Development of a risk assessment model for cardiac injury in patients newly diagnosed with acute myeloid leukemia based on a multicenter, real-world analysis in China.

BACKGROUND: Studies have revealed that acute myeloid leukemia (AML) patients are prone to combined cardiac injury. We aimed to identify hematological risk factors associated with cardiac injury in newly diagnosed AML patients before chemotherapy and develop a personalized predictive model. METHODS: The population baseline, blood test, electrocardiogram, echocardiograph, and genetic and cytogenetic data were collected from newly diagnosed AML patients. The data were subdivided into training and validation cohorts. The independent risk factors were explored by univariate and multivariate logistic regression analysis respectively, and data dimension reduction and variable selection were performed using the least absolute shrinkage and selection operator (LASSO) regression models. The nomogram was generated and the reliability and generalizability were verified by receiver operating characteristic (ROC) curves, the area under the curve (AUC) and calibration curves in an external validation cohort. RESULTS: Finally, 499 AML patients were included. After univariate logistic regression, LASSO regression and multivariate logistic regression analysis, abnormal NT-proBNP, NPM1 mutation, WBC, and RBC were independent risk factors for cardiac injury in AML patients (all P < 0.05). The nomogram was constructed based on the above four variables with high accuracy. The area under the curve was 0.742, 0.750, and 0.706 in the training, internal validation, and external validation cohort, respectively. The calibration curve indicated that the model has good testing capability. The Kaplan-Meier curve showed that the higher the risk of combined cardiac injury in AML patients, the lower their probability of survival. CONCLUSIONS: This prediction nomogram identifies hematological risk factors associated with cardiac injury in newly diagnosed AML patients and can help hematologists identify the risk and provide precise treatment options.

Prevalence trends of anemia impairment in adolescents and young adults with HIV/AIDS.

BACKGROUND: Anemia is a common complication of HIV/AIDS, particularly in adolescents and young adults across various countries and regions. However, little is known about the changing prevalence trends of anemia impairment in this population over time. METHODS: Data on anemia in adolescents and young adults with HIV/AIDS from 1990 to 2019 were collected from the Global Burden of Disease. Prevalence was calculated by gender, region, and country for individuals aged 10-24, and trends were measured using estimating annual percentage changes (EAPC). RESULTS: Globally, the prevalence of adolescents and young adults with HIV/AIDS increased from 103.95 per 100,000 population in 1990 to 203.78 in 2019. However, anemia impairment has decreased over the past three decades, with a global percentage decreasing from 70.6% in 1990 to 34.7% in 2019, mainly presenting as mild to moderate anemia and significantly higher in females than males. The largest decreases were observed in Central Sub-Saharan Africa, North America, and Eastern Sub-Saharan Africa, with EAPCs of -2.8, -2.34, and -2.17, respectively. Tajikistan (78.76%) and Madagascar (74.65%) had the highest anemia impairment percentage in 2019, while China (16.61%) and Iceland (13.73%) had the lowest. Anemia impairment was closely related to sociodemographic index (SDI) levels, with a high proportion of impairment in low SDI regions but a stable decreasing trend (EAPC = -0.37). CONCLUSION: Continued anemia monitoring and management are crucial for patients with HIV, especially in high-prevalence regions and among females. Public health policies and interventions can improve the quality of life and reduce morbidity and mortality.

FLT3-selective PROTAC: Enhanced safety and increased synergy with Venetoclax in FLT3-ITD mutated acute myeloid leukemia.

Acute myeloid leukemia (AML) patients carrying Fms-like tyrosine kinase 3-internal tandem duplication (FLT3-ITD) mutations often face a poor prognosis. While some FLT3 inhibitors have been used clinically, challenges such as short efficacy and poor specificity persist. Proteolytic targeting chimera (PROTAC), with its lower ligand affinity requirement for target proteins, offers higher and rapid targeting capability. Gilteritinib, used as the ligand for the target protein, was connected with different E3 ligase ligands to synthesize several series of PROTAC targeting FLT3-ITD. Through screening and structural optimization, the optimal lead compound PROTAC Z29 showed better specificity than Gilteritinib. Z29 induced FLT3 degradation through the proteasome pathway and inhibited tumor growth in subcutaneous xenograft mice. We verified Z29's minimal impact on platelets in a patient-derived xenografts (PDX) model compared to Gilteritinib. The combination of Z29 and Venetoclax showed better anti-tumor effects, lower platelet toxicity, and lower hepatic toxicity in FLT3-ITD+ models. The FLT3-selective PROTAC can mitigate the platelet toxicity of small molecule inhibitors, ensuring safety and efficacy in monotherapy and combination therapy with Venetoclax. It is a promising strategy for FLT3-ITD+ patients, especially those with platelet deficiency or liver damage.

