Causal Association of Iron Status With Functional Outcome After Ischemic Stroke.

BACKGROUND: Iron status has been associated with functional outcomes after ischemic stroke (IS). Nonetheless, this association may be affected by confounders. We perform Mendelian randomization to clarify the causal association between iron status and functional outcome after IS. METHODS: We obtained summary-level statistics related to iron status biomarkers from a meta-analysis of a gene-wide association study conducted by the Genetics of Iron Status Consortium, which included 11 discovery cohorts and 8 replication cohorts. We also took genetic variants related to 4 biomarkers of iron status from combining gene-wide association study results of Iceland, the United Kingdom, and Denmark to perform a replicate Mendelian randomization analysis. This data set included 4 iron status biomarkers, namely, ferritin, total iron binding capacity, iron, and transferrin saturation (TSAT). The confounders in these data sets have been adjusted to mitigate the collider bias. We acquired summary statistics data sets for functional outcomes following IS from the gene-wide association study meta-analysis conducted by the Genetics of Ischemic Stroke Functional Outcome Consortium. The genetic estimates for functional outcomes at 90 days after IS were evaluated by the modified Rankin Scale score, including 3741 cases with good functional outcomes (modified Rankin Scale score, 0-2) and 2280 subjects with poor functional outcomes poststroke (modified Rankin Scale score, 3-6). Inverse variance weighting was used as the primary method, complemented by sensitivity analyses for pleiotropy and increasing robustness. RESULTS: Reported with odds ratios (ORs) of stroke outcome with per SD unit increase in genetically determined iron status biomarker, TSAT and iron were associated with poor functional outcome after IS (TSAT: OR, 1.36 [95% CI, 1.23-1.50]; P=2.27×10-9; iron: OR, 1.44 [95% CI, 1.13-1.85]; P=0.0033). In replicate Mendelian randomization analysis, the detrimental effects of iron on poor functional outcome after IS remained stable (OR, 1.60 [95% CI, 1.24-2.08]; P=0.0003). In the meta-analysis, iron and TSAT were associated with poor functional outcomes after IS (TSAT: ORmeta, 1.35 [95% CI, 1.23-1.48]; iron: ORmeta, 1.51 [95% CI, 1.27-1.81]). Through sensitivity analyses and reverse Mendelian randomization analyses, we confirmed the robustness of the results. CONCLUSIONS: Our study provides evidence suggesting a potential causal relationship between iron status and poor functional outcomes after IS. Future studies are required to illuminate the underlying mechanism.

Treatment Modalities and Outcomes in Brainstem Cavernous Malformations: A Large Multicenter Observational Cohort Study.

BACKGROUND: Symptomatic brainstem cavernous malformations (BSCMs) pose a high risk of morbidity and mortality due to recurrent hemorrhage, warranting aggressive management. However, few studies have compared the effectiveness of different treatment modalities for BSCMs. We aimed to assess the association of treatment modalities with recurrent hemorrhage and neurological outcomes in patients with BSCM. METHODS: We conducted a retrospective cohort study using an observational registry database covering population of southwest and southeast China. Adult patients with BSCM were included and followed up between March 1, 2011, to March 31, 2023. We compared outcomes between microsurgery and stereotactic radiosurgery (SRS) in propensity score-matched case pairs, incorporating demographic, medical history, and lesion characteristics. The outcomes studied included recurrent hemorrhage and poor prognosis (defined as a Glasgow Outcome Scale score, <4). Absolute rate differences and hazard ratios (HRs) with 95% CIs were calculated using Cox models. RESULTS: Among 736 diagnosed patients with BSCM, 96 (48 matched pairs) were included after exclusions and propensity score matching (mean age, 43.1 [SD, 12.1] years; 50% women). During the median 5-year follow-up, no significant differences in recurrent hemorrhage (4.2% [microsurgery] versus 14.6% [SRS], HR, 3.90 [95% CI, 0.46-32.65]; P=0.21) and poor prognosis (12.5% [microsurgery] versus 8.3% [SRS], HR, 0.29 [95% CI, 0.08-1.08]; P=0.07) were observed between microsurgery and SRS recipients. Furthermore, either microsurgery or SRS correlated with fewer recurrent hemorrhage (HR, 0.09 [95% CI, 0.02-0.39]; P=0.001; HR, 0.21 [95% CI, 0.07-0.69]; P=0.01) compared with conservative treatment. CONCLUSIONS: In this study, both microsurgery and SRS were safe and effective for BSCM, demonstrated comparable outcomes in recurrent hemorrhage and poor prognosis. However, interpretation should be cautious due to the potential for residual confounding. REGISTRATION: URL: https://www.chictr.org.cn/; Unique identifier: ChiCTR2300070907.

Development and Validation of a Supplementary Grading Scale for Outcomes of Brainstem Cavernous Malformations.

