The beta agonist lung injury trial prevention. A randomized controlled trial.

RATIONALE: Experimental studies suggest that pretreatment with ß-agonists might prevent acute lung injury (ALI). OBJECTIVES: To determine if in adult patients undergoing elective esophagectomy, perioperative treatment with inhaled ß-agonists effects the development of early ALI. METHODS: We conducted a randomized placebo-controlled trial in 12 UK centers (2008-2011). Adult patients undergoing elective esophagectomy were allocated to prerandomized, sequentially numbered treatment packs containing inhaled salmeterol (100 µg twice daily) or a matching placebo. Patients, clinicians, and researchers were masked to treatment allocation. The primary outcome was development of ALI within 72 hours of surgery. Secondary outcomes were ALI within 28 days, organ failure, adverse events, survival, and health-related quality of life. An exploratory substudy measured biomarkers of alveolar-capillary inflammation and injury. MEASUREMENTS AND MAIN RESULTS: A total of 179 patients were randomized to salmeterol and 183 to placebo. Baseline characteristics were similar. Treatment with salmeterol did not prevent early lung injury (32 [19.2%] of 168 vs. 27 [16.0%] of 170; odds ratio [OR], 1.25; 95% confidence interval [CI], 0.71-2.22). There was no difference in organ failure, survival, or health-related quality of life. Adverse events were less frequent in the salmeterol group (55 vs. 70; OR, 0.63; 95% CI, 0.39-0.99), predominantly because of a lower number of pneumonia (7 vs. 17; OR, 0.39; 95% CI, 0.16-0.96). Salmeterol reduced some biomarkers of alveolar inflammation and epithelial injury. CONCLUSION: Perioperative treatment with inhaled salmeterol was well tolerated but did not prevent ALI. Clinical trial registered with International Standard Randomized Controlled Trial Register (ISRCTN47481946) and European Union database of randomized Controlled Trials (EudraCT 2007-004096-19).

Electrical Stimulation of Eye Blink in Individuals with Acute Facial Palsy: Progress toward a Bionic Blink.

BACKGROUND: Elicitation of eye closure and other movements via electrical stimulation may provide effective treatment for facial paralysis. The authors performed a human feasibility study to determine whether transcutaneous neural stimulation can elicit a blink in individuals with acute facial palsy and to obtain feedback from participants regarding the tolerability of surface electrical stimulation for daily blink restoration. METHODS: Forty individuals with acute unilateral facial paralysis, HB grades 4 through 6, were prospectively studied between 6 and 60 days of onset. Unilateral stimulation of zygomatic facial nerve branches to elicit eye blink was achieved with brief bipolar, charge-balanced pulse trains, delivered transcutaneously by adhesive electrode placement; results were recorded on a high-speed video camera. The relationship between stimulation parameters and cutaneous sensation was analyzed using the Wong-Baker Faces Pain Rating Scale. RESULTS: Complete eye closure was achieved in 55 percent of participants using stimulation parameters reported as tolerable. In those individuals, initial eye twitch was observed at an average current of 4.6 mA (±1.7; average pulse width of 0.7 ms, 100 to 150 Hz), with complete closure requiring a mean of 7.2 mA (±2.6). CONCLUSIONS: Transcutaneous facial nerve stimulation may artificially elicit eye blink in a majority of patients with acute facial paralysis. Although individuals varied widely in their reported degrees of discomfort from blink-eliciting stimulation, most of them indicated that such stimulation would be tolerable if it could restore eye closure. These patients would therefore benefit from a biomimetic device to facilitate eye closure until the recovery process is complete. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, IV.

Fast kilovoltage/megavoltage (kVMV) breathhold cone-beam CT for image-guided radiotherapy of lung cancer.

Long image acquisition times of 60-120 s for cone-beam CT (CBCT) limit the number of patients with lung cancer who can undergo volume image guidance under breathhold. We developed a low-dose dual-energy kilovoltage-megavoltage-cone-beam CT (kVMV-CBCT) based on a clinical treatment unit reducing imaging time to < or =15 s. Simultaneous kVMV-imaging was achieved by dedicated synchronization hardware controlling the output of the linear accelerator (linac) based on detector panel readout signals, preventing imaging artifacts from interference of the linac's MV-irradiation and panel readouts. Optimization was performed to minimize the imaging dose. Single MV-projections, reconstructed MV-CBCT images and images of simultaneous 90 degrees kV- and 90 degrees MV-CBCT (180 degrees kVMV-CBCT) were acquired with different parameters. Image quality and imaging dose were evaluated and compared to kV-imaging. Hardware-based kVMV synchronization resulted in artifact-free projections. A combined 180 degrees kVMV-CBCT scan with a total MV-dose of 5 monitor units was acquired in 15 s and with sufficient image quality. The resolution was 5-6 line pairs cm(-1) (Catphan phantom). The combined kVMV-scan dose was equivalent to a kV-radiation scan dose of approximately 33 mGy. kVMV-CBCT based on a standard linac is promising and can provide ultra-fast online volume image guidance with low imaging dose and sufficient image quality for fast and accurate patient positioning for patients with lung cancer under breathhold.