Comprehensive analysis of clinical prognostic features and tumor microenvironment landscape of CD11b+CD64+ patients with acute myeloid leukemia.

BACKGROUND: Immunophenotyping surface molecules detected in the clinic are mainly applied in diagnostic confirmation and subtyping. However, the immunomodulatory molecules CD11b and CD64, are highly associated with leukemogenesis. Hence, the prognostic value of them and their potential biological functions merit further investigation. METHODS: Flow cytometry was operated to detect immunophenotypic molecules from AML bone marrow samples. Multivariate cox regression, Kaplan-Meier analyses, and nomogram were conducted to predict survival. Transcriptomic data, lymphocyte subsets, and immunohistochemical staining were incorporated to identify potential biological functions of prognostic immunophenotype in acute myeloid leukemia (AML). RESULTS: We classified 315 newly diagnosed AML patients of our center based on the expression of CD11b and CD64. The CD11b+CD64+ populations were identified as independent risk factors for overall survival and event-free survival of AML, exhibiting specific clinicopathological features. The predictive models based on CD11b+CD64+ showed high classification performance. In addition, the CD11b+CD64+ subset, characterized by high inhibitory immune checkpoints, M2-macrophage infiltration, low anti-tumor effector cells infiltration, as well as abnormal somatic mutation landscape, presented a distinctive tumor microenvironmental landscape. The CD11b+CD64+ population showd a higher expression of BCL2, and the drug sensitivity indicated that they presented a lower half-maximal inhibitory concentration value for BCL2 inhibitor, and could benefit more from the above medicine. CONCLUSIONS: This work might be of benefit to enhanced understanding of CD11b+CD64+ in the prognosis and leukemogenesis, and yielded novel biomarkers to guide immunotherapy and targeted therapy for AML.

Global burden of hematologic malignancies and evolution patterns over the past 30 years.

Hematologic malignancies are among the most common cancers, and understanding their incidence and death is crucial for targeting prevention, clinical practice improvement, and research resources appropriately. Here, we investigated detailed information on hematological malignancies for the period 1990-2019 from the Global Burden of Disease study. The age-standardized incidence rate (ASIR), the age-standardized death rate (ASDR), and the corresponding estimated annual percentage changes (EAPC) were calculated to assess temporal trends in 204 countries and territories over the past 30 years. Globally, incident cases of hematologic malignancies have been increasing since 1990, reaching 1343.85 thousand in 2019, but the ASDR for all types of hematologic malignancies has been declining. The ASDR for leukemia, multiple myeloma, non-Hodgkin lymphoma, and Hodgkin lymphoma were 4.26, 1.42, 3.19, and 0.34 per 100,000 population in 2019, respectively, with Hodgkin lymphoma showing the most significant decline. However, the trend varies by gender, age, region, and the country's economic situation. The burden of hematologic malignancies is generally higher in men, and this gender gap decreases after peaking at a given age. The regions with the largest increasing trend in the ASIR of leukemia, multiple myeloma, non-Hodgkin lymphoma, and Hodgkin lymphoma were Central Europe, Eastern Europe, East Asia, and Caribbean, respectively. In addition, the proportion of deaths attributed to high body-mass index continued to rise across regions, especially in regions with high socio-demographic indices (SDI). Meanwhile, the burden of leukemia from occupational exposure to benzene and formaldehyde was more widespread in areas with low SDI. Thus, hematologic malignancies remain the leading cause of the global tumor burden, with growing absolute numbers but sharp among several age-standardized measures over the past three decades. The results of the study will inform analysis of trends in the global burden of disease for specific hematologic malignancies and develop appropriate policies for these modifiable risks.

Distributions and Trends of the Global Burden of Colorectal Cancer Attributable to Dietary Risk Factors over the Past 30 Years.

