CAPRL Scoring System for Prediction of 30-day Mortality in 949 Patients with Coronavirus Disease 2019 in Wuhan, China: A Retrospective, Observational Study

Background:Coronavirus disease 2019 (COVID-19) is a serious and even lethal respiratory illness. The mortality of critically ill patients with COVID-19, especially short term mortality, is considerable. It is crucial and urgent to develop risk models that can predict the mortality risks of patients with COVID-19 at an early stage, which is helpful to guide clinicians in making appropriate decisions and optimizing the allocation of hospital resoureces.Methods:In this retrospective observational study, we enrolled 949 adult patients with laboratory-confirmed COVID-19 admitted to Tongji Hospital in Wuhan between January 28 and February 12, 2020. Demographic, clinical and laboratory data were collected and analyzed. A multivariable Cox proportional hazard regression analysis was performed to calculate hazard ratios and 95% confidence interval for assessing the risk factors for 30-day mortality.Results:The 30-day mortality was 11.8% (112 of 949 patients). Forty-nine point nine percent (474) patients had one or more comorbidities, with hypertension being the most common (359 [37.8%] patients), followed by diabetes (169 [17.8%] patients) and coronary heart disease (89 [9.4%] patients). Age above 50 years, respiratory rate above 30 beats per minute, white blood cell count of more than10 × 109/L, neutrophil count of more than 7 × 109/L, lymphocyte count of less than 0.8 × 109/L, platelet count of less than 100 × 109/L, lactate dehydrogenase of more than 400 U/L and high-sensitivity C-reactive protein of more than 50 mg/L were independent risk factors associated with 30-day mortality in patients with COVID-19. A predictive CAPRL score was proposed integrating independent risk factors. The 30-day mortality were 0% (0 of 156), 1.8% (8 of 434), 12.9% (26 of 201), 43.0% (55 of 128), and 76.7% (23 of 30) for patients with 0, 1, 2, 3, ≥4 points, respectively.Conclusions:We designed an easy-to-use clinically predictive tool for assessing 30-day mortality risk of COVID-19. It can accurately stratify hospitalized patients with COVID-19 into relevant risk categories and could provide guidance to make further clinical decisions. © 2021 The Chinese Medical Association, Published by Wolters Kluwer Health, Inc.

Advances in traditional Chinese medicine for respiratory disease therapy in 2021

Respiratory diseases are common conditions that endanger human health. Their etiology, pathogenesis, and prognosis are complex, and clinical research has been extensive. This paper reviews studies from the PubMed database to assess the progress of traditional Chinese medicine in the treatment of respiratory diseases in 2021, focusing on related animal and cell models of coronavirus disease 2019. Traditional Chinese medicine extracts, such as polysaccharides and emodin, and classic prescriptions, such as Mahuang decoction, respond to the treatment of influenza by reducing viral infections and regulating the body’s immune response. Chinese herbal extracts, such as schizandra B and andrographolide, treat asthma by inhibiting inflammatory response pathway formation, NLRP3 inflammasome formation, oxidative stress, and autophagy. Traditional Chinese medicine extracts such as fucoxanthin, and proprietary Chinese medicines such as the Xihuang pill is used in the treatment of lung cancer, as it regulates the cell cycle, inhibit tumor cell proliferation, and enhance the body’s immune function. Classic formulas such as the kidney tonic lung formula and proprietary Chinese medicine, such as compound grass stone silkworm granules, relieve airway inflammation and improve lung function in chronic obstructive pulmonary disease. Chinese herbal extracts, such as jostilbene and sage phenol, inhibit epithelial cell–mesenchymal transformation and regulate the levels of inflammatory factors to treat idiopathic pulmonary fibrosis to provide a reliable basis for the treatment of respiratory diseases.

