Postoperative intra-abdominal hypertension predicts worse hospital outcomes in children after cardiac surgery: a pilot study†.

OBJECTIVES: Our goal was to determine the incidence and characteristics of postoperative intra-abdominal hypertension (IAH) in paediatric patients undergoing open-heart surgery. METHODS: This single-centre study included consecutive children (aged <16 years) who underwent open-heart surgery between July 2020 and February 2021. Patients who entered the study were followed until in-hospital death or hospital discharge. The study consisted of 2 parts. Part I was a prospective observational cohort study that was designed to discover the association between exposures and IAH. Postoperative intra-abdominal pressure was measured immediately after admission to the intensive care unit and every 6 h thereafter. Part II was a cross-sectional study to compare the hospital-related adverse outcomes between the IAH and the no-IAH cohorts. RESULTS: Postoperatively, 24.7% (38/154) of the patients exhibited IAH, whereas 3.9% (6/154) developed abdominal compartment syndrome. The majority (29/38, 76.3%) of IAH cases occurred within the first 24 h in the intensive care unit. Multivariable analysis showed that the Society of Thoracic Surgeons-European Association for Cardio-Thoracic Surgery score [odds ratio (OR) = 1.86, 95% confidence interval (CI) 1.23-2.83, P = 0.004], right-sided heart lesion (OR = 5.60, 95% CI 2.34-13.43, P < 0.001), redo sternotomy (OR = 4.35, 95% CI 1.64-11.57, P = 0.003), high baseline intra-abdominal pressure (OR = 1.43, 95% CI 1.11-1.83, P = 0.005), prolonged cardiopulmonary bypass duration (OR = 1.01, 95% CI 1.00-1.01, P = 0.005) and deep hypothermic circulatory arrest (OR = 5.14, 95% CI 1.15-22.98, P = 0.032) were independent predictors of IAH occurrence. IAH was associated with greater inotropic support (P < 0.001), more gastrointestinal complications (P = 0.001), sepsis (P = 0.003), multiple organ dysfunction syndrome (P < 0.001) and prolonged intensive care unit stay (z = -4.916, P < 0.001) and hospitalization (z = -4.710, P < 0.001). The occurrence of a composite outcome (P = 0.009) was significantly increased in patients with IAH. CONCLUSIONS: IAH is common in children undergoing cardiac surgery and is associated with worse hospital outcomes. Several factors may be associated with the development of IAH, including basic cardiac physiology and perioperative factors. TRIAL INFORMATION: This study was registered in the Chinese Clinical Trial Registry (Trial number: ChiCTR2000034322)URL site: https://www.chictr.org.cn/hvshowproject.html?id=41363&v=1.4.

Safety and feasibility of ultrasound-guided serratus anterior plane block and intercostal nerve block for management of post-sternotomy pain in pediatric cardiac patients: A prospective, randomized trial.

BACKGROUND: Postoperative analgesia in the cardiothoracic ICU has traditionally relied on intravenous opioids. Thoracic nerve blocks are attractive alternatives for analgesia that reduce the requirement for opioids, but their safety and feasibility remain unclear. METHODS: Sixty children were allocated randomly to three groups: group C received intravenous opioids alone, while group SAPB (deep serratus anterior plane block) and group ICNB (intercostal nerve block) received opioids combined with ultrasound-guided regional nerve blocks (0.2% ropivacaine 2.5 mg.kg-1) after patients were transferred to the ICU. The primary outcome was opioid requirement in the first 24 h after surgery. Other outcomes included the postoperative FLACC scale value, tracheal extubation time, and plasma ropivacaine concentrations after the block. RESULTS: The mean [sd] cumulative dose of opioids administered postoperatively within 24 h in the SAPB (168.6 [76.9] µg.kg-1) and ICNB groups (170.0 [86.8] µg.kg-1) were significantly lower by nearly 53% than those in group C (359.3 [125.3] µg.kg-1, p = 0.000). The tracheal extubation time was shorter in the regional block groups than that in the control group, but the difference was not statistically significant (p = 0.177). The FLACC scale values at 0, 1, 3, 6, 12, and 24 h post-extubation were similar in the three groups. The mean peak plasma ropivacaine concentrations in the SAP and ICNB groups were 2.1 [0.8] and 1.8 [0.7] mg.L-1, respectively, 10 min post-block and then slowly decreased. No noticeable complications associated with regional anesthesia were observed. CONCLUSIONS: Ultrasound-guided SAPB and ICNB provided safe and satisfactory early postoperative analgesia while reducing opioid consumption following sternotomy in pediatric patients. CLINICAL TRIAL REGISTRATION: Chinese Clinical Trial Registry ChiChiCTR2100046754.

