15-Month Health Outcomes and the Related Risk Factors of Hospitalized COVID-19 Patients From Onset: A Cohort Study.

Objective: The long-term impact of COVID-19 on patient health has been a recent focus. This study aims to determine the persistent symptoms and psychological conditions of patients hospitalized with COVID-19 15 months after onset, that patients first developed symptoms. The potential risk factors were also explored. Methods: A cohort of COVID-19 patients discharged from February 20, 2020 to March 31, 2020 was recruited. Follow-ups were conducted using validated questionnaires and psychological screening scales at 15 months after onset to evaluate the patients' health status. The risk factors for long-term health impacts and their associations with disease severity was analyzed. Findings: 534 COVID-19 patients were enrolled. The median age of the patients was 62.0 years old (IQR 52.0-70.0) and 295 were female (55.2%). The median time from onset to follow-up was 460.0 (451.0-467.0) days. Sleep disturbance (18.5%, 99/534) and fatigue (17.2%, 92/534) were the most common persistent symptoms. 6.4% (34/534) of the patients had depression, 9.2% (49/534) were anxious, 13.0% (70/534) had insomnia and 4.7% (25/534) suffered from post-traumatic stress disorder (PTSD). Multivariate adjusted logistic regression analysis showed that glucocorticoid use during hospitalization (OR 3.58, 95% CI 1.12-11.44) was significantly associated with an increased risk of fatigue. The OR values for anxiety and sleep disorders were 2.36 (95% CI 1.07-5.20) and 2.16 (95% CI 1.13-4.14) in females to males. The OR value of PTSD was 25.6 (95% CI 3.3-198.4) in patients with persistent symptoms to those without persistent symptoms. No significant associations were observed between fatigue syndrome or adverse mental outcomes and disease severity. Conclusions: 15-month follow-up in this study demonstrated the need of extended rehabilitation intervention for complete recovery in COVID-19 patients.

Mesenchymal stem cells alleviate the early brain injury of subarachnoid hemorrhage partly by suppression of Notch1-dependent neuroinflammation: involvement of Botch.

BACKGROUND: Activated microglia-mediated neuroinflammation has been regarded as an underlying key player in the pathogenesis of subarachnoid hemorrhage (SAH)-induced early brain injury (EBI). The therapeutic potential of bone marrow mesenchymal stem cells (BMSCs) transplantation has been demonstrated in several brain injury models and is thought to involve modulation of the inflammatory response. The present study investigated the salutary effects of BMSCs on EBI after SAH and the potential mechanism mediated by Notch1 signaling pathway inhibition. METHODS: The Sprague-Dawley rats SAH model was induced by endovascular perforation method. BMSCs (3 × 106 cells) were transplanted intravenously into rats, and N-[N-(3,5-difluorophenacetyl-L-alanyl)]-S-phenylglycine t-butyl ester (DAPT), a Notch1 activation inhibitor, and Notch1 small interfering RNA (siRNA) were injected intracerebroventricularly. The effects of BMSCs on EBI were assayed by neurological score, brain water content (BWC), blood-brain barrier (BBB) permeability, magnetic resonance imaging, hematoxylin and eosin staining, and Fluoro-Jade C staining. Immunofluorescence and immunohistochemistry staining, Western blotting, and quantitative real-time polymerase chain reaction were used to analyze various proteins and transcript levels. Pro-inflammatory cytokines were measured by enzyme-linked immunosorbent assay. RESULTS: BMSCs treatment mitigated the neurobehavioral dysfunction, BWC and BBB disruption associated with EBI after SAH, reduced ionized calcium binding adapter molecule 1 and cluster of differentiation 68 staining and interleukin (IL)-1 beta, IL-6 and tumor necrosis factor alpha expression in the left hemisphere but concurrently increased IL-10 expression. DAPT or Notch1 siRNA administration reduced Notch1 signaling pathway activation following SAH, ameliorated neurobehavioral impairments, and BBB disruption; increased BWC and neuronal degeneration; and inhibited activation of microglia and production of pro-inflammatory factors. The augmentation of Notch1 signal pathway agents and phosphorylation of nuclear factor-κB after SAH were suppressed by BMSCs but the levels of Botch were upregulated in the ipsilateral hemisphere. Botch knockdown in BMSCs abrogated the protective effects of BMSCs treatment on EBI and the suppressive effects of BMSCs on Notch1 expression. CONCLUSIONS: BMSCs treatment alleviated neurobehavioral impairments and the inflammatory response in EBI after SAH; these effects may be attributed to Botch upregulation in brain tissue, which subsequently inhibited the Notch1 signaling pathway.

