Opioid Prescribing Patterns Following Lateral Skull Base Spontaneous Cerebrospinal Fluid Leak Repair.

OBJECTIVE: To characterize the opioid prescribing patterns for and requirements of patients undergoing repair of spontaneous cerebrospinal fluid (sCSF) leaks of the lateral skull base. STUDY DESIGN: Retrospective chart review. SETTING: Tertiary referral center. PATIENTS: Adults with lateral skull base sCSF leaks who underwent repairs between September 1, 2014, and December 31, 2020. MAIN OUTCOME MEASURE: Mean morphine milligram equivalents (MMEs) of opioids dispensed to inpatients and prescribed at discharge, additional pain control medications dispensed, and outpatient additional opioid requests were compared between groups. RESULTS: Of 78 patients included, 46 (59%) underwent repair via a transmastoid (TM), 6 (7.7%) via a middle cranial fossa (MCF), and 26 (33.3%) via a combined TM-MCF approach. Inpatients received a mean of 21.3, 31.4, and 37.6 MMEs per day during admission for the TM, MCF, and combined TM-MCF approaches, respectively ( p = 0.019, ηp 2 = 0.101). Upon discharge, nearly all patients (n = 74, 94.9%) received opioids; 27.3, 32.5, and 37.6 MMEs per day were prescribed after the TM, MCF, and TM-MCF approaches, respectively ( p = 0.015, ηp 2 = 0.093). Five (6.4%) patients requested additional outpatient pain medication, after which three were prescribed 36.7 MMEs per day. Patients with idiopathic intracranial hypertension required significantly more inpatient MMEs than those without (41.5 versus 25.2, p = 0.02, d = 0.689), as did patients with a history of headaches (39.6 versus 23.6, p = 0.042, d = 0.684). CONCLUSIONS: Patients undergoing sCSF leak repair via the MCF or TM-MCF approaches are prescribed more opioids postoperatively than patients undergoing the TM approach. Patients with a history of headaches or idiopathic intracranial hypertension might require more opioids postoperatively.

A Scoping Review of Otologic Manifestations of Hematologic Malignancies.

OBJECTIVE: To examine the otologic and neurotologic symptoms, physical examination findings, and imaging features secondary to hematologic malignancies. METHODS: Following Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines, databases, including PubMed, Scopus, and CINAHL, were searched for articles including patients with otologic manifestations of leukemia, lymphoma and multiple myeloma. Data collected included patient and study demographics, specific hematologic malignancy, timing and classification of otologic symptoms, physical examination findings, imaging features and methods of diagnosis. Pooled descriptive analysis was performed. RESULTS: Two hundred seventy-two articles, of which 255 (93.8%) were case reports and 17 (6.2%) were case series, reporting on 553 patients were identified. Otologic manifestations were reported on 307 patients with leukemia, 204 patients with lymphoma and 42 patients with multiple myeloma. Hearing loss and unilateral facial palsy were the most common presenting symptoms for 111 reported subjects with leukemia (n = 46, 41.4%; n = 43, 38.7%) and 90 with lymphoma (n = 38, 42.2%; n = 39, 43.3%). Hearing loss and otalgia were the most common presenting symptoms for 21 subjects with multiple myeloma (n = 10, 47.6%; n = 6, 28.6%). Hearing loss and unilateral facial palsy were the most common otologic symptoms indicative of relapse in subjects with leukemia (n = 14, 43.8%) and lymphoma (n = 5, 50%). CONCLUSION: Hearing loss, facial palsy, and otalgia might be the first indication of a new diagnosis or relapse of leukemia, lymphoma, or multiple myeloma. Clinicians should have a heightened level of suspicion of malignant etiologies of otologic symptoms in patients with current or medical histories of these malignancies.

Unilateral Tonsillar Enlargement as Initial Presentation of Bilateral Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma.

