Multi-center study on sellar reconstruction after endoscopic transsphenoidal pituitary surgery.

INTRODUCTION: Surgical techniques for sellar reconstruction include no reconstruction, use of synthetic materials, autologous grafts, and/or vascularized flaps. The aim of this study was to conduct a multi-center study comparing the efficacy and postoperative morbidity associated with different sellar reconstruction techniques. METHODS: A retrospective chart review of patients who underwent endoscopic transsphenoidal surgery for pituitary tumors from five participating sites between January 2021 and March 2023 was performed. The variables included demographics, tumor characteristics, reconstruction technique, postoperative cerebrospinal fluid leak (CSF) leak, and 22-item Sino-Nasal Outcome Test (SNOT-22) scores. Comparisons of postoperative complications, SNOT-22 scores, and duration of surgery by type of onlay reconstruction were evaluated using Fisher's exact test, analysis of variance, and Kruskal‒Wallis test. RESULTS: Five hundred and one patients were identified. The median tumor size was 2.1 cm, and 64% were non-functioning. Intraoperative CSF leak was identified in 38% of patients. A total of 89% of patients underwent onlay reconstruction: 49% were reconstructed with mucosal grafts, 35% with nasoseptal flaps, and 5% with other onlay techniques. Nasoseptal flaps were utilized more frequently in the setting of giant pituitary adenomas (>3 cm), medial cavernous sinus wall resection, and high-flow intraoperative CSF leaks. Cases who utilized mucosal grafts had an overall shorter operating time (median: 183 min vs. 240 min; p < 0.001). Five postoperative CSF leaks were identified, and therefore, statistical analysis could not be performed for this complication. CONCLUSION: The effectiveness and morbidity of different sellar reconstruction techniques are comparable. Vascularized flaps were utilized more frequently in the setting of larger tumors and high-flow intraoperative CSF leaks.

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.

Environmental air pollution and chronic rhinosinusitis: A systematic review.

Objective: Chronic rhinosinusitis (CRS) is a highly prevalent and burdensome disease. The pathophysiology is not fully elucidated, but environmental pollutants have been suggested to impact the inflammatory component of the disease process. This review aims to summarize the role of environmental pollution in CRS onset and disease severity. Methods: A systematic review was performed following Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. PubMed, EMBASE, Cochrane Library, Web of Science, and Scopus databases were queried in August 2021. Original articles reporting on air pollution exposure in CRS were included. Other forms of sinonasal disease were excluded. Results: Literature search produced 11,983 articles, of which 10 met inclusion criteria. Outcomes evaluated included incidence/prevalence, disease severity, quality of life, and histopathologic/microbial changes. Air pollutant exposure was associated with higher odds of CRS, particularly with particulate matter (PM) exposure. Increasing air pollution exposure was also associated with worsened disease severity and detectable histopathologic changes. Impact on quality of life was less clear. Conclusion: Air pollution (particularly PM) is correlated with CRS incidence/prevalence and disease severity, with evidence of histopathologic changes in CRS tissue samples. Further research is warranted to better understand the mechanisms by which air pollution components may cause CRS and type 2 inflammation. Level of Evidence: 3a.

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.

Association of Frailty Status and Dietary Patterns in a Nationally Representative Sample of United States Adults with Olfactory Dysfunction.

BACKGROUND: Olfactory dysfunction (OD) is a strong, independent predictor of frailty and mortality risk. This study evaluated the association of dietary patterns and frailty status in older adults with OD. METHODS: This cross-sectional study utilized the 2013-2014 National Health and Nutrition Examination Survey. Dietary patterns (DPs) characteristic of OD were derived using exploratory factor analysis (EFA). Multiple logistic regressions adjusted for demographics and frailty risk factors assessed the association of DPs with two frailty metrics: the frailty index (FI) and physical frailty (PF). RESULTS: EFA yielded six distinct DPs in persons with OD. The protein/selenium (OR 0.82 [95% CI 0.74-0.92], p = 0.041) and ß-carotene/vitamin A DPs (OR 0.76 [95% CI 0.66-0.88], p = 0.028) were independently associated with frailty by FI. Only the protein/selenium DP (OR 0.82 [95% CI 0.74-0.92], p = 0.036) was associated with frailty by PF. No DPs were associated with either frailty measure in normosmic persons. CONCLUSIONS: Dietary patterns high in protein/selenium and ß-carotene/vitamin A are associated with lower frailty prevalence in adults with OD. While the relationship between OD and frailty is likely multifaceted, these findings suggest that dietary patterns are uniquely associated with frailty in older adults with OD.

Psychophysical chemosensory dysfunction in eating disorders: a qualitative systematic review.

