Pregnant women account for 40% of all epilepsy patients, and the economic burden of pregnant women with epilepsy is 5 times higher than that of non-pregnant patients. Additionally, the rates of stillbirth and congenital malformations in pregnant women with epilepsy are 5 times greater than those in normal pregnant women. Therefore, it is crucial to comprehensively review and summarize the management of pregnant women with epilepsy to reduce the burden of the disease. This study provides a thorough review on teratogenic effects of anti-seizure medications (ASMs) used during pregnancy, and summarizes the effects of ASMs on health of offspring and offers clinical management recommendations for pregnant women with epilepsy, aiming to provide guidance for safe use of medications during pregnancy.

Objective:To explore the genetic background and clinical features of patients with long QT syndrome type 3 (LQT3).Methods:This retrospective cohort included patients diagnosed with LQT3 at the Department of Cardiology, Renmin Hospital of Wuhan University from January 1998 to December 2022. Patients were categorized into compound type group and single type group based on the presence of a single SCN5A mutation. The two groups were followed up and the differences in baseline characteristics, electrocardiograms, and clinical events between the two groups and probands were compared. Kaplan-Meier curves were used for survival analysis, and the log-rank test was employed to compare the event-free survival rates of first cardiac events between the groups and probands.Results:A total of 97 LQT3 patients were enrolled, including 59 probands. The age at diagnosis was (23.45±19.86) years, with 46 patients (47.4%) being male. Among them, 89 patients were classified as single type group, while 8 patients were classified as compound type group. Genetic testing identified 49 SCN5A mutations, with missense mutations being the majority (91.8%), primarily located in transmembrane regions (40.8%, n=20), interdomain linker regions (28.6%, n=14), and C-terminus (22.4%, n=11). The first cardiac event occurred in 44 patients (45.4%), with an onset age of (13.82±12.50) years. The main trigger was identified as rest or sleep (54.5%, n=24). Compared with patients in single type group, patients in compound type group were younger at diagnosis ((10.35±10.28) years vs. (24.63±20.13) years, P=0.040), had a significantly higher proportion of syncope (87.5% (7/8) vs. 33.7% (30/89), P=0.009), aborted cardiac arrest (62.5% (5/8) vs. 11.2% (10/89), P=0.001), and a lower incidence of event-free survival rates of first cardiac events (12.5% (1/8) vs.58.4% (52/89), log-rank P=0.001). The probands in compound type group had a significantly higher proportion of aborted cardiac arrest comparing to probands in single type group (62.5% (5/8) vs. 17.6% (9/51), P=0.020), while the difference in the incidence rate of event-free survival rates of first cardiac events between the probands in two groups was not statistically significant (12.5% (1/8) vs. 39.2% (20/51), log-rank P=0.08). Conclusion:Compound type LQT3 patients are not uncommon. Such patients are diagnosed at a younger age and exhibit more severe phenotypes, requiring close follow-up and proactive intervention strategies.

Objective To monitor the susceptibility of clinical isolates to antimicrobial agents in tertiary hospitals in major regions of China in 2022.Methods Clinical isolates from 58 hospitals in China were tested for antimicrobial susceptibility using a unified protocol based on disc diffusion method or automated testing systems.Results were interpreted using the 2022 Clinical &Laboratory Standards Institute(CLSI)breakpoints.Results A total of 318 013 clinical isolates were collected from January 1,2022 to December 31,2022,of which 29.5％were gram-positive and 70.5％were gram-negative.The prevalence of methicillin-resistant strains in Staphylococcus aureus,Staphylococcus epidermidis and other coagulase-negative Staphylococcus species(excluding Staphylococcus pseudintermedius and Staphylococcus schleiferi)was 28.3％,76.7％and 77.9％,respectively.Overall,94.0％of MRSA strains were susceptible to trimethoprim-sulfamethoxazole and 90.8％of MRSE strains were susceptible to rifampicin.No vancomycin-resistant strains were found.Enterococcus faecalis showed significantly lower resistance rates to most antimicrobial agents tested than Enterococcus faecium.A few vancomycin-resistant strains were identified in both E.faecalis and E.faecium.The prevalence of penicillin-susceptible Streptococcus pneumoniae was 94.2％in the isolates from children and 95.7％in the isolates from adults.The resistance rate to carbapenems was lower than 13.1％in most Enterobacterales species except for Klebsiella,21.7％-23.1％of which were resistant to carbapenems.Most Enterobacterales isolates were highly susceptible to tigecycline,colistin and polymyxin B,with resistance rates ranging from 0.1％to 13.3％.The prevalence of meropenem-resistant strains decreased from 23.5％in 2019 to 18.0％in 2022 in Pseudomonas aeruginosa,and decreased from 79.0％in 2019 to 72.5％in 2022 in Acinetobacter baumannii.Conclusions The resistance of clinical isolates to the commonly used antimicrobial agents is still increasing in tertiary hospitals.However,the prevalence of important carbapenem-resistant organisms such as carbapenem-resistant K.pneumoniae,P.aeruginosa,and A.baumannii showed a downward trend in recent years.This finding suggests that the strategy of combining antimicrobial resistance surveillance with multidisciplinary concerted action works well in curbing the spread of resistant bacteria.

