OPG and sRANKL Serum Concentrations in Osteopenic,Postmenopausal Women After 2‐Year Genistein Administration

Introduction : RANKL and its decoy receptor osteoprotegerin (OPG) constitute a complex physiological mediator system involved in the regulation of bone resorption and may be responsible for the homeostatic mechanism of normal bone remodeling. Genistein, an isoflavone representing 1–5% of total phytoestrogen content in soybean products, may positively regulate cellular bone metabolism, but its mechanism of action on bone is not yet fully understood. Materials and Methods : We studied the serum levels of both soluble RANKL (sRANKL) and OPG and the sRANKL/OPG ratio in 389 postmenopausal women (age, 49–67 yr) with a femoral neck BMD <0.795 g/cm² and no significant comorbid conditions after 24‐mo therapy with genistein, (n = 198; 54 mg/d) or placebo (n = 191). Both intervention and placebo contained calcium and vitamin D₃. All patients received dietary instruction in an isocaloric fat‐reduced diet. Results : In comparison with placebo, sRANKL level was lower (p < 0.001 versus placebo) and OPG higher in genistein recipients (p < 0.001 versus placebo) at 1 and 2 yr, respectively. Moreover, at the end of 24 mo, genistein produced a significant reduction in the sRANKL/OPG ratio compared with placebo (genistein = ?0.021, 95% CI, ?0.020 to ?0.022; placebo = +0.004, 95% CI, 0.003–0.005; difference = ?0.020, 95% CI, ?0.015 to ?0.025, p < 0.001). Conclusions : Our findings suggest that genistein plus calcium and vitamin D₃ as part of a healthy diet is able to positively modulate bone turnover in a cohort of osteopenic, postmenopausal women and improve sRANKL‐OPG balance after 24 mo of treatment.     

Effects of antiresorptive therapies on glucose metabolism: Results from the FIT,HORIZON‐PFT,and FREEDOM trials

In rodent models, undercarboxylated osteocalcin (ucOC) acts as a hormone that promotes insulin sensitivity and secretion. If ucOC plays a similar role in humans, then antiresorptive therapies, which reduce ucOC levels, may increase the risk of insulin resistance and diabetes. We tested whether antiresorptive therapies result in higher fasting glucose, increased weight, or greater diabetes incidence in post hoc analyses of three randomized, placebo‐controlled trials in postmenopausal women: Fracture Intervention Trial (FIT) (N = 6151) of alendronate (4 years), Health Outcomes and Reduced Incidence with Zoledronic Acid Once Yearly Pivotal Fracture Trial (HORIZON‐PFT) (N = 7113) of zoledronic acid (3 years), and Fracture Reduction Evaluation of Denosumab in Osteoporosis Every 6 Months (FREEDOM) trial (N = 7076) of denosumab (3 years). Fasting glucose was measured annually in FIT and HORIZON in a subset of women, and every 6 months in FREEDOM in all participants. Weight was measured annually in all trials. Incident diabetes was identified from adverse event reports, initiation of diabetes medication, or elevated fasting glucose. Differences in fasting glucose changes from randomization to trial conclusion between treatment and placebo groups were not statistically significant: ?0.47 mg/dL in FIT, 0.20 mg/dL in HORIZON‐PFT, and 0.09 mg/dL in FREEDOM, all p > 0.6. Weight change differed between treatment and placebo groups in FIT (0.32 kg, p = 0.003) and FREEDOM (0.31 kg, p = 0.023) but not in HORIZON‐PFT (0.15 kg, p = 0.132). In the three trials combined, diabetes occurred in 203 and 225 women assigned to treatment or placebo, respectively. Diabetes incidence was not increased in any of the treatment groups or in the pooled estimate (pooled relative risk [RR] = 0.90; 95% confidence interval [CI] 0.74–1.10). Antiresorptive therapy does not have a clinically important effect on fasting glucose, weight, or diabetes risk in postmenopausal women. Contrary to predictions from mouse models, reduced bone turnover does not appear to play a significant role in glucose metabolism in humans.     

Peri‐operative intravenous administration of magnesium sulphate and postoperative pain: a meta‐analysis

Intravenous magnesium has been reported to improve postoperative pain; however, the evidence is inconsistent. The objective of this quantitative systematic review is to evaluate whether or not the peri‐operative administration of intravenous magnesium can reduce postoperative pain. Twenty‐five trials comparing magnesium with placebo were identified. Independent of the mode of administration (bolus or continuous infusion), peri‐operative magnesium reduced cumulative intravenous morphine consumption by 24.4% (mean difference: 7.6 mg, 95% CI ?9.5 to ?5.8 mg; p < 0.00001) at 24 h postoperatively. Numeric pain scores at rest and on movement at 24 h postoperatively were reduced by 4.2 (95% CI ?6.3 to ?2.1; p < 0.0001) and 9.2 (95% CI ?16.1 to ?2.3; p = 0.009) out of 100, respectively. We conclude that peri‐operative intravenous magnesium reduces opioid consumption, and to a lesser extent, pain scores, in the first 24 h postoperatively, without any reported serious adverse effects.     

