Dual Hip DXA. Is it Time to Change Standard Protocol?

Previous studies have examined the utility of bilateral DXA hip bone mineral density (BMD) scans. While most studies demonstrate an advantage of bilateral hip scanning, the studies have been limited by size, or have not included simultaneous lumbar spine scans. To analyse the utility of dual hip scans in a clinical environment, a large retrospective study was performed of DXA BMD of both hips, and lumbar spine, in 17,169 individuals assessed at one centre over 10 years. There was no clinically significant difference in the population mean femoral neck BMD of the left vs the right leg (0.878 vs 0.881g/cm2) or total proximal femoral BMD of the left vs the right leg (0.920 vs 0.919g/cm2). There were however discrepancies in individuals between hip t-scores. For the total hip 1,977 (11.5 %) and 147 (0.9 %) of subjects had absolute t score differences ≥ 0.50 or ≥ 1.00. respectively. For the femoral neck 3,320 (19.3%) and 337 (2.0%) of subjects had absolute t score differences ≥ 0.50 or ≥ 1.00. respectively. Of the total 17,169 individuals there were 2,776 subjects with osteoporosis (T≤ -2.5) using the lumbar spine and right hip, compared to 2,834 subjects using the lumbar spine and left hip. Using the lumbar spine and both hips identified 3,214 individuals with osteoporosis. Diagnosis based on use of the lumbar spine and right hip BMD, or lumbar spine and left hip BMD, therefore failed to identify 15.8%, or 13.4%, of osteoporotic subjects respectively. Additional scanning time required was assessed in 40 subjects prospectively. Performing lumbar spine and both hips, compared to lumbar spine and one hip, required an average additional scan time of 55 seconds. The recommendation of best practise for DXA BMD measurements should be reviewed to consider lumbar spine and dual hip DXA as standard of care.

The Effect of Green Tea Ingestion and Interval Sprinting Exercise on the Body Composition of Overweight Males: A Randomized Trial.

The combined effect of green tea ingestion and interval sprinting exercise on body and abdominal fat of overweight males was investigated. Participants were randomly assigned into control (C), green tea (GT), interval sprinting exercise (ISE), and green tea and ISE (GT + ISE) groups. The GT, GT + ISE, and C groups consumed three GT capsules daily. The ISE and GT + ISE groups completed 36 ISE sessions over 12 weeks. Forty eight overweight males with a mean BMI of 28.5 ± 0.92 kg/m² and age of 26 ± 0.7 years acted as participants. There was a significant reduction in total and abdominal fat mass for the ISE and GT + ISE groups, p < 0.05, however, total and abdominal fat mass did not significantly change in the GT and C groups. There was a significant increase in total lean mass, p < 0.05, after the intervention for the ISE and GT + ISE groups only. There was a significant increase in fat oxidation during submaximal aerobic exercise, p < 0.05, after the intervention for the ISE, GT + ISE, and GT groups with no change for the C group. Following the 12-week intervention the ISE and GT + ISE groups, compared to C, recorded a significantly greater decrease in body and abdominal fat, and a significant increase in total lean mass. Ingestion of green tea by itself, however, did not result in a significant decrease in body or abdominal fat, but increased fat utilization during submaximal exercise. The combination of 12 weeks of GT ingestion and ISE did not result in greater total and abdominal fat reduction compared to 12 weeks of ISE alone.

The effect of a lifestyle intervention on metabolic health in young women.

