The αvβ3 integrin has been shown to promote aggressive phenotypes in many types of cancers, including prostate cancer. We show that GFP-labeled αvβ3 derived from cancer cells circulates in the blood and is detected in distant lesions in NOD scid gamma (NSG) mice. We, therefore, hypothesized that αvβ3 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 αvβ3 integrin is found in patient blood exosomes purified by sucrose or iodixanol density gradients. In addition, we provide evidence that the αvβ3 integrin is transferred through ExVs isolated from prostate cancer patient plasma to β3-negative recipient cells. We also demonstrate the intracellular localization of β3-GFP transferred via cancer cell-derived ExVs. We show that the ExVs present in plasma from prostate cancer patients contain higher levels of αvβ3 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 αvβ3 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 αvβ3, CD63, and CD9 remain unaltered in ExVs isolated from the blood of prostate cancer patients treated with enzalutamide. Our results suggest that detecting exosomal αvβ3 integrin in prostate cancer patients could be a clinically useful and non-invasive biomarker to follow prostate cancer progression. Moreover, the ability of αvβ3 integrin to be transferred from ExVs to recipient cells provides a strong rationale for further investigating the role of αvβ3 integrin in the pathogenesis of prostate cancer and as a potential therapeutic target.

Objectives In otolaryngology, postoperative pain management lacks evidence‐based guidelines. We designed a prospective, multiphasic study aimed to develop evidence‐based guidelines for postoperative pain management within our institution. In this first phase of our project, we investigated opioid prescription and consumption as well as pain trends for common otolaryngologic procedures. Methods Patients (n = 161) who underwent procedures between July 2018 and February 2019 were surveyed on their postoperative opioid usage and pain from day of discharge to first clinic visit. Opioid prescriptions were converted to standardized units of morphine milligram equivalents (MME). The procedures selected for analysis were parathyroidectomy/thyroidectomy, parotidectomy, sialendoscopy, and transoral robotic surgery resection (TORS). Results In total, 19,748 MME were prescribed: 8,588 MME (43.5%) were used, leaving 11,159 MME (56.5%) unused. TORS average MME used: 221 ± 227; total MME unused: 38%. Sialendoscopy average MME used: 31 ± 46; total MME unused: 67%. Parathyroidectomy/thyroidectomy average MME used: 30 ± 37; total MME unused: 66%. Parotidectomy average MME used: 43 ± 53; total MME unused: 65%. Male gender, smoking (current and former), and psychiatric medication use were positive predictors of opioid consumption in postoperative patients (P < 0.001). Conclusion At our institution, over 50% of prescribed postoperative opioids went unused. This was most pronounced for nonmucosal surgeries. Postoperative pain management should account for this to minimize unnecessary opioid prescriptions. Based on our findings and review of current literature, we are in the process of developing prescribing recommendations to be implemented within our institution. Level of Evidence 2 Laryngoscope, 130:659–665, 2020

Purpose of review Interspinous process devices (IPDs) are used in the surgical treatment of lumbar spinal stenosis. The purpose of this review is to compare the first generation with the next-generation devices in terms of complications, device failure, reoperation rates, symptom relief, and outcome. Recent findings Thirty-seven studies were included from 2011 to 2016. Device failure occurred at a mean of 3.7%, with a lower tendency to happen with next-generation IPDs. Reoperations occurred at a lower rate with the nextgeneration devices, with a mean follow up of 24 months (3.7% vs. 11.1%). The clinical outcome is not influenced by the type of IPD. Summary The long-term functionality of these devices is questionable, with radiologic changes and recurrence of symptoms often seen by 2 years following implantation. Next-generation devices do not appear to be subject to the same "bounce back" effect of symptom re-emergence after several years.