Objective:To investigate the effect of pre-treatment plasma Epstein-Barr virus(EBV)DNA copy number on the clinical features and prognosis of patients with adult secondary hemophagocytic lymphohistiocytosis(sHLH).Methods:The clinical characteristics,survival rate,and prognostic factors of 171 patients with adult sHLH treated at Jiangsu Province Hospital from June 2017 to January 2022 were retrospectively analyzed in this study.Patients were divided into three groups,including the EBV DNA-negative group(＜5.0 × 102 copies/ml),lower EBV-DNA loads group(5.0 × 102-8.51 × 104 copies/ml),and higher EBV-DNA loads group(＞8.51 × 104 copies/ml),according to pre-treatment plasma EBV-DNA copy number.Cox regression model was established for screening prognostic factors.Adult sHLH survival prediction model was constructed and realized through the nomogram based on EBV-DNA load after adjusted the factors affecting survival of etiology and treatment strategy.Concordance index(C-index)and calibration curves were calculated to verify model predictive and discriminatory capacity.Results:Among 171 adult sHLH patients,84 patients were not infected with EBV(EBV DNA-negative group),and 87 with EBV(EBV DNA-positive group,48 lower EBV-DNA loads group and 39 higher EBV-DNA loads group).Consistent elevations in the levels of liver enzymes(ALT and AST),LDH,TG,β2-microglobulin and ferritin across the increasing of EBV-DNA load(all P＜0.05),while the levels of fibrinogen decrease(P＜0.001).The median follow-up time was 52 days(range 20-230 days),and 123 patients died.The overall survival(OS)rate of patients in EBV DNA-positive group was lower than that in EBV DNA-negative group(median OS:40 days vs 118 days,P＜0.001).Higher EBV-DNA loads had worse OS(median OS:24 days vs 45 days vs 118 days,P＜0.0001 for trend)compared to lower EBV-DNA loads and EBV DNA-negative group.Multivariate Cox analysis revealed that higher EBV-DNA loads(P=0.005),fibrinogen≤ 1.5 g/L(P=0.012),ferritin(P=0.041),associated lymphoma(P=0.002),and anti-tumor based strategy(P=0.001)were independent prognostic factors for OS.The C-indexes of 30 day,90 days,365 days survival rate were all greater than 0.8 of the nomogram model and calibration curves provided credibility to their predictive capability.Subgroup analysis showed that patients with higher EBV-DNA loads had a significantly worse prognosis in adult sHLH who were women,ferritin＞5 000 μg/L,β2-microglobulin＞7.4 mmol/L and regardless of age,etiologies,HScore points.Conclusion:The EBV-DNA load is a strong and independent predictor for survival in patients with sHLH.The prognostic nomogram based on EBV-DNA loads was dependable and provides a visual tool for evaluating the survival of adult sHLH.

