Fibrous Dysplasia With Atypical Bilateral Upper Extremity Pattern.

ABSTRACT: Fibrous dysplasia (FD) typically presents unilaterally in the lower limbs, or in the skull, mandible, or pelvis. Bilateral presentation is rarely reported. Most cases are diagnosed in the teens with 75% of patients diagnosed before the age of 30 years. In this case, a 63-year-old woman with suspected diagnosis of malignancy was referred to 99mTc-MDP scan and found to have polyostotic FD in bilateral upper extremities. Nuclear medicine can play an important role in diagnosing FD cases with atypical presentation and help risk stratification for more aggressive transformation.

Waist-To-Hip Ratio Predicts Abnormal Overnight Oximetry in Men Independent of Body Mass Index.

Background: Ambulatory overnight oximetry (OXI) has emerged as a cost-effective initial test for sleep disordered breathing. Obesity is closely associated with obstructive sleep apnea (OSA); however, whether body mass index (BMI) or waist-to-hip ratio (WHR) predicts abnormal overnight OXI remains unknown. Methods: We performed a retrospective cross-sectional study of 393 men seen in the Executive Health Program at Mayo Clinic in Rochester, Minnesota who underwent ambulatory overnight OXI ordered by preventive medicine physicians between January 1, 2004 through December 31, 2010. We compared participant/spouse-reported symptoms (sleepiness, snoring), physician indications for OXI (obesity, fatigue), Epworth Sleepiness Scale scores, anthropomorphic measurements (WHR, BMI), and comorbid medical conditions (hypertension, diabetes) with OXI results. Results: 295 of the 393 men who completed OXI had abnormal results. During multivariate analysis, the strongest independent predictor of abnormal OXI for men was WHR (≥1.0, OR = 5.59) followed by BMI (≥30.0 kg/m2, OR = 2.75), age (≥55 yrs, OR = 2.06), and the presence of snoring (OR = 1.91, P < 0.05 for all). A strong association was observed between WHR and abnormal OXI in obese (BMI ≥ 30.0 kg/m2, OR = 6.28) and non-obese (BMI < 29.9 kg/m2, OR = 6.42, P < 0.01 for both) men. Furthermore, 88 men with abnormal OXI underwent polysomnography with 91% being subsequently diagnosed with OSA. Conclusions: In ambulatory, predominantly middle-aged men undergoing preventive services evaluation many physician indications for OXI were not predictors of abnormal results; however, WHR strongly predicted abnormal OXI in obese and non-obese men. As such, we suggest middle-aged men who snore and have a WHR ≥1.0 should be directly referred to a sleep clinic for polysomnography.

Semiquantitative Parameters in PSMA-Targeted PET Imaging with [18F]DCFPyL: Intrapatient and Interpatient Variability of Normal Organ Uptake.

PURPOSE: Prostate-specific membrane antigen (PSMA)-targeted positron emission tomography (PET) imaging has impacted the management of patients with prostate cancer (PCa) in many parts of the world. PSMA-targeted endoradiotherapies are also being increasingly utilized and for these applications, the radiopharmaceutical distribution in normal organs is particularly important because it may limit the dose that can be delivered to tumors. In this study, we measured both interpatient and intrapatient variability of [18F]DCFPyL uptake in the most relevant normal organs. PROCEDURES: Baseline and 6-month follow-up PSMA-targeted [18F]DCFPyL PET/computed tomography (CT) scans from 39 patients with PCa were reviewed. Volumes of interest were manually drawn using the best visual approximation of the organ edge for both lacrimal glands, all four major salivary glands, the liver, the spleen, and both kidneys for all patients. The average SUVmean, the COVs, and intraclass correlation coefficients (ICCs) across scans were calculated. Bland-Altman analyses were performed for all organs to derive repeatability coefficients (RCs). RESULTS: The liver demonstrated the lowest interpatient variability (13.0 and 16.6 % at baseline and follow-up, respectively), while the spleen demonstrated the largest interpatient variability (44.6 and 51.0 % at baseline and follow-up, respectively). The lowest intrapatient variability was found in the spleen (ICC 0.86) while the highest intrapatient variability was in the kidneys (ICCs 0.40-0.50). Bland-Altman analyses showed 95 % repeatability coefficients for mean uptake > 40 % for multiple organs and were highest for the lacrimal glands, kidneys, and spleen. CONCLUSIONS: Normal organs demonstrate significant variability in uptake of the PSMA-targeted radiotracer [18F]DCFPyL. Depending on the organ, different contributions of interpatient and intrapatient factors affect the intrinsic variability. The RCs also vary significantly among the different organs were highest for the lacrimal glands, kidneys, and spleen. These findings may have important implications for the design of clinical protocols and personalized dosimetry for PSMA-targeted endoradiotherapies.

