Risk factors for premature rupture of membranes in pregnant women: a systematic review and meta-analysis.

OBJECTIVE: To identify risk factors for premature rupture of membranes (PROM) in pregnant women. DESIGN: Systematic review and meta-analysis. DATA SOURCES: Web of Science, PubMed, Embase, Cochrane Library, China National Knowledge Infrastructure, Wanfang Database, Chinese Scientific Journal Database (VIP) and China Biology Medicine Disc were searched from inception to October 2022. ELIGIBILITY CRITERIA: Cross-sectional, case-control and cohort studies published in English or Chinese that reported the risk factors for PROM were eligible for inclusion. DATA EXTRACTION AND SYNTHESIS: Two reviewers independently extracted the data and evaluated the risk of bias using the Newcastle-Ottawa Scale and American Agency for Healthcare Research and Quality tools. Analyses were performed using RevMan 5.4 software, and heterogeneity was assessed using χ2 tests and I2 statistics. The sensitivity analyses included a methodological transition between fixed-effect and random-effect models and the systematic stepwise exclusion of studies. RESULTS: A total of 21 studies involving 18 174 participants with 18 risk factors were included. The significant risk factors were low Body Mass Index (BMI) (OR 2.18, 95% CI 1.32 to 3.61), interpregnancy interval (IPI) <2 years (OR 2.99, 95% CI 1.98 to 4.50), previous abortion (OR 2.35, 95% CI 1.76 to 3.14), previous preterm birth (OR 5.72, 95% CI 3.44 to 9.50), prior PROM (OR 3.95, 95% CI 2.48 to 6.28), history of caesarean section (OR 3.06, 95% CI 1.72 to 5.43), gestational hypertension (OR 3.84, 95% CI 2.36 to 6.24), gestational diabetes mellitus (GDM) (OR 2.16, 95% CI 1.44 to 3.23), abnormal vaginal discharge (OR 2.17, 95% CI 1.45 to 3.27), reproductive tract infection (OR 2.16, 95% CI 1.70 to 2.75), malpresentation (OR 2.26, 95% CI 1.78 to 2.85) and increased abdominal pressure (OR 1.45, 95% CI 1.07 to 1.97). The sensitivity analysis showed that the pooled estimates were stable. CONCLUSIONS: This meta-analysis indicated that low BMI, IPI <2 years, previous abortion, previous preterm birth, prior PROM, history of caesarean section, gestational hypertension, GDM, abnormal vaginal discharge, reproductive tract infection, malpresentation and increased abdominal pressure might be associated with a greater risk of PROM. Associations between smoking status, short cervical length, fine particulate matter (PM2.5) and PROM require further investigation. PROSPERO REGISTRATION NUMBER: CRD42022381485.

Vemurafenib combined with chemotherapy achieved sustained remission in pediatric LCH: a multi-center observational study.

BACKGROUND: Langerhans cell histiocytosis (LCH) is a myeloid neoplasia with potentially fatal consequences, and about 2/3 of cases involve the BRAFV600E kinase-activated mutation. Vemurafenib, a BRAF inhibitor, has demonstrated significant clinical improvements in LCH. However, the high relapse rate of LCH following cessation of vemurafenib therapy remains a major challenge, and alternative treatment strategies require further investigation. METHODS: In this retrospective multi-center study, we evaluated the efficacy and safety of vemurafenib combined with conventional chemotherapy in patients with severe or refractory LCH. RESULTS: Seventeen patients were enrolled in the study, with eleven classified as risk organ involvement (RO +). Six received the combination therapy as the primary treatment, and eleven after being refractory to prior chemotherapy. The overall response rate was 94.1%. Progression-free survival among all 17 patients was 70.6% (12/17) at a median follow-up of 32 months, and relapse-free survival among the 15 patients with discontinuation after a response was 73.3%(11/15) at a median follow-up of 34 months. Five of six patients (83.3%) with myeloid BRAFV600E mutations demonstrated molecular remission. The overall survival rate was 100%. Adverse events were mostly classified as grades 1 or 2. CONCLUSION: Our data suggest that the combination of vemurafenib and chemotherapy can achieve sustained clinical and molecular level relief in children with LCH, and side effects are tolerable.

Structural elucidation of a non-starch polysaccharides from Lilii Bulbus and its protective effects against corticosterone-induced neurotoxicity in PC12 cells.

