Distinctive Features and Outcomes of Hepatocellular Carcinoma in Patients With Alcohol-Related Liver Disease: A US Multicenter Study

Introduction: The burden of hepatocellular carcinoma (HCC) occurring in patients with alcoholic liver disease (ALD) is increasing at an alarming rate. The aims of this study were to compare the patient and tumor characteristics of HCC occurring in ALD-alone relative to and in addition to other chronic liver diseases. Methods: Patients diagnosed with HCC between 2000 and 2014 were identified at 5 US clinical centers. The patients were categorized as ALD-alone, ALD plus viral hepatitis, or a non-ALD etiology. Clinical and tumor characteristics among the 3 groups were compared, and survival probability was estimated by the Kaplan-Meier method. The frequency of noncirrhotic HCC was compared across the 3 groups. Results: A total of 5,327 patients with HCC were analyzed. Six hundred seventy (12.6%) developed HCC due to underlying ALD. Ninety-one percent of ALD-related HCC arose in men, in contrast to non-ALD etiologies where men accounted for 70% of HCCs cases (P < 0.001). Patients with ALD-alone-related HCC were older at diagnosis and had tumors less likely to be detected as part of routine surveillance. The ALD-alone cohort was least likely to be within the Milan criteria and to undergo liver transplantation. Overall survival in the ALD-alone HCC cohort was lower than the other 2 groups (1.07 vs 1.31 vs 1.41 years, P < 0.001). HCC in the noncirrhotic ALD cohorts occurred in only 3.5% of the patients compared with 15.7% in patients with non-ALD etiologies (P < 0.001). Discussion: HCC occurring in patients with ALD occurred mostly in older men and almost exclusively in a cirrhotic background. They present with advanced tumors, and their survival is lower than HCCs occurring in non-ALD

Incidence of Dementia and Alzheimer Disease Over Time: A Meta-Analysis

Background/Objectives: Population-based incidence estimates of dementia and Alzheimer’s disease (AD) provide important information for public health policy and resource allocation. We conducted a meta-analysis of published studies that reported age-specific incidence rates of dementia and AD to determine whether dementia and AD incidence rates are changing over time. Design: PubMed and MEDLINE were searched for publications through June 30, 2017 using keywords dementia, Alzheimer, and incidence. Inclusion criteria for the meta-analysis are: (1) population-based studies using personal interviews and direct examinations of the study subjects, (2) Standardized clinical diagnosis criteria, (3) Reporting age-specific incidence rates, (4) Published in English, and (5) Sample size greater or equal to 500 and length of follow-up greater or equal than two years. Mixed effects models were used to determine the association between birth year and incidence rates. Measurements: Age-specific dementia/AD incidence rates and their standard errors reported in each study. Results: Thirty-eight articles with 53 cohorts on dementia incidence and 31 articles with 35 cohorts on AD incidence met the inclusion criteria. There were significant associations between later birth years and decreased dementia incidence rates in all three age groups (65-74, 75-84 and 85+). There were no significant associations between birth year and AD incident rates in any of the three age groups. In particular, AD incidence rates reported from Western countries stayed steady in all age groups while studies in non-Western countries showed significantly increased AD incidence rates for the 65-74 age group (OR=2.78, p=0.04), but non-significant association for the 75-84 or 85+ groups. Conclusion: Dementia incidence declined over the last four decades, but AD incidence did not decline. Further research, especially from non-Western countries, is needed to elucidate the mechanism underlying the trends in dementia and AD incidence over time

A Retrospective Analysis of 287 Patients Undergoing Prophylactic Radiation Therapy for the Prevention of Heterotopic Ossification

Purpose: Heterotopic ossification (HO) is a potentially disabling disorder of ectopic bone formation secondary to orthopedic surgery or trauma. In this retrospective analysis we evaluated the outcomes of patients who received radiation therapy (RT) for HO prophylaxis. Methods and materials: A total of 287 patients who received RT for HO prophylaxis at a major trauma center from 2007 to 2018 were analyzed. Data collected included types of injury, surgery, time intervals between key events, development of postprophylaxis HO, and secondary malignancies. Associations between various factors and the risk of developing HO were analyzed. Kaplan-Meier analysis was used to estimate failure rates. Results: The most common indication for RT was traumatic acetabular fracture (83.3%). Twelve patients (4.2%) developed postprophylaxis HO with a median time to failure of 8.6 months (2.8-24.5). Kaplan-Meier 1-, 2-, and 5-year failure rates were 3.7%, 4.4%, and 7.4%, respectively. Injury type and timing of RT were not associated with the risk of failure, but we observed a trend of increased risk of failure in patients with longer time between surgery and RT (odd ration [OR] 1.68, P = .056). Current or former smokers (51.7%) were less likely to fail (OR 0.10, P = .03). There was no incidence of in-field secondary malignancy. Conclusions: There was no significant association between injury and fracture type, surgical approach, or timing of RT and development of HO, contrary to published reports of increased HO risk with certain surgical approaches and longer time intervals between injury and surgery, suggesting that prophylactic RT might play a role in mitigating these effects. Decreased risk of postprophylaxis HO among former or current smokers was unexpected. No secondary malignancy in the RT field was identified, although the median follow-up was only 17 months. Compared with published HO incidences (17%-39%) in patients who receive no prophylaxis after traumatic acetabular fractures, our results are highly suggestive of the efficacy of prophylactic RT

