Pharyngo-laryngeal involvement in systemic amyloidosis with cardiac involvement: a prospective observational study.

Background: Systemic amyloidosis with cardiac involvement (CA) is a severe disease caused by the aggregation of misfolded proteins infiltrating organs and tissues and leading to their dysfunction. No study has yet focused on potential pharyngo-laryngeal impairments associated to CA. Our objective was to define its prevalence and describe pharyngo-laryngeal involvement patterns in a population with CA (light chain: AL, wild-type transthyretin: ATTRwt, variant transthyretin: ATTRv). Methods: Consecutive patients with a confirmed diagnosis of CA were prospectively investigated for pharyngo-laryngeal involvement. This included questionnaires on symptoms of dysphonia/dysphagia and quality of life Voice Handicap Index (VHI). In cases of dysphonia, a nasofibroscopy was performed to evaluate potential laryngeal organic lesions of amyloid infiltration and induced laryngeal dysfunction (mobility, glottic air leak). In cases of dysphagia, Video Endoscopy Swallowing Study (VESS) was performed to evaluate the presence of hypopharyngeal pooling at rest and during swallowing and the time of swallowing 80 ml of water. Results: Ninety-five CA patients were enrolled, of whom 19 were ATTRv, 36 AL and 40 ATTRwt. Their mean age was 73.8 ± 9.2 years and the sex ratio was 2.6 in favor of men. Dysphagia was reported in 17% of the patients and 40% had more specific oropharyngeal symptoms (food sticking, regurgitation, change in dietary habits), preceding the CA diagnosis by 7 (0-24) months. Recent weight loss was reported in 60% of the patients (mean loss of 10 ± 6.3 kg). VESS showed functional swallowing impairment in only 4 patients without any macroscopic organic lesion. Dysphonia was reported in 36% of the patients (44% and 47% in AL and ATTRv sub-groups, respectively) of whom 40% had functional or organic laryngeal abnormality (14% of vocal fold mobility dysfunction and 26% of abnormal mucosa) without any macroscopic-specific lesions of amyloid infiltration in these patients. Conclusions: This prospective study suggests, for the first time, that amyloid associated with CA could infiltrate the various anatomical structures of the pharyngo-larynx, responsible for functional impairment and potential nutritional depletion and poor quality of life.

Group size elicits specific physiological response in herbivores.

With increasing group size, individuals commonly spend less time standing head-up (scanning) and more time feeding. In small groups, a higher predation risk is likely to increase stress, which will be reflected by behavioural and endocrine responses. However, without any predator cues, we ask how the predation risk is actually processed by animals as group size decreases. We hypothesize that group size on its own acts as a stressor. We studied undisturbed groups of sheep under controlled pasture conditions, and measured in situ the cortisol and vigilance responses of identified individuals in groups ranging from 2 to 100 sheep. Both vigilance and average cortisol concentration decreased as group size increased. However, the cortisol response varied markedly among individuals in small groups, resulting in a lack of correlation between cortisol and vigilance responses. Further experiments are required to explore the mechanisms that underlie both the decay and the convergence of individual stress in larger groups, and whether these mechanisms promote adaptive anti-predator responses.