Although a rare injury, stress fractures cause considerable morbidity for high school athletes of both sexes. Future research should evaluate risks of stress fractures to drive development of targeted prevention efforts.

BackgroundRupture of the fetal membranes is a common harbinger of imminent labor and delivery. Telomere shortening is a surrogate for oxidative stress (OS) and senescence. Fetal leukocyte and placental membrane DNA telomere lengths were evaluated to determine their association with preterm prelabor rupture of the membranes (pPROM) or spontaneous preterm births with intact membranes (PTB), compared to term birth.MethodsTelomere lengths were quantified in cord blood leukocytes (n = 133) from three major groups: 1) pPROM (n = 28), 2) PTB (n = 69) and 3) uncomplicated full term births (controls, n = 35), using real-time quantitative PCR. Placental membrane specimens (n = 18) were used to correlate fetal leukocyte and placental telomere lengths. Telomere length differences among the groups were analyzed by ANOVA. Pearson correlation coefficients determined relationships between leukocyte and placental membrane telomere lengths.ResultsIn pregnancies with intact membranes, fetal leukocyte telomere length was inversely proportional to gestational age. The mean telomere length decreased as gestation progressed, with the shortest at term. pPROM had telomere lengths (9962±3124 bp) that were significantly shorter than gestational age-matched PTB (11546±4348 bp, p = 0.04), but comparable to term births (9011±2497 bp, p = 0.31). Secondary analyses revealed no effects of race (African American vs. Caucasian) or intraamniotic infection on telomere length. A strong Pearson's correlation was noted between fetal leukocyte and placental membrane telomere lengths (ρ = 0.77; p<0.01).ConclusionsFetal leukocyte telomere length is reduced in pPROM compared to PTB but is similar to term births. pPROM represents a placental membrane disease likely mediated by OS-induced senescence.

Improving emergency care of pediatric sepsis is a public health priority, but optimal early diagnostic approaches are unclear. Measurement of lactate levels is associated with improved outcomes in adult septic shock, but pediatric guidelines do not endorse its use, in part because the association between early lactate levels and mortality is unknown in pediatric sepsis. OBJECTIVE To determine whether the initial serum lactate level is associated with 30-day mortality in children with suspected sepsis. DESIGN, SETTING, AND PARTICIPANTS This observational cohort study of a clinical registry of pediatric patients with suspected sepsis in the emergency department of a tertiary children's hospital from April 1, 2012, to December 31, 2015, tested the hypothesis that a serum lactate level of greater than 36 mg/dL is associated with increased mortality compared with a serum lactate level of 36 mg/dL or less. Consecutive patients with sepsis were identified and included in the registry following consensus guidelines for clinical recognition (infection and decreased mental status or perfusion). Among 2520 registry visits, 1221 were excluded for transfer from another medical center, no measurement of lactate levels, and patients younger than 61 days or 18 years or older, leaving 1299 visits available for analysis. Lactate testing is prepopulated in the institutional sepsis order set but may be canceled at clinical discretion. EXPOSURES Venous lactate level of greater than 36 mg/dL on the first measurement within the first 8 hours after arrival. MAIN OUTCOMES AND MEASURES Thirty-day in-hospital mortality was the primary outcome. Odds ratios were calculated using logistic regression to account for potential confounders. RESULTS Of the 1299 patients included in the analysis (753 boys [58.0%] and 546 girls [42.0%]; mean [SD] age, 7.3 [5.3] years), 899 (69.2%) had chronic medical conditions and 367 (28.3%) had acute organ dysfunction. Thirty-day mortality occurred in 5 of 103 patients (4.8%) with lactate levels greater than 36 mg/dL and 20 of 1196 patients (1.7%) with lactate levels of 36 mg/dL or less. Initial lactate levels of greater than 36 mg/dL were significantly associated with 30-day mortality in unadjusted (odds ratio, 3.00; 95% CI, 1.10-8.17) and adjusted (odds ratio, 3.26; 95% CI, 1.16-9.16) analyses. The sensitivity of lactate levels greater than 36 mg/dL for 30-day mortality was 20.0% (95% CI, 8.9%-39.1%), and specificity was 92.3% (90.7%-93.7%). CONCLUSIONS AND RELEVANCE In children treated for sepsis in the emergency department, lactate levels greater than 36 mg/dL were associated with mortality but had a low sensitivity. Measurement of lactate levels may have utility in early risk stratification of pediatric sepsis.

Please cite this paper as: Brou L, Almli L, Pearce B, Bhat G, Drobek C, Fortunato S, Menon R. Dysregulated biomarkers induce distinct pathways in preterm birth. BJOG 2012;119:458–473. Objective  To document racial disparity in biomarker concentrations in maternal/fetal plasma and amniotic fluid between African Americans and European Americans with spontaneous preterm birth (PTB; cases) and normal term birth (controls), and their contribution to distinct pathophysiological pathways of PTB. Design  Nested case–control study. Setting  The Perinatal Research Center, Nashville, Tennessee, USA. Sample  Maternal and fetal plasma and amniotic fluid samples were collected from 105 cases (59 African American and 46 European American) and 86 controls (40 African American and 46 European American). Methods  Thirty‐six biomarkers were analysed using the protein microarray approach. Main outcome measures  Differences in biomarker concentrations between cases and controls of different races in maternal, fetal and intra‐amniotic compartments, and the risk of PTB. Dysregulated biomarker‐induced PTB pathways associated with PTB in each race were determined using ingenuity pathway analysis (IPA). Results  Racial disparity was observed in biomarker concentrations in each compartment between cases and controls: amniotic fluid, IL8 and MIP1α differed between case and controls in European Americans, whereas ANGPT2, Eotaxin, ICAM‐1, IL‐1β, IL1RA, RANTES and TNFα differed between case and controls in African Americans. In both races the FAS ligand, MCP‐3 and TNFR‐I differed between cases and controls. For fetal plasma, ANGPT2, Eotaxin, FGF basic, ICAM‐1, IGF‐I, IL10, IL‐1β, IL2, IP10 KGF, MCP‐3, MIP1α, PDGF‐BB, TGFα, TGFβ1, TIMP1, TNFα, TNFR‐I, TNFR‐II and VEGF differed between cases and controls in European Americans, whereas only MMP7 differed between cases and controls in African Americans. IL‐8 differed between cases and controls in both races. For maternal plasma, IL1RA, MMP7 and VEGF differed between cases and controls in European Americans, whereas ANGPT2, FGF basic, IL‐1β, IL5, IL6R, KGF, MCP‐3, MIP1α, TIMP1 and TNFα differed between cases and controls in African Americans. ANG, IL8 and TNFR‐I differed between cases and controls in both races. Conclusions  We conclude that: (1) biomarker concentrations in maternal, fetal and intra‐amniotic compartments differ between cases and controls; (2) there is racial disparity in the biomarker profile in each of the compartments; (3) substantial numbers of dysregulated fetal plasma biomarkers contribute to PTB in European Americans, whereas maternal plasma biomarkers contribute to PTB in African Americans; and (4) both inflammation and haematological functions are associated with PTB in European Americans, but maternal proinflammatory changes dominate PTB in African Americans. Biomarker analyses document racial disparity and the distinct pathophysiological contributions from different compartments that can determine pregnancy outcome.