Statistical Analysis Plan for the INTEnsive Care Bundle with Blood Pressure Reduction in Acute Cerebral Hemorrhage Trial: A Stepped-Wedge Cluster Randomized Controlled Trial.

The third INTEnsive care bundle with blood pressure Reduction in Acute Cerebral hemorrhage Trial (INTERACT3) is an international, multicenter, stepped-wedge (4 phases/3 steps) cluster randomized trial involving 110 hospitals in mainly low- and middle-income countries during 2017-2022. The aim is to determine the effectiveness of a goal-directed care bundle of intensive blood pressure (BP) lowering, glycemic control, antipyrexia, and anticoagulation reversal treatment versus usual standard of care, in patients with acute intracerebral hemorrhage (ICH). After a "usual care" period, hospitals were randomly allocated to implementing care-bundle protocols for control targets (systolic BP <140 mm Hg; glucose 6.1-7.8/7.8-10.0 mmol/L according to diabetes mellitus status; temperature ≤37.5°C; normalization of anticoagulation). A sample size of 8,360 patients (mean 19 per phase per site) provides 90% power (α = 0.05) for a 5.6% absolute improvement in the primary outcome of scores on the modified Rankin scale at 6 months, analyzed by ordinal logistic regression. A detailed statistical analysis plan (SAP) was developed to prespecify the method of analysis for all outcomes and key variables collected in the trial. The primary analysis will use ordinal logistic regression adjusted for the stepped-wedge design. The SAP also includes planned sensitivity analyses, including covariate adjustments, missing data imputations, and subgroup analysis. This SAP allows transparent, verifiable, and prespecified analyses in consideration of the challenges in conducting the study during the COVID pandemic. It also avoids analysis bias arising from prior knowledge of the findings in determining the benefits and harms of a care bundle in acute ICH.

COVID-19 lung infection segmentation from chest CT images based on CAPA-ResUNet.

Coronavirus disease 2019 (COVID-19) epidemic has devastating effects on personal health around the world. It is significant to achieve accurate segmentation of pulmonary infection regions, which is an early indicator of disease. To solve this problem, a deep learning model, namely, the content-aware pre-activated residual UNet (CAPA-ResUNet), was proposed for segmenting COVID-19 lesions from CT slices. In this network, the pre-activated residual block was used for down-sampling to solve the problems of complex foreground and large fluctuations of distribution in datasets during training and to avoid gradient disappearance. The area loss function based on the false segmentation regions was proposed to solve the problem of fuzzy boundary of the lesion area. This model was evaluated by the public dataset (COVID-19 Lung CT Lesion Segmentation Challenge-2020) and compared its performance with those of classical models. Our method gains an advantage over other models in multiple metrics. Such as the Dice coefficient, specificity (Spe), and intersection over union (IoU), our CAPA-ResUNet obtained 0.775 points, 0.972 points, and 0.646 points, respectively. The Dice coefficient of our model was 2.51% higher than Content-aware residual UNet (CARes-UNet). The code is available at https://github.com/malu108/LungInfectionSeg.

Effect of corticosteroids in patients with COVID-19: a Bayesian network meta-analysis.

OBJECTIVES: We sought to perform a network meta-analysis to compare the safety and efficacy of the systemic administration of corticosteroids for the treatment of COVID-19. METHODS: A Bayesian network meta-analysis was performed to combine the direct and indirect evidence. The surface under the cumulative ranking curve was obtained to estimate the ranking probability of the treatment agents for each outcome. The efficacy outcome was 28-day all-cause mortality. The safety outcome was serious adverse events. RESULTS: A total of 16 trials with 2992 patients comparing four treatments (dexamethasone, hydrocortisone, methylprednisolone, and placebo) were identified. Direct analysis showed that corticosteroids were associated with a reduced risk of 28-day mortality compared with usual care (risk ratio [RR] 0.83; 95% confidence interval [CrI] 0.70-0.99). Network analysis showed that the pooled RR was 0.63 (95% CrI 0.39-0.93) for all-cause mortality at 28 days comparing methylprednisolone with usual care or placebo (surface under the cumulative ranking curve: 91%). Our analysis demonstrated that patients who received a low dose of corticosteroids (RR 0.80; 95% CrI 0.70-0.91) and a long course of treatment (RR 0.81; 95% CrI 0.71-0.91) had higher survival rates than patients in the placebo group. CONCLUSION: Administration of corticosteroids was associated with a reduced all-cause mortality at 28 days compared with placebo or usual care. Our analysis also confirmed the mortality benefit associated with low-dose and long-term treatment with corticosteroids.