Unilateral tonsillar enlargement is a common indication for tonsillectomy, but there are varying rates of malignancy among tonsils removed for asymmetry and a lack of clear guidelines for management within the literature. Lymphoma of the palatine tonsils is among the concerns leading to tonsillectomy, but chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) of the tonsil is rare. We report a case of primary CLL/SLL of the palatine tonsil in a 51-year-old gentleman who presented with tonsillar asymmetry and obstructive sleep apnea (OSA) but lacked signs and symptoms suspicious for malignancy, including lymphadenopathy and "B-symptoms." To our knowledge, only 7 cases of CLL/SLL of the palatine tonsil have been reported in the English literature, with the tonsil being the primary site of involvement in only 4 of those cases. Our unique case highlights the importance of thorough physical exam, family history, and tissue biopsy in patients presenting to the otolaryngologist with OSA and asymmetric tonsils.

Outcomes of Spontaneous Cerebrospinal Fluid Leak Repair With Concurrent Eustachian Tube Dysfunction.

OBJECTIVE: To compare the presentation and outcomes of patients with and without obstructive eustachian tube dysfunction (oETD) undergoing repair of lateral skull base spontaneous cerebrospinal fluid (sCSF) leaks. STUDY DESIGN: Retrospective chart review. SETTING: Tertiary referral center. PATIENTS: Adults with lateral skull base sCSF leaks who underwent repairs from January 1, 2011, to December 31, 2020, were collected. MAIN OUTCOME MEASURE: Comparative statistics and effect sizes were used to compare clinical features, operative findings, and outcomes between groups. RESULTS: Of 92 ears from 89 patients included, 51.1% (n = 47) had oETD. There were no differences in demographics between patients with and without oETD. Mean age was 60.7 ± 13.1 versus 58.5 ± 12.8 years ( d = -0.17 [-0.58 to 0.24]), mean body mass index was 33.8 ± 8.5 versus 36.0 ± 8.0 kg/m 2 ( d = 0.27 [-0.14 to 0.68]), and female sex preponderance was 59.6% (n = 28) versus 68.8% (n = 31; Φ = -0.09), respectively. There were no differences in the radiologic number, size, and locations of defects. Patients with oETD had less pneumatized mastoids than those without oETD ( p = 0.001; Φ = 0.43). Mean change from preoperative to postoperative air pure-tone average for those with and without oETD was -1.1 ± 12.6 versus 0.1 ± 17.2 dB ( d = 0.09 [-0.04 to 0.58]), respectively. Six ears (6.5%; three with and three without oETD) underwent revisions for rhinorrhea/otorrhea between 5 and 28 months postoperatively, during which four leaks were found, the two patients without leaks had oETD. CONCLUSIONS: The presentation of sCSF leaks and outcomes of repairs in patients with oETD do not differ from those without oETD. Although postoperative otorrhea might represent an inflammatory or infectious process in patients with oETD, reexploration is warranted if patients do not improve with conservative treatment.

Proteasome inhibition suppress microgravity elevated RANK signaling during osteoclast differentiation.

Microgravity (µXg) induces bone loss in astronauts during space missions. Therefore, it is necessary to delineate the underlying mechanisms which leads to bone loss for developing countermeasures. Osteoclasts (OCLs) are multinucleated cells, which resorb bone. Previously, we have demonstrated that simulated µXg enhances OCL formation. However, control of osteoclast bone resorption activity under µXg remains unclear. The OCL formation has been shown to be regulated by ubiquitin-proteasome pathway. Hence, we hypothesized that proteasome inhibition could regulate osteoclast differentiation under µXg. In this study, we identified that RAW264.7 preosteoclast cells treated with proteasome inhibitor (MG-132) suppress RANK receptor expression essential for OCL differentiation, but no effect on TRAF-6. We identified that MG-132 treatment abolished K48-linked poly-ubiquitination under µXg. Immunostaining confirms inhibition of protein ubiquitination and RANK expression in preosteoclast cells. Furthermore, proteasome inhibition suppresses the expression of SQSTM1/p62 under both the ground based Xg and µXg conditions. Also, confocal microscopy using Lyso-Tracker demonstrated that proteasomal inhibition suppress the co-localization of p62 and lysosomes. MG-132 inhibited RANKL induced proteasome activity. RAW264.7 cells treated with the proteasome inhibitor showed an increased level of p-c-Jun activity in control cultures, however decreased under µXg. In contrast, c-Fos and NFATc1 expression was decreased. In-addition, mouse bone marrow cultures treated with MG-132 suppress OCL formation and bone resorption activity. Thus, our findings suggest that proteasome inhibition represents a novel therapeutic approach for bone loss under µXg in space environment.