Dietary risk has always been a major risk factor for colorectal cancer (CRC). However, the contribution of dietary risk factors to CRC at the level of region, gender, and age has not been fully characterized. Based on the Global Burden of Disease (GBD) 2019 study, the death rates, age-standardized mortality rates (ASDRs), and estimated annual percentage changes (EAPCs) were calculated to assess the trends of CRC attributable to dietary risk factors over the past 30 years. Globally, the death cases of CRC increased to 1,085,797 in 2019, and the number of deaths attributed to dietary risk factors increased to 365,752 in 2019, representing approximately one-third of all CRC-related fatalities. Overall, the ASDR attributable to dietary risks was 4.61 per 100,000 in 2019, with a slight downward trend (EAPC = -0.29). Notably, there is a rising trend in early-onset colorectal cancer mortality associated with dietary factors. To alleviate CRC burdens, it is recommended to elevate the intake of whole grains, milk, calcium, and fiber while reducing consumption of red and processed meats. The results will improve the understanding, and provide guidance on the diet of CRC in different regions, gender, and age groups worldwide.

Magnetically Actuated Hydrogel Stamping-Assisted Cellular Mechanical Analyzer for Stored Blood Quality Detection.

Cellular mechanical property analysis reflecting the physiological and pathological states of cells plays a crucial role in assessing the quality of stored blood. However, its complex equipment needs, operation difficulty, and clogging issues hinder automated and rapid biomechanical testing. Here, we propose a promising biosensor assisted by magnetically actuated hydrogel stamping to fulfill it. The flexible magnetic actuator triggers the collective deformation of multiple cells in the light-cured hydrogel, and it allows for on-demand bioforce stimulation with the advantages of portability, cost-effectiveness, and simplicity of operation. The magnetically manipulated cell deformation processes are captured by the integrated miniaturized optical imaging system, and the cellular mechanical property parameters are extracted from the captured images for real-time analysis and intelligent sensing. In this work, 30 clinical blood samples with different storage durations (<14 days and >14 days) were tested. A deviation of 3.3% in the differentiation of blood storage durations by this system compared to physician annotation demonstrated its feasibility. This system should broaden the application of cellular mechanical assays in diverse clinical settings.

Valve-Adjustable Optofluidic Bio-Imaging Platform for Progressive Stenosis Investigation.

The clinical evidence has proven that valvular stenosis is closely related to many vascular diseases, which attracts great academic attention to the corresponding pathological mechanisms. The investigation is expected to benefit from the further development of an in vitro model that is tunable for bio-mimicking progressive valvular stenosis and enables accurate optical recognition in complex blood flow. Here, we develop a valve-adjustable optofluidic bio-imaging recognition platform to fulfill it. Specifically, the bionic valve was designed with in situ soft membrane, and the internal air-pressure chamber could be regulated from the inside out to bio-mimic progressive valvular stenosis. The developed imaging algorithm enhances the recognition of optical details in blood flow imaging and allows for quantitative analysis. In a prospective clinical study, we examined the effect of progressive valvular stenosis on hemodynamics within the typical physiological range of veins by this way, where the inhomogeneity and local enhancement effect in the altered blood flow field were precisely described and the optical differences were quantified. The effectiveness and consistency of the results were further validated through statistical analysis. In addition, we tested it on fluorescence and noticed its good performance in fluorescent tracing of the clotting process. In virtue of theses merits, this system should be able to contribute to mechanism investigation, pharmaceutical development, and therapeutics of valvular stenosis-related diseases.

A novel organic arsenic derivative MZ2 remodels metabolism and triggers mtROS-mediated apoptosis in acute myeloid leukemia.

