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AbstractBackground/AimsHypothyroidism has been associated with hepatocellular carcinoma (HCC) incidence; however, the relationship between hypothyroidism and HCC patient outcomes is unclear. We investigated the impact of hypothyroidism on outcomes after liver transplantation for HCC.Materials and MethodsWe retrospectively studied HCC patients transplanted between January 2000 and December 2015. Hypothyroidism was defined as a thyroid‐stimulating hormone (TSH) level continuously greater than 5 mIU/L, a documented history of hypothyroidism, or treatment with thyroid hormone replacement therapy. Multivariate Cox regression was used to assess the impact of hypothyroidism on overall survival (OS) and recurrence‐free survival (RFS) adjusting for potential confounders. Subgroup analyses and interaction tests were conducted to compare the impact of hypothyroidism in different subgroups and assess for possible synergistic effects. Sensitivity analyses were performed among different cohorts to verify the stability of the results.ResultsA total of 343 HCC patients who underwent liver transplantation were included in the analysis. The primary analysis was conducted among 288 patients diagnosed with HCC prior to transplantation. Hypothyroidism was independently associated with worse OS and RFS, as was elevated TSH. The adjusted hazard ratio (AHR) of hypothyroidism was 2.45 (95% confidence interval [CI], 1.44‐4.18) for OS and 5.54 (2.36, 13.01) for RFS. The AHR of TSH for OS was 1.05 (1.02, 1.09) and 1.08 (1.03, 1.13) for RFS. No interaction was found among different subgroups categorized by etiology and comorbidity. The results were stable to sensitivity analyses.ConclusionHypothyroidism is associated with poorer overall and recurrence‐free survival of HCC patients receiving liver transplantation. These results require validation.

Background: Although inflammation has been implicated in the pathogenesis of Alzheimer’s disease, the effects of systemic inflammation on brain amyloid deposition remain unclear. Objective: We examined the association of midlife and late-life systemic inflammation with late-life brain amyloid levels in a community sample of non-demented older adults from the Atherosclerosis Risk in Communities (ARIC) – PET Study. Methods: 339 non-demented participants (age: 75 [SD 5]) were recruited from the ARIC Study to undergo florbetapir PET (amyloid) imaging. Blood levels of high sensitivity C-reactive protein (CRP), a marker of systemic inflammation, were measured 22 years (Visit 2), 16 years (Visit 4), and up to 2 years before PET imaging (Visit 5). Elevated brain amyloid deposition (standardized uptake value ratio >1.2) was the primary outcome. Results: Our primary analyses found no association of midlife and late-life CRP with late-life brain amyloid levels. However, in secondary stratified analyses, we found that higher midlife (Visit 2) CRP was associated with elevated amyloid among males (OR 1.65, 95% CI: 1.13–2.42), and among white (OR 1.33, 95% CI: 1.02–1.75), but not African American, participants ( p-interactions<0.05). Among male participants, those who maintained high CRP levels (≥3 mg/L) throughout mid- and late-life were most likely to have elevated brain amyloid (OR, 8.81; 95% CI: 1.23, 62.91). Conclusions: Although our primary analysis does not support an association between systemic inflammation and brain amyloid deposition, we found evidence for sex- and race-dependent associations. However, findings from subgroup analyses should be interpreted with caution.

Introduction: In 2015, the US Alzheimer’s Disease Centers (ADC) implemented Version 3 of the Uniform Data Set (UDS). This paper describes the history of Version 3 development and the UDS data that are freely available to researchers. Methods: UDS Version 3 was developed after years of coordination between the National Institute on Aging-appointed Clinical Task Force (CTF), clinicians from ∼30 ADCs, and the National Alzheimer’s Coordinating Center (NACC). The CTF recognized the need for updates to align with the state of the science in dementia research, while being flexible to the diverse needs and diseases studied at the ADCs. Version 3 also developed a nonproprietary neuropsychological battery. Results: This paper focuses on the substantial Version 3 changes to the UDS forms related to clinical diagnosis and characterization of clinical symptoms to match updated consensus-based diagnostic criteria. Between March 2015 and March 2018, 4820 participants were enrolled using UDS Version 3. Longitudinal data were available for 25,337 of the 37,568 total participants using all UDS versions. Discussion: The results from utilization of the UDS highlight the possibility for numerous research institutions to successfully collaborate, produce, and use standardized data collection instruments for over a decade.

