Impact of Non-Cardiac Clinicopathologic Characteristics on Survival in Transthyretin Amyloid Polyneuropathy.

INTRODUCTION: Hereditary (variant) transthyretin amyloidosis (ATTRv) with polyneuropathy (ATTR-PN) is a rare genetic disorder that causes progressive autonomic and sensorimotor neuropathy, severe disability, and death within 10 years of onset. Previous studies have primarily focused on how baseline cardiac characteristics affect mortality, but the impact of non-cardiac baseline characteristics is less defined. METHODS: We systematically searched PubMed/Medline (1990-2019) to identify studies that assessed the impact of baseline ATTR-PN characteristics on survival. Outcomes were first summarized descriptively. Extracted survival data were then disaggregated, and parametric mixture models were used to assess survival differences among patient groups defined by factors known to affect survival. RESULTS: The search yielded 1193 records, of which 35 were retained for analysis. Median survival ranged from 0.5 to > 25 years. The largest survival differences were between cohorts who underwent liver transplantation (LTx) versus those who did not. Among LTx cohorts, pre-LTx ATTR-PN disease duration ≥ 7 years, poor nutritional status, and late disease onset reduced median survival by 13, 12, and 10 years, respectively. Other prognostic survival factors included non-Val30Met genotype and baseline presence of urinary incontinence, erectile dysfunction, or muscle weakness. CONCLUSION: Survival in patients with ATTR-PN is highly variable and affected by non-cardiac baseline characteristics, such as autonomic dysfunction, large fiber involvement, late-onset disease, and non-Val30Met mutation. Careful interpretation of these findings is warranted given that this synthesis did not control for differences between studies. Survival in patients with ATTR-PN remains poor among those who are untreated or with delayed diagnosis.

Epidemiological and clinical characteristics of symptomatic hereditary transthyretin amyloid polyneuropathy: a global case series.

We describe 542 cases of symptomatic hereditary transthyretin amyloid polyneuropathy (ATTR-PN) identified through a review of the literature published between 2005 and 2016. Approximately 18% of the cases were from countries where ATTR-PN is traditionally considered to be endemic (i.e., Portugal, Japan, and Sweden). East Asia (Japan, China, Taiwan, and South Korea) contributed a sizeable combined proportion (37.0%, n = 200) with Japan (n = 92) and China (n = 71) being the primary contributors. The most common genotypes among the 65 genotypes represented in the sample were Val30Met (47.6%), Ser77Tyr (10%), Ala97Ser (6.5%), and Phe64Leu (4.4%). Cases with genotypes other than the aforementioned four had the lowest ages at onset (mean 49.2 [standard deviation {SD} 21.0; inter-quartile range {IQR}14.7]) and diagnosis (mean 53.4 [SD 21.0; IQR 14.7]). Conversely, Phe64Leu mean age of onset was 67.5 (SD 8.8; IQR 5.2) and mean age of diagnosis was 71.3 (SD 8.8; IQR 5.4). The prevalence of upper and lower limb involvement at the time of diagnosis (67 and 41%) observed across all cases is consistent with the typical presentation of ATTR-PN. Other notable findings at the time of diagnosis included a high rate of impotence among the Ala97Ser cases versus all others (67% vs. 21%) and a high rate of non-motor visual symptoms (i.e., visual opacities and glaucoma) in the Ser77Tyr cases versus all others (93% vs. 16%). Though comparisons were made descriptively and were hindered by inconsistency of reporting across the cases, these findings support the notion that ATTR-PN is a more phenotypically and geographically variable disease than is typically considered.

Crystal Modification on Lithium Disilicate Glass Ceramics Sintered Using Microwaves / Modificación de Cristales de Cerémicas de Vidrio de Disilicato de Litio Sinterizadas con Microondas

ABSTRACT: Microwaves are an interesting alternative to process dental ceramics. It is well documented that Microwave Hybrid Sintering (MHS) allows important savings in time and energy consumption. However, little is known about its effect on lithium disilicate glass ceramics, a popular material in dentistry today. We analyzed the microstructure of lithium disilicate glass ceramics sintered with MHS compared with conventional sintering. We sintered lithium disilicate glass ceramics using MHS and conventional furnaces, and we analyzed the samples using X-Ray diffraction and SEM. Samples sintered with MHS showed an increased crystalline phase, with an increased number of crystals. These crystals have larger perimeters compared with samples sintered in conventional furnaces. MHS produced a different crystallization pattern and crystal/ matrix ration in lithium disilicate glass ceramics when compared to conventional sintering. This can be associated with the improved mechanical properties of these materials reported previously.

RESUMEN: Las microondas son una interesante alternativa para procesar cerámicas dentales. Está bien documentado que el Sinterizado Híbrido por Microondas (MHS) permite ahorros importantes de tiempo y energía. Sin embargo, poco se ha publicado respecto a sus efectos en cerámicas de disilicato de litio, un material bastante popular en odontología en estos días. En este artículo analizamos la micro estructura de cerámicas de disilicato de litio sinterizada con MHS comparada con el sinterizado convencional. Sinterizamos muestras de cerámicas de disilicato de litio usando MHS y hornos convencionales, y analizamos las muestras usando difracción de rayos X y SEM. Las muestras sintetizadas usando MHS tienen una mayor fase cristalina, con mayor número de cristales. Estos cristales tienen además perímetros mayores, comparados con las muestras sinterizadas en hornos convencionales. MHS produce patrones de cristalización y proporción de cristal/matrix diferentes a las producidos por sinterizado convencional. Esto puede asociarse a las mejoras en propiedades mecánicas reportadas previamente.