Lilii Bulbus is a folk medicine for both culinary and medicinal purpose. In traditional medicine theory, Lilii Bulbus is usually used as an complementary therapy for nourishing the heart and lung, clearing heat in the treatment of mental instability and depression. In this study, NLPS-1a (Mw = 2610 Da, DP = 16), a water-soluble non-starch Lilii Bulbus polysaccharides, was isolated and purified. Structural analysis showed that NLPS-1a mainly contained Man and Glc with a molar ratio of 11.137 and 9.427. The glycosidic linkages of NLPS-1a were 1,3-Manp (59.93%), 1,2-Glcp (37.93%), T-Glcp (1.21%) and T-Manp (0.93%), indicating the highly-linear structures. In addition, NLPS-1a could significantly repair the injury of PC12 cells induced by corticosterone (CORT), reduce Lactate dehydrogenase (LDH) leakage and decrease the cell apoptosis in a dose-dependent manner. Above all, the results indicated that NLPS-1a had protective effects against CORT-induced neurotoxicity in PC12 cells, and might be a natural antidepressant, which enriched the study of the metabolic mechanism between herbal polysaccharides and antidepressant.

Poor outcome of pediatric B-cell acute lymphoblastic leukemia associated with high level of CRLF2 gene expression in distinct molecular subtypes.

Background: Overexpression of the cytokine receptor-like factor 2 (CRLF2) gene is the most common feature in the Philadelphia chromosome (Ph)-like subtype of B-cell acute lymphoblastic leukemia (B-ALL). However, the predictive value of CRLF2 overexpression for the prognosis of pediatric B-ALL patients remain controversial. The molecular mechanisms that upregulate CRLF2 expression level in patients has not been fully elucidated. Methods: In this study, the prognostic impact of CRLF2 expression level on molecular types of B-ALL in pediatric patients from Zhujiang Hospital (n = 111) was retrospectively analyzed. Youden index analysis was used to categorize CRLF2 expression into 3 groups, and these categories more precisely described the differences in the prognosis of patients with varying expression levels of CRLF2 in both the Zhujiang Hospital cohort and the TARGET cohort. Results: We used the Zhujiang Hospital cohort as a discovery cohort to determine the cutoff value of CRLF2 expression. CRLF2-high patients accounted for approximately 6%. In addition, the percentage of bone marrow blast cells and initial white blood cell count in CRLF2-high patients were higher than those in CRLF2-low patients, and MRD turned negative slower. The results were validated in the TARGET cohort and indicated that CRLF2 overexpression could be subdivided by CRLF2 expression levels into 2 categories: CRLF2-high with a poor survival and CRLF2-medium with a good OS and EFS. Such heterogeneity was attributed to the different molecular mechanisms leading to CLRF2 upregulation, where the CRLF2 overexpression level was high in Ph-like B-ALL and medium in high hyperdiploid B-ALL. Conclusion: This study highlights the importance of the molecular mechanisms of the upregulation of CRLF2 expression in predicting the prognosis of pediatric B-ALL patients.

Comprehensive Need as a Mediator Between Psychological Stress and Quality of Life Among Caregivers of Patients With Cancer.

BACKGROUND: Caregivers of patients with cancer are susceptible to profound psychological distress and low quality of life owing to the substantial demands of caregiving. The comprehensive needs of caregivers are closely linked to their quality of life. However, little is known about the relationship between these factors. OBJECTIVE: This study aimed to determine whether comprehensive needs mediate the relationships between psychological stress and quality of life in caregivers of patients with cancer. METHODS: A cross-sectional design was used to recruit 382 participants through convenience sampling. Psychological stress, comprehensive needs, and quality of life were measured using a questionnaire. RESULTS: Psychological stress was associated with higher comprehensive needs (r = 0.30, P < .01) and lower quality of life (r = -0.20, P < .01). Comprehensive needs were negatively associated with quality of life (r = -0.28, P < .01). Mediation analysis findings revealed that both the indirect effect of psychological stress on quality of life via comprehensive needs (ß = -0.10; P < .001) and its direct effect on quality of life (ß = -0.16; P < .01) were statistically significant, suggesting a partial mediatory effect of comprehensive needs between psychological stress and quality of life. CONCLUSIONS: Our findings suggest that reducing psychological stress can improve quality of life by promoting satisfaction with comprehensive needs. IMPLICATIONS FOR PRACTICE: Interventions that help reduce psychological stress and meet the comprehensive needs of caregivers of patients with cancer can improve their quality of life.

