A Combined Ultrasonic Backscatter Parameter for Bone Status Evaluation in Neonates

Metabolic bone disease (MBD) is one of the major complications of prematurity. Ultrasonic backscatter technique has the potential to be a portable and noninvasive method for early diagnosis of MBD. This study firstly applied CAS to neonates, which was defined as a linear combination of the apparent integrated backscatter coefficient (AIB) and spectral centroid shift (SCS). The objective was to evaluate the feasibility of ultrasonic backscatter technique for assessing neonatal bone health using AIB, SCS, and CAS. Ultrasonic backscatter measurements at 3.5 MHz, 5.0 MHz, and 7.5 MHz were performed on a total of 505 newborns within 48 hours after birth. The values of backscatter parameters were calculated and compared among gestational age groups. Correlations between backscatter parameters, gestational age, anthropometric indices, and biochemical markers were analyzed. The optimal predicting models for CAS were determined. The results showed term infants had lower SCS and higher AIB and CAS than preterm infants. Gestational age and anthropometric indices were negatively correlated with SCS (|r| = 0.45 – 0.57, P < 0.001), and positively correlated with AIB (|r| = 0.36 – 0.60, P < 0.001) and CAS (|r| = 0.56 – 0.69, P < 0.001). Biochemical markers yielded weak or nonsignificant correlations with backscatter parameters. CAS had relatively stronger correlations with the neonatal variables than AIB and SCS. At 3.5 MHz and 5.0 MHz, only gestational age (P < 0.001) independently contributed to the measurements of CAS, and could explain up to 40.5% – 44.3% of CAS variation. At 7.5 MHz, the combination of gestational age (P < 0.001), head circumference (P = 0.002), and serum calcium (P = 0.037) explained up to 40.3% of CAS variation. This study suggested ultrasonic backscatter technique was feasible to evaluate neonatal bone status. CAS was a promising parameter to provide more information about bone health than AIB or SCS alone

Pregnancy and fertility-related adverse outcomes associated with Chlamydia trachomatis infection: a global systematic review and meta-analysis.

BACKGROUND: Genital chlamydia infection in women is often asymptomatic, but may result in adverse outcomes before and during pregnancy. The purpose of this study was to examine the strength of the relationships between chlamydia infection and different reproductive health outcomes and to assess the certainty of the evidence. METHODS: This review was registered and followed the Cochrane guidelines. We searched three databases to quantitatively examine adverse outcomes associated with chlamydia infection. We included pregnancy and fertility-related outcomes. We performed meta-analyses on different study designs for various adverse outcomes using unadjusted and adjusted analyses. RESULTS: We identified 4730 unique citations and included 107 studies reporting 12 pregnancy and fertility-related outcomes. Sixty-eight studies were conducted in high-income countries, 37 studies were conducted in low-income or middle-income countries, and 2 studies were conducted in both high-income and low-income countries. Chlamydia infection was positively associated with almost all of the 12 included pregnancy and fertility-related adverse outcomes in unadjusted analyses, including stillbirth (OR=5.05, 95% CI 2.95 to 8.65 for case-control studies and risk ratio=1.28, 95% CI 1.09 to 1.51 for cohort studies) and spontaneous abortion (OR=1.30, 95% CI 1.14 to 1.49 for case-control studies and risk ratio=1.47, 95% CI 1.16 to 1.85 for cohort studies). However, there were biases in the design and conduct of individual studies, affecting the certainty of the overall body of evidence. The risk of adverse outcomes associated with chlamydia is higher in low-income and middle-income countries compared with high-income countries. CONCLUSION: Chlamydia is associated with an increased risk of several pregnancy and fertility-related adverse outcomes in unadjusted analyses, especially in low-income and middle-income countries. Further research on how to prevent the sequelae of chlamydia in pregnant women is needed. TRIAL REGISTRATION NUMBER: CRD42017056818

Contemporary Incidence and Predictors of Stent Thrombosis and Other Major Adverse Cardiac Events in the Year After XIENCE V Implantation Results From the 8,061-Patient XIENCE V United States Study

ObjectivesThe aim of this study was to identify predictors of clinical events after XIENCE V (Abbott Vascular, Santa Clara, California) stenting.BackgroundThe XIENCE V USA (XIENCE V Everolimus Eluting Coronary Stent System [EECSS] USA Post-Approval) study is a prospective, multicenter, Food and Drug Administration-required post-approval study to examine safety and effectiveness in real-world settings. After an initial 5,062 patients, 2,999 more were included as part of the DAPT (Dual Antiplatelet Therapy) trial (total n = 8,061).MethodsOne-year clinical events, including stent thrombosis (ST), cardiac death/myocardial infarction (MI), target lesion failure, and target lesion revascularization, were adjudicated according to Academic Research Consortium criteria, with ST and cardiac death/MI as primary and co-primary endpoints. Demographic, clinical, and procedural variables were assessed by multivariable analysis. A time-dependent covariate assessed the association between DAPT usage and ST.ResultsRoughly 61% were off-label; 85.6% remained on DAPT without interruption through 1 year. Incidences of definite/probable ST, cardiac death/MI, target lesion failure, and target lesion revascularization were 0.80% (95% confidence interval [CI]: 0.61% to 1.03%), 7.1% (95% CI: 6.51% to 7.68%), 8.9% (95% CI: 8.30% to 9.60%), and 4.3% (95% CI: 3.82% to 4.75%), respectively. Several independent clinical and angiographic predictors were identified for each outcome. Predictors of ST included DAPT interruption ≤30 days (hazard ratio [HR]: 8.63, 95% CI: 2.69 to 27.73, p = 0.0003), renal insufficiency (HR: 3.72, 95% CI: 1.71 to 8.09, p = 0.0009), and total stent length (HR: 1.30, 95% CI: 1.16 to 1.47, p < 0.0001). A DAPT interruption >30 days was not predictive of ST.ConclusionsIn this large, real-world population, XIENCE V demonstrated low event rates at 1 year, with several independent predictors. Early DAPT interruption (≤30 days) was the most potent predictor of ST, whereas delayed interruption (>30 days) was not predictive. (XIENCE V Everolimus Eluting Coronary Stent System [EECSS] USA Post-Approval Study; NCT00676520

