The prevalence of hematologic and metabolic abnormalities during chronic kidney disease stages in different ethnic groups

We conducted an observational cross-sectional study to determine if the prevalence of hematologic and metabolic abnormalities in chronic kidney disease (CKD) varied in different ethnic groups. We used a CKD provincial database where a complete data set at the time of registration was available as well as an estimated glomerular filtration rate (eGFR), which showed using the abbreviated MDRD formula that the patients had CKD of stages 3-5. We included patients with self-reported race of Caucasian, Oriental Asian, or South Asian. Primary outcomes were the prevalence of at least one of the following: anemia, hypocalcemia, hyperphosphatemia, hyperparathyroidism, hypoalbuminemia, and three or more laboratory abnormalities. All definitions were consistent with K/DOQI guidelines. When compared with Caucasians, Oriental Asians and South Asians had a higher prevalence of many of the metabolic abnormalities during most stages of CKD and were more likely to have any abnormality at all levels of eGFR. The prevalence of three or more laboratory abnormalities was higher in Oriental Asians at all stages and in South Asians at some levels of eGFR. These results were unchanged or exaggerated when controlled for age, gender, diabetes, and a primary diagnosis of renal disease. Hence, it appears that South Asians and Oriental Asians have more laboratory abnormalities compared with Caucasians at most levels of eGFR.     

Examining bone surfaces across puberty: a 20-month pQCT trial.

This follow-up study assessed sex differences in cortical bone growth at the tibial midshaft across puberty. In both sexes, periosteal apposition dominated over endosteal resorption. Boys had a greater magnitude of change at both surfaces, and thus, a greater increase in bone size across puberty. Relative increase in cortical bone area was similar between sexes. INTRODUCTION: Generally, sex differences in bone size become most evident as puberty progresses. This was thought to be caused, in part, by greater periosteal apposition in boys, whereas endosteal apposition prevailed in girls. However, this premise is based on evidence from cross-sectional studies and planar measurement techniques. Thus, our aim was to prospectively evaluate sex-specific changes in cortical bone area across puberty. MATERIALS AND METHODS: We used pQCT to assess the tibial midshaft (50% site) at baseline and final (20 months) in girls (N = 68) and boys (N = 60) across early-, peri-, and postpuberty. We report total bone cross-sectional area (ToA, mm2), cortical area (CoA, mm2), marrow cavity area (CavA, mm2), and CoA/ToA ratio. RESULTS: Children were a mean age of 11.9 +/- 0.6 (SD) years at baseline. At the tibia, CoA ranged from 230 +/- 44, 261 +/- 50, and 258 +/- 46 in early-, peri-, and postpubertal girls. In boys, comparable values were 223 +/- 36 (early), 264 +/- 38 (peri), and 281 +/- 77 (postpubertal). There was no sex difference for ToA or CoA at baseline. Increase in ToA and CoA was, on average, 10% greater for boys than girls across maturity groups. The area of the marrow cavity increased in all groups, but with considerable variability. The increase in CavA was significantly less for girls than boys in the early- and postpubertal groups. Change in CoA/ToA was similar between sexes across puberty. CONCLUSION: Both sexes showed a similar pattern of change in CoA at the tibial midshaft, where periosteal apposition dominated over endosteal resorption. Boys showed a greater magnitude of change at both surfaces, and thus, showed a greater increase in bone size across puberty. The relative increase in cortical area was similar between sexes. These pQCT findings provide no evidence for endosteal apposition in postmenarchal girls.     

Tumor necrosis factor-alpha induces skeletal muscle insulin resistance in healthy human subjects via inhibition of Akt substrate 160 phosphorylation

Most lifestyle-related chronic diseases are characterized by low-grade systemic inflammation and insulin resistance. Excessive tumor necrosis factor-alpha (TNF-alpha) concentrations have been implicated in the development of insulin resistance, but direct evidence in humans is lacking. Here, we demonstrate that TNF-alpha infusion in healthy humans induces insulin resistance in skeletal muscle, without effect on endogenous glucose production, as estimated by a combined euglycemic insulin clamp and stable isotope tracer method. TNF-alpha directly impairs glucose uptake and metabolism by altering insulin signal transduction. TNF-alpha infusion increases phosphorylation of p70 S6 kinase, extracellular signal-regulated kinase-1/2, and c-Jun NH(2)-terminal kinase, concomitant with increased serine and reduced tyrosine phosphorylation of insulin receptor substrate-1. These signaling effects are associated with impaired phosphorylation of Akt substrate 160, the most proximal step identified in the canonical insulin signaling cascade regulating GLUT4 translocation and glucose uptake. Thus, excessive concentrations of TNF-alpha negatively regulate insulin signaling and whole-body glucose uptake in humans. Our results provide a molecular link between low-grade systemic inflammation and the metabolic syndrome.     

Biochemical recurrence rate in patients with positive surgical margins at radical prostatectomy with further negative resected tissue

OBJECTIVE

To determine the biochemical recurrence (BCR) rate in patients with positive surgical margins (PSMs) on the prostate specimen who have additional negative tissue resected from that site (M+ ?), compared to patients with negative margins (M?) and those with persistent PSM (M+), as those with PSM at radical prostatectomy (RP) are at greater risk of BCR, and in some instances where suspicious tissue is noted in the prostate bed or when frozen‐section analysis shows PSM, additional tissue is resected from the suspect site of the PSM.

