF-Consortium-acute-on-chronic liver failure score (CLIF-C-ACLFs) models, we assessed the predictive accuracy of the nomogram using the concordance index (C-index), and its discriminative ability using time-dependent receiver operating characteristics (td-ROC) analysis, respectively.ResultsMultivariate logistic regression analysis of the development set carried out to predict mortality revealed that γ-glutamyl transpeptidase, albumin, total bilirubin, urea nitrogen, creatinine, international normalized ratio, and neutrophil-to-lymphocyte ratio were independent factors, all of which were incorporated into the new nomogram to predict the mortality of HEV-ALF patients. The area under the curve of this nomogram for mortality prediction was 0.671 (95% confidence interval: 0.602–0.740), which was higher than that of the MELD and CLIF-C-ACLFs models. Moreover, the td-ROC and decision curves analysis showed that both discriminative ability and threshold probabilities of the nomogram were superior to those of the MELD and CLIF-C-ACLFs models. A similar trend was observed in the validation set.ConclusionsThe novel nomogram is an accurate and efficient mortality prediction method for HEV-ALF patients.

Investigation of the current situation of nipple-sparing mastectomy: a large multicenter study in China (CSBrs-003).

Background:Mastectomy techniques have been extended to nipple-sparing mastectomy (NSM). This study aimed to assess the actual application of NSM in China and identify the factors influencing postoperative complications.Methods:The clinical data of 615 patients (641 surgeries) undergoing NSM from January 1st, 2018 to December 31st, 2018 at 28 centers nationwide were retrospectively analyzed to obtain the rate of NSM and investigate factors related to NSM surgery.Results:The proportion of NSM surgery performed in this study was 2.67% (17/641). Malignant breast tumors accounted for the majority of NSM surgery (559/641, 87.2%). A total of 475 (77.3%) patients underwent NSM combined with reconstructive surgery. The rate of reconstruction decreased with age in our study, and implants were the most common option (344/641, 53.7%) in reconstruction. Radial incision was the most selected method regardless of reconstruction. However, for those who underwent reconstruction surgery, 18.4% (85/462) of cases also chose curvilinear incision, while in the simple NSM surgery group, more patients chose circumareolar incision (26/136, 19.1%). The tumor-to-nipple distance (TND) influenced postoperative complications (P = 0.004). There were no relationships between postoperative complications and tumor size, tumor location, histologic grade, molecular subtype, nipple discharge, and axillary lymph nodes.Conclusions:NSM surgery is feasible and only TND influenced postoperative complications of NSM surgery. But the proportion of NSM surgery performed is still low in nationwide centers of China. The selection criteria for appropriate surgical methods are important for NSM in clinical practice. To optimize clinical applications of NSM, further multicenter prospective randomized controlled studies are needed.Trial Registration:ChiCTR.org.cn, ChiCTR1900027423; http://www.chictr.org.cn/showprojen.aspx?proj=38739

Thyroid Parenchyma Microcalcifications on Ultrasound for Predicting Lymph Node Metastasis in Papillary Thyroid Carcinoma: A Prospective Multicenter Study in China.

Objective: Cervical lymph node metastasis (LNM) was found to be clinically significant prognostic factors of patients with papillary thyroid carcinomas (PTC). Ultrasound (US) characteristics of thyroid nodules and thyroid parenchyma may be used to predict LNM. To investigate the value of nodular US features as well as thyroid parenchymal microcalcifications on US in predicting LNM in patients with PTC.Methods: This prospective study was approved by the Institutional Review Board. From January 2018 to June 2019, 971 consecutive patients with solitary PTC who underwent preoperative neck US evaluation were included from six hospitals in China. The US features of thyroid nodules as well as thyroid parenchyma microcalcifications were carefully evaluated based on the static images and dynamic clips. Univariate and multivariate analyses were performed to determine independent predictors of LNM.Results: Of the 971 patients, 760 were female, 211 were male. According to the pathological examination, 241(24.82%) patients were found with cervical LNM (LNM positive group), while 730 (75.18%) patients were not (LNM negative group). Multiple logistic regression analysis showed that young age (<55 years old) (OR = 1.522, P = 0.047), large size (>10 mm) (OR = 1.814, P < 0.001), intratumoral microcalcifications (OR = 1.782, P = 0.002) and thyroid parenchyma microcalcifications (OR = 1.635, P = 0.046) were independent risk factors for LNM of PTC.Conclusions: Young age, large nodule size, intratumoral microcalcifications, as well as thyroid parenchyma microcalcifications on US are independent predictors of cervical LNM for patients with PTC.

