HR‐pQCT measures of bone microarchitecture predict fracture : systematic review and meta‐analysis

HR‐pQCT is a non‐invasive imaging modality for assessing volumetric bone mineral density (vBMD) and microarchitecture of cancellous and cortical bone. The objective was to (i) assess fracture‐associated differences in HR‐pQCT bone parameters and (ii) to determine if HR‐pQCT is sufficiently precise to reliably detect these differences in individuals. We systematically identified 40 studies that used HR‐pQCT (39/40 used XtremeCT scanners) to assess 1291‐3253 and 3389‐10,687 individuals with and without fractures, respectively, ranging in age from 10.9 to 84.7 years with no comorbid conditions. Parameters describing radial and tibial bone density, microarchitecture, and strength were extracted and percentage differences between fracture and control subjects were estimated using a random effects meta‐analysis. An additional meta‐analysis of short‐term in vivo reproducibility of bone parameters assessed by XtremeCT was conducted to determine whether fracture‐associated differences exceeded the least significant change (LSC) required to discern measured differences from precision error. Radial and tibial HR‐pQCT parameters, including failure load, were significantly altered in fracture subjects, with differences ranging from −2.6% (95% CI: −3.4 to −1.9) in radial cortical vBMD to −12.6% (95% CI: −15.0 to −10.3) in radial trabecular vBMD. Fracture‐associated differences reported by prospective studies were consistent with those from retrospective studies, indicating that HR‐pQCT can predict incident fracture. Assessment of study quality, heterogeneity and publication biases verified the validity of these findings. Finally, we demonstrated that fracture‐associated deficits in total and trabecular vBMD, and certain tibial cortical parameters, can be reliably discerned from HR‐pQCT‐related precision error and can be used to detect fracture‐associated differences in individual patients. Although differences in other HR‐pQCT measures, including failure load, were significantly associated with fracture, improved reproducibility is needed to ensure reliable individual cross‐sectional screening and longitudinal monitoring. In conclusion, our study supports the use of HR‐pQCT in clinical fracture prediction

Gene-expression patterns in whole blood identify subjects at risk for recurrent tuberculosis

Background. The majority of patients with tuberculosis who comply with appropriate treatment are cured. However, ∼5% subsequently have a repeat disease episode, usually within 2 years of successful combination therapy. Presently, there is no way of predicting which patients will experience a relapse. Methods. We identified 10 subjects who had previously experienced recurrent tuberculosis and carefully matched them to cured subjects who had had only 1 episode of tuberculosis, to patients with active tuberculosis, and to latently infected healthy subjects. We compared their ex vivo whole-blood gene-expression profiles by use of DNA array technology and confirmed the results by use of quantitative reverse-transcriptase polymerase chain reaction (qRT-PCR). Results. The 4 clinical tuberculosis groups exhibited distinct patterns of gene expression. The gene-transcript profiles of the patients with recurrent tuberculosis were more similar to those of the patients with active tuberculosis than to those of the cured or latently infected subjects. Discriminant analysis of a training data set showed that 9 genes were sufficient to classify the subjects. We confirmed that measurement of the expression of these genes by qRT-PCR can accurately discriminate between subjects in a test set of samples. Conclusions. A simple test based on gene-expression patterns may be used as a biomarker of cure while identifying patients who are at risk for relapse. This would facilitate the introduction of new tuberculosis drugs. © 2006 by the Infectious Diseases Society of America. All rights reserved.Articl

Baseline sputum time to detection predicts month two culture conversion and relapse in non-HIV-infected patients

BACKGROUND: Few biomarkers are available to identify tuberculosis (TB) patients at risk of delayed sputum conversion and relapse. OBJECTIVES: To investigate whether baseline pretreatment time to detection (TTD) of culture predicted 2-month bacteriological conversion and TB relapse. METHODS: A total of 263 non-HIV-infected smearpositive previously untreated pulmonary TB patients were prospectively followed from diagnosis until treatment outcome after 6 months' treatment and TB recurrence within 24 months. RESULTS: The median TTD was 3 days (range 1-17). Of 211 (80.2%) patients with favourable treatment outcome, 22 (10.4%) had recurrence, while 12 (5.7%) had confi rmed relapse. Culture conversion at 2 months was associated in univariate analysis with the presence and number of cavities, extensive parenchymal involvement, male sex, sputum smear grading and TTD. In multiple logistic regression, TTD or smear grading and extensive parenchymal involvement both predicted month 2 conversion. Relapse was predicted by TTD, sex, body mass index, smear grading and number of cavities in univariate analysis, and in multivariate regression by TTD and sputum smear grading. CONCLUSIONS: Baseline TTD and smear grading predicted month 2 culture conversion, relapse and also recurrence. These markers may be useful to identify non-HIV-infected patients at risk of recurrence, and may be relevant in clinical trials. © 2010 The Union.Articl