Predictive value of suPAR in AKI: a systematic review and meta-analysis.

BACKGROUND: Some clinical trials have shown that soluble urokinase-type plasminogen activator receptor (suPAR) has good predictive value for acute kidney injury (AKI), but there is still a lack of evidence-based proof. Therefore, we conducted this systematic review and meta-analysis to evaluate the predictive value of suPAR for AKI. METHODS: Pubmed, EMBASE, Cochrane Library, and Web of Science databases were searched until December 2021 to obtain the literature on the prediction of suPAR for AKI. The quality of the included studies was assessed using the QUADAS-2 scoring system, and a bivariate random-effect model was used for the meta-analysis. The present study has been registered on PROSPERO (Registration No. CRD42022324978). RESULTS: Seven articles were included, involving 2,319 patients, 635 of whom were AKI patients. The meta-analysis results showed that the combined sensitivity of suPAR in predicting AKI was 0.77 (95% CI 0.67-0.84); the specificity was 0.64 (95% CI 0.53-0.75); the odds ratio of diagnosis was 6 (95% CI 3-10); the pooled positive likelihood ratio was 2.2 (95% CI 1.6-2.9); the pooled negative likelihood ratio was 0.36 (95% CI 0.26-0.52); and the area under the summary receiver-operating characteristic (SROC) curve was 0.77 (95% CI 0.12~0.99). Deek's funnel plot suggested no potential publication bias among included studies. CONCLUSION: suPAR is a valuable biomarker for the prediction of AKI with relatively high predictive accuracy, but its clinical application needs improvements. SuPAR should be considered as an indicator in the subsequent development of more effective predictive tools for AKI.

Identification of circRNAs linked to Alzheimer's disease and related dementias.

INTRODUCTION: Circular RNAs (circRNAs) exhibit selective expression in the brain and differential regulation in Alzheimer's disease (AD). To explore the role of circRNAs in AD, we investigated how circRNA expression varies between brain regions and with AD-related stress in human neuronal precursor cells (NPCs). METHODS: Ribosomal RNA-depleted hippocampus RNA-sequencing data were generated. Differentially regulated circRNAs in AD and related dementias were detected using CIRCexplorer3 and limma. circRNA results were validated using quantitative real-time PCR of cDNA from the brain and NPCs. RESULTS: We identified 48 circRNAs that were significantly associated with AD. We observed that circRNA expression differed by dementia subtype. Using NPCs, we demonstrated that exposure to oligomeric tau elicits downregulation of circRNA similar to that observed in the AD brain. DISCUSSION: Our study shows that differential expression of circRNA can vary by dementia subtype and brain region. We also demonstrated that circRNAs can be regulated by AD-linked neuronal stress independently from their cognate linear messenger RNAs (mRNAs).

Individual prediction of motor vehicle accidents for patients with epilepsy.

The objective of the study was to design a clinically useful tool to predict the risk of seizure-related motor vehicle accidents (MVAs) for people with epilepsy (PWE). Participants were patients who visited our epilepsy center in West China Hospital from October 2012 to October 2019 and were divided into a primary cohort and a validation cohort. Ultimately, we included 525 patients in the primary cohort and 86 patients in the validation cohort. Proportional hazard regression was performed to measure the prognostic factors of car accidents. The outcome was used to create a nomogram model. The final model had 7 factors, with a C-index of 0.85 (95% CI, 0.80-0.91), to predict the possibility of non-MVA for PWE. For the validation cohort, the C-index was 0.83 (95% CI, 0.72-0.95). This nomogram model can offer more individualized advice to PWE who are still driving by estimating the risk of car accidents.

Severe psychological distress among patients with epilepsy during the COVID-19 outbreak in southwest China.

