Approximately one‐third of Merkel cell carcinoma (MCC) patients eventually develop distant metastatic disease. Little is known about whether the location of the primary lesion is predictive of initial distant metastatic site, or if survival likelihood differs depending on the metastatic site. Such data could inform imaging/surveillance practices and improve prognostic accuracy. Multivariate and competing‐risk analyses were performed on a cohort of 215 MCC patients with distant metastases, 31% of whom had two or more initial sites of distant metastasis. At time of initial distant metastasis in the 215 patients, metastatic sites (n = 305) included non‐regional lymph nodes (present in 41% of patients), skin/body wall (25%), liver (23%), bone (21%), pancreas (8%), lung (7%), and brain (5%). Among the 194 patients who presented with MCC limited to local or regional sites (stage I‐III) but who ultimately developed distant metastases, distant progression occurred in 49% by 1 year and in 80% by 2 years following initial diagnosis. Primary MCC locations differed in how likely they were to metastasize to specific organs/sites (P < .001). For example, liver metastases were far more likely from a head/neck primary (43% of 58 patients) versus a lower limb primary (5% of 39 patients; P < .0001). Skin‐only distant metastasis was associated with lower MCC‐specific mortality as compared to metastases in multiple organs/sites (HR 2.7; P = .003), in the liver (HR 2.1; P = .05), or in distant lymph nodes (HR 2.0; P = .045). These data reflect outcomes before PD1‐pathway inhibitor availability, which may positively impact survival. In conclusion, primary MCC location is associated with a pattern of distant spread, which may assist in optimizing surveillance. Because it is linked to survival, the site of initial distant metastasis should be considered when assessing prognosis.

Summary Background Merkel cell carcinoma (MCC) is an aggressive, high‐grade, cutaneous neuroendocrine tumour (NET). Agents blocking programmed death 1/programmed death ligand 1 have efficacy in metastatic MCC (mMCC), but half of patients do not derive durable benefit. Somatostatin analogues (SSAs) are commonly used to treat low‐ and moderate‐grade NETs that express somatostatin receptors (SSTRs). Objectives To assess SSTR expression and the efficacy of SSAs in mMCC, a high‐grade NET. Methods In this retrospective study of 40 patients with mMCC, SSTR expression was assessed radiologically by somatostatin receptor scintigraphy (SRS; n = 39) and/or immunohistochemically when feasible (n = 9). Nineteen patients (18 had SRS uptake in MCC tumours) were treated with SSA. Disease control was defined as progression‐free survival (PFS) of ≥ 120 days after initiation of SSA. Results Thirty‐three of 39 patients (85%) had some degree (low 52%, moderate 23%, high 10%) of SRS uptake. Of 19 patients treated with SSA, seven had a response‐evaluable target lesion; three of these seven patients (43%) experienced disease control, with a median PFS of 237 days (range 152–358). Twelve of 19 patients did not have a response‐evaluable lesion due to antecedent radiation; five of these 12 (42%) experienced disease control (median PFS of 429 days, range 143–1757). The degree of SSTR expression (determined by SRS and/or immunohistochemistry) did not correlate significantly with the efficacy endpoints. Conclusions In contrast to other high‐grade NETs, mMCC tumours appear frequently to express SSTRs. SSAs can lead to clinically meaningful disease control with minimal side‐effects. Targeting of SSTRs using SSA or other novel approaches should be explored further for mMCC.

Background The association between olfactory dysfunction (OD) and cognitive decline is becoming apparent in the emerging literature. However, the literature demonstrating a similar effect between gustatory dysfunction (GD) and cognition is not well established. Objective To determine whether OD and GD are independently associated with cognitive impairment. Methods The 2013–2014 National Health and Nutrition Examination Survey was queried for 1376 older adults, corresponding to a weighted population sample of 50 816 529, to assess olfactory and gustatory status and cognition using univariate and multivariate regression analyses. OD and GD were determined using objective measurements with validated protocols. Participants were stratified as normal or abnormal cognition status using accepted cutoff values as indicated for the Consortium to Establish a Registry for Alzheimer’s Disease (CERAD) neuropsychological test, Animal Fluency Test (AFT), and Digit Symbol Substitution Test (DSST). Results OD was associated with both mild cognitive impairment (odds ratio [OR] 1.809, P = .004) and dementia (OR 3.173, P < .001) with CERAD testing, abnormal AFT (OR 2.424, P < .001), and abnormal DSST (OR 4.028, P < .001). GD based on 1M NaCl whole mouth taste testing was associated with dementia on CERAD testing (OR 2.217, P = .004). When smell and taste parameters were included together in the regression model, both OD and GD remained significant independent predictors of dementia status based on CERAD testing (OR 3.133, P < .001, OR 1.904, P = .015). Conclusions OD and severe GD represent independent predictors of cognitive impairment in a nationally representative sample of older adults.