Specific Clearance of Lipopolysaccharide from Blood Based on Peptide Bottlebrush Polymer for Sepsis Therapy.

Lipopolysaccharide (LPS) is the primary bacterial toxin that is vital to the pathogenesis and progression of sepsis associated with extremely high morbidity and mortality worldwide. However, specific clearance of LPS from circulating blood is highly challenging because of the structural complexity and its variation between/within bacterial species. Herein, a robust strategy based on phage display screening and hemocompatible peptide bottlebrush polymer design for specific clearance of targeted LPS from circulating blood is proposed. Using LPS extracted from Escherichia coli as an example, a novel peptide (HWKAVNWLKPWT) with high affinity (KD < 1.0 nм), specificity, and neutralization activity (95.9 ± 0.1%) against the targeted LPS is discovered via iterative affinity selection coupled with endotoxin detoxification screening. A hemocompatible bottlebrush polymer bearing the short peptide [poly(PEGMEA-co-PEP-1)] exhibits high LPS selectivity to reduce circulating LPS level from 2.63 ± 0.01 to 0.78 ± 0.05 EU mL-1 in sepsis rabbits via extracorporeal hemoperfusion (LPS clearance ratio > 70%), reversing the LPS-induced leukocytopenia and multiple organ damages significantly. This work provides a universal paradigm for developing a highly selective hemoadsorbent library fully covering the LPS family, which is promising to create a new era of precision medicine in sepsis therapy.

MR neurography showed brachial plexus abnormalities in syringomyelia with shoulder Charcot arthropathy: a case report.

Charcot shoulder is occasionally seen with syringomyelia. To the best of our knowledge this is the first report of brachial plexus abnormalities detected by magnetic resonance(MR) neurography in these patients. MR neurography is useful to evaluate small nerves and their disorders, and may contribute to the early diagnosis and differential diagnoses of such patients.

Ferulic acid and feruloylated oligosaccharides alleviate anxiety and depression symptom via regulating gut microbiome and microbial metabolism.

Incidence of anxiety and depression has been surging in recent years, causing unignorable mental health crisis across the globe. Mounting studies demonstrated that overgrowth of detrimental gut microbes is driving the development of anxiety and depression. Our previous studies suggested that ferulic acid (FA) and feruloylated oligosaccharides (FOs) were potent in regulating gut microbiome and microbial metabolism in a variety of disease settings, including neuroinflammation. Given the increasing evidence solidifying the role of gut-brain axis in neurological disorders, we here investigated the therapeutic potential of FA and FOs in anxiety and depression. In present study we found that FA and FOs effectively alleviated anxiety and depression-like behavior in mice, while increasing the abundance of Firmicutes, Solibacillus, Acinetobacter and Arthrobacter, and decreasing the abundance of Parabacteroides, Oscollospira and Rummeliibacillus. In addition, FA and FOs were efficacious in enhancing phenylalanine, tyrosine and tryptophan biosynthesis, phenylalanine and caffeine metabolism in mice having depression. Our results validated FA and FOs as effective nutrition to prevent anxiety and depression, as well as provided mechanistic insight into their anti-anxiety and anti-depression function. We suggested that FOs mitigated the symptom of depression in mice potentially via changing gut microbiome structure and microbial metabolism.

Effects of exercise interventions on cancer-related fatigue in breast cancer patients: an overview of systematic reviews.