Laparoendoscopic single‐site (LESS) vs laparoscopic living‐donor nephrectomy: a systematic review and meta‐analysis

The aim of this study was to provide a systematic review and meta‐analysis of reports comparing laparoendoscopic single‐site (LESS) living‐donor nephrectomy (LDN) vs standard laparoscopic LDN (LLDN). A systematic review of the literature was performed in September 2013 using PubMed, Scopus, Ovid and The Cochrane library databases. Article selection proceeded according to the search strategy based on Preferred Reporting Items for Systematic Reviews and Meta‐analyses criteria. Weighted mean differences (WMDs) were used to measure continuous variables and odds ratios (ORs) to measure categorical ones. Nine publications meeting eligibility criteria were identified, including 461 LESS LDN and 1006 LLDN cases. There were more left‐side cases in the LESS LDN group (96.5% vs 88.6%, P < 0.001). Meta‐analysis of extractable data showed that LLDN had a shorter operative time (WMD 15.06 min, 95% confidence interval [CI] 4.9–25.1; P = 0.003), without a significant difference in warm ischaemia time (WMD 0.41 min, 95% CI –0.02 to 0.84; P = 0.06). Estimated blood loss was lower for LESS LDN (WMD ?22.09 mL, 95% CI –29.5 to –14.6; P < 0.001); however, this difference was not clinically significant. There was a greater likelihood of conversion for LESS LDN (OR 13.21, 95% CI 4.65–37.53; P < 0.001). Hospital stay was similar (WMD –0.11 days, 95% CI –0.33 to 0.12; P = 0.35), as well as the visual analogue pain score at discharge (WMD –0.31, 95% CI –0.96 to 0.35; P = 0.36), but the analgesic requirement was lower for LESS LDN (WMD –2.58 mg, 95% CI –5.01 to –0.15; P = 0.04). Moreover, there was no difference in the postoperative complication rate (OR 1.00, 95% CI 0.65–1.54; P = 0.99). Renal function of the recipient, as based on creatinine levels at 1 month, showed similar outcomes between groups (WMD 0.10 mg/dL, –0.09 to 0.29; P = 0.29). In conclusion, LESS LDN represents an emerging option for living kidney donation. This procedure offers comparable surgical and early functional outcomes to the conventional LLDN, with a lower analgesic requirement. However, it is more technically challenging than LLDN, as shown by a greater likelihood of conversion. The role of LESS LDN remains to be defined.     

Once‐Weekly Risedronate in Men With Osteoporosis: Results of a 2‐Year,Placebo‐Controlled,Double‐Blind,Multicenter Study

Male osteoporosis is increasingly recognized as a major public health issue. This multinational, 2‐yr, randomized, double‐blind, placebo‐controlled study was conducted to determine the efficacy and safety of 35 mg once‐a‐week risedronate in men with osteoporosis. Patients had to be men ≥30 yr old, with lumbar spine T‐score ≤ ?2.5 and femoral neck T‐score ≤ ?1 SD or lumbar spine T‐score ≤ ?1 and femoral neck T‐score ≤ ?2 SD (based on young normal men). Patients were randomized 2:1 to risedronate 35 mg once a week or placebo for 2 yr; all patients took 1000 mg elemental calcium and 400–500 IU vitamin D daily. Lumbar spine BMD at month 24 using last observation carried forward was the primary endpoint. Other endpoints included lumbar spine BMD at time points other than month 24, proximal femur BMD, bone turnover markers (BTMs), new vertebral fractures, clinical fractures, and adverse event (AE) assessment. There were 284 men enrolled in the study. Treatment with risedronate resulted in a significant increase from baseline to endpoint in lumbar spine BMD compared with placebo (4.5%; 95% CI: 3.5%, 5.6%; p < 0.001). Few new vertebral and nonvertebral fractures were reported, with no differences in fracture rates between the two groups. There was a significant (p < 0.01) reduction from baseline in BTMs for the risedronate group compared with placebo at all time points. No apparent differences in the pattern or distribution of AEs including serious and upper gastrointestinal AEs were observed. Risedronate therapy was well tolerated during this 2‐yr study and was rapidly effective as indicated by significant BTM decreases at month 3 and BMD increases at month 6 (the earliest time points tested). The effects of risedronate treatment on BMD and BTMs in this study were similar to those previously shown to be associated with fracture risk reductions in women with postmenopausal osteoporosis.     

