Effect of body mass index on the outcomes of patients with upper and lower urinary tract cancers treated by radical surgery: Results from a Canadian multicenter collaboration

ObjectiveTo evaluate the effect of body mass index (BMI) on the outcomes of patients with urinary tract carcinoma treated with radical surgery.Materials and methodsData were collected from 10 Canadian centers on patients who underwent radical cystectomy (RC) (1998–2008) or radical nephroureterectomy (RNU) (1990–2010). Various parameters among subsets of patients (BMI<25, 25≤BMI<30, and BMI≥30 kg/m²) were analyzed. Kaplan-Meier and multivariate analyses were performed to assess the effect of BMI on overall survival, disease-specific survival, and recurrence-free survival (RFS).ResultsAmong the 847 RC and 664 RNU patients, there was no difference in histology, stage, grade, and margin status among the 3 patient subsets undergoing either surgery. However, RC patients with lower BMIs (<25 kg/m²) were significantly older (P = 0.004), had more nodal metastasis (P = 0.03), and trended toward higher stage (P = 0.052). RNU patients with lower BMIs (<25 kg/m²) were significantly older (P = 0.0004) and fewer received adjuvant chemotherapy (P = 0.04) compared with those with BMI≥30 kg/m²; however, there was no difference in tumor location (P = 0.20), stage (P = 0.48), and management of distal ureter among the groups (P = 0.30). On multivariate analysis, BMI was not prognostic for overall survival, disease-specific survival, and RFS in the RC group. However, BMI≥30 kg/m² was associated with more bladder cancer recurrences and worse RFS in the RNU group (HR = 1.588; 95% CI: 1.148–2.196; P = 0.0052).ConclusionsIncreased BMI did not influence survival among RC patients. BMI≥30 kg/m² is associated with worse bladder cancer recurrences among RNU patients; whether this is related to difficulty in obtaining adequate bladder cuff in patients with obesity requires further evaluation.     

Arterial “inflammaging” drives vascular calcification in children on dialysis

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Loss of APKC expression independently predicts tumor recurrence in superficial bladder cancers

ObjectivesEpithelial-mesenchymal transition (EMT) is known to play an important role in the development of tumor invasion and progression in tumors of epithelial origin. Our aim was to investigate the role of tight junction proteins, Par3/Par6/atypical protein kinase C (APKC), Discs large (Dlg), and Scribble in human bladder pathogenesis.MethodsWe evaluated levels of APKC, Dlg, and Scribble in 92 superficial bladder tumors using tissue microarrays and immunohistochemistry, and correlated expression with pathologic variables and clinical outcomes.ResultsThere was a slight apparent enrichment in strong vs. weak staining for APKC (54.9% vs. 45.1%), Dlg (65.7% vs. 34.3%), and a marked enrichment for Scribble (75% vs. 25%) in the superficial bladder tumors. Univariate analysis determined that both tumor focality and APKC expression were significantly associated with tumor recurrence (P < 0.05). Multivariate analysis using the Cox's proportional hazards model revealed that only APKC (P = 0.025) as well as tumor focality (P = 0.018) were independent and significant prognostic factors for tumor recurrence in all patients. We found that no immunohistochemical staining of any of the cell polarity proteins significantly predicted for tumor progression on either univariate or multivariate analysis.ConclusionsLoss of APKC expression in superficial bladder tumors is a strong predictor of tumor recurrence.     

MRI detection of myocardial perfusion defects due to coronary artery stenosis with MS-325

PURPOSE: To assess the value of an intravascular, albumin-targeted contrast agent, MS-325, in visualizing myocardial ischemia with magnetic resonance imaging (MRI). MATERIALS and METHODS: Left anterior descending coronary artery (LAD) stenosis was created in 19 pigs using a closed-chest modified angioplasty technique. Myocardial ischemia was detected by first-pass, contrast-enhanced MRI at peak dipyridamole stress and was compared to Technetium-99m (Tc-99m) sestamibi single photon emission computed tomography (SPECT). Regional coronary blood flow was determined using microspheres. RESULTS: Inducible myocardial ischemia with >40% reduction in stress myocardial blood flow was created in eight animals. An MRI defect, classified as > or=75% reduction in peak myocardial signal intensity in the affected territory, was detected in 92.3% of these animals. In the presence of mild coronary stenosis, there was uniform enhancement with MRI and tracer uptake by SPECT. Concordance of MRI and SPECT for detecting perfusion defects was 85%. CONCLUSION: The pattern of prolonged and persistent MR hypoenhancement of the ischemic myocardial bed using MS-325, which is retained primarily in the vascular bed due to its albumin-binding properties, facilitates the detection of myocardial perfusion defects.     

