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RATIONALE: Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive interstitial lung disease that has no cure. Many current research efforts center on diagnostic and therapeutic modalities for IPF while other risk factors affecting disease pathogenesis receive less attention. Emerging data support the clinical importance of weight loss in patients with IPF. However, factors associated with weight loss and the impact of weight loss on mortality remain incompletely explored. OBJECTIVES: Explore the association between weight loss and transplant-free survival in patients with IPF and identify clinical variables associated with weight loss in this population. METHODS: Kaplan-Meier and Cox proportional hazard regression analyses were generated and stratified by weight loss or use of antifibrotic medications. Conditional logistic regression was used to evaluate for factors associated with weight loss. RESULTS: There was a significant increase in mortality in patients who lost ≥ 5% of their body weight loss (HR 2.21, [1.29, 4.43] p = .021). The use of supplemental oxygen (adjusted OR 13.16), and ≥ 200 mL loss of FVC over 1 year (adjusted OR 5.44) were both associated with a ≥ 5% weight loss in the year following a diagnosis of IPF. The use of antifibrotic medication did not significantly change median transplant-free survival in patients who lost more than ≥ 5% of their body mass. CONCLUSIONS: Weight loss over the first year following a diagnosis of IPF is strongly associated with decreased transplant-free survival. More research is needed to determine the mechanisms surrounding weight loss in patients with IPF.

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BACKGROUND: Cardiac intensive care units (CICUs) serve medically complex patients with multiorgan dysfunction. Whether a CICU that is staffed full time by heart failure (HF) specialists is associated with decreased mortality is unclear. METHODS AND RESULTS: A retrospective review of consecutive CICU admissions from January 1, 2012, to December 31, 2016, was performed. In January 2014, the CICU changed from an open unit staffed by any cardiologist to a closed unit managed by HF specialists. Patients' baseline characteristics were determined, and a multivariate regression analysis was performed to ascertain mortality rates in the CICU. Baseline severity of illness was higher in the closed/HF specialist CICU model (P< 0.001). Death occurred in 101 of 1185 patients admitted to the CICU (8.5%) in the open-unit model and in 139 of 2163 patients (6.4%) admitted to the closed/HF specialist model (absolute risk reduction 2.1%, 95% confidence interval [CI] 0.1-4.0%; P = 0.01). The transition from an open to a closed/HF specialist model was associated with a lower overall CICU mortality rate (odds ratio [OR] 0.63; 95% CI 0.43-0.93). Prespecified interaction with a mechanical circulatory support device and unit model showed that treatment with such a device was associated with lower mortality rates in the closed/HF specialist model of a CICU (OR 0.6; 95% CI 0.18-0.78; P for interaction <0.01). CONCLUSION: Transition to a closed unit model staffed by a dedicated HF specialist is associated with lower CICU mortality rates.

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An empyema is a collection of pus in the pleural space, often due to aerobic bacteria, that requires drainage typically done with a small bore chest tube and fibrinolytics. The large majority of empyemas are unilateral. Bilateral empyemas are rare, usually non-infectious and typically require surgical management. We report a case of Hemophilus influenzae epiglottitis complicated by bilateral culture proven empyema successfully managed without surgery. The aim of this report is to present a rare complication of epiglottitis and discuss the theoretical issues with management of multiple infected pleural spaces requiring fibrinolytics.

