Trial of Endovascular Therapy for Acute Ischemic Stroke with Large Infarct.

BACKGROUND: The role of endovascular therapy for acute stroke with a large infarction has not been extensively studied in differing populations. METHODS: We conducted a multicenter, prospective, open-label, randomized trial in China involving patients with acute large-vessel occlusion in the anterior circulation and an Alberta Stroke Program Early Computed Tomography Score of 3 to 5 (range, 0 to 10, with lower values indicating larger infarction) or an infarct-core volume of 70 to 100 ml. Patients were randomly assigned in a 1:1 ratio within 24 hours from the time they were last known to be well to undergo endovascular therapy and receive medical management or to receive medical management alone. The primary outcome was the score on the modified Rankin scale at 90 days (scores range from 0 to 6, with higher scores indicating greater disability), and the primary objective was to determine whether a shift in the distribution of the scores on the modified Rankin scale at 90 days had occurred between the two groups. Secondary outcomes included scores of 0 to 2 and 0 to 3 on the modified Rankin scale. The primary safety outcome was symptomatic intracranial hemorrhage within 48 hours after randomization. RESULTS: A total of 456 patients were enrolled; 231 were assigned to the endovascular-therapy group and 225 to the medical-management group. Approximately 28% of the patients in both groups received intravenous thrombolysis. The trial was stopped early owing to the efficacy of endovascular therapy after the second interim analysis. At 90 days, a shift in the distribution of scores on the modified Rankin scale toward better outcomes was observed in favor of endovascular therapy over medical management alone (generalized odds ratio, 1.37; 95% confidence interval, 1.11 to 1.69; P = 0.004). Symptomatic intracranial hemorrhage occurred in 14 of 230 patients (6.1%) in the endovascular-therapy group and in 6 of 225 patients (2.7%) in the medical-management group; any intracranial hemorrhage occurred in 113 (49.1%) and 39 (17.3%), respectively. Results for the secondary outcomes generally supported those of the primary analysis. CONCLUSIONS: In a trial conducted in China, patients with large cerebral infarctions had better outcomes with endovascular therapy administered within 24 hours than with medical management alone but had more intracranial hemorrhages. (Funded by Covidien Healthcare International Trading [Shanghai] and others; ANGEL-ASPECT ClinicalTrials.gov number, NCT04551664.).

Female reproductive health during the COVID-19 pandemic: latest evidence and understanding.

PURPOSE: The ongoing coronavirus disease 2019 (COVID-19) pandemic, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has imposed a heavy burden on medical systems. In addition to the respiratory system, the virus also causes injuries to other organs and systems such as the gastroenteric system, kidneys, and reproductive system. Female reproductive health requires more attention in this context. METHODS: We have performed a thorough review of the relevant literature that addresses the impacts of SARS-CoV-2 infection and COVID-19 vaccination on the female reproductive system. RESULTS: Most evidence shows that SARS-CoV-2 does not infect the female reproductive system. However, the virus may indirectly influence sex hormone concentrations through inflammation associated with cytokine storms and nervous system damage. Menstrual disorders in women infected with SARS-CoV-2 may be caused by down-regulation of angiotensin-converting enzyme 2, abnormal hormone levels, medications, and stress. There is no significant difference in ovarian follicle quality and in vitro fertilization parameters between the pre- and post-COVID-19 vaccination groups. In addition, most symptoms due to side effects of vaccination could recover within a short period of time. CONCLUSION: SARS-CoV-2 infection affects female reproductive system function through multiple mechanisms. It is recommended that women of childbearing age be vaccinated with COVID-19 vaccine.

Aloe polymeric acemannan inhibits the cytokine storm in mouse pneumonia models by modulating macrophage metabolism.

The cytokine storm is highly associated with inflammatory-type disease severity and patients' survival. Plant polysaccharides, the main natural phytomedicine source, have a great potential to be an effective drug to treat cytokine storm. Herein we found that a polymeric acemannan (ABPA1) isolated from Aloe Vera Barbadensis extract C (AVBEC) exerted prominent inhibitory effects on inflammation-induced cytokine storm. The results displayed that ABPA1 effectively suppressed LPS-induced proinflammatory cytokines release in vitro. Moreover, ABPA1 treatment alleviated the cytokine storm and tissue damage in LPS- and IAV-induced mouse pneumonia models, and altered the phenotypic balance of macrophages in lung tissues. Functionally, ABPA1 enhanced macrophage M2 polarization and phagocytosis in RAW264.7 cells and inhibited LPS-induced M1 polarization. Mechanistically, ABPA1 enhanced mitochondrial metabolism and OXPHOS through activated PI3K/Akt/GSK-3ß signalling pathway. Overall, our findings suggest that ABPA1 may modulate macrophage activation and mitochondrial metabolism by targeting PI3K/Akt/GSK-3ß signalling pathway, thereby alleviating cytokine storm and inflammation.

