Neutrophil-lymphocyte ratio is a simple and novel biomarker for prediction of survival after radioembolization for metastatic colorectal cancer.

PURPOSE: Previous studies have reported that an elevated preoperative Neutrophil-Lymphocyte Ratio (NLR) is associated with poor prognosis in patients with various solid tumors including colorectal cancer (CRC). Here, we examine whether NLR predicts survival in patients with unresectable CRC metastases undergoing hepatic radioembolization. METHODS: A retrospective review of 104 consecutive patients with unresectable metastatic CRC who were treated with radioembolization after failing first and second-line chemotherapy. RESULTS: Between 2002 and 2012, the median NLR for all patients was 4.6. Using receiver operating curve analysis, there was no difference between using an NLR cut-off of 4.6 or 5. Forty-eight patients had a high NLR of ≥5 and 56 patients had an NLR of <5. Patients in both groups had similar previous extensive chemotherapy and liver-directed interventions. The median survival of patients with high NLR was 5.6 months (range 4.9-7.9 months) compared with 10.6 months (range 8.3-17.0 months) for patients with low NLR; a significant difference was found in overall survival (log-rank test; p = 0.001). Other factors associated with risk of death were extrahepatic spread of disease, presence of pulmonary nodules, previous liver-targeted intervention, and radiographic response. On multivariate analysis, high NLR, progressive radiographic response, and presence of extrahepatic disease remained independently associated with increased risk of death. CONCLUSIONS: NLR is a simply attainable, inexpensive, and useful biomarker to predict outcome in patients with metastatic colorectal cancer receiving radioembolization.

The Prognostic Role of Neutrophil-to-Lymphocyte Ratio in Patients with Unresectable Hepatocellular Carcinoma Treated with Radioembolization.

PURPOSE: To assess the prognostic value of neutrophil-to-lymphocyte ratio (NLR) in patients with unresectable intermediate- or advanced-stage hepatocellular carcinoma (HCC) treated with yttrium-90 radioembolization (RE). MATERIALS AND METHODS: Retrospective chart review was performed for 176 patients with intermediate- or advanced-stage HCC treated with RE between August 2000 and November 2012. The appropriate NLR cutoff was determined by receiver operating characteristic curves. Demographic, clinical, radiographic, and pathologic parameters were compared between patients with a normal NLR (< 5) and those with an elevated NLR (≥ 5) before RE. Barcelona Clinic Liver Cancer (BCLC) stage-stratified univariate and multivariate analyses were conducted to determine variables associated with overall survival. RESULTS: Under univariate analyses, patients with a normal NLR were found to have longer survival than individuals with a high NLR in intermediate/advanced-disease and advanced-disease cohorts. A multivariate Cox proportional-hazards model in the advanced-disease group confirmed that elevated NLR, high α-fetoprotein level, and low albumin level were independent predictors of worse survival. CONCLUSIONS: This study provides stage-dependent evidence for the prognostic role of NLR in the radioembolized HCC cohort. Patients with BCLC stage C disease with elevated NLR may not derive benefit from RE, and other intervening modalities should be explored in this subpopulation.

Survival and tolerability of liver radioembolization: a comparison of elderly and younger patients with metastatic colorectal cancer.

AIM: To evaluate the outcomes among elderly (≥70 years) and younger patients (<70 years) with liver-dominant metastatic colorectal cancer (mCRC) who received radioembolization (RE) as salvage therapy. METHODS: A retrospective review of 107 consecutive patients with unresectable mCRC treated with RE after failing first- and second-line chemotherapy. RESULTS: From 2002 to 2012, 44 elderly and 63 younger (<70 years) patients received RE. Patients had similar previous extensive chemotherapy and liver-directed interventions. Using modified Response Evaluation Criteria in Solid Tumors (mRECIST) criteria, either a stable or a partial radiographical response was seen in 65.8% of the younger compared with 76.5% of the elderly patients. RE was equally well tolerated in both groups and common procedure-related adverse events were predominantly grade 1-2 and of short duration. No significant difference was found with regard to overall median survival between younger [8.4 months; 95% confidence interval (CI) = 6.2-10.6] or elderly patients (8.2 months; 95% CI = 5.9-10.5, P = 0.667). The presence of extrahepatic disease at the time of RE was associated with a significantly worse median survival in both groups. CONCLUSION: Radioembolization appears to be as well tolerated and effective for the elderly as it is for younger patients with mCRC. Age alone should not be a discriminating factor for the use of radioembolization in the management of mCRC patients.