Risk factors for post-traumatic stress disorder in nurses from the regional medical alliance during the COVID-19 epidemic: A prospective cross-sectional study.

Mental health issues among nursing professionals have been increasingly reported during the coronavirus disease (COVID-19) pandemic. However, there is a paucity of research on post-traumatic stress disorder (PTSD) among nurses working in Medical Alliances. In this study, we aimed to investigate the risk factors associated with PTSD in the Regional Medical Alliance (MA) in Shantou (China) during the COVID-19 pandemic. A total of 1286 nurses from four MA hospitals participated in the study from February to March 2020. Our findings revealed that the incidences of PTSD, depression, anxiety, and sleep disorders among nurses from MA were 15.6%, 35.5%, 18.3%, and 36.4%, respectively. Moreover, PTSD was positively correlated with depression, anxiety, and sleep disorders. In addition, the results of logistic regression analysis showed that working in a tertiary hospital, older age, more severe depression, more severe anxiety, and prevalent sleep disorders were independent risk factors for PTSD among nurses. Therefore, mental health interventions targeting high-risk nurses in MA with an incidence of PTSD are urgently needed.

Prognostic factors of sepsis in children with acute leukemia admitted to the pediatric intensive care unit.

OBJECTIVE: To analyze the prognostic factors of sepsis in children with acute leukemia admitted to the pediatric intensive care unit (PICU) and to compare the efficacy of different scoring systems for predicting the outcome of children. METHODS: Patients with an acute leukemia diagnosis admitted to a tertiary care university hospital PICU due to sepsis during chemotherapy between May 2015 and August 2022 were retrospectively analyzed through an electronic medical record system. RESULTS: During this period, 693 children with acute leukemia initially diagnosed were admitted to the center, and 155 (22.3%) of them were transferred to PICU due to deterioration of the disease during treatment. Total 109 (70.3%) patients were transferred to PICU due to sepsis. Here, 17 patients was excluded (prior treatment from another hospital; referring from other hospitals; discontinued treatment; incomplete medical record). Of the 92 patients studied, the mortality rate was 35.9%. Multivariate analysis revealed that remission status, lactate level, invasive mechanical ventilation (IMV), and inotropic support within 48 hours after PICU transfer were independent risk factors for PICU mortality. The pediatric sequential organ failure assessment (PSOFA) score had the greatest predictive validity for hospital mortality (area under the receiver operating characteristic curve [AUROC]: 0.83, 95% confidence intervals [CI]: 0.74-0.92), followed by the pediatric early warning score (PEWS) (0.82, 0.73-0.91) and pediatric critical illness score (PCIS) (0.79, 0.69-0.88). CONCLUSION: The mortality rate among children with acute leukemia complicated with sepsis is high after being transferred to the PICU. Various scoring systems can be used to monitor the clinical status of patients, identify sepsis early, detect critical illness, and determine the optimal time for transfer to the PICU for supportive treatment, thereby improving the prognosis of these patients.

Population pharmacokinetics of posaconazole in Chinese pediatric patients with acute leukaemia: Effect of food on bioavailability and dose optimization.

This study aimed to investigate the effect of food on the pharmacokinetics of posaconazole suspension in pediatric patients with acute leukaemia and to recommend optimal dosing strategies. This single-site, prospective, open-label, observational study was conducted in 42 patients and included 186 plasma concentrations of posaconazole. Sparse data were analyzed using population pharmacokinetic modeling. Monte Carlo simulations were conducted to predict the morning trough concentrations at steady-state with the proposed dose of 2-7 mg/kg three times daily (tid) or four times daily (qid) for bodyweights of 10-36 kg. The target concentrations were 700 ng/mL for prophylaxis and 1000 ng/mL for treatment. Dosage regimens with percentage of target attainment (PTA) ≥70% were recommended. A one-compartment model with allometric scaling adequately described the pharmacokinetic profile. The apparent clearance was 9.05 L/h (95% confidence interval [CI] 7.14-11.09) and the apparent volume of distribution was 283 L (95% CI 168-491) for a typical individual of 17.5 kg. The relative bioavailability with high-fat diet was as high as 1.95-fold compared with regular food. Following the intake of regular meals, 4 mg/kg qid was adequate with a PTA ≥ 71.8% for prophylaxis. A dosage of 6 mg/kg qid under a regular diet reached a PTA ≥ 73.4% for treatment. The recommended dosage of posaconazole for prophylaxis and treatment could be predicted by the pharmacokinetic model based on bodyweight and diet type in pediatric patients.