Myocardial contractile reserve and perfusion defect severity with rest and stress dobutamine (99m)Tc-sestamibi SPECT in canine stunning and subendocardial infarction.

Myocardial contractile reserve and resting perfusion scintigraphy provide independent information to assess myocardial viability. The purpose of this study was to simultaneously evaluate both with (99m)Tc-sestamibi SPECT and low-dose dobutamine in canine stunning and subendocardial infarction (SEMI). METHODS: Eighteen dogs were included in the study: 7 normal, 7 stunned, and 4 with SEMI. Closed-chest stunning and SEMI were produced by angioplasty balloon occlusion of the left anterior descending artery (20 and 90 min, respectively). Subsequent radiolabeled mircospheres confirmed reflow, and (99m)Tc-sestamibi was then administered at rest. Gated SPECT and MRI tagging were performed at rest and during low-dose dobutamine infusion (5 microg/kg/min). SPECT systolic wall thickening index (SWI) and MRI radial strain quantified myocardial contraction. Postmortem 2,3,5-triphenyltetrazolium chloride staining quantified SEMI. RESULTS: Defect severity by SPECT in the anterior wall was mild and was not statistically different for the stunned versus SEMI groups (P = not significant). At rest, anterior wall SPECT SWI was significantly higher in the normal versus stunned groups (21.1 +/- 3.1 vs. 10.1 +/- 9.0; P = 0.0002) and the normal versus SEMI groups (21.1 +/- 3.1 vs. 2.6 +/- 6.0; P = 0.000002). With low-dose dobutamine, SWI increased significantly compared with rest for the stunned group (29.1 +/- 10.4 vs. 10.1 +/- 9.0; P = 0.000007) but did not increase significantly for the SEMI group (11.0 +/- 11.3 vs. 2.6 +/- 6.0; P = 0.09); SWI during low-dose dobutamine infusion for the stunned group was comparable to that for the normal group (29.1 +/- 10.4 vs. 28.2 +/- 7.0; P = 0.80). SWI also showed correlation with MRI radial strain (r = 0.42; P = 0.00015). CONCLUSION: Defect severity for stunned myocardium and SEMI was mild and was not significantly different. Contractile reserve was significantly different in stunned myocardium and SEMI. (99m)Tc-Sestamibi SPECT at rest and with low-dose dobutamine is a promising new technique to simultaneously assess myocardial perfusion and contractile reserve.     

Superior Long-Term Results of Simultaneous Pancreas–Kidney Transplantation from Pediatric Donors

The shortage of cadaveric donors for simultaneous pancreas-kidney transplantation has prompted the use of cadaveric organs from pediatric donors. The long-term outcome and its impact on overall long-term survival are unknown. A total of 680 recipients receiving cadaver Simultaneous pancreas-kidney (SPK) transplantation from pediatric and adult donors between July 1986 and September 2001 were analyzed and compared. Ten-year kidney and pancreas graft survival for SPK transplantation from donors aged <18 years (n = 142) were 80% and 72%, respectively, compared to 61% pancreas and kidney graft survival from donors > or =18 years of age (n = 538; p = 0.03 and 0.05, respectively). Five years post-transplant, blood glucose, HbA1c and creatinine clearance were significantly better in recipients from pediatric donors (85.3 +/- 13 mg/dL, 5.5 +/- 3.5% and 65.6 +/- 16 mL/min, respectively), compared to recipients from adult donors (95.1 +/- 29 mg/dL, 5.9 +/- 3.5% and 58.3 +/- 17 mL/min; p = 0.001, 0.01 and 0.002, respectively). Causes of graft failure for kidney and pancreas transplants were similar between the two groups. No statistically significant difference was observed in patient survival between recipients from pediatric donors compared to adult donors (85% vs. 76%, p = 0.29). When recipients of SPK from pediatric donors were stratified according to age (3-11 years and 12-17 years) and compared, no difference in kidney or pancreas graft survival was observed (kidney 76.4% vs. 81.3%, p = 0.15; pancreas 75% vs. 76%, p = 0.10, respectively). Pediatric donors represent a valuable source of organs, providing excellent short- and long-term outcomes. Wide utilization of pediatric organs will substantially increase the donor pool.     