Associations between social support and anxiety during the COVID-19 lockdown in young and middle-aged Israelis: A cross-sectional study.

BACKGROUND: This study examined the associations between social support and anxiety during the coronavirus disease 2019 (COVID-19) in an Israeli sample. AIM: To examine the associations between social support and anxiety during the COVID-19 in an Israeli sample. METHODS: Data for this cross-sectional study were retrieved from an online survey. Linear regression, logistic regression and restricted cubic spline models were conducted to test for associations between social support and anxiety. RESULTS: A total of 655 individuals took part in the present study. In the univariate linear regression model, there is a negative correlation between the Generalized Anxiety Disorder-7 score (GAD-7) and the Multidimensional Perceived Social Support Scale (MSPSS) score. For MSPSS score, the multivariable adjusted regression coefficient and 95% confidence interval (CI) of GAD-7 score were -0.779 (-1.063 to -0.496). In the univariate logistic regression model, there was a negative correlation between anxiety (GAD-7 ≥ 9) and MSPSS score, and there was still a negative correlation in multivariate logical regression analysis. The odds ratios and 95%CI were 0.709 (0.563-0.894). CONCLUSION: Social support was inversely correlated with anxiety during COVID-19 in an Israeli sample.

Post-COVID-19 Development of Transnational Education in China: Challenges and Opportunities

Transnational education is education delivered to students in a country other than the country in which the awarding institution is based. While the outbreak of COVID-19 has significantly affected higher education, transnational education has exhibited its resilience against the pandemic, and has been continuously expanding in China. In parallel with the golden opportunities for the expansion of transnational education in China after the pandemic, a series of challenges resulting from the transnational context needs to be taken into due consideration, and to be properly addressed. In this paper, the opportunities and challenges for the post-COVID-19 development of transnational education in China are systematically discussed, based on the transnational education delivery at a Sino-Foreign cooperative university. Following our observations on opportunities and challenges, several suggestions are proposed, to address the potential challenges for the stable post-COVID-19 development of transnational education in China.

Parameter estimation of the COVID-19 transmission model using an improved quantum-behaved particle swarm optimization algorithm.

The outbreak of coronavirus disease (COVID-19) and its accompanying pandemic have created an unprecedented challenge worldwide. Parametric modeling and analyses of the COVID-19 play a critical role in providing vital information about the character and relevant guidance for controlling the pandemic. However, the epidemiological utility of the results obtained from the COVID-19 transmission model largely depends on accurately identifying parameters. This paper extends the susceptible-exposed-infectious-recovered (SEIR) model and proposes an improved quantum-behaved particle swarm optimization (QPSO) algorithm to estimate its parameters. A new strategy is developed to update the weighting factor of the mean best position by the reciprocal of multiplying the fitness of each best particle with the average fitness of all best particles, which can enhance the global search capacity. To increase the particle diversity, a probability function is designed to generate new particles in the updating iteration. When compared to the state-of-the-art estimation algorithms on the epidemic datasets of China, Italy and the US, the proposed method achieves good accuracy and convergence at a comparable computational complexity. The developed framework would be beneficial for experts to understand the characteristics of epidemic development and formulate epidemic prevention and control measures.

Impact of COVID-19 Outbreak on the Gynecological Outpatients HPV Infection Rate in Wuhan, China: A Retrospective Observational Study.

Background: The recent severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) outbreak has caused millions of deaths and greatly influenced the timely diagnosis and treatment of other diseases. Throughout the pandemic, there was a dramatic reduction in the prevalence of several sexually transmitted infections. However, the impact of the ongoing pandemic on human papillomavirus (HPV) infection rates has not been investigated thus far. Materials and Methods: We retrospectively collected data regarding HPV and cervical cancer screening results of outpatients from gynecological clinics of a tertiary hospital from 1 December 2018 to 31 December 2020 in Wuhan. Based on the timeline of the SARS-CoV-2 pandemic in Wuhan, we divided this period into four relatively independent stages to compare the HPV screening visit numbers and infection rates. Results: There was a 50% drop in HPV screening visits and a 10% drop in HPV infection rates throughout the pandemic when compared with the numbers collected before the pandemic. Strict lockdown measures greatly decreased the HPV infection rate (17.03 vs. 8.29, P = 0.003). During the pandemic, the most prevalent HPV genotypes were HPV 16, 52, 58, and 53. After the pandemic, the HPV infection rate recovered quickly, but it was still slightly lower than the infection rate found before the outbreak (23.3 vs. 21.2%). Conclusion: During coronavirus disease 2019 (COVID-19) pandemic, cervical cancer screening visits and HPV infection rates have decreased dramatically. The HPV transmission has also decreased after strict lockdown. Effective HPV and cervical cancer screening programs should be strengthened immediately to reduce the transmission of HPV during and after the pandemic.