The Scintigraphic Drooping Lily Sign.

The "drooping lily" sign is identified on intravenous urography or voiding cystourethrography in patients with a duplicated renal collecting system and refers to inferolateral displacement of a functioning lower pole moiety by an obstructed upper pole collecting system. In this case, a 2-month-old girl with a prenatal diagnosis of hydronephrosis was found to have a "scintigraphic drooping lily" sign on Tc-dimercaptosuccinic acid renal scan. Evaluation with ultrasound and voiding cystourethrography confirmed a duplicated collecting system and obstructed upper pole moiety. Correlation with anatomic imaging can help avoid mistaking the scintigraphic "drooped" lower pole for an inferiorly positioned normal kidney.

Ethnic differences in all-cause and cardiovascular mortality by physical activity levels among older adults in the US.

AIMS: This study sought to determine whether the association between varying levels of physical activity (PA) and all-cause and cardiovascular mortality differ by race/ethnicity in older adults. METHODS: The sample comprised 2520 women and 2398 men drawn from National Health and Nutrition Examination Survey III (1988-1994) aged ≥ 60 years. We used the metabolic equivalent (MET) of self-reported PA levels to define activity groups (inactive: those who did not report any PA; active: those who reported 3-6 METs for ≥5 times/week or >6 METs, ≥3 times/week; insufficiently active: those meeting neither criteria). Racial/Ethnic differences were modeled using proportional hazard regression (HR) adjusting for age, education, smoking, diabetes, and hypertension. RESULTS: Among those classified as inactive, Non-Hispanic Blacks (NHB) (HR: 0.72, 95% CI: 0.58-0.90) and Mexican Americans (HR: 0.59, 95%CI: 0.45-0.78) had a lower risk of all-cause mortality when compared to non-Hispanic Whites (NHW). Among those classified as insufficiently active, Mexican Americans (HR: 0.63, 95% CI: 0.51-0.77), but not NHB (HR: 0.81, (95% CI: 0.64-1.02) had a lower risk of all-cause mortality when compared to NHWs Similar results were observed for cardiovascular mortality. CONCLUSION: Overall, PA in the elderly (either insufficient or active) is associated with a lower all-cause mortality across all race/ethnic groups as compared to NHW. Further investigation, including studies with larger sample, is needed to address the health consequences of varying degrees of PA in ethnically diverse populations.

Normal-Weight Central Obesity: Implications for Total and Cardiovascular Mortality.

BACKGROUND: The relationship between central obesity and survival in community-dwelling adults with normal body mass index (BMI) is not well-known. OBJECTIVE: To examine total and cardiovascular mortality risks associated with central obesity and normal BMI. DESIGN: Stratified multistage probability design. SETTING: NHANES III (Third National Health and Nutrition Examination Survey). PARTICIPANTS: 15,184 adults (52.3% women) aged 18 to 90 years. MEASUREMENTS: Multivariable Cox proportional hazards models were used to evaluate the relationship of obesity patterns defined by BMI and waist-to-hip ratio (WHR) and total and cardiovascular mortality risk after adjustment for confounding factors. RESULTS: Persons with normal-weight central obesity had the worst long-term survival. For example, a man with a normal BMI (22 kg/m2) and central obesity had greater total mortality risk than one with similar BMI but no central obesity (hazard ratio [HR], 1.87 [95% CI, 1.53 to 2.29]), and this man had twice the mortality risk of participants who were overweight or obese according to BMI only (HR, 2.24 [CI, 1.52 to 3.32] and 2.42 [CI, 1.30 to 4.53], respectively). Women with normal-weight central obesity also had a higher mortality risk than those with similar BMI but no central obesity (HR, 1.48 [CI, 1.35 to 1.62]) and those who were obese according to BMI only (HR, 1.32 [CI, 1.15 to 1.51]). Expected survival estimates were consistently lower for those with central obesity when age and BMI were controlled for. LIMITATIONS: Body fat distribution was assessed based on anthropometric indicators alone. Information on comorbidities was collected by self-report. CONCLUSION: Normal-weight central obesity defined by WHR is associated with higher mortality than BMI-defined obesity, particularly in the absence of central fat distribution. PRIMARY FUNDING SOURCE: National Institutes of Health, American Heart Association, European Regional Development Fund, and Czech Ministry of Health.