Genetic Ancestry–dependent Differences in Breast Cancer–induced Field Defects in the Tumor-adjacent Normal Breast

Purpose: Genetic ancestry influences evolutionary pathways of cancers. However, whether ancestry influences cancer-induced field defects is unknown. The goal of this study was to utilize ancestry-mapped true normal breast tissues as controls to identify cancer-induced field defects in normal tissue adjacent to breast tumors (NATs) in women of African American (AA) and European (EA) ancestry. Experimental Design: A tissue microarray comprising breast tissues of ancestry-mapped 100 age-matched healthy women from the Komen Tissue Bank (KTB) at Indiana University (Indianapolis, IN) and tumor-NAT pairs from 100 women (300 samples total) was analyzed for the levels of ZEB1, an oncogenic transcription factor that is central to cell fate, mature luminal cell–enriched estrogen receptor alpha (ERα), GATA3, FOXA1, and for immune cell composition. Results: ZEB1+ cells, which were localized surrounding the ductal structures of the normal breast, were enriched in the KTB-normal of AA compared with KTB-normal of EA women. In contrast, in EA women, both NATs and tumors compared with KTB-normal contained higher levels of ZEB1+ cells. FOXA1 levels were lower in NATs compared with KTB-normal in AA but not in EA women. We also noted variations in the levels of GATA3, CD8+ T cells, PD1+ immune cells, and PDL1+ cell but not CD68+ macrophages in NATs of AA and EA women. ERα levels did not change in any of our analyses, pointing to the specificity of ancestry-dependent variations. Conclusions: Genetic ancestry–mapped tissues from healthy individuals are required for proper assessment and development of cancer-induced field defects as early cancer detection markers. This finding is significant in light of recent discoveries of influence of genetic ancestry on both normal biology and tumor evolution

Testing Influences of APOE and BDNF Genes and Heart Failure on Cognitive Function

Background Apolipoprotein E ( APOE) ε2, ε4 and brain-derived neurotrophic factor ( BDNF) Val66Met alleles have been associated with cognition. Associations of these alleles with cognition in heart failure (HF) and influences of HF across the cognitive spectrum (i.e., cognitively normal to Alzheimer's dementia [AD]) remain unexplored. Objectives To investigate influences of APOE ε2, ε4, BDNF Met and HF on cognition among participants across the cognitive spectrum. Methods Genetic association study using national databases ( N = 7,166). Results APOE ε2 frequencies were similar across the cognitive spectrum among participants with HF. APOE ε4 frequency was lower among participants with HF and AD than non-HF participants with AD. BDNF Met frequencies did not differ across the spectrum. HF was associated with worse attention and language. In the HF subsample, ε4 was associated with worse memory. Conclusion Associations between APOE and cognition may differ in HF but need to be tested in a larger sample

Initiation of Dialysis Is Associated With Impaired Cardiovascular Functional Capacity

Background The transition to dialysis period carries a substantial increased cardiovascular risk in patients with chronic kidney disease. Despite this, alterations in cardiovascular functional capacity during this transition are largely unknown. The present study therefore sought to assess ventilatory exercise response measures in patients within 1 year of initiating dialysis. Methods and Results We conducted a cross‐sectional study of 241 patients with chronic kidney disease stage 5 from the CAPER (Cardiopulmonary Exercise Testing in Renal Failure) study and from the intradialytic low‐frequency electrical muscle stimulation pilot randomized controlled trial cohorts. Patients underwent cardiopulmonary exercise testing and echocardiography. Of the 241 patients (age, 48.9 [15.0] years; 154 [63.9%] men), 42 were predialytic (mean estimated glomerular filtration rate, 14 mL·min −1 ·1.73 m −2 ), 54 had a dialysis vintage ≤12 months, and 145 had a dialysis vintage &gt;12 months. Dialysis vintage ≤12 months exhibited a significantly impaired cardiovascular functional capacity, as assessed by oxygen uptake at peak exercise (18.7 [5.8] mL·min −1 ·kg −1 ) compared with predialysis (22.7 [5.2] mL·min −1 ·kg −1 ; P &lt;0.001). Dialysis vintage ≤12 months also exhibited reduced peak workload, impaired peak heart rate, reduced circulatory power, and increased left ventricular mass index ( P &lt;0.05 for all) compared with predialysis. After excluding those with prior kidney transplant, dialysis vintage &gt;12 months exhibited a lower oxygen uptake at peak exercise (17.0 [4.9] mL·min −1 ·kg −1 ) compared with dialysis vintage ≤12 months (18.9 [5.9] mL·min −1 ·kg −1 ; P =0.033). Conclusions Initiating dialysis is associated with a significant impairment in oxygen uptake at peak exercise and overall decrements in ventilatory and hemodynamic exercise responses that predispose patients to functional dependence. The magnitude of these changes is comparable to the differences between low‐risk New York Heart Association class I and higher‐risk New York Heart Association class II to IV heart failure