Case report: Compound heterozygous mutations in the KDSR gene cause progressive keratodermia and thrombocytopenia.

KDSR (3-ketodihydrosphingosine reductase) is a short-chain dehydrogenase located in the endoplasmic reticulum. Mutations in KDSR cause defects in ceramides, which play a key role in the biological processes of the skin and other tissues. Herein, we report a case of compound heterozygous mutations in KDSR that caused progressive keratodermia and thrombocytopenia in a 2-year-old male patient.

Case Report: Reversible Hyperglycemia Following Rapamycin Treatment for Atypical Choroid Plexus Papilloma in an Infant.

In this study, atypical choroid plexus papilloma was treated with high-dose rapamycin for 17 days preoperatively in an infant. Rapamycin significantly reduced the blood supply to the tumor while reducing the tumor volume, and most of the tumor was resected successfully. However, the infant developed hyperglycemia related to the rapamycin dose, which was effectively controlled by adjusting the dose and applying insulin.

GD2-specific chimeric antigen receptor-modified T cells for the treatment of refractory and/or recurrent neuroblastoma in pediatric patients.

PURPOSE: This study aimed to evaluate the safety and efficacy of chimeric antigen receptor (CAR) disialoganglioside 2 (GD2)-specific (4SCAR-GD2) T cells for treatment of refractory and/or recurrent neuroblastoma (NB) in pediatric patients. EXPERIMENTAL DESIGN: A phase I clinical study using 4SCAR-GD2 T cells for the treatment of NB in pediatric patients was conducted. This study was registered at www. CLINICALTRIALS: gov (NCT02765243). A lentiviral CAR with the signaling domains of CD28/4-1BB/CD3ζ-iCasp9 was transduced into activated T cells. The response to 4SCAR-GD2 T-cell treatment, and 4SCAR-GD2 T-cell expansion and persistence in patients were evaluated. Toxicities were determined based on the National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE) v4.03. RESULTS: Twelve patients were enrolled and finally ten patients were included in this clinical trial which started from January 1, 2016, to August 1, 2017. These patients had progressive disease (PD) before CAR T-cell infusion. After 4SCAR-GD2 T-cell treatment, 6 (6/10) had stable disease (SD) at 6 months, and 4 (4/10) remained SD at 1 year and alive after 3-4 years of follow-up. Six patients died due to disease progression by the end of July 1, 2020. The median overall survival (OS) time was 25 months (95% CI, 0.00-59.43), and the median progression-free survival (PFS) time was 8 months (95% CI, 0.25-15.75). Grade 3 or 4 hematological toxicities were the common adverse events frequently occurred after fludarabine and cyclophosphamide (Flu/cy) chemotherapy. Grade 1-2 toxicities such as cytokine release syndrome (CRS) and neuropathic pain were common, but were transient and mild. CONCLUSIONS: The 4SCAR-GD2 T-cell therapy demonstrated antitumor effect and manageable toxicities, indicating its potential to benefit children with refractory and/or recurrent NB.

Prognostic Value and Outcome for ETV6/RUNX1-Positive Pediatric Acute Lymphoblastic Leukemia: A Report From the South China Children's Leukemia Group.