The effects of zinc supplementation on wound healing and metabolic status in patients with diabetic foot ulcer: A randomized,double‐blind,placebo‐controlled trial

This study was performed to determine the effects of zinc supplementation on wound healing and metabolic status in patients with diabetic foot ulcer. The current randomized, double‐blind, placebo‐controlled trial was conducted among 60 patients (aged 40–85 years old) with grade 3 diabetic foot ulcer. Participants were randomly divided into two groups (30 participants in each group) to take either 220 mg zinc sulfate supplements containing 50 mg elemental zinc or placebo daily for 12 weeks. After the 12‐week intervention, compared with the placebo, zinc supplementation was associated with significant reductions in ulcer length (?1.5 ± 0.7 vs. ?0.9 ± 1.2 cm, p = 0.02) and width (?1.4 ± 0.8 vs. ?0.8 ± 1.0 cm, p = 0.02). In addition, changes in fasting plasma glucose (?40.5 ± 71.0 vs. ?3.9 ± 48.5 mg/dl, p = 0.02), serum insulin concentration (?8.0 ± 15.4 vs. +1.1 ± 10.3 µIU/ml, p = 0.009), homeostasis model of assessment‐estimated insulin resistance (?3.9 ± 7.1 vs. +0.8 ± 5.9, p = 0.007), the quantitative insulin sensitivity check index (+0.01 ± 0.03 vs. ?0.002 ± 0.02, p = 0.04) and HbA1c (?0.5 ± 0.8 vs. ?0.1 ± 0.5%, p = 0.01) in the supplemented group were significantly different from the changes in these indicators in the placebo group. Additionally, significant increases in serum HDL‐cholesterol (+4.1 ± 4.3 vs. +1.1 ± 5.1 mg/dl, p = 0.01), plasma total antioxidant capacity (+91.7 ± 213.9 vs. ?111.9 ± 188.7 mmol/L, p < 0.01) and total glutathione (+68.1 ± 140.8 vs. ?35.0 ± 136.1 µmol/L, p = 0.006), and significant decreases in high sensitivity C‐reactive protein (?20.4 ± 24.6 vs. ?6.8 ± 21.3 µg/ml, p = 0.02) and plasma malondialdehyde concentrations (?0.6 ± 0.9 vs. ?0.2 ± 0.7 µmol/L, p = 0.03) were seen following supplementation with zinc compared with the placebo. Zinc supplementation for 12 weeks among diabetic foot ulcer patients had beneficial effects on parameters of ulcer size and metabolic profiles.     

Treatment with LL‐37 is safe and effective in enhancing healing of hard‐to‐heal venous leg ulcers: a randomized,placebo‐controlled clinical trial

Venous leg ulcers (VLUs) are one of the most prevalent types of chronic wounds. The aim of this study was to determine the safety and dose–response efficacy of the human synthetic peptide LL‐37 in the treatment of hard‐to‐heal VLUs. This first‐in‐man trial included 34 participants with VLUs and comprised a 3‐week, open‐label, run‐in period on placebo, followed by a 4‐week randomized double‐blind treatment phase with twice weekly applications of LL‐37 (0.5, 1.6, or 3.2 mg/mL) or placebo, and a 4‐week follow‐up. The healing rate constants for 0.5 and 1.6 mg/mL of LL‐37 were approximately six‐ and threefold higher than for placebo (p = 0.003 for 0.5 mg/mL and p = 0.088 for 1.6 mg/mL). Square‐root transformed wound area data showed improved healing for the 0.5 and 1.6 mg/mL dose groups compared with pretreatment values (p < 0.001 and p = 0.011, respectively). Consistently, treatment with the two lower doses markedly decreased the mean ulcer area (68% for 0.5 mg/mL and 50% for 1.6 mg/mL groups). No difference in healing was observed between the groups receiving 3.2 mg/mL of LL‐37 and placebo. There were no safety concerns regarding local or systemic adverse events. In conclusion, topical treatment with LL‐37 for chronic leg ulcers was safe and well tolerated with the marked effect on healing predictors at the two lower doses warranting further investigations.     

Tramadol (opioid) abuse is associated with a dose‐ and time‐dependent poor sperm quality and hyperprolactinaemia in young men

Tramadol, one of the most commonly abused drugs in Middle East, impacts spermatogenesis and disturbs reproductive hormones in animal studies. We aimed to investigate tramadol impact on sperm quality and on levels of testosterone, prolactin and gonadotropins, in tramadol abusers (n = 30) to age‐matched control (n = 30). Abusers had significantly low percentages of sperm motility, normal forms and vitality compared with control (95% CI ?40.7 to ?19.3, ?13.5 to ?9.3 and ?31.9 to ?9.7 respectively). Hypoandrogenism (95% CI ?4.5 to ?2.8), hyperprolactinaemia (CI (95%) 4.9 to 9.4) and hypergonadotropinaemia (95% CI 2.9 to 7.2 for FSH and 2.0 to 7.8 for LH) were observed in tramadol abusers vs controls. Smokers (26 of 30), concurrently abusing other drugs (11 of 30) and asymptomatic leucocytospermic (15 of 30) patients subgroups significantly abused tramadol beyond 3 years (p = .02, <.001, = .03 respectively) and in excess >450 mg/day (p = .02, = .01, = .005 respectively). Progressive motility (a + b%) was significantly low in young men <25 years old (p = .03) subgroup. Tramadol abuse is associated with poor sperm quality, hyperprolactinaemia and hypergonadotropic hypogonadism. We recommend semen analysis for tramadol long‐intakes, question sperm donors and follow‐up studies to prevent and reverse tramadol‐induced testicular damage.     