BACKGROUND: Surgical risk assessment is intriguing for clinical decision-making of brainstem cavernous malformation (BSCM) treatment. While the BSCM grading scale, encompassing size, developmental venous anomaly, crossing axial midpoint, age, and timing of intervention, is increasingly utilized, the clinical relevance of neurological fluctuation and recurrent hemorrhage has not been incorporated. This study aimed to propose a supplementary grading scale with enhanced predictive efficacy. METHODS: Using a retrospective nationwide registry of consecutive patients with BSCMs undergoing surgery in China from March 2011 to May 2023, a new supplementary BSCM grading scale was developed from a derivative cohort of 260 patients and validated in an independent concurrent cohort of 67 patients. The primary outcome was unfavorable neurological function (modified Rankin Scale score >2) at the latest follow-up. The performance of the supplementary grading system was evaluated for discrimination, calibration, and clinical utility and further compared with its original counterpart. RESULTS: Over a follow-up of at least 6 months after surgery, the unfavorable outcomes were 31% in the overall cohort (101/327 patients). A preoperative motor deficit (odds ratio, 3.13; P=0.001), recurrent hemorrhage (odds ratio, 3.05; P<0.001), timing of intervention (odds ratio, 7.08; P<0.001), and crossing the axial midpoint (odds ratio, 2.57; P=0.006) were associated with the unfavorable outcomes and composed the initial Huashan grading variables. A supplementary BSCM grading system was subsequently developed by incorporating the Huashan grading variables into the original BSCM grading scale. The predictive capability of the supplementary scale was consistently superior to the original counterpart in either the derivative cohort (area under the receiver operating characteristic curve, 0.74 [95% CI, 0.68-0.80] for the supplementary versus 0.68 [95% CI, 0.61-0.74] for the original) or the validation cohort (0.75 [95% CI, 0.62-0.87] versus 0.64 [95% CI, 0.48-0.81]). CONCLUSIONS: This study highlights the neurological relevance of BSCM hemorrhage in surgical risk assessment. Via compositing preoperative motor function and recurrent hemorrhages, a supplementary grading scale may improve a dynamic risk assessment for clinical decisions in the management of BSCMs.

Electrically Induced Crystal Field Distortion in a Ferroelectric Perovskite Revealed by Electron Paramagnetic Resonance.

The magnetoelectric material has attracted multidisciplinary interest in the past decade for its potential to accommodate various functions. Especially, the external electric field can drive the quantum behaviors of such materials via the spin-electric coupling effect, with the advantages of high spatial resolution and low energy cost. In this work, the spin-electric coupling effect of Mn2+-doped ferroelectric organic-inorganic hybrid perovskite [(CH3)3NCH2Cl]CdCl3 with a large piezoelectric effect was investigated. The electric field manipulation efficiency for the allowed transitions was determined by the pulsed electron paramagnetic resonance. The orientation-included Hamiltonian of the spin-electric coupling effect was obtained via simulating the angle-dependent electric field modulated continuous-wave electron paramagnetic resonance. The results demonstrate that the applied electric field affects not only the principal values of the zero-field splitting tensor but also its principal axis directions. This work proposes and exemplifies a route to understand the spin-electric coupling effect originating from the crystal field imposed on a spin ion being modified by the applied electric field, which may guide the rational screening and designing of hybrid perovskite ferroelectrics that satisfy the efficiency requirement of electric field manipulation of spins in quantum information applications.

The third Intensive Care Bundle with Blood Pressure Reduction in Acute Cerebral Haemorrhage Trial (INTERACT3): an international, stepped wedge cluster randomised controlled trial.