The role of NK cells in fighting the virus infection and sepsis.

Natural killer cells, one of the important types of innate immune cells, play a pivotal role in the antiviral process in vivo. It has been shown that increasing NK cell activity may promote the alleviation of viral infections, even severe infection-induced sepsis. Given the current state of the novel coronavirus (SARS-CoV-2) global pandemic, clarifying the anti-viral function of NK cells would be helpful for revealing the mechanism of host immune responses and decipher the progression of COVID-19 and providing important clues for combating this pandemic. In this review, we summarize the roles of NK cells in viral infection and sepsis as well as the potential possibilities of NK cell-based immunotherapy for treating COVID-19.

Prevalence of mental health problems among children and adolescents during the COVID-19 pandemic: A systematic review and meta-analysis.

BACKGROUND: This systematic review and meta-analysis examined the prevalence of depression, anxiety, sleep disorders, and posttraumatic stress symptoms among children and adolescents during global COVID-19 pandemic in 2019 to 2020, and the potential modifying effects of age and gender. METHODS: A literature search was conducted in PubMed, Web of Science, PsycINFO, and two Chinese academic databases (China National Knowledge Infrastructure and Wanfang) for studies published from December 2019 to September 2020 that reported the prevalence of above mental health problems among children and adolescents. Random-effects meta-analyses were used to estimate the pooled prevalence. RESULTS: Twenty-three studies (21 cross-sectional studies and 2 longitudinal studies) from two countries (i.e., China and Turkey) with 57,927 children and adolescents were identified. Depression, anxiety, sleep disorders, and posttraumatic stress symptoms were assessed in 12, 13, 2, and 2 studies, respectively. Meta-analysis of results from these studies showed that the pooled prevalence of depression, anxiety, sleep disorders, and posttraumatic stress symptoms were 29% (95%CI: 17%, 40%), 26% (95%CI: 16%, 35%), 44% (95%CI: 21%, 68%), and 48% (95%CI: -0.25, 1.21), respectively. The subgroup meta-analysis revealed that adolescents and females exhibited higher prevalence of depression and anxiety compared to children and males, respectively. LIMITATIONS: All studies in meta-analysis were from China limited the generalizability of our findings. CONCLUSIONS: Early evidence highlights the high prevalence of mental health problems among children and adolescents during the COVID-19 pandemic, especially among female and adolescents. Studies investigating the mental health of children and adolescents from countries other than China are urgently needed.

Changes in Characteristics, Treatment and Outcome in Patients with Hemorrhagic Stroke During COVID-19.

BACKGROUND AND PURPOSE: The coronavirus disease 2019 (COVID-19) pandemic has had a comprehensive impact on healthcare services worldwide. We sought to determine whether COVID-19 affected the treatment and prognosis of hemorrhagic stroke in a regional medical center in mainland China. METHODS: Patients with hemorrhagic stroke admitted in the Neurosurgery Department of West China Hospital from January 24, 2020, to March 25, 2020 (COVID-19 period), and from January 24, 2019, to March 25, 2019 (pre-COVID-19 period), were identified. Clinical characteristics, hospital arrival to neurosurgery department arrival time (door-to-department time), reporting rate of pneumonia and 3-month mRS (outcome) were compared. RESULTS: A total of 224 patients in the pre-COVID-19 period were compared with 126 patients in the COVID-19 period. Milder stroke severity was observed in the COVID-19 period (NIHSS 6 [2-20] vs. 3 [2-15], p = 0.005). The median door-to-department time in the COVID-19 period was approximately 50 minutes longer than that in the pre-COVID-19 period (96.5 [70.3-193.3] vs. 144.5 [93.8-504.5], p = 0.000). A higher rate of pneumonia complications was reported in the COVID-19 period (40.6% vs. 60.7%, p = 0.000). In patients with moderate hemorrhagic stroke, the percentage of good outcomes (mRS < 3) in the pre-COVID-19 period was much higher than that in the COVID-19 period (53.1% vs. 26.3%, p = 0.047). CONCLUSIONS: COVID-19 may have several impacts on the treatment of hemorrhagic stroke and may influence the clinical outcomes of specific patients. Improvements in the treatment process for patients with moderate stroke may help to improve the overall outcome of hemorrhagic stroke during COVID-19.