Abstract Objectives Working Group 2 was convened to address topics relevant to prosthodontics and dental implants. Systematic reviews were developed according to focused questions addressing (a) the number of implants required to support fixed full‐arch restorations, (b) the influence of intentionally tilted implants compared to axial positioned implants when supporting fixed dental prostheses ( FDP s), (c) implant placement and loading protocols, (d) zirconia dental implants, (e) zirconia and metal ceramic implant supported single crowns and (f) zirconia and metal ceramic implant supported FDP s. Materials and methods Group 2 considered and discussed information gathered in six systematic reviews. Group participants discussed statements developed by the authors and developed consensus. The group developed and found consensus for clinical recommendations based on both the statements and the experience of the group. The consensus statements and clinical recommendations were presented to the plenary (gathering of all conference attendees) and discussed. Final versions were developed after consensus was reached. Results A total of 27 consensus statements were developed from the systematic reviews. Additionally, the group developed 24 clinical recommendations based on the combined expertise of the participants and the developed consensus statements. Conclusions The literature supports the use of various implant numbers to support full‐arch fixed prostheses. The use of intentionally tilted dental implants is indicated when appropriate conditions exist. Implant placement and loading protocols should be considered together when planning and treating patients. One‐piece zirconia dental implants can be recommended when appropriate clinical conditions exist although two‐piece zirconia implants should be used with caution as a result of insufficient data. Clinical performance of zirconia and metal ceramic single implant supported crowns is similar and each demonstrates significant, though different, complications. Zirconia ceramic FDP s are less reliable than metal ceramic. Implant supported monolithic zirconia prostheses may be a future option with more supporting evidence.

Background: Increasing evidence points to intracranial atherosclerosis as a risk factor not only for stroke but also for dementia, but whether it is linked to Alzheimer’s disease-specific pathology itself is less understood. In the community-based Atherosclerosis Risk in Communities (ARIC) study, we evaluated the cross-sectional association between intracranial atherosclerosis and cerebral amyloid deposition, in nondemented participants. Methods: In 2011-2014, a subset of participants from the ARIC Neurocognitive Study underwent both a brain MRI, including high-resolution vessel wall imaging, and florbetapir PET, as a marker of amyloid deposition. We analyzed the association between elevated amyloid (defined as a global cortical florbetapir standardized uptake value ratio (SUVR)>1.2) and intracranial arterial plaque presence, frequency, and extent of stenosis, with adjustment for demographic and vascular risk factors. We tested effect modification by APOE ε4 genotype. Results: In 300 participants (mean age of 76y, 44% African-American, 56% female, 31% carriers of at least one APOE ε4 allele), intracranial plaque was found in 105 (35%) participants. Mean SUVR was higher in individuals with vs without plaque (1.34 ± 0.29 vs 1.27 ± 0.23, p=0.03). In adjusted models, plaque presence was not associated significantly with elevated SUVR in the total sample, nor was number of plaques. Associations between plaque presence and extent were generally stronger in APOE ε4 carriers than noncarriers (p<0.05 for interaction for some plaque features; see Table). Conclusions: Although intracranial arterial plaque or stenosis was not definitively associated with brain amyloid in this sample of nondemented older adults, associations with brain amyloid appeared stronger in carriers of an APOE ε4 allele, consistent with studies demonstrating a similar relationship as that seen with other more traditionally measured vascular risk factors.

OBJECTIVELatent autoimmune diabetes in adults (LADA) shares clinical features with both type 1 and type 2 diabetes; however, there is ongoing debate regarding the precise definition of LADA. Understanding its genetic basis is one potential strategy to gain insight into appropriate classification of this diabetes subtype.RESEARCH DESIGN AND METHODSWe performed the first genome-wide association study of LADA in case subjects of European ancestry versus population control subjects (n = 2,634 vs. 5,947) and compared against both case subjects with type 1 diabetes (n = 2,454 vs. 968) and type 2 diabetes (n = 2,779 vs. 10,396).RESULTSThe leading genetic signals were principally shared with type 1 diabetes, although we observed positive genetic correlations genome-wide with both type 1 and type 2 diabetes. Additionally, we observed a novel independent signal at the known type 1 diabetes locus harboring PFKFB3, encoding a regulator of glycolysis and insulin signaling in type 2 diabetes and inflammation and autophagy in autoimmune disease, as well as an attenuation of key type 1–associated HLA haplotype frequencies in LADA, suggesting that these are factors that distinguish childhood-onset type 1 diabetes from adult autoimmune diabetes.CONCLUSIONSOur results support the need for further investigations of the genetic factors that distinguish forms of autoimmune diabetes as well as more precise classification strategies.

Lung ultrasound (US) surface wave elastography (SWE) is a novel technique that measures superficial lung tissue elastic properties. A thin pleural fluid layer covers a lung, but its effect on lung measurements in SWE is unknown. We modeled a lung and pleural fluid with sponges and a thin layer of US transmission gel. Sponge surface wave speeds measured from SWE were compared for sponges without and with the thin US gel layer at 3 wave excitation frequencies. The comparison showed that the sponge surface wave speed measurements were not affected by the thin gel layer.