Sporadic and MEN1‐Related Primary Hyperparathyroidism: Differences in Clinical Expression and Severity

Primary hyperparathyroidism (PHPT) is a common endocrine disease that is associated with multiple endocrine neoplasia type 1 (MEN1) in ～2% of PHPT cases. Lack of a family history and other specific expressions may lead to underestimated MEN1 prevalence in PHPT. The aim of this study was to identify clinical or biochemical features predictive of MEN1 and to compare the severity of the disease in MEN1‐related versus sporadic PHPT (sPHPT). We performed a 36‐mo cross‐sectional observational study in three tertiary referral centers on an outpatient basis on 469 consecutive patients with sporadic PHPT and 64 with MEN1‐related PHPT. Serum calcium, phosphate, PTH, 25(OH)D₃, and creatinine clearance were measured, and ultrasound examination of the urinary tract/urography was performed in all patients. In 432 patients, BMD was measured at the lumbar spine (LS) and femoral neck (FN). MEN1 patients showed lower BMD Z‐scores at the LS (?1.33 ± 1.23 versus ?0.74 ± 1.4, p = 0.008) and FN (?1.13 ± 0.96 versus ?0.6 ± 1.07, p = 0.002) and lower phosphate (2.38 ± 0.52 versus 2.56 ± 0.45 mg/dl, p = 0.003) and PTH (113.8 ± 69.5 versus 173.7 ± 135 pg/ml, p = 0.001) levels than sPHPT patients. Considering probands only, the presence of MEN1 was more frequently associated with PTH values in the normal range (OR, 3.01; 95% CI, 1.07–8.50; p = 0.037) and younger age (OR, 1.61; 95% CI, 1.28–2.02; p = 0.0001). A combination of PTH values in the normal range plus age <50 yr was strongly associated with MEN1 presence (OR, 13.51; 95% CI, 3.62–50.00; p = 0.0001). In conclusion, MEN1‐related PHPT patients show more severe bone but similar kidney involvement despite a milder biochemical presentation compared with their sPHPT counterparts. Normal PTH levels and young age are associated with MEN1 presence.     

Bone Mineral Density and Parathyroid Hormone as Independent Risk Factors for Mortality in Community‐Dwelling Older Adults: A Population‐Based Prospective Cohort Study in Brazil. The São Paulo Ageing & Health (SPAH) Study

Previous studies have shown a relationship between osteoporosis and increased mortality risk. However, none of these studies performed a concomitant evaluation of the parathyroid hormone (PTH)‐calcium‐vitamin D axis and bone mass to accurately determine the contribution of each of these parameters to survival in older subjects. Thus, we sought to investigate the association between bone parameters and mortality in a longitudinal, prospective, population‐based cohort of 839 elderly subjects. Clinical data (including history of fractures and cardiovascular events) were assessed using a specific questionnaire. Laboratory exams, including serum 25OHD and PTH, were also performed. Bone mineral density (BMD) at the lumbar spine and hip were evaluated using DXA. All analyses were performed at baseline (2005 to 2007). Mortality was recorded during follow‐up. Multivariate Cox proportional regression was used to compute hazard ratios for all‐cause and cardiovascular mortality. Over a mean 4.06 ± 1.07 years, there were 132 (15.7%) deaths. These individuals were compared to 707 subjects who were alive at the end of the coverage period for mortality data collection. In a multivariate Cox proportional hazards model, age (HR 1.32; 95% CI, 1.13 to 1.55; p = 0.001, for each 5‐year increase), male gender (HR 1.90; 95% CI, 1.30 to 2.79; p = 0.001), recurrent falls (more than two in the previous year; HR 1.65; 95% CI, 1.06 to 2.56; p = 0.026), diabetes mellitus (HR 2.17; 95% CI, 1.46 to 3.21; p < 0.001), low physical activity score (HR 1.78; 95% CI, 1.14 to 2.79; p = 0.011), prior cardiovascular event (HR 1.76; 95% CI, 1.18 to 2.63; p = 0.006), total hip BMD (HR 1.41; 95% CI, 1.15 to 1.72; p = 0.001, per each 1 SD decrease), and intact PTH (iPTH) (HR 1.06; 95% CI, 1.04 to 1.08; p < 0.001, per each 10 pg/mL increase) were independently associated with all‐cause mortality. The subjects in the highest quartile of PTH (>49 pg/mL) were at a higher risk of cardiovascular death (HR 3.09; 95% CI, 1.36 to 6.99; p = 0.007) compared with the subjects in the lowest quartile (<26 pg/mL). Low BMD and higher PTH were significantly associated with mortality in community‐dwelling older adults. These findings support the notion that careful screening of these bone parameters might lead to better management of older patients and improve outcomes in this population. © 2016 American Society for Bone and Mineral Research.     

