A Multicenter Randomized Controlled Trial of Zephyr Endobronchial Valve Treatment in Heterogeneous Emphysema (LIBERATE).

RATIONALE: This is the first multicenter randomized controlled trial to evaluate the effectiveness and safety of Zephyr Endobronchial Valve (EBV) in patients with little to no collateral ventilation out to 12 months. OBJECTIVES: To evaluate the effectiveness and safety of Zephyr EBV in heterogeneous emphysema with little to no collateral ventilation in the treated lobe. METHODS: Subjects were enrolled with a 2:1 randomization (EBV/standard of care [SoC]) at 24 sites. Primary outcome at 12 months was the ΔEBV-SoC of subjects with a post-bronchodilator FEV1 improvement from baseline of greater than or equal to 15%. Secondary endpoints included absolute changes in post-bronchodilator FEV1, 6-minute-walk distance, and St. George's Respiratory Questionnaire scores. MEASUREMENTS AND MAIN RESULTS: A total of 190 subjects (128 EBV and 62 SoC) were randomized. At 12 months, 47.7% EBV and 16.8% SoC subjects had a ΔFEV1 greater than or equal to 15% (P < 0.001). ΔEBV-SoC at 12 months was statistically and clinically significant: for FEV1, 0.106 L (P < 0.001); 6-minute-walk distance, +39.31 m (P = 0.002); and St. George's Respiratory Questionnaire, -7.05 points (P = 0.004). Significant ΔEBV-SoC were also observed in hyperinflation (residual volume, -522 ml; P < 0.001), modified Medical Research Council Dyspnea Scale (-0.8 points; P < 0.001), and the BODE (body mass index, airflow obstruction, dyspnea, and exercise capacity) index (-1.2 points). Pneumothorax was the most common serious adverse event in the treatment period (procedure to 45 d), in 34/128 (26.6%) of EBV subjects. Four deaths occurred in the EBV group during this phase, and one each in the EBV and SoC groups between 46 days and 12 months. CONCLUSIONS: Zephyr EBV provides clinically meaningful benefits in lung function, exercise tolerance, dyspnea, and quality of life out to at least 12 months, with an acceptable safety profile in patients with little or no collateral ventilation in the target lobe. Clinical trial registered with www.clinicaltrials.gov (NCT 01796392).

Rapid effect of benralizumab in fulminant eosinophilic myocarditis in the setting of uncontrolled eosinophilic asthma.

A 51-year-old male with uncontrolled asthma and recent convalescence from severe acute respiratory syndrome coronavirus-2c pneumonia presented with cough, dyspnea, and chest pain. Evaluation revealed significant peripheral eosinophilia, elevated troponin, and biventricular failure resulting in cardiogenic shock. He was diagnosed with eosinophilic myocarditis and was subsequently started on high-dose steroids. As he was also diagnosed with eosinophilic asthma and continued to clinically decline requiring inotropic support, he received benralizumab, an anti-eosinophilic monoclonal antibody, as rescue therapy. After benralizumab administration he demonstrated improvement in his left ventricular ejection fraction, normalization of his right ventricular function, and improvement in symptoms with resolution of his hypereosinophilia. Currently, benralizumab is approved for add-on maintenance treatment of patients with an eosinophilic phenotype of severe asthma. To date, only few observational studies have been published revealing rapid improvement in symptoms of acute, severe eosinophilic asthma and eosinophilic myocarditis caused by eosinophilic granulomatosis with polyangiitis after administration of benralizumab. This clinical case demonstrates that benralizumab can be used safely in conjunction with steroid therapy for eosinophilic myocarditis. This case also emphasizes the need for further clinical research for utilizing benralizumab in the treatment of eosinophilic myocarditis, eosinophilic asthma, and other hypereosinophilic syndromes in the acute setting. Learning objective: Benralizumab has been approved for add-on maintenance treatment of patients with an eosinophilic phenotype of severe asthma. However, few cases have been published demonstrating the drug's use in acute severe exacerbations. This case presents a patient with fulminant eosinophilic myocarditis and asthma with improvement after administration of benralizumab in addition to high-dose steroids. The future role of the drug in acute eosinophilic exacerbation should continue to be explored.

Does this patient have influenza?

