Risk assessment and outcome of chronic graft-versus-host disease after allogeneic peripheral blood progenitor cell transplantation in pediatric patients

We retrospectively evaluated the incidence, risk factors for chronic graft-versus-host disease (cGvHD) and outcome in 80 pediatric patients (36 male) (median age 13 years) who underwent allogeneic peripheral blood progenitor cell transplantation. Patients were grafted from an HLA-identical sibling after myeloablative conditioning (total body irradiation (TBI) based 52; non-TBI 28). GvHD prophylaxis used were: cyclosporin A (CsA)+ short methotrexate (MTX) in 52 and CsA+/-prednisone in 28. The median number of CD34+ cells infused were 5.8 x 10(6)/kg (range: 1.4-32.8). The median follow-up was 24 months (range: 3-94). In all, 28 patients had cGvHD (confidence interval (CI): 54.2+/-10%). Factors that were significant on univariate analysis were diagnosis (P=0.03) and GvHD prophylaxis administered (P=0.04). On multivariate analysis, only GvHD prophylaxis used was associated with a significant risk of cGvHD (hazard ratio (HR): 3.94; 95% CI: 1.41-10.91, P=0.009). The CI of cGvHD for patients receiving CsA+MTX was 40.9+/-12 vs 76.5+/-18% for patients who did not (P=0.03). The probability of relapse was 36+/-6% for all patients (12.5+/-8% for patients with cGvHD vs 47.9+/-8% without cGvHD). The probability of disease-free survival was better for patients with cGvHD (69.9+/-10 vs 37.9+/-7%; HR: 3.59, 95% CI: 1.47-5.56; P=0.001). Our data suggest that the GvHD prophylaxis used is the most relevant predictor of cGvHD. Patients with cGvHD had a lower risk of relapse and a better survival.     

Automatic quantification of liver fibrosis: design and validation of a new image analysis method: comparison with semi-quantitative indexes of fibrosis

BACKGROUND/AIMS: Liver fibrosis is one of the most important and characteristic histologic alterations in progressive and chronic liver diseases. Thus, in both clinical and experimental practice, it is fundamental to have a reliable and objective method for its precise quantification. Several semi-quantitative scoring systems have been described. All are time-consuming and produce partially subjective fibrosis evaluations that are not very precise. This paper describes the design and validation of an original image analysis-based application, FibroQuant, for automatically and rapidly quantifying perisinusoidal, perivenular and portal-periportal and septal fibrosis and portal-periportal and septal morphology in liver histologic specimens. METHODS: The implemented image-processing algorithms automatically segment interstitial fibrosis areas, while extraction of portal-periportal and septal region is carried out with an automatic algorithm and a simple interactive step. For validation, all automatically extracted areas were also manually segmented and quantified. RESULTS: Statistical analysis showed significant intra- and interoperator variability in manual segmentation of all areas. Automatic quantifications did not significantly differ from mean manual evaluations of the same areas. Comparison of our image analysis quantifications with staging histologic evaluations of liver fibrosis showed significant correlations (Spearman's, 0.72相似文献   

Body fat distribution in Alaskan Eskimos of the Bering Straits region: the Alaskan Siberia Project

OBJECTIVE: To describe the body fat content and distribution of adult Alaska Natives of the Bering Straits Region. DESIGN: Cross-sectional screening in the spring of 1994. SUBJECTS: 454 non-pregnant native residents from four rural Alaskan villages. MEASUREMENTS: Height, weight, waist, hip and thigh circumference, bioelectrical impedance, sagittal abdominal diameter, and triceps, biceps, suprailiac, subscapular and thigh skinfolds. RESULTS: Mean height, weight and subscapular-to-triceps ratio were higher in men than women. The women had larger waist, hip and thigh circumferences, higher body fatness, as well as larger skinfolds than the men. There were no demonstrable differences between men and women in measures of body fat distribution. The proportions of women and men with high waist-to-hip ratio (>/=0.8 for women, >/=0.9 for men) for low (<25 kg/m2), medium (25-30 kg/m2) and high (>30 kg/m2) body mass index (BMI) groups were compared with a Canadian study of all races. 1 In the lowest BMI subgroup (<25 kg/m2) a much higher proportion of Eskimo women exhibited a high waist-to-hip ratio (91%) than Eskimo men (42%) or Canadian women (29%) or men (51%). In the highest BMI subgroup (>30 kg/m2) Eskimo women were similar in proportion of high waist-to-hip ratio (99%) compared to Eskimo men (100%), but still demonstrated a much greater proportion of subjects with high waist-to-hip ratio than either Canadian men (90%) or women (76%). CONCLUSIONS: The large abdominal fat depots found in Eskimo women were similar to men, and may indicate that future increases in diabetes mellitus and other metabolic alterations can be anticipated. International Journal of Obesity (2000) 24, 171-179     

The effect of hormonal replacement therapy on the vascular reactivity and endothelial function of healthy individuals and individuals with type 2 diabetes