OBJECTIVE: To compare the severity of psychological distress between patients with epilepsy and healthy controls during the COVID-19 outbreak in southwest China, as well as identify potential risk factors of severe psychological distress among patients with epilepsy. METHODS: This cross-sectional case-control study examined a consecutive sample of patients older than 15 years treated at the epilepsy center of West China Hospital between February 1 and February 29, 2020. As controls, sex- and age-matched healthy visitors of inpatients (unrelated to the patients) were also enrolled during the same period. Data on demographics and attention paid to COVID-19 were collected by online questionnaire, data on epilepsy features were collected from electronic medical records, and psychological distress was evaluated using the 6-item Kessler Psychological Distress Scale (K-6). Potential risk factors of severe psychological distress were identified using multivariate logistic regression. RESULTS: The 252 patients and 252 controls in this study were similar along all demographic variables except family income. Patients with epilepsy showed significantly higher K-6 scores than healthy controls and spent significantly more time following the COVID-19 outbreak (both P < .001). Univariate analyses associated both diagnosis of drug-resistant epilepsy and time spent paying attention to COVID-19 with severe psychological distress (defined as K-6 score >12; both P ≤ .001). Multivariate logistic regression identified two independent predictors of severe psychological distress: time spent paying attention to COVID-19 (odds ratio [OR] = 1.172, 95% confidence interval [CI] = 1.073-1.280) and diagnosis of drug-resistant epilepsy (OR = 0.283, 95% CI = 0.128-0.623). SIGNIFICANCE: During public health outbreaks, clinicians and caregivers should focus not only on seizure control but also on mental health of patients with epilepsy, especially those with drug-resistant epilepsy. K-6 scores > 12 indicate severe psychological distress. This may mean, for example, encouraging patients to engage in other activities instead of excessively following media coverage of the outbreak.

New onset acute symptomatic seizure and risk factors in coronavirus disease 2019: A retrospective multicenter study.

Our aim was to clarify the incidence and risk of acute symptomatic seizures in people with coronavirus disease 2019 (COVID-19). This multicenter retrospective study enrolled people with COVID-19 from January 18 to February 18, 2020 at 42 government-designated hospitals in Hubei province, the epicenter of the epidemic in China; Sichuan province; and Chongqing municipality. Data were collected from medical records by 11 neurologists using a standard case report form. A total of 304 people were enrolled, of whom 108 had a severe condition. None in this cohort had a known history of epilepsy. Neither acute symptomatic seizures nor status epilepticus was observed. Two people had seizurelike symptoms during hospitalization due to acute stress reaction and hypocalcemia, and 84 (27%) had brain insults or metabolic imbalances during the disease course known to increase the risk of seizures. There was no evidence suggesting an additional risk of acute symptomatic seizures in people with COVID-19. Neither the virus nor potential risk factors for seizures seem to be significant risks for the occurrence of acute symptomatic seizures in COVID-19.

Clinical characteristics, treatments, and outcomes of patients with anti-N-methyl-d-aspartate receptor encephalitis: A systematic review of reported cases.

Anti-N-methyl-d-aspartate receptor (NMDAR) encephalitis is a recently recognized autoimmune disorder which is responsive to immunotherapy. However, the outcomes of different immunotherapies have not been defined and there have been few studies that carried out a comparison among them. To provide an overview of the clinical characteristics, treatments, and outcomes of anti-NMDAR encephalitis, we systematically reviewed the literature in the PubMed, Medline, Embase, Cochrane Library, BioMedical Literature Database (CBM), China National Knowledge Infrastructure (CNKI), and Wan-fang databases. Eighty-three studies with a total of 432 patients were included. The median age was 22years. Two hundred ninety-three (68%) patients were female, 87 (21%) of 412 patients had a tumor, including 68 (78%) patients with ovarian teratoma. Pediatric patients had a higher ratio of seizures to psychiatric symptoms as the initial manifestation (p=0.0012), a lower proportion with a tumor (p<0.0001) and CSF pleocytosis (p=0.0163), and a better outcome (p=0.0064) than adults. Patients who died had a higher proportion of CSF pleocytosis than the patients who survived (p=0.0021). There were no significant differences among three first-line immunotherapy used alone (p=0.9172) or among combinations of every two of them (p=0.3059). With regard to the use of corticosteroid and IVIG, there were no significant differences between the outcomes of early combined treatment and sequential treatment (p=0.7277), or between using corticosteroid first and IVIG first (p=0.5422). Our findings suggest that the clinical characteristics and outcomes for pediatric patients were different from adult patients, and no significant differences were found among different immunotherapies.

Brain functional connectivity patterns in focal cortical dysplasia related epilepsy.