BACKGROUND: Early control of elevated blood pressure is the most promising treatment for acute intracerebral haemorrhage. We aimed to establish whether implementing a goal-directed care bundle incorporating protocols for early intensive blood pressure lowering and management algorithms for hyperglycaemia, pyrexia, and abnormal anticoagulation, implemented in a hospital setting, could improve outcomes for patients with acute spontaneous intracerebral haemorrhage. METHODS: We performed a pragmatic, international, multicentre, blinded endpoint, stepped wedge cluster randomised controlled trial at hospitals in nine low-income and middle-income countries (Brazil, China, India, Mexico, Nigeria, Pakistan, Peru, Sri Lanka, and Viet Nam) and one high-income country (Chile). Hospitals were eligible if they had no or inconsistent relevant, disease-specific protocols, and were willing to implement the care bundle to consecutive patients (aged ≥18 years) with imaging-confirmed spontaneous intracerebral haemorrhage presenting within 6 h of the onset of symptoms, had a local champion, and could provide the required study data. Hospitals were centrally randomly allocated using permuted blocks to three sequences of implementation, stratified by country and the projected number of patients to be recruited over the 12 months of the study period. These sequences had four periods that dictated the order in which the hospitals were to switch from the control usual care procedure to the intervention implementation of the care bundle procedure to different clusters of patients in a stepped manner. To avoid contamination, details of the intervention, sequence, and allocation periods were concealed from sites until they had completed the usual care control periods. The care bundle protocol included the early intensive lowering of systolic blood pressure (target <140 mm Hg), strict glucose control (target 6·1-7·8 mmol/L in those without diabetes and 7·8-10·0 mmol/L in those with diabetes), antipyrexia treatment (target body temperature ≤37·5°C), and rapid reversal of warfarin-related anticoagulation (target international normalised ratio <1·5) within 1 h of treatment, in patients where these variables were abnormal. Analyses were performed according to a modified intention-to-treat population with available outcome data (ie, excluding sites that withdrew during the study). The primary outcome was functional recovery, measured with the modified Rankin scale (mRS; range 0 [no symptoms] to 6 [death]) at 6 months by masked research staff, analysed using proportional ordinal logistic regression to assess the distribution in scores on the mRS, with adjustments for cluster (hospital site), group assignment of cluster per period, and time (6-month periods from Dec 12, 2017). This trial is registered at Clinicaltrials.gov (NCT03209258) and the Chinese Clinical Trial Registry (ChiCTR-IOC-17011787) and is completed. FINDINGS: Between May 27, 2017, and July 8, 2021, 206 hospitals were assessed for eligibility, of which 144 hospitals in ten countries agreed to join and were randomly assigned in the trial, but 22 hospitals withdrew before starting to enrol patients and another hospital was withdrawn and their data on enrolled patients was deleted because regulatory approval was not obtained. Between Dec 12, 2017, and Dec 31, 2021, 10 857 patients were screened but 3821 were excluded. Overall, the modified intention-to-treat population included 7036 patients enrolled at 121 hospitals, with 3221 assigned to the care bundle group and 3815 to the usual care group, with primary outcome data available in 2892 patients in the care bundle group and 3363 patients in the usual care group. The likelihood of a poor functional outcome was lower in the care bundle group (common odds ratio 0·86; 95% CI 0·76-0·97; p=0·015). The favourable shift in mRS scores in the care bundle group was generally consistent across a range of sensitivity analyses that included additional adjustments for country and patient variables (0·84; 0·73-0·97; p=0·017), and with different approaches to the use of multiple imputations for missing data. Patients in the care bundle group had fewer serious adverse events than those in the usual care group (16·0% vs 20·1%; p=0·0098). INTERPRETATION: Implementation of a care bundle protocol for intensive blood pressure lowering and other management algorithms for physiological control within several hours of the onset of symptoms resulted in improved functional outcome for patients with acute intracerebral haemorrhage. Hospitals should incorporate this approach into clinical practice as part of active management for this serious condition. FUNDING: Joint Global Health Trials scheme from the Department of Health and Social Care, the Foreign, Commonwealth & Development Office, and the Medical Research Council and Wellcome Trust; West China Hospital; the National Health and Medical Research Council of Australia; Sichuan Credit Pharmaceutic and Takeda China.

Causal association between circulating inflammatory cytokines and intracranial aneurysm and subarachnoid hemorrhage.

BACKGROUND AND PURPOSE: The causal association between inflammatory cytokines and the development of intracranial aneurysm (IA), unruptured IA (uIA) and subarachnoid hemorrhage (SAH) lacks clarity. METHODS: The summary-level datasets for inflammatory cytokines were extracted from a genome-wide association study of the Finnish Cardiovascular Risk in Young Adults Study and the FINRISK survey. The summary statistics datasets related to IA, uIA and SAH were obtained from the genome-wide association study meta-analysis of the International Stroke Genetics Consortium and FinnGen Consortium. The primary method employed for analysis was inverse variance weighting (false discovery rate), supplemented by sensitivity analyses to address pleiotropy and enhance robustness. RESULTS: In the International Stroke Genetics Consortium, 10, six and eight inflammatory cytokines exhibited a causal association with IA, uIA and SAH, respectively (false discovery rate, p < 0.05). In FinnGen datasets, macrophage Inflammatory Protein-1 Alpha (MIP_1A), MIP_1A and interferon γ-induced protein 10 (IP_10) were verified for IA, uIA and SAH, respectively. In the reverse Mendelian randomization analysis, the common cytokines altered by uIA and SAH were vascular endothelial growth factor (VEGF), MIP_1A, IL_9, IL_10 and IL_17, respectively. The meta-analysis results show that MIP_1A and IP_10 could be associated with the decreased risk of IA, and MIP_1A and IP_10 were associated with the decreased risk of uIA and SAH, respectively. Notably, the levels of VEGF, MIP_1A, IL_9, IL_10 and TNF_A were increased with uIA. Comprehensive heterogeneity and pleiotropy analyses confirmed the robustness of these results. CONCLUSION: Our study unveils a bidirectional association between inflammatory cytokines and IA, uIA and SAH. Further investigations are essential to validate their relationship and elucidate the underlying mechanisms.

The association of glaucoma with ischemic stroke and functional outcome after ischemic stroke from the perspective of causality.