PURPOSE: Patients with chemosensory dysfunction experience significant quality of life disruptions, including reduced enjoyment of eating. While chemosensory dysfunction has been associated with eating disorders, the relationship is poorly understood. This systematic review aims to characterize psychophysical gustation and olfaction in patients with eating disorders. METHODS: Systematic review of investigations assessing psychophysical chemosensory function in patients with organic eating disorders. RESULTS: 26 studies were included. Five studies assessed both chemosenses, while 12 and 9 assessed exclusively gustation or olfaction, respectively. In total, 779 patients were included [72.4% anorexia nervosa (AN), 26.7% bulimia nervosa (BN), 0.8% combined AN/BN]. Patients with eating disorders experienced rates of hypogeusia up to 87% in AN and 84.6% in BN. There was evidence for alterations in psychophysical olfaction, but orientation of trends were less clear. Chemosensory dysfunction was more evident in AN patients. Treatment correlated with improved chemosensory function. CONCLUSIONS: Despite heterogeneity in study methodology and results, this review demonstrates that patients with eating disorders experience some degree of chemosensory dysfunction, particularly in gustation. This symptomatology overlaps with those experienced by patients with other causes of chemosensory impairment. These findings suggest potential broad psychosocial, dietary, and mental health implications in patient populations experiencing chemosensory dysfunction. LEVEL OF EVIDENCE: Level II.

Role of Environmental Air Pollution in Chronic Rhinosinusitis.

PURPOSE OF REVIEW: Chronic rhinosinusitis (CRS) is a highly prevalent disease with large social and financial burdens. The pathophysiology is multifactorial. Environmental pollutants have been suggested to play a role in the inflammatory component of the disease process. RECENT FINDINGS: Recent work has focused on exposure to various pollutants, primarily particulate matter (PM). Exposure to environmental pollutants leads to upregulation of inflammatory markers and ciliary dysfunction at the cellular level. Mouse models suggest a role for epithelial barrier dysfunction contributing to inflammatory changes after pollutant exposure. Clinical studies support the role of pollutants contributing to disease severity in certain populations, but the role in CRS incidence or prevalence is less clear. Research is limited by the retrospective nature of most studies. This review focuses on recent advancements in our understanding of the impact of environmental pollutants in CRS, limitations of the available data, and potential opportunities for future studies.

A Systematic Review and Meta-Analysis of Taste Dysfunction in Chronic Rhinosinusitis.

OBJECTIVES: Patients with chronic rhinosinusitis (CRS) often describe alterations in sense of taste. These complaints have historically been attributed to olfactory dysfunction; however, there is evidence of direct, objective, gustatory disturbances in the setting of CRS that are not thoroughly characterized. This study sought to investigate and summarize gustatory dysfunction experienced by patients with CRS. METHODS: PubMed, EMBASE, Cochrane Library, Web of Science, and Scopus databases were reviewed following PRISMA guidelines. English language, original studies investigating objective taste in adult patients with CRS were included. A meta-analysis with inverse variance, random-effects model was performed. RESULTS: Of 2750 studies screened, 11 articles with 471 unique patients were included. Patients with CRS exhibit worse gustatory function compared to healthy controls (standardized mean difference 0.94 [95% CI, 0.44-1.45]). Hypogeusia was identified in 32/95 (33.7%) patients from three studies that used methods with a validated definition of hypogeusia. Older age, male gender, and smoking history were associated with taste dysfunction, while objective gustatory and olfactory dysfunction were not correlated. Subjective taste and quality of life measures were also not associated with objective taste. The impact of sinus surgery on objective taste is unclear. CONCLUSION: Approximately 34% of patients with CRS experience hypogeusia. Neither olfactory function nor subjective taste were associated with objective gustatory function. Given the substantial prevalence of taste dysfunction patients with CRS, there is significant potential for growth in understanding of pathogenesis, impact on quality of life, and potential treatment strategies of taste impairment in the CRS patient population. LEVEL OF EVIDENCE: 1 Laryngoscope, 131:482-489, 2021.

The DNA deaminase APOBEC3B interacts with the cell-cycle protein CDK4 and disrupts CDK4-mediated nuclear import of Cyclin D1.

Apolipoprotein B mRNA editing enzyme catalytic subunit-like protein 3B (APOBEC3B or A3B), as other APOBEC3 members, is a single-stranded (ss)DNA cytosine deaminase with antiviral activity. A3B is also overexpressed in multiple tumor types, such as carcinomas of the bladder, cervix, lung, head/neck, and breast. A3B generates both dispersed and clustered C-to-T and C-to-G mutations in intrinsically preferred trinucleotide motifs (TCA/TCG/TCT). A3B-catalyzed mutations are likely to promote tumor evolution and cancer progression and, as such, are associated with poor clinical outcomes. However, little is known about cellular processes that regulate A3B. Here, we used a proteomics approach involving affinity purification coupled to MS with human 293T cells to identify cellular proteins that interact with A3B. This approach revealed a specific interaction with cyclin-dependent kinase 4 (CDK4). We validated and mapped this interaction by co-immunoprecipitation experiments. Functional studies and immunofluorescence microscopy experiments in multiple cell lines revealed that A3B is not a substrate for CDK4-Cyclin D1 phosphorylation nor is its deaminase activity modulated. Instead, we found that A3B is capable of disrupting the CDK4-dependent nuclear import of Cyclin D1. We propose that this interaction may favor a more potent antiviral response and simultaneously facilitate cancer mutagenesis.