Sharp schedule compression in urgent emergency construction projects via activity crashing, substitution and overlapping: a case study of Huoshengshan and Leishenshan Hospital projects in Wuhan

Purpose To meet the rapidly increasing demand for medical treatment during the outbreak of COVID-19, Huoshengshan and Leishenshan Hospital are rapidly built (9-12 days) in Wuhan. These two urgent emergency projects are unprecedented. In general, substantial literature suggests that the possibility of shortening a schedule by more than a quarter of its original duration is implausible. By contrast, the two projects had successfully compressed the schedules from months and years to about ten days. This study aims to investigate how this was done and provide references for future projects. Design/methodology/approach The study uses qualitative case study techniques to analyze the project practices in two urgent emergency projects. Data were gathered through semi-structured interviews and archival research. During interviews, interviewees were asked to describe the project practices adopted to overcome the challenges and freely share their experiences and knowledge. Findings The results illustrate that a high degree of schedule compression is achievable through tactful crashing, substitution and overlapping applications. The successful practices heavily rely on the high capacity of participants and necessary organization, management and technology innovations, such as three-level matrix organizational structure, reverse design method, site partition, mock-up room first strategies and prefabricated construction technology. For instance, the reverse design method is one of the most significant innovations to project simplification and accelerate and worthy of promotion for future emergency projects. Practical implications The empirical findings are significant as they evoke new thinking and direction for addressing the main challenges of sharp schedule compression and provide valuable references for future emergency projects, including selecting high-capacity contractors and replacing the conventional design methods with reverse design. Originality/value Substantial studies indicate that the maximum degree of schedule compression is highly unlikely to exceed 25%, but this study suggests that sharp compression is possible. Although with flaws in its beauty (i.e. compressing schedule at the expense of construction cost and quality), it is also a breakthrough. It provides the building block for future research in this fertile and unexplored area.

Phase 1 trial of anti-CD22 recombinant immunotoxin moxetumomab pasudotox combined with rituximab for relapsed/refractory hairy cell leukemia

Background: Anti-CD22 recombinant immunotoxin moxetumomab pasudotox (Moxe) is FDA-approved for hairy cell leukemia (HCL) patients who have received at least two prior systemic therapies including a purine nucleoside analog. In phase 3 testing the complete remission (CR) rate was 41%, and response was higher in patients with lower tumor burden and lower titers of antidrug antibodies (ADA). Phase 1 testing indicated that most CRs were without minimal residual disease (MRD) and eradication of MRD was associated with prolonged CR duration. Monoclonal antibody (Mab) rituximab binds to CD20 on HCL cells and induces apoptosis or immune-mediated killing, but as a single-agent achieved only 13% CRs in relapsed HCL requiring therapy. In a phase 1 trial to determine safety, rituximab was combined with Moxe, with the goal to help reduce tumor burden and to prevent or delay ADA by killing normal B-cells. Methods: To allow rituximab sufficient time to accomplish both goals, it was infused 3 days before day 1 of cycle 1 at 375 mg/m2 , and Moxe was given by 30-minute infusion on days 1, 3 and 5. On repeat cycles of Moxe days 1, 3 and 5, rituximab was given on day 1. Cycles were generally spaced 4 weeks apart. Moxe was begun at a lower dose, 30 rather than the 40 mcg/kg dose used in phase 3 in case the rituximab would increase its toxicity. Bone marrow aspirate flow cytometry, which can detect 0.002% HCL cells, was the most sensitive test used for MRD detection, much more sensitive than BRAF V600E digital droplet PCR (ddPCR) or bone marrow biopsy immunohistochemistry (IHC). Patients could receive 4 cycles past MRD-free CR, but not more than 8 cycles. Results: Three patients received Moxe at 30 mcg/Kg/dose and 6 received 40 mcg/Kg/dose, all without dose limiting toxicity (DLT). There was no evidence of hemolytic uremic syndrome or capillary leak syndrome. To prevent intravascular hypovolemia due to expected third spacing, patients were encouraged to drink one cup per hour of water or other fluid from days 1 to 8 and take dexamethasone 4 mg orally if headache or nausea prevented good oral hydration. Of the 9 patients, 7 (78%) achieved CR after 2 (n = 6) or 3 (n = 1) cycles, and achieved MRD-free CR after 2 (n = 3), 4 (n = 3) or 6 (n = 1) cycles. No patients became infected with COVID-19. Conclusions: This phase 1 trial met its primary endpoint of determining whether rituximab could be safely combined with Moxe and will enroll 4 additional patients to further access clinical activity. Further testing will determine whether addition of a CD20 Mab to Moxe significantly improves clinical outcome compared to Moxe alone, particularly long-term MRD-free CR rate.