INTRODUCTION: Glaucoma may be related to ischemic stroke (IS) and poor outcomes after IS in observational studies, while the causal association remains unclear. METHODS: We obtained single nucleotide polymorphisms (SNPs) related to glaucoma from the gene-wide association study (GWAS) conducted by the FinnGen consortium. The GWAS included a total of 13,614 cases and 295,540 controls. The summary-level of datasets regarding IS were collected from the MEGASTROKE consortium, including 34,217 cases and 406,111 controls. Furthermore, we acquired summary statistics datasets for functional outcomes following IS from the GWAS meta-analysis conducted by the GISCOME consortium, which involved 6,021 individuals. The genetic association estimates for functional outcomes at 90 days after IS were evaluated by the modified Rankin Score (mRS), including 3,741 cases with good functional outcomes (mRS=0-2) and 2,280 subjects with poor functional outcomes post-stroke (mRS=3-6). Inverse variance weighting (IVW) was used as the primary method, complemented by sensitivity analyses for pleiotropy and increasing robustness. RESULTS: Genetically, glaucoma is associated with an increased risk of IS (odds ratio [OR]=1.08, 95% confidence interval [CI] = 1.02-1.14, P = 0.0039), as well as poor prognosis after IS with adjustment for severity (OR=1.64; 95% CI=1.27-2.13, P=0.0001) and functional outcome after IS (OR=1.45, 95% CI=1.12-1.87, P=0.0038). Through sensitivity analyses, we confirmed the robustness of the results. In addition, we did not identify any causal association between IS, functional outcome after IS, and glaucoma in reverse analysis. CONCLUSION: Our study provides evidence suggesting a potential genetic causal relationship between glaucoma and an increased risk of IS, as well as a poor functional outcome following IS. Future studies are necessary to confirm these findings.

Evaluation of diagnostic potential of CD38 in rickets.

BACKGROUND: Rickets occurs in infants and children (aged 2 months to 3 years), compromising their skeletal development and damaging nervous, hematopoietic, immune, and other system functions. This study aimed to explore the significance of CD38 in rickets. METHODS: The microarray dataset GSE22523 was analyzed to obtain differentially expressed genes in rickets patients. A total of 36 rickets patients and healthy controls were recruited for the study, and their blood samples were collected, followed by detecting mRNA levels of CD38 using quantitative real-time polymerase chain reaction (qRT-PCR). Moreover, the significance of CD38 in rickets patients was analyzed by receiver operating characteristic (ROC) analysis, while the correlation between CD38 and 25-hydroxy-vitamin D (25OHD)/parathyroid hormone (PTH) was analyzed with Pearson's correlation. RESULTS: Results showed that CD38 mRNA levels and PTH contents were significantly increased in the rickets patients while 25OHD contents were decreased. Correlation analysis indicated that CD38 was positively correlated with PTH and negatively correlated with 25OHD in both serum and plasma samples of rickets patients. Moreover, ROC analysis showed that serum CD38 was 0.9005 (95 % CI: 0.8313-0.9696), and the AUCs of plasma CD38 was 0.7215 (95 % CI: 0.6031-0.8398) in differentiating rickets patients from healthy persons, advocating serum CD38 had better diagnostic value. CONCLUSION: CD38 mRNA levels were upregulated in rickets patients and closely correlated with PTH and 25OHD contents, indicating CD38 might be a diagnostic marker of rickets patients. Further research on the diagnostic utility of CD38 is necessary for the diagnosis and treatment of ricketsin rickets in the future.

Enhancing Multi-species Liver Microsomal Stability Prediction through Artificial Intelligence.

Liver microsomal stability, a crucial aspect of metabolic stability, significantly impacts practical drug discovery. However, current models for predicting liver microsomal stability are based on limited molecular information from a single species. To address this limitation, we constructed the largest public database of compounds from three common species: human, rat, and mouse. Subsequently, we developed a series of classification models using both traditional descriptor-based and classic graph-based machine learning (ML) algorithms. Remarkably, the best-performing models for the three species achieved Matthews correlation coefficients (MCCs) of 0.616, 0.603, and 0.574, respectively, on the test set. Furthermore, through the construction of consensus models based on these individual models, we have demonstrated their superior predictive performance in comparison with the existing models of the same type. To explore the similarities and differences in the properties of liver microsomal stability among multispecies molecules, we conducted preliminary interpretative explorations using the Shapley additive explanations (SHAP) and atom heatmap approaches for the models and misclassified molecules. Additionally, we further investigated representative structural modifications and substructures that decrease the liver microsomal stability in different species using the matched molecule pair analysis (MMPA) method and substructure extraction techniques. The established prediction models, along with insightful interpretation information regarding liver microsomal stability, will significantly contribute to enhancing the efficiency of exploring practical drugs for development.

Association between antithrombotic therapy and mortality in patients hospitalized for COVID­19.