The Effects of Calcium Supplementation on Verified Coronary Heart Disease Hospitalization and Death in Postmenopausal Women: A Collaborative Meta‐Analysis of Randomized Controlled Trials

Calcium supplementation, particularly with vitamin D, has been an approved public health intervention to reduce fracture risk. Enthusiasm for this intervention has been mitigated by meta‐analyses suggesting that calcium supplementation with or without vitamin D increases myocardial infarction (MI) risk; however, concern has been raised over the design of these meta‐analyses. We, therefore, undertook a meta‐analysis of randomized controlled trials with placebo or no‐treatment control groups to determine if these supplements increase all‐cause mortality and coronary heart disease (CHD) risk including MI, angina pectoris and acute coronary syndrome, and chronic CHD verified by clinical review, hospital record, or death certificate in elderly women. The Cochrane Central Register of Controlled Trials, MEDLINE, and EMBASE databases were searched from January 1, 1966, to May 24, 2013, for potentially eligible studies, reference lists were checked, and trial investigators were contacted where additional unpublished data were required. The search yielded 661 potentially eligible reports of which 18 met the inclusion criteria and contributed information on 63,563 participants with 3390 CHD events and 4157 deaths. Two authors extracted the data independently with trial data combined using random‐effects meta‐analysis to calculate the relative risk (RR). Five trials contributed CHD events with pooled relative RR of 1.02 (95% confidence interval [CI], 0.96–1.09; p = 0.51). Seventeen trials contributed all‐cause mortality data with pooled RR of 0.96 (95% CI, 0.91–1.02; p = 0.18). Heterogeneity among the trials was low for both primary outcomes (I² = 0%). For secondary outcomes, the RR for MI was 1.08 (95% CI, 0.92–1.26; p = 0.32), angina pectoris and acute coronary syndrome 1.09 (95% CI, 0.95–1.24; p = 0.22) and chronic CHD 0.92 (95% CI, 0.73–1.15; p = 0.46). In conclusion, current evidence does not support the hypothesis that calcium supplementation with or without vitamin D increases coronary heart disease or all‐cause mortality risk in elderly women. © 2014 American Society for Bone and Mineral Research.     

Efficacy of intralesional recombinant human epidermal growth factor in diabetic foot ulcers in Mexican patients: A randomized double‐blinded controlled trial

The healing process in diabetic foot ulcer (DFU) is hindered by factors such as chronic inflammation, defects in fibroblast function, poor angiogenesis, and lack of cell migration. Recombinant human epidermal growth factor (rhEGF) has been shown to enhance extracellular matrix formation, cellular proliferation, and angiogenesis. Therefore, intralesional application of rhEGF in DFU could accelerate wound healing. Our objective was to determine the efficacy and safety of rhEGF in patients with DFU. A randomized, double‐blinded, placebo‐controlled study was conducted comparing a thrice‐per‐week intralesional application of rhEGF (75 μg) or placebo in patients with DFU for 8 weeks. The number of completely healed ulcers, size, and wound bed characteristics were evaluated to determine the efficacy of rhEGF. Adverse events were recorded and analyzed to establish its safety. A total of 34 patients were recruited for the study. After three dropouts, we were able to follow and analyze 16 patients in the placebo group and 15 patients in the rhEGF study to the end of the trial. Baseline testing showed that both groups were similar. Compared to the placebo group, more ulcers achieved complete healing in the rhEGF group (rhEGF, n = 4; placebo, n = 0; p = 0.033); ulcers in the rhEGF group decreased in area size (12.5 cm2 [rhEGF] vs. 5.2 cm2 [placebo]; p = 0.049); and more epithelial islands in the wound bed were present (28% vs. 3%; p = 0.025). Mild transitory dizziness was the only side effect that was more frequently noted in the rhEGF group. Our results showed that in patients with DFU who received standard care, intralesional rhEGF application resulted in complete healing in more patients, promoted the epithelialization of the wound bed, and significantly reduced the area of the DFU treated. Therefore, rhEGF resulted in better outcomes for patients suffering from DFU.     