[Epidemiological investigation on a cluster epidemic of COVID-19 in a collective workplace in Tianjin].

Objective: To investigate and analysis the epidemiological characteristics of a cluster epidemic of COIVD-19 in a collective workplace in Tianjin, evduate the prevention and control measures based on limited evidence and experience in early period of COVID-19 epidemic. Methods: Descriptive research method was used to describe the distribution and other epidemiological characteristics of the cluster cases of COVID-19. Results: Since the onset of the first index case on January 15, ten confirmed COVID-19 cases had occurred in the workplace, and the epidemic had spread from the workplace to 4 families, infecting 7 family members. The median age of 17 cases was 55 (19-79) years. All the 10 employee cases were males, and in the family cases, 3 were males and 4 were females. Of the employee cases, 8 worked in CW workshop and 2 worked in administrative office building. The median exposure-onset interval of all the cases was 4 days, and the median exposure-onset interval was 4.5 days in the employee cases and 4 days in the family cases. The median onset-medical care seeking interval was 4 days in the non-isolated cases, 2.5 days in the cases with home isolation after onset, and 0.5 day in the cases with home isolation before onset. Conclusions: The clustering of COVID-19 cases was observed in this workplace in Tianjin, which affected 4 families. In the early stage of the epidemic, accurate and rapid blocking and control measures can completely prevent the large-scale spread of COVID-19.

Can Yin-Chai-Xiao-Du decoction be useful of COVID-19? the mechanism research based on network pharmacology

Background: In this study, we preliminarily investigated the mechanism of Yin-Chai-Xiao-Du decoction for the treatment of COVID-19 by the method of network pharmacology. Methods: The potential targets and pathways of Yin-Chai-Xiao-Du decoction for the treatment of COVID-19 were examined using network pharmacology;the ingredient and active targets of Yin-Chai-Xiao-Du decoction were collected from the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform and PharmMapper databases;the COVID-19-related targets were obtained from the online Mendelian inheritance in man, GeneCards, and GeneMANIA databases;the STRING database and Cytoscape were used to build a protein-protein interaction network, and a Network Analyzer tool was used to perform topology analysis to screen for the key ingredients and targets;the ClueGO and KOBAS 3.0 databases were for the enrichment analysis of gene function (Gene Oncology) and gene pathway (Kyoto Encyclopedia of Genes and Genomes);the herb-ingredient-target-pathway network diagram was constructed by Cytoscape. Results: The core herbs screened by the network pharmacological analysis were Jinyinhua (Lonicerae japonicae flos), Lianqiao (Forsythia suspensa), Chaihu (Bupleuri radix), Huangqin (Scutellariae radix), Yinchen (Herba Artemisiae Scopariae), Guanghuoxiang (Pogostemonis herba), Roudoukou (Semen myristicae) and Qinghao (Artemisiae annuae herba). A total of 293 active ingredients were screened by Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform, and the key ingredients were quercetin, kaempferol, isorhamnetin, stigmasterol, beta-sitosterol, and luteolin. Yin-Chai-Xiao-Du decoction has 138 COVID-19-related targets, and the key targets were mitogen-activated protein kinase 3, interleukin-6, tumor necrosis factor, vascular endothelial growth factor A, and CC motif ligand 2. Kyoto Encyclopedia of Genes and Genomes analysis revealed 120 enriched gene pathways, and the key pathways were signaling by interleukins, immune system, cytokine signaling in the immune system, and the signaling pathways of interleukin-17, tumor necrosis factor, and relaxin. Conclusion: The core herbs of Yin-Chai-Xiao-Du decoction are Jinyinhua (Lonicerae japonicae flos), Lianqiao (Forsythia suspensa), Chaihu (Bupleuri radix), Huangqin (Scutellariae radix), Yinchen (Herba Artemisiae Scopariae), Guanghuoxiang (Pogostemonis herba), Roudoukou (Semen myristicae) and Qinghao (Artemisiae annuae herba). The key ingredients are quercetin, kaempferol, isorhamnetin, stigmasterol, and beta-sitosterol;the critical targets are luteolin, interleukin-6, mitogen-activated protein kinase 3, tumor necrosis factor, and CC motif ligand 2;and the core signaling pathways are those mediated by interleukin-17, tumor necrosis factor, and relaxin.