OBJECTIVE: This overview of systematic reviews aims to critically appraise and consolidate evidence from current systematic reviews (SRs)/meta-analyses on the effects of exercise interventions on cancer-related fatigue (CRF) in breast cancer patients. METHODS: SRs/meta-analyses that explored the effects of exercise interventions on CRF in breast cancer patients compared with the routine methods of treatment and care were retrieved from nine databases. The methodological quality of the included SRs was appraised using A MeaSurement Tool to Assess systematic Reviews II (AMSTAR II). The Grading of Recommendations Assessment, Development and Evaluation (GRADE) was used to calculate the grading of outcomes in the included SRs. The exercise type, frequency, duration, and inclusion/absence of supervision were further evaluated with subgroup analyses. The Stata 16.0 software was utilized for data analysis. RESULTS: Twenty-nine reviews were included. The overall methodological quality and level of evidence of the included reviews were unsatisfactory, with only three reviews rated as high methodological quality and no review identified as high-quality evidence. Moderate certainty evidence indicated that exercise could improve fatigue in breast cancer patients (SMD = - 0.40 [95%CI - 0.58, - 0.22]; P = 0.0001). Subgroup analysis based on the types of exercise showed that yoga (SMD = - 0.30 [95%CI - 0.56, - 0.05]; I2 = 28.7%) and aerobic exercise (SMD = - 0.29 [95%CI - 0.56, - 0.02]; I2 = 16%) had a significantly better effect on CRF in breast cancer patients; exercising for over 6 months (SMD = - 0.88 [95%CI - 1.59, - 0.17]; I2 = 42.7%; P = 0.0001), three times per week (SMD = - 0.77 [95%CI - 1.04, - 0.05]; I2 = 0%; P = 0.0001), and for 30 to 60 min per session (SMD = - 0.81 [95%CI - 1.15, - 0.47]; I2 = 42.3%; P = 0.0001) can contribute to a moderate improvement of CRF. Supervised exercise (SMD = - 0.48 [95%CI - 0.77, - 0.18]; I2 = 87%; P = 0.001) was shown to relieve CRF. CONCLUSION: Exercise played a favorable role in alleviating CRF in breast cancer. Yoga was recommended as a promising exercise modality for CRF management in the majority of the included studies. Exercising for at least three times per week with 30 to 60 min per session could be recommended as a suitable dosage for achieving improvement in CRF. Supervised exercise was found to be more effective in alleviating CRF than unsupervised exercise. More rigorously designed clinical studies are needed to specify the exact exercise type, duration, frequency, and intensity to have an optimal effect on CRF in breast cancer patients. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: CRD42020219866.

Effects of single-nucleotide polymorphism on the pharmacokinetics and pharmacodynamics of metformin.

INTRODUCTION: Metformin has been recognized as the first-choice drug for type 2 diabetes mellitus (T2DM). The potency of metformin in the treatment of type 2 diabetes has always been in the spotlight and shown significant individual differences. Based on previous studies, the efficacy of metformin is related to the single-nucleotide polymorphisms of transporter genes carried by patients, amongst which a variety of gene polymorphisms of transporter and target protein genes affect the effectiveness and adverse repercussion of metformin. AREAS COVERED: Here, we reviewed the current knowledge about gene polymorphisms impacting metformin efficacy based on transporter and drug target proteins. EXPERT OPINION: The reason for the difference in clinical drug potency of metformin can be attributed to the gene polymorphism of drug transporters and drug target proteins in the human body. Substantial evidence shows that genetic polymorphisms in transporters such as organic cation transporter 1 (OCT1) and organic cation transporter 2 (OCT2) affect the glucose-lowering effectiveness of metformin. However, optimization of individualized dosing regimens of metformin is necessary to clarify the role of several polymorphisms.

Differentiation between glioma recurrence and treatment effects using amide proton transfer imaging: A mini-Bayesian bivariate meta-analysis.

Background: Amide proton transfer (APT) imaging as an emerging MRI approach has been used for distinguishing tumor recurrence (TR) and treatment effects (TEs) in glioma patients, but the initial results from recent studies are different. Aim: The aim of this study is to systematically review and quantify the diagnostic performance of APT in assessing treatment response in patients with post-treatment gliomas. Methods: A systematic search in PubMed, EMBASE, and the Web of Science was performed to retrieve related original studies. For the single and added value of APT imaging in distinguishing TR from TEs, we calculated pooled sensitivity and specificity by using Bayesian bivariate meta-analyses. Results: Six studies were included, five of which reported on single APT imaging parameters and four of which reported on multiparametric MRI combined with APT imaging parameters. For single APT imaging parameters, the pooled sensitivity and specificity were 0.85 (95% CI: 0.75-0.92) and 0.88 (95% CI: 0.74-0.97). For multiparametric MRI including APT, the pooled sensitivity and specificity were 0.92 (95% CI: 0.85-0.97) and 0.83 (95% CI: 0.55-0.97), respectively. In addition, in the three studies reported on both single and added value of APT imaging parameters, the combined imaging parameters further improved diagnostic performance, yielding pooled sensitivity and specificity of 0.91 (95% CI: 0.80-0.97) and 0.92 (95% CI: 0.79-0.98), respectively, but the pooled sensitivity was 0.81 (95% CI: 0.65-0.93) and specificity was 0.82 (95% CI: 0.61-0.94) for single APT imaging parameters. Conclusion: APT imaging showed high diagnostic performance in assessing treatment response in patients with post-treatment gliomas, and the addition of APT imaging to other advanced MRI techniques can improve the diagnostic accuracy for distinguishing TR from TE.