PURPOSE: To analyzed the outcome of ETV6/RUNX1-positive pediatric acute B lymphoblastic leukemia (B-ALL) with the aim of identifying prognostic value. METHOD: A total of 2,530 pediatric patients who were diagnosed with B-ALL were classified into two groups based on the ETV6/RUNX1 status by using a retrospective cohort study method from February 28, 2008, to June 30, 2020, at 22 participating ALL centers. RESULTS: In total, 461 (18.2%) cases were ETV6/RUNX1-positive. The proportion of patients with risk factors (age <1 year or ≥10 years, WB≥50×109/L) in ETV6/RUNX1-positive group was significantly lower than that in negative group (P<0.001), while the proportion of patients with good early response (good response to prednisone, D15 MRD < 0.1%, and D33 MRD < 0.01%) in ETV6/RUNX1-positive group was higher than that in the negative group (P<0.001, 0.788 and 0.004, respectively). Multivariate analysis of 2,530 patients found that age <1 or ≥10 years, SCCLG-ALL-2016 protocol, and MLL were independent predictor of outcome but not ETV6/RUNX1. The EFS and OS of the ETV6/RUNX1-positive group were significantly higher than those of the negative group (3-year EFS: 90.11 ± 4.21% vs 82 ± 2.36%, P<0.0001, 3-year OS: 91.99 ± 3.92% vs 88.79 ± 1.87%, P=0.017). Subgroup analysis showed that chemotherapy protocol, age, prednisone response, and D15 MRD were important factors affecting the prognosis of ETV6/RUNX1-positive children. CONCLUSIONS: ETV6/RUNX1-positive pediatric ALL showed an excellent outcome but lack of independent prognostic significance in South China. However, for older patients who have the ETV6/RUNX1 fusion and slow response to therapy, to opt for more intensive treatment.

Development and Validation of a Hydrophilic Interaction Liquid Chromatography Tandem Mass Spectrometry Method for the Determination of Asparagine in Human Serum.

L-Asparagine (ASN) is the catalyze substrate of L-asparaginase (ASNase), which is an important drug for acute lymphoblastic leukemia (ALL) patients. The ASN level is found to be closely associated with the effectiveness of ASNase treatment. In this study, a hydrophilic interaction liquid chromatography tandem mass spectrometry (HILIC-MS/MS) method was developed for the determination of ASN in the human serum using a stable isotope-labeled internal standard (ASN-D3). Serum samples were prepared by a one-step precipitation procedure using methanol and separated by an Agilent HILIC Plus column with the mobile phase of methanol-water (95 : 5, v/v, containing 5 mM ammonium formate and 0.1% formic acid), at a constant flow rate of 0.3 mL/min. Mass spectrometric analysis was conducted using multiple-reaction monitoring in the positive electrospray ionization mode. Serum ASN concentrations were determined over a linear calibration curve range of 2-200 µM, with acceptable accuracies and precisions. The validated HILIC-MS/MS method was successfully applied to the quantification of ASN levels in the serum from patients with ALL. Collectively, the research may shed new light on an alternative rapid, simple, and convenient quantitative method for determination of serum ASN in ALL patients treated with ASNase.

Endoplasmic reticulum stress plays an important role in methotrexate-related cognitive impairment in adult rats.

The patients receiving methotrexate (MTX) treatment are inclined to suffer from cognition impairment, since MTX can induce apoptosis of neurons, while the underlying molecular mechanisms remain unknown. Thus we hypothesized that MTX-induced apoptosis of hippocampal neurons via activating endoplasmic reticulum stress (ERS) pathway, which leads to cognitive impairment in adult rats. In order to confirm our hypothesis, twenty male Sprague-Dawley rats weighting 180-220 g were divided into two groups: the control group (physiological saline) and the MTX60 group (MTX 60 mg/kg). Spatial memory was assayed by the Morris water maze test (MWM). In the mean time, another twenty-four rats were divided into four groups: the control group (physiological saline), MTX60 (MTX, 60 mg/kg), MTX100 (MTX, 100 mg/kg) and MTX250 (MTX, 250 mg/kg). Then, we observed the pathological changes of the hippocampus by hematoxylin-eosin stained. The expressions of C/EBP homologous protein (CHOP) and caspase-12 in the hippocampus were determined by Western blot and immunofluorescence. The apoptosis of neurons were assessed by TUNEL assay. The Morris water maze test showed that MTX induced spatial memory impairment in adult rats (P<0.05). The degenerated or apoptotic neurons were condensed and the number of neurons with nuclear pyknosis increased significantly in hippocampus CA1 area of rats in MTX groups. Additionally, both protein expressions of CHOP and caspase-12 and number of TUNEL positive cells were significantly increased in these MTX groups (P<0.05). The present results suggested that ERS mediated by apoptosis of hippocampal neurons might play an important role in the mechanism of MTX-induced cognitive impairment in adult rats.