Background: Accurate risk prediction of clinical outcome would usefully inform clinical decisions and intervention targeting in COVID-19. The aim of this study was to derive and validate risk prediction models for poor outcome and death in adult inpatients with COVID-19. Methods: Model derivation using data from Wuhan, China used logistic regression with death and poor outcome (death or severe disease) as outcomes. Predictors were demographic, comorbidity, symptom and laboratory test variables. The best performing models were externally validated in data from London, UK. Findings: 4.3% of the derivation cohort (n=775) died and 9.7% had a poor outcome, compared to 34.1% and 42.9% of the validation cohort (n=226). In derivation, prediction models based on age, sex, neutrophil count, lymphocyte count, platelet count, C-reactive protein and creatinine had excellent discrimination (death c-index=0.91, poor outcome c-index=0.88), with good-to-excellent calibration. Using two cut-offs to define low, high and very-high risk groups, derivation patients were stratified in groups with observed death rates of 0.34%, 15.0% and 28.3% and poor outcome rates 0.63%, 8.9% and 58.5%. External validation discrimination was good (c-index death=0.74, poor outcome=0.72) as was calibration. However, observed rates of death were 16.5%, 42.9% and 58.4% and poor outcome 26.3%, 28.4% and 64.8% in predicted low, high and very-high risk groups. Interpretation: Our prediction model using demography and routinely-available laboratory tests performed very well in internal validation in the lower-risk derivation population, but less well in the much higher-risk external validation population. Further external validation is needed. Collaboration to create larger derivation datasets, and to rapidly externally validate all proposed prediction models in a range of populations is needed, before routine implementation of any risk prediction tool in clinical care. Funding: MRC, Wellcome Trust, HDR-UK, LifeArc, participating hospitals, NNSFC, National Key R&D Program, Pudong Health and Family Planning Commission Research in context: Evidence before this study: Several prognostic models for predicting mortality risk, progression to severe disease, or length of hospital stay in COVID-19 have been published. ¹ Commonly reported predictors of severe prognosis in patients with COVID-19 include age, sex, computed tomography scan features, C-reactive protein (CRP), lactic dehydrogenase, and lymphocyte count. Symptoms (notably dyspnoea) and comorbidities (e.g. chronic lung disease, cardiovascular disease and hypertension) are also reported to have associations with poor prognosis. ² However, most studies have not described the study population or intended use of prediction models, and external validation is rare and to date done using datasets originating from different Wuhan hospitals. ³ Given different patterns of testing and organisation of healthcare pathways, external validation in datasets from other countries is required. Added value of this study: This study used data from Wuhan, China to derive and internally validate multivariable models to predict poor outcome and death in COVID-19 patients after hospital admission, with external validation using data from King’s College Hospital, London, UK. Mortality and poor outcome occurred in 4.3% and 9.7% of patients in Wuhan, compared to 34.1% and 42.9% of patients in London. Models based on age, sex and simple routinely available laboratory tests (lymphocyte count, neutrophil count, platelet count, CRP and creatinine) had good discrimination and calibration in internal validation, but performed only moderately well in external validation. Models based on age, sex, symptoms and comorbidity were adequate in internal validation for poor outcome (ICU admission or death) but had poor performance for death alone. Implications of all the available evidence: This study and others find that relatively simple risk prediction models using demographic, clinical and laboratory data perform well in internal validation but at best moderately in external validation, either because derivation and external validation populations are small (Xie et al ³ ) and/or because they vary greatly in casemix and severity (our study). There are three decision points where risk prediction may be most useful: (1) deciding who to test; (2) deciding which patients in the community are at high-risk of poor outcomes; and (3) identifying patients at high-risk at the point of hospital admission. Larger studies focusing on particular decision points, with rapid external validation in multiple datasets are needed. A key gap is risk prediction tools for use in community triage (decisions to admit, or to keep at home with varying intensities of follow-up including telemonitoring) or in low income settings where laboratory tests may not be routinely available at the point of decision-making. This requires systematic data collection in community and low-income settings to derive and evaluate appropriate models.