Aspartic Acid-Modified Phospholipids Regulate Cell Response and Rescue Memory Deficits in APP/PS1 Transgenic Mice.

Misfolding and accumulation of amyloid-ß (Aß) to form senile plaques are the main neuropathological signatures of Alzheimer's disease (AD). Decreasing Aß production, inhibiting Aß aggregation, and clearing Aß plaques are thus considered an important strategy for AD treatment. However, numerous drugs cannot enter the AD clinical trials due to unsatisfactory biocompatibility, poor blood-brain barrier penetration, little biomarker impact, and/or low therapeutic indicators. Here, a pair of chiral aspartic acid-modified 1,2-dipalmitoyl-sn-glycero-3-phosphoethanolamine (l- and d-Asp-DPPE) are prepared to build stabilized chiral liposomes. We find that both l- and d-liposomes are able to rescue Aß aggregation-induced apoptosis, oxidative stress, and calcium homeostasis, in which the effect of d-liposomes is more obvious than that of l-ones. Furthermore, in AD model mice (APPswe/PS1d9 double-transgenic mice), chiral liposomes not only show biosafety but also strongly improve cognitive deficits and reduce Aß deposition in the brain. Our results suggest that chiral liposomes, particularly, d-liposomes, could be a potential therapeutic approach for AD treatment. This study opens new horizons by showing that liposomes will be used for drug development in addition to delivery and targeting functions.

Prevention of ulcerative colitis by Huangqin decoction: reducing the intestinal epithelial cell apoptosis rate through the IFN-γ/JAK/ETS signalling pathway.

CONTEXT: Ulcerative colitis (UC) is a chronic idiopathic inflammatory bowel disease that is closely related to inflammation and apoptosis. The traditional Chinese medicine compound preparation Huangqin decoction (HQD) has been widely used in the clinical treatment of UC, but the specific mechanism of its function is still inconclusive. OBJECTIVE: To explore the pathogenesis of UC based on the IFN-γ/JAK/ETS signalling pathway, and to clarify the biological mechanism of HQD. MATERIALS AND METHODS: Forty 8-week-old male C57BL/6 mice were randomly divided into four groups: normal control, model, model + salazosulfapyridine group (500 mg/kg, p.o., pd) and model + HQD (9.1 g/kg, p.o., pd). Using Dextran sulphate sodium (DSS) salt (2.5%, p.o.)+high-fat diet + hot and humid environment to build a mouse model of UC. One month later, the changes of colon morphology, serum inflammatory factors, intestinal epithelial cell apoptosis and IFN-γ/JAK/ETS signalling pathway related protein changes in mice were observed. RESULTS: Compared with the model group, HQD significantly reduced the pathological score of the model mice's colon (2.60 ± 0.25 vs. 4.80 ± 0.37), and reduced the serum IFN-γ (200.30 ± 8.45 vs. 413.80 ± 6.97) and other inflammatory factors, and reduced intestinal epithelial cell apoptosis (24.85 ± 4.87 vs. 214.90 ± 39.21). In terms of mechanism, HQD down-regulated IFN-γ/JAK/ETS signalling pathway related proteins in colon tissue of UC model mice. CONCLUSIONS: These data indicate that HQD can improve UC by reducing intestinal inflammation and apoptosis, providing experimental evidence for the wide application of HQD in clinical practice of UC.

Study protocol for a single-centre randomised controlled trial to investigate the effect of lung recruitment in paediatric patients after cardiac surgery.

INTRODUCTION: A number of published studies have revealed that lung recruitment can improve oxygenation, shorten the duration of mechanical ventilation (MV) and decrease mortality in adults with acute hypoxaemic respiratory failure, especially patients with acute respiratory distress syndrome. However, few articles have assessed lung recruitment in paediatric patients, especially after cardiac surgery. This clinical trial aimed to determine whether lung recruitment can reduce the duration of MV in paediatric patients with hypoxaemic respiratory failure after cardiac surgery. METHOD AND ANALYSIS: In this trial, we will randomly assign 234 paediatric patients (aged 28 days to 14 years) within 72 hours after cardiac surgery with an arterial oxygen tension (PaO2) to fraction of inspired oxygen (FiO2) ratio (PaO2/FiO2) of <300 to either a lung recruitment group or a conventional group. The primary endpoint will be the duration of MV. The secondary endpoints will be ventilator-free days, PaO2/FiO2, respiratory system compliance, duration of non-invasive ventilation, reintubation rate, length of intensive care unit stay, length of hospital stay, occurrence of serious adverse events (barotrauma, persistent hypotension and arrhythmia), postoperative pulmonary complications. ETHICS AND DISSEMINATION: The ethics committee of West China Hospital of Sichuan University granted ethics approval for this study (20 August 2019). The results will be published in peer-reviewed journals and presented at conferences. TRIAL REGISTRATION NUMBER: ChiCTR1900025990.

