Objective To determine if sarcopenia is a predictor of blood transfusion requirements in head and neck cancer free flap reconstruction (HNCFFR). Methods A single‐institution, retrospective review was performed of HNCFFR patients with preoperative abdominal imaging from 2014 to 2019. Demographics, comorbidities (modified Charlson Comorbidity Index [mCCI]), skeletal muscle index (cm2/m2), oncologic history, intraoperative data, and 30‐day postoperative complications (Clavien‐Dindo score [CD]) were collected. Binary logistic regression was performed to determine predictors of transfusion. Results Eighty (33.5%), 66 (27.6%), and 110 (46.0%) of n = 239 total patients received an intraoperative, postoperative, or any perioperative blood transfusion, respectively. Sixty‐two (25.9%) patients had sarcopenia. Patients receiving intraoperative transfusions had older age (P = .035), more frequent alcoholism (P = .028) and sarcopenia (P < .001), greater mCCI (P < .001), lower preoperative hemoglobin (P < .001), reconstruction with flaps other than forearm (P = .003), and greater operative times (P = .001), intravenous fluids (P < .001), and estimated blood loss (EBL, P < .001). Postoperative transfusions were associated with major complications (CD ≥ 3; P < .001). Multivariate regression determined sarcopenia (P = .023), mCCI (P = .013), preoperative hemoglobin (P = .002), operative time (P = .036), and EBL (P < .001) as independent predictors of intraoperative transfusion requirements. Postoperative transfusions were predicted by preoperative hemoglobin (P = .007), osseous flap (P = .036), and CD ≥ 3 (P < .001). A perioperative transfusion was predicted by sarcopenia (P = .021), preoperative hemoglobin (P < .001), operative time (P = .008), and CD ≥ 3 (P = .018). Conclusion Sarcopenia is associated with increased blood transfusions in HNCFFR. Patients should be counseled preoperatively on the associated risks, and the increased blood product requirement should be accounted in resource‐limited scenarios. Level of Evidence 4.

Objectives To identify the frequency and primary site of metastatic pathologies to the temporal bone and characterize the associated symptomatology. Methods The MEDLINE, Embase, and Web of Science databases were systematically reviewed according to the PRISMA guidelines to identify all cases of pathologically confirmed distant temporal bone metastases published with English translation until October 2019. Descriptive statistics were performed. Results Out of 576 full‐length articles included for review, 109 met final criteria for data extraction providing 255 individual cases of distant temporal bone metastases. There was a male predominance (54.9%) with median age of 59.0 years (range 2–90). The most common locations of primary malignancy included the breasts (19.6%), lungs (16.1%), and prostate (8.6%). Most tumors were carcinomas of epithelial origin (75.3%) and predominantly adenocarcinoma (49.4%). The commonest metastatic sites encountered within the temporal bone were the petrous (72.0%) and mastoid (49.0%) portions. Bilateral temporal bone metastases occurred in 39.8% of patients. Patients were asymptomatic in 32.0% of cases. Symptomatic patients primarily reported hearing loss (44.3%), facial palsy (31.2%), and otalgia (16.6%) for a median duration of 1 month. Petrous lesions were associated with asymptomatic cases (P = .001) while mastoid lesions more often exhibited facial palsy (P = .026), otalgia (P < .001), and otorrhea (P < .001). Non‐carcinomatous tumors were associated with petrosal metastasis (P = .025) and asymptomatic cases (P = .109). Carcinomatous metastases more often presented with otalgia (P = .003). Conclusions Temporal bone metastasis is uncommon but should be considered in patients with subacute otologic symptoms or facial palsy and history of distant malignancy. Laryngoscope, 131:1101–1109, 2021

Objectives/Hypothesis: Patients with spontaneous cerebrospinal fluid leaks (sCSF-L) of the temporal bone have isolated calvarial and skull base thinning that is independent of obesity. This study determines if anterior skull base (ASB) sCSF-L patients also have calvarial thinning.Study Design: Retrospective Cohort Study. Methods: This was a retrospective cohort study of ASB sCSF-L patients compared to nonobese (body mass index [BMI] < 30 kg/m 2 ) and obese (BMI ≥ 30) control groups. Twenty-one patients in the ASB sCSF-L group and 25 patients in each control group were included. Calvarium and extracranial zygoma thicknesses were measured bilaterally with blinded, standardized, volumetric analysis.Results: ASB sCSF-L patients had a mean (SD) age of 50.43 (10.19) years, an average (SD) BMI of 38.81 (8.92) kg/m 2 , and most were female (85.71%). The calvarium in patients with ASB sCSF-L was significantly thinner than the nonobese (2.55 mm [0.77] vs. 2.97 [0.67] mm; P = .006; 95% confidence intervals [CI], 0.12-0.30; Cohen d, 0.58) and obese control groups (2.55 [0.77] vs. 2.92 [0.76] mm; P = .02; 95% CI, 0.05-0.34; Cohen d, 0.66). The calvarium thickness of the nonobese patients was not significantly different from the obese patient controls (2.97 [0.67] vs. 2.92 [0.76] mm, P = .9). The extracranial zygoma was not significantly different among the groups (analysis of variance, P = .33).Conclusions: ASB sCSF-L patients have isolated calvarial thinning that is independent of obesity. Like lateral skull base sCSF-L patients, these data suggest that the additional obesity-associated intracranial process contributes to skull thinning.