OBJECTIVE: Focal cortical dysplasia (FCD) appears to be strongly associated with intractable epilepsy. Although patients with FCD are candidates for epilepsy surgery, gray matter structural abnormalities can extend beyond the primary lesion, which makes surgery less effective. The objective of this study was to evaluate functional connectivity patterns in epilepsy associated with FCD to explore the underlying pathological mechanism of this disorder. METHODS: A total of 34 patients (14 men) with FCD and epilepsy [mean age ± standard deviation (SD), 24.5 ± 9.8 years; range, 8-47 years] and 34 age-matched healthy controls (14 men, 24.6 ± 9.7 years) underwent functional magnetic resonance imaging. Independent component analysis (ICA), seed-based functional connectivity, and graph theory were applied to analyze functional connectivity patterns in the brain. RESULTS: Patients showed more connections among dorsal attention network, anterior default mode network, and sensorimotor brain networks than healthy controls based on ICA. Analysis of connectivity between regions of interest (ROIs) showed greater functional connectivity in patients between frontal and temporal regions, but lower connectivity between the cerebellum and frontal regions. The normalized characteristic path length was significantly higher in group of patients, but the two groups showed no significant differences in global or regional efficiency, clustering coefficient or characteristic path length. CONCLUSIONS: Analysis of ICA-derived and ROI-based functional connectivity suggests that disrupted interactions and dysconnectivity in large-scale neural networks and frontotemporal-cerebellar regions may contribute to underlying pathological mechanisms in FCD-related epilepsy.

Risk factors for suicidal tendency in people with epilepsy in China: a case-control study.

People with epilepsy (PWE) have an increased suicide prevalence. This study aimed to identify the risk factors for suicidal tendency among PWE in West China. A nested case-control study was designed in a cohort of patients with epilepsy (n = 2087). In total, 28 variates were calculated. In the univariate analysis, unemployment, low income, seizure frequency, seizure-free time, infectious or structural etiology, levetiracetam or phenobarbital use, anxiety, depression, and stigma were associated with suicidal tendency. A multivariate analysis indicated that unemployment (odds ratio [OR] 5.74, 95% confidence interval [CI] 2.13-15.48), levetiracetam use (OR 2.80, 95%CI 1.11-7.05), depression (C-NDDI-E score ≥ 13; OR 3.21, 95%CI 1.26-8.21), and stigma (SSCI score ≥ 16; OR 6.67, 95%CI 1.80-24.69) were independently associated with suicidal tendency. Conditional inference tree analysis indicated that SSCI and C-NDDI-E scores could effectively identify patients with suicidal tendency. Thus, this study suggests that unemployment, levetiracetam use, depression, and stigma are independent risk factors for suicidal tendency in PWE in China.

Incidence and risk factors associated with the development of epilepsy in patients with intracranial alveolar echinococcosis.

Parasitic infection remains a critical health problem in Ganzi Tibetan Autonomous Prefecture of China. The association of epilepsy and intracranial alveolar echinococcosis (IAE) is still largely unclear. This study primarily aimed to assess both the incidence and possible risk factors of epilepsy in patients with IAE. According to the occurrence of seizures, patients were separated into two different groups consisting of patients with epilepsy and those without epilepsy. Univariate and multivariate logistic regression analysis was used to identify the potential risk factors associated with the development of epilepsy in patients with IAE. A total of 97 patients (42 women, 55 men; age 19-76 years) were enrolled. Epilepsy was observed in almost 20 % of patients with IAE. The use of anti-seizure medications was not standardized, as 83.3 % of female patients of childbearing age used sodium valproate. It was observed that cortical lesions (hazard ratio (HR) = 29.740, P = 0.006) were significantly associated with development of epilepsy. In addition, epilepsy had no significant effect on the overall survival rate of patients with IAE.

Co-expression of NMDA-receptor subunits NR1, NR2A, and NR2B in dysplastic neurons of teratomas in patients with paraneoplastic NMDA-receptor-encephalitis: a retrospective clinico-pathology study of 159 patients.