BACKGROUND: The prothrombotic state is a common abnormality in patients with coronavirus disease 2019 (COVID-19). However, there is controversy over the use of anticoagulants, especially oral anticoagulants (OAC) due to limited studies. We sought to evaluate the association between antithrombotic therapy on mortality and clinical outcomes in patients hospitalized for COVID-19 through propensity score matching (PSM) analysis. METHODS: A retrospective cohort study was performed to include adult patients with COVID-19 in a university hospital. The primary outcome was in-hospital mortality. Secondary outcomes included intensive care unit (ICU) admission, mechanical ventilation, and acute kidney injury (AKI) during hospitalization. PSM was used as a powerful tool for matching patients' baseline characteristics. Adjusted odds ratios (aOR) with 95% confidence intervals (CI) were calculated from the models. RESULTS: Of 4,881 COVID-19 patients during the study period, 690 (14.1%) patients received antithrombotic therapy and 4,191 (85.9%) patients were under no antithrombotic therapy. After adjustment with multivariate regression analysis, patients receiving OAC, compared with those who did not receive any antithrombotic therapy, had significantly lower odds for in-hospital mortality (aOR: 0.46. 95% CI: 0.24 to 0.87; P= 0.017). PSM analysis observed similar results (aOR: 0.35. 95% CI: 0.19 to 0.61; P< 0.001). Moreover, in critically ill patients who received mechanical ventilation, antithrombotic treatment (aOR: 0.54. 95% CI: 0.32 to 0.89; P= 0.022) was associated with reduced risk of mortality. CONCLUSIONS: The application OACs was associated with reduced hospital mortality and mechanical ventilation requirement in COVID-19 patients. Besides, antithrombotic treatment was associated with a reduction in in-hospital mortality among critically ill COVID-19 patients who required mechanical ventilation.

Angular-resolved Rabi oscillations of orthorhombic spins in a Co(II) molecular qubit.

Magnetic molecules are promising candidates for quantum information processing (QIP) due to their tunable electron structures and quantum properties. A high spin Co(II) complex, CoH2dota, is studied for its potential to be used as a quantum bit (qubit) utilizing continuous wave (CW) and pulsed electron paramagnetic resonance (EPR) spectroscopy at low temperature. On the X-band microwave energy scale, the system can be treated as an effective spin 1/2 with a strongly anisotropic g-tensor resulting from the significant spin-orbital coupling. An experimental and theoretical study is conducted to investigate the anisotropic Rabi oscillations of the two magnetically equivalent spin centres with different orientations in a single crystal sample, which aims to verify the relationship between the Rabi frequency and the orientation of the g-tensor. The findings of this study show that an effective quantum manipulation method is developed for orthorhombic spin systems.

Association between postoperative changes in natremia and outcomes in patients undergoing elective craniotomy.

Postoperative dysnatremias, characterized by imbalances in serum sodium levels, have been linked to increased resource utilization and mortality in surgical and intensive care patients. The management of dysnatremias may involve medical interventions based on changes in sodium levels. In this study, we aimed to investigate the impact of postoperative changes in natremia on outcomes specifically in patients undergoing craniotomy.We conducted a retrospective analysis of patient records from the Department of Neurosurgery at West China Hospital, Sichuan University, covering the period from January 2011 to March 2021. We compared the highest and lowest sodium values in the first 14 postoperative days with the baseline values to define four categories for analysis: no change < 5 mmol/L; decrease > 5 mmol/L; increase > 5 mmol/L; both increase and decrease > 5 mmol/L. The primary outcome measure was 30-day mortality.A total of 12,713 patients were included in the study, and the overall postoperative mortality rate at 30 days was 2.1% (264 patients). The increase in sodium levels carried a particularly high risk, with a tenfold increase (OR 10.21; 95% CI 7.25-14.39) compared to patients with minimal or no change. Decreases in sodium levels were associated with an increase in mortality (OR 1.60; 95% CI 1.11-2.23).Moreover, the study revealed that postoperative sodium decrease was correlated with various complications, such as deep venous thrombosis, pneumonia, intracranial infection, urinary infection, seizures, myocardial infarction, and prolonged hospital length of stay. On the other hand, postoperative sodium increases were associated with acute kidney injury, deep venous thrombosis, pneumonia, intracranial infection, urinary infection, surgical site infection, seizures, myocardial infarction, and prolonged hospital length of stay.Changes in postoperative sodium levels were associated with increased complications, prolonged length of hospital stay, and 30-day mortality. Moreover, the severity of sodium change values correlated with higher mortality rates.

Association between elevated preoperative red cell distribution width and mortality after brain tumor craniotomy.