Leptin, adiposity, and mortality: results from the National Health and Nutrition Examination Survey III, 1988 to 1994.

OBJECTIVE: To determine whether leptin is related to all-cause and cardiovascular (CV) mortality in older adults. PATIENTS AND METHODS: Participants 60 years and older with plasma leptin level measurements from the National Health and Nutrition Examination Survey III (1988-1994) and mortality data linked to the National Death Index were included. We created sex-specific tertiles of leptin (men: 4.2-7.7 µg/L; women: 11.5-21.4 µg/L) to identify the effect of leptin on all-cause and CV mortality. We also determined whether leptin predicted mortality in patients with obesity. We classified obesity using 4 possible definitions: body mass index 30 kg/m(2) or greater; body fat 25% or more in men and 35% or more in women; waist circumference 102 cm or greater in men and 88 cm or greater in women; and waist-hip ratio 0.85 or higher in women and 0.95 or higher in men. Sex-specific proportional hazard models were used to assess the effect of leptin on all-cause and CV mortality. RESULTS: Of 1794 participants, 51.6% were women; the mean age was 70.3±0.4 years, and the follow-up period was 12.5 years with 994 deaths (469 were CV deaths). All-cause mortality in the highest leptin tertile was significant neither in men (hazard ratio [HR], 1.23; 95% CI, 0.93-1.63) nor in women (HR, 0.97; 95% CI, 0.68-1.40). CV mortality was the highest in the highest leptin tertile in men (HR, 1.69; 95% CI, 1.06-2.70) but not in women (HR, 1.21; 95% CI, 0.73-1.98). Evaluating the effect of leptin in subgroups of different obesity definitions, we found that high leptin levels as predict CV mortality in men as measured by waist circumference or body fat. CONCLUSION: Elevated leptin level is predictive of CV mortality only in men. Leptin may provide additional mortality discrimination in obese men.

Decreased exercise capacity and sleep-disordered breathing in patients with hypertrophic cardiomyopathy.

BACKGROUND: Mechanisms of decreased exercise capacity in patients with hypertrophic cardiomyopathy (HCM) are not well understood. Sleep-disordered breathing (SDB) is a highly prevalent but treatable disorder in patients with HCM. The role of comorbid SDB in the attenuated exercise capacity in HCM has not been studied previously. METHODS: Overnight oximetry, cardiopulmonary exercise testing, and echocardiographic studies were performed in consecutive patients with HCM seen at the Mayo Clinic. SDB was considered present if the oxygen desaturation index (number of ≥ 4% desaturations/h) was ≥ 10. Peak oxygen consumption (VO2 peak) (the most reproducible and prognostic measure of cardiovascular fitness) was then correlated with the presence and severity of SDB. RESULTS: A total of 198 patients with HCM were studied (age, 53 ± 16 years; 122 men), of whom 32% met the criteria for the SDB diagnosis. Patients with SDB had decreased VO2 peak compared with those without SDB (16 mL O2/kg/min vs 21 mL O2/kg/min, P < .001). SDB remained significantly associated with VO2 peak after accounting for confounding clinical variables (P < .001) including age, sex, BMI, atrial fibrillation, and coronary artery disease. CONCLUSIONS: In patients with HCM, the presence of SDB is associated with decreased VO2 peak. SDB may represent an important and potentially modifiable contributor to impaired exercise tolerance in this unique population.

Normal weight obesity and functional outcomes in older adults.

