Olfactory Dysfunction Following Moderate to Severe Traumatic Brain Injury: A Systematic Review and Meta-Analysis.

OBJECTIVE: Reports of smell loss following traumatic brain injury (TBI) are a well-documented but understudied phenomenon. Given the broad consequences of olfactory loss, we characterized psychophysical olfactory dysfunction in individuals with moderate to severe TBI using systematic review and meta-analytic methods. METHODS: Following Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) protocol, five databases (PubMed, EMBASE, Cochrane Library, Web of Science, Scopus) were reviewed for studies investigating olfactory dysfunction in persons with moderate to severe TBI. Of the 5,223 studies reviewed, 19 met our inclusion criteria for the systematic review and 11 met inclusion criteria for meta-analysis. We calculated effect sizes (Hedges' g) to characterize the degree of olfactory dysfunction between patients with moderate to severe TBI and controls. RESULTS: A total of 951 moderate-severe TBI patients from 19 studies were included in the systematic review, which largely demonstrated poorer olfactory psychophysical performances in this patient population. Meta-analysis demonstrated a large effect size for olfactory dysfunction in moderate-severe TBI relative to healthy controls (g=-2.43, 95%CI: -3.16 < δ<-1.69). The magnitude of the effect was moderated by age and patient sex, with larger effect sizes associated with older age (following exclusion of a pediatric population) and larger compositions of women in the patient group. CONCLUSION: Moderate to severe TBI is associated with prominent olfactory dysfunction. Significant research gaps remain regarding the mechanism, recovery and natural history of olfactory dysfunction following moderate to severe TBI, which has significant clinical implications for the identification and treatment for those with post-traumatic olfactory dysfunction.

Transoral Thyroidectomy: Safety and Outcomes of 200 Consecutive North American Cases.

BACKGROUND: North American adoption of the transoral endoscopic thyroidectomy vestibular approach (TOETVA) has been limited due to concerns regarding the generalizability of published outcomes, as data are predominantly from Asian cohorts with a different body habitus. We describe our experience with TOETVA in a North American population in the context of the conventional transcervical approach thyroidectomy (TCA). STUDY DESIGN: Cases of TOETVA and TCA were reviewed from August 2017 to March 2020 at a tertiary care center. Outcomes included operative time, major (permanent recurrent laryngeal nerve (RLN) injury, permanent hypoparathyroidism, hematoma, conversion to open surgery), and minor complications. The TOETVA cohort was stratified into body mass index (BMI) classes of underweight/normal < 25 kg/m2, overweight 25-29.9 kg/m2, and obese ≥ 30 kg/m2 for comparative analysis. Multivariable logistic regression analyses were performed for odds of cumulative complication. RESULTS: Two hundred TOETVA and 333 TCA cases were included. There was no difference in incidence of major complications between the TOETVA and TCA cohorts (1.5% vs. 2.1%, p = 0.75). No difference was found in the rate of temporary RLN injury (4.5% vs. 2.1%, p = 0.124) or temporary hypoparathyroidism (18.2% vs. 12.5%, p = 0.163) for TOETVA and TCA, respectively. Surgical technique (TOETVA vs TCA) did not alter the odds of cumulative complication (OR 0.69 95% CI [0.26-1.85]) on logistic regression analysis. In the TOETVA cohort, higher BMI did not lead to a significantly greater odds of cumulative complication, 0.52 (95% CI [0.17-1.58]) and 1.69 (95% CI [0.74-3.88]) for the overweight and obese groups, respectively. CONCLUSION: TOETVA can be performed in a North American patient population without a difference in odds of complication compared to TCA. Higher BMI is not associated with greater likelihood of complication with TOETVA.

Modulation of hypoxia by magnetic nanoparticle hyperthermia to augment therapeutic index.

A hypoxic microenvironment in solid tumors has been known to cause resistance to standard therapies and to increase the malignant potential of tumors. The utilization of magnetic nanoparticle hyperthermia (mNPH) has shown promise in improving therapeutic outcome by (1) killing of hypoxic tumor cells directly and (2) increasing tumor oxygenation and therefore susceptibility to therapies. In this study, the interaction of a hypoxic microenvironment with mNPH efficacy was investigated in a human breast cancer orthotopic xenograft model. Using electron paramagnetic resonance (EPR) to assess in vivo oxygen concentration in tumors repeatedly and non-invasively, we found that mNPH increased tumor pO2 from 3.5 to 68.8 mmHg on average for up to 10 days. Tumors treated once with mNPH showed growth delay. On Transmission Electron Microscopy, magnetic nanoparticles (mNPs) were localized intracellularly in multiple vesicles in the cytoplasm of cells within tumors 48 h after incubation of mNP. In conclusion, mNPH increased tumor oxygenation in vivo and resulted in decreased growth of hypoxic tumors. Future studies will establish tumor pO2-guided multimodal therapies, such as mNPH and radiation, to improve therapeutic efficacy.

Female Surgical Ergonomics in Otolaryngology: A National Survey Study.