A Machine Learning Algorithm to Estimate Sarcopenia on Abdominal CT.

RATIONALE AND OBJECTIVES: To assess whether a fully-automated deep learning system can accurately detect and analyze truncal musculature at multiple lumbar vertebral levels and muscle groupings on abdominal CT for potential use in the detection of central sarcopenia. MATERIALS AND METHODS: A computer system for automated segmentation of truncal musculature groups was designed and created. Abdominal CT scans of 102 sequential patients (mean age 68 years, range 59-81 years; 53 women, 49 men) conducted between January 2015 and February 2015 were assembled as a data set. Truncal musculature was manually segmented on axial CT images at multiple lumbar vertebral levels as reference standard data, divided into training and testing subsets, and analyzed by the system. Dice similarity coefficients were calculated to evaluate system performance. IRB approval was obtained, with waiver of informed consent in this retrospective study. RESULTS: System performance as gauged by the Dice coefficients, for detecting the total abdominal muscle cross-section at the level of the third and fourth lumbar vertebrae, were, respectively, 0.953 ± 0.015 and 0.953 ± 0.011 for the training set, and 0.938 ± 0.028 and 0.940 ± 0.026 for the testing set. Dice coefficients for detecting total psoas muscle cross-section at the level of the third and fourth lumbar vertebrae, were, respectively, 0.942 ± 0.040 and 0.951 ± 0.037 for the training set, and 0.939 ± 0.028 and 0.946 ± 0.032 for the testing set. CONCLUSION: This system fully-automatically and accurately segments multiple muscle groups at all lumbar spine levels on abdominal CT for detection of sarcopenia.

Associations of Quadriceps Torque Properties with Muscle Size, Attenuation, and Intramuscular Adipose Tissue in Older Adults.

Background: Atrophy and fatty infiltration of muscle with aging are associated with fractures and falls, however, their direct associations with muscle function are not well described. It was hypothesized that participants with lower quadriceps muscle attenuation, area, and greater intramuscular adipose tissue (IMAT) will exhibit slower rates of torque development (RTD) and lower peak knee extension torques. Methods: Data from 4,842 participants (2,041 men, 2,801 women) from the Age Gene/Environment Susceptibility Reykjavik Study (mean age 76 ± 0.1 years) with complete thigh computed tomography and isometric knee testing. Regression models were adjusted for health, behavior, and comorbidities. Muscle attenuation was further adjusted for muscle area and IMAT; muscle area adjusted for IMAT and attenuation; and IMAT adjusted for muscle area and attenuation. Standardized betas (ß) indicate association effect sizes. Results: In the fully-adjusted models, attenuation (men ß = 0.06, 95% CI: 0.01, 0.11; women ß = 0.07, 95% CI: 0.03, 0.11) and muscle area (men ß = 0.13, 95% CI: 0.07, 0.19; women ß = 0.10, 95% CI: 0.06, 0.15) were associated with knee RTD. Attenuation (men ß = 0.12, 95% CI: 0.08, 0.16; women ß = 0.12, 95% CI: 0.09, 0.16) and muscle area (men ß = 0.38, 95% CI: 0.33, 0.43; women ß = 0.33, 95% CI: 0.29, 0.37) were associated with peak torque. Conclusions: These data suggest that muscle attenuation and area are independently associated with RTD and peak torque; and that area and attenuation demonstrate similar contributions to RTD.

Associations Between Lean Mass, Muscle Strength and Power, and Skeletal Size, Density and Strength in Older Men.