BACKGROUND: Obesity defined by body mass index (BMI) is associated with higher levels of functional impairment. However, BMI strata misrepresent true adiposity, particularly in those with a normal BMI but elevated body fat (BF%) (normal weight obesity [NWO]) whom are at higher metabolic and mortality risk. Whether this subset of patients is associated with worsening functional outcomes is unclear. METHODS: Subjects aged ≥60 years with a BMI ≥18.5 kg/m(2) from NHANES III (1988-1994) were included. We created sex-specific tertiles of BF%. Data on physical limitations (PL), instrumental (IADL) and basic activities of daily living (BADL) were obtained. The analysis focused on the association between NWO and these outcomes. Comparative rates among each tertile using logistic regression (referent=lowest tertile) were assessed, incrementally adding co-variates. RESULTS: Of the 4484 subjects aged ≥60 years, 1528 had a normal BMI, and the range of the mean age of tertiles was 69.9-71.2 years. Lean mass was lowest in the elevated BF% group than in the middle or low tertiles (42.6 vs 44.9 vs 45.8; p<0.001). Those with NWO had higher PL risk than the referent in females only in our adjusted model (males OR 1.18 [0.63-2.21]; females OR 1.90 [1.04-3.48]) but not after incorporating lean mass (males OR 1.11[0.56-2.20]; females (1.73 [0.92-3.25]). Neither sex with high BF% had higher IADL risk than the corresponding tertiles (males OR 0.67 [0.35-1.33]; females OR 1.20 [0.74-1.93]). NWO was protective in males only (OR 0.28 [0.10-0.83]) but not in females (OR 0.64 [0.40-1.03]). CONCLUSIONS: NWO is associated with increased physical impairment in older adults in females only, highlighting the importance of recognizing the association of obesity with disability in elders.

Normal weight obesity and mortality in United States subjects ≥60 years of age (from the Third National Health and Nutrition Examination Survey).

Current body mass index (BMI) strata likely misrepresent the accuracy of true adiposity in older adults. Subjects with normal BMI with elevated body fat may metabolically have higher cardiovascular and overall mortality than previously suspected. We identified 4,489 subjects aged ≥60 years (BMI = 18.5 to 25 kg/m(2)) with anthropometric and bioelectrical impedance measurements from the National Health and Nutrition Examination Surveys III (1988 to 1994) and mortality data linked to the National Death Index. Normal weight obesity (NWO) was classified in 2 ways: creation of tertiles with highest percentage of body fat and body fat percent cutoffs (men >25% and women >35%). We compared overall and cardiovascular mortality rates, models adjusted for age, gender, smoking, race, diabetes, and BMI. The final sample included 1,528 subjects, mean age was 70 years, median (interquartile range) follow-up was 12.9 years (range 7.5 to 15.3) with 902 deaths (46.5% cardiovascular). Prevalence of NWO was 27.9% and 21.4% in men and 20.4% and 31.3% in women using tertiles and cutoffs, respectively. Subjects with NWO had higher rates of abnormal cardiovascular risk factors. Lean mass decreased, whereas leptin increased with increasing tertile. There were no gender-specific differences in overall mortality. Short-term mortality (<140 person-months) was higher in women, whereas long-term mortality (>140 person-months) was higher in men. We highlight the importance of considering body fat in gender-specific risk stratification in older adults with normal weight. In conclusion, NWO in older adults is associated with cardiometabolic dysregulation and is a risk for cardiovascular mortality independent of BMI and central fat distribution.

Differential bone marrow homing capacity of VLA-4 and CD38 high expressing chronic lymphocytic leukemia cells.