PURPOSE: Acute myeloid leukemia (AML) is one of the most common neoplasms in adults, and it is difficult to achieve satisfactory results with conventional drugs. Here, we synthesized a novel organic arsenic derivative MZ2 and evaluated its ability to remodel energy metabolism to achieve anti-leukemia. METHODS: MZ2 was characterized by the average 1-min full mass spectra analysis. Biological methods such as Western blot, qPCR, flow cytometry and confocal microscopy were used to assess the mode and mechanism of MZ2-induced death. The in vivo efficacy of MZ2 was assessed by constructing a patient-derived xenograft (PDX) AML model. RESULTS: Unlike the precursor organic arsenical Z2, MZ2 can effectively reduce the level of aerobic glycolysis. Our in-depth found that MZ2 inhibited the expression of PDK2 in a dose-dependent manner and did not affect the expression of LDHA, another key enzyme of the glycolytic pathway. MZ2 reconstituted energy metabolism to induce the generation of mitochondrial ROS (mtROS) and then triggerd intrinsic apoptosis pathway. We also assessed whether MZ2 generates autophagy and results showed that MZ2 can induce autophagy of AML cells, which may be associated with the precursor organic arsenic drug. In vivo, MZ2 effectively attenuated leukemia progression in mice, and immunohistochemical results suggested its PDK2 inhibitory effect. CONCLUSION: In summary, the novel organic arsine derivative MZ2 exhibited excellent anti-tumor effects in acute myeloid leukemia, which may provide a potential strategy for the treatment of acute myeloid leukemia.

A microfluidic hemostatic diagnostics platform: Harnessing coagulation-induced adaptive-bubble behavioral perception.

Clinical viscoelastic hemostatic assays, which have been used for decades, rely on measuring biomechanical responses to physical stimuli but face challenges related to high device and test cost, limited portability, and limited scalability.. Here, we report a differential pattern using self-induced adaptive-bubble behavioral perception to refresh it. The adaptive behaviors of bubble deformation during coagulation precisely describe the transformation of viscoelastic hemostatic properties, being free of the precise and complex physical devices. And the integrated bubble array chip allows microassays and enables multi-bubble tests with good reproducibility. Recognition of the developed bubble behaviors empowers automated and user-friendly diagnosis. In a prospective clinical study (clinical model development [n = 273]; clinical assay [n = 44]), we show that the diagnostic accuracies were 99.1% for key viscoelastic hemostatic assay indicators (reaction time [R], kinetics time [K], alpha angle [Angle], maximum amplitude [MA], lysis at 30 min [LY30]; n = 220) and 100% (n = 44) for hypercoagulation, healthy, and hypocoagulation diagnoses. This should provide fresh insight into existing paradigms and help more clinical needs.

Serum proteomics screening intercellular adhesion molecule-2 improves intermediate-risk stratification in acute myeloid leukemia.

Background: The clinical risk classification of acute myelocytic leukemia (AML) is largely based on cytogenetic and molecular genetic detection. However, the optimal treatment for intermediate-risk AML patients remains uncertain. Further refinement and improvement of prognostic stratification are therefore necessary. Objectives: The aim of this study was to identify serum protein biomarkers to refine risk stratification in AML patients. Design: This study is a retrospective study. Methods: Label-free proteomics was used to identify the differential abundance of serum proteins in AML patients. Transcriptomic data were combined to identify key altered markers that could indicate the risk rank of AML patients. The survival status was assessed by Kaplan-Meier and multivariate Cox regression analyses. Results: We delineated serum protein expression in a population of AML patients. Many biological processes were influenced by the identified differentially expressed proteins. Association analysis of transcriptome data showed that intercellular adhesion molecule-2 (ICAM2) had a higher survival prediction value in the intermediate-risk AML group. ICAM2 was detrimental for intermediate-risk AML, regardless of whether patients received bone marrow transplantation. ICAM2 well distinguishes the intermediate group of patients, whose probability of survival is comparable to that of patients with the ELN-2017 according to the reference classification. In addition, newly established stratified clinical features were associated with leukemia stem cell scores. Conclusion: The inclusion of ICAM2 expression into the AML risk classification according to ELN-2017 was a good way to transfer patients from three to two groups. Thus, providing more information for clinical decision-making to improve intermediate-risk stratification in AML patients.

Space-time-regulated imaging analyzer for smart coagulation diagnosis.

The development of intelligent blood coagulation diagnoses is awaited to meet the current need for large clinical time-sensitive caseloads due to its efficient and automated diagnoses. Herein, a method is reported and validated to realize it through artificial intelligence (AI)-assisted optical clotting biophysics (OCB) properties identification. The image differential calculation is used for precise acquisition of OCB properties with elimination of initial differences, and the strategy of space-time regulation allows on-demand space time OCB properties identification and enables diverse blood function diagnoses. The integrated applications of smartphones and cloud computing offer a user-friendly automated analysis for accurate and convenient diagnoses. The prospective assays of clinical cases (n = 41) show that the system realizes 97.6%, 95.1%, and 100% accuracy for coagulation factors, fibrinogen function, and comprehensive blood coagulation diagnoses, respectively. This method should enable more low-cost and convenient diagnoses and provide a path for potential diagnostic-markers finding.

