Predictors of Subjective Olfactory Dysfunction and Sinonasal Quality-of-Life After Endoscopic Transsphenoidal Pituitary Surgery.

BACKGROUND: This is the largest study in North America investigating olfactory outcomes after pituitary surgery to date. OBJECTIVE: Characterize factors associated with subjective olfactory dysfunction (OD) and worsened sinonasal quality-of-life (QOL) after endoscopic TSA. METHODS: Patients undergoing primary TSA for secreting and non-secreting pituitary adenomas between 2017 and 2021 with pre- and post-operative SNOT-22 scores were included. Subjective OD was determined by the smell/taste dysfunction question on the SNOT-22 (smell-SNOT). RESULTS: 159 patients with pre- and post-operative SNOT-22 scores were included. Average total SNOT-22 scores worsened from pre-operative (16.91 ± 16.91) to POM1 (25.15 ± 20.83, P < .001), with no difference from pre-operative (16.40 ± 15.88) to POM6 (16.27 ± 17.92, P = .936) or pre-operative (13.63 ± 13.54) to POM12 (12.60 ± 16.45, P = .651). Average smell-SNOT scores worsened from pre-operative (0.40 ± 1.27) to POM1 (2.09 ± 2.01, P < .001), and pre-operative (0.46 ± 1.29) to POM6 (1.13 ± 2.45, P = .002), with no difference from pre-operative (0.40 ± 1.07) to POM12 (0.71 ± 1.32, P = .100). Female gender had a 0.9-point (95% CI 0.1 to 1.6) P = .021, increase in smell-SNOT at POM1, resolving by POM6 (0.1 [-0.9 to 1.1], P = .800) and POM12 (0.0 [-1.0 to 0.9], P = .942). Septoplasty with tunnel approach had a 1.1 [0.2 to 2.0] out of 5-point (P = .023) increase in smell-SNOT at POM1, resolving by POM6 (0.2 [-1.1 to 1.6], P = .764) and POM12 (0.4 [-0.9 to 1.6], P = .567). Female gender had a 9.5 (4.0 to 15.1)-point (P = .001) increase in SNOT-22 scores at POM1, resolving by POM6 (3.4 [-3.0 to 9.8], P = .292) and POM12 (6.4 [-5.4 to 18.2], P = .276). Intra-operative CSF leak had an 8.6 [2.1 to 15.1]-point (P = .009) increase in SNOT-22 scores at POM1, resolving by POM6 (5.4 [-1.7 to 12.5], P = .135), and POM12 (1.1 [-12.9 to 15.1], P = .873). CONCLUSION: Changes in subjective olfaction and sinonasal QOL after TSA may be associated with gender, operative approach, and intra-operative CSF leak, resolving 6-12 months post-operatively.

Sleep Subdomain of the Sinonasal Outcome Test as a Potential Screening Tool for Sleep Apnea in Chronic Rhinosinusitis.

OBJECTIVES: Approximately 20% of patients with chronic rhinosinusitis (CRS) have comorbid obstructive sleep apnea (OSA). Patients with undiagnosed OSA are at high risk for perioperative complications. The Sinonasal Outcomes Test (SNOT-22) Questionnaire is commonly administered to CRS patients, whereas OSA screening tools are less routinely employed. This study compared SNOT-22 sleep subdomain (Sleep-SNOT) scores among non-OSA CRS versus OSA-CRS patients undergoing ESS, and assessed sensitivity, specificity, and diagnostic accuracy of the Sleep-SNOT for OSA screening. METHODS: Retrospective review of patients that underwent endoscopic sinus surgery (ESS) for CRS from 2012 to 2021. Patients either carried a reported OSA diagnosis and completed the SNOT-22, or had undocumented OSA status and completed both STOP-BANG and SNOT-22. Demographics, questionnaire scores, and OSA status were collected. A receiver operating characteristic (ROC) curve assessed cutoff scores, sensitivity, and specificity of the Sleep-SNOT for OSA screening. RESULTS: Of 600 patients reviewed, 109 were included. 41% had comorbid OSA. OSA patients had a higher BMI (32.1 ± 7.7 vs. 28.35 ± 6.7 kg/m2 ; p = 0.02), Sleep-SNOT (21.96 ± 12.1 vs. 16.8 ± 11.2; p = 0.021) and STOP-BANG (3.1 ± 1.44 vs. 2.06 ± 1.27; p = 0.038) scores. A Sleep-SNOT score of 17.5 had a sensitivity of 68.9%, specificity of 55.7%, and diagnostic accuracy of 63% for OSA detection (p = 0.022). CONCLUSIONS: Sleep-SNOT scores are greater for CRS-OSA patients. The Sleep-SNOT ROC curve demonstrates a high sensitivity, specificity, and accuracy for OSA screening in CRS patients. A Sleep-SNOT score of ≥17.5 should prompt further OSA evaluation. The Sleep-SNOT may be considered as a surrogate OSA screening tool when other validated tools are not employed. LEVEL OF EVIDENCE: Retrospective chart review, Level 3 Laryngoscope, 133:2029-2034, 2023.

