Vertebral bone quality score predicts fragility fractures independently of bone mineral density

BackgroundCurrent evidence suggests that dual-energy x-ray absorptiometry (DXA) scans, the conventional method defining osteoporosis, is underutilized and, when used, may underestimate patient risk for skeletal fragility. It has recently been suggested that other imaging modalities may better estimate bone quality, such as the magnetic resonance imaging (MRI)-based vertebral bone quality (VBQ) score which also may assess vertebral compression fracture risk in patients with spine metastases.PurposeTo evaluate whether VBQ score is predictive of fragility fractures in a population with pre-existing low bone density and at high-risk for fracture.Study Design/SettingRetrospective single-center cohort.Patient SamplePatients followed at a metabolic bone clinic for osteopenia and/or osteoporosis.Outcome MeasuresRadiographically-documented new-onset fragility fracture.MethodsPatients with a DXA and MRI scans at the time of consultation and ≥2-year follow-up were included. Details were gathered about patient demographics, health history, current medication use, and serological studies of kidney function and bone turnover. For each patient, VBQ score was calculated using T1-weighted lumbar MRI images. Univariable and multivariable analyses were used to identify the independent predictors of a new fragility fracture. To support the construct validity of VBQ, patient VBQ scores were compared to those in a cohort of 45 healthy adults.ResultsSeventy-two (39.1%) study participants suffered fragility fractures, the occurrence of which was associated with higher VBQ score (3.50 vs. 3.01; p<.001), chronic glucocorticoid use (30.6% vs. 15.2%; p=.014), and a history of prior fragility fracture (36.1% vs. 21.4%; p=.030). Mean VBQ score across all patients in the study cohort was significantly higher than the mean VBQ score in the healthy controls (p<.001). In multivariable analysis, new-onset fracture was independently associated with history of prior fracture (OR=6.94; 95% confidence interval [2.48–19.40]; p<.001), higher VBQ score (OR=2.40 per point; [1.30–4.44]; p=.003), higher body mass index (OR=1.09 per kg/m²; [1.01–1.17]; p=.03), and chronic glucocorticoid use (OR=2.89; [1.03–8.17]; p=0.043). Notably, DXA bone mineral density (BMD) was not found to be significantly predictive of new-onset fractures in the multivariable analysis (p=.081).ConclusionsHere we demonstrate the novel, MRI-derived VBQ score is both an independent predictor of fragility fracture in at-risk patients and a superior predictor of fracture risk than DXA-measured BMD. Given the frequency with which MRIs are obtained by patients undergoing spine surgery consultation, we believe the VBQ score could be a valuable tool for estimating bone quality in order to optimize the management of these patients.     

Discovery and Validation of a Urinary Exosome mRNA Signature for the Diagnosis of Human Kidney Transplant Rejection

BackgroundDeveloping a noninvasive clinical test to accurately diagnose kidney allograft rejection is critical to improve allograft outcomes. Urinary exosomes, tiny vesicles released into the urine that carry parent cells’ proteins and nucleic acids, reflect the biologic function of the parent cells within the kidney, including immune cells. Their stability in urine makes them a potentially powerful tool for liquid biopsy and a noninvasive diagnostic biomarker for kidney-transplant rejection.MethodsUsing 192 of 220 urine samples with matched biopsy samples from 175 patients who underwent a clinically indicated kidney-transplant biopsy, we isolated urinary exosomal mRNAs and developed rejection signatures on the basis of differential gene expression. We used crossvalidation to assess the performance of the signatures on multiple data subsets.ResultsAn exosomal mRNA signature discriminated between biopsy samples from patients with all-cause rejection and those with no rejection, yielding an area under the curve (AUC) of 0.93 (95% CI, 0.87 to 0.98), which is significantly better than the current standard of care (increase in eGFR AUC of 0.57; 95% CI, 0.49 to 0.65). The exosome-based signature’s negative predictive value was 93.3% and its positive predictive value was 86.2%. Using the same approach, we identified an additional gene signature that discriminated patients with T cell–mediated rejection from those with antibody-mediated rejection (with an AUC of 0.87; 95% CI, 0.76 to 0.97). This signature’s negative predictive value was 90.6% and its positive predictive value was 77.8%.ConclusionsOur findings show that mRNA signatures derived from urinary exosomes represent a powerful and noninvasive tool to screen for kidney allograft rejection. This finding has the potential to assist clinicians in therapeutic decision making.     

