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COVID-19 induces both acute and chronic neurological changes. Existing evidence suggests that chemosensory changes, particularly olfactory loss, may reflect central neurological dysfunction in neurodegenerative diseases and mark progression from mild cognitive impairment to Alzheimer's. This scoping review summarizes the available literature to evaluate the relationship between neurocognition and olfaction in young to middle-aged adults with minimal comorbidities following COVID-19 infection. A literature search of PubMed, Ovid Embase, Web of Science, and Cochrane Library was conducted. Studies underwent title/abstract and full text screening by two reviewers, with a third reviewer resolving any conflicts. Remaining studies underwent data extraction. Seventeen studies were eligible for data extraction after the review process, where 12 studies found significantly poorer cognition in those suffering from olfactory dysfunction, four studies showed no association between cognition and olfaction, and one study reported lower anosmia prevalence among patients with cognitive impairment. The majority of studies in this review find that olfactory dysfunction is associated with poorer cognition. More rigorous studies are needed to further elucidate the relationship between olfaction and cognition after COVID-19.

Persistent COVID-19-associated olfactory dysfunction (C19OD), along with other neurologic and cognitive deficits are common features of long COVID. This study aims to evaluate longitudinal trends in neurocognitive performance within a cohort with C19OD. In individuals with perceived C19OD we performed serial psychophysical olfactory and neurocognitive assessments at baseline and follow-up one year later. At baseline evaluation, individuals with C19OD were found to have diminished cognitive functioning compared to normosmic counterparts across several domains, including attention, executive functioning, language, learning and memory, and psychomotor speed. At subsequent one-year follow-up assessment, C19OD participants demonstrated cognitive recovery, with performance comparable to normosmic counterparts. These findings suggest that early associations between C19OD and certain neurocognitive domains may dissipate upon repeated longitudinal evaluation, with partial resolution of cognitive deficits despite persistent C19OD.

Smell and taste alteration are closely linked to infection with SARS-CoV-2 and may be associated with a more indolent disease course. Serologic response rates among individuals with mild disease remains limited. We sought to identify whether chemosensory changes associated with COVID-19 were predictive of a serologic response. Cross-sectional study. The sample consisted of 306 adults (≥18 years old) volunteering for convalescent plasma donation following perceived COVID-19 illness from April-June 2020. Documentation of COVID-19 PCR status, clinical symptoms at time of illness, and treatment course occurred at the time of serologic analysis, where we assessed chemosensory function using patient-perceived deficits. We implemented previously validated ELISA screening to determine serologic status regarding anti-Spike immunoglobulins. Statistical analysis using stepwise logistic models were employed to identify predictive factors of serologic response. Of 306 patients undergoing serologic and chemosensory evaluation, 196 (64.1%) and 195 (63.7%) reported subjective olfactory and taste dysfunction, respectively, during the first two weeks of COVID-19 infection. In unadjusted models, the odds of developing suprathreshold IgG antibody titers were 1.98 times higher among those who reported altered smell (95% CI 1.14-3.42, p = 0.014) and 2.02 times higher among those with altered taste (95% CI 1.17-3.48, p = 0.011) compared to those with normal smell and taste. Multivariable logistic models adjusting for sex, age, race/ethnicity, symptom duration, smoking status and comorbidities index demonstrated that altered smell and taste remained significant predictors of positive anti-spike IgG response (smell OR = 1.90, 95% CI 1.05-3.44, p = 0.033; taste OR = 2.01, 95% CI = 1.12-3.61, p = 0.019). Subjective chemosensory dysfunction, as self-reported smell or taste deficiency, is highly predictive of serologic response following SARS-CoV-2 infection. This information may be useful for patient counseling. Additional longitudinal research should be performed to better understand the onset and duration of the serologic response in these patients.

Objective Proficiency in endoscopic endonasal skull base surgery requires both substantial baseline training and progressive lifelong learning. Endoscopic simulation models continue to evolve in an effort to optimize trainee education and preoperative preparation and improve surgical outcomes. The current scoping review systematically reviews all available literature and synthesizes the current paradigms of simulation models for endoscopic skull base surgery training and skill enhancement. Methods In accordance with Preferred Reporting Items for Systemic Review and Meta‐Analyses guidelines, we systematically searched PubMed, Embase, CINAHL, and Cochrane databases. Studies were categorized according to the type of simulation models investigated. Results We identified 238 unique references, with 55 studies ultimately meeting inclusion criteria. Of these, 19 studies described cadaveric dissection models, 17 discussed three‐dimensional (3D) printed models, 14 examined virtual surgical planning and augmented reality‐based models, and five 5 articles described task trainers. Conclusions There are a wide variety of simulation models for endoscopic skull base surgery, including high‐fidelity cadaveric, virtual reality, and 3D‐printed models. These models are an asset for trainee development and preoperative surgical preparation.

