RESUMEN
ATTR amyloidosis is a phenotypically heterogeneous disease characterized by the pathological deposition of transthyretin in the form of amyloid fibrils into various organs. ATTR amyloidosis may stem from mutations in variant (ATTRv) amyloidosis, or aging in wild-type (ATTRwt) amyloidosis. ATTRwt generally manifests as a cardiomyopathy phenotype, whereas ATTRv may present as polyneuropathy, cardiomyopathy, or mixed, in combination with many other symptoms deriving from secondary organ involvement. Over 130 different mutational variants of transthyretin have been identified, many of them being linked to specific disease symptoms. Yet, the role of these mutations in the differential disease manifestation remains elusive. Using cryo-electron microscopy, here we structurally characterized fibrils from the heart of an ATTRv patient carrying the V122Δ mutation, predominantly associated with polyneuropathy. Our results show that these fibrils are polymorphic, presenting as both single and double filaments. Our study alludes to a structural connection contributing to phenotypic variation in ATTR amyloidosis, as polymorphism in ATTR fibrils may manifest in patients with predominantly polyneuropathic phenotypes.
RESUMEN
ATTR amyloidosis is a systemic disease characterized by the deposition of amyloid fibrils made of transthyretin, a protein integral to transporting retinol and thyroid hormones. Transthyretin is primarily produced by the liver and circulates in blood as a tetramer. The retinal epithelium also secretes transthyretin, which is secreted to the vitreous humor of the eye. Because of mutations or aging, transthyretin can dissociate into amyloidogenic monomers triggering amyloid fibril formation. The deposition of transthyretin amyloid fibrils in the myocardium and peripheral nerves causes cardiomyopathies and neuropathies, respectively. Using cryo-electron microscopy, here we determined the structures of amyloid fibrils extracted from cardiac and nerve tissues of an ATTRv-V30M patient. We found that fibrils from both tissues share a consistent structural conformation, similar to the previously described structure of cardiac fibrils from an individual with the same genotype, but different from the fibril structure obtained from the vitreous humor. Our study hints to a uniform fibrillar architecture across different tissues within the same individual, only when the source of transthyretin is the liver. Moreover, this study provides the first description of ATTR fibrils from the nerves of a patient and enhances our understanding of the role of deposition site and protein production site in shaping the fibril structure in ATTRv-V30M amyloidosis.
RESUMEN
BACKGROUND: Motor vehicle collisions (MVCs) are a leading cause of injury in the US. While the probability of collision with a pedestrian (PMVC) has declined in recent years, the probability of a pedestrian fatality has risen. Our objective was to determine whether older age impacts potential outcomes in patients involved in low-velocity PMVCs. MATERIALS AND METHODS: We performed a retrospective-cohort study of adult patients aged >14 years involved in low-velocity pedestrian-MVCs (<15 miles per hour [24.14 km/h]), presenting to an urban level I trauma center from January to November 2013. Subjects were identified via trauma registry and stratified: ages 15-49 years and ≥50 years. Electronic medical records were reviewed for demographics, vital signs, and laboratory results on initial presentation, presence or absence of systemic inflammatory response syndrome (SIRS), shock index (SI), injury-severity score (ISS), length of stay (LOS), and survival to discharge. For statistical analysis, χ2 or Student's t-tests were utilized. RESULTS: Our study included 145 patients (77 female) with a mean age of 41.9±3 years; 95 patients were aged 15-49 years (mean 31.9±2.2 years), and 50 patients were aged ≥50 years or older (mean 62.44±2.9 years). Mean ISS was 10.05±1.95, mean SI was 0.68±0.03, and mean LOS was 3.67±0.57 days. A total of 41 patients met SIRS criteria on arrival, and nine patients expired (6.2%). Mean ISS (15.64±4.42 vs 7.1±1.64, P<0.001) and mean SI (0.75±0.07 vs 0.65±0.03, P=0.002) were higher in patients aged ≥50 years. Mean LOS was longer in older patients (5.22±1.14 vs 2.85±0.58 days, P<0.001). Older age was associated with SIRS on arrival (P=0.023) and associated with mortality (P=0.004). CONCLUSION: Age ≥50 years is associated with greater severity of injury and poor outcomes for patients involved in low-velocity PMVCs. Increased clinical attention and resource allocation should be directed toward older patients after low-velocity PMVCs.
RESUMEN
Primary leiomyosarcoma is a disease with <50 documented cases in the literature worldwide. The standard of care for these tumors has not been established. Physicians who have seen these cases in the past have used wide local excision with or without adjunctive chemo-radiation therapy. We review the literature concerning the mainstay of treatment as well as present a new case of an adolescent with primary leiomyosarcoma.