With the increasing obesity rates in Western countries, an effective lifestyle intervention for fat reduction and metabolic benefits is needed. High-intensity intermittent exercise (HIIE), Mediterranean eating habits (Mediet), and fish oil (ω-3) consumption positively impact metabolic health and adiposity, although the combined effect has yet to be determined. A 12-week lifestyle intervention on adiposity, insulin resistance, and interleukin-6 (IL-6) levels of young overweight women was administered. Thirty women with a body mass index of 26.6±0.5 kg/m(2), blood pressure of 114/66±1.9/1.5 mmHg, and age of 22±0.8 years were randomly assigned to either an intervention group receiving Mediet advice, daily ω-3 supplementation, and HIIE 3 days/week for 12 weeks or a control group. The group receiving Mediet advice, daily ω-3 supplementation, and HIIE experienced a significant reduction in total body fat mass (P<0.001), abdominal adiposity (P<0.05), waist circumference (P<0.001), systolic blood pressure (P<0.05), fasting plasma insulin (P<0.05), IL-6 (P<0.001), and triglycerides (P<0.05). The greatest decreases in fasting plasma insulin (P<0.05) and IL-6 (P<0.001) occurred by week 6 of the intervention. Significant improvements in eating habits (P<0.05) and aerobic fitness (P<0.001) were also found following the intervention. A multifaceted 12-week lifestyle program comprising a Mediet, ω-3 supplementation, and HIIE induced significant improvements in fat loss, aerobic fitness, and insulin and IL-6 levels, positively influencing metabolic health.

Regional adiposity distribution and insulin resistance in young Chinese and European Australian women.

OBJECTIVE: Lower than normal leg fat mass and excessive trunk fat mass are predictive of insulin resistance (IR) in obese women of European descent. Whether this regional adiposity relationship applies to moderately overweight women of Chinese descent is undetermined. Thus, the relationship between leg and trunk fat mass and IR of young (22.3 ± 0.3 years) sedentary Australian women of either Chinese (CW; n = 22) or European (EW; n = 36) descent was examined. MATERIAL AND METHODS: Subjects underwent a maximal oxygen uptake test, blood draw, and dual energy x-ray absorptiometry to measure body composition. Fasting insulin levels and C-reactive protein (CRP) were assessed by ELISA and IR was calculated by HOMA-IR. Blood lipids and glucose were quantified by an automated enzymatic method (Cholestech LDX, USA). RESULTS: Total, arm, trunk, and leg fat was significantly greater (p < 0.05) for the EW group, whereas IR was significantly higher for CW. Fasting lipids and glucose were within normal levels for both groups, whereas CRP levels were significantly higher in EW. For EW trunk fat mass was the only variable significantly correlated with IR (r = 0.40, p < 0.05). In contrast, for CW leg fat mass was significantly correlated with IR (r = − 0.49, p < 0.05). CONCLUSIONS: Greater trunk fat mass was associated with higher IR of Australian women of European descent, whereas smaller leg fat mass was associated with higher IR of women of Chinese descent.

Dual-time-point (18)F-FDG-PET/CT imaging in the assessment of suspected malignancy.

UNLABELLED: INTRODUCTION (PURPOSE OF THE STUDY): The objective of this study was to assess whether dual-time-point (18)F-fluoro-2-deoxyglucose ((18)F-FDG)-PET/CT imaging improved the evaluation of suspected malignancy and if there was any resulting change in management. METHODS: A total of 53 patients with suspected malignancy were investigated by performing two static acquisitions started at mean times t = 64 and t = 155 min after the tracer injection. The total number of malignant lesions was 133 and the total number of benign lesions was 61. Visual and semiquantitative analysis was performed on both the early and delayed images. RESULTS: Overall, there was a significant improvement (P < 0.001) in the sensitivity of delayed imaging (94%) compared with early imaging (77%) in detecting malignant lesions, without a reduction in specificity. In 10 patients, 13 malignant lesions were undetected on early imaging alone but detected on delayed imaging. In seven patients, 10 malignant lesions were incorrectly classified as 'likely benign' on early imaging but correctly reported as 'likely malignant' on delayed imaging. Management was altered in 2 out of 17 patients. Overall, delayed imaging altered management in 2 out of 53 studied patients. Dual-time-point (18)FDG-PET/CT imaging was useful in differentiating malignant from benign intra-abdominal lesions but did not improve the evaluation of pulmonary lesions. CONCLUSIONS: (18)F-FDG-PET/CT imaging should be performed as late as reasonably possible after tracer administration in order to increase tumour-to-background contrast and thereby improve the sensitivity of demonstrating additional sites of disease. Dual-time-point (18)FDG-PET/CT may be of benefit in the evaluation of intra-abdominal lesions but does not improve the overall evaluation of pulmonary lesions.