Cardiac-Related Lesions in Newly Diagnosed Patients With Acute Leukemia: A Chinese Population-Based Real-World Study.

The relationship between newly diagnosed acute leukemia (AL) and heart-related lesions remains unclear. This study aimed to investigate baseline cardiac function and risk of cardiovascular diseases (CVDs) in patients with new-onset AL, and provide data on cardiac management strategies for patients with AL. We retrospectively collected data on baseline characteristics, echocardiography, and biochemical blood indicators (e.g., myocardial enzymes) from 408 patients, 200 with newly diagnosed AL, 103 with coronary artery disease (CAD), and 105 controls from January 1, 2015 to August 31, 2019. The creatine kinase isoenzyme myocardial band, lactate dehydrogenase, highly sensitive troponin-I, and B-type natriuretic peptide levels and left ventricular internal diameter (LVID) were significantly higher in patients with newly diagnosed AL than in the control group. The degree of cardiac damage was lower in newly diagnosed AL patients than in CAD patients. The best predictor of heart damage was LVID (AUC [area under the curve] = 0.709; 95% CI [confidence interval]: 0.637-0.781; p < 0.001), and independent prognostic risk factors were age and ejection fraction (HR [hazard ratio] = 1.636; 95% CI: 1.039-2.575; p = 0.033). The ratio of leukemia blasts among patients with AL was positively correlated with cardiac damage. Our data indicated that newly diagnosed AL patients had certain myocardial damage before treatment. Clinicians need to pay attention to these manifestations, which may be related to the prognosis.

Touchable cell biophysics property recognition platforms enable multifunctional blood smart health care.

As a crucial biophysical property, red blood cell (RBC) deformability is pathologically altered in numerous disease states, and biochemical and structural changes occur over time in stored samples of otherwise normal RBCs. However, there is still a gap in applying it further to point-of-care blood devices due to the large external equipment (high-resolution microscope and microfluidic pump), associated operational difficulties, and professional analysis. Herein, we revolutionarily propose a smart optofluidic system to provide a differential diagnosis for blood testing via precise cell biophysics property recognition both mechanically and morphologically. Deformation of the RBC population is caused by pressing the hydrogel via an integrated mechanical transfer device. The biophysical properties of the cell population are obtained by the designed smartphone algorithm. Artificial intelligence-based modeling of cell biophysics properties related to blood diseases and quality was developed for online testing. We currently achieve 100% diagnostic accuracy for five typical clinical blood diseases (90 megaloblastic anemia, 78 myelofibrosis, 84 iron deficiency anemia, 48 thrombotic thrombocytopenic purpura, and 48 thalassemias) via real-world prospective implementation; furthermore, personalized blood quality (for transfusion in cardiac surgery) monitoring is achieved with an accuracy of 96.9%. This work suggests a potential basis for next-generation blood smart health care devices.

Developments, Evolution, and Implications of National Diagnostic Criteria for COVID-19 in China.

Recently WHO has characterized COVID-19 as a pandemic. Diagnosing the disease accurately and decreasing misdiagnoses and missed diagnoses is very important for management. Therefore, we have analyzed the seven versions of China's national guidelines to examine how the diagnostic criteria roadmap has developed and evolved, in order to share our experience worldwide. In this article, we present the developments from the first to seventh versions, involving changes of case classification, changes to "suspected case," changes in "confirmed case," changes in clinical classifications, changes in "severe case," and unchanged criteria. We have also discussed the reasons and implications for these changes and are looking forward to providing suggestions for worldwide understanding and management of this pandemic. A nucleic acid test is currently accepted as the gold standard method to confirm diagnosis. In addition, imaging examination and epidemiological history should also be considered as auxiliary diagnosis methods.

Methodological quality (risk of bias) assessment tools for primary and secondary medical studies: what are they and which is better?

