Safety and Stability of Antibody-Dye Conjugate in Optical Molecular Imaging.

PURPOSE: The development of molecularly targeted tracers is likely to improve the accuracy of diagnostic, screening, and therapeutic tools. Despite the many therapeutic antibodies that are FDA-approved with known toxicity, only a limited number of antibody-dye conjugates have been introduced to the clinic. Thorough evaluation of the safety, stability, and pharmacokinetics of antibody conjugates in the clinical setting compared with their parental components could accelerate the clinical approval of antibodies as agents for molecular imaging. Here we investigate the safety and stability of a near-infrared fluorescent dye (IRDye800CW) conjugated panitumumab, an approved therapeutic antibody, and report on the product stability, pharmacokinetics, adverse events, and QTc interval changes in patients. PROCEDURES: Panitumumab-IRDye800CW was made under good manufacturing practice (GMP) conditions in a single batch on March 26, 2014, and then evaluated over 4.5 years at 0, 3, and 6 months, and then at 6-month intervals thereafter. We conducted early phase trials in head and neck, lung, pancreas, and brain cancers with panitumumab-IRDye800CW. Eighty-one patients scheduled to undergo standard-of-care surgery were infused with doses between 0.06 to 2.83 mg/kg of antibody. Patient ECGs, blood samples, and adverse events were collected over 30-day post-infusion for analysis. RESULTS: Eighty-one patients underwent infusion of the study drug at a range of doses. Six patients (7.4 %) experienced an adverse event that was considered potentially related to the drug. The most common event was a prolonged QTc interval which occurred in three patients (3.7 %). Panitumumab-IRDye800CW had two OOS results at 42 and 54 months while meeting all other stability testing criteria. CONCLUSIONS: Panitumumab-IRDye800CW was safe and stable to administer over a 54-month window with a low rate of adverse events (7.4 %) which is consistent with the rate associated with panitumumab alone. This data supports re-purposing therapeutic antibodies as diagnostic imaging agents with limited preclinical toxicology studies.

Quality and Readability of Online Information on In-Office Vocal Fold Injections.

OBJECTIVES: Vocal fold injection augmentations are increasingly being performed in the office setting on awake patients, as opposed to the operating room. These procedures thus require patient cooperation and education. As the Internet is a widely-used resource for patients, our aim was to assess the quality and readability of online resources on in-office awake vocal fold injections. METHODS: An online Google search using the terms "office vocal fold injection medialization" and "awake vocal fold injection" was conducted. The first 50 English-language websites were categorized into professional- and patient-targeted, and major and minor sources. They were analyzed using the Flesch Reading Ease Score (FRES), Flesch-Kincaid Grade Level (FKGL) test, and DISCERN quality score. RESULTS: Fifty websites were evaluated, and the overall DISCERN score was 2.60 ± 1.01, the mean FRES was 32.16 ± 19.10, and the mean FKGL was 13.76 ± 4.12. Between the 25 professional-targeted and 25 patient-targeted websites, professional-targeted sites had significantly higher DISCERN (P < .05) and FKGL (P < .05) scores, and lower FRES (P < .05) scores. Between the 30 major and 20 minor websites, major websites had significantly lower FRES (P < .05) and higher FKGL (P < .05) scores, and there was a trend toward significance for higher DISCERN scores (P = .052). CONCLUSIONS: Our study shows that half of the top Google results for our topic were not written for patient education, but rather for health care professionals. The reading level of this information exceeds the recommended grade level for patient education materials, and may be less comprehensible than intended. While patient-targeted materials are easier to read than professional-targeted sites, they are of lower quality. The quality of the available online information on this topic is suboptimal for both patients and health care providers. This research highlights the need for more appropriate patient education materials given low health literacy rates.

Effect of Nerve Stimulation Use on the Success Rate of Ultrasound-Guided Subsartorial Saphenous Nerve Block: A Randomized Controlled Trial.

BACKGROUND AND OBJECTIVES: Ultrasound-guided subsartorial saphenous nerve block is commonly used to provide complete surgical anesthesia of the foot and ankle in combination with a popliteal sciatic nerve block. However, in part owing to its small caliber and absence of a prominent vascular landmark in the subsartorial plane distal to the adductor canal, the saphenous nerve is more difficult to reliably block than the sciatic nerve in the popliteal fossa. Although the saphenous nerve is a sensory nerve only, neurostimulation can be used to elicit a "tapping" sensation on the anteromedial aspect of the lower leg extending toward the medial malleolus. Our objective was to test the hypothesis that the addition of nerve stimulation use to an ultrasound (US)-guided technique will increase the success rate of subsartorial saphenous nerve block. METHODS: With institutional human ethics board approval and participants' written informed consent, we enrolled 80 patients undergoing foot and ankle surgery in a randomized, single-blinded, parallel-group clinical trial. Patients were randomly assigned to receive US-guided subsartorial saphenous nerve block either alone (US group) or with the use of additional nerve stimulation (NS group; time limit, 5 minutes). For saphenous nerve blockade, all patients received 10 mL of 0.5% ropivacaine. The primary end point was complete absence of sensation to pinprick at 30 minutes at two different anatomic areas in the distribution of the saphenous nerve (2 cm proximal to the medial malleolus and 10 cm distal to the medial tibial condyle). Secondary end points included decreased sensation at 30 minutes and block failure (normal sensation) at 30 minutes. This trial was registered at ClinicalTrials.gov: NCT02382744. RESULTS: All 80 patients completed the trial (40 patients in each group). Twenty-two patients (55%) in the NS group versus 18 (45%) in the US group had complete absence of sensation to pinprick at 30 minutes at both anatomic areas of assessment (Fisher exact test, P = 0.25 [one sided]; 95% confidence interval of difference in proportions, -11.9% to 31.9%). The percentages of patients with any evidence of block (decreased or complete absence of sensation) at both areas at 30 minutes were 92.5% (NS) and 97.5% (US), respectively (P = 0.62 [two sided]); corresponding failure rates (normal sensation) were 7.5% (NS) and 2.5% (US). In the NS group, no response in the saphenous nerve distribution was elicited within 5 minutes of stimulation time limit in 20% of patients (n = 8). All of the patients in the NS group with normal sensation at 30 minutes (n = 3) were among this subcohort. CONCLUSIONS: The addition of the use of nerve stimulation did not improve the success rate of US-guided subsartorial saphenous nerve block. However, in the NS group, an inability to elicit a "tapping" sensation in the saphenous nerve distribution was associated with block failure.