Effects of vitamin E-coated dialysis membranes on anemia,nutrition and dyslipidemia status in hemodialysis patients: a meta-analysis

Abstract

Background: This was controversial whether vitamin E-coated dialyzer therapy was beneficial for the complications associated with hemodialysis. Therefore, we performed this systematic review to evaluate the effects of vitamin E-coated dialyzer. Methods: Related trials were searched from multiple electronic databases. We conducted meta-analysis to assess changes in the predefined outcomes using RevMan 5.3 software. Results: Meta-analysis showed vitamin E-coated dialyzer therapy could decrease erythropoietin (EPO) resistance index (SMD, ?0.24; 95% CI, ?0.47 to ?0.01; p?=?0.04). However, pooled-analysis showed vitamin E-coated dialyzer therapy could not decrease weekly EPO dose (SMD, ?0.11; 95% CI, ?0.32 to 0.09; p?=?0.28) and intima–media thickness (IMT) of the carotid artery (MD, ?0.09; 95% CI, ?0.2 to 0.01; p?=?0.09), and vitamin E-coated dialyzer therapy did not improve the serum hemoglobin (MD, ?0.03; 95% CI, ?0.18 to 0.13; p?=?0.74), albumin levels (SMD, ?0.64; 95% CI, ?1.62 to 0.34; p?=?0.2), in addition, there was no significant difference in serum cholesterol (SMD, ?0.07; 95% CI, ?0.45 to 0.31; p?=?0.71), triglycerides (MD, ?2.77; 95% CI, ?32.42 to 26.87; p?=?0.85), high density lipoprotein (HDL) (SMD, 0.24; 95% CI, ?0.14 to 0.62; p?=?0.22) and low density lipoprotein (LDL) (SMD, 0.00; 95% CI, ?0.38 to 0.37; p?=?0.98) levels. Conclusions: Vitamin E-coated dialyzer may reduce the EPO resistance, but there is no conclusive evidence that vitamin E-coated dialyzer can improve the renal anemia, malnutrition, dyslipidemia and atherosclerosis status in hemodialysis (HD) patients. However, high-quality trials with hard clinical endpoints are required to fully elucidate the clinical value of vitamin E-coated dialyzer therapy.     

High cystatin C levels predict undesirable outcome for diabetic foot ulcerations

We investigated the relationship between serum cystatin C levels and the prognosis of diabetic foot ulcerations (DFU). A population‐based cohort study involving 1018 patients with type 2 diabetes was conducted. These patients recruited and divided into two groups: nondiabetic foot ulcer group (NDF, n = 865, 85.5%) and diabetic foot ulcer group (DFU, n = 147, 14.5%).After a 1‐year‐follow‐up, DFUs were grouped into healing (n = 110, 74.8%) and nonhealing (n = 37, 25.2%) group based on the clinical prognosis. Compared with the healing group, the nonhealing group were older, had long diabetic duration and had significantly increased serum cystatin C concentrations in DFU (p < 0.01). After adjustments for age, diabetes duration, renal function and infection control, multiple logistical regression analysis revealed that cystatin C remained associated increased risk of undesirable DFU outcome (OR = 7.279, 95% CI: 1.299–40.784, p < 0.05). When divided into quartiles according to cystatin C levels, the healing rate of Quartile 4 was significantly lower (57.9%) compared with other groups (p < 0.01). The odd is ratio (OR) analysis showed that the risk of undesirable DFU outcome in Quartile 4 was significantly higher (OR = 4.554, 95% CI: 3.14–5.12, p < 0.05) compared with that in Quartile 1. We concluded that there was a strong and independent association between serum cystatin C and diabetic foot ulceration prognosis, cystatin C > 1.35 mg/L predicts more than sixfold increased risk of incurable foot ulceration.     

Risk factors for the recurrence of diabetic foot ulcers among diabetic patients: a meta‐analysis

This study aimed to systematically review and identify the risk factors for the recurrence of diabetic foot ulcers (DFUs) among diabetic patients. PUBMED, EMBASE, Web of Science, Cochrane Library, China Biology Medicine (CBM), China National Knowledge Infrastructure (CNKI), WanFang, and VIP databases were electronically searched to identify eligible studies updated to January 2019 to collect case‐control studies or cohort studies on the risk factors for the recurrence of DFUs. Two reviewers independently screened the literature, extracted data, and assessed the risk of bias of included studies using the Newcastle‐Ottawa Scale. A meta‐analysis was performed using RevMan 5.3. Nine retrospective cohort studies were included, in which 1426 patients were enrolled, 542 in the DFU recurrence group and 884 in the non‐recurrent DFU group. Risk factors for the recurrence of DFUs included male gender (odds ratio [OR] = 1.38, 95% confidence interval [CI], 1.07‐1.78, P < .05), smoking (OR = 1.66, 95% CI, 1.26‐2.20, P = .0004), duration of diabetes (OR = 4.43, 95% CI, 1.96‐6.90, P = .0004), duration of past DFUs (OR = 1.02, 95% CI, 1.00‐1.03, P = .006), plantar ulcers (OR = 5.31, 95% CI, 4.93‐5.72, P <.00001), peripheral artery disease (OR = 1.65, 95% CI, 1.20‐2.28, P = .002), and diabetic peripheral neuropathy (OR = 2.15, 95% CI, 1.40‐3.30, P = .0005). No significant differences were found in age, body mass index, total cholesterol, diabetic nephropathy, diabetic retinopathy, or hypertension. Health care staff should pay attention to the identified risk factors for the recurrence of DFUs. Because of the limited quality and quantity of the included studies, rigorous studies with adequate sample sizes are needed to verify the conclusion.     