Novel Multiparametric Nomogram for Overall Survival Prediction in Complicated Intra-Abdominal Infection: A Multicenter Study in China.

Background: Complicated intra-abdominal infections (cIAIs) in the abdominal cavity or within an abdominal organ are numerous and frequent dangerous entities in the treatment of critically ill patients. Early clinical evaluation is necessary.Methods: This retrospective multicenter study included patients from 10 intensive care units (ICUs). Risk factors for the overall survival (OS) of patients with cIAI were selected using least absolute shrinkage and selection operator regression, and a nomogram was constructed subsequently. Calibration curve and receiver operating characteristic (ROC) curve were used to evaluate the calibration and discriminative ability.Results: In total, 544 patients diagnosed with cIAI were enrolled and divided into the study (n = 276) and validation (n = 268) sets. Sex, acute gastrointestinal injury, acute kidney injury, rare bacterium infection, Charlson score, and APACHE II score were identified as independent risk factors and were constructed for the nomogram. The nomogram showed marked calibration capability with a concordance index (C-index) of 0.909 and 0.831 in the study and validation set, respectively. Compared with the common clinical prognostic scoring system, the nomogram achieved the highest discrimination ability with an area under the curve (AUC) value of 0.91 and 0.83 in the study set and validation set, respectively.Conclusions: Our newly constructed nomogram provides a useful tool for risk stratification and prognosis evaluation of cIAI.

Comment on "Antibiotic Resistance Profiles of Haemophilus influenzae Isolates from Children in 2016: A Multicenter Study in China".

Comment on "Antibiotic Resistance Profiles of Haemophilus influenzae Isolates from Children in 2016: A Multicenter Study in China".

Response to: Comment on "Antibiotic Resistance Profiles of Haemophilus influenzae Isolates from Children in 2016: A Multicenter Study in China".

Response to: Comment on "Antibiotic Resistance Profiles of Haemophilus influenzae Isolates from Children in 2016: A Multicenter Study in China".

The predictive effect of the platelet-to-lymphocyte ratio (PLR) and the neutrophil-to-lymphocyte ratio (NLR) on the risk of death in patients with severe fever with thrombocytopenia syndrome (SFTS): a multi-center study in China.

BackgroundSevere fever with thrombocytopenia syndrome is caused by infection with the severe fever with thrombocytopenia syndrome virus.MethodsBetween April 2011 and December 2019, data on consecutive patients who were diagnosed with severe fever with thrombocytopenia syndrome were prospectively collected from five medical centers in China. The score of the death risk model was correlated with the platelet-to-lymphocyte ratio and the neutrophil-to-lymphocyte ratio. Multivariable Cox analyses were used to identify the independent factors associated with mortality.ResultsDuring the study period, 763 patients were diagnosed with severe fever with thrombocytopenia syndrome; 415 of these patients were enrolled in our study. We found that the neutrophil-to-lymphocyte ratio of the group that died was significantly higher on admission (P=0.007) than that of the group that survived, and the neutrophil-to-lymphocyte ratio showed a positive correlation with the score of the death risk model. Multivariate Cox regression suggested that a neutrophil-to-lymphocyte ratio greater than 5.4 was an independent risk factor for survival time (HR=6.767, P=0.011). Platelet-to-lymphocyte ratio did not show a special role in this study.ConclusionsA neutrophil-to-lymphocyte ratio greater than 5.4 can increase the risk of death and decrease the survival time of patients. In summary, the neutrophil-to-lymphocyte ratio provides a supplementary means for effectively managing severe fever with thrombocytopenia syndrome (SFTS).