Transient association between semen exposure and biomarkers of genital inflammation in South African women at risk of HIV infection

IntroductionSemen induces mucosal changes in the female reproductive tract to improve pregnancy outcomes. Since semen‐induced alterations are likely short‐lived and genital inflammation is linked to HIV acquisition in women, we investigated the contribution of recent semen exposure on biomarkers of genital inflammation in women at high HIV risk and the persistence of these associations.MethodsWe assessed stored genital specimens from 152 HIV‐negative KwaZulu‐Natal women who participated in the CAPRISA 008 trial between November 2012 and October 2014. During the two‐year study period, 651 vaginal specimens were collected biannually (mean five samples per woman). Cervicovaginal lavage (CVL) was screened for prostate‐specific antigen (PSA) by ELISA, whereas Y‐chromosome DNA (YcDNA) detection and quantification were conducted by RT‐PCR, representing semen exposure within 48 hours (PSA+YcDNA+) and semen exposure within three to fifteen days (PSA−YcDNA+). Soluble protein concentrations were measured in CVLs by multiplexed ELISA. T‐cell frequencies were assessed in cytobrushes by flow‐cytometry, and vulvovaginal swabs were used to detect common vaginal microbes by PCR. Linear mixed models adjusting for factors associated with genital inflammation and HIV risk were used to assess the impact of semen exposure on biomarkers of inflammation over multiple visits.ResultsHere, 19% (125/651) of CVLs were PSA+YcDNA+, 14% (93/651) were PSA−YcDNA+ and 67% (433/651) were PSA−YcDNA−. Semen exposure was associated with how often women saw their partners, the frequency of vaginal sex in the past month, HSV‐2 antibody detection, current gonorrhoea infection and Nugent Score. Both PSA detection (PSA+YcDNA+) and higher cervicovaginal YcDNA concentrations predicted increases in several cytokines, barrier‐related proteins (MMP‐2, TIMP‐1 and TIMP‐4) and activated CD4+CCR5+HLA‐DR+ T cells (β = 0.050; CI 0.001 to 0.098; p = 0.046) and CD4+HLA‐DR+ T cells (β = 0.177; CI 0.016 to 0.339; p = 0.032) respectively. PSA detection was specifically associated with raised pro‐inflammatory cytokines (including IL‐6, TNF‐α, IP‐10 and RANTES), and with the detection of BVAB2 (OR = 1.755; CI 1.116 to 2.760; p = 0.015), P. bivia (OR = 1.886; CI 1.102 to 3.228; p = 0.021) and Gardnerella vaginalis (OR = 1.815; CI 1.093 to 3.015; p = 0.021).ConclusionsMore recent semen exposure was associated with raised levels of inflammatory biomarkers and the detection of BV‐associated microbes, which declined by three to fifteen days of post‐exposure. Although transient, semen‐induced alterations may have implications for HIV susceptibility in women.     

Powdered infant formula as a source of Salmonella infection in infants.

Powdered infant formula is not sterile and may be intrinsically contaminated with pathogens, such as Salmonella enterica, that can cause serious illness in infants. In recent years, at least 6 outbreaks of Salmonella infection in infants that have been linked to the consumption of powdered infant formula have been reported. Many of these outbreaks were identified because the Salmonella strains were unique in some way (e.g., a rare serotype) and a well-established Salmonella surveillance network, supported by laboratories capable of serotyping isolates, was in place. Another common feature of the outbreaks was the low level of salmonellae detected in the implicated formula (salmonellae may be missed in routine testing). These outbreaks likely represent only a small proportion of the actual number of Salmonella infections in infants that have been linked to powdered infant formula. Managing this problem requires a multidimensional approach in which manufacturers, regulators, and caregivers to infants can all play a role.