Comparison between short- and long-acting erythropoiesis-stimulating agents in hemodialysis patients: target hemoglobin,variability, and outcome

Purpose

Maintaining target hemoglobin (Hb) with minimal variability is a challenge in hemodialysis (HD) patients. The aim of this study is to compare the long- and short-acting erythropoietin-stimulating agents such as Aranesp and Eprex in achieving these targets.

Methods

Randomized, prospective, open-labeled study of 24 weeks includes stable patients on HD >3 months, age >18 years, and on Eprex for >3 months. Patients were randomized into two groups: A-(Aranesp group):HD patients on Eprex Q TIW or BIW were converted to Aranesp Q weekly, by using the conversion factor of 200:1 and those on Eprex Q weekly to Aranesp Q 2 weeks; B-(Eprex group):patients continued on Eprex treatment. Hemoglobin target was set at (105–125 g/l). Primary end points were percentage of patients achieving target Hb, hemoglobin variability, and number of dose changes in each group.

Results

This study consisted of 139 HD patients: 72 in the Aranesp and 67 in the Eprex—mean (SD) age 54 (16.2) years, 77 (55 %) males. About 46 % were diabetic. Target Hb achieved in 64.8 % of the Aranesp and 59.7 % in the Eprex (p = 0.006). Hb variability was less frequent in the Aranesp group (p = 0.2). Mean number of dose changes was 1.3 (0.87) in the Aranesp and 1.9 (1.2) in the Eprex (p < 0.001). There was 1 vascular access thrombosis in the Aranesp and 8 in the Eprex (p < 0.001). There was no difference in hospitalization and death number between the 2 groups.

Conclusions

Aranesp Q weekly or every 2 weeks is more efficient in achieving target Hb, with less dose changes and minor vascular access complications.     

Specific MUC1 Splice Variants Are Correlated With Tumor Progression in Esophageal Cancer

Background

Mucin 1 (MUC1) is a complex glycoprotein expressed on the apical surface of normal glandular epithelial cells. It plays a role in a number of biologic processes, and its overexpression is associated with various malignancies. A growing body of literature suggests that MUC1 is a potential diagnostic and therapeutic marker. Increasing numbers of variants are being identified for the MUC1 gene, but their role in carcinogenesis is unclear. Alternative splicing and a specific region on a variable number of tandem repeats are characteristic features of MUC1. However, the underlying mechanisms, overall prevalence, and the function of various MUC1 isoforms are not well characterized.

Methods

In the present study, mRNA expression of nine variants of the MUC1 gene (A–D, X–Z, REP, SEC) was evaluated in normal and tumor tissues obtained from 50 patients with esophageal squamous cell carcinoma (ESCC). Associations between expression of various isoforms of MUC1 and important clinicopathologic factors were studied.

Results

Specific MUC1 splice variants (i.e., MUC1/C, D, and Z) are correlated with tumor progression in ESCC, whereas MUC1/B—previously suggested as a “normal” variant in some other cancers—has protective effects and is associated with more favorable tumor behavior and better prognosis.

Conclusions

Specific isoforms of ESCC are associated with prognosis. Further characterization of different isoforms of MUC1 and their biologic effects is needed to explore their diagnostic and prognostic potential in clinical practice.     

Carbetocin at elective Cesarean delivery: a sequential allocation trial to determine the minimum effective dose

Purpose

The purpose of this study was to determine the intravenous dose of carbetocin required to produce effective uterine contraction in 90% of females (ED₉₀) undergoing elective Cesarean delivery (CD) under spinal anesthesia.

Methods

We conducted a double-blind dose-finding study of carbetocin. Forty females undergoing elective CD received carbetocin intravenously upon delivery of the fetus. The dose of carbetocin for each patient was determined according to a biased-coin up-and-down sequential allocation scheme designed to cluster doses close to ED₉₀. The initial dose was 10 μg, with increments/decrements of 5 μg. The anesthesiologist, obstetrician, and patient were blinded to the dose. The obstetrician assessed the uterine tone at one-minute intervals for five minutes after carbetocin administration. In case of unsatisfactory tone, additional uterotonics were administered. The primary outcome was requirement for additional intraoperative uterotonics. Secondary outcomes were postoperative requirement for additional uterotonics within 24 hr of delivery, estimated blood loss and side effects.