High prevalence of brown adipose tissue in adult humans.

CONTEXT: Positron emission tomography (PET)-computed tomography (CT) has identified metabolically active supraclavicular fat in adult humans based on uptake of labeled glucose and confirmed to be brown adipose tissue (BAT) histologically. However, PET-CT has estimated a prevalence of BAT as low as 5% in adult humans, casting doubt on its significance. The true prevalence of BAT is unknown because of the suboptimal sensitivity of standard PET-CT. OBJECTIVE: The objective of the study was to determine whether BAT is present in PET-negative supraclavicular fat. DESIGN: This was a prospective cohort study. SETTING: The study was conducted at a tertiary referral hospital. PATIENTS: Seventeen patients who underwent preoperative PET-CT for staging of head and neck malignancy participated in the study. MAIN OUTCOME: The main outcome was signature BAT gene transcripts and protein in biopsies of supraclavicular fat with sc fat as negative control. RESULTS: PET-CT was positive in three and negative in 14 patients. PET-positive fat harbored multilobulated lipid droplets and stained strongly for uncoupling protein 1 (UCP1). These features are absent in sc fat. By contrast, PET-negative fat contained a predominance of cells with unilobulated lipid droplets, with scattered cells containing multilobulated lipid droplets and variable UCP1 staining. Molecular analyses of fat biopsies showed lower but clear expression of UCP1, NDUFS3 (NADH dehydrogenase (ubiquinone) iron-sulfur protein 3), ß3-adrenoceptor, and PRDM16 (PR domain containing 16) transcripts. CONCLUSIONS: BAT is present in supraclavicular fat, regardless of PET status. BAT is highly prevalent in adult humans, and its abundance determines PET status.

Safety and efficacy of consecutive cycles of granulocyte-colony stimulating factor, and an intracoronary CD133+ cell infusion in patients with chronic refractory ischemic heart disease: the G-CSF in angina patients with IHD to stimulate neovascularization (GAIN I) trial.

BACKGROUND: Preclinical studies suggest granulocyte-colony stimulating factor (G-CSF) holds promise for treating ischemic heart disease; however; its clinical safety and efficacy in this setting remain unclear. We elected to evaluate the safety and efficacy of G-CSF administration in patients with refractory "no-option" ischemic heart disease. METHODS: Twenty patients (18 males, 2 females, mean age 62.4 years) were enrolled and underwent baseline cardiac ischemia assessment (CA) (angina questionnaire, exercise stress test [EST], technetium Tc 99m sestamibi and dobutamine-stress echocardiographic imaging). Patients then received open-label G-CSF commencing at 10 microg/kg SC for 5 days, with an EST on days 4 and 6 (to facilitate myocardial cytokine generation and stem cell trafficking). After 3 months, CA and the same regimen of G-CSF+ESTs were repeated but, in addition, leukapheresis and a randomized double-blinded intracoronary infusion of CD133+ or unselected cells were performed. Final CA occurred 3 months thereafter. RESULTS: There were no deaths, but only 16 patients were permitted to complete the study. Eight events fulfilled prespecified "adverse event" criteria, including 4 troponin I-positive events and 2 episodes of thrombocytopenia. Also, frequent minor troponin I-positive events (troponin I<0.9 microg/L) were observed, which did not meet adverse event criteria. The administration of consecutive cycles of G-CSF resulted in stepwise improvements in anginal frequency, EST performance, and Duke treadmill scores (all P<.005). However, from baseline to final follow-up, technetium Tc 99m sestamibi and dobutamine-stress echocardiographic results were unchanged. CONCLUSIONS: Granulocyte-colony stimulating factor administration was associated with improvement in a range of subjective outcomes. However, adverse events were common, and objective measures of cardiac perfusion/ischemia were unchanged.

Anterior abdominal wall uptake in intrahepatic arterial brachytherapy with yttrium-90 sir spheres for hepatic malignancy.