An Oral SARS-CoV-2 Mpro Inhibitor Clinical Candidate for the Treatment of COVID-19 (preprint)

The worldwide outbreak of coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has become an established global pandemic. Alongside vaccines, antiviral therapeutics are an important part of the healthcare response to counter the ongoing threat presented by COVID-19. Here, we report the discovery and characterization of PF-07321332, an orally bioavailable SARS-CoV-2 main protease inhibitor with in vitro pan-human coronavirus antiviral activity, and excellent off-target selectivity and in vivo safety profiles. PF-07321332 has demonstrated oral activity in a mouse-adapted SARS-CoV-2 model and has achieved oral plasma concentrations exceeding the in vitro antiviral cell potency, in a phase I clinical trial in healthy human participants. Clinical Trial Registration ID #: NCT04756531

Clinical characteristics and risk factors for symptomatic venous thromboembolism in hospitalized COVID-19 patients: A multicenter retrospective study.

BACKGROUND: High incidence of asymptomatic venous thromboembolism (VTE) has been observed in severe COVID-19 patients, but the characteristics of symptomatic VTE in general COVID-19 patients have not been described. OBJECTIVES: To comprehensively explore the prevalence and reliable risk prediction for VTE in COVID-19 patients. METHODS/RESULTS: This retrospective study enrolled all COVID-19 patients with a subsequent VTE in 16 centers in China from January 1 to March 31, 2020. A total of 2779 patients were confirmed with COVID-19. In comparison to 23,434 non-COVID-19 medical inpatients, the odds ratios (ORs) for developing symptomatic VTE in severe and non-severe hospitalized COVID-19 patients were 5.94 (95% confidence interval [CI] 3.91-10.09) and 2.79 (95% CI 1.43-5.60), respectively. When 104 VTE cases and 208 non-VTE cases were compared, pulmonary embolism cases had a higher rate for in-hospital death (OR 6.74, 95% CI 2.18-20.81). VTE developed at a median of 21 days (interquartile range 13.25-31) since onset. Independent factors for VTE were advancing age, cancer, longer interval from symptom onset to admission, lower fibrinogen and higher D-dimer on admission, and D-dimer increment (DI) ≥1.5-fold; of these, DI ≥1.5-fold had the most significant association (OR 14.18, 95% CI 6.25-32.18, p = 2.23 × 10-10 ). A novel model consisting of three simple coagulation variables (fibrinogen and D-dimer levels on admission, and DI ≥1.5-fold) showed good prediction for symptomatic VTE (area under the curve 0.865, 95% CI 0.822-0.907, sensitivity 0.930, specificity 0.710). CONCLUSIONS: There is an excess risk of VTE in hospitalized COVID-19 patients. This novel model can aid early identification of patients who are at high risk for VTE.

Epidemiological and clinical characteristics of 47 corona virus disease 2019 non-survivors in Huoshenshan Hospital

Objective To provide a basis for further optimizing the diagnosis and treatment strategies of severe and critical corona virus disease 2019 (COVID-19) by investigating and analyzing the epidemiological and clinical characteristics of the death cases. Methods The epidemiological and clinical characteristics of 47 death cases obtained from Huoshenshan Hospital in Whuhan, Hubei Province were retrospectively analyzed. Results All the patients developed initial symptoms in Wuhan. The time from onset to admission was (12.60±5.60) days. Most of them were male (68.09%) with non-nosocomial infection (91.49%), advanced age (>60 years, 89.36%). Over half of the cases (51.06%) reported a history of contact with suspected or confirmed patients, and comorbidity of chronic diseases (70.21%). Multiple organ dysfunction syndrome (MODS) occurred in 29 cases (61.70%) with heart failure (51.06%) and renal failure (36.17%). The main clinical symptoms included fever, fatigue, dyspnea and cough. At admission,most cases were severe (55.32%) or critical (42.55%), and the in-hospital survival was longer for the severe than for the critical (P=0.02). 76.59% of the patients received invasive mechanical ventilation, and they had a longer in-hospital survival than those with non-invasive mechanical ventilation (P<0.05). Conclusions This group of cases occurred during the peak of the COVID-19 outbreak in China, characterized by male, elder and history of chronic diseases. Acute respiratory distress syndrome (ARDS) caused by COVID-19 was responsible for patients' death, and MODS manifestated by heart and kidney failure also implicated in the process. Disease severity and invasive mechanical ventilation were related to in-hospital survival.