Rapid Classification of Multilocus Sequence Subtype for Group B Streptococcus Based on MALDI-TOF Mass Spectrometry and Statistical Models

Group B Streptococcus (GBS) is an important etiological agent of maternal and neonatal infections as well as postpartum women and individuals with impaired immunity. We developed and evaluated a rapid classification method for sequence types (STs) of GBS based on statistic models with Matrix-Assisted Laser Desorption/Ionization Time-of Flight Mass Spectrometry (MALDI-TOF/MS). Whole-cell lysates MALDI-TOF/MS analysis was performed on 235 well-characterized GBS isolates from neonatal invasive infections in a multi-center study in China between 2015 and 2017. Mass spectra belonging to major STs (ST10, ST12, ST17, ST19, ST23) were selected for model generation and validation. Recognition and cross validation values were calculated by Genetic Algorithm-K Nearest Neighbor (GA-KNN), Supervised Neural Network (SNN), QuickClassifier (QC) to select models with the best performance for validation of diagnostic efficiency. Informative peaks were further screened through peak statistical analysis, ST subtyping MSP peak data and mass spectrum visualization. For major STs, the ML models generated by GA-KNN algorithms attained highest cross validation values in comparison to SNN and QC algorithms. GA-KNN models of ST10, ST17, and ST12/ST19 had good diagnostic efficiency, with high sensitivity (95–100%), specificity (91.46%–99.23%), accuracy (92.79–99.29%), positive prediction value (PPV, 80%–92.68%), negative prediction value (NPV, 94.32%–99.23%). Peak markers were firstly identified for ST10 (m/z 6250, 3125, 6891) and ST17 strains (m/z 2956, 5912, 7735, 5218). Statistical models for rapid GBS ST subtyping using MALDI-TOF/MS spectrometry contributes to easier epidemical molecular monitoring of GBS infection diseases.

Ambient air pollution and obesity in school-aged children and adolescents: A multicenter study in China

BackgroundEnvironmental factors such as air pollution may contribute to the development of childhood obesity. However, current epidemiological evidence is limited and inconsistent. ObjectiveWe investigated the associations between long-term air pollution exposure and obesity in a large population of Chinese children and adolescents. MethodsA total of 44,718 children and adolescents (50.5% boys) aged 7 to 18 years were recruited from seven provinces/municipalities in China. Body mass index (BMI), waist circumference, waist-to-height ratio (WHtR) and the prevalence of general and central obesity were measured. Satellite-based spatial-temporal models were used to estimate ambient concentrations of particulate matter with aerodynamic diameter < 1.0 μm (PM1), <2.5 μm (PM2.5), <10.0 μm (PM10) and nitrogen dioxide (NO2). We used mixed-effects linear and logistic regression models to examine the associations between air pollution exposure and body weight measures. ResultsExposure to PM1, PM2.5, PM10 and NO2 was associated with increased BMI Z-score, waist circumference and WHtR, and higher prevalence of both general and central obesity. Generally, stronger associations were observed for particles, especially PM1 and PM2.5, than for NO2. Also, the associations of particles were generally more stable in two-pollutant models. Overall, the associations were more pronounced in boys than in girls except for general obesity. ConclusionsLong-term exposure to air pollution was associated with increased body weight and higher prevalence of obesity in children and adolescents, suggesting potential obesogenic effects of air pollution.

Distinct Cause of Death Profiles of Hospitalized Non-alcoholic Fatty Liver Disease: A 10 Years' Cross-Sectional Multicenter Study in China.

Background: The clinical burden and natural history of non-alcoholic fatty liver disease (NAFLD) vary globally. We aimed to investigate NAFLD-related mortality profiles in hospitalized patients in southern China.Methods: A multicenter retrospective investigation with a 10-year study period (2009–2018) analyzed 10,071 deaths during hospitalization (NAFLD: 2,015; other liver diseases: 1,140; without liver diseases: 6,916) was performed using a multiple cause of death analysis. Medical histories and biochemistry and imaging findings were extracted from the electronic medical record system. The underlying causes of death were classified by 10th Revision of the International Classification of Diseases (ICD-10) codes.Results: The distribution of death causes in patients with NAFLD has stabilized over time, with cardio- and cerebral vascular disease (CVD) ranked first (35.6%), followed by extrahepatic malignancies (22.6%), infection (11.0%), kidney disease (7.5%), liver-related diseases (5.2%), respiratory diseases (3.9%), digestive diseases (3.5%), endocrine diseases (3.5%), and other diseases (7.2%). NAFLD patients had more deaths attributable to CVD, extrahepatic malignancies, liver-related diseases (all P < 0.001) and multiorgan failure than the deceased controls. The severity of steatosis was independently associated with these relationships (liver-related diseases: OR = 1.37, 95% CI: 1.20–1.59, cardio- and cerebrovascular diseases: OR = 1.23, 95% CI: 1.19–1.31, infectious diseases: OR = 1.14, 95% CI: 1.04–1.26, and renal diseases: OR = 1.21, 95% CI: 1.02–1.47, all P < 0.05) after adjustment for sex, body mass index (BMI), fasting blood glucose, low-density lipoprotein cholesterol, uric acid, metabolic syndromes and fibrosis index based on the 4 factors.Conclusion : NAFLD patients had higher proportions of death due to underlying CVD and liver-related diseases than the general population in China; these proportions positively correlated with steatosis degree.