Objective Endoscopic approaches for sinus and skull base surgery are increasing in popularity. The objective of this narrative review is to characterize risk factors for internal carotid artery injury in endoscopic endonasal surgery (EES), highlight preventative measures, and illustrate key management principles. Data Sources Comprehensive literature review. Methods Relevant literature was reviewed using PubMed/MEDLINE. Results Carotid artery injury in EES is rare, with most studies reporting an incidence below 0.1%. Anatomic aberrancies, wide dissection margins, as well as specific provider and hospital factors, may increase the risk of injury. Multidisciplinary teams, comprehensive preoperative imaging, patient risk assessment, and formal training in vascular emergencies may reduce the risk. Management protocols should emphasize proper visualization of the injury site, fluid replacement, rapid packing, angiography, and endovascular techniques to achieve hemostasis. Conclusions While EES is a relatively safe procedure, carotid artery injury is a devastating complication that warrants full consideration in surgical planning. Important preventative measures include identifying patients with notable risk factors and obtaining preoperative imaging. Multidisciplinary teams and management protocols are ultimately necessary to reduce morbidity and mortality. Highlights Internal carotid artery (ICA) injury is a rare complication of endoscopic endonasal surgery. Risk factors for ICA injury may include vascular anatomic variants, invasive pathology, and prior radiation therapy. Surgical team preparation and experience are key to successful management of operative complications.

Overexpression of CD24, a glycosyl phosphatidylinositol-linked sialoglycoprotein, is associated with poor outcome in urothelial carcinoma and contributes to experimental tumor growth and metastasis. However, the requirement for CD24 (Cd24a in mice) in tumorigenesis and spontaneous metastasis from the orthotopic site remains uncharacterized. Using N -butyl- N -(4-hydroxybutyl) nitrosamine induction of invasive and metastatic bladder cancer, we show that Cd24a -deficient male mice developed fewer bladder tumors than C57BL/6 control male mice. Evaluating only mice with evidence of primary tumors, we observed that Cd24a- deficient male mice also had fewer metastases than wild-type counterparts. In parallel observations, stratification of patients based on CD24 immunohistochemical expression in their tumors revealed that high levels of CD24 are associated with poor prognosis in males. In female patients and mice the above observations were not present. Given the significant role of CD24 in males, we sought to assess the relationship between androgen and CD24 regulation. We discovered that androgen receptor knockdown in UM-UC-3 and TCCSUP human urothelial carcinoma cell lines resulted in suppression of CD24 expression and cell proliferation. Androgen treatment also led to increased CD24 promoter activity, dependent on the presence of androgen receptor. In vivo, androgen deprivation resulted in reduced growth and CD24 expression of UM-UC-3 xenografts, and the latter was rescued by exogenous CD24 overexpression. These findings demonstrate an important role for CD24 in urothelial tumorigenesis and metastasis in male mice and indicate that CD24 is androgen regulated, providing the foundation for urothelial bladder cancer therapy with antiandrogens.

Background Aging in postmitotic tissues is associated with clonal expansion of somatic mitochondrial deletions, the origin of which is not well understood. Such deletions are often flanked by direct nucleotide repeats, but this alone does not fully explain their distribution. Here, we hypothesized that the close proximity of direct repeats on single-stranded mitochondrial DNA (mtDNA) might play a role in the formation of deletions. Results By analyzing human mtDNA deletions in the major arc of mtDNA, which is single-stranded during replication and is characterized by a high number of deletions, we found a non-uniform distribution with a “hot spot” where one deletion breakpoint occurred within the region of 6–9 kb and another within 13–16 kb of the mtDNA. This distribution was not explained by the presence of direct repeats, suggesting that other factors, such as the spatial proximity of these two regions, can be the cause. In silico analyses revealed that the single-stranded major arc may be organized as a large-scale hairpin-like loop with a center close to 11 kb and contacting regions between 6–9 kb and 13–16 kb, which would explain the high deletion activity in this contact zone. The direct repeats located within the contact zone, such as the well-known common repeat with a first arm at 8470–8482 bp (base pair) and a second arm at 13,447–13,459 bp, are three times more likely to cause deletions compared to direct repeats located outside of the contact zone. A comparison of age- and disease-associated deletions demonstrated that the contact zone plays a crucial role in explaining the age-associated deletions, emphasizing its importance in the rate of healthy aging. Conclusions Overall, we provide topological insights into the mechanism of age-associated deletion formation in human mtDNA, which could be used to predict somatic deletion burden and maximum lifespan in different human haplogroups and mammalian species.