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BACKGROUND: Since June, 2019, more than 1000 new cases of e-cigarette, or vaping, product use associated lung injury (EVALI) have been reported in the USA. Patients presented with dyspnoea, cough, and were found to be hypoxaemic with bilateral airspace opacities on chest imaging. Most patients required management in the intensive care unit and steroid therapy. All patients recovered with cessation of vaping, supportive care, and steroid therapy and remained symptom free at follow up. E-cigarette use continues to rapidly escalate in the USA, particularly among youth. METHODS: Cases were defined as patients admitted to the University of Rochester Medical Center (Rochester, NY, USA) who had used e-cigarettes or another vaping device in the 30 days before presentation, and who had bilateral airspace opacification on chest imaging (CT or x-ray). Case details were obtained via medical record review and patient interviews over the past 3 months including symptomatology, physical exam data, imaging studies, laboratory data, vaping history, and subsequent outpatient follow-up data. In collaboration with the New York State Department of Health, our hospital developed a novel clinical practice algorithm based on statewide physician feedback along with input from experts in environmental health, medical toxicology, infectious disease, epidemiology, and chronic disease prevention. FINDINGS: We report 12 cases treated for suspected EVALI at our medical centre between June 6, 2019, and Sept 15, 2019. Ten (83%) patients had dyspnoea, fever, and emesis and nine (75%) had cough. 11 (92%) patients reported the use of e-cigarette cartridges containing tetrahydrocannabinol oil. Although eight (67%) patients required admission to the intensive care unit for hypoxaemic respiratory failure, no deaths occurred. The median hospitalisation duration was 7 days (IQR 7-8). All patients completing follow up (6 [50%]) had resolution of previous chest CT findings and normal spirometry. The clinical algorithm focuses on the key signs and symptoms of EVALI and the importance of ruling out infection and other cardiopulmonary conditions before making a presumptive diagnosis of EVALI. INTERPRETATION: Patients with suspected EVALI in our cohort had life-threatening hypoxaemia, with 67% requiring management in the intensive care unit. Despite the severity of presentation, similar to previous reports of patients with EVALI, most patients improved within 1-2 weeks of initial presentation after vaping cessation and administration of systemic corticosteroids when needed. Almost all (92%) patients with suspected EVALI reported vaping a THC product, making THC containing e-liquids or oils a key focus on the ongoing nationwide investigations into the cause of EVALI. Additional research is required to understand the potential toxins, underlying pathophysiological mechanisms, and identification of susceptible individuals at higher risk for hospitalisation due to EVALI. To our knowledge we present the first clinical practice algorithm for the evaluation and management of EVALI, which will be useful for both acute management and improved accurate reporting of this life-threatening respiratory illness. FUNDING: None.

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Spontaneous coronary artery dissection (SCAD) is a rare but lethal cause of acute coronary syndrome that occurs in young women during the peripartum/postpartum periods. We present a case of a 41-year-old woman with no significant medical history, but was a habitual e-cigarette smoker who presented with atypical chest pain 2 weeks after an uncomplicated delivery while breast feeding. The patient was found to have elevated cardiac enzymes and ST segment elevations in the anterior leads. An urgent cardiac catheterisation was performed, which revealed dissection and occlusion of the left anterior descending artery, and a drug-eluting stent was placed that resulted in the resolution of chest pain. Physiological changes during the postpartum period may be linked to an increased risk of developing SCAD.1 In addition, e-cigarette smoking is associated with increased oxidative stress and sympathetic activity, which may predispose patients to an increased risk of acute coronary syndrome.

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To maintain normal metal metabolism, bacteria use metal-sensing metalloregulators to control transcription of metal resistance genes. Depending on their metal-binding states, the MerR-family metalloregulators change their interactions with DNA to suppress or activate transcription. To understand their functions fundamentally, we study how CueR, a Cu(1+)-responsive MerR-family metalloregulator, interacts with DNA, using an engineered DNA Holliday junction (HJ) as a protein-DNA interaction reporter in single-molecule fluorescence resonance energy transfer measurements. By analyzing the single-molecule structural dynamics of the engineered HJ in the presence of various concentrations of both apo- and holo-CueR, we show how CueR interacts with the two conformers of the engineered HJ, forming variable protein-DNA complexes at different protein concentrations and changing the HJ structures. We also show how apo- and holo-CueR differ in their interactions with DNA, and discuss their similarities and differences with other MerR-family metalloregulators. The surprising finding that holo-CueR binds more strongly to DNA than to apo-CueR suggests functional differences among MerR-family metalloregulators, in particular in their mechanisms of switching off gene transcription after activation. The study also corroborates the general applicability of engineered HJs as single-molecule reporters for protein-DNA interactions, which are fundamental processes in gene replication, transcription, recombination, and regulation.

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