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

Radiation therapy is an effective cancer treatment modality although tumors invariably become resistant. Using the transgenic adenocarcinoma of mouse prostate (TRAMP) model system, we report that a hypofractionated radiation schedule (10 Gy/day for 5 consecutive days) effectively blocks prostate tumor growth in wild type (β1wt /TRAMP) mice as well as in mice carrying a conditional ablation of β1 integrins in the prostatic epithelium (β1pc-/- /TRAMP). Since JNK is known to be suppressed by β1 integrins and mediates radiation-induced apoptosis, we tested the effect of SP600125, an inhibitor of c-Jun amino-terminal kinase (JNK) in the TRAMP model system. Our results show that SP600125 negates the effect of radiation on tumor growth in β1pc-/- /TRAMP mice and leads to invasive adenocarcinoma. These effects are associated with increased focal adhesion kinase (FAK) expression and phosphorylation in prostate tumors in β1pc-/- /TRAMP mice. In marked contrast, radiation-induced tumor growth suppression, FAK expression and phosphorylation are not altered by SP600125 treatment of β1wt /TRAMP mice. Furthermore, we have reported earlier that abrogation of insulin-like growth factor receptor (IGF-IR) in prostate cancer cells enhances the sensitivity to radiation. Here we further explore the β1/IGF-IR crosstalk and report that β1 integrins promote cell proliferation partly by enhancing the expression of IGF-IR. In conclusion, we demonstrate that β1 integrin-mediated inhibition of JNK signaling modulates tumor growth rate upon hypofractionated radiation.

Cells are known to release different types of vesicles such as small extracellular vesicles (sEVs) and large extracellular vesicles (LEVs). sEVs and LEVs play important roles in intercellular communication, pre-metastatic niche formation, and disease progression; both can be detected cell culture media and biological fluids. sEVs and LEVs contain a variety of protein and RNA cargo, and they are believed to impact many biological functions of the recipient cells upon their internalization or binding to cell surface proteins. It has recently been established that standard isolation techniques, such as differential ultracentrifugation, yield a mixed population of EVs. However, density gradient ultracentrifugation has been reported to allow the isolation of sEVs without cellular debris. Here, we describe the most common methods used to isolate sEVs from cell culture medium, mouse and human plasma, and a new technique for isolating sEVs from tissues as well. This article also provides detailed procedures to isolate LEVs.

ObjectivesAmong the transsphenoidal (TSS) approaches to pituitary tumors, the microscopic approach (MA) has historically been the predominant technique with the increasing adoption of the endoscopic approach (EA). This study investigates national trends in TSS approaches and postoperative outcomes for MA and EA through 2021.MethodsThe TriNetX database was queried for patients undergoing TSS (MA and EA) between 2010 and 2021. Data were collected on demographics, geographic distribution of surgical centers, postoperative complications, stereotactic radiosurgery (SRT), repeat surgery, and postoperative emergency department (ED) visits.Results8644 TSS cases were queried between 2010 and 2021. MA rates were highest until 2013 when rates of EA (52%) surpassed MA (48%) and continued to increase through 2021 (81%). From 2010 to 2015 EA had higher odds of a postoperative CSF leak (OR 3.40) and diabetes insipidus (DI (OR 2.30)) versus MA (p < 0.05); from 2016 to 2021 differences were not significant. Although there was no significant difference among approaches from 2010 to 2015 for syndrome of inappropriate antidiuretic hormone (SIADH), hyponatremia, or bacterial meningitis, from 2016 to 2021 EA had lower odds of SIADH (OR 0.54) and hyponatremia (OR 0.71), and higher odds of meningitis (OR 1.79) versus MA (p < 0.05). EA had higher odds of additional surgery (either EA or MA) after initial surgery from 2010 to 2021. From 2010 to 2015 EA had lower odds of postoperative SRT compared to MA, whereas in 2016–2021 there was no statistical difference among approaches.ConclusionThis study demonstrates increasing EA adoption for TSS in the United States since 2013. Complication rates have overall improved for EA compared to MA, potentially as a result of improving surgeon familiarity and experience.Level of Evidence4 Laryngoscope, 133:2135–2140, 2023

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