Objectives Persistent olfactory dysfunction (OD) following loss of smell associated with SARS‐CoV‐2 infection is a major feature of long COVID. Perspectives on the prevalence of persistent OD predominantly rely on self‐reported olfactory function. Few studies have tracked longitudinal rates of recovery using psychophysical assessment among patients presenting for evaluation of persistent OD beyond a window of acute recovery. Data anchored in standardized testing methods are needed to counsel patients who fail to acutely regain their sense of smell. This study aims to quantify the degree of persistent OD in post‐COVID‐19 patients who experience subjective and psychophysical OD. Methods We grouped participants presenting for OD evaluation into cohorts based on both subjective and psychophysical olfactory status at a baseline assessment and assessed their olfactory abilities with a visual analogue scale and the Sniffin' Sticks extended test at baseline and 1‐year time points. Participants had confirmed a history of COVID‐19 by lab evaluation or clinical diagnosis if lab evaluation was not available. Results Baseline olfactory evaluation was completed by 122 participants, 53 of whom completed the 1‐year follow‐up assessment. Among participants presenting with perceived OD, 74.5% had confirmed psychophysical OD at baseline, with 55.1% at 1‐year follow‐up. Participants had reliable trends in self‐rated versus psychophysically tested olfactory function at both time points. The total threshold, discrimination, and identification (TDI) score improved by +3.25 points in the cohort with psychophysical OD (p = 0.0005), with this improvement largely attributable to an increase in median threshold scores (+2.75 points; p = 0.0004). Conclusions OD persists in a significant number of patients who fail to acutely recovery their sense of smell after COVID‐19, with many demonstrating lingering deficits at 1‐year. Improvements in threshold, but not discrimination or identification, most significantly mediate improvement of total TDI score at follow‐up. Key points 19.4% of individuals with persistent psychophysical olfactory dysfunction (OD) at a baseline assessment at least 3 months after acute loss of smell experience olfactory normalization at 1‐year follow‐up. Improvement in total threshold, discrimination, and identification score for patients with subjective and psychophysical OD appears to be mediated by increases in median threshold scores. Prevalence of persistent OD as part of long‐COVID is further reinforced via psychophysical assessment when trended longitudinally across olfactory subdomains.

Background Historically sinonasal malignancies were always addressed via open craniofacial surgery for an oncologic resection. Increasingly esthesioneuroblastomas are excised using an exclusively endoscopic approach, however, the rarity of this disease limits the availability of long‐term and large scale outcomes data. Objective The primary objective is to evaluate the treatment modalities used and the overall survival of patients with esthesioneuroblastoma managed with exclusively endoscopic surgery. Methods In accordance with PRISMA guidelines, PubMed was queried to identify studies describing outcomes associated with endoscopic management of esthesioneuroblastomas. Results Forty‐four out of 2462 articles met inclusion criteria, totaling 399 patients with esthesioneuroblastoma treated with an exclusively endoscopic approach. Seventy‐two patients (18.0%) received adjuvant chemotherapy and 331 patients (83.0%) received postoperative radiation therapy. The average age was 50.6 years old (range 6–83). Of the 399 patients, 57 (16.6%) were Kadish stage A, 121 (35.2%) were Kadish stage B, 145 (42.2%) were Kadish stage C, and 21 (6.1%) were Kadish stage D. Pooled analysis demonstrated that 66.0% of patients had Hyams histologic Grade Ⅰ or Ⅱ, while 34.0% of patients had Grade Ⅲ or Ⅳ disease. Negative surgical margins were achieved in 86.9% of patients, and recurrence was identified in 10.3% of patients. Of those with 5‐year follow‐up, reported overall survival was 91.1%. Conclusion Exclusively endoscopic surgery for esthesioneuroblastoma is performed for a wide range of disease stages and grades, and the majority of these patients are also treated with adjuvant chemotherapy or radiation therapy. Reported overall recurrence rate is 10.3% and 5‐year survival is 91.1%. Exclusively endoscopic surgery for esthesioneuroblastoma is performed for a wide range of disease stages and grades with minimal associated morbidity and low complication rates. The majority of these patients are also treated with adjuvant chemotherapy or radiation therapy.

Craniopharyngiomas (CP) are suprasellar tumors that can grow into vital nearby structures and thus cause significant visual, endocrine, and hypothalamic dysfunction. Debate persists as to the optimal treatment strategy for these benign lesions, particularly with regards to the extent of surgical resection. The goals of tumor resection are to eliminate the compressive effect of the tumor on surrounding structures and minimize recurrence. It remains unclear whether a gross total resection (GTR) or subtotal resection (STR) with adjuvant therapy confers a better prognosis. Chemotherapy and radiation therapy (RT) have been explored as both neoadjuvant and adjuvant treatments to decrease tumor burden and prevent recurrence. The objective of this paper is to review the risks and benefits of GTR versus STR, specifically with regard to risk of recurrence and postoperative morbidity. Aggregated data suggest that STR monotherapy is associated with higher rates of recurrence relative to GTR (50.6% ± 22.1% vs 20.2% ± 13.5%), while STR combined with RT leads to recurrence rates similar to GTR. However, both GTR and RT are independently associated with higher rates of comorbidities including panhypopituitarism, diabetes insipidus, and visual deficits. The treatment strategy for CPs should ultimately be tailored to each patient’s individual tumor characteristics, risk, symptoms, and therapeutic goals.