Faculty Bibliography

OBJECTIVES: Based on our laboratory's newly confirmed motor pathway for glottic closure, we measured the glottic closing force (GCF) during isolated stimulation of the external branch of the superior laryngeal nerve (eSLN) in the porcine model. Glottic closure is 1 of the primary mechanisms for prevention of aspiration during deglutition. METHODS: The recurrent laryngeal nerve (RLN) and eSLN were identified bilaterally in 4 porcine necks. Subsequently, GCF was measured with a pressure transducer as the distal ends of individual nerves were stimulated in 4 animals. The RLN mediated GCF was measured first, followed by isolated eSLN mediated GCF, followed by transection of the RLN and repeat measurement of the eSLN GCF. Ultimately, the cricothyroid (CT) muscle attachment was released and the GCF measured. RESULTS: The GCF during isolated eSLN stimulation before and after RLN transection is approximately 89% of the RLN mediated GCF in each animal. The GCF after CT release is approximately 84% of the RLN perceived GCF. Transection of the RLN did not alter the eSLN observed GCF. CONCLUSIONS: The GCF obtained during isolated eSLN stimulation is adequate for delivery of an appropriate laryngeal protective response and may be considered a target motor nerve for augmenting GCF in selected rehab settings.

BACKGROUND: Signal transducer and activator 1 (STAT-1) mutations are rare and have been implicated in combined immunodeficiency, enhanced tumorigenesis, and vascular defects. METHODS: A 60-year-old woman with a novel STAT-1 mutation and resulting immunodeficiency, squamous cell carcinoma, and vascular disease presented with profuse epistaxis secondary to rupture of an aberrant artery that she developed in part because of this mutation. After unsuccessful posterior packing, embolization was initiated but subsequently aborted because of a bovine origin carotid artery and a history of multiple carotid dissections. RESULTS: After repeat posterior packing, hemostasis was achieved. No additional episodes of epistaxis occurred in the subsequent 13 months. CONCLUSION: Vascular anomalies can present challenges in epistaxis management. In patients with conditions known to cause vascular anomalies, it is critical to obtain vascular imaging before intervention.

A craniotomy over the superior cerebellar convexity for approaches to this region typically involves a small infratentorial craniotomy and then drilling down of the bone to expose some portion of the transverse/sigmoid sinuses. The authors describe the anatomy of the region and the method for a two-part paramedian occipital and suboccipital craniotomy (supra and infratentorial) that may have time-saving, safety, and cosmetic advantages. For this technique, a supratentorial craniotomy is used to expose the transverse sinus from above, and subsequently, dissection across the sinus over the cerebellar convexity can be done under direct vision. The two bone pieces are joined on the inner table side while plates for fixation above the superior nuchal line can be counter-sunk to avoid post-operative pain from the prominence of screws. There is no need for cranioplasty materials since there is no burring down of bone for adequate exposure of the transverse sinus. The technique has been used by two senior surgeons over the years convincing them of the speed, safety, and utility of the technique. Here, the authors present a single example of the technique.

PURPOSE: AZD6244 is a MEK1/2 inhibitor with significant preclinical activity in multiple myeloma cells. This phase II study used a two-stage Simon design to determine the AZD6244 response rate in patients with relapsed or refractory multiple myeloma. EXPERIMENTAL DESIGN: AZD6244 (75 mg) was administered orally, twice a day, continuously for 28-day cycles. Response was evaluated after three cycles. RESULTS: Thirty-six patients received therapy. The median age was 65 years (range: 43-81) and the median number of prior therapies was 5 (range: 2-11). The most common grade 3 and 4 toxicities included anemia, neutropenia, thrombocytopenia, diarrhea, and fatigue. Three deaths occurred possibly related to AZD6244 (2 due to sepsis, 1 due to acute kidney injury). After AZD6244 discontinuation, three additional deaths occurred due to disease progression. The response rate (CR + PR) was 5.6% with a mean duration of response of 4.95 months and median progression-free survival time of 3.52 months. One patient had a very good partial response (VGPR), 1 patient had a partial response, 17 patients had stable disease, 13 patients had progressive disease, and 4 patients could not be assessed for response. Pharmacodynamic studies revealed variable effects on bone marrow CD138(+) cell MEK1/2 and ERK1/2 phosphorylation. The best clinical response, a prolonged VGPR, occurred in a patient with an MMSET translocation. CONCLUSIONS: Single-agent AZD6244 was tolerable and had minimal activity in this heavily pretreated population.