Prognostic factors for pyrrolizidine alkaloid-induced hepatic sinusoidal obstruction syndrome: a multicenter study in China.

BackgroundIn China, one of the major causes of hepatic sinusoidal obstruction syndrome (HSOS) is the intake of herbals containing pyrrolizidine alkaloid (PA). However, prognostic factors for PA-induced HSOS are poorly understood. The aim of this study was to identify the independent prognostic factors for PA-induced HSOS using a multi-center study.MethodsA total of 117 PA-induced HSOS patients were enrolled for data collection in three university hospitals from November 2003 to September 2018. Univariate and multivariate Cox proportional hazards analysis were used to determine prognostic factors for PA-induced HSOS.ResultsThe median age of the PA-induced HSOS patients was 61 years (range, 21–88 years), and 64% of them were male. The survival rates at 1, 3, and 36 months were 89.71%, 72.60%, and 69.19%, respectively. Significant differences in prothrombin time (PT), international normalized ratio, total bilirubin, severity grading [new criteria for severity grading of hematopoietic stem cell transplantation (HSCT)-related HSOS in adults] were found between patients who survived and those who died. Univariate and multivariate survival analysis using Cox’s regression model demonstrated low serum albumin (<35 g/L), elevated serum urea (>8.2 mmol/L) and severe or very severe HSOS (European Society for Blood and Marrow Transplantation 2016 criteria) were independent prognostic factors of survival.ConclusionsSerum albumin, serum urea, and severity grading were independent prognostic factors for patients with PA-induced HSOS, and can contribute to identifying potentially high-risk patients for early effective intervention.Trial registrationChiCTR-DRD-17010709 (www.chictr.org.cn).

Evaluation of the body mass index in breast cancer prognosis in a cohort of small-stature overweight patients: multi-center study in China.

Overweight and obesity have become a major health issue in the past 30 years. Several studies have already shown that obesity is significantly associated with a higher risk of developing breast cancer. However, few studies have assessed the prognostic value of the body mass index (BMI) in Asian populations. The purpose of this study was to retrospectively analyze the impact of BMI on the prognosis of breast cancer in overweight, under 160 cm tall patients from southern China. We retrospectively analyzed data from 525 breast cancer patients diagnosed between 2003 to 2010 in a multi-center of China. After applying the exclusion criteria, 315 patients with complete data were retained. Their clinical and pathological characteristics were compared using the chi-square test. Survival analysis was performed with the Kaplan-Meier method. Univariate and multivariate analyses were performed using Cox regression to calculate hormone receptor status, HER-2 status, lymph node status, age, BMI and tumor size hazard ratio (HR), and 95% confidence intervals (95% CI). There was a strong correlation between BMI and age in the baseline feature analysis (P=0.001). After grouping the patients according to the molecular type of cancer, we found that in Luminal A and B, the BMI was related to age (P=0.002, P=0.010). The disease-free survival (DFS) and overall survival (OS) of patients with different BMI were not significantly different. This conclusion was also reached by pairwise comparison of subgroups. There was no significant difference in recurrence in patients from different BMI groups. We did not find a critical weight threshold associated with higher risk of recurrence. There were no statistically significant differences in treatment among the three BMI groups of overweight patients. We found that the BMI of Chinese breast cancer patients is related to age but not prognosis.

Primary immunodeficiency-related genes in neonatal intensive care unit patients with various genetic immune abnormalities: a multicentre study in China.