PATIENTS AND METHODS

Between January 1999 and June 2007, 4217 consecutive patients underwent open or laparoscopic RP with no previous radiotherapy or hormonal therapy. The median (interquartile range) follow‐up was 37.4 (21.1–60.7) months.

RESULTS

Pathological organ‐confined (OC) cancer was present in 2901 men, of whom 2659 had M?, 216 had M+, and 26 had M+ ?. Extracapsular extension (ECE) alone with no seminal vesicle or lymph node involvement was present in 843 men, of whom 657 had M?, 174 had M+ and 12 had M+ ?. For patients with OC cancer, the 36‐month actuarial BCR‐free probability was 97.9% (95% confidence interval 97.3–98.5) for M?, vs 89.0 (84.1–93.9)% for M+ vs 100% for M+ ?. For patients with ECE, the 36‐month actuarial BCR‐free probability was 83.7 (80.0–87.4)% for M? vs 73.7 (66.1–81.3)% for M+ vs 90.0 (71.4–100)% for M+ ?. The main limitation of the study was its retrospective nature, with the reason for resection of additional tissue not always well documented.

CONCLUSIONS

While the few patients with PSMs and further negative resected tissue limited the statistical analysis, it would appear that in these patients the disease behaves as in those with negative margins.     

Quality improvement in laparoscopic radical prostatectomy for pT2 prostate cancer: impact of video documentation review on positive surgical margin

PURPOSE: We correlated intraoperative video documentation and pathology findings to understand the mechanisms by which positive surgical margins occur and improve the surgical technique. MATERIALS AND METHODS: Between January 2003 and May 2004, 240 consecutive patients underwent laparoscopic radical prostatectomy, of whom 180 had pT2 prostate cancer and represent the population of this study. After the first 90 patients (group 1) we started a quality assurance study, analyzing intraoperative video recordings and correlating them with pathology findings in patients with a positive margin. The cancer characteristics and positive margin rate were compared between the first 90 patients and the subsequent 90 after the study was initiated (group 2). RESULTS: Of the 12 cases of positive surgical margins studied the video review helped identify 8 with a technical error. In all 4 cases in which a technical error could not be identified the positive margin site was at the distal apex. The most frequent identifiable mechanism by which positive margins occurred was a capsular tear during neurovascular bundle dissection. The 2 groups were comparable in regard to preoperative cancer characteristics and total tumor volume. In patients who underwent bilateral nerve sparing the positive margin rate was 10.6% in group 1 and 5.4% in group 2 (p = 0.18). All positive margins in group 2 involved the prostatic apex. CONCLUSIONS: Quality assurance efforts through pathological and intraoperative documentation review can help decrease the positive margin rate, particularly in organ confined disease. However, eradicating positive margins at the distal prostatic apex remains a challenge.     

Accuracy of DXA scanning of the thoracic spine: cadaveric studies comparing BMC, areal BMD and geometric estimates of volumetric BMD against ash weight and CT measures of bone volume

Biomechanical studies of the thoracic spine often scan cadaveric segments by dual energy X-ray absorptiometry (DXA) to obtain measures of bone mass. Only one study has reported the accuracy of lateral scans of thoracic vertebral bodies. The accuracy of DXA scans of thoracic spine segments and of anterior-posterior (AP) thoracic scans has not been investigated. We have examined the accuracy of AP and lateral thoracic DXA scans by comparison with ash weight, the gold-standard for measuring bone mineral content (BMC). We have also compared three methods of estimating volumetric bone mineral density (vBMD) with a novel standard–ash weight (g)/bone volume (cm³) as measured by computed tomography (CT). Twelve T5–T8 spine segments were scanned with DXA (AP and lateral) and CT. The T6 vertebrae were excised, the posterior elements removed and then the vertebral bodies were ashed in a muffle furnace. We proposed a new method of estimating vBMD and compared it with two previously published methods. BMC values from lateral DXA scans displayed the strongest correlation with ash weight (r=0.99) and were on average 12.8% higher (p<0.001). As expected, BMC (AP or lateral) was more strongly correlated with ash weight than areal bone mineral density (aBMD; AP: r=0.54, or lateral: r=0.71) or estimated vBMD. Estimates of vBMD with either of the three methods were strongly and similarly correlated with volumetric BMD calculated by dividing ash weight by CT-derived volume. These data suggest that readily available DXA scanning is an appropriate surrogate measure for thoracic spine bone mineral and that the lateral scan might be the scan method of choice.     

Improvement in quality of life of patients with AL amyloidosis treated with high-dose melphalan and autologous stem cell transplantation

Treatment of AL amyloidosis patients with high-dose melphalan chemotherapy followed by autologous peripheral blood stem cell transplantation (HDM/SCT) can produce hematologic complete responses (CRs) and improvement in organ function. To determine whether these responses are accompanied by improvement in quality of life (QOL), we employed the Medical Outcomes Study (MOS) 36-item Short Form General Health Survey (SF-36) questionnaire for 544 patients evaluated between 1994 and 2002. At baseline, the scores were significantly lower on all 8 SF-36 scales compared with age-matched population norms: the composite physical component summary (PCS) for the AL patients was 34.5 versus the population norm of 46.8, and the mental component summary (MCS) was 45.0 versus the norm of 51.5. All SF-36 scores improved at 1 year, with the MCS reaching the population norm. The PCS, though improved, was still lower than normal but was greater in the subgroup of patients who achieved a hematologic CR; the PCS normalized at 2 years in these patients. Thus, treatment of AL amyloidosis patients with HDM/SCT produces measurable and sustained improvements in quality of life, particularly in those patients who achieve hematologic CR.