Simotang Alleviates the Gastrointestinal Side Effects of Chemotherapy by Altering Gut Microbiota.

Simotang oral liquid (SMT) is a traditional Chinese medicine (TCM) consisting of four natural plants and is used to alleviate gastrointestinal side effects after chemotherapy and functional dyspepsia (FD). However, the mechanism by which SMT helps cure these gastrointestinal diseases is still unknown. Here, we discovered that SMT could alleviate gastrointestinal side effects after chemotherapy by altering gut microbiota. C57BL/6J mice were treated with cisplatin (DDP) and SMT, and biological samples were collected. Pathological changes in the small intestine were observed, and the intestinal injury score was assessed. The expression levels of the inflammatory factors IL-1ß and IL-6 and the adhesive factors Occludin and ZO-1 in mouse blood or small intestine tissue were also detected. Moreover, the gut microbiota was analyzed by high-throughput sequencing of 16S rRNA amplicons. SMT was found to effectively reduce gastrointestinal mucositis after DDP injection, which lowered inflammation and tightened the intestinal epithelial cells. Gut microbiota analysis showed that the abundance of the anti-inflammatory microbiota was downregulated and that the inflammatory microbiota was upregulated in DDP-treated mice. SMT upregulated anti-inflammatory and anticancer microbiota abundance, while the inflammatory microbiota was downregulated. An antibiotic cocktail (ABX) was also used to delete mice gut microbiota to test the importance of gut microbiota, and we found that SMT could not alleviate gastrointestinal mucositis after DDP injection, showing that gut microbiota might be an important mediator of SMT treatment. Our study provides evidence that SMT might moderate gastrointestinal mucositis after chemotherapy by altering gut microbiota.

Different Effects of Hematoma Expansion on Short-Term Functional Outcome in Basal Ganglia and Thalamic Hemorrhages.

PURPOSE: To investigate the impact of hematoma expansion (HE) on short-term functional outcome of patients with thalamic and basal ganglia intracerebral hemorrhage. METHODS: Data of 420 patients with deep intracerebral hemorrhage (ICH) that received a baseline CT scan within 6 hours from symptom onset and a follow-up CT scan within 72 hours were retrospectively analyzed. The poor functional outcome was defined as modified Rankin score (mRS) > 3 at 30 days. Receiver operating characteristic (ROC) curves for relative and absolute growth of HE were generated and compared. Multivariable logistic regression models were used to analyze the impact of HE on the functional outcome in basal ganglia and thalamic hemorrhages. The predictive values for different thresholds of HE were calculated, and correlation coefficient matrices were used to explore the correlation between the covariables. RESULTS: Basal ganglia ICH showed a higher possibility of absolute hematoma growth than thalamic ICH. The area under the curve (AUC) for absolute and relative growth of thalamic hemorrhage was lower than that of basal ganglia hemorrhage (AUC 0.71 and 0.67, respectively) in discriminating short-term poor outcome with an AUC of 0.59 and 0.60, respectively. Each threshold of HE independently predicted poor outcome in basal ganglia ICH (P < 0.001), with HE > 3 ml and > 6 ml showing higher positive predictive values and accuracy compared to HE > 33%. In contrast, thalamic ICH had a smaller baseline volume (BV, 9.55 ± 6.85 ml) and was more likely to initially involve the posterior limb of internal capsule (PLIC) (85/153, 57.82%), and the risk of HE was lower without PLIC involvement (4.76%, P = 0.009). Therefore, in multivariate analysis, the effect of thalamic HE on poor prognosis was largely replaced by BV and the involvement of PLIC, and the adjusted odds ratios (ORs) of HE was not significant (P > 0.05). CONCLUSION: Though HE is a high-risk factor for short-term poor functional outcome, it is not an independent risk factor in thalamic ICH, and absolute growth is more predictive of poor outcome than relative growth for basal ganglia ICH.