Patients with primary or secondary liver cancer who are not suitable for surgical resection may be treated with selective internal radiation therapy with yttrium-90. This may cause down staging of the tumor to a resectable size in some patients, and in these and other patients may prolong survival. It delivers a high dose of radiation therapy directly to the tumor, thus minimizing exposure to liver sensitive to radiation. Prior scanning with Tc-99m macroaggregated albumin is performed to assess lung shunting and potential extrahepatic deposition, which can cause significant clinical sequelae. Two patients with hepatic malignancy are presented who demonstrated extrahepatic deposition of Tc-99m macroaggregated albumin in the anterior abdominal wall. This is thought to be related to a patent hepatic falciform ligament artery.

Profound thrombocytopenia related to G-CSF.

Severe thrombocytopenia in association with G-CSF therapy is extremely rare. Here we report a case of profound thrombocytopenia in a 57-year-old male with refractory cardiac ischemia, who received G-CSF during an angiogenesis trial. After 5 days of G-CSF therapy (10 microg/kg/day) the platelet count fell progressively to a nadir of 5x10(9)/L. The patient received steroid, immunoglobulin and platelet support and recovered without sequelae. Subsequent investigations suggested an underlying immune-mediated thrombocytopenia, which we hypothesize was exacerbated by G-CSF therapy.

Reversibility of lipoatrophy in HIV-infected patients 2 years after switching from a thymidine analogue to abacavir: the MITOX Extension Study.

OBJECTIVE: To determine if long-term improvement in HIV lipoatrophy can be attained by substitution of thymidine analogues zidovudine (ZDV) or stavudine (d4T) with abacavir (ABC). DESIGN: Long-term follow-up (104 weeks) of a randomized, open-label study. SETTING: Seventeen ambulatory HIV clinics in Australia and London. SUBJECTS: Patients with HIV lipodystrophy were randomized to switch from a thymidine analogue to ABC, while continuing all other antiretroviral therapy (ABC arm) (n = 42) or continue current therapy (ZDV/d4T arm) (n = 43). INTERVENTION: At week 24, all control patients could switch to ABC. Of the original 111 patients randomized, 85 had long-term follow-up data, with 77 having imaging data available at 104 weeks. MAIN OUTCOME MEASURE: The primary endpoint was time-weighted change in limb fat mass, measured by dual-energy X-ray absorptiometry (DEXA). RESULTS: At week 104, the mean increase in limb fat for the ABC and ZDV/d4T group was 1.26 +/- 2.02 kg and 0.49 +/- 1.38 kg, respectively. The time-weighted change for limb fat was significantly different between the two arms (0.43 kg; P = 0.008). On-treatment analysis demonstrated a trend for increased limb fat in patients in the ABC arm. Visceral fat accumulation, buffalo hump, self-assessed lipodystrophy or the lipodystrophy case definition score (LCDS) did not improve. CONCLUSIONS: In patients with moderate-to-severe lipodystrophy, significant improvements in subcutaneous fat continued over 104 weeks after switching from a thymidine analogue to ABC. Nevertheless, the lipodystrophy syndrome was still evident, indicating additional strategies need evaluating.

Discordance in lumbar spine T-scores and nonstandardization of standard deviations.

Previous studies have demonstrated differences in proximal femur bone mineral density T-scores depending on the reference range used. This subsequently was addressed by the recommended adoption of the National Health and Nutrition Examination Survey III reference range. There is, however, no accepted reference range for interpretation of lumbar spine bone mineral density (BMD), and the use of different reference populations by different manufacturers could result in inconsistencies in diagnosis of osteopenia or osteoporosis. We compared lumbar spine BMD, as well as T- and Z-scores, in 59 women measured using Lunar DPXL and Norland Excel densitometers. BMD measured by the instruments was highly correlated (r = 0.98, p < 0.0001). The instruments however assigned significantly different values when BMD was expressed as T-scores. There were also significant differences in BMD assignments between instruments, when expressed as Z-scores. The observed differences relate to the different young normal mean, and SD employed in calculating the T- and Z scores. To conclude, in the lumbar spine, two commonly used DXA instruments provide comparable absolute values but there are significant differences in derived T-scores due to differences in manufacturer- specific reference ranges. There is a need for standardization of the reference ranges used in the lumbar spine.

