Citations

Introduction: Low levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) among older adults are associated with mortality, and reportedly with lower cognitive performance, biomarkers of neurodegeneration, and dementia. We tested the associations of liver enzymes with cognition in ARIC-NCS. Methods: We studied 3191 participants (mean age 79 years, 59% female, 23% black) free of chronic liver disease and cirrhosis, and with AST:ALT ratio ≤2 at visit in 2016-2017. Serum ALT and AST were examined continuously and by quintiles, with the 3 rd quintile as the distribution-based modal reference range. Cognitive status (normal, mild cognitive impairment [MCI], dementia) was ascertained by an expert adjudication panel. A composite global cognition score was estimated from memory, executive function, and language tests. We used demographic and ApoE4 adjusted multinomial logistic and linear regressions. Results: Participants were classified as cognitively unimpaired (2375), MCI (602) or dementia (214). Lower levels of ALT and AST, and a higher AST:ALT ratio were associated with higher prevalence of dementia and lower global cognition scores ( Figure ). The prevalence odds ratio of dementia and MCI for the 1 st quintile, vs 3 rd quintile of ALT, were 1.73 (95% CI:1.06-2.81) and 1.27 (0.92-1.76), respectively. The corresponding estimates for AST were 1.71 (1.03-2.84) and 1.17 (0.87-1.59). Global cognition scores were lower in the 1 st vs 3 rd quintiles of ALT and AST by 0.13 (0.06-0.21) and 0.08 (0-0.15) standard deviation units, respectively. Additional adjustment for alcohol intake did not change the results. Conclusions: Liver hypometabolism is linked to reduced brain glucose metabolism, impaired production of neurotransmitters and synaptic maintenance, systemic insulin resistance and inflammation, while hepatic metabolite profiles are altered in dementia. Prospective assessments are warranted to characterize the role of hepatic metabolic dysfunction in cognitive impairment among older adults.

ObjectiveThe mechanism by which recurrent croup occurs is unknown. Gastroesophageal reflux is commonly implicated, although this relationship is only loosely documented. We conducted a systematic review with a meta‐analysis component to evaluate the relationship between recurrent croup and gastroesophageal reflux disease (GERD), and to assess for evidence of improvement in croup symptoms when treated.Style DesignSystematic Review and Meta Analysis.MethodsWe searched five separate databases. Studies were included if they discussed the relationship between croup and GERD in children, >5 subjects, and available in English. Literature retrieved was assessed according to pre‐specified criteria. Retrieved articles were reviewed by two independent authors and decisions mediated by a third author. If there was a difference of opinion after first review, a second review was performed to obtain consensus. Heterogeneity was calculated and summarized in forest plots.ResultsOf 346 initial records, 15 met inclusion criteria. These were two retrospective cohort and 13 cross‐sectional studies. Thirteen of 15 articles support an association between recurrent croup and GERD. Although heterogeneity is high among studies that reported prevalence of GERD, there is less uncertainty in results for improvement to recurrent croup after GERD treatment. Most studies lacked a control group and all carry a moderate‐to‐high risk of bias.ConclusionThere is limited evidence linking GERD to recurrent croup; Further research is needed to assess for causality as most studies are retrospective, lack a control group, and have a study design exposing them to bias. Patients treated with reflux medication appear to demonstrate a reduced incidence of croup symptoms.Level of Evidence1 Laryngoscope, 131:209–217, 2021

Pontocerebellar hypoplasia (PCH) is a group of neurological disorders that affect the development of the brain, in particular, the pons and cerebellum. Homozygous mutations of TBC1D23 have been found recently to lead to PCH; however, the underlying molecular mechanisms remain unclear. Here, we show that the crystal structure of the TBC1D23 C-terminal domain adopts a Pleckstrin homology domain fold and selectively binds to phosphoinositides, in particular, PtdIns(4)P, through one surface while binding FAM21 via the opposite surface. Mutation of key residues of TBC1D23 or FAM21 selectively disrupts the endosomal vesicular trafficking toward the Trans-Golgi Network. Finally, using the zebrafish model, we show that PCH patient-derived mutants, impacting either phosphoinositide binding or FAM21 binding, lead to abnormal neuronal growth and brain development. Taken together, our data provide a molecular basis for the interaction between TBC1D23 and FAM21, and suggest a plausible role for PtdIns(4)P in the TBC1D23-mediating endosome-to-TGN trafficking pathway. Defects in this trafficking pathway are, at least partially, responsible for the pathogenesis of certain types of PCH.