Clinical characterization of NTCP deficiency in paediatric patients : A case-control study based on SLC10A1 genotyping analysis.

Na+ -taurocholate cotransporting polypeptide deficiency (NTCPD) is a newly described disorder arising from biallelic mutations of the SLC10A1 gene. As a result of a lack of compelling evidence from case-control studies, its genotypic and phenotypic features remain open for in-depth investigation. This study aimed to explore the genotypic and clinical phenotypic characteristics of paediatric patients with NTCPD. The SLC10A1 genotypes of all NTCPD patients were confirmed by screening for the prevalent variant c.800C>T and Sanger sequencing when necessary. The clinical presentations and laboratory changes were collected, reviewed and analysed, and then qualitatively and quantitatively compared with the relevant controls. A total of 113 paediatric NTCPD patients were diagnosed while c.374dupG and c.682_683delCT were detected as two novel pathogenic mutations. Hypercholanemia was observed in 99.12% of the patients. Indirect hyperbilirubinemia in affected neonates exhibited higher positive rates in comparison to controls. Moreover, transient cholestatic jaundice, elevated liver enzymes and 25-hydroxyvitamin D (Vit D) deficiency during early infancy were more commonly observed in patients than in controls. All NTCPD patients exhibited favourable clinical outcomes as a result of symptomatic and supportive treatment. The findings enriched the SLC10A1 mutation spectrum and provided comprehensive insights into the phenotypic characteristics of NTCPD. NTCPD should be considered and SLC10A1 gene should be analysed in patients with above age-dependent clinical features. Furthermore, over investigation and intervention should be avoided in the management of NTCPD patients.

Are computed-tomography-based hematoma radiomics features reproducible and predictive of intracerebral hemorrhage expansion? an in vitro experiment and clinical study.

OBJECTIVES: To identify reproducible hematoma radiomics features (RFs) for use in predicting hematoma expansion (HE) in patients with acute intracerebral hemorrhage (ICH). METHODS: For test-retest analysis, three syringes with different volumes of blood collected at the same time (to mimic homogeneous hematoma) and a phantom (FT/HK 2000; Huake, Szechwan, China) containing three cylindrical inserts were scanned seven times within 6 h on the same CT scanner. Three additional syringes with mixed blood collected at different time points (to mimic heterogeneous hematoma) were tied together with the first three syringes as well as the phantom were scanned using modified CT acquisition parameters for intra CT analysis. A coefficient of variation below 10% served as the cutoff value for reproducibility. Finally, reproducible and potentially useful RFs were used to predict HE in 144 acute ICH patients, with the area under the receiver operating characteristic curves (AUC) used to evaluate their diagnostic performance. RESULTS: A total of 630 RFs including 18 first-order, 24 gray-level co-occurrence matrix (GLCM), 16 gray-level run length matrix (GLRLM), five neighborhood gray-tone difference matrix (NGTDM), 63 Laplacian of Gaussian (LoG), and 504 Wavelet features were evaluated. In the test-retest analysis, the percentages of reproducible RFs ranged from 42.54% (268/630) to 45.4% (286/630) for the three homogeneous hematoma samples and 79.05% (498/630) to 81.43% (513/630) for the phantom. In the intra-CT analysis, the percentages varied from 31.43% (198/630) to 42.38% (267/630) for the six hematoma samples and 48.89% (308/630) to 53.97% (340/630) for the phantom. In the in vitro experiment, 148 RFs were reproducible for all hematoma samples in both the test-retest and intra-CT analyses; however, only 80 were statistically different between homogeneous and heterogeneous hematoma samples. Finally, HE occurred in 25% (growth >6 ml, 36/144) to 31.94% (growth >3 ml or 33%, 46/144) of the patients. The AUCs in predicting HE ranged from 0.625 to 0.703. CONCLUSIONS: Only a few CT-based RFs from the in vitro hematoma were reproducible and can distinguish between homogeneous and heterogeneous hematomas. The use of RFs alone to predict HE in acute ICH showed only a moderate performance. ADVANCES IN KNOWLEDGE: Using an in vitro experiment and clinical validation, this study demonstrated for the first time that CT-based hematoma RFs can be used to predict HE in acute ICH; nonetheless, only a few RFs are reproducible and can be used for prediction.

Neonatal Intrahepatic Cholestasis caused by Citrin Deficiency: In vivo and in vitro studies of the aberrant transcription arising from two novel splice-site variants in SLC25A13.