CONTEXT: Influenza vaccination lowers, but does not eliminate, the risk of influenza. Making a reliable, rapid clinical diagnosis is essential to appropriate patient management that may be especially important during shortages of antiviral agents caused by high demand. OBJECTIVES: To systematically review the precision and accuracy of symptoms and signs of influenza. A secondary objective was to review the operating characteristics of rapid diagnostic tests for influenza (results available in <30 min). DATA SOURCES: Structured search strategy using MEDLINE (January 1966-September 2004) and subsequent searches of bibliographies of retrieved articles to identify articles describing primary studies dealing with the diagnosis of influenza based on clinical signs and symptoms. The MEDLINE search used the Medical Subject Headings EXP influenza or EXP influenza A virus or EXP influenza A virus human or EXP influenza B virus and the Medical Subject Headings or terms EXP sensitivity and specificity or EXP medical history taking or EXP physical examination or EXP reproducibility of results or EXP observer variation or symptoms.mp or clinical signs.mp or sensitivity.mp or specificity.mp. STUDY SELECTION: Of 915 identified articles on clinical assessment of influenza-related illness, 17 contained data on the operating characteristics of symptoms and signs using an independent criterion standard. Of these, 11 were eliminated based on 4 inclusion criteria and availability of nonduplicative primary data. DATA EXTRACTION: Two authors independently reviewed and abstracted data for estimating the likelihood ratios (LRs) of clinical diagnostic findings. Differences were resolved by discussion and consensus. DATA SYNTHESIS: No symptom or sign had a summary LR greater than 2 in studies that enrolled patients without regard to age. For decreasing the likelihood of influenza, the absence of fever (LR, 0.40; 95% confidence interval [CI], 0.25-0.66), cough (LR, 0.42; 95% CI, 0.31-0.57), or nasal congestion (LR, 0.49; 95% CI, 0.42-0.59) were the only findings that had summary LRs less than 0.5. In studies limited to patients aged 60 years or older, the combination of fever, cough, and acute onset (LR, 5.4; 95% CI, 3.8-7.7), fever and cough (LR, 5.0; 95% CI, 3.5-6.9), fever alone (LR, 3.8; 95% CI, 2.8-5.0), malaise (LR, 2.6; 95% CI, 2.2-3.1), and chills (LR, 2.6; 95% CI, 2.0-3.2) increased the likelihood of influenza to the greatest degree. The presence of sneezing among older patients made influenza less likely (LR, 0.47; 95% CI, 0.24-0.92). CONCLUSIONS: Clinical findings identify patients with influenza-like illness but are not particularly useful for confirming or excluding the diagnosis of influenza. Clinicians should use timely epidemiologic data to ascertain if influenza is circulating in their communities, then either treat patients with influenza-like illness empirically or obtain a rapid influenza test to assist with management decisions.

Real-time tumor tracking in the lung using an electromagnetic tracking system.

PURPOSE: To describe the first use of the commercially available Calypso 4D Localization System in the lung. METHODS AND MATERIALS: Under an institutional review board-approved protocol and an investigational device exemption from the US Food and Drug Administration, the Calypso system was used with nonclinical methods to acquire real-time 4-dimensional lung tumor tracks for 7 lung cancer patients. The aims of the study were to investigate (1) the potential for bronchoscopic implantation; (2) the stability of smooth-surface beacon transponders (transponders) after implantation; and (3) the ability to acquire tracking information within the lung. Electromagnetic tracking was not used for any clinical decision making and could only be performed before any radiation delivery in a research setting. All motion tracks for each patient were reviewed, and values of the average displacement, amplitude of motion, period, and associated correlation to a sinusoidal model (R(2)) were tabulated for all 42 tracks. RESULTS: For all 7 patients at least 1 transponder was successfully implanted. To assist in securing the transponder at the tumor site, it was necessary to implant a secondary fiducial for most transponders owing to the transponder's smooth surface. For 3 patients, insertion into the lung proved difficult, with only 1 transponder remaining fixed during implantation. One patient developed a pneumothorax after implantation of the secondary fiducial. Once implanted, 13 of 14 transponders remained stable within the lung and were successfully tracked with the tracking system. CONCLUSIONS: Our initial experience with electromagnetic guidance within the lung demonstrates that transponder implantation and tracking is achievable though not clinically available. This research investigation proved that lung tumor motion exhibits large variations from fraction to fraction within a single patient and that improvements to both transponder and tracking system are still necessary to create a clinical daily-use system to assist with actual lung radiation therapy.