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Importance: When hospitals are at capacity, accurate deterioration indices could help identify low-risk patients as potential candidates for home care programs and alleviate hospital strain. To date, many existing deterioration indices are based entirely on structured data from the electronic health record (EHR) and ignore potentially useful information from other sources., Objective: To improve the accuracy of existing deterioration indices by incorporating unstructured imaging data from chest radiographs., Design, Setting, and Participants: Machine learning models were trained to predict deterioration of patients hospitalized with acute dyspnea using existing deterioration index scores and chest radiographs. Models were trained on hospitalized patients without coronavirus disease 2019 (COVID-19) and then subsequently tested on patients with COVID-19 between January 2020 and December 2020 at a single tertiary care center who had at least one radiograph taken within 48 hours of hospital admission., Main Outcomes and Measures: Patient deterioration was defined as the need for invasive or non-invasive mechanical ventilation, heated high flow nasal cannula, IV vasopressor administration or in-hospital mortality at any time following admission. The EPIC deterioration index was augmented with unstructured data from chest radiographs to predict risk of deterioration. We compared discriminative performance of the models with and without incorporating chest radiographs using area under the receiver operating curve (AUROC), focusing on comparing the fraction and total patients identified as low risk at different negative predictive values (NPV)., Results: Data from 6278 hospitalizations were analyzed, including 5562 hospitalizations without COVID-19 (training cohort) and 716 with COVID-19 (216 in validation, 500 in held-out test cohort). At a NPV of 0.95, the best-performing image-augmented deterioration index identified 49 more (9.8%) individuals as low-risk compared to the deterioration index based on clinical data alone in the first 48 hours of admission. At a NPV of 0.9, the EPIC image-augmented deterioration index identified 26 more individuals (5.2%) as low-risk compared to the deterioration index based on clinical data alone in the first 48 hours of admission., Conclusion and Relevance: Augmenting existing deterioration indices with chest radiographs results in better identification of low-risk patients. The model augmentation strategy could be used in the future to incorporate other forms of unstructured data into existing disease models., Competing Interests: The authors have declared that no competing interests exist.

Background: The prevalence of pulmonary embolism (PE) in the acute exacerbation of chronic obstructive pulmonary disease (AE-COPD) is highly controversial. We conducted a systematic review and meta-analysis to summarize the epidemiology and characteristics of PE with AE-COPD for current studies., Methods: We searched the PubMed, EMBASE, Cochrane Library and Web of Science databases for studies published prior to October 21, 2020. Pooled proportions with 95% confidence intervals (95% CIs) were calculated using a random effects model. Odds ratios (ORs) and mean differences (MDs) with 95% confidence intervals were used as effect measures for dichotomous and continuous variables, respectively., Results: A total of 17 studies involving 3170 patients were included. The prevalence of PE and deep vein thrombosis (DVT) in AE-COPD patients was 17.2% (95% CI: 13.4%-21.3%) and 7.1% (95% CI: 3.7%-11.4%%), respectively. Dyspnea (OR = 6.77, 95% CI: 1.97-23.22), pleuritic chest pain (OR = 3.25, 95% CI: 2.06-5.12), lower limb asymmetry or edema (OR = 2.46, 95% CI:1.51-4.00), higher heart rates (MD = 20.51, 95% CI: 4.95-36.08), longer hospital stays (MD = 3.66, 95% CI: 3.01-4.31) were associated with the PE in the AE-COPD patients. Levels of D-dimer (MD = 1.51, 95% CI: 0.80-2.23), WBC counts (MD = 1.42, 95% CI: 0.14-2.70) were significantly higher and levels of PaO2 was lower (MD = -17.20, 95% CI: -33.94- -0.45, P<0.05) in the AE-COPD with PE group. The AE-COPD with PE group had increased risk of fatal outcome than the AE-COPD group (OR = 2.23, 95% CI: 1.43-3.50)., Conclusions: The prevalence of PE during AE-COPD varies considerably among the studies. AE-COPD patients with PE experienced an increased risk of death, especially among the ICU patients. Understanding the potential risk factors for PE may help clinicians identify AE-COPD patients at increased risk of PE., Prospero Registration Number: CRD42021226568., Competing Interests: The authors have declared that no competing interests exist.