Neonatal Intrahepatic Cholestasis caused by Citrin Deficiency (NICCD) is an autosomal recessive disease resulting from biallelic SLC25A13 mutations, and its diagnosis relies on genetic analysis. This study aimed to characterize the pathogenicity of 2 novel splice-site variants of SLC25A13 gene. Two patients (C0476 and C0556) suspected to have NICCD, their family members and 9 healthy volunteers were recruited as the research subjects. The SLC25A13 genotypes NG_012247.2(NM_014251.3): c.[852_855del]; [69+5G > A] in patient C0476 and c.[1453-1G > A]; [1751-5_1751-4ins (2684)] in patient C0556 were identified by means of polymerase chain reaction, long and accurate polymerase chain reaction, as well as Sanger sequencing. The 2 splice-site variants were absent in control databases and predicted to be pathogenic by computational analysis. The alternative splice variants in monocyte-derived macrophages from patient C0476 demonstrated exon 2 skipping [r.16_69del; p.(Val6_Lys23del)] in vivo, while minigene analysis revealed both exon 2-skipping and retained products from c.69+5G > A in vitro. In the patient C0556, an aberrant transcript [r.1453del; p.(Gly485Valfs*22)] resulting from c.1453-1G > A was detected on minigene splicing study. Thus, c.69+5G > A and c.1453-1G > A were both proved to be pathogenic. The 2 novel splice-site variants expanded the SLC25A13 mutation spectrum and provided reliable molecular markers for the definite diagnosis and genetic counseling of NICCD in the affected families.

Preoperative Hemoglobin Level, Oxygen Saturation and Postoperative Outcomes in Children With Cyanotic Congenital Heart Disease: A Propensity-Score Matching Analysis.

BACKGROUND: The optimal preoperative hemoglobin (Hb) level is difficult to define in children with cyanotic congenital heart disease (CHD) due to hypoxemia-induced secondary erythrocytosis. This retrospective study integrated preoperative Hb and pulse oxygen saturation (SpO2) using the product of Hb × SpO2 to predict postoperative outcomes in children with cyanotic CHD. PATIENTS AND METHODS: Children aged <18 years undergoing cardiac surgery with cyanotic CHD were included. The cutoff value of Hb × SpO2 was the age-adjusted lower limit of normal Hb (aaHb) in healthy children. The main outcomes were in-hospital death and the composite outcome of severe postoperative events. Multivariate logistic regression analysis and propensity score matching analysis were used to adjust for important confounders. RESULTS: The presence of preoperative Hb × SpO2 < aaHb was observed in 21.6% of cyanotic children (n = 777). Children with Hb × SpO2 < aaHb had higher in-hospital mortality (12.5% vs. 4.6%, P < 0.001) and composite outcome incidence (69.6% vs. 32.3%, P < 0.001) than those with Hb × SpO2 ≥ aaHb. After propensity score matching, 141 pairs of children were successfully matched. Multivariate analysis showed that preoperative Hb × SpO2 < aaHb was significantly associated with the composite outcome in the entire population (odds ratio = 4.092, 95% confidence interval = 2.748-6.095, P < 0.001) and the matched cohorts (odds ratio = 2.277, 95% confidence interval = 1.366-3.795, P = 0.002). CONCLUSION: Our results suggest that a preoperative Hb × SpO2 value below the lower limit of normal hemoglobin is a prognostic factor in cyanotic children undergoing cardiac surgery and is a potential criterion to evaluate preoperative anemia in this population.

Hemodynamics in Shock Patients Assessed by Critical Care Ultrasound and Its Relationship to Outcome: A Prospective Study.