ObjectivesThe present phenotype‐based disease classification causes ambiguity in diagnosing and determining timely, effective treatment options for primary immunodeficiency (PID). In this study, we aimed to examine the characteristics of early‐onset PID and proposed a JAK‐STATopathy subgroup based on their molecular defects.MethodsWe reviewed 72 patients (< 100 days) retrospectively. These patients exhibited various immune‐related phenotypes and received a definitive molecular diagnosis by next‐generation sequencing (NGS)‐based tests. We evaluated the PID‐causing genes and clinical parameters. We assessed the genes that shared the JAK‐STAT signalling pathway. We also examined the potential high risks related to the 180‐day death rate.ResultsWe identified PID disorders in 25 patients (34.72%, 25/72). The 180‐day mortality was 26.39% (19/72). Early onset of disease (cut‐off value of 3.5 days of age) was associated with a high 180‐day death rate (P = 0.009). Combined immunodeficiency with associated or syndromic features comprised the most common PID class (60.00%, 15/25). Patients who presented life‐threatening infections were most likely to exhibit PID (odds ratio [OR] = 2.864; 95% confidence interval [CI]: 1.047‐7.836). Twelve out of 72 patients shared JAK‐STAT pathway defects. Seven JAK‐STATopathy patients were categorised as PID. They were admitted to NICUs as immunological emergencies. Most of them experienced severe infections and thrombocytopenia, with 4 succumbing to an early death.ConclusionsThis study confirmed that NGS can be utilised as an aetiological diagnostic method of complex immune‐related conditions in early life. Through the classification of PID as pathway‐based subtypes, we see an opportunity to dissect the heterogeneity and to direct targeted therapies.

Polymyxin resistance in carbapenem-resistant Enterobacteriaceae isolates from patients without polymyxin exposure: a multicentre study in China

Polymyxins were recently approved for the clinical treatment of carbapenem-resistant Enterobacteriaceae (CRE) infections in China. The aim of this study was to determine the prevalence and molecular mechanisms of polymyxin-resistant CRE prior to the clinical application of polymyxin and to evaluate the potential for emerging polymyxin resistance in China. A total of 504 unique CRE isolates were collected from six tertiary-care hospitals in China between October 2016 and September 2017. All isolates underwent antimicrobial susceptibility testing. Clinical, demographic, antimicrobial exposure and infection data were collected from patients' medical charts. PCR detection, Sanger sequencing and reverse transcription real-time fluorescence quantitative PCR (RT-qPCR) were used to investigate the molecular mechanism of polymyxin resistance. A total 19 (3.8%) polymyxin-resistant isolates were identified, including Klebsiella pneumoniae, Escherichia coli, Klebsiella aerogenes and Enterobacter cloacae. Genetic analysis in K. pneumoniae strains identified insertion sequence (IS) elements (n=3), a stop codon (n=1) and gene deletion (n=2) in mgrB and a pmrB missense mutation (T157P) (n=1). Two E. coli isolates contained mcr-1 and an E. cloacae strain harboured a frameshift in mgrB. Further transcriptional analysis showed that pmrA, pmrB, pmrC and pmrK were significantly upregulated in polymyxin-resistant isolates. Despite the lack of polymyxin exposure, 3.8% of CRE were resistant to polymyxin in China. Both chromosomal and plasmid-encoded mechanisms were identified. Our study suggests that clinical practice should be alert to pre-existing polymyxin resistance among CRE isolates to avoid further dissemination of polymyxin resistance.

Clinical and Economic Impact of Third-Generation Cephalosporin-Resistant Infection or Colonization Caused by Escherichia coli and Klebsiella pneumoniae: A Multicenter Study in China.

