Muscle-Nerve-Nerve Grafting Improves Facial Reanimation in Rats Following Facial Nerve Injury.

Nerve injury resulting in muscle paralysis from trauma or surgery is a major medical problem. Repair of such injuries with existing nerve grafting and reconstructive techniques often results in less than optimal outcomes. After previously demonstrating significant return of function using muscle-nerve-muscle (MNM) grafting in a rat facial nerve model, this study compares a variant of the technique, muscle-nerve-nerve (MNN) neurotization to MNM and interposition (IP) nerve grafting. Thirty male rats were randomized into four groups (1) control with no intervention, (2) repair with IP grafts, (3) MNM grafts and (4) MNN grafts. All groups had the buccal and marginal mandibular branches of the right facial nerve resected. Return of vibrissae movement, orientation, and snout symmetry was measured over 16 weeks. Functional recovery and muscle atrophy were assessed and quantified. All interventions resulted in significant improvement in vibrissae movement and orientation as compared to the control group (p < 0.05). The MNM and MNN groups had significantly less time to forward vibrissae movement as compared to controls (p < 0.05), and a large number of animals in the MNN group had coordinated vibrissae movement at 16 weeks. MNN and IP grafts retained significantly more muscle mass as compared to control (p < 0.05). Thus, MNN grafting is a promising adjuvant or alternative technique for reanimation for patients with unilateral peripheral nerve injury who are not candidates for primary neurorrhaphy.

Targeted 595-gene genomic profiling demonstrates low tumor mutational burden in olfactory neuroblastoma.

BACKGROUND: Olfactory neuroblastoma (ONB) is a rare skull-base malignancy associated with delayed local recurrence. Treatment options in recurrent disease are few and unreliable. We undertook analysis of the ONB exome and immune environment in order to identify potential future immunotherapy treatment options. METHODS: Retrospective chart review and next-generation targeted 595-gene genomic profiling was performed on a cohort of 14 ONB cases utilizing Tempus proprietary DNA and RNA sequencing technology. Tempus analysis provided a measurement of tumor mutational burden (TMB) and composition of the immune cell infiltrate present in tumor samples. Clinically relevant genomic alterations and associated targeted therapies were identified using cancer.gov and clinicaltrials.gov. TMB was tested by univariate analysis against clinical stage, pathologic grade, recurrence risk, and immune cell infiltration. RESULTS: The mean age for the subjects was 50 years (range, 13 to 76 years) with a male:female ratio of 1:1. TMB for ONB samples ranged from 1.3 to 9.6 mutations/megabase (Mb) with mean of 3.8 mutations/Mb. Univariate analysis showed no association between TMB and tumor stage, pathologic grade, risk of recurrence, or immune cell infiltration. Genomic profile revealed that 6 of 13 tumors had genetic alterations with targeted therapies in clinical trials, whereas 1 tumor demonstrated KRAS Q61R mutation with U.S. Food and Drug Administration (FDA)-approved targeted therapies. CONCLUSION: TMB is a novel biomarker guiding the classification of neoplasms in the emerging era of immunotherapy. The characterization of ONB as a low-TMB pathology contributes to the overall taxonomy of all cancers and suggests limited utility of immunotherapy treatment.

Biologic Agents for the Treatment of Chronic Rhinosinusitis With Nasal Polyps.

BACKGROUND: Chronic rhinosinusitis with nasal polyposis is a complex inflammatory disorder, which is often recalcitrant to medical and surgical management. Recently, biologic agents have been studied as an adjunct treatment for this patient population. OBJECTIVE: The purpose of this study is to examine the role of biologic agents for chronic rhinosinusitis patients by reviewing literature and clinical trials. METHODS: A comprehensive review of literature and clinical trials-both recently completed and ongoing-was undertaken to examine up-to-date evidence of current biologic therapy and its role in chronic rhinosinusitis patients-including anti-IgE, anti-IL-4, anti-IL-5, anti-IL-13, and GATA-3 DNAzyme. RESULTS: Specific biologic agents discussed include omalizumab, reslizumab, mepolizumab, benralizumab, dupilumab, and Hgd40/SB010. Risks, side effects, and administration information are also reviewed. An algorithm for the use of biologics in patients with chronic rhinosinusitis with nasal polyposis is proposed. CONCLUSION: These treatments have promising results and may prove to be an important adjunct for patients with recalcitrant sinus disease.