Estrogens protect healthy women from cardiovascular disease. However, epidemiological data suggest that women with diabetes are denied the cardioprotection associated with estrogens. Whether or not hormonal replacement therapy (HRT) confers cardiovascular benefits in postmenopausal women with diabetes is not known. The aim of this study was to examine the effects of HRT on the microvascular reactivity and endothelial function of individuals with and without diabetes. We studied the following groups of individuals: premenopausal healthy women [n = 28, age 41 +/- 8 yr (mean +/- SD)], premenopausal women with type 2 diabetes (n = 16, age 43 +/- 6 yr); postmenopausal healthy women (n = 12, age 57 +/- 4 yr), postmenopausal women with diabetes (n = 17, age 62 +/- 5 yr); postmenopausal healthy women on HRT (n = 13, age 51 +/- 5 yr), postmenopausal women with diabetes on HRT (n = 11, age 57 +/- 7 yr). We used laser Doppler flowmetry to measure forearm cutaneous vasodilatation in response to iontophoresis of 1% acetylcholine (endothelium dependent) and 1% sodium nitroprusside (endothelium independent). The endothelium-dependent vasodilation was significantly higher in premenopausal healthy women (180 +/- 67%; increase over baseline) compared to premenopausal diabetic women (87 +/- 41%; P < 0.001). endothelium-dependent vasodilation was also higher in postmenopausal healthy women on HRT (143 +/- 52) compared with postmenopausal diabetic women on HRT (86 +/- 61), postmenopausal healthy women without HRT (104 +/- 43), and postmenopausal diabetic women without HRT (74 +/- 28; P < 0.001). A similar pattern of responses was observed in the endothelium-independent vasodilation (premenopausal healthy women, 126 +/- 56; premenopausal diabetic women, 88 +/- 26; postmenopausal healthy women on HRT, 121 +/- 37; postmenopausal diabetic women on HRT, 88 +/- 41; postmenopausal healthy women without HRT, 84 +/- 36; and postmenopausal diabetic women without HRT, 73 +/- 36; P < 0.001). Soluble intercellular adhesion molecule (sICAM) was also measured among all the women with diabetes. Premenopausal women with diabetes (248.9 +/- 56 ng/ml) and postmenopausal women with diabetes on HRT (257.7 +/- 49 ng/ml) had lower sICAM levels compared with the postmenopausal diabetic women without HRT (346.4 +/- 149 ng/ml; P < 0.05). We conclude that menopausal status and type 2 diabetes are associated with impaired microvascular reactivity. HRT substantially improves microvascular reactivity in postmenopausal healthy women. In contrast, the effect of HRT on the microvascular reactivity of postmenopausal diabetic women is less apparent. However, the use of HRT among women with diabetes is associated with lower sICAM levels, suggesting an attenuation in endothelial activation.     

Elderly age and prior autologous transplantation have a deleterious effect on survival following allogeneic peripheral blood stem cell transplantation with reduced-intensity conditioning: results from the Spanish multicenter prospective trial

Over a 3-year period, 145 patients ineligible for myeloablative conditioning underwent reduced-intensity conditioning (RIC) hematopoietic stem cell transplantation (SCT) from an HLA-identical sibling in a prospective study. The median age was 54 years, 88 patients were male and 61 patients were beyond the early-intermediate phase of their disease. The 100-day probability of developing grade II-IV acute graft-versus-host disease (GVHD) was 34%, and the 1-year probability of developing chronic extensive GVHD was 41%. The 1-year probabilities of transplant-related mortality (TRM), overall (OS) and progression-free survival were 20, 60 and 52%, respectively. Multivariate analyses found a better OS in: (i) patients <60 years; and (ii) recipients of a first SCT; and a higher TRM in: (i) age >60 years, (ii) recipients of a prior autologous SCT, and (iii) an ECOG performance status >1. The 1-year TRM in patients with 0 or 1 and >2 of the above-mentioned adverse prognostic factors were 17 vs 53%, respectively (P<0.001). In summary, our study shows that elderly patients have a higher TRM following an RIC protocol. However, age by itself should not preclude these RIC transplants, since TRM appears to be unacceptably high only in the presence of additional adverse factors.     

Antibiotic prophylaxis with meropenem after allogeneic stem cell transplantation

In the present study, we analyze the efficacy of prophylaxis with meropenem in patients receiving a matched related donor allogeneic transplant. In total, 38 patients were sequentially treated with meropenem starting on the day of the first febrile episode (n=17, group A) vs prophylactic meropenem starting on the first day with <500/mm(3) granulocytes (n=21, group B), and maintained until resolution of fever or after granulocyte count >500/mm(3). Of these, 16 (94%) patients in group A developed fever as compared to 16 (76%) in group B (P=0.02). While only one patient in group A did not require first-line antibiotherapy, there were seven (33%) in group B who did not require it (P=0.01) since fever lasted less than 72 h. In addition, 52% patients in group B did not require second-line antibiotics as compared to 11% among patients in group A (P=0.04). In multivariate analysis prophylaxis with meropenem (HR=2.83, 95% CI (1-8.02); P=0.04) and disease status at transplant (HR for early stage=0.15, 95% CI (0.04-0.62); P=0.04) significantly influenced the development of fever. In conclusion, the current pilot study suggests that the use of prophylaxis with meropenem during the period of neutropenia in patients undergoing allogeneic transplantation favorably affects the morbidity of the procedure by reducing febrile episodes.