Results

The ED₉₀ of carbetocin was 14.8 μg (95% confidence interval 13.7 to 15.8). Thirty-seven patients (92.5%) had adequate uterine tone with no requirement of additional intraoperative uterotonics. Two patients (5%) required postoperative uterotonics within 24 hr. The overall mean (SD) estimated blood loss was 786 (403) mL and the overall incidence of hypotension (decrease in systolic blood pressure ≥ 20% baseline) was 37.5%.

Conclusion

Based on our study, the ED₉₀ of carbetocin at elective CD is less than one-fifth the currently recommended dose of 100 μg. This study was registered at clinicaltrials.gov (NCT-01651130).     

Decreased posterior cruciate and altered collateral ligament loading following ACL transection: A longitudinal study in the ovine model

Although ACL deficiency is shown to lead to joint degeneration, few quantitative data are reported on its effect on soft tissue structures surrounding the knee joint, specifically, the posterior cruciate and collateral ligaments. The kinematics of the stifle joint of sheep (N = 5) were measured during “normal” gait, as well as 4 and 20 weeks after ACL transection. These motions were reproduced using a unique robotic manipulator and the loads borne by PCL, MCL, and LCL during gait were determined. Our results demonstrated a significant decrease in mean PCL loads 20 weeks post‐ACL injury, at hoof‐strike (0% of gait, p = 0.034), hoof‐off (66% of gait, p = 0.006), peak‐swing (85% of gait, p = 0.026), and extension‐before‐hoof‐strike (95% of gait, p = 0.028). Mean MCL loads did not significantly increase following ACL transection, maybe due to large between‐animal variation. Finally, mean LCL loads indicated a significant decrease (p < 0.047) at 20 weeks across the entire gait cycle. From a clinical perspective, the load redistributions observed in cruciate and collateral ligaments following ACL injury indicate that these tissues can carry/adapt to the altered mechanical environment of the joint. The considerable variability in the magnitudes of change following ACL injury among animals also simulates clinical variability in humans after trauma. © 2013 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 32:431–438, 2014.     

Acid and Microhardness of Mineral Trioxide Aggregate and Mineral Trioxide Aggregate–like Materials

Introduction

The aim of this study was to compare the surface microhardness of BioAggregate, ProRoot MTA, and CEM Cement when exposed to an acidic environment or phosphate-buffered saline (PBS) as a synthetic tissue fluid.

Methods

Ninety cylindrical molds made of polymethyl methacrylate with an internal diameter of 6 mm and height of 4 mm (according to ASTM E384 standard for microhardness tests) were fabricated and filled with BioAggregate (n = 30), tooth-colored ProRoot MTA (n = 30), or CEM Cement (n = 30). Each group was then divided into 3 subgroups of 10 specimens consisting of those exposed to distilled water, exposed to PBS (pH = 7.4), or exposed to butyric acid (pH = 5.4). After 1 week the Vickers surface microhardness test was performed. Statistical analysis included 2-way analysis of variance, followed by post hoc Dunnett T3 in cases with lack of homoscedasticity and Tukey honestly significant difference in cases with homoscedasticity.

Results

The indentations obtained from the CEM Cement specimens exposed to an acidic pH were not readable because of incomplete setting. There was a significant difference between the microhardness of the materials regardless of the environmental conditions (P < .001). In all the environmental conditions, MTA had significantly higher and CEM Cement had significantly lower microhardness values (P < .001). All experimental cements had significantly higher microhardness values when exposed to PBS (P < .001) and had significantly lower microhardness values when exposed to butyric acid (P < .001).

Conclusions

The surface microhardness of BioAggregate, ProRoot MTA, and CEM Cement was reduced significantly by exposure to butyric acid and increased significantly by exposure to PBS. In all environmental conditions, MTA had significantly higher microhardness values.