OBJECTIVE: To investigate the expression and clinical significance of soluble Fas (sFas) and sFasL in patients with secondary hemophagocytic lymphohistiocytosis (sHLH). METHODS: From September 2015 to December 2020, 86 sHLH patients who met the HLH2004 diagnostic criteria were collected. They were divided into 55 cases in the MAHLH group and 31 cases in the NonMAHLH group according to the etiology. Thirty healthy persons were chosen as the normal control group, and 20 patients with systemic lupus erythematosus (SLE) were chosen as the disease control group. The expression levels of sFas and sFasL in the serum of patients with each group were detected by ELISA, and the clinical data were collected for statistical analysis. The significance of sFas and sFasL in sHLH was analyzed by ROC curve. RESULTS: Serum levels of sFas and sFasL in patients with newly diagnosed sHLH were significantly higher than those in disease control group and normal control group (P<0.01). The levels of sFas and sFasL in MAHLH group were significantly higher than those in nonMAHLH (infection related HLH and autoimmune disease related HLH) group (P<0.01). The serum levels of sFas and sFasL in 17 newly treated patients with sHLH (17/86) after treatment were significantly lower than those before treatment (P<0.01). The serum sFas level in newly diagnosed sHLH patients was positively correlated with SF(r=0.35), sCD25(r=0.79) and sFasL(r=0.73). The serum sFasL level was positively correlated with SF(r=0.39), sCD25(r=0.64) and sFas(r=0.73). Compared with the NonMAHLH group, the area under the ROC curve was 0.707 (95% CI: 0.593-0.821) (P=0.0015). The optimal critical value for diagnosing MAHLH by sFas level was 12 743 pg/ml, and the sensitivity and specificity were 70.9% and 71% respectively. Compared with the NonMAHLH group, the area under the ROC curve was 0.765(95% CI: 0.659-0.87)(P<0.01). The median OS time of sFas high expression group (≥16798.5 pg/ml) and sFasL high expression group (≥4 785 pg/ml) was significantly shorter than that of the low expression group (P<0.001). CONCLUSION Serum levels of sFas and sFasL can be used for the early diagnosis and differential diagnosis of sHLH disease, and are the factor related to the poor prognosis of sHLH.
Humans ; Lymphohistiocytosis, Hemophagocytic ; Clinical Relevance ; ROC Curve ; Sensitivity and Specificity ; Lupus Erythematosus, Systemic

Objective: To investigate the epidemiological characteristics of human adenovirus (HADV) 2, 3 and 7 in hospitalized children with respiratory infection. Methods: A total of 25 686 children with respiratory infection hospitalized at Children's Hospital of Hebei Province from January 2018 to December 2020 were retrospectively included.Deep sputum or nasopharyngeal aspirates of those children were collected. Then thirteen common respiratory pathogens were detected by multiplex PCR. 510 HADV positive specimens were randomly selected via random number and classified for type 2, 3 and 7 using a multiplex real-time quantitative PCR. SPSS 21.0 software was used to perform all of the statistical analyses. Enumeration data were expressed by frequency and percentage. χ² test was used for comparison between groups. Results: The HADV-positive rate was 7.99% (2 052/25 686). Children at age 3-<6 years had the highest HADV-positive rate (11.44%). The HADV-positive rate in 2019 was highest (10.64%). Among the 510 HADV-positive specimens, the proportion of type 3 was the highest (31.16%), followed by type 7 (21.37%) and type 2 (11.18%). The rate of type 2 in 2019 was significantly lower than that in 2018 and 2020 (χ²=8.954 and 16.354; P=0.003 and <0.01), while the rate of type 3 was significantly higher than that in 2018 and 2020 (χ²=5.248 and 4.811; P=0.022 and 0.028). The rate of type 2, type 3 and type 7 were lowest in winter, spring and autumn, respectively. The rate of type 2 increased significantly in autumn and the rate of type 3 and type 7 increased significantly in winter.The co-detection rate of HADV with other respiratory pathogens was 43.33%(221/510). Among, the co-detection rate of type 3 was highest (47.32%), and the co-detection rate of type 2, 3 and 7 was significantly higher than the alone detection rate (χ²=20.438, P<0.01; χ²=42.105, P<0.01; χ²=27.573, P<0.01).The proportion of severe pneumonia in children with type 7 positive (15.89%) was higher than that in children with non-type 7 positive (8.23%) (χ²=5.260, P=0.022). Conclusion: HADV is one of the important pathogens of children with respiratory infection in Children's Hospital of Hebei Province. The susceptible population of HADV is preschool children aged 3 to 6 years. HADV often co-detects with other respiratory pathogens. Type 3 and 7 is likely to be the dominant genotypes in this region, and type 7 may be one of the risk factors of severe pneumonia in children.