The natural history of COVID-19 and predictors of mortality in older adults need to be investigated to inform clinical operations and healthcare policy planning. A retrospective study took place in 80 long-term nursing homes in Catalonia, Spain collecting data from March 1st to May 31st, 2020. Demographic and clinical data from 2,092 RT-PCR confirmed cases of SARS-CoV-2 infection were registered, including structural characteristics of the facilities. Descriptive statistics to describe the demographic, clinical, and molecular characteristics of our sample were prepared, both overall and by their symptomatology was performed and an analysis of statistically significant bivariate differences and constructions of a logistic regression model were carried out to assess the relationship between variables. The incidence of the infection was 28%. 71% of the residents showed symptoms. Five major symptoms included: fever, dyspnea, dry cough, asthenia and diarrhea. Fever and dyspnea were by far the most frequent (50% and 28%, respectively). The presentation was predominantly acute and symptomatology persisted from days to weeks (mean 9.1 days, SD = 10,9). 16% of residents had confirmed pneumonia and 22% required hospitalization. The accumulated mortality rate was 21.75% (86% concentrated during the first 28 days at onset). A multivariate logistic regression analysis showed a positive predictive value for mortality for some variables such as age, pneumonia, fever, dyspnea, stupor refusal to oral intake and dementia (p<0.01 for all variables). Results suggest that density in the nursing homes did not account for differences in the incidence of the infection within the facilities. This study provides insights into the natural history of the disease in older adults with high dependency living in long-term nursing homes during the first pandemic wave of March-May 2020 in the region of Catalonia, and suggests that some comorbidities and symptoms have a strong predictive value for mortality., Competing Interests: The authors have declared that no competing interests exist.

Introduction: Patients at intermediate-high risk of developing a pulmonary embolism (PE) are very likely to experience adverse outcomes, such as cardiovascular instability and death. The role of thrombolytic therapy in intermediate-high-risk PE remains controversial., Objectives: This study aimed to determine the efficacy and safety of low-dose urokinase (UK) thrombolytic therapy for intermediate-high-risk PE., Patients and Methods: This retrospective study included 81 consecutive patients with intermediate-high-risk PE from two centers. Patients received low-dose UK or low-molecular-weight heparin (anticoagulant therapy group). The efficacy outcomes were mortality, computed tomography pulmonary angiography (CTPA)-confirmed absorption, and dyspnea. Safety was assessed as the incidence of bleedings., Results: The in-hospital mortality, 9-month mortality, and long-term mortality at the last follow-up were comparable for the low-dose UK group and the anticoagulant therapy group (6.45% vs. 0%, p = 0.144, 9.68% vs. 8.16%, p = 0.815, and 12.90% vs. 12.24%, p = 0.931, respectively). CTPA-confirmed absorption at one month after admission was higher in the low-dose UK group than in the anticoagulant therapy group (p = 0.016). The incidences of short-term dyspnea at discharge and long-term dyspnea at the last follow-up were lower in the low-dose UK group than in the anticoagulant therapy group (27.59% vs. 52%, p = 0.035, 33.33% vs. 58.14%, p = 0.043, respectively). No major bleeding occurred. The incidence of minor bleeding was not significantly different between the two groups (3.23% vs. 6%, p = 0.974)., Conclusion: In intermediate-high-risk PE, a low-dose UK might increase CTPA-confirmed absorption and improve short-term and long-term dyspnea without affecting mortality or increasing the bleeding risk., Competing Interests: The authors declare no conflict of interest.

Introduction: Interstitial lung diseases (ILDs) include a wide variety of chronic progressive pulmonary diseases characterized by lung inflammation, fibrosis and hypoxemia and can progress to respiratory failure and even death. ILDs are associated with varying degrees of quality of life impairments in affected people. Studies on the quality of life in patients with ILDs are still limited, and there are few studies with long-term follow-up periods in these patients., Methods: Data from patients who were clinically diagnosed with ILDs in the Respiratory Department, Beijing Chaoyang Hospital, Capital Medical University from January 2017 to February 2018 were collected. Clinical status and HRQoL were assessed at baseline and subsequently at 6- and 12-month intervals with the LCQ, mMRC, HADS, SF-36, and SGRQ. Multivariate linear regression was used to evaluate the determinants of the decline in HRQoL., Results: A total of 139 patients with idiopathic interstitial pneumonia (IIP) and 30 with connective tissue disease-associated ILD (CTD-ILD) were enrolled, 140 of whom completed the follow-up. The mean age was 63.7 years, and 92 patients were men. At baseline, the decline in HRQoL assessed by the SF-36 and SGRQ was significantly associated with the mMRC, LCQ and HADS depression score. In the follow-up, changes in FVC%, DLco%, mMRC and LCQ were significantly associated with changes in HRQoL., Conclusions: HRQoL in both IIP and CTD-ILD patients deteriorates to varying degrees, and the trend suggests that poor HRQoL in these patients is associated with many determinants, primarily dyspnea, cough and depression. Improving HRQoL is the main aim when treating patients living with ILDs., Competing Interests: The authors have declared that no competing interests exist.