Rapid simultaneous measurement of rat alpha- and thyrotropin (TSH) beta-subunit messenger ribonucleic acids (mRNAs) by solution hybridization: regulation of TSH subunit mRNAs by thyroid hormones

Using a sensitive method for the simultaneous measurement of TSH subunit mRNAs, we have investigated their hormonal regulation in the pituitary glands of normal and hypothyroid rats. Oligodeoxyribonucleotides (probes) complementary to coding regions of rat alpha- and TSH beta-subunit mRNAs were synthesized. These probes were 5'-end labeled with gamma-[32P] ATP and hybridized with total pituitary RNA obtained from T3-treated and untreated normal and hypothyroid rats. The samples were then exposed to S1 nuclease to digest single stranded nucleic acids. Specific hybridization of probes to the TSH subunit mRNAs would yield double stranded structures resistant to this enzyme. Measurement of the amount of undigested probes by denaturing polyacrylamide gel electrophoresis, autoradiography, and densitometry permits quantification of these mRNAs. Both rat alpha and TSH beta mRNAs were detected with as little as 0.1 microgram total pituitary RNA, representing a more than 10-fold increase in sensitivity compared to a standard RNA blot hybridization assay. Thyroidectomy resulted in a 3- to 5-fold increase, whereas T3 treatment caused a significant decrease in the subunit mRNAs in both normal and hypothyroid animals. However, in all treatment groups, the TSH beta mRNA was affected to a greater extent than the alpha mRNA by the changes in thyroid status. The ratio of alpha- to beta-subunit mRNAs was decreased with hypothyroidism and increased with T3 treatment. This assay allows simultaneous quantification of multiple mRNAs from a single pituitary gland within 48 h and should facilitate studies of the regulation of mRNAs encoding TSH subunits specifically and other pituitary proteins in general.     

Pitfalls and Important Issues in Testing Reliability Using Intraclass Correlation Coefficients in Orthopaedic Research

Background

Intra-class correlation coefficients (ICCs) provide a statistical means of testing the reliability. However, their interpretation is not well documented in the orthopedic field. The purpose of this study was to investigate the use of ICCs in the orthopedic literature and to demonstrate pitfalls regarding their use.

Methods

First, orthopedic articles that used ICCs were retrieved from the Pubmed database, and journal demography, ICC models and concurrent statistics used were evaluated. Second, reliability test was performed on three common physical examinations in cerebral palsy, namely, the Thomas test, the Staheli test, and popliteal angle measurement. Thirty patients were assessed by three orthopedic surgeons to explore the statistical methods testing reliability. Third, the factors affecting the ICC values were examined by simulating the data sets based on the physical examination data where the ranges, slopes, and interobserver variability were modified.

Results

Of the 92 orthopedic articles identified, 58 articles (63%) did not clarify the ICC model used, and only 5 articles (5%) described all models, types, and measures. In reliability testing, although the popliteal angle showed a larger mean absolute difference than the Thomas test and the Staheli test, the ICC of popliteal angle was higher, which was believed to be contrary to the context of measurement. In addition, the ICC values were affected by the model, type, and measures used. In simulated data sets, the ICC showed higher values when the range of data sets were larger, the slopes of the data sets were parallel, and the interobserver variability was smaller.

Conclusions

Care should be taken when interpreting the absolute ICC values, i.e., a higher ICC does not necessarily mean less variability because the ICC values can also be affected by various factors. The authors recommend that researchers clarify ICC models used and ICC values are interpreted in the context of measurement.     

The effects of age, physical activity level, and body anthropometry on calcaneal speed of sound value in men

Summary

The influences of age, physical activity, and body anthropometry on calcaneal speed of sound are different among young adults, middle-aged, and elderly men.

Introduction

Quantitative ultrasound assessment of bone health status is much needed for developing countries in the screening of osteoporosis, but further studies on the factors that influence the quantitative ultrasound indices are required.

Objectives

The present study examined the influence of age, lifestyle factors, and body anthropometry on calcaneal speed of sound (SOS) in a group of Malaysian men of diverse age range.

Subjects and methods

A cross-sectional study was conducted, and data from 687 eligible males were used for analysis. They answered a detailed questionnaire on their physical activity status, and their anthropometric measurements were taken. Their calcaneal SOS values were evaluated using the CM-200 sonometer (Furuno, Nishinomiya City, Japan).

Results

Subjects with higher body mass index (BMI) had higher calcaneal SOS values albeit significant difference was only found in the elderly subjects (p?<?0.05). Sedentary subjects had lower calcaneal SOS values than physically active subjects, but significant difference was only found in the middle-aged subjects (p?<?0.05). Calcaneal SOS was significantly (p?<?0.05) correlated with age in young men; height, BMI, and physical activity score in middle-aged men; height and physical activity score in elderly men; and age and physical activity score for overall subjects. In a multivariate regression model, significant (p?<?0.05) predictors for calcaneal SOS included age for young men; physical activity, BMI, body fat percentage, and height for middle-aged men; height for elderly men; and age, height, physical activity, weight, and body fat percentage for overall subjects.

Conclusion

Age, body anthropometry, and physical activity level have significant effects on the calcaneal SOS value in men.