Olfactory Outcomes After Middle Turbinate Resection in Endoscopic Transsphenoidal Surgery: A Prospective Randomized Study.

OBJECTIVE: Endoscopic endonasal transsphenoidal surgery is safe and effective for sellar and parasellar tumor removal. Partial middle turbinate (MT) resection is sometimes performed to optimize the surgical field and facilitate postoperative care. Disturbances in olfaction are concerning because of the lack of randomized studies in this field. STUDY DESIGN: Prospective randomized trial. SETTING: Single academic medical center. METHODS: We resected the lower halves of bilateral MTs in the resected group and laterally fractured bilateral MTs in the preserved group. Olfactory outcomes and sinonasal conditions were assessed by using the validated Taiwan Smell Identification Test and Lund-Kennedy Endoscopy Score, respectively. Forty-nine patients were enrolled in the final analysis, of whom 23 underwent partial MT resection. RESULTS: The average Taiwan Smell Identification Test result was 36.9 one month after surgery, with a significant change of -4.4 ± 3.1 (mean ± SD; P < .01) from baseline. The impact was not significant at 3 months (-2.1 ± 2.6, P = .13) or 6 months (0.3 ± 2.0, P = .79). Between the MT resection and preservation groups, there were no significant differences at postoperative 1 month (P = .60), 3 months (P = .86), and 6 months (P > .99). Lund-Kennedy Endoscopy Score was still higher at 3 months (P = .006) after surgery but returned to the preoperative level at 6 months (P = .63). CONCLUSIONS: Endoscopic endonasal transsphenoidal surgery may affect olfaction at 1 month after surgery, and olfactory function is expected to return after 3 months. Partial MT resection did not result in additional olfactory loss. It is safe to perform partial MT resection during surgery without compromising the olfactory outcomes.

Using ovality to predict nonmutagenic, orally efficacious pyridazine amides as cell specific spleen tyrosine kinase inhibitors.

Inhibition of spleen tyrosine kinase has attracted much attention as a mechanism for the treatment of cancers and autoimmune diseases such as asthma, rheumatoid arthritis, and systemic lupus erythematous. We report the structure-guided optimization of pyridazine amide spleen tyrosine kinase inhibitors. Early representatives of this scaffold were highly potent and selective but mutagenic in an Ames assay. An approach that led to the successful identification of nonmutagenic examples, as well as further optimization to compounds with reduced cardiovascular liabilities is described. Select pharmacokinetic and in vivo efficacy data are presented.

3-Amido pyrrolopyrazine JAK kinase inhibitors: development of a JAK3 vs JAK1 selective inhibitor and evaluation in cellular and in vivo models.

The Janus kinases (JAKs) are involved in multiple signaling networks relevant to inflammatory diseases, and inhibition of one or more members of this class may modulate disease activity or progression. We optimized a new inhibitor scaffold, 3-amido-5-cyclopropylpyrrolopyrazines, to a potent example with reasonable kinome selectivity, including selectivity for JAK3 versus JAK1, and good biopharmaceutical properties. Evaluation of this analogue in cellular and in vivo models confirmed functional selectivity for modulation of a JAK3/JAK1-dependent IL-2 stimulated pathway over a JAK1/JAK2/Tyk2-dependent IL-6 stimulated pathway.