Studies examining the relationship between muscle parameters and bone strength have not included multiple muscle measurements and/or both central and peripheral skeletal parameters. The purpose of this study was to explore the relationship between lean mass, muscle strength and power, and skeletal size, bone density, and bone strength. We studied the association between appendicular lean mass (ALM), grip strength, and leg power, and central quantitative computed tomography (QCT) parameters in 2857 men aged 65 years or older; peripheral QCT was available on a subset (n = 786). ALM, grip strength, and leg power were measured by dual-energy X-ray absorptiometry (DXA), Jamar dynamometer, and the Nottingham Power Rig, respectively. Multivariable models adjusting for potential confounders including age, race, study site, BMI, and muscle measurements were developed and least squares means were generated from linear regression models. For the multivariable model, percent differences of bone parameters between lowest (Q1) and highest quartiles (Q4) of ALM, grip strength, and leg power were reported. ALM was significantly associated with central and peripheral QCT parameters: percent higher values (Q4 versus Q1) ranging from 3.3% (cortical volumetric bone mineral density [vBMD] of the femoral neck) to 31% (vertebral strength index of the spine). Grip strength was only significantly associated with radial parameters: percent higher values (Q4 versus Q1) ranging from 2.5% (periosteal circumference) to 7.5% (33% axial strength index [SSIx]). Leg power was associated with vertebral strength and lower cross-sectional area with percent lower values (Q4 versus Q1) of -11.9% and -2.7%, respectively. In older men, stronger associations were observed for ALM compared to muscle strength and power. Longitudinal studies are needed to examine the relationship between independent changes in muscle measurements and skeletal size, density and strength. © 2018 American Society for Bone and Mineral Research.

Frailty and Risk of Cardiovascular Diseases in Older Persons: The Age, Gene/Environment Susceptibility-Reykjavik Study.

Frailty is a risk factor for cardiovascular diseases (CVD), but the studies available have not considered the presence of subclinical atherosclerotic disease as potential confounders. We investigated the association between frailty and the onset of CVD independently of subclinical atherosclerotic disease. For this reason, a sample of 3818 older participants participating in the Age, Gene/Environment Susceptibility-Reykjavik Study without CVD at baseline was followed for a median of 8.7 years. Frailty was defined as the presence of ≥3 among five Fried's criteria (unintentional weight loss, low physical activity level, weakness, exhaustion, and slow gait speed). Incident CVD was defined as onset of coronary artery disease, heart failure, stroke, and CVD-related mortality identified using hospital, medical, and death records. Subclinical atherosclerotic disease was evaluated as the maximum value of carotid intima media thickness, presence of carotid plaque (moderate or high), and total coronary calcifications (CACs). At baseline, frail participants (n = 300) were more frequently obese, diabetic, and had a greater presence of metabolic syndrome than the nonfrail (n = 3518). Frail participants also showed a higher presence of carotid plaques and CACs. Using a Cox's regression analysis, adjusted for clinical, biochemical, and subclinical atherosclerosis estimates, frailty increased the risk of CVD (hazard ratio [HR] = 1.35; 95% confidence interval [CI]: 1.05-1.74), with results stronger for women than men (HR = 1.51, p = 0.006 and 1.19, p = 0.44, respectively). Among Fried's criteria, exhaustion was the only criterion significantly associated with the onset of new CVD events (HR = 1.30; 95% CI: 1.00-1.73). In conclusion, frailty was associated with the onset of CVD in older people even after adjusting for subclinical atherosclerotic disease.

Echocardiographic left ventricular systolic dysfunction early after resuscitation from cardiac arrest does not predict mortality or vasopressor requirements.