BACKGROUND: Red cell distribution width (RDW) has been recognized as a potential inflammatory biomarker, with elevated levels associated with adverse outcomes in various diseases. However, its role in predicting outcomes after brain tumor craniotomy remains unclear. We aimed to assess whether preoperative RDW influences mortality and postoperative complications in patients undergoing brain tumor craniotomy. METHODS: This retrospective cohort study analyzed serum RDW levels in patients undergoing brain tumor craniotomy at West China Hospital. RDW was evaluated in two forms: RDW-CV and RDW-SD, and was categorized into four quartiles for analysis by using logistic regression and multivariate analysis to adjust for confounding. RESULTS: The study encompassed 10,978 patients undergoing brain tumor craniotomy. our analysis revealed no significant difference in 30-day mortality across various RDW-CV levels. However, we observed a dose-response relationship with preoperative RDW-CV levels in assessing long-term mortality risks. Specifically, patients with RDW-CV levels of 12.6-13.2% (HR 1.04, 95% CI 1.01-1.18), 13.2-13.9% (HR 1.12, 95% CI 1.04-1.26), and > 13.9% (HR 1.34, 95% CI 1.18-1.51) exhibited a significantly higher hazard of long-term mortality compared to those with RDW-CV < 12.6%. When preoperative RDW-CV was analyzed as a continuous variable, for each 10% increase in RDW-CV, the adjusted OR of long-term mortality was 1.09 (95% CI 1.05-1.13). we also observed significant associations between preoperative higher RDW-CV levels and certain postoperative complications including acute kidney injury (OR 1.46, 95% CI: 1.10-1.94), pneumonia infection (OR 1.19 95% CI: 1.05-1.36), myocardial infarction (OR 1.32, 95% CI: 1.05-1.66), readmission (OR 1.15, 95% CI: 1.01-1.30), and a prolonged length of hospital stay (OR 1.11, 95% CI: 1.02-1.21). For RDW-SD levels, there was no significant correlation for short-term mortality, long-term mortality, and postoperative complications. CONCLUSIONS: Our study showed elevated preoperative RDW-CV is significantly associated with increased long-term mortality and multiple postoperative complications, but no such association is observed with RDW-SD. These findings show the prognostic importance of RDW-CV, reinforcing its potential as a valuable tool for risk stratification in the preoperative evaluation of brain tumor craniotomy patients.

Clinical analysis of 1301 children with hand and foot fractures and growth plate injuries.

BACKGROUND: Fractures of hands and feet are common in children, but relevant epidemiological studies are currently lacking. We aim to study the epidemiological characteristics of hand and foot fractures and growth plate injuries in children and provide a theoretical basis for their prevention, diagnosis, and treatment. METHODS: We retrospectively analyzed the data of children with hand and foot fractures who were hospitalized at Shenzhen Children's Hospital between July 2015 and December 2020. Data on demographic characteristics, fracture site, treatment method, etiology of injury, and accompanying injuries were collected. The children were divided into four age groups: infants, preschool children, school children, and adolescents. The fracture sites were classified as first-level (the first-fifth finger/toe, metacarpal, metatarsal, carpal, and tarsal) and second-level (the first-fifth: proximal phalanx, middle phalanx, distal phalanx, metacarpal, and metatarsal) sites. The changing trends in fracture locations and injury causes among children in each age group were analyzed. RESULTS: Overall, 1301 children (1561 fractures; 835 boys and 466 girls) were included. The largest number of fractures occurred in preschool children (n = 549, 42.20%), with the distal phalanx of the third finger being the most common site (n = 73, 15.57%). The number of fractures in adolescents was the lowest (n = 158, 12.14%), and the most common fracture site was the proximal phalanx of the fifth finger (n = 45, 29.61%). Of the 1561 fractures, 1143 occurred in the hands and 418 in the feet. The most and least common first-level fracture sites among hand fractures were the fifth (n = 300, 26.25%) and first (n = 138, 12.07%) fingers, respectively. The most and least common first-level foot fracture locations were the first (n = 83, 19.86%) and fourth (n = 26, 6.22%) toes, respectively. The most common first-level and second level etiologies were life related injuries (n = 1128, 86.70%) and clipping injuries (n = 428, 32.90%), respectively. The incidence of sports injuries gradually increased with age, accounting for the highest proportion in adolescents (26.58%). Hand and foot fractures had many accompanying injuries, with the top three being nail bed injuries (570 cases, 36.52%), growth plate injuries (296 cases, 18.96%), and distal severed fracture (167 cases, 10.70%). Among the 296 growth plate injuries, 246 occurred on the hands and 50 on the feet. CONCLUSIONS: In contrast to previous epidemiological studies on pediatric hand and foot fractures, we mapped the locations of these fractures, including proximal, shaft, distal, and epiphyseal plate injuries. We analyzed the changing trends in fracture sites and injury etiologies with age. Hand and foot fractures have many accompanying injuries that require attention during diagnosis and treatment. Doctors should formulate accident protection measures for children of different ages, strengthen safety education, and reduce the occurrence of accidental injuries.

Hematocrit drift and outcomes in surgical patients with aneurysmal subarachnoid hemorrhage.