Methodological quality (risk of bias) assessment is an important step before study initiation usage. Therefore, accurately judging study type is the first priority, and the choosing proper tool is also important. In this review, we introduced methodological quality assessment tools for randomized controlled trial (including individual and cluster), animal study, non-randomized interventional studies (including follow-up study, controlled before-and-after study, before-after/ pre-post study, uncontrolled longitudinal study, interrupted time series study), cohort study, case-control study, cross-sectional study (including analytical and descriptive), observational case series and case reports, comparative effectiveness research, diagnostic study, health economic evaluation, prediction study (including predictor finding study, prediction model impact study, prognostic prediction model study), qualitative study, outcome measurement instruments (including patient - reported outcome measure development, content validity, structural validity, internal consistency, cross-cultural validity/ measurement invariance, reliability, measurement error, criterion validity, hypotheses testing for construct validity, and responsiveness), systematic review and meta-analysis, and clinical practice guideline. The readers of our review can distinguish the types of medical studies and choose appropriate tools. In one word, comprehensively mastering relevant knowledge and implementing more practices are basic requirements for correctly assessing the methodological quality.

Tracing asymptomatic SARS-CoV-2 carriers among 3674 hospital staff:a cross-sectional survey.

BACKGROUND: Asymptomatic carriers were positive for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) without developing symptoms, which might be a potential source of infection outbreak. Here, we aim to clarify the epidemiologic and influencing factors of asymptomatic carriers in the general population. METHODS: In our hospital, all hospital staff have received throat swab RT-PCR test, plasma COVID-19 IgM/IgG antibodies test and chest CT examination. We analyzed the correlation between infection rates and gender, age, job position, work place and COVID-19 knowledge training of the staff. After that, all asymptomatic staff were re-examined weekly for 3 weeks. FINDINGS: A total of 3764 hospital staff were included in this single-center cross-sectional study. Among them, 126 hospital staff had abnormal findings, and the proportion of asymptomatic infection accounted for 0.76% (28/3674). There were 26 staff with IgM+, 73 with IgG+, and 40 with ground glass shadow of chest CT. Of all staff with abnormal findings, the older they are, the more likely they are to be the staff with abnormal results, regardless of their gender. Of 3674 hospital staff, the positive rate of labor staff is obviously higher than that of health care workers (HCWs) and administrative staff (P<0.05). In the course of participating in the treatment of COVID-19, there was no statistically significant difference in positive rates between high-risk departments and low-risk departments (P>0.05). The positive rate of HCWs who participated in the COVID-19 knowledge training was lower than those did not participate in early training (P <0.01). Importantly, it was found that there was no statistical difference between the titers of IgM antibody of asymptomatic infections and confirmed patients with COVID-19 in recovery period (P>0.05). During 3 weeks follow-up, all asymptomatic patients did not present the development of clinical symptoms or radiographic abnormalities after active intervention in isolation point. INTERPRETATION: To ensure the safety of resumption of work, institutions should conduct COVID-19 prevention training for staff and screening for asymptomatic patients, and take quarantine measures as soon as possible in areas with high density of population. FUNDING: The Key Project for Anti-2019 novel Coronavirus Pneumonia from the Ministry of Science and Technology, China; Wuhan Emergency Technology Project of COVID-19 epidemic, China.

Coronavirus Disease 2019 Related Clinical Studies: A Cross-Sectional Analysis.

OBJECTIVE: The quality and rationality of many recently registered clinical studies related to coronavirus disease 2019 (COVID-19) needs to be assessed. Hence, this study aims to evaluate the current status of COVID-19 related registered clinical trial. METHODS: We did an electronic search of COVID-19 related clinical studies registered between December 1, 2019 and February 21, 2020 (updated to May 28, 2020) from the ClinicalTrials.gov, and collected registration information, study details, recruitment status, characteristics of the subjects, and relevant information about the trial implementation process. RESULTS: A total of 1,706 studies were included 10.0% of which (n=171) were from France, 943 (55.3%) used an interventional design, and 600 (35.2%) used an observational design. Most of studies (73.6%) aimed to recruit fewer than 500 people. Interferon was the main prevention program, and antiviral drugs were the main treatment program. Hydroxychloroquine and chloroquine (230/943, 24.4%) were widely studied. Some registered clinical trials are incomplete in content, and 37.4% of the 1,706 studies may have had insufficient sample size. CONCLUSION: The quality of COVID-19 related studies needs to be improved by strengthening the registration process and improving the quality of clinical study protocols so that these clinical studies can provide high-quality clinical evidence related to COVID-19.