Background Selecting the optimal surgical approach for resection of sinonasal inverted papilloma (SIP) remains a challenge, with endoscopic, external, and combined approaches being utilized. This systematic review was conducted as an update to a 2006 systematic review to determine the preferred surgical approach for tumor control. Methods The study protocol was developed a priori following the Preferred Reporting Items for Systematic Reviews and Meta‐Analyses (PRISMA) process. Data were collected and outcomes were analyzed according to surgical approach and sites of tumor involvement. Results A total of 96 papers and 4134 SIP patients were included. The overall recurrence rate was 12.80% (322/2515) for the endoscopic approach group, 16.58% (182/1098) for the external approach group, and 12.60% (65/516) for the combined approach group. Meta‐analysis by random effects model showed that the summarized risk ratio (RR) of recurrence was 0.61 (95% confidence interval [CI], 0.44 to 0.85, p = 0.003), I 2 = 37.95% for the endoscopic vs external approach; 0.98 (95% CI, 0.69 to 1.39, p = 0.901), I 2 = 9.06% for the endoscopic vs combined approach; 1.61 (95% CI, 1.06 to 2.43, p = 0.025), I 2 = 0.00% for the external vs combined approach. After adjusting for publication bias, the adjusted RRs were 0.66 ( p = 0.014) for endoscopic vs external; 0.99 ( p = 0.955) for endoscopic vs combined; and 1.33 ( p = 0.224) for external vs combined. Conclusion An enlarging and maturing body of literature continues to indicate that endoscopic approaches result in significantly lower recurrence rates than open approaches for surgical resection of SIP.

Background While Eustachian tube dysfunction (ETD) is a known comorbidity of chronic rhinosinusitis (CRS), the prevalence of ETD symptoms in the CRS population is poorly understood. We sought to determine the cross‐sectional prevalence of ETD in patients with CRS using the validated Eustachian Tube Dysfunction Questionnaire (ETDQ‐7) and to correlate ETDQ‐7 scores with 22‐item Sino‐Nasal Outcome Test (SNOT‐22) scores, endoscopy scores, and computed tomography (CT) scores. Methods A total of 101 patients with confirmed CRS completed the ETDQ‐7 and SNOT‐22 at their initial visit to our rhinology clinic. Lund‐Mackay CT and Lund‐Kennedy endoscopy scores were also obtained. Spearman's correlation coefficient (ρ) was calculated. Results Among the 101 patients, 49 patients (48.5%) had an ETDQ‐7 score of ≥14.5, signifying clinically significant ETD. The mean ± standard deviation (SD) ETDQ‐7 score of the entire cohort was 17.8 ± 10.1. There was a moderately strong correlation between ETDQ‐7 and the SNOT‐22 ear subdomain (ρ = 0.691, p < 0.001). The correlation coefficient between ETDQ‐7 and total SNOT‐22 scores was ρ = 0.491 ( p < 0.001), indicating moderate correlation. ETDQ‐7 scores were poorly correlated to objective measures of sinonasal disease, including Lund‐Mackay CT score (ρ = −0.055, p = 0.594) and Lund‐Kennedy endoscopy score (ρ = −0.099, p = 0.334). Conclusion Symptoms of ETD are highly prevalent among patients with CRS as documented by patient‐reported outcome measures. The correlation between ETDQ‐7 scores and SNOT‐22 ear subdomain scores is moderately strong, while the correlation between ETDQ‐7 scores and SNOT‐22 scores is moderate. ETD severity does not correlate with CT score or nasal endoscopy score.