Eumelanin-Inspired Antimicrobial with Biocidal Activity against Methicillin-Resistant Staphylococcus aureus.

The reliance on antibiotics and antimicrobials to treat bacterial infectious diseases is threatened by the emergence of antibiotic resistance and multi-drug-resistant organisms, thus having the potential to greatly impact human health. Thus, the discovery and development of antimicrobials capable of acting on antibiotic-resistant bacteria is a major area of significance in scientific research. Herein, we present the development of a eumelanin-inspired antimicrobial capable of killing methicillin-resistant Staphylococcus aureus (MRSA). By ligating quaternary ammonium-functionalized "arms" to a eumelanin-inspired indole with intrinsic antimicrobial activity, an antimicrobial agent with enhanced activity was prepared. This resulting antimicrobial, EIPE-1, had a minimum inhibitory concentration of 16 µg/mL (17.1 µM) against a clinical isolate of MRSA obtained from an adult cystic fibrosis patient. The biocidal activity occurred within 30 min of exposure and resulted in changes to the bacterial cell surface as visualized with a scanning electron microscope. Taken together, these studies demonstrate that EIPE-1 is effective at killing MRSA.

Multi-center validation of the Bowel Injury Predictive Score (BIPS) for the early identification of need to operate in blunt bowel and mesenteric injuries.

INTRODUCTION: The Bowel Injury Prediction Score (BIPS) is a tool for identifying patients at risk for blunt bowel and mesenteric injury (BBMI) requiring surgery. BIPS is calculated by assigning one point for each of the following: (1) WBC ≥ 17,000, (2) abdominal tenderness, and (3) injury grade ≥ 4 (mesenteric contusion or hematoma with bowel wall thickening or adjacent interloop fluid collection) on CT scan. A total score ≥ 2 is associated with BBMI requiring surgery. We aimed to validate the BIPS as a predictor for patients with BBMIs requiring operative intervention in a multi-center prospective study. MATERIALS AND METHODS: Patients were prospectively enrolled at 15 U.S. trauma centers following blunt trauma with suspicion of BBMI on CT scan between July 1, 2018 and July 31, 2019. The BIPS was calculated for each patient enrolled in the study. RESULTS: Of 313 patients, 38% had BBMI requiring operative intervention. Patients were significantly more likely to require surgery in the presence of abdominal tenderness (OR, 3.6; 95% CI, 1.6-8.0) and CT grade ≥ 4 (OR, 11.7; 95% CI, 5.7-23.7). Patients with a BIPS ≥ 2 were more than ten times more likely to require laparotomy than those with a BIPS < 2 (OR, 10.1; 95% CI, 5.0-20.4). The sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of a BIPS ≥ 2 for BBMI requiring surgery was 72% (CI 0.6-0.8), 78% (CI 0.7-0.8), 67% (CI 0.6-0.8), and 82% (CI 0.8-0.9), respectively. The AUROC curve for BIPS ≥ 2 was 0.75. The sensitivity, specificity, PPV, and NPV of a BIPS ≥ 2 for BBMI requiring surgery in patients with severe alteration in mental status (GCS 3-8) was 70% (CI 0.5-0.9), 92% (CI 0.8-1.0), 82% (CI 0.6-1.0), and 86% (CI 0.7-1.0), respectively. CONCLUSION: This prospective multi-center trial validates BIPS as a predictor of BBMI requiring surgery. Calculation of BIPS during the initial evaluation of trauma patients is a useful adjunct to help general surgeons taking trauma call determine operative versus non-operative management of patients with BBMI including those with severe alteration in mental status.

Effect of glenohumeral elevation on subacromial supraspinatus compression risk during simulated reaching.

Mechanical subacromial rotator cuff compression is one theoretical mechanism in the pathogenesis of rotator cuff disease. However, the relationship between shoulder kinematics and mechanical subacromial rotator cuff compression across the range of humeral elevation motion is not well understood. The purpose of this study was to investigate the effect of humeral elevation on subacromial compression risk of the supraspinatus during a simulated functional reaching task. Three-dimensional anatomical models were reconstructed from shoulder magnetic resonance images acquired from 20 subjects (10 asymptomatic, 10 symptomatic). Standardized glenohumeral kinematics from a simulated reaching task were imposed on the anatomic models and analyzed at 0, 30, 60, and 90° humerothoracic elevation. Five magnitudes of humeral retroversion were also imposed on the models at each angle of humerothoracic elevation to investigate the impact of retroversion on subacromial proximities. The minimum distance between the coracoacromial arch and supraspinatus tendon and footprint were quantified. When contact occurred, the magnitude of the intersecting volume between the supraspinatus tendon and coracoacromial arch was also quantified. The smallest minimum distance from the coracoacromial arch to the supraspinatus footprint occurred between 30 and 90°, while the smallest minimum distance to the supraspinatus tendon occurred between 0 and 60°. The magnitude of humeral retroversion did not significantly affect minimum distance to the supraspinatus tendon except at 60 or 90° humerothoracic elevation. The results of this study provide support for mechanical rotator cuff compression as a potential mechanism for the development of rotator cuff disease. © 2017 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 35:2329-2337, 2017.