The role of wall shear stress in the parent artery as an independent variable in the formation status of anterior communicating artery aneurysms.

OBJECTIVES: The study aimed to determine which hemodynamic parameters independently characterize anterior communicating artery (AcomA) aneurysm formation and explore the threshold of wall shear stress (WSS) of the parent artery to better illustrate the correlation between the magnitude of WSS and AcomA aneurysm formation. METHODS: Eighty-one patients with AcomA aneurysms and 118 patients without intracranial aneurysms (control population), as confirmed by digital subtraction angiography (DSA) from January 2014 to May 2017, were included in this cross-sectional study. Three-dimensional-DSA was performed to evaluate the morphologic characteristics of AcomA aneurysms. Local hemodynamic parameters were obtained using transcranial color-coded duplex (TCCD). Multivariate logistic regression and a two-piecewise linear regression model were used to determine which hemodynamic parameters are independent predictors of AcomA aneurysm formation and identify the threshold effect of WSS of the parent artery with respect to AcomA aneurysm formation. RESULTS: Univariate analyses showed that the WSS (p < 0.0001), angle between the A1 and A2 segments of the anterior cerebral artery (ACA) (p < 0.001), hypertension (grade II) (p = 0.007), fasting blood glucose (FBG; > 6.0 mmol/L) (p = 0.005), and dominant A1 (p < 0.001) were the significant parameters. Multivariate analyses showed a significant association between WSS of the parent artery and AcomA aneurysm formation (p = 0.0001). WSS of the parent artery (7.8-12.3 dyne/cm2) had a significant association between WSS and aneurysm formation (HR 2.0, 95% CI 1.3-2.8, p < 0.001). CONCLUSIONS: WSS ranging between 7.8 and 12.3 dyne/cm2 independently characterizes AcomA aneurysm formation. With each additional unit of WSS, there was a one-fold increase in the risk of AcomA aneurysm formation. KEY POINTS: • Multivariate analyses and a two-piecewise linear regression model were used to evaluate the risk factors for AcomA aneurysm formation and the threshold effect of WSS on AcomA aneurysm formation. • WSS ranging between 7.8 and 12.3 dyne/cm 2 was shown to be a reliable hemodynamic parameter in the formation of AcomA aneurysms. The probability of AcomA aneurysm formation increased one-fold for each additional unit of WSS. • An ultrasound-based TCCD technique is a simple and accessible noninvasive method for detecting WSS in vivo; thus, it can be applied as a screening tool for evaluating the probability of aneurysm formation in primary care facilities and community hospitals because of the relatively low resource intensity.

CDKN2BAS gene polymorphisms and the risk of intracranial aneurysm in the Chinese population.

BACKGROUND: CDKN2BAS gene polymorphisms has been shown to correlation with intracranial aneurysm(IA) in the study of foreign people. The study, the author selected the Chinese people as the research object to explore whether CDKN2BAS gene polymorphisms associated with Chinese patients with IA. METHODS: We selected 200 patients(52.69 ± 11.50) with sporadic IA as experimental group, 200 participants(49.99 ± 13.00) over the same period to the hospital without cerebrovascular diseases as control group. Extraction of peripheral blood DNA, applying polymerase chain reaction(PCR)-ligase detection reaction (LDR) identified CDKN2BAS Single nucleotide polymorphism(SNP) locus genotype: rs6475606, rs1333040, rs10757272, rs3217992, rs974336, rs3217986, rs1063192. The differences in allelic and genotype frequencies between the patient and control groups were evaluated by the chi-square test or Fisher's exact tests. RESULTS: The genotype of rs1333040 and rs6475606 shown association with sporadic IA(X2 = 8.545, P = 0.014; X2 = 10.961, P = 0.004; respectively);the C allele of rs6475606 showed reduction the occurrence of IA; the rs1333040 and rs6475606 associated with hemorrhage, the C allele of rs1333040 could lower the risk of hemorrhage, and rs6475606 will not, rs1333040 also associated with aneurysm size. CONCLUSION: Our research shows that variant rs1333040 and rs6475606 of CDKN2BAS related to the Chinese han population of sporadic IAs occurs. This study confirms the association between CDKN2BAS and IAs.