Characteristics, aetiologies and trends of hepatocellular carcinoma in patients without cirrhosis: A United States multicentre study

Background Limited data exist on the burden and features of non‐cirrhotic hepatocellular carcinoma (HCC) in the United States. Aim To evaluate characteristics, aetiologies, trends and outcomes of non‐cirrhotic HCC from 2000 to 2014 at five large US centres Methods Patient, tumour and liver disease aetiology data were collected. The presence of underlying cirrhosis was assessed based on published criteria. Results Of 5144 eligible patients with HCC, 11.7% had no underlying cirrhosis. Non‐cirrhotic patients were older (64.1 vs 61.2 years), more frequently females (33.9% vs 20.8%) and less frequently black (8.3% vs 12.4%) (P < .001 for all). Among non‐cirrhotic patients, non‐alcoholic fatty liver disease (NAFLD) was the most common liver disease (26.3%), followed by hepatitis C virus (HCV) (12.1%) and hepatitis B virus (HBV) (10%) infections. As of 2014, there was increased percentage of cirrhotic HCC and a decline in non‐cirrhotic HCC mainly due to significant annual increases in cirrhotic HCC due to HCV (0.96% [P < .0001]) and NAFLD (0.66% [P = .003]). Patients with non‐cirrhotic HCC had larger tumours (8.9 vs 5.3 cm), were less frequently within Milan criteria (15% vs 39%), more frequently underwent resection (43.6% vs 8%) (P < .001 for all) and had better overall survival than cirrhotic HCC patients (median 1.8 vs 1.3 years, P = .004). Conclusions Nearly 12% of HCCs occurred in patients without underlying cirrhosis. NAFLD was the most common liver disease in these patients. During the study, the frequency of non‐cirrhotic HCC decreased, whereas that of cirrhotic HCC increased. Although non‐cirrhotic patients presented with more advanced HCC, their survival was better

A Retrospective Analysis of 287 Patients Undergoing Prophylactic Radiation Therapy for the Prevention of Heterotopic Ossification

Purpose: Heterotopic ossification (HO) is a potentially disabling disorder of ectopic bone formation secondary to orthopedic surgery or trauma. In this retrospective analysis we evaluated the outcomes of patients who received radiation therapy (RT) for HO prophylaxis. Methods and Materials: A total of 287 patients who received RT for HO prophylaxis at a major trauma center from 2007 to 2018 were analyzed. Data collected included types of injury, surgery, time intervals between key events, development of postprophylaxis HO, and secondary malignancies. Associations between various factors and the risk of developing HO were analyzed. Kaplan-Meier analysis was used to estimate failure rates. Results: The most common indication for RT was traumatic acetabular fracture (83.3%). Twelve patients (4.2%) developed postprophylaxis HO with a median time to failure of 8.6 months (2.8-24.5). Kaplan-Meier 1-, 2-, and 5-year failure rates were 3.7%, 4.4%, and 7.4%, respectively. Injury type and timing of RT were not associated with the risk of failure, but we observed a trend of increased risk of failure in patients with longer time between surgery and RT (odd ration [OR] 1.68, P = .056). Current or former smokers (51.7%) were less likely to fail (OR 0.10, P = .03). There was no incidence of in-field secondary malignancy. Conclusions: There was no significant association between injury and fracture type, surgical approach, or timing of RT and development of HO, contrary to published reports of increased HO risk with certain surgical approaches and longer time intervals between injury and surgery, suggesting that prophylactic RT might play a role in mitigating these effects. Decreased risk of postprophylaxis HO among former or current smokers was unexpected. No secondary malignancy in the RT field was identified, although the median follow-up was only 17 months. Compared with published HO incidences (17%-39%) in patients who receive no prophylaxis after traumatic acetabular fractures, our results are highly suggestive of the efficacy of prophylactic RT