Context:Denosumab and zoledronic acid (ZOL) are parenteral treatments for patients with osteoporosis.Objective:The objective of the study was to compare the effect of transitioning from oral bisphosphonates to denosumab or ZOL on bone mineral density (BMD) and bone turnover.Design and Setting:This was an international, multicenter, randomized, double-blind trial.Participants:A total of 643 postmenopausal women with osteoporosis previously treated with oral bisphosphonates participated in the study.Interventions:Subjects were randomized 1:1 to sc denosumab 60 mg every 6 months plus iv placebo once or ZOL 5 mg iv once plus sc placebo every 6 months for 12 months.Main Outcome Measures:Changes in BMD and bone turnover markers were measured.Results:BMD change from baseline at month 12 was significantly greater with denosumab compared with ZOL at the lumbar spine (primary end point; 3.2% vs 1.1%; P < .0001), total hip (1.9% vs 0.6%; P < .0001), femoral neck (1.2% vs −0.1%; P < .0001), and one-third radius (0.6% vs 0.0%; P < .05). The median decrease from baseline was greater with denosumab than ZOL for serum C-telopeptide of type 1 collagen at all time points after day 10 and for serum procollagen type 1 N-terminal propeptide at month 1 and at all time points after month 3 (all P < .05). Median percentage changes from baseline in serum intact PTH were significantly greater at months 3 and 9 with denosumab compared with ZOL (all P < .05). Adverse events were similar between groups. Three events consistent with the definition of atypical femoral fracture were observed (two denosumab and one ZOL).Conclusions:In postmenopausal women with osteoporosis previously treated with oral bisphosphonates, denosumab was associated with greater BMD increases at all measured skeletal sites and greater inhibition of bone remodeling compared with ZOL.
Background:The prognostic impact of tumour-promoting immune cells in cervical cancer is
unclear.Methods:Federation of Gynaecology and Obstetrics (FIGO) stage IB and IIA cervical cancer
patients (N=101) were assessed for tumour-associated
CD66b+ neutrophils and CD163+ macrophages by
immunohistochemistry in whole tissue sections using stereology. Results were correlated
with previous results on tumour-infiltrating CD3+, CD4+,
and CD8+ lymphocytes in the same cohort with recurrence-free survival
(RFS) as end point.Results:The highest densities of CD66b+ neutrophils and CD163+
macrophages were observed in the peritumoural compartment (median
53.1 cells mm−2 and 1.3% area fraction,
respectively). Above median peritumoural and stromal CD66b+ neutrophils
and peritumoural CD163+ macrophages were significantly associated with
short RFS. Multivariate analysis identified high peritumoural neutrophils (HR 2.27;
95% CI 1.09–4.75; P=0.03), low peritumoural
CD8+ lymphocytes (HR 3.67; 95% CI 1.63–8.25;
P=0.002), and lymph node metastases (HR 2.70; 95% CI
1.26–5.76; P=0.01) as independent prognostic factors for short
RFS, whereas CD163+ macrophages were not significant. An index of
combined intratumoral and peritumoral CD66b+ neutrophils to
CD8+ lymphocytes had good discriminatory power for each quartile with
5-year RFS of 92%, 80%, 62%, and 44%
(P=0.001).Conclusion:Tumour-associated neutrophil count is an independent prognostic factor for short RFS in
localised cervical cancer. Combining CD66b and CD8 may further improve prognostic
stratification. These findings require prospective validation.
The purpose of this study was to investigate the prognostic value of the primary in situ cellular immune response in cervical squamous cell carcinoma. A study of 102 women treated for stage IB and IIA disease, between 1990 and 2000, was performed. Paraffinembedded cervical tissue processed at the time of diagnosis was immunostained for CD3 þ (T cells), CD4 þ (T helper/regulatory T cells) and CD8 þ (cytotoxic T cells) cells. Immune cell profile densities were estimated using stereology. Both intra-and peritumoural cell densities were estimated. Using Cox's proportional hazards regression modelling we found an increase in cell density to decrease the risk of relapse for all three cell types. The density of peritumoural CD3 þ cells seems to have the strongest potential for predicting relapse. An increase in CD3 þ cell density from 795 to 2043 cells per mm 2 (25 -75 percentile) reduced the hazard ratio to 0.27.
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