Reactive oxidative species (ROS) is a known byproduct of mitochondrial dysfunction and is believed to contribute to inflammation signaling commonly found in insulin resistance. Ceramide is a sphingolipid that serves as an important second messenger in an increasing number of stress‐related pathways. Ceramide has long been known to have morphological and physiological effects on mitochondria, which could potentially alter levels of ROS. The focus of this study is to determine whether increased ceramide levels result in ROS generation and decreased mitochondrial respiration in myotubes via altered mitochondrial morphology. C2C12 Skeletal muscle cells were used to assess the effect of ceramide on ROS generation and electron microsopy was used to image the morphological changes. Ceramide synthesis can be stimulated by treatment with exogenous fatty acid, thus myotubes were simultaneously treated with exogenous fatty acid following SPT2 knockdown (SPT is the rate limiting enzyme in ceramide synthesis), ROS increased within the myotubes and cellular respiration dropped. To verify the disruptive effect of ceramide on respiration caused by a change of mitochondrial morphology, cells were treated with a fission inhibitor (Mdivi‐1) prior to the addition of exogenous fatty acid. The resulting inhibition of mitochondrial fission via Mdivi‐1 helped protect the myotubes from ceramide‐induced metabolic disruption, including maintained mitochondrial respiration, and reduced ROS levels. Images taken with the confocal microscope verify that cells with increased levels of ceramide undergo mitochondrial fission while cells treated with Mdivi‐1 are protected from morphological changes. Altogether, these data suggest a critical role for mitochondrial fission as a mediator of ceramide‐induced metabolic disruption.

Background: Axonal regeneration following SCI is crucial if individuals are to avoid permanent neurological damage. A plausible solution to circumvent neuronal death/ axonal degeneration may be in the conversion of ubiquitously distributed astrocytes into neurons. Previous research has shown that the neuronal transcription factor SOX-2 has the potential to convert mature glial cells into neuroblasts (iANBs). Furthermore, iANBs possess the capability to differentiate into functional neurons. Our study employs an in vivo mouse model to demonstrate the functional recovery that SOX-2 mediated conversion of astrocytes to neurons may pose following SCI.    Methods: Our study utilized two populations of mice. The first population received thoracic T10 contusion injuries while the second population received cervical C5 dorsal hemi-sections. Mice were subsequently blindly categorized into groups A, B, and C (treatment groups) depending on which injection they would be receiving: LV-hNG2-GFP, LV-hNG2-SOX2, or LV-p75-2. Following injection, behavioral studies including Hargreaves, roto-rod, grid walk, BMS (contusion mice) and pellet retrieval (DH mice) were performed to assess functional recovery at 2 week intervals.  Results: The astrocyte conversion to neuron project spans more than 16 weeks. Here we present data obtained in the first eight weeks which includes behavioral analyses of contusion injury mice. Currently grid walk, BMS, and Hargreaves testing show similar trends in spontaneous recovery however no significant difference is observed between the independent injection groups. On the contrary roto-rod analyses showed injection group C had a significantly lower latency to fall time in comparison to groups A and B six weeks post injection (wpi).  Conclusion: The treatments are hypothesized to not take effect until approximately 8 wpi thus we expect subsequent behavioral testing to reveal significant differences between treatment groups, ultimately taking one step closer towards therapeutic intervention following traumatic SCI.

OBJECTIVES To review the audiological outcomes after cochlear implantation (CI) for TMPRSS3-associated autosomal recessive non-syndromic hearing loss (ARNSHL) and evaluate the spatial expression pattern of TMPRSS3 within the human cochlea. METHODS Review all published cases of CI in patients with TMPRSS3-associated ARNSHL to compare postoperative consonant-nucleus-consonant (CNC) word performance to published adult CI cohorts. Protein structural modeling of TMPRSS3 variants associated with post-lingual hearing loss. Determine TMPRSS3 expression pattern in human inner ear organoids and human cochlea. RESULTS Nine articles detailed 27 patients (30 total CI ears) with TMPRSS3-associated hearing loss treated with CI. Of these, 6 cases reported prelingual onset (< 2yo) and 24 cases reported post-lingual onset (≥2yo) of hearing loss. Subjectively, 85% of cases had a favorable outcome. Objectively, the postoperative mean (SD) post-operative CNC word score was not significantly different than other adults [66.2% (25.8%) correct vs. 50.1% (12.5%); F(1,6) = 1.97, P = 0.21]. In the TMPRSS3 cohort, poor performers (CNC < 30% correct) were significantly older than good performers [49 (± 13.3) years vs. 17.4 (± 18.4) years; P < 0.01] and all harbored the A138E variant. TMPRSS3 immunostaining is restricted to the otic epithelial cells and is not expressed within auditory neurons of human cochlea and human inner ear organoids. CONCLUSIONS Patients with TMPRSS3-related hearing loss exhibit similar postoperative performance to other adult CI patients. TMPRSS3 is not expressed in human auditory neurons and the duration of hearing loss prior to CI likely contributes to poor performance.

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