The French way of voice rehabilitation post total laryngectomy: current clinical practices and tendencies.

BACKGROUND: Vocal rehabilitation post total laryngectomy (TL) lacks clinical guidelines, especially with the presence of multiple modalities. OBJECTIVES: To describe the tendencies of vocal rehabilitation post TL in France and compare it with other countries. We try to identify the most practiced modalities and recognize statistically significant influencing factors. MATERIALS AND METHODS: An electronic anonymous survey was answered by 75 ENT surgeons from France. The survey outlined the common practiced vocal rehabilitation modalities and had two versions depending on if the participant practices the tracheoesophageal speech (TES) or not. RESULTS: 96% use TES in their practice. Single modality TES and double modality TES with esophageal speech (ES) are the two most practiced modalities. 99% agreed that there is no age limit for the TES. Single modality ES was offered 92% more when more than 10 TL were performed per year (p < .05). No influencing factors found for single modality TES or double modality TES with ES (p > .05).Conclusion: In line with tendencies from other countries, the TES is the most practiced modality of vocal rehabilitation coupled or not with the ES. TES has no age limit as per our participants. The least practiced modality is the singe modality ALS.

Virtual-reality-enhanced mannequin to train emergency physicians to examine dizzy patients using the HINTS method.

Introduction: Acute vertigo is a frequent chief complaint in the emergency departments, and its efficient management requires thorough training. The HINTS protocol is a valid method to screen patients in the emergency room, but its application in routine is hindered by the lack of training. This study aimed to evaluate the training of emergency physicians for the HINTS method based on a mannequin-based virtual reality simulator (MBVRS). Methods: We conducted a monocenter, prospective, longitudinal, and randomized cohort study in an Emergency Department at a regional university hospital. We included 34 emergency physicians randomized into two equal groups matched by age and professional experience. The control group attended a theoretical lesson with video demonstrations and the test group received a simulation-based training in addition to the lecture. Results: We showed that the test group had a higher diagnosis performance for the HINTS method compared to the control group as evaluated by the simulator at 1 month (89% sensitivity versus 45, and 100% specificity versus 86% respectively, p < 001, Fisher's exact test). Evaluation at 6 months showed a similar advantage to the test group. Discussion: The MBVRS is a useful pedagogic tool for the HINTS protocol in the emergency department. The advantage of a unique training session can be measured up to 6 months after the lesson.

Clinical Deep Phenotyping of ABCA7 Mutation Carriers.

BACKGROUND AND OBJECTIVES: Putative loss-of-function (pLOF) ABCA7 variants that increase Alzheimer disease (AD) risk were identified; however, deep phenotypic characterization of these variants in mutation carriers is limited. We aimed to obtain deep clinical phenotypes of ABCA7 pLOF mutation carriers from a large retrospectively reviewed series. METHODS: Genotypes were determined for 5,353 individuals evaluated at Mayo Clinic for 6 reported ABCA7 pLOF variants (p.E709fs, p.Trp1214X, p.L1403fs, c.4416+2T>G, p.E1679X, and c.5570+5G>C). Medical records of 100 mutation carriers were reviewed for demographics, clinical phenotypes, and diagnoses. Eleven mutation carriers had autopsy-based neuropathologic diagnoses. RESULTS: We confirmed that ABCA7 pLOF mutations confer AD risk in our series of 2,495 participants with AD and 2,858 cognitively unaffected participants. Clinical review of 100 mutation carriers demonstrated phenotypic variability of clinical presentations with both memory and nonmemory cognitive impairment and a subset presenting with motor symptoms. There was a wide range of age at onset of cognitive symptoms (ages 56-92 years, mean = 75.6). Ten of the 11 autopsied mutation carriers had AD neuropathology. ABCA7 pLOF mutation carriers had higher rates of depression (41.6%) and first-degree relatives with cognitive impairment (38.1%) compared with the general population. DISCUSSION: Our study provides a deep clinical review of phenotypic characteristics of mutation carriers for 6 ABCA7 pLOF mutations. Although memory impairment was the most common initial symptom, nonmemory cognitive and/or motor symptoms were present in a substantial number of mutation carriers, highlighting the heterogeneity of clinical features associated with these mutations. Likewise, although AD neuropathology is the most common, it is not the only autopsy-based diagnosis. Presence of earlier ages at onset, higher rates of depression, and first-degree relatives with cognitive impairment among mutation carriers suggest that these genetic variants may have more aggressive clinical features than AD in the general population. This deep phenotyping study of ABCA7 pLOF mutation carriers provides essential genotype-phenotype correlations for future precision medicine approaches in the clinical setting.

MAPT haplotype-stratified GWAS reveals differential association for AD risk variants.

INTRODUCTION: MAPT H1 haplotype is implicated as a risk factor for neurodegenerative diseases including Alzheimer's disease (AD). METHODS: Using Alzheimer's Disease Genetics Consortium (ADGC) genome-wide association study (GWAS) data (n = 18,841), we conducted a MAPT H1/H2 haplotype-stratified association to discover MAPT haplotype-specific AD risk loci. RESULTS: We identified 11 loci-5 in H2-non-carriers and 6 in H2-carriers-although none of the MAPT haplotype-specific associations achieved genome-wide significance. The most significant H2 non-carrier-specific association was with a NECTIN2 intronic (P = 1.33E-07) variant, and that for H2 carriers was near NKX6-1 (P = 1.99E-06). The GABRG2 locus had the strongest epistasis with MAPT H1/H2 variant rs8070723 (P = 3.91E-06). Eight of the 12 genes at these loci had transcriptome-wide significant differential expression in AD versus control temporal cortex (q < 0.05). Six genes were members of the brain transcriptional co-expression network implicated in "synaptic transmission" (P = 9.85E-59), which is also enriched for neuronal genes (P = 1.0E-164), including MAPT. DISCUSSION: This stratified GWAS identified loci that may confer AD risk in a MAPT haplotype-specific manner. This approach may preferentially enrich for neuronal genes implicated in synaptic transmission.

ABCA7 loss-of-function variants, expression, and neurologic disease risk.

OBJECTIVE: To investigate and characterize putative "loss-of-function" (LOF) adenosine triphosphate-binding cassette, subfamily A member 7 (ABCA7) mutations reported to associate with Alzheimer disease (AD) risk. METHODS: We genotyped 6 previously reported ABCA7 putative LOF variants in 1,465 participants with AD, 381 participants with other neuropathologies (non-AD), and 1,043 controls and assessed the overall mutational burden for association with different diagnosis groups. We measured brain ABCA7 protein and messenger RNA (mRNA) levels using Western blot and quantitative PCR, respectively, in 11 carriers of the 3 most common variants, and sequenced all 47 ABCA7 exons in these participants to screen for other coding variants. RESULTS: At least one of the investigated variants was identified in 45 participants with late-onset Alzheimer disease, 12 participants with other neuropathologies, and 11 elderly controls. Association analysis revealed a significantly higher burden of these variants in participants with AD (p = 5.00E-04) and those with other neuropathologies (p = 8.60E-03) when compared with controls. Concurrent analysis of brain ABCA7 mRNA and protein revealed lower protein but not mRNA in p.L1403fs carriers, lower mRNA but not protein in p.E709fs carriers, and additional deleterious mutations in some c.5570+5G>C carriers. CONCLUSIONS: Our results suggest that LOF may not be a common mechanism for these ABCA7 variants and expand the list of neurologic diseases enriched for them.