Centralized assessment of dual-energy X-ray absorptiometry (DEXA) in multicenter studies of HIV-associated lipodystrophy.

BACKGROUND: The accurate measurement of total body and subcutaneous fat is essential if therapeutic interventions, aimed at preventing or reversing lipodystrophy syndrome, are to be adequately assessed. The aim of this study was to investigate the variability of dual-energy X-ray absorptiometry (DEXA) scans analysis performed at local sites compared to central analysis in a multicenter clinical trial. METHOD: The PIILR study was a multicenter randomized clinical trial in which 80 HIV-infected patients with physician-documented lipodystrophy had serial measurements of body composition performed with Lunar DEXA scans. Scans were analyzed at local sites and then were reanalyzed centrally. RESULTS: DEXA scans from 73 patients who completed 24 weeks study were compared. Greater variation in the locally analyzed results than in the centrally reanalyzed data was noted, with arm, leg, and combined limb fat being most divergent between the local and centralized assessments (ratio of local to central standard deviation was 1.28, 1.31, and 1.35, respectively). The magnitude of this variance was enough to alter statistically relevant differences between study populations. CONCLUSION: Quality assurance is an important issue in the use of DEXA scans to determine body fat composition in multicenter research studies. A central quality assurance site should be incorporated to reduce variability in results.

Abacavir substitution for nucleoside analogs in patients with HIV lipoatrophy: a randomized trial.

CONTEXT: Peripheral lipoatrophy may complicate antiretroviral therapy of human immunodeficiency virus (HIV) infection, often related to duration and type of nucleoside analog therapy, and may have a mitochondrial pathogenesis. No proven therapy exists for lipoatrophy, but abacavir is a nucleoside analog that may be less toxic to mitochondria. OBJECTIVE: To determine if substitution of stavudine or zidovudine with abacavir improves HIV lipoatrophy without affecting control of HIV replication. DESIGN: Randomized, open-label 24-week study. SETTING: Seventeen hospital HIV outpatient clinics and primary care centers in Australia and England, with randomization from June 2000 through January 2001. PARTICIPANTS: A total of 111 adults (109 men) with moderate or severe lipoatrophy who were receiving stavudine (n = 85) or zidovudine (n = 26) and had stable plasma HIV RNA levels below 400 copies/mL and no prior abacavir therapy. INTERVENTION: Patients were randomly assigned to switch from stavudine or zidovudine to abacavir, 300 mg twice per day, while continuing all other antiretroviral therapy (n = 54) or to continue all antiretroviral therapy (n = 57). MAIN OUTCOME MEASURES: The primary end point was limb fat mass, measured by dual-energy x-ray absorptiometry; key secondary end points were plasma HIV RNA levels, adverse events, physician-assessed (via subjective measures) lipodystrophy severity, total and central fat mass, and fasting metabolic (lipid, glycemic, and lactate) levels. RESULTS: There was a significant increase in limb fat in the abacavir group relative to the stavudine/zidovudine group (0.39 vs 0.08 kg; mean difference, 0.31; 95% confidence interval [CI], 0.06-0.57 kg), as well as significant relative increases in subcutaneous thigh (P =.01), arm (P<.001), and abdominal (P =.001) fat areas on computed tomography. Switching had no significant effect on secondary end points, including plasma HIV RNA (for unadjusted comparison between groups at week 24, odds ratio, 1.38; 95% CI, 0.48-3.96). Change in limb fat mass at week 24 did not correlate with change in subjectively determined perceived lipoatrophy severity (r = -0.06; P =.53 by Spearman correlation). Hypersensitivity to abacavir was seen in 5 patients (10%). CONCLUSIONS: In this sample of lipoatrophic HIV-infected adults, switching from stavudine or zidovudine to abacavir for 24 weeks led to significant, albeit modest, objectively measured increases in limb fat. Clinical lipoatrophy, as assessed subjectively, did not resolve, however, and at the rate of increase observed may take years to resolve with use of this strategy. Longer-term follow-up is needed.