BACKGROUND: VLA-4 and CD38 predict a poor clinical outcome in chronic lymphocytic leukemia (CLL). We used CLL samples with discordant VLA-4/CD38 risk to address their individual roles in human bone marrow infiltration (BM), CLL cell homing to murine BM, and in supportive CLL cell-stromal cell interactions. METHODS: VLA-4, CD38, and Ki-67 expression was measured in CLL cells from peripheral blood (PB) and bone marrow (BM) aspirates. CLL BM infiltration rates, routinely determined by Pathology, were correlated to VLA-4 and CD38 expression. Short-term homing capacity of CLL cells was evaluated by adoptive transfer experiments. CLL cell viability and adhesion in stromal cell co-culture was determined. RESULTS: About 20% of CLL samples in our cohort displayed discordant VLA-4 and CD38 risk, with either high VLA-4 and low CD38 risk or vice versa. Using particularly such samples, we observed that VLA-4, and not CD38, was responsible for recirculation of CLL cells to murine BM. Human BM infiltration was also significantly higher in patients with high VLA-4 risk but not high CD38 risk. However, both molecules acted as independent prognostic markers. While both VLA-4 and CD38 expression were increased in BM-derived CLL cells, and VLA-4+ and CD38+ subpopulations showed enriched Ki-67 expression, VLA-4 did not contribute to CLL cell protection by stromal cells in vitro. CONCLUSIONS: Our data argue for a prominent role of VLA-4 but not CD38 expression in the homing of CLL cells to BM niches and in human BM infiltration, but only a limited role in their protection by stromal cells.

The 25-year cumulative incidence of lower extremity amputations in people with type 1 diabetes.

OBJECTIVE: To examine the 25-year cumulative incidence of lower-extremity amputation (LEA) in people with type 1 diabetes. RESEARCH DESIGN AND METHODS: Cumulative incidence of LEA was ascertained in Wisconsin Epidemiologic Study of Diabetic Retinopathy participants (n = 943) using the Kaplan-Meier approach accounting for competing risk of death. Relationships of baseline characteristics with incidence of LEA were explored using a proportional hazards approach with discrete linear regression modeling. RESULTS: The overall 25-year incidence of LEA was 10.1%. In multivariate analyses (results reported as odds ratio; 95% CI), being male (3.90; 2.29-6.65), heavy smoking (2.07; 1.11-3.85), having hypertension (3.36; 1.91-5.93), diabetic retinopathy (2.62; 1.13-6.09), neuropathy (1.68; 1.02-2.76), and higher HbA(1c) (per 1% 1.40; 1.24-1.58) were independently associated with the incidence of LEA. CONCLUSIONS: Our results show a high 25-year incidence of LEA and suggest that glycemic control and blood pressure control and preventing heavy smoking may result in reduction in its incidence.

Serum cystatin C and the incidence of hypertension in type 1 diabetes mellitus.

BACKGROUND: Serum cystatin has been shown to be associated with hypertension in the general population. Little is known on the relationship of serum cystatin C with the long-term hypertension incidence in persons with diabetes. We examined the association of serum cystatin C with the incidence of hypertension over a 15-year period in people with type 1 diabetes mellitus. METHODS: The 15-year cumulative incidence of hypertension was measured in Wisconsin Epidemiologic Study of Diabetic Retinopathy participants. Hypertension was defined as a systolic blood pressure (BP) of ≥140 mm Hg and/or a diastolic BP of ≥90 mm Hg and/or history of use of antihypertensive treatment. The relation of cystatin C and other risk factors to hypertension incidence was determined with generalized linear modeling with the complementary log-log link function. RESULTS: After controlling for age, gender, diabetes duration, body mass index (BMI), glycosylated hemoglobin, and baseline systolic and diastolic BP, the baseline serum cystatin C was associated with the 15-year cumulative incidence of hypertension (hazard ratio (HR) per mg/l of cystatin C: 3.43, and 95% confidence interval: 1.36, 8.63). CONCLUSIONS: These findings show a relationship of serum cystatin C with the incidence of hypertension in type 1 diabetes mellitus. The underlying biological processes remain to be determined.

Novel risk factors in long-term hypertension incidence in type 1 diabetes mellitus.

