Impact of Calcium and Two Doses of Vitamin D on Bone Metabolism in the Elderly: A Randomized Controlled Trial

The optimal dose of vitamin D to optimize bone metabolism in the elderly is unclear. We tested the hypothesis that vitamin D, at a dose higher than recommended by the Institute of Medicine (IOM), has a beneficial effect on bone remodeling and mass. In this double‐blind trial we randomized 257 overweight elderly subjects to receive 1000 mg of elemental calcium citrate/day, and the daily equivalent of 3750 IU/day or 600 IU/day of vitamin D3 for 1 year. The subjects’ mean age was 71 ± 4 years, body mass index 30 ± 4 kg/m², 55% were women, and 222 completed the 12‐month follow‐up. Mean serum 25 hydroxyvitamin D (25OHD) was 20 ng/mL, and rose to 26 ng/mL in the low‐dose arm, and 36 ng/mL in the high‐dose arm, at 1 year (p < 0.05). Plasma parathyroid hormone, osteocalcin, and C‐terminal telopeptide (Cross Laps) levels decreased significantly by 20% to 22% in both arms, but there were no differences between the two groups for any variable, at 6 or 12 months, with the exception of serum calcitriol, which was higher in the high‐dose group at 12 months. Bone mineral density (BMD) increased significantly at the total hip and lumbar spine, but not the femoral neck, in both study arms, whereas subtotal body BMD increased in the high‐dose group only, at 1 year. However, there were no significant differences in percent change BMD between the two study arms at any skeletal site. Subjects with serum 25OHD <20 ng/mL and PTH level >76 pg/mL showed a trend for higher BMD increments at all skeletal sites, in the high‐dose group, that reached significance at the hip. Adverse events were comparable in the two study arms. This controlled trial shows little additional benefit in vitamin D supplementation at a dose exceeding the IOM recommendation of 600 IU/day on BMD and bone markers, in overweight elderly individuals. © 2017 American Society for Bone and Mineral Research.     

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.     

Laparoscopic correction of biliary duct stenosis in choledochal cyst

Background/Purposes

Laparoscopy has been widely accepted as a technique for the excision of choledochal cyst, but there has been little experience using it as a therapeutic modality for hepatic duct stenosis. The aim of this study is to present our experiences in laparoscopic excision of biliary stenosis and Roux-en-Y reconstruction for patients with choledochal cysts.

Methods

Eight patients, 3 boys and 5 girls (ranged from 6 months to 12 years; median age, 3.6 years), with hepatic duct stenosis underwent laparoscopic excision of the cyst and ductoplasty, with a Roux-en-Y hepaticoenterostomy between July 2001 and January 2005. Seven of the 8 patients had common hepatic duct stenosis with intrahepatic duct dilatation, and 1 had right hepatic duct stenosis with proximal dilatation.Four ports were inserted for instruments of 3- and 5-mm sizes. Each patient underwent a laparoscopic cholangiography. The gallbladder and dilated bile ducts were completely excised. The strictures of the hepatic ducts were treated by ductoplasty. The cut end of the duct was widened by incising along the anterior wall of the hepatic duct after excision of the narrow segment. By using intraoperative bile duct endoscopy, the optimal level of resection of the common hepatic duct was determined safely without endangering the orifices of the hepatic ducts or leaving any redundant duct, and the stone debris in the bile duct was identified and washed out. The Roux-en-Y jejunal loop was fashioned extracorporeally by exteriorizing the jejunum through the umbilical incision (1.0-1.5 cm) and passed up retrocolically followed by an end-to-side hepaticojejunostomy.

Results

The median duration of the operation was 4.3 hours (3.8-5.6 hours). Intraoperative bleeding was minimal, with no patients requiring blood transfusion. In 7 of the 8 cases, postoperative hospital stay ranged from 4 to 6 days; the other case had bile leak, which was cured by draining for 26 days without surgical intervention. All the patients had been followed up for 6 to 51 months. They stayed asymptomatic and well with no delayed complication.

Conclusions

Laparoscopically assisted hepatic ductoplasty is effective and safe for children with choledochal cyst. Bile duct endoscopy proved to be a valuable instrument in showing detailed variations of the biliary system and allowed a safe hepatic hilum exploration and accurate placed hepaticojejunal anastomosis.     

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.