Musculoskeletal manifestations associated with transthyretin-mediated (ATTR) amyloidosis: a systematic review.

BACKGROUND: Hereditary and wild-type transthyretin-mediated (ATTRv and ATTRwt) amyloidoses result from the misfolding of transthyretin and aggregation of amyloid plaques in multiple organ systems. Diagnosis of ATTR amyloidosis is often delayed due to its heterogenous and non-specific presentation. This review investigates the association of musculoskeletal (MSK) manifestations with ATTR amyloidosis and the delay from the onset of these manifestations to the diagnosis of ATTR amyloidosis. METHODS: This systematic review utilized Medline and EMBASE databases. Search criteria were outlined using a pre-specified patient, intervention, comparator, outcome, time, study (PICOTS) criteria and included: amyloidosis, ATTR, and MSK manifestations. Publication quality was assessed utilizing Joanna Briggs Institute (JBI) critical appraisal checklists. The search initially identified 7,139 publications, 164 of which were included. PICOTS criteria led to the inclusion of epidemiology, clinical burden and practice, pathophysiology, and temporality of MSK manifestations associated with ATTR amyloidosis. 163 publications reported on ATTR amyloidosis and MSK manifestations, and 13 publications reported on the delay in ATTR amyloidosis diagnosis following the onset of MSK manifestations. RESULTS: The MSK manifestation most frequently associated with ATTR amyloidosis was carpal tunnel syndrome (CTS); spinal stenosis (SS) and osteoarthritis (OA), among others, were also identified. The exact prevalence of different MSK manifestations in patients with ATTR amyloidosis remains unclear, as a broad range of prevalence estimates were reported. Moreover, the reported prevalence of MSK manifestations showed no clear trend or distinction in association between ATTRv and ATTRwt amyloidosis. MSK manifestations precede the diagnosis of ATTR amyloidosis by years, and there was substantial variation in the reported delay to ATTR amyloidosis diagnosis. Reports do suggest a longer diagnostic delay in patients with ATTRv amyloidosis, with 2 to 12 years delay in ATTRv versus 1.3 to 1.9 years delay in ATTRwt amyloidosis. CONCLUSION: These findings suggest that orthopedic surgeons may play a role in the early diagnosis of and treatment referrals for ATTR amyloidosis. Detection of MSK manifestations may enable earlier diagnosis and administration of effective treatments before disease progression occurs.

Managers Can Support Employees in Working-Class Contexts by Promoting Growth Mindsets.

White-collar workplaces are critical "gateway" contexts. They play a crucial role in providing valuable opportunities and upward social mobility. Some groups are less likely, however, to feel they belong in these settings. For example, those with a college degree may feel relatively at ease. However, those without may be uncertain about whether they will be fully included. We examine one possibility for addressing these class-based belonging gaps. A growing education literature demonstrates the power of growth mindsets. We extend this research to the workplace and test its benefits. In two preregistered experiments (N = 1,777), we find that endorsing growth mindsets can support working-class (WK) individuals. When managers have a growth mindset, WK individuals report high sense of belonging. The effect occurred because managers with growth mindsets reduced identity threat. A preregistered survey of employees in the real world (N = 300) triangulated these findings. Sense of belonging was higher among those who believed their manager had a growth mindset. Furthermore, they reported greater job satisfaction and commitment. These findings have important implications for the growing conversation on addressing class divides.

Six-minute walk test as clinical end point in cardiomyopathy clinical trials, including ATTR-CM: a systematic literature review.

Aim: The six-minute walk test (6MWT) is a common measure of functional capacity in patients with heart failure (HF). Primary clinical study end points in cardiomyopathy (CM) trials, including transthyretin-mediated amyloidosis with CM (ATTR-CM), are often limited to hospitalization and mortality. Objective: To investigate the relationship between the 6MWT and hospitalization or mortality in CM, including ATTR-CM. Method: A PRISMA-guided systematic literature review was conducted using search terms for CM, 6MWT, hospitalization and mortality. Results: Forty-one studies were identified that reported 6MWT data and hospitalization or mortality data for patients with CM. The data suggest that a greater 6MWT distance is associated with a reduced risk of hospitalization or mortality in CM. Conclusion: The 6MWT is an accepted alternative end point in CM trials, including ATTR-CM.