BACKGROUND: Data from longitudinal studies suggest that biomarkers of inflammation and endothelial dysfunction are associated with development of hypertension. None of these studies have examined the association of these markers with hypertension risk in persons with diabetes. We examined the associations of inflammatory and endothelial dysfunction markers with long-term hypertension incidence in persons with type 1 diabetes mellitus. METHODS: The 15-year cumulative incidence of hypertension was measured in Wisconsin Epidemiologic Study of Diabetic Retinopathy participants (n = 795). Hypertension was defined as a systolic blood pressure > or =140 mm Hg and/or a diastolic blood pressure > or =90 mm Hg and/or history of current antihypertensive treatment. We measured serum high-sensitivity C-reactive protein, interleukin-6, tumor necrosis factor-alpha, soluble vascular cell adhesion molecule-1 (sVCAM-1), soluble intercellular adhesion molecule-1, and serum total homocysteine as "novel" markers of hypertension development. The relation of risk factors to hypertension incidence was determined using a proportional hazards approach with discrete linear logistic regression modeling. RESULTS: After controlling for age, gender, diabetes duration, body mass index, glycosylated hemoglobin, baseline systolic and diastolic blood pressure, proteinuria, and chronic kidney disease status, sVCAM-1 was significantly related to higher odds of developing incident hypertension (odds ratio per log sVCAM-1 1.95, 95% CI 1.01-3.74). None of the other markers of inflammation and endothelial dysfunction were related to incident hypertension in the cohort. CONCLUSIONS: Our data showed that sVCAM-1 as a marker of endothelial dysfunction was the strongest predictor of hypertension risk in individuals with type 1 diabetes. This association was independent of the presence of diabetic nephropathy.

Inflammatory and endothelial dysfunction markers and proteinuria in persons with type 1 diabetes mellitus.

OBJECTIVE: We examined the relationship of inflammatory and endothelial dysfunction markers with the prevalence and incidence of gross proteinuria (GP) in persons with type 1 diabetes mellitus. DESIGN: A longitudinal population-based cohort of persons with type 1 diabetes mellitus was followed from 1990-1992 through 2005-2007. METHODS: Prevalence and 15-year cumulative incidence of GP were defined as outcome variables. Serum high-sensitivity C-reactive protein (hsCRP), interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-alpha), soluble vascular cell adhesion molecule-1 (VCAM-1), soluble intercellular adhesion molecule-1, and serum total homocysteine were measured. Multivariate logistic and discrete linear logistic regression modeling was used for data analysis. RESULTS: After controlling for duration of diabetes and other confounding factors, TNF-alpha (odds ratio (OR) 3.64; 95% confidence interval (CI) 2.33, 5.70), IL-6 (OR 1.41; 95% CI 1.06, 1.88), VCAM-1 (OR 13.35; 95% CI 5.39, 33.07), and homocysteine (OR 2.98; 95% CI 1.73, 5.16) were associated with prevalent proteinuria. Only hsCRP (OR 1.47; 95% CI 1.02, 2.11) was associated with incident proteinuria. CONCLUSIONS: These findings suggest a role of inflammation and endothelial dysfunction as markers and contributors of the development of diabetic nephropathy in persons with type 1 diabetes mellitus.

Comparison of functional status after coronary artery bypass grafting in patients with and without diabetes mellitus.

Although previous studies have shown increased risk of morbidity and mortality in patients with diabetes mellitus (DM) who undergo coronary artery bypass grafting (CABG), data are conflicting on whether the gains in physical function and mental health after CABG achieved by patients with DM are similar to, or less than, those achieved by patients without DM. We compared the gains in physical function and mental health at 6 months after CABG surgery between 696 consecutive patients with DM and 376 without DM who underwent their first CABG from February 1999 to February 2001. Physical function and mental health were measured using the Short Form 36-item Health Survey. From the baseline and follow-up Short Form 36-item Health Survey data, the physical and mental component scales were derived. At 6 months, the patients with and without DM had significant improvement in physical function and mental health, but those without DM had improved significantly more than those with DM with respect to physical functioning. After adjusting for baseline characteristics, a lower proportion of patients with DM had experienced improvement (an increase of > or = 5 points) in the physical component scale score compared with those without DM (45.0% vs 58.0.%, RR = 0.78, p = 0.002). Moreover, a higher proportion of patients with DM experienced a decrease in the physical component scale score compared with those without DM (14.9% vs 7.8%, RR = 1.91, p = 0.006). In contrast, no significant differences were found in the mental component scale score changes by DM status. In conclusion, CABG is associated with lower gains in physical function in those with DM than in those without DM. Special attention should be paid to the physical function of patients with DM after CABG, and any barriers to functional recovery in this group should be promptly identified and addressed.