BACKGROUND: Shock is one of the causes of mortality in the intensive care unit (ICU). Traditionally, hemodynamics related to shock have been monitored by broad-spectrum devices with treatment guided by many inaccurate variables to describe the pathophysiological changes. Critical care ultrasound (CCUS) has been widely advocated as a preferred tool to monitor shock patients. The purpose of this study was to analyze and broaden current knowledge of the characteristics of ultrasonic hemodynamic pattern and investigate their relationship to outcome. METHODS: This prospective study of shock patients in CCUS was conducted in 181 adult patients between April 2016 and June 2017 in the Department of Intensive Care Unit of West China Hospital. CCUS was performed within the initial 6 hours after shock patients were enrolled. The demographic and clinical characteristics, ultrasonic pattern of hemodynamics, and outcome were recorded. A stepwise bivariate logistic regression model was established to identify the correlation between ultrasonic variables and the 28-day mortality. RESULTS: A total of 181 patients with shock were included in our study (male/female: 113/68). The mean age was 58.2 ± 18.0 years; the mean Acute Physiology and Chronic Health Evaluation II (APACHE II score) was 23.7 ± 8.7, and the 28-day mortality was 44.8% (81/181). The details of ultrasonic pattern were well represented, and the multivariate analysis revealed that mitral annular plane systolic excursion (MAPSE), mitral annular peak systolic velocity (S'-MV), tricuspid annular plane systolic excursion (TAPSE), and lung ultrasound score (LUSS) were the independent risk factors for 28-day mortality in our study, as well as APACHE II score, PaO2/FiO2, and lactate (p = 0.047, 0.041, 0.022, 0.002, 0.027, 0.028, and 0.01, respectively). CONCLUSIONS: CCUS exam on admission provided valuable information to describe the pathophysiological changes of shock patients and the mechanism of shock. Several critical variables obtained by CCUS were related to outcome, hence deserving more attention in clinical decision-making. Trial Registration. The study was approved by the Ethics Committee of West China Hospital Review Board for human research with the following reference number 201736 and was registered on ClinicalTrials. This trial is registered with NCT03082326 on 3 March 2017 (retrospectively registered).

UPLC-Q-Exactive Orbitrap MS Analysis for Identification of Lipophilic Components in Citri Sarcodactylis Fructus from Different Origins in China Using Supercritical CO2 Fluid Extraction Method.

To thoroughly evaluate the quality of Citri Sarcodactylis Fructus (CSF) and acquire knowledge of the lipophilic components of CSF from different origins, a simple and efficient approach based on supercritical fluid extraction (SFE) combined with ultraperformance liquid chromatography plus Q-Exactive Orbitrap tandem mass spectrometry (UPLC-Q-Exactive Orbitrap/MS) detection for the discrimination of components from CSF was set up for the first time in this work. Eight batches of CSF samples from five main producing areas were extracted by SFE under optimized conditions, and then SFE extracts were dissected via UPLC-Q-Exactive Orbitrap/MS. The results indicated that 39 lipophilic compounds were successfully separated and unambiguously or tentatively identified, where 4 coumarins, 6 polymethoxyflavones, 3 phthalides, 6 terpenes, and 4 phenolics were not reported formerly. It was illustrated that CSF may be abundant in polymethoxyflavones, as in coumarins. Moreover, there were significant differences in the components of CSF from different origins. Especially, coumarin, dehydrocostus lactone, atractylenolide II, and atractylenolide I were exclusively found in CSF from the Guangdong province; isopsoralen was almost exclusively found in CSF from the Guangxi province; and ferulic acid was exclusively found in CSF from the Zhejiang province. These observations indicated that SFE joint with UPLC-Q-Exactive Orbitrap/MS owing to the potential of characterizing the lipophilic components could be used to promote quality assessment and chemotaxonomic investigation in phytology sciences of CSF.

Urgent recommendation and practice of prevention and control of novel coronavirus disease 2019 (COVID-19) in intensive care units in West China Hospital of Sichuan University during the epidemics / 中国胸心血管外科临床杂志

@#Objective    To provide recommendations for the management of intensive care unit patients without novel coronavirus disease 2019 (COVID-19). Methods    We set up a focus group urgently and identified five key clinical issues through discussion. Total 23 databases or websites including PubMed, National Guideline Clearing-House, Chinese Center for Disease Control and Prevention and so on were searched from construction of the library until February 28, 2020. After group discussion and collecting information, we used GRADE system to classify the evidence and give recommendations. Then we apply the recommendations to manage pediatric intensive care unit in the department of  critical care medicine in our hospital. Results    We searched 13 321 articles and finally identified 21 liteteratures. We discussed twice, and five recommendations were proposed: (1) Patients should wear medical surgical masks; (2) Family members are not allowed to visit the ward and video visitation are used; (3) It doesn’t need to increase the frequency of environmental disinfection; (4) We should provide proper health education about the disease to non-medical staff (workers, cleaners); (5) Medical staff do not need wear protective clothing. We used these recommendations in intensive care unit management for 35 days and there was no novel coronavirus infection in patients, medical staff or non-medical staff. Conclusion    The use of evidence-based medicine for emergency recommendation is helpful for the scientific and efficient management of wards, and is also suitable for the management of general intensive care units in emergent public health events.