Effect of alendronate and vitamin D3 on fractional calcium absorption in a double‐blind,randomized, placebo‐controlled trial in postmenopausal osteoporotic women

Menopause and increasing age are associated with a decrease in calcium absorption that can contribute to the pathogenesis of osteoporosis. We hypothesized that alendronate plus vitamin D₃ (ALN + D) would increase fractional calcium absorption (FCA). In this randomized, double‐blind, placebo‐controlled multicenter clinical trial, 56 postmenopausal women with 25‐hydroxyvitamin D [25(OH)D] concentrations of 25 ng/mL or less and low bone mineral density (BMD) received 5 weekly doses of placebo or alendronate 70 mg plus vitamin D₃ 2800 IU (ALN + D). Calcium intake was stabilized to approximately 1200 mg/d prior to randomization. FCA was determined using a dual‐tracer stable‐calcium isotope method. FCA and 25(OH)D were similar between treatment groups at baseline (0.31 ± 0.12 ng/mL and 19.8 ± 4.7 ng/mL, respectively). After 1 month of treatment, subjects randomized to ALN + D experienced a significant least squares (LS) mean [95% confidence interval (CI)] increase in FCA [0.070 (0.042, 0.098)], whereas FCA did not change significantly in the placebo group [?0.016 (?0.044, 0.012)]. After ALN + D treatment, patients had higher 25(OH)D levels (LS mean difference 7.3 ng/mL, p < .001). The rise in serum 1,25‐dihydroxyvitamin D₃ (p < .02) and parathyroid hormone (p < .001) were greater in the ALN + D group than in placebo‐treated patients. ALN + D was associated with an increase in FCA of 0.07. To our knowledge, there is no other trial showing such a marked rise in calcium absorption owing to treatment with a bisphosphonate or owing to a small rise in 25(OH)D. This unique response of ALN + D is important for the treatment of osteoporosis, but the exact mechanism requires further study. © 2011 American Society for Bone and Mineral Research     

Antioxidants in the chemoprevention of colorectal cancer and colorectal adenomas in the general population: a systematic review and meta‐analysis

Aim Antioxidants, such as vitamin A, C and E, selenium and β‐carotene, have been proposed as possible agents in the chemoprevention of colorectal cancer and have been the subject of recent trials and reviews. This review aimed to assess the present evidence on the effect of antioxidants on the incidence of colorectal neoplasms in the general population. Method A systematic review of randomized controlled trials was undertaken comparing antioxidants alone or in combination with other agents vs placebo. The following databases were searched for published and unpublished literature: Cochrane Library, MEDLINE, PreMEDLINE, CINAHL, EMBASE, Web of Science, and Biological Abstracts and Research Registers. Studies were quality appraised and extracted. Meta‐analysis was performed. Results Twelve studies were identified as relevant. In the nine comparing antioxidants with no antioxidants (n = 148 922), there was no difference in the incidence of colorectal cancer [relative risk (RR) 1.00, 95% confidence interval (CI) 0.88–1.13]. One study assessed the effect of antioxidants on adenoma formation (n = 15 538) and did not demonstrate a statistically significant effect (RR 1.47, 95% CI 0.97–2.23). Of 14 discrete analyses for different combinations of antioxidants, only one reported a statistically significant increase in relative risk of adenoma formation in participants receiving vitamin E (RR 1.74, 95% CI 1.09–1.79, P = 0.02) or vitamin E plus β‐carotene (RR 1.63, 95% CI 1.01–2.63, P = 0.04). Effectiveness did not seem to differ between healthy populations, participants with cardiovascular risk factors or populations exposed to smoking or asbestos. Conclusion The review demonstrates that antioxidants (vitamin A, C and E, selenium and β‐carotene), as single agents, in combination with other antioxidants or in combination with other agents, are not effective in the chemoprevention of colorectal neoplasia in the general population. This questions their involvement in future randomized controlled trials of chemoprevention in colorectal cancer.     

Pre‐operative vitamin B infusion and prevention of nitrous oxide‐induced homocysteine increase

Nitrous oxide inactivates vitamin B₁₂ with detrimental consequences for folate and methionine metabolism, detectable by an increase in total plasma homocysteine. We hypothesised that a pre‐operative vitamin B₁₂ and folate infusion prevents nitrous oxide‐induced homocysteine increase. Sixty‐three healthy patients having elective surgery were randomly allocated to receive either B‐vitamin plus nitrous oxide; placebo plus nitrous oxide or placebo plus air. Fifty‐nine patients completed the study. After intravenous B‐vitamin infusion, plasma vitamin B₁₂ and folate concentrations increased 35‐fold and 12‐fold, respectively, on the first postoperative measurement. Patients who received B‐vitamins developed a similar increase (18%) in homocysteine after nitrous oxide (1.9 μmol.l^?1; 95% CI 0.2–3.6 μmol.l^?1) as those who did not (22%; 2.7 μmol.l^?1; 95% CI 0.6–4.8 μmol.l^?1). Patients not receiving nitrous oxide had no homocysteine change (0.5 μmol.l^?1; 95% CI ?0.8–1.9 μmol.l^?1), indicating that pre‐operative intravenous B‐vitamins may not prevent nitrous oxide‐induced hyperhomocysteinaemia.     