OBJECTIVE: To assess the nature and impact surgical ergonomic challenges experienced by female otolaryngologists. STUDY DESIGN: National survey study. SETTING: Female otolaryngology residents, fellows and attendings recruited via social media posting and email distribution. METHODS: We distributed a survey study to female otolaryngologists throughout the United States. The height and glove size of participants reporting difficulties with equipment and instruments were compared to those not reporting difficulties. RESULTS: Ninety-six female otolaryngologists participated in our study, comprised of 43% residents, 10% fellows, and 47% attendings. Ninety percent of participants reported difficulties using equipment and 77% of participants reported difficulty with instruments, the most common being nasal endoscopic instruments (28%). The vast majority of participants reported pain during and (or) after the operation (92%). Head and neck (53%) and rhinology (44%) were identified as particularly challenging specialities, but only 25% of participants reported that ergonomics affected their career plans. Participants felt that adjustable equipment (60%), a variety of sizes of instruments (43%), and more discussion around ergonomics (47%) would help. Respondents reported adjusting the operating room to accommodate their size took extra time (44%) and was a mental burden (39%). Participants reporting difficulties with operating room equipment were significantly shorter than those without difficulties (64 inches vs 67 inches, P = .037), and those reporting difficulties with instruments had a smaller median glove size (6 vs 6.5, P = .018). CONCLUSION: Surgical ergonomics represent a challenge for female otolaryngologists, particularly those with smaller hands and shorter height. Partnering with industry, we must address the needs of an increasingly diverse workforce to ensure that all surgeons can operate effectively and comfortably.

Olfactory Loss and Beyond: A Practical Review of Chemosensory Dysfunction.

BACKGROUND: Our ability to smell and taste is dictated by 3 chemosensory systems with distinct physiologic mechanisms - olfaction, gustation, and chemesthesis. Although often overlooked, dysfunction of these special senses may have broad implications on multiple facets of patients' lives -including safety, nutritional status, quality of life, mental health, and even cognitive function. As "loss of smell or taste" emerged as a common symptom of coronavirus disease 2019 (COVID-19), the importance of intact chemosensory function has been thrust into the spotlight. Despite the growing recognition of chemosensory dysfunction, this already highly prevalent condition will increasingly impact a larger and more diverse population, highlighting the need for improved awareness and care of these patients. METHODS: Comtemporary review of chemosensory function and assessments. CONCLUSIONS: Although patient-reported chemosensory function measures highlight the ease of screening of chemosensory dysfunction, self-reported measures underestimate both the prevalence and degree of chemosensory dysfunction and do not adequately distinguish between olfaction, gustation, and chemesthesis. Meanwhile, psychophysical assessment tools provide opportunities for more accurate, thorough assessment of the chemosenses when appropriate. Primary care providers are uniquely situated to identify patients burdened by chemosensory dysfunction and raise patient and provider awareness about the importance of chemosensory dysfunction. Identification of chemosensory dysfunction, particularly olfactory dysfunction, may raise suspicion for many underlying medical conditions, including early detection of neurodegenerative conditions. Furthermore, identification and awareness of patients with chemosensory dysfunction may help primary care providers to identify those who may benefit from additional therapeutic and safety interventions, or consultations with specialists for more detailed evaluations and management.

The Landscape of Persistent Viral Genomes in ART-Treated SIV, SHIV, and HIV-2 Infections.

Evaluation of HIV cure strategies is complicated by defective proviruses that persist in ART-treated patients but are irrelevant to cure. Non-human primates (NHP) are essential for testing cure strategies. However, the persisting proviral landscape in ART-treated NHPs is uncharacterized. Here, we describe viral genomes persisting in ART-treated, simian immunodeficiency virus (SIV)-infected NHPs, simian-human immunodeficiency virus (SHIV)-infected NHPs, and humans infected with HIV-2, an SIV-related virus. The landscapes of persisting SIV, SHIV, and HIV-2 genomes are also dominated by defective sequences. However, there was a significantly higher fraction of intact SIV proviral genomes compared to ART-treated HIV-1 or HIV-2 infected humans. Compared to humans with HIV-1, SIV-infected NHPs had more hypermutated genomes, a relative paucity of clonal SIV sequences, and a lower frequency of deleted genomes. Finally, we report an assay for measuring intact SIV genomes which may have value in cure research.

Oxygen microenvironment affects the uptake of nanoparticles in head and neck tumor cells.

Survival of head and neck cancer patients has not improved in several decades despite advances in diagnostic and therapeutic techniques. Tumor hypoxia in head and neck cancers is a critical factor that leads to poor prognosis, resistance to radiation and chemotherapies, and increased metastatic potential. Magnetic nanoparticle hyperthermia (mNPHT) is a promising therapy for hypoxic tumors because nanoparticles (NP) can be directly injected into, or targeted to, hypoxic tumor cells and exposed to alternating magnetic fields (AMF) to induce hyperthermia. Magnetic NPHT can improve therapeutic effectiveness by two modes of action: 1) direct killing of hypoxic tumor cells; and 2) increase in tumor oxygenation, which has the potential to make the tumor more susceptible to adjuvant therapies such as radiation and chemotherapy. Prior studies in breast cancer cells demonstrated that a hypoxic microenvironment diminished NP uptake in vitro; however, mNPHT with intratumoral NP injection in hypoxic tumors increased tumor oxygenation and delayed tumor growth. In this study, head and neck squamous cell carcinoma (HNSCC) cell lines were incubated in normoxic, hypoxic, and hyperoxic conditions with iron oxide NP for 4-72 hours. After incubation, the cells were analyzed for iron uptake by mass spectrometry, Prussian blue staining, and electron microscopy. In contrast to breast cancer cells, uptake of NPs was increased in hypoxic microenvironments as compared to normoxic conditions in HNSCC cells. In future studies, we will confirm the effect of the oxygen microenvironment on NP uptake and efficacy of mNPHT both in vitro and in vivo.