Lung transplantation in children following bone marrow transplantation: A multi‐center experience

Allogenic BMT has been successfully performed as a treatment for hematologic diseases with an expected long‐term survival. This survival is truncated by respiratory complications including airway obstruction especially BO. Chronic GVHD has been reported to precede almost all cases reported. LTx has become a therapeutic life‐saving option for patients with end‐stage lung disease that maybe offered for the treatment of GVHD. We report a multi‐center experience of pediatric LTx following BMT in 11 patients age‐ and gender‐matched with 11 controls who received LTx for end‐stage lung disease secondary to CF. Overall death was 36.4% over a follow‐up period of 19 months (range 3–36 months) for the cases and 27.3% for the control group followed for 17 months (range 8–32 months). Median FEV₁ one yr post‐transplant for the cases was 78% predicted compared with 67.3% predicted for the controls. The median for episodes of infection was comparable at a median of one episode per patient through the entire follow‐up period among both groups. Acute rejection episodes were significantly higher in the control group with a median of one episode per patient in the control group compared to none within the cases. Our data suggest that LTx may be a valuable therapeutic option for children with end‐stage lung disease post‐BMT with comparable survival outcome to that after LTx in children for other indications such as CF. Hospital stay was significantly longer in our case group. Infection rate was comparable between groups albeit type of infection varied. Significantly and of interest is that acute rejection episodes were non‐existent in these cases.     

Evaluation and prognostic significance of human tissue kallikrein-related peptidase 6 (KLK6) in colorectal cancer

The prognosis of patients with colorectal cancer (CRC) is assessed through conventional clinicopathological parameters, which are not always accurate. Members of the human kallikrein-related peptidases gene family represent potential cancer biomarkers. The aim of this study was to investigate the expression of human tissue kallikrein-related peptidase 6 (KLK6) by immunohistochemistry in CRC to correlate this expression with various histopathological and clinical variables, and to evaluate its significance as a predictor of disease outcome. KLK6 expression was evaluated by immunohistochemistry and an expression score was calculated for each case. In CRC, KLK6 expression was decreased compared to normal colonic mucosa. A statistically significant, positive association was observed between KLK6 and tumor stage (p=0.036), lymph node metastases (p=0.030), and liver metastases (p=0.025). Univariate analysis showed that KLK6 expression and stage had statistically significant correlation with disease-free survival (p=0.045 and p<0.001, respectively) and overall survival (p=0.027 and p<0.001, respectively). Cox multivariate analysis showed that KLK6 expression was an independent predictor of unfavorable overall survival (p=0.041). Kaplan-Meier survival curves showed that KLK6-positive patients have statistically significant lower disease-free and overall survival. In conclusion, KLK6 immunostaining is an independent prognostic marker in patients with CRC.     

Monocyte proliferation and differentiation to osteoclasts is affected by density of collagen covalently bound to a poly(dimethyl siloxane) culture surface

Osteoclast differentiation is affected by substrate characteristics and environmental conditions; these parameters are therefore of interest for understanding bone remodeling. As a step toward osteoclast mechanotransduction experiments, we aimed to optimize conditions for osteoclast differentiation on extendable poly(dimethylsiloxane) (PDMS) substrates. Because cells attach poorly on PDMS alone, chemical modification by covalent attachment of collagen type I was performed. Effects of collagen surface concentrations on monocyte fusion and osteoclast differentiation were examined. Osteoclasts differentiated on modified PDMS were fewer in number (by ～50%) than controls on polystyrene physically modified by nonspecific attachment of collagen, and exhibited somewhat different morphologies. Nevertheless, for certain choices of the chemical modification procedures, appropriate differentiation on PDMS was still evident by qRT-PCR analysis for tartrate-resistant acid phosphate (TRAP) and cathepsin K (CTSK) gene expression, positive TRAP staining, fluorescent phalloidin staining showing actin ring formation and bone resorption assays. At relatively high collagen surface densities, monocyte clumps appeared on PDMS suggesting substrate-induced alterations to monocyte fusion. Covalently bound collagen can therefore be used to promote osteoclast differentiation on extendable PDMS substrates. Under appropriate conditions osteoclasts retain similar functionality as on polystyrene, which will enable future studies of osteoclast interactions with microstructured surfaces and mechanostimulation.     