Purpose: Using transrenal DNA to detect KRAS mutations in non-small cell lung cancer (NSCLC), the study addressed the clinical impact for longitudinal monitoring and prognostic value for disease outcome. Methods: Digital droplet PCR was used to detect the mutant DNA. A total of 200 NSCLC patients were recruited with varying molecular profiles. To ascertain the specificity of transrenal DNA to accurately profile the disease, primary tissues were compared. Subsequently, serial samplings were performed at different treatment cycles to gauge the predictive value. Results: Transrenal DNA was successfully detected in all 200 patients. Overall concordance rate for mutant KRAS DNA within urine specimens and primary tissue biopsies was 95% (k = 0.87; 95% CI: 0.82–0.95). Patients with positive results at baseline had lower median overall survival (OS) than the wildtype group. More importantly, longitudinal monitoring of urine specimens showed an increase in the quantity of transrenal DNA, which were highly associated with disease progression and outcome. Conclusions: Our study showed a highly associative link to the patient’s tumor KRAS profile. Monitoring its variations aided in stratifying patients with worse outcome. Urinary specimens that can be extracted non-invasively presents new opportunities to track patients with KRAS mutation undergoing therapy.

Objective: Allergic asthma is a growing burden on national public health services due to its high prevalence. The aim of this experiment was to investigate whether miR-26a-5p affects cellular fibrosis and thus airway remodeling in asthmatic mice through the regulation of target genes. Methods: Screening for differentially expressed miRNAs in asthma model mice was carried out by constructing a mouse model of allergic asthma. qRT-PCR was performed to determine candidate miRNAs in each group of bronchial tissues. Western blot detection of the expression levels of predicted candidate target genes in each group of bronchial tissues was conducted. A dual luciferase assay was performed to validate the binding of miR-26a-5p to target genes. Fibronectin, a marker of cellular fibrosis, was detected via flow cytometry. CCK8 and BrdU staining were used to detect the proliferation ability of each group of cells. Results: miR-26a-5p is able to target and bind to ABL2 3′-UTR, MMP16 3′-UTR and PDE7A 3′-UTR sequences. After interference with miR-26a-5p, improved bronchial histopathology and reduced peribronchial collagen deposition were found. Compared with the model group, interference with miR-26a-5p reduced lung fibrosis, decreased fibroblasts and increased apoptosis in mouse bronchial tissues; overexpression of miR-26a-5p decreased apoptosis in mouse bronchial tissues. Compared with the model group, the serum levels of IL-4, IL-5, IL-13 and I IFN-γ were decreased in the miR-26a-5p inhibitor group and increased in the miR-26a-5p mimic group. The immunohistochemical results showed that the expression of ABL2, MMP16 and PDE7A was significantly reduced after intervention with miR-26a-5p. Compared with the model group, the apoptosis rate of cells in the miR-26a-5p inhibitor group of the allergic asthma model was upregulated, the levels of IL-4, IL-5, IL-13, IFN-γ and ROS were decreased, the expression of the miRNA and proteins of ABL2, MMP16 and PDE7A was decreased, the expression of LC3A and P62 was significantly increased and the expression of LC3B, Beclin1, Atg5 and fibrosis markers collagen I and α-SMA was decreased. Conclusion: miR-26a-5p affects cellular fibrosis and thus airway remodeling in asthmatic mice by regulating target genes.

Rationale: Bronchial artery aneurysm (BAA) is a rare disease that can be life-threatening if it ruptures. Tandem connections of multiple aneurysms are even rarer and more challenging to manage. Patient concerns: A 46-year-old woman presented to the hospital with intermittent hemoptysis for a week. A bronchial artery computed tomographic angiography scan revealed 2 BAAs associated with bronchial artery-to-pulmonary artery fistulas in the left lung. Three-dimensional CT reconstruction showed 2 bronchial aneurysms in tandem and 1 aneurysm adjacent to the descending aorta. Diagnoses: Giant tandem bronchial aneurysms were confirmed using computerized tomographic angiography. Interventions: Nine interlocking detachable coils and 11 standard pushable coils were introduced into aneurysms for embolization. Outcomes: There was no episodes of hemoptysis. CT angiography indicated that the coils were closely knit and in their proper position 1 month later; at follow-up, the patient had no adverse effects and no recurrence of hemoptysis. Lessons: BAA is a rare disease that can be life-threatening if it ruptures. It should be treated aggressively to determine the presence of symptoms.

Fibrosing mediastinitis (FM) is a rare and benign fibroproliferative disease that presents with the proliferation of extensive, dense fibrous tissue in the mediastinum. Hemoptysis is a common clinical manifestation of FM. Clinically, most patients exhibit mild to moderate hemoptysis. We report a case of FM complicated with life-threatening massive hemoptysis. The patient was successfully rescued through a combination of bronchoscopic balloon closure, bronchial artery embolization (BAE), and surgical interventions. Although FM is frequently benign, vascular involvement can progress to life-threatening massive hemoptysis and must be treated appropriately.