Rationale: Pulmonary artery enlargement (PAE) is associated with exacerbations in Chronic Obstructive Pulmonary Disease (COPD) and with survival in moderate to severe patients. The potential role of PAE in survival prediction has not been compared with other clinical and physiological prognostic markers., Methods: In 188 patients with COPD, PA diameter was measured on a chest CT and the following clinical and physiological parameters registered: age, gender, smoking status, pack-years history, dyspnea, lung function, exercise capacity, Body Mass Index, BODE index and history of exacerbations in year prior to enrolment. Proportional Cox regression analysis determined the best predictor of all cause survival., Results: During 83 months (±42), 43 patients died. Age, pack-years history, smoking status, BMI, FEV1%, six minute walking distance, Modified Medical Research Council dyspnea scale, BODE index, exacerbation rate prior to enrollment, PA diameter and PAE (diameter≥30mm) were associated with survival. In the multivariable analysis, age (HR: 1.08; 95%CI: 1.03-1.12, p<0.001) and PAE (HR: 2.78; 95%CI: 1.35-5.75, p = 0.006) were the most powerful parameters associated with all-cause mortality., Conclusions: In this prospective observational study of COPD patients with mild to moderate airflow limitation, PAE was the best predictor of long-term survival along with age.

Background: Congestive physical findings such as pulmonary rales and third heart sound (S3) are hallmarks of acute heart failure (AHF). However, their role in outcome prediction remains unclear. We sought to investigate the association between congestive physical findings upon admission, steady-state biomarkers at the time of discharge, and long-term outcomes in AHF patients., Methods: We analyzed the data of 133 consecutive AHF patients with an established diagnosis of ischemic or non-ischemic (dilated or hypertrophic) cardiomyopathy, admitted to a single-center university hospital between 2006 and 2010. The treating physician prospectively recorded major symptoms and congestive physical findings of AHF: paroxysmal nocturnal dyspnea, orthopnea, pulmonary rales, jugular venous distension (JVD), S3, and edema. The primary endpoint was defined as rehospitalization for HF., Results: Majority (63.9%) of the patients had non-ischemic etiology and, at the time of admission, S3 was seen in 69.9% of the patients, JVD in 54.1%, and pulmonary rales in 43.6%. The mean follow-up period was 726 ± 31 days. Patients with pulmonary rales (p < 0.001) and S3 (p  =  0.011) had worse readmission rates than those without these findings; the presence of these findings was also associated with elevated troponin T (TnT) levels at the time of discharge (odds ratio [OR] 2.8; p  =  0.02 and OR 2.6; p  =  0.05, respectively)., Conclusion: Pulmonary rales and S3 were associated with inferior readmission rates and elevated TnT levels on discharge. The worsening of the readmission rate owing to congestive physical findings may be a consequence of on-going myocardial injury.

Background: The association of right ventricular (RV) structure and function with symptoms in individuals without cardiopulmonary disease is unknown. We hypothesized that greater RV mass and RV end-diastolic volume (RVEDV), smaller RV stroke volume (RVSV), and lower RV ejection fraction (RVEF) measured by cardiac magnetic resonance imaging (MRI) in participants free of clinical cardiovascular disease at baseline would be associated with a greater risk of self-reported dyspnea., Methods: The Multi-Ethnic Study of Atherosclerosis (MESA) performed cardiac MRIs on participants without clinical cardiovascular disease between 2000 and 2002. We excluded subjects who reported "prevalent" dyspnea at the first assessment (24 months). The presence of dyspnea was assessed at 24 months, 42 months, and 60 months from baseline. Cox proportional hazards models were used to examine the relationship between RV measures and incident dyspnea., Results: In the final study sample (N = 2763), there were significant interactions between RV measures and sex in terms of the risk of dyspnea (p<0.05). Among men (N = 1453), lower RV mass (p = 0.003), smaller RVEDV (p<0.001), smaller RV end-systolic volume (RVESV) (p = 0.03) and decreased RVSV (p<0.001) were associated with an increased risk of developing dyspnea after adjusting for covariates. Associations remained after adjusting for left ventricular function and lung function. However, there were no significant associations between RV measures and the risk of dyspnea in women., Conclusions: Lower RV mass and smaller RV volumes were associated with an increased risk of dyspnea in men, but not in women.

The spectrum of the clinical presentation and severity of malaria infections is broad, ranging from uncomplicated febrile illness to severe forms of disease such as cerebral malaria (CM), acute lung injury (ALI), acute respiratory distress syndrome (ARDS), pregnancy-associated malaria (PAM) or severe anemia (SA). Rodent models that mimic human CM, PAM and SA syndromes have been established. Here, we show that DBA/2 mice infected with P. berghei ANKA constitute a new model for malaria-associated ALI. Up to 60% of the mice showed dyspnea, airway obstruction and hypoxemia and died between days 7 and 12 post-infection. The most common pathological findings were pleural effusion, pulmonary hemorrhage and edema, consistent with increased lung vessel permeability, while the blood-brain barrier was intact. Malaria-associated ALI correlated with high levels of circulating VEGF, produced de novo in the spleen, and its blockage led to protection of mice from this syndrome. In addition, either splenectomization or administration of the anti-inflammatory molecule carbon monoxide led to a significant reduction in the levels of sera VEGF and to protection from ALI. The similarities between the physiopathological lesions described here and the ones occurring in humans, as well as the demonstration that VEGF is a critical host factor in the onset of malaria-associated ALI in mice, not only offers important mechanistic insights into the processes underlying the pathology related with malaria but may also pave the way for interventional studies.