Microvascular density as an independent predictor of clinical outcome in renal cell carcinoma: an automated image analysis study

Tumor microvascular density (MVD) has been shown to correlate with the aggressiveness of several cancers. With the introduction of targeted anti-angiogenic therapy, assessment of MVD has the potential not only as a prognostic but also as a therapeutic marker. The significance of tumor vascularity in clear cell renal cell carcinoma (ccRCC) has been debated, with studies showing contradictory results. Previous studies were limited by manual quantification of MVD within a small area of tumor. Since then, the validity of this method has been questioned. To avoid the inaccuracies of manual quantification, we employed a computerized image analysis, which allowed assessment of large areas of tumor and adjacent normal tissue. The latter was used as an internal reference for normalization. MVD and vascular endothelial growth factor (VEGF) were assessed in 57 cases of ccRCC. Sections were immunostained for CD34 and VEGF. Areas of ccRCC and normal kidney medulla were analyzed within scanned images using software that counted CD34-positive vessels and measured the intensity of VEGF staining. We obtained unadjusted values from tumoral areas and calculated adjusted values as tumor/normal ratios. Unadjusted MVD had no association with clinical outcome. However, similarly to tumor stage, higher adjusted MVD was associated with shorter disease-free survival (log-rank P=0.037, Cox P=0.02). This was significant in univariate and multivariate analyses. MVD did not correlate with tumor stage, pointing to its independent prognostic value. As expected due to the known molecular abnormalities in ccRCC, most tumors showed higher VEGF expression than normal tissue. Higher adjusted VEGF was associated with high tumor grade (P=0.049). The finding of increased MVD as an independent marker of tumor aggressiveness may prove useful in the development of new tests for prognostic and therapeutic guidance. Digital techniques can provide more accurate assessment of immunomarkers and may reveal less obvious associations.     

Sickle cell disease subphenotypes in patients from Southwestern Province of Saudi Arabia

Sickle cell disease (SCD) is common in the Eastern and Southwestern (SW) Provinces of Saudi Arabia. We studied 159 patients with SCD to better characterize its phenotype in the SW Province, where patients usually have a HBB haplotype of African origin. All cases had history and examination, chart review, and laboratory testing. Blood tests were obtained during steady state and included: complete blood count, reticulocytes, hemoglobin electrophoresis, lactate dehydrogenase, and G6PD level. HBB haplotype and presence of α-thalassemia were also determined. Frequency of various SCD complications was as follows: painful episodes of variable severity occurred in majority of patients (98%), osteonecrosis (14%), acute chest syndrome (22%), splenic sequestration (23%), gallstones (34%), stroke (7.5%), priapism (2.6%), serious infections (11.5%), and persistent splenomegaly (11%) beyond 5 years of age. No patient had leg ulcer. History of asthma and high steady state white blood cells count were associated with increased risk of acute chest syndrome. Coinheritance of α-thalassemia was associated with a lower frequency of gallstones. Higher fetal hemoglobin level was associated with persistent splenomegaly but not with other complications. Splenic sequestration was more common among males and was associated with lower steady state hemoglobin. SCD phenotype in the SW Province is variable and comparable with African Americans except for the rarity of priapism and the absence of leg ulcers. Fetal hemoglobin level was not associated with SCD vaso-occlusive complications. New genetic modifiers and environmental factors might modulate the phenotype of SCD in Saudi Arabia.     

Effect of physical activity and sun exposure on vitamin D status of Saudi children and adolescents

Background

1) To evaluate calcium absorption in infants fed a formula containing prebiotics (PF) and one without prebiotics (CF). 2) To compare calcium absorption from these formulas with a group of human milk-fed (HM) infants.

Methods

A dual tracer stable isotope method was used to assess calcium absorption in infants exclusively fed CF (n?=?30), PF (n?=?25) or HM (n?=?19). Analysis of variance was used to analyze calcium intake, fractional calcium absorption, and the amount of calcium absorbed.

Results

Calcium intake (Mean ± SEM) for PF was 534?±?17?mg/d and 557?±?16?mg/d for CF (p?=?0.33). Fractional calcium absorption was 56.8?±?2.6?% for PF and 59.2?±?2.3?% for CF (p?=?0.49). Total calcium absorbed for PF was 300?±?14?mg/d and 328?±?13?mg/d for CF (p?=?0.16). For HM infants calcium intake was 246?±?20?mg/d, fractional calcium absorption was 76.0?±?2.9?% and total calcium absorbed was 187?±?16?mg/d (p <0.001, compared to either PF or CF).

Conclusions

Despite lower fractional calcium absorption of CF and PF compared to HM, higher calcium content in both led to higher total calcium absorption compared to HM infants. No significant effect of prebiotics was observed on calcium absorption or other markers of bone mineral metabolism.