Perceived infection transmission routes, infection control practices, psychosocial changes, and management of COVID-19 infected healthcare workers in a tertiary acute care hospital in Wuhan: a cross-sectional survey.

BACKGROUND: Many healthcare workers were infected by coronavirus disease 2019 (COVID-19) early in the epidemic posing a big challenge for epidemic control. Hence, this study aims to explore perceived infection routes, influencing factors, psychosocial changes, and management procedures for COVID-19 infected healthcare workers. METHODS: This is a cross-sectional, single hospital-based study. We recruited all 105 confirmed COVID-19 healthcare workers in the Zhongnan Hospital of Wuhan University from February 15 to 29, 2020. All participants completed a validated questionnaire. Electronic consent was obtained from all participants. Perceived causes of infection, infection prevention, control knowledge and behaviour, psychological changes, symptoms and treatment were measured. RESULTS: Finally, 103 professional staff with COVID-19 finished the questionnaire and was included (response rate: 98.1%). Of them, 87 cases (84.5%) thought they were infected in working environment in hospital, one (1.0%) thought their infection was due to the laboratory environment, and 5 (4.9%) thought they were infected in daily life or community environment. Swab of throat collection and physical examination were the procedures perceived as most likely causing their infection by nurses and doctors respectively. Forty-three (41.8%) thought their infection was related to protective equipment, utilization of common equipment (masks and gloves). The top three first symptoms displayed before diagnosis were fever (41.8%), lethargy (33.0%) and muscle aches (30.1%). After diagnosis, 88.3% staff experienced psychological stress or emotional changes during their isolation period, only 11.7% had almost no emotional changes. Arbidol (Umifenovir; an anti-influza drug; 69.2%) was the drug most commonly used to target infection in mild and moderate symptoms. CONCLUSION: The main perceived mode of transmission was not maintaining protection when working at a close distance and having intimate contact with infected cases. Positive psychological intervention is necessary.

Chemoprophylaxis, diagnosis, treatments, and discharge management of COVID-19: An evidence-based clinical practice guideline (updated version).

The novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the cause of a rapidly spreading illness, coronavirus disease 2019 (COVID-19), affecting more than seventeen million people around the world. Diagnosis and treatment guidelines for clinicians caring for patients are needed. In the early stage, we have issued "A rapid advice guideline for the diagnosis and treatment of 2019 novel coronavirus (2019-nCoV) infected pneumonia (standard version)"; now there are many direct evidences emerged and may change some of previous recommendations and it is ripe for develop an evidence-based guideline. We formed a working group of clinical experts and methodologists. The steering group members proposed 29 questions that are relevant to the management of COVID-19 covering the following areas: chemoprophylaxis, diagnosis, treatments, and discharge management. We searched the literature for direct evidence on the management of COVID-19, and assessed its certainty generated recommendations using the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) approach. Recommendations were either strong or weak, or in the form of ungraded consensus-based statement. Finally, we issued 34 statements. Among them, 6 were strong recommendations for, 14 were weak recommendations for, 3 were weak recommendations against and 11 were ungraded consensus-based statement. They covered topics of chemoprophylaxis (including agents and Traditional Chinese Medicine (TCM) agents), diagnosis (including clinical manifestations, reverse transcription-polymerase chain reaction (RT-PCR), respiratory tract specimens, IgM and IgG antibody tests, chest computed tomography, chest x-ray, and CT features of asymptomatic infections), treatments (including lopinavir-ritonavir, umifenovir, favipiravir, interferon, remdesivir, combination of antiviral drugs, hydroxychloroquine/chloroquine, interleukin-6 inhibitors, interleukin-1 inhibitors, glucocorticoid, qingfei paidu decoction, lianhua qingwen granules/capsules, convalescent plasma, lung transplantation, invasive or noninvasive ventilation, and extracorporeal membrane oxygenation (ECMO)), and discharge management (including discharge criteria and management plan in patients whose RT-PCR retesting shows SARS-CoV-2 positive after discharge). We also created two figures of these recommendations for the implementation purpose. We hope these recommendations can help support healthcare workers caring for COVID-19 patients.