Bone quality, as measured by trabecular bone score in patients with adrenal incidentalomas with and without subclinical hypercortisolism

Patients with adrenal incidentalomas (AIs) and subclinical hypercortisolism (SH) have increased risk of fracture independent of bone mineral density (BMD) and possibly due to reduced bone quality. The trabecular bone score (TBS) has been proposed as a index of bone microarchitecture. The aim of the study was to investigate TBS in AI. In 102 AI patients, SH was diagnosed in the presence of at least two of the following: (1) urinary free cortisol >70 µg/24 h (193.1 nmol/L); (2) cortisol after 1‐mg dexamethasone suppression test (1‐mg DST) >3.0 µg/dL (82.8 nmol/L); or (3) adrenocorticotropic hormone (ACTH) <10 pg/mL (<2.2 pmol/L). In patients and in 70 matched controls, BMD was measured at lumbar spine (LS) and femur (neck [FN] and total [FT]) by dual X‐ray absorptiometry and TBS was assessed in the region of LS‐BMD; BMD and TBS data were reported as Z‐scores. In patients, vertebral deformities were assessed by radiograph. Patients with SH (n = 34) had lower LS‐BMD (?0.31 ± 1.17), FT‐BMD (?0.29 ± 0.91), and TBS (?3.18 ± 1.21) than patients without SH (n = 68, 0.31 ± 1.42, p = 0.03; 0.19 ± 0.97, p = 0.01; ?1.70 ± 1.54, p < 0.0001, respectively) and controls (0.42 ± 1.52, p = 0.02; 0.14 ± 0.76, p = 0.02; ?1.19 ± 0.99, p < 0.0001, respectively). TBS was inversely correlated with 1‐mg DST (β = ?0.26, t = ?2.79, p = 0.006) regardless of age, LS‐BMD, body mass index (BMI), and gender. The presence of fracture was associated with low TBS alone (odds ratio [OR], 4.8; 95% confidence interval [CI], 1.85–12.42, p = 0.001) and with the cluster low TBS plus low LS‐BMD (OR, 4.37; 95% CI, 1.71–11.4, p = 0.002), after adjustment for age, BMI, and gender. Low TBS plus low LS‐BMD showed a good specificity (79%) for predicting fractures, whereas normal TBS (ie, > ?1.5) plus normal LS‐BMD high specificity (88.1%) for excluding fractures. Finally, TBS predicted the occurrence of a new fracture in 40 patients followed for 24 months (OR, 11.2; 95%CI, 1.71–71.41, p = 0.012) regardless of LS‐BMD, BMI, and age. In SH, bone quality, as measured by TBS, is altered. TBS is useful in detecting AI patients at risk of fractures. © 2012 American Society for Bone and Mineral Research.     

Effects of vitamin E-coated dialyzer on oxidative stress and inflammation status in hemodialysis patients: a systematic review and meta-analysis

Background: Vitamin E-coated dialyzer may have an effect on oxidative stress and inflammation status in hemodialysis (HD) patients. Therefore, we performed a systematic review to assess the anti-oxidation and anti-inflammatory effects of vitamin E-coated dialyzer in HD patients. Methods: The randomized controlled trials (RCTs) and quasi-RCTs of vitamin E-coated dialyzer versus conventional dialyzer for HD patients were searched from multiple databases. We screened relevant studies according to predefined inclusion criteria and performed meta-analyses using RevMan 5.1 software. Results: Meta-analysis showed vitamin E-coated dialyzer therapy could significantly decrease the serum thiobarbituric acid reacting substances (TBARS) (SMD, ?0.95; 95% CI, ?1.28 to ?0.61; p?p?=?0.005), interleukin-6 (IL-6) (SMD, ?0.65; 95% CI, ?0.97 to ?0.32; p?p?=?0.03) compared with that of the control group. However, vitamin E-coated dialyzer did not result in increasing the total antioxidant status (TAS) (SMD, 0.23; 95% CI, ?0.16 to 0.61; p?=?0.25) and the fractional clearance of urea index (Kt/v) levels (MD, ?0.07; 95% CI, ?0.14 to 0.00; p?=?0.06), in addition, there was no significant difference in plasma superoxide dismutase (SOD) level compared with that of the conventional dialyzer &; oral vitamin E group (SMD, 0.28; 95% CI, ?0.20 to 0.75; p?=?0.26). Conclusions: Vitamin E-coated dialyzer can reduce the oxidative stress and inflammation status reflected by the decreasing of serum TBARS, oxLDL, CRP, and IL-6 levels, and this new dialyzer does not affect the dialysis adequacy.