Child, Preschool ; Child ; Humans ; Infant ; Adenoviruses, Human/genetics* ; Child, Hospitalized ; Retrospective Studies ; Adenovirus Infections, Human/epidemiology* ; Respiratory Tract Infections/epidemiology* ; Pneumonia ; Hospitals

Objective: To understand the infection status of Enterovirus (EV) in cases of acute respiratory infections (ARIs) in Luohe City, Henan Province from 2017 to 2021, and analyze the prevalence and type composition of EV in ARIs. Methods: From October 2017 to May 2021, pharyngeal swab samples were collected from 1 828 patients with ARIs in Luohe Central Hospital and the clinical epidemiological data of these cases were also collected. EV-positive samples were identified by Quantitative Real-time Polymerase Chain Reaction (qPCR). The 5'-untranslated region (5'UTR) was amplified by Reverse Transcription-Polymerase Chain Reaction (RT-PCR). The results of 5'UTR region were initially typed by Enterovirus Genotyping Tool Version 1.0. Based on the typing results, the full-length of VP1 region was amplified by RT-PCR. The EV typing was identified again by VP1 region. Results: Among 1 828 cases of ARIs, 56.7% (1 036) were males. The median (Q₁, Q₃) age was about 3 (1, 5) years. Patients under 5 years old accounted for 71.6% (1 309 cases). Among all cases, a total of 71 EV-positive samples were identified by qPCR, with a detection rate of 3.88% (71/1 828). The EV detection rates for men and women were 3.28% (34/1 036) and 4.67% (37/792), without statistically significant differences (χ²=2.32, P=0.14). The EV detection rates for 2 to <6 years, 6 months to <2 years, 6 to <10 years, and <6 months were 6.29% (48/763), 3.00% (18/600), 2.52% (4/159), and 1.67% (1/60) (χ²=27.91, P<0.001). The EV detection rate was 0.92% (3/326) in autumn and winter of 2017. The EV detection rates were 1.18% (6/508), 2.47% (12/485) and 8.31% (34/409) in each year from 2018 to 2020, with an increasing trend year by year(χ²_trend=29.76, P<0.001). The main prevalent seasons were summer and autumn. The detection rate in spring of 2021 was 4.00% (4/100). A total of 12 types were identified and classified as CVA2, CVA4, CVA5, CVA6, CVA10, CVB3, CVB5, E5, E11, E30, PV-1, and EV-D68. The types of CVA2, CVA10, CVA6, and CVB3 were the dominant phenotypes. In 59 sample of EV typing, the main clinical manifestation was upper respiratory tract infection (36/59, 61.01%). The dominant types detected in upper respiratory tract infections were CVA10 (10/36, 27.78%), CVA6 (9/36, 25.00%) and CVB3 (8/36, 22.22%). The dominant type detected in lower respiratory tract infections was CVA2 (7/19, 36.84%). Conclusion: In Luohe City, Henan Province from 2017 to 2021, EV infection in ARIs cases has clear seasonal and age-specific patterns, and the dominant types of upper and lower respiratory tract infections are different.