BACKGROUND: There is a paucity of conclusive evidence regarding the impact of downward drift in hematocrit levels among patients who have undergone surgical clipping for aneurysmal subarachnoid hemorrhage (aSAH). This study endeavors to explore the potential association between hematocrit drift and mortality in this specific patient population. METHODS: A cohort study was conducted, encompassing adult patients diagnosed with aSAH at a university hospital. The primary endpoint was follow-up mortality. Propensity score matching was employed to align patients based on their baseline characteristics. Discrimination capacity across various models was assessed and compared using net reclassification improvement (NRI). RESULTS: Among the 671 patients with aSAH in the study period, 118 patients (17.6%) experienced an in-hospital hematocrit drift of more than 25%. Following adjustment with multivariate regression analysis, patients with elevated hematocrit drift demonstrated significantly increased odds of mortality (aOR: 2.12, 95% CI: 1.14 to 3.97; P = 0.019). Matching analysis yielded similar results (aOR: 2.07, 95% CI: 1.05 to 4.10; P = 0.036). The inclusion of hematocrit drift significantly improved the NRI (P < 0.0001) for mortality prediction. When in-hospital hematocrit drift was served as a continuous variable, each 10% increase in hematocrit drift corresponded to an adjusted odds ratio of 1.31 (95% CI 1.08-1.61; P = 0.008) for mortality. CONCLUSIONS: In conclusion, the findings from this comprehensive cohort study indicate that a downward hematocrit drift exceeding 25% independently predicts mortality in surgical patients with aSAH. These findings underscore the significance of monitoring hematocrit and managing anemia in this patient population.

Effect of Statin Treatment in Patients with Aneurysmal Subarachnoid Hemorrhage: A Network Meta-Analysis.

BACKGROUND: There are knowledge gaps regarding the relative efficacy of statins for aneurysmal subarachnoid hemorrhage (aSAH). This study aims to examine the comparative effectiveness and determine the ranking of different statins with network meta­analysis in patients with aSAH. METHODS: MEDLINE, Embase, Pubmed, and Cochrane Central Register of Controlled Trials were searched from database inception until December 15, 2022. Outcomes included delayed cerebral ischemia (DCI), functional recovery, and mortality. Relative risk (RRs) ratios and associated 95% confidence intervals (CIs) were estimated. The values derived from surface under the cumulative ranking curve were obtained to rank the treatment hierarchy in the analysis. RESULTS: We identified 13 trials involving 1,885 patients. Atorvastatin 20 mg (RR 0.68, 95% CI 0.53-0.86), pravastatin 40 mg (RR 0.51, 95% CI 0.31-0.77), and simvastatin 80 mg (RR 0.54, 95% CI 0.40-0.70) were superior to the placebo in preventing DCI. Additionally, simvastatin 80 mg (RR 0.60, 95% CI 0.42-0.84) and pravastatin 40 mg (RR 0.56, 95% CI 0.32-0.93) were associated with a decreased risk of DCI than simvastatin 40 mg. Comparisons across treatment durations suggested that short-term (RR 0.62, 95% CI 0.50-0.76) statin therapy reduced risk of DCI. CONCLUSIONS: Simvastatin 80 mg might be the most effective intervention in reducing DCI. Additionally, short-term therapy might provide more benefits. Further research with longer follow-up is warranted to validate the current findings in patients with aSAH who are at high risk of DCI.

Mesenchymal stem cell-derived exosomes as a new drug carrier for the treatment of spinal cord injury: A review.

Spinal cord injury (SCI) is a devastating traumatic disease seriously impairing the quality of life in patients. Expectations to allow the hopeless central nervous system to repair itself after injury are unfeasible. Developing new approaches to regenerate the central nervous system is still the priority. Exosomes derived from mesenchymal stem cells (MSC-Exo) have been proven to robustly quench the inflammatory response or oxidative stress and curb neuronal apoptosis and autophagy following SCI, which are the key processes to rescue damaged spinal cord neurons and restore their functions. Nonetheless, MSC-Exo in SCI received scant attention. In this review, we reviewed our previous work and other studies to summarize the roles of MSC-Exo in SCI and its underlying mechanisms. Furthermore, we also focus on the application of exosomes as drug carrier in SCI. In particular, it combs the advantages of exosomes as a drug carrier for SCI, imaging advantages, drug types, loading methods, etc., which provides the latest progress for exosomes in the treatment of SCI, especially drug carrier.

The prognostic value and immune landscaps of m6A/m5C-related lncRNAs signature in the low grade glioma.