BACKGROUND/AIMS: Echocardiographic abnormalities are common after resuscitation from cardiac arrest. The association between echocardiographic findings with vasopressor requirements and mortality are not well described. We sought to determine the associations between echocardiographic abnormalities and mortality, vasopressor requirements and organ failure after cardiac arrest. METHODS: We prospectively evaluated 55 adult subjects undergoing transthoracic echocardiography within 24h after resuscitation from cardiac arrest. We evaluated the association between 2D echocardiographic and Doppler measurements and mortality, Sequential Organ Failure Assessment (SOFA) scores and vasopressor requirements. RESULTS: Inpatient mortality was 60%. Mean left ventricular ejection fraction (LVEF) was 43.6%; LVEF was <40% in 36% of subjects. None of the measured echocardiographic parameters (including LVEF) was significantly associated with inpatient mortality (all p>0.1). Subjects with LVEF <40% more often had shockable arrest rhythms and patients resuscitated from shockable rhythms had lower mean LVEF (36.2% vs. 52.3%, p=0.001). There was no correlation between markers of right and left ventricular systolic or diastolic function (including LVEF and Doppler parameters) with vasopressor requirements, lactate levels or SOFA scores. CONCLUSION: Echocardiographic parameters (including LVEF) were not associated with inpatient mortality after cardiac arrest. Vasopressor requirements and organ failure severity were not associated with multiple echocardiographic markers of systolic function.

Areal and volumetric bone mineral density and risk of multiple types of fracture in older men.

Although many studies have examined the association between low bone mineral density (BMD) and fracture risk in older men, none have simultaneously studied the relationship between multiple BMD sites and risk of different types of fractures. Using data from the Osteoporotic Fractures in Men study, we evaluated the association between areal BMD (aBMD) by dual-energy X-ray absorptiometry (DXA) and volumetric BMD (vBMD) by quantitative computed tomography (QCT) measurements, and different types of fractures during an average of 9.7years of follow-up. Men answered questionnaires about fractures every 4months (>97% completions). Fractures were confirmed by centralized review of radiographic reports; pathological fractures were excluded. Risk of fractures was assessed at the hip, spine, wrist, shoulder, rib/chest/sternum, ankle/foot/toe, arm, hand/finger, leg, pelvis/coccyx, skull/face and any non-spine fracture. Age and race adjusted Cox proportional-hazards modeling was used to assess the risk of fracture in 3301 older men with both aBMD (at the femoral neck (FN) and lumbar spine) and vBMD (at the trabecular spine and FN, and cortical FN) measurements, with hazard ratios (HRs) expressed per standard deviation (SD) decrease. Lower FN and spine aBMD were associated with an increased risk of fracture at the hip, spine, wrist, shoulder, rib/chest/sternum, arm, and any non-spine fracture (statistically significant HRs per SD decrease ranged from 1.24-3.57). Lower trabecular spine and FN vBMD were associated with increased risk of most fractures with statistically significant HRs ranging between 1.27 and 3.69. There was a statistically significant association between FN cortical vBMD and fracture risk at the hip (HR=1.55) and spine sites (HR=1.26), but no association at other fracture sites. In summary, both lower aBMD and vBMD were associated with increased fracture risk. The stronger associations observed for trabecular vBMD than cortical vBMD may reflect the greater metabolic activity of the trabecular compartment.

Association of Serum Klotho with Loss of Bone Mineral Density and Fracture Risk in Older Adults.

OBJECTIVES: Klotho deficiency has been previously linked to aging-like phenotypes such as osteoporosis, cognitive impairment, and sarcopenia. Low serum klotho was shown to be related to grip strength and disability. Nonetheless, no previous study has explored the association between serum klotho and fractures. The purpose of this report is to examine the relationship of serum klotho with bone mineral density (BMD) loss and fractures in older adults. DESIGN: The Health, Aging, and Body Composition (Health ABC) Study is a longitudinal cohort study of 3,075 community-dwelling older adults. SETTING: US clinical centers. PARTICIPANTS: Two thousand seven hundred and seventy six well-functioning black and white adults aged 70 to 79 years with serum klotho measurements were followed up for a median of 5 years. MEASUREMENTS: Percent annualized BMD change and fracture risk were compared across klotho quartiles. A Poisson distribution was used to calculate age-adjusted fracture incidence rates, and Cox proportional hazards models for multivariable-adjusted hazard ratios. RESULTS: The annualized percent changes in hip, femoral neck, and vertebral BMD were similar across klotho quartiles. Participants experienced 507 nonspine fractures, 203 hip fractures, and 135 vertebral fractures. The Incidence rate (IR) of nonspine fractures was 17 per 1,000 person-years. The most frequent site was hip (IR = 6 per 1,000 person-years) and the IR of vertebral fractures was 3 per 1,000 person-years. There was no association between the lowest quartile of plasma klotho and nonspine (hazard ratio (HR) = 1.19, 95% confidence interval (CI) = 0.86-1.65), hip (HR = 1.34, 95% CI = 0.79-2.27), or vertebral fractures (HR = 1.17, 95% CI = 0.65-2.11). CONCLUSION: Although klotho gene is a susceptible gene for reduced BMD, klotho blood concentration does not appear to be a predictor of bone loss or fracture risk in well-functioning older adults.