Male ; Female ; Humans ; Enterovirus/genetics* ; 5' Untranslated Regions ; Enterovirus Infections/epidemiology* ; Phenotype ; Antigens, Viral/genetics* ; Respiratory Tract Infections/epidemiology* ; Phylogeny

We wished to establish an expert consensus on late stage of critical care (CC) management. The panel comprised 13 experts in CC medicine. Each statement was assessed based on the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) principle. Then, the Delphi method was adopted by 17 experts to reassess the following 28 statements. (1) ESCAPE has evolved from a strategy of delirium management to a strategy of late stage of CC management. (2) The new version of ESCAPE is a strategy for optimizing treatment and comprehensive care of critically ill patients (CIPs) after the rescue period, including early mobilization, early rehabilitation, nutritional support, sleep management, mental assessment, cognitive-function training, emotional support, and optimizing sedation and analgesia. (3) Disease assessment to determine the starting point of early mobilization, early rehabilitation, and early enteral nutrition. (4) Early mobilization has synergistic effects upon the recovery of organ function. (5) Early functional exercise and rehabilitation are important means to promote CIP recovery, and gives them a sense of future prospects. (6) Timely start of enteral nutrition is conducive to early mobilization and early rehabilitation. (7) The spontaneous breathing test should be started as soon as possible, and a weaning plan should be selected step-by-step. (8) The waking process of CIPs should be realized in a planned and purposeful way. (9) Establishment of a sleep-wake rhythm is the key to sleep management in post-CC management. (10) The spontaneous awakening trial, spontaneous breathing trial, and sleep management should be carried out together. (11) The depth of sedation should be adjusted dynamically in the late stage of CC period. (12) Standardized sedation assessment is the premise of rational sedation. (13) Appropriate sedative drugs should be selected according to the objectives of sedation and drug characteristics. (14) A goal-directed minimization strategy for sedation should be implemented. (15) The principle of analgesia must be mastered first. (16) Subjective assessment is preferred for analgesia assessment. (17) Opioid-based analgesic strategies should be selected step-by-step according to the characteristics of different drugs. (18) There must be rational use of non-opioid analgesics and non-drug-based analgesic measures. (19) Pay attention to evaluation of the psychological status of CIPs. (20) Cognitive function in CIPs cannot be ignored. (21) Delirium management should be based on non-drug-based measures and rational use of drugs. (22) Reset treatment can be considered for severe delirium. (23) Psychological assessment should be conducted as early as possible to screen-out high-risk groups with post-traumatic stress disorder. (24) Emotional support, flexible visiting, and environment management are important components of humanistic management in the intensive care unit (ICU). (25) Emotional support from medical teams and families should be promoted through"ICU diaries"and other forms. (26) Environmental management should be carried out by enriching environmental content, limiting environmental interference, and optimizing the environmental atmosphere. (27) Reasonable promotion of flexible visitation should be done on the basis of prevention of nosocomial infection. (28) ESCAPE is an excellent project for late stage of CC management.
Humans ; Consensus ; Critical Care/methods* ; Intensive Care Units ; Pain/drug therapy* ; Analgesics/therapeutic use* ; Delirium/therapy* ; Critical Illness

Objective: To analyze the report content, the methods and results of prenatal diagnosis of high risk of sex chromosome aneuploidy (SCA) in non-invasive prenatal testing (NIPT). Methods: A total of 227 single pregnancy pregnant women who received genetic counseling and invasive prenatal diagnosis at Drum Tower Hospital Affiliated to the Medical School of Nanjing University from January 2015 to April 2022 due to the high risk of SCA suggested by NIPT were collected. The methods and results of prenatal diagnosis were retrospectively analyzed, and the results of chromosome karyotype analysis and chromosome microarray analysis (CMA) were compared. The relationship between NIPT screening and invasive prenatal diagnosis was analyzed. Results: (1) Prenatal diagnosis methods for 277 SCA high risk pregnant women included 73 cases of karyotyping, 41 cases of CMA and 163 cases of karyotyping combined with CMA, of which one case conducted amniocentesis secondly for further