OBJECTIVE: To comprehensively describe the pathological features of neurons in patients with ovarian teratomas and paraneoplastic anti-NMDAR encephalitis (anti-NMDARE), emphasizing on NMDA-receptor expression and infiltrating lymphocytes. METHODS: A retrospective study was performed in a large series of 159 patients from the West China Hospital. We retrospectively identified 12 patients with paraneoplastic anti-NMDARE (11 case with ovarian teratomas and 1 case with mixed germ cell tumor), which were compared to 35 patients with teratomas and no encephalitis and to 147 patients with anti-NMDARE and no evidence for tumors. Patient history and outcome were reviewed from the clinical charts and compared between all three groups. Histopathological examination, including double-immunofluorescence of NMDAR subunits and IgG was performed in all teratoma tissues. Magnetic Luminex Assay Human Premixed Multi-Analyte Kit was performed to investigate cytokines profile of CSF. RESULTS: Patients with paraneoplastic anti-NMDARE had a more severe clinical presentation, i.e. they required more mechanical ventilation and intensive care (p < 0.001). Though immunotherapy was initiated earlier in this group, repeated intravenous immunoglobulin administration (IVIG) was more common (p = 0.002) and with higher cerebrospinal fluid (CSF) antibody titres (p = 0.004). Following tumor resection, the outcome did not differ between groups. A peculiar population of floating-frog like dysplastic neurons were observed only in teratomas of patients with paraneoplastic anti-NMDARE, co-expressing NR1, NR2A, NR2B subunits and IgG. Also, CD20 positive B-cells were more common in anti-NMDARE teratomas. In CSF of paraneoplastic anti-NMDARE patients, TNF-α, IL-10 and GM-CSF concentrations were higher than in negative symptom control and VEGF-A and IL-1a were lower than in anti-NMDARE patients (0.25 < p < 0.05). CONCLUSIONS: Patients with teratomas and paraneoplastic anti-NMDARE revealed a cellular population of dysplastic neurons co-expressing NMDAR subunits, which were the potential source of autoantigens triggering anti-NMDARE. Some inflammatory cytokines may be involved in pathogenesis of paraneoplastic anti-NMDARE.

New onset neurologic events in people with COVID-19 in 3 regions in China.

OBJECTIVE: To investigate new-onset neurologic impairments associated with coronavirus disease 2019 (COVID-19). METHODS: A retrospective multicenter cohort study was conducted between January 18 and March 20, 2020, including people with confirmed COVID-19 from 56 hospitals officially designated in 3 Chinese regions; data were extracted from medical records. New-onset neurologic events as assessed by neurology consultants based on manifestations, clinical examination, and investigations were noted, in which critical events included disorders of consciousness, stroke, CNS infection, seizures, and status epilepticus. RESULTS: We enrolled 917 people with average age 48.7 years and 55% were male. The frequency of new-onset critical neurologic events was 3.5% (32/917) overall and 9.4% (30/319) among those with severe or critical COVID-19. These were impaired consciousness (n = 25) or stroke (n = 10). The risk of critical neurologic events was highly associated with age above 60 years and previous history of neurologic conditions. Noncritical events were seen in fewer than 1% (7/917), including muscle cramp, unexplained headache, occipital neuralgia, tic, and tremor. Brain CT in 28 people led to new findings in 9. Findings from lumbar puncture in 3 with suspected CNS infection, unexplained headache, or severe occipital neuralgia were unremarkable. CONCLUSIONS: People with COVID-19 aged over 60 and with neurologic comorbidities were at higher risk of developing critical neurologic impairment, mainly impaired consciousness and cerebrovascular accidents. Brain CT should be considered when new-onset brain injury is suspected, especially in people under sedation or showing an unexplained decline in consciousness. Evidence of direct acute insult of severe acute respiratory syndrome coronavirus 2 to the CNS is lacking.

Epilepsy in China: Factors influencing marriage status and fertility.

PURPOSE: To investigate the current status of marriage and fertility of patients with epilepsy (PWE) and characterize its influencing factors. METHODS: A total of 1,823 adult patients (males age 22 years or older, females age 20 years or older) were included in this study. Data concerning sociodemographic and clinical characteristics were collected. Descriptive analyses, followed by univariate and multivariate logistic regression analyses were utilized to examine factors associated with marriage and fertility of PWE. Marital status of PWE was compared with Chinese population. Standardized marriage rate (SMR) for age and sex was estimated based on the 2010 sixth national population census. RESULTS: 1,132 patients (62.1%) were married and 823 (45.1%) had a history of fertility. Patients had lower marriage rates than Chinese population (62.1% vs 78.4%). Patients with adult-onset epilepsy (>18 years) had a significantly higher rate of marriage and fertility (p ＜ 0.001) compared to those with childhood-onset epilepsy (≤18 years). Employed patients had higher marriage rates than unemployed patients (64.9% vs 58.6%, p = 0.006), with only male patients being significantly affected by employment status (p ＜ 0.001). Multiple logistic regression revealed that age, age at first seizure onset, and employment status were related to both marriage and fertility. CONCLUSION: Epilepsy had negative effects on marriage and fertility status. Marriage and fertility rates were lower in patients with Childhood-onset epilepsy (≤18 years). Furthermore, employment status mainly affected the marriage rate of male patients.