Impact of COVID-2019 on stroke services in China: survey from the Chinese Stroke Association.

BACKGROUND: The COVID-19 pandemic and physical distancing guidelines have compelled stroke practices worldwide to reshape their delivery of care significantly. We aimed to illustrate how the stroke services were interrupted during the pandemic in China. METHODS: A 61-item questionnaire designed on Wenjuanxing Form was completed by doctors or nurses who were involved in treating patients with stroke from 1 February to 31 March 2020. RESULTS: A total of 415 respondents completed the online survey after informed consent was obtained. Of the respondents, 37.8%, 35.2% and 27.0% were from mild, moderate and severe epidemic areas, respectively. Overall, the proportion of severe impact (reduction >50%) on the admission of transient ischaemic stroke, acute ischaemic stroke (AIS) and intracerebral haemorrhage (ICH) was 45.0%, 32.0% and 27.5%, respectively. Those numbers were 36.9%, 27.9% and 22.3%; 36.5%, 22.1% and 22.6%; and 66.4%, 47.5% and 41.1% in mild, moderate and severe epidemic areas, respectively (all p<0.0001). For AIS, thrombolysis was moderate (20%-50% reduction) or severely impacted (>50%), as reported by 54.4% of the respondents, while thrombectomy was 39.3%. These were 44.4%, 26.3%; 44.2%, 39.4%; and 78.2%, 56.5%, in mild, moderate and severe epidemic areas, respectively (all p<0.0001). For patients with acute ICH, 39.8% reported the impact was severe or moderate for those eligible for surgery who had surgery. Those numbers were 27.4%, 39.0% and 58.1% in mild, moderate and severe epidemic areas, respectively. For staff resources, about 20% (overall) to 55% (severe epidemic) of the respondents reported moderate or severe impact on the on-duty doctors and nurses. CONCLUSION: We found a significant reduction of admission for all types of patients with stroke during the pandemic. Patients were less likely to receive appropriate care, for example, thrombolysis/thrombectomy, after being admitted to the hospital. Stroke service in severe COVID-19 epidemic areas, for example, Wuhan, was much more severely impacted compared with other regions in China.

Systematic profiling of ACE2 expression in diverse physiological and pathological conditions for COVID-19/SARS-CoV-2.

Recent retrospective studies of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) disease (COVID-19) revealed that the patients with common comorbidities of cancers and chronic diseases face significantly poorer clinical outcomes than those without. Since the expression profile of ACE2, a crucial cell entry receptor for SARS-CoV-2, could indicate the susceptibility to SARS-CoV-2 infection, here we systematically dissected ACE2 expression using large-scale multi-omics data from 30 organs/tissues, 33 cancer types and some common chronic diseases involving >28 000 samples. It was found that sex and age could be correlated with the susceptibility of SARS-CoV-2 infection for certain tissues. Strikingly, ACE2 was up-regulated in cervical squamous cell carcinoma and endocervical adenocarcinoma, colon adenocarcinoma, oesophageal carcinoma, kidney renal papillary cell carcinoma, lung adenocarcinoma and uterine corpus endometrial carcinoma compared to controls. Furthermore, the patients with common chronic diseases regarding angiocardiopathy, type 2 diabetes, liver, pneumonia and hypertension were also with higher ACE2 expression compared to related controls, which were validated using independent data sets. Collectively, our study may reveal a novel important mechanism that the patients with certain cancers and chronic diseases may express higher ACE2 expression compared to the individuals without diseases, which could lead to their higher susceptibility to multi-organ injury of SARS-CoV-2 infection.