Prostate cancer sheds the αvß3 integrin in vivo through exosomes.

The αvß3 integrin has been shown to promote aggressive phenotypes in many types of cancers, including prostate cancer. We show that GFP-labeled αvß3 derived from cancer cells circulates in the blood and is detected in distant lesions in NOD scid gamma (NSG) mice. We, therefore, hypothesized that αvß3 travels through exosomes and tested its levels in pools of vesicles, which we designate extracellular vesicles highly enriched in exosomes (ExVs), and in exosomes isolated from the plasma of prostate cancer patients. Here, we show that the αvß3 integrin is found in patient blood exosomes purified by sucrose or iodixanol density gradients. In addition, we provide evidence that the αvß3 integrin is transferred through ExVs isolated from prostate cancer patient plasma to ß3-negative recipient cells. We also demonstrate the intracellular localization of ß3-GFP transferred via cancer cell-derived ExVs. We show that the ExVs present in plasma from prostate cancer patients contain higher levels of αvß3 and CD9 as compared to plasma ExVs from age-matched subjects who are not affected by cancer. Furthermore, using PSMA antibody-bead mediated immunocapture, we show that the αvß3 integrin is expressed in a subset of exosomes characterized by PSMA, CD9, CD63, and an epithelial-specific marker, Trop-2. Finally, we present evidence that the levels of αvß3, CD63, and CD9 remain unaltered in ExVs isolated from the blood of prostate cancer patients treated with enzalutamide. Our results suggest that detecting exosomal αvß3 integrin in prostate cancer patients could be a clinically useful and non-invasive biomarker to follow prostate cancer progression. Moreover, the ability of αvß3 integrin to be transferred from ExVs to recipient cells provides a strong rationale for further investigating the role of αvß3 integrin in the pathogenesis of prostate cancer and as a potential therapeutic target.

The Role of Free Tissue Transfer in the Management of Chronic Frontal Sinus Osteomyelitis.

OBJECTIVES/HYPOTHESIS: Chronic frontal sinus infection is managed with a combination of medical and surgical interventions. Frontal bone osteomyelitis due to recurrent infection following trauma or prior open surgery may require more significant debridement. Free tissue transfer may allow for extensive debridement with replacement of tissue, and definitive eradication of osteomyelitis. STUDY DESIGN: Retrospective chart review. METHODS: Patients undergoing free flap obliteration of the frontal sinus for frontal bone osteomyelitis at a single institution were included in the study. Clinical, radiologic, and surgical data were collected. Surgeries before and after free flap obliteration were compared by Wilcoxon signed rank test. RESULTS: Fifteen patients were identified; however, one patient had less than 6 months of follow-up and was excluded from analysis. Of the remaining 14 patients, mean follow-up duration was 26 months (range, 6-120 months). Mean number of surgeries prior to free flap was 3.7 (range, 1-8 surgeries). Free flap obliteration resolved chronic frontal sinusitis in all patients. Two patients experienced postoperative infection, and the overall complication rate was 29%. Eight patients underwent cranioplasty (six immediate, two delayed) without complication. All patients received planned courses of postoperative antibiotics. A statistically significant decrease in the number of surgeries after free flap obliteration was observed P ≤ .01). CONCLUSIONS: Extensive debridement followed by free tissue transfer and antibiotics offers a definitive treatment for complicated, recurrent frontal osteomyelitis. Simultaneous cranioplasty provides immediate protective and aesthetic benefit without complication. Consideration should be given for free tissue transfer and cranioplasty earlier in the algorithm for treatment of refractory frontal sinus osteomyelitis. LEVEL OF EVIDENCE: 4 Laryngoscope, 129:1497-1504, 2019.