fluorescence in situ hybridization (FISH) testing. Results of invasive prenatal diagnosis were normal in 166 cases (59.9%, 166/277), and the abnormal results including one case of 45,X (0.4%, 1/277), 18 cases of 47,XXX (6.5%, 18/277), 36 cases of 47,XXY (13.0%, 36/277), 20 cases of 47,XYY (7.2%, 20/277), 1 case of 48,XXXX (0.4%, 1/277), 20 cases of mosaic SCA (7.2%, 20/277), 5 cases of sex chromosome structural abnormality or large segment abnormality (1.8%, 5/277), and 10 cases of other abnormalities [3.6%, 10/277; including 9 cases of copy number variation (CNV) and 1 case of balanced translocation]. Positive predictive value (PPV) for SCA screening by NIPT was 34.7% (96/277). (2) Among the 163 cases tested by karyotyping combined with CMA, 11 cases (6.7%, 11/163) showed inconsistent results by both methods, including 5 cases of mosaic SCA, 1 case of additional balanced translocation detected by karyotyping and 5 cases of additional CNV detected by CMA. (3) NIPT screening reports included 149 cases of "sex chromosome aneuploidy"(53.8%, 149/277), 54 cases of "number of sex chromosome increased" (19.5%, 54/277), and 74 cases of "number of sex chromosome or X chromosome decreased" (26.7%, 74/277). The PPV of "number of sex chromosome increased" and "number of sex chromosome or X chromosome decreased" were 72.2% (39/54) and 18.9% (14/74), respectively, and the difference was statistically significant (χ²=34.56, P<0.01). Conclusions: NIPT could be served as an important prenatal screening technique of SCA, especially for trisomy and mosaicism, but the PPV is comparatively low. More information of NIPT such as the specific SCA or maternal SCA might help improving the confidence of genetic counseling and thus guide clinic management. Multi technology platforms including karyotyping, CMA and FISH could be considered in the diagnosis of high risk of SCA by NIPT.
Female ; Pregnancy ; Humans ; Retrospective Studies ; DNA Copy Number Variations ; In Situ Hybridization, Fluorescence ; Aneuploidy ; Prenatal Diagnosis/methods* ; Sex Chromosome Aberrations ; Sex Chromosomes/genetics*

Objective: To explore the efficacy of chemotherapy re-challenge in the third-line setting for patients with metastatic colorectal cancer (mCRC) in the real world. Methods: The clinicopathological data, treatment information, recent treatment efficacy, adverse events and survival data of mCRC patients who had disease progression after treatment with oxaliplatin-based and/or irinotecan-based chemotherapy and received third-line chemotherapy re-challenge from January 2013 to December 2020 at Tianjin Medical University Cancer Institute and Hospital were retrospectively collected. Survival curves were plotted with the Kaplan-Meier method, and the Cox proportional hazard model was used to analyze the prognostic factors. Results: A total of 95 mCRC patients were included. Among them, 32 patients (33.7%) received chemotherapy alone and 63 patients (66.3%) received chemotherapy combined with targeted drugs. Eighty-three patients were treated with dual-drug chemotherapy (87.4%), including oxaliplatin re-challenge in 35 patients and irinotecan re-challenge in 48 patients. The remaining 12 patients were treated with triplet chemotherapy regimens (12.6%). Among them, as 5 patients had sequential application of oxaliplatin and irinotecan in front-line treatments, their third-line therapy re-challenged both oxaliplatin and irinotecan; 7 patients only had oxaliplatin prescription before, and these patients re-challenged oxaliplatin in the third-line treatment. The overall response rate (ORR) and disease control rate (DCR) reached 8.6% (8/93) and 61.3% (57/93), respectively. The median progression free survival (mPFS) and median overall survival (mOS) were 4.9 months and 13.0 months, respectively. The most common adverse events were leukopenia (34.7%) and neutropenia (34.7%), followed by gastrointestinal adverse reactions such as nausea (32.6%) and vomiting (31.6%). Grade 3-4 adverse events were mostly hematological toxicity. Cox multivariate analysis showed that gender (HR=1.609, 95% CI: 1.016-2.548) and the PFS of front-line treatments (HR=0.598, 95% CI: 0.378-0.947) were independent prognostic factors. Conclusion: The results suggested that it is safe and effective for mCRC patients to choose third-line chemotherapy re-challenge, especially for patients with a PFS of more than one year in front-line treatments.
Humans ; Irinotecan/therapeutic use* ; Oxaliplatin/therapeutic use* ; Colorectal Neoplasms/pathology* ; Retrospective Studies ; Fluorouracil ; Colonic Neoplasms/chemically induced* ; Rectal Neoplasms/drug therapy* ; Antineoplastic Combined Chemotherapy Protocols/adverse effects* ; Camptothecin/adverse effects*