Risk of Nonspine Fractures in Older Adults with Sarcopenia, Low Bone Mass, or Both.

OBJECTIVES: To test the hypothesis that men and women with low bone mineral density (BMD) and sarcopenia have a higher risk of fracture than those with only one or neither conditions. DESIGN: The Osteoporotic Fractures in Men Study and the Study of Osteoporotic Fractures in women are prospective observational studies with a mean follow up of 9 (2000-2012) and 8 years (1997-2009), respectively. SETTING: U.S. clinical centers. PARTICIPANTS: Men (n = 5,544; mean age 73.7) and women (n = 1,114; mean age 77.6) aged 65 and older, able to walk without assistance, and without bilateral hip replacement. MEASUREMENTS: Sarcopenia was defined as low appendicular lean mass plus slowness or weakness and low BMD according to the World Health Organization definition of a T-score less than -1.0. Participants were classified as having normal BMD and no sarcopenia (3,367 men, 308 women), sarcopenia only (79 men, 48 women), low BMD only (1,986 men, 626 women), and low BMD and sarcopenia (112 men, 132 women). RESULTS: Men with low BMD and sarcopenia (hazard ratio (HR)=3.79, 95% confidence interval (CI)=2.65-5.41) and men with low BMD only (HR=1.67, 95% CI=1.45-1.93) but not men with sarcopenia only (HR=1.14, 95% CI=0.62-2.09) had greater risk of fracture than men with normal BMD and no sarcopenia. Women with low BMD and sarcopenia (HR=2.27, 95% CI=1.37-3.76) and women with low BMD alone (HR=2.62, 95% CI=1.74-3.95), but not women with only sarcopenia, had greater risk of fracture than women with normal BMD and no sarcopenia. CONCLUSION: Men with low BMD and sarcopenia are at especially high risk of fracture. Sarcopenia alone did not increase fracture risk in either group.

Geographic and ethnic disparities in osteoporotic fractures.

Osteoporotic fractures are a major worldwide epidemic. Here, we review global variability, ethnic differences and secular changes in osteoporotic fractures. Worldwide, age-standardized incidence rates of hip fracture vary >200-fold in women and >140-fold in men when comparing the country in which incidence rates are the highest with that in which they are the lowest. Median age-standardized rates are highest in North America and Europe, followed by Asia, Middle East, Oceania, Latin America and Africa. Globally, rates of hip fracture are greater in women than in men, with an average ratio of ∼2:1. The incidence of radiographic vertebral fractures is much higher than that of hip fractures, whereas the incidence rates of clinical vertebral fractures mirror hip fracture rates in most countries. Methodological challenges of defining and ascertaining vertebral fractures limit the interpretation of these data. Secular declines in hip fracture rates have been reported in populations from North America, Europe and Oceania. These declines are especially notable in women, suggesting that reproductive factors might contribute to this reduction. By contrast, hip fracture rates are increasing in parts of Asia and Latin America. Global indicators of health, education and socioeconomic status are positively correlated with fracture rates suggesting that lifestyles in developed countries might contribute to hip fracture. Improvements in fracture assessment, in particular for nonhip fractures, and identification of factors that contribute to this variability might substantially influence our understanding of osteoporotic fracture aetiology and provide new avenues for prevention.