Human CD200 suppresses macrophage-mediated xenogeneic cytotoxicity and phagocytosis

Purpose

Various strategies, such as the generation of alpha-1,3-galactosyltransferase knocked-out pigs and CD55 transgenic pigs, have been investigated to inhibit pig to human xenogeneic rejection. Our aim is to develop strategies to overcome the hurdle of not only hyper acute rejection, but also that of cellular xenogeneic rejection (CXR). Although macrophages have been well known to play a critical role in CXR, monocyte/macrophage-mediated xenogeneic rejection has not been well studied. In this study, we evaluated the effect of CD200 in xenogeneic rejection by macrophages.

Methods

Naïve swine endothelial cells (SEC) and SEC/CD200 were co-cultured with M0 macrophages and the cytotoxicity was measured by a WST-8 assay. The phagocytosis of SEC and SEC/CD200 by macrophages was analyzed by flow cytometry.

Results

While CD200 failed to suppress a significant amount of cytotoxicity against SEC by monocytes, M0 macrophage-mediated cytotoxicity was significantly suppressed by human CD200. The phagocytosis by M0 macrophages was also tested. The phagocytosis assay revealed that human CD200 suppresses M0 macrophage-mediated phagocytosis.

Conclusions

Our findings indicate that human CD200 suppresses the xenogeneic rejection by CD200R⁺ macrophages and that the generation of hCD200 transgenic pigs for use in xenografts is very attractive for preventing the macrophage-mediated rejection.

     

Comparison of Oral Iron Supplement Formulations for Normalization of Iron Status Following Roux-EN-y Gastric Bypass Surgery: a Randomized Trial

Background

The evidence behind recommendations for treatment of iron deficiency (ID) following roux-en-y gastric bypass surgery (RYGB) lacks high quality studies.

Setting

Academic, United States

Objective

The objective of the study is to compare the effectiveness of oral iron supplementation using non-heme versus heme iron for treatment of iron deficiency in RYGB patients.

Methods

In a randomized, single-blind study, women post-RYGB and iron deficient received non-heme iron (FeSO₄, 195 mg/day) or heme iron (heme-iron-polypeptide, HIP, 31.5 to 94.5 mg/day) for 8 weeks. Measures of iron status, including blood concentrations of ferritin, soluble transferrin receptor (sTfR), and hemoglobin, were assessed.

Results

At baseline, the mean ± standard deviation for age, BMI, and years since surgery of the sample was 41.5 ± 6.8 years, 34.4 ± 5.9 kg/m², and 6.9 ± 3.1 years, respectively; and there were no differences between FeSO₄ (N = 6) or HIP (N = 8) groups. Compliance was greater than 94%. The study was stopped early due to statistical and clinical differences between groups. Values before and after FeSO₄ supplementation, expressed as least square means (95% CI) were hemoglobin, 10.8 (9.8, 11.9) to 13.0 (11.9, 14.0) g/dL; sTfR, 2111 (1556, 2864) to 1270 (934, 1737) μg/L; ferritin, 4.9 (3.4, 7.2) to 15.5 (10.6, 22.6) μg/L; and sTfR:ferritin ratio, 542 (273, 1086) to 103 (51, 204); all p < 0.0001. With HIP supplementation, no change was observed in any of the iron status biomarkers (all p > 0.05).

Conclusions

In accordance with recommendations, oral supplementation using FeSO₄, but not HIP, was efficacious for treatment of iron deficiency after RYGB.

     

Development and psychometric characteristics of the SCI-QOL Pressure Ulcers scale and short form

ObjectiveTo develop a self-reported measure of the subjective impact of pressure ulcers on health-related quality of life (HRQOL) in individuals with spinal cord injury (SCI) as part of the SCI quality of life (SCI-QOL) measurement system.DesignGrounded-theory based qualitative item development methods, large-scale item calibration testing, confirmatory factor analysis (CFA), and item response theory-based psychometric analysis.SettingFive SCI Model System centers and one Department of Veterans Affairs medical center in the United States.ParticipantsAdults with traumatic SCI.Results189 individuals with traumatic SCI who experienced a pressure ulcer within the past 7 days completed 30 items related to pressure ulcers. CFA confirmed a unidimensional pool of items. IRT analyses were conducted. A constrained Graded Response Model with a constant slope parameter was used to estimate item thresholds for the 12 retained items.ConclusionsThe 12-item SCI-QOL Pressure Ulcers scale is unique in that it is specifically targeted to individuals with spinal cord injury and at every stage of development has included input from individuals with SCI. Furthermore, use of CFA and IRT methods provide flexibility and precision of measurement. The scale may be administered in its entirety or as a 7-item “short form” and is available for both research and clinical practice.     

Measuring anxiety after spinal cord injury: Development and psychometric characteristics of the SCI-QOL Anxiety item bank and linkage with GAD-7

ObjectiveTo develop a calibrated item bank and computer adaptive test to assess anxiety symptoms in individuals with spinal cord injury (SCI), transform scores to the Patient Reported Outcomes Measurement Information System (PROMIS) metric, and create a statistical linkage with the Generalized Anxiety Disorder (GAD)-7, a widely used anxiety measure.DesignGrounded-theory based qualitative item development methods; large-scale item calibration field testing; confirmatory factor analysis; graded response model item response theory analyses; statistical linking techniques to transform scores to a PROMIS metric; and linkage with the GAD-7.SettingFive SCI Model System centers and one Department of Veterans Affairs medical center in the United States.ParticipantsAdults with traumatic SCI.ResultsSeven hundred sixteen individuals with traumatic SCI completed 38 items assessing anxiety, 17 of which were PROMIS items. After 13 items (including 2 PROMIS items) were removed, factor analyses confirmed unidimensionality. Item response theory analyses were used to estimate slopes and thresholds for the final 25 items (15 from PROMIS). The observed Pearson correlation between the SCI-QOL Anxiety and GAD-7 scores was 0.67.ConclusionsThe SCI-QOL Anxiety item bank demonstrates excellent psychometric properties and is available as a computer adaptive test or short form for research and clinical applications. SCI-QOL Anxiety scores have been transformed to the PROMIS metric and we provide a method to link SCI-QOL Anxiety scores with those of the GAD-7.     

A Comparison of Single-, Two- and Three-Port Laparoscopic Myomectomy

Background and Objective:

A recent FDA safety communication has discouraged the use of a power morcellator for myoma extraction and has called for a change in surgical techniques for myomectomy. The objective of this study was to compare surgical outcomes of laparoscopic single-, two-, and conventional three-port myomectomy and to evaluate the feasibility of contained manual morcellation for uterine myoma.

Methods:

This retrospective study was a review and analysis of data from 191 consecutive women who underwent single-, two-, or three-port myomectomy for the management of uterine myoma from January 1, 2009, through December 31, 2014.

Results:

The 3 study groups did not differ demographically. Apart from operative time, the single- and two-port groups showed operative outcomes comparable to those of the multiport group. The single-port group had significantly longer operative times (P = .0053) than the two- and three-port groups. However, in the latter half of the single-port cases, the operative time was similar to those in the three-port group. The two-port surgery group showed a consistent operative time without a learning period.

Conclusion:

Single- or two-port myomectomy with transumbilical myoma morcellation is feasible and safe, with outcomes comparable to those of three-port myomectomy. These results suggest the potential for minimally invasive management of symptomatic uterine myoma, without the use of a power morcellator.