Quantifying economic and clinical outcomes for interventions could help to reduce third-generation cephalosporin resistance and Escherichia coli or Klebsiella pneumoniae. We aimed to compare the differences in clinical and economic burden between third-generation cephalosporin-resistant E. coli (3GCREC) and third-generation cephalosporin-susceptible E. coli (3GCSEC) cases, and between third-generation cephalosporin-resistant K. pneumoniae (3GCRKP) and third-generation cephalosporin-susceptible K. pneumoniae (3GCSKP) cases. A retrospective and multicenter study was conducted. We collected data from electronic medical records for patients who had clinical samples positive for E. coli or K. pneumoniae isolates during 2013 and 2015. Propensity score matching (PSM) was conducted to minimize the impact of potential confounding variables, including age, sex, insurance, number of diagnoses, Charlson comorbidity index, admission to intensive care unit, surgery, and comorbidities. We also repeated the PSM including length of stay (LOS) before culture. The main indicators included economic costs, LOS and hospital mortality. The proportions of 3GCREC and 3GCRKP in the sampled hospitals were 44.3% and 32.5%, respectively. In the two PSM methods, 1804 pairs and 1521 pairs were generated, and 1815 pairs and 1617 pairs were obtained, respectively. Compared with susceptible cases, those with 3GCREC and 3GCRKP were associated with significantly increased total hospital cost and excess LOS. Inpatients with 3GCRKP were significantly associated with higher hospital mortality compared with 3GCSKP cases, however, there was no significant difference between 3GCREC and 3GCSEC cases. Cost reduction and outcome improvement could be achieved through a preventative approach in terms of both antimicrobial stewardship and preventing the transmission of organisms.

Analysis of the Correlation Between the Clinical Effect of Sacral Neuromodulation and Patient Age: A Retrospective Multicenter Study in China

This study aimed to evaluate whether patients stratified by age have the same level of benefits after a sacral neuromodulation (SNM) procedure for refractory lower urinary tract dysfunction. This retrospective study comprised 211 patients with refractory lower urinary tract dysfunction who had been treated with SNM and recruited from multiple medical centers across China. Patients were grouped according to age: <40 (n = 58), 40-64 (n = 94), and > 64 (n = 59) years. Data were compared using voiding diaries and subjective scores pre-operatively, post-implantation of a stage I tined lead, and during a short-term follow-up period postimplantation of a stage II implanted pulse generator. In all groups, voiding diary data and subjective scores improved significantly over different periods. Residual urine improved in the 40-64 and > 64-year-old age groups. Quality of life scores improved in the <40-year-old age group. Voiding diary data among age groups varied at baseline; however, average urinary frequency did not differ at the last follow-up. Urgency and sexual life scores differed at baseline and these differences had resolved at the last follow-up. O'Leary-Sant and Pelvic Pain and Urgency/Frequency Symptoms Scale scores did not differ at baseline; however, significant differences were observed at the last follow-up. SNM success is unrelated to age, and age alone should not be considered a limiting factor in SNM. For older patients, an overactive bladder appears a better indication for SNM treatment; however, further studies are required to confirm this finding.

Fine particulate matter constituents and sub-clinical outcomes of cardiovascular diseases: A multi-center study in China

BackgroundLimited evidence is available on the associations of long-term exposure to various fine particulate matter (PM2.5) constituents with sub-clinical outcomes of cardiovascular disease (CVD) in China. ObjectivesWe aimed to explore the associations of PM2.5 and its constituents with blood pressure (BP), fasting glucose, and cardiac electrophysiological (ECG) properties based on a national survey of 5852 Chinese adults, who participated in the Sub-Clinical Outcome of Polluted Air study, from July 2017 to March 2019. MethodsAnnual residential exposure to PM2.5 and its constituents of each subject was predicted by a satellite-based mode. We assessed the associations between five main constituents [organic matter (OM), black carbon (BC), sulfate (SO42−), nitrate (NO3−), ammonium (NH4+)] of PM2.5 and systolic BP (SBP), diastolic BP (DBP), fasting glucose, and ECG measurements (PR, QRS, QT, and QTc interval) using multivariable linear regression models. ResultsLong-term PM2.5 exposure was significantly associated with increased levels of fasting glucose, DBP, and ECG measurements. An IQR increase in OM (8.2 μg/m3) showed considerably stronger associations with an elevated fasting glucose of 0.39 mmol/L (95%CI confidence interval: 0.28, 0.49) compared with other PM2.5 constituents. Meanwhile, an IQR increase in NO3−, NH4+ and OM had stronger associations with DBP and ECG parameters compared with BC and SO42−. ConclusionsThis nationwide multi-center study in China indicated that some constituents (i.e., OM, NO3−, and NH4+) might be mainly responsible for the association of PM2.5 with sub-clinical outcomes of CVD including BP, fasting glucose, and ECG measurements.