Didier Chalhoub

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.

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

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.

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.

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.

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 (β) indicate association effect sizes. Results In the fully-adjusted models, attenuation (men β = 0.06, 95% CI: 0.01, 0.11; women β = 0.07, 95% CI: 0.03, 0.11) and muscle area (men β = 0.13, 95% CI: 0.07, 0.19; women β = 0.10, 95% CI: 0.06, 0.15) were associated with knee RTD. Attenuation (men β = 0.12, 95% CI: 0.08, 0.16; women β = 0.12, 95% CI: 0.09, 0.16) and muscle area (men β = 0.38, 95% CI: 0.33, 0.43; women β = 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: MUSCLE-BONE ASSOCIATIONS 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.

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

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.

CONCORDANCE BETWEEN SPECKLE TRACKING ECHOCARDIOGRAPHY AND PHASE ANALYSIS OF MYOCARDIAL SPECT FOR LV SEGMENT OF LATEST MECHANICAL ACTIVATION

To determine concordance between speckle tracking echo and myocardial SPECT for the determination of the latest activated LV segment. Out of 187 patients enrolled in the Speckle Tracking Assisted Resynchronization Therapy for Electrode Region trial, 54 had both echo and SPECT at baseline, of whom