Objectives/Hypothesis Statins have long been used in the management of cardiovascular disease for their lipid‐lowering properties. However, recent research suggests that statins may also have anti‐inflammatory effects via modulation of lipid‐containing enzymes and mediators, and therefore may have therapeutic value in the treatment of chronic rhinosinusitis (CRS). Study Design Retrospective database review. Methods The 2006 to 2015 National Ambulatory Medical Care Survey (NAMCS) data were queried to analyze the relationship between statin use and rates of CRS. CRS was indicated by the presence of an International Classification of Diseases, Ninth Revision code for CRS in one of the five diagnosis variables. Statin use was indicated by the presence of a statin medication in any of the 30 medication variables using the Multum Lexicon Drug Database, with newly prescribed medications excluded. Relevant demographic, socioeconomic, and comorbid factors were included in a multivariate logistic regression model, which accounted for the complex, stratified, multistage survey design of the NAMCS. Results There were 390,538 unweighted visit records used in the weighted analysis dataset, corresponding to 9,612,613,668 weighted visits. Statin use was associated with a decreased rate of CRS in both a univariate analysis (odds ratio [OR] = 0.53, P < .001) and the multivariate logistic regression accounting for comorbid, socioeconomic, and demographic factors (OR = 0.79, P = .030). Conclusions Statin use is associated with decreased rates of CRS based on a nationally representative sample of outpatient visits in the United States. This supports research that suggests statin medications may have protective properties against CRS, and further research is warranted into their potential therapeutic value for this indication. Level of Evidence NA Laryngoscope, 130:848–851, 2020

Objectives To characterize the association between quantitative olfactory dysfunction (OD) and gustatory dysfunction and depression in older adults. Methods The 2013–2014 National Health and Nutrition Examination Survey (NHANES) data were used to investigate the relationship between smell and taste dysfunction and depression. Adults aged 65 years and older were included in the analysis. For smell status, subjects were divided into hyposmia, anosmia, and OD (hyposmia + anosmia) using the Pocket Smell Test. For taste status, subjects were evaluated using quinine, 1M NaCl, and 0.32M NaCl solutions. Indicator variables were made for subjects with both smell and taste dysfunction to determine whether a combination of symptoms could predict depression. Depression status was evaluated by the 9-item Patient Health Questionnaire using accepted cutoff values. Relevant demographic, socioeconomic, and comorbid factors were included in multivariate logistic regression models, which accounted for the complex survey design of NHANES. Results A total of 931 subjects aged 65 years or older were included in the weighted analysis. Anosmia significantly predicted depressive symptoms in multivariate analysis (odds ratio [OR] = 2.484, P = .032) but not univariate. In univariate analysis, hyposmia + anosmia (OR = 2.193, P = .006) and hyposmia (OR = 2.512, P < .001) significantly predicted depression. Significance was lost in multivariate analysis. Conclusions Smell dysfunction is an independent predictor of depressive symptoms in a representative sample of older adults in the United States after adjusting for relevant demographic factors and comorbidities.