BACKGROUND: N6-methyladenosine (m6A) and 5-methylcytosine (m5C) are the main RNA methylation modifications involved in the oncogenesis of cancer. However, it remains obscure whether m6A/m5C-related long non-coding RNAs (lncRNAs) affect the development and progression of low grade gliomas (LGG). METHODS: We summarized 926 LGG tumor samples with RNA-seq data and clinical information from The Cancer Genome Atlas and Chinese Glioma Genome Atlas. 105 normal brain samples with RNA-seq data from the Genotype Tissue Expression project were collected for control. We obtained a molecular classification cluster from the expression pattern of sreened lncRNAs. The least absolute shrinkage and selection operator Cox regression was employed to construct a m6A/m5C-related lncRNAs prognostic signature of LGG. In vitro experiments were employed to validate the biological functions of lncRNAs in our risk model. RESULTS: The expression pattern of 14 sreened highly correlated lncRNAs could cluster samples into two groups, in which various clinicopathological features and the tumor immune microenvironment were significantly distinct. The survival time of cluster 1 was significantly reduced compared with cluster 2. This prognostic signature is based on 8 m6A/m5C-related lncRNAs (GDNF-AS1, HOXA-AS3, LINC00346, LINC00664, LINC00665, MIR155HG, NEAT1, RHPN1-AS1). Patients in the high-risk group harbored shorter survival times. Immunity microenvironment analysis showed B cells, CD4 + T cells, macrophages, and myeloid-derived DC cells were significantly increased in the high-risk group. Patients in high-risk group had the worse overall survival time regardless of followed TMZ therapy or radiotherapy. All observed results from the TCGA-LGG cohort could be validated in CGGA cohort. Afterwards, LINC00664 was found to promote cell viability, invasion and migration ability of glioma cells in vitro. CONCLUSION: Our study elucidated a prognostic prediction model of LGG by 8 m6A/m5C methylated lncRNAs and a critical lncRNA regulation function involved in LGG progression. High-risk patients have shorter survival times and a pro-tumor immune microenvironment.

Nomogram to Predict Good Collateral Formation After the STA-MCA Bypass Surgery in Adult Patients With Moyamoya Disease.

BACKGROUND: Collateral formation from the extracranial carotid artery to ischemic brain tissue determines the clinical success of superficial temporal artery (STA) to middle cerebral artery (MCA) bypass surgery in adult patients with moyamoya disease, but postoperative collateral formation (PCF) after STA-MCA bypass surgery is unpredictable. Accurate preoperative prediction of acceptable PCF could improve patient selection. This study aims to develop a prediction nomogram model for PCF in this patient population. METHODS: Adult patients with moyamoya disease undergoing the STA-MCA bypass surgery between January 2013 and December 2020 at a single institution were retrospectively or prospectively enrolled in this observational study. Data including potential clinical and radiological predictors were obtained from hospital records. A nomogram was generated based on a multivariate logistic regression analysis, to identify potential predictors associated with good PCF. The performance of the nomogram was evaluated for discrimination, calibration, and clinical utility. RESULTS: Data from 243 patients with moyamoya disease who underwent the STA-MCA bypass surgery were analyzed to build the nomogram. After 1-year follow-up, 162 (66.7%) hemispheres had good PCF and 81 (33.3%) had poor PCF. Good PCF is associated with 3 preoperative factors: age at operation, a diameter of donor branch of STA, and the preinfarction period stage. Incorporating these 3 factors, the model achieved a concordance index of 0.88 (95% CI, 0.84-0.92) and had a well-fitted calibration curve and good clinical application value. A cutoff value of 100 was determined to predict good PCF via this nomogram. CONCLUSIONS: The nomogram exhibits high accuracy in predicting good PCF after the STA-MCA bypass surgery in adult patients with moyamoya disease and may allow surgeons to better evaluate preoperatively candidacy for successful bypass surgery.

COVPRIG robustly predicts the overall survival of IDH wild-type glioblastoma and highlights METTL1+ neural-progenitor-like tumor cell in driving unfavorable outcome.

BACKGROUND: Accurately predicting the outcome of isocitrate dehydrogenase (IDH) wild-type glioblastoma (GBM) remains hitherto challenging. This study aims to Construct and Validate a Robust Prognostic Model for IDH wild-type GBM (COVPRIG) for the prediction of overall survival using a novel metric, gene-gene (G × G) interaction, and explore molecular and cellular underpinnings. METHODS: Univariate and multivariate Cox regression of four independent trans-ethnic cohorts containing a total of 800 samples. Prediction efficacy was comprehensively evaluated and compared with previous models by a systematic literature review. The molecular underpinnings of COVPRIG were elucidated by integrated analysis of bulk-tumor and single-cell based datasets. RESULTS: Using a Cox-ph model-based method, six of the 93,961 G × G interactions were screened to form an optimal combination which, together with age, comprised the COVPRIG model. COVPRIG was designed for RNA-seq and microarray, respectively, and effectively identified patients at high risk of mortality. The predictive performance of COVPRIG was satisfactory, with area under the curve (AUC) ranging from 0.56 (CGGA693, RNA-seq, 6-month survival) to 0.79 (TCGA RNAseq, 18-month survival), which can be further validated by decision curves. Nomograms were constructed for individual risk prediction for RNA-seq and microarray-based cohorts, respectively. Besides, the prognostic significance of COVPRIG was also validated in GBM including the IDH mutant samples. Notably, COVPRIG was comprehensively evaluated and externally validated, and a systemic review disclosed that COVPRIG outperformed current validated models with an integrated discrimination improvement (IDI) of 6-16%. Moreover, integrative bioinformatics analysis predicted an essential role of METTL1+ neural-progenitor-like (NPC-like) malignant cell in driving unfavorable outcome. CONCLUSION: This study provided a powerful tool for the outcome prediction for IDH wild-type GBM, and preliminary molecular underpinnings for future research.