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To determine the prognostic significance of neurologic symptoms at progression for patients with brain metastases (BM) undergoing stereotactic radiosurgery (SRS), all patients completing an initial course of SRS between 1/2015 and 12/2020 were identified across two institutions. Intracranial progression (ICP) was recorded, with symptomatic ICP (SICP) defined as new/worsening neurologic symptoms without another etiology. Overall survival (OS), freedom from ICP (FFICP), and freedom from symptomatic ICP (FFSICP) were assessed via Kaplan-Meier method. For FFSICP, patients were censored at time of death or asymptomatic ICP. Logistic regression models tested parameter association to neurologic symptoms. Cox proportional hazard models tested parameters impacting FFICP and FFSICP. Among 1383 patients, median age was 63.4 years, 54.8% were female, and 45.6% had KPS ≥90. Common primary sites were non-small cell lung (48.7%), breast (14.7%), and melanoma (8.5%). 46.9% had oligometastatic disease (≤5 foci), and 53.4% had &gt;1 BM. 26.1% patients had prior surgical resection, and 10.3% had WBRT. With a median follow up of 8.7 months, 504 (36%) and 194 (14%) experienced asymptomatic and symptomatic ICP respectively. OS was worse for patients experiencing SICP (median 10.2 vs 17.9 months, p&lt;0.001). Among patients with ICP, SICP was associated with total treated tumor volume (per-ml, OR 1.01, 95% CI 1.00-1.02), while those with more recent MRI imaging and post-SRS systemic therapy was associated with asymptomatic ICP. Patients who received post-SRS chemotherapy (HR 0.64, 95% CI 0.45-0.90), immunotherapy (HR 0.49, 95% CI 0.34-0.71), or targeted therapy (HR 0.49, 95% CI 0.33-0.73) had better FFSCIP. Worse FFSCIP was associated with melanoma (HR 2.56, 95% CI 1.49-4.38), and greater than 2 BMs (HR 2.24, 95% CI 1.56-3.22). SICP is prognostic for OS, and is associated with melanoma, no systemic therapy post-SRS, and greater number of BMs. These data further support the use of SICP as a meaningful clinical endpoint.

2013 Background: While brain metastasis (BM) velocity is a valuable prognostic metric at time of intracranial progression (ICP), pre-SRS risk factors for post-SRS high-burden intracranial progression (ICP) remain poorly characterized. We hypothesized that pre-SRS clinical parameters are associated with subsequent high-burden (ICP), defined as either ≥5 (ICP5) or new/progressive ≥11 BMs (ICP11). Methods: All patients completing an initial SRS course for BMs at two institutions from 1/2015-12/2020 were retrospectively identified. Patients with prior whole brain radiation therapy (WBRT) and/or BM resection were eligible. Demographic and clinical parameters were collected. ICP was defined as any radiographic concern for distant and/or in-field progression per multidisciplinary consensus. Overall survival (OS) and freedom from ICP were estimated via the Kaplan Meier method. Cox models assessed association between parameters and freedom from ICP5 and ICP11. Results: We identified 1383 patients completed SRS, with a median follow up of 8.7 months. Patients were 54.8% female, 45.6% with KPS ≥90, and a median of 63.4 years old. Primary tumor types included non-small cell lung (48.7%), breast (14.7%), and melanoma (8.5%). 46.9% had oligometastatic disease (≤5 metastatic foci: including BMs) at SRS, and 53.4% underwent SRS for > 1 BM. 10.3% of patients had undergone prior WBRT and 26.1% surgical resection. 555 patients (40.1%) experienced ICP following SRS, of whom 72.6% had 1-4, 11.5% had 5-10, and 15.9% had ≥11 new/progressive BMs. Among patients with ICP, 6-month freedom from ICP was 35.5% (95% CI: 31.1-40.5%) for those with 1-4 BMs at time of ICP, 29.7% (95% CI: 20.4-43.3%) for 5-10 BMs, and 20.5% (95% CI: 13.5-30.1%) for ≥11 BMs (p = 0.016). Respective 12-month OS rates were 56.8% (95% CI: 52.1-61.9%), 46.0% (95% CI: 35.1-60.1%), and 38.7% (95% CI: 29.4-50.9%; p < 0.001). Neurologic symptoms at time of ICP were observed in 21.1% of patients with 1-4 BMs, 28.1% with 5-10 BMs, and 50.0% with new/progressive ≥11 BMs (p < 0.001). On multivariable analysis, superior freedom from high-burden ICP was associated with the following pre-SRS parameters: oligometastatic burden (ICP5: HR 0.68, 95% CI: 0.47-0.99; ICP11: 0.59; 95% CI: 0.36-0.97), no prior immunotherapy (ICP11: HR 0.57, 95% CI: 0.34-0.57), and a single BM at time of initial SRS (1 vs 2 BM, ICP 5: HR 0.51, 95% CI: 0.31-0.82; ICP11: HR 0.45, 95% CI: 0.24-0.84), while primary tumor type was not associated with ICP5 or ICP11. Conclusions: Pre-SRS parameters including polymetastatic burden, prior receipt of immunotherapy, and > 1 BM were associated with post-SRS high-burden ICP. High burden ICP developed earlier following SRS completion and was associated with higher rates of neurologic decline and inferior OS.