Acyloxyacyl hydrolase promotes the resolution of lipopolysaccharide-induced acute lung injury.

Pulmonary infection is the most common risk factor for acute lung injury (ALI). Innate immune responses induced by Microbe-Associated Molecular Pattern (MAMP) molecules are essential for lung defense but can lead to tissue injury. Little is known about how MAMP molecules are degraded in the lung or how MAMP degradation/inactivation helps prevent or ameliorate the harmful inflammation that produces ALI. Acyloxyacyl hydrolase (AOAH) is a host lipase that inactivates Gram-negative bacterial endotoxin (lipopolysaccharide, or LPS). We report here that alveolar macrophages increase AOAH expression upon exposure to LPS and that Aoah+/+ mice recover more rapidly than do Aoah-/- mice from ALI induced by nasally instilled LPS or Klebsiella pneumoniae. Aoah-/- mouse lungs had more prolonged leukocyte infiltration, greater pro- and anti-inflammatory cytokine expression, and longer-lasting alveolar barrier damage. We also describe evidence that the persistently bioactive LPS in Aoah-/- alveoli can stimulate alveolar macrophages directly and epithelial cells indirectly to produce chemoattractants that recruit neutrophils to the lung and may prevent their clearance. Distinct from the prolonged tolerance observed in LPS-exposed Aoah-/- peritoneal macrophages, alveolar macrophages that lacked AOAH maintained or increased their responses to bioactive LPS and sustained inflammation. Inactivation of LPS by AOAH is a previously unappreciated mechanism for promoting resolution of pulmonary inflammation/injury induced by Gram-negative bacterial infection

AOAH promotes the resolution of pulmonary inflammation induced by Gram-negative bacteria.

<p>(A) <i>Aoah</i>^<i>+/+</i> and <i>Aoah</i>^<i>-/-</i> mice were instilled i.n. with heat-inactivated 5 X 10⁶ <i>Klebsiella pneumoniae</i>. BALF was harvested for immune cell analysis before instillation and one and four days afterward. (B) The AM surface markers were measured using flow cytometry. (C) The lungs were excised and homogenized for cytokine and chemokine mRNA measurement. Data were combined from 2 experiments. Two-way ANOVA was used. n = 4–7.</p

AOAH ameliorates LPS-induced lung injury and promotes recovery.

<p>(A) <i>Aoah</i>^<i>-/-</i> and <i>Aoah</i>^<i>+/+</i> mice were instilled with 200 μg LPS i.n. and their survival was monitored. Log-rank test was used. n = 28 (<i>Aoah</i>^<i>+/+</i>) and 33 (<i>Aoah</i>^<i>-/-</i>). (B) Body weight was measured daily in the mice that survived LPS instillation. Two-way ANOVA test was used. n = 26 (<i>Aoah</i>^<i>+/+</i>) and 18 (<i>Aoah</i>^<i>-/-</i>). (C) The mice that survived were also quantitatively assessed for signs of illness (weight loss, ruffled fur, ocular discharge, rapid shallow breathing, and lethargy). Data were combined from 5 experiments. Two-way ANOVA test was used. n = 26 (<i>Aoah</i>^<i>+/+</i>) and 18 (<i>Aoah</i>^<i>-/-</i>). (D) On days 0, 1, 4, and 7 after 150 μg LPS i.n., <i>Aoah</i>^<i>+/+</i> and <i>Aoah</i>^<i>-/-</i> mouse BALF was collected and the protein concentration was determined. Two-way ANOVA test was used. n = 6–10. (E) In separate experiments, mice were injected with Evans Blue 1 hr before euthanasia. The extravascular dye in the lungs was extracted and measured. Two-way ANOVA test was used. n = 3–6. (F) Before and 1, 4, and 7 days after 150 μg LPS i.n., MPO activity in lung homogenates was measured. Two-way ANOVA test was used. n = 8–9. (G) Hematoxylin-Eosin stained sections of paraformaldehyde-fixed lungs are shown. <i>Aoah</i>^<i>+/+</i> and <i>Aoah</i>^<i>-/-</i> mice were treated with PBS or 150 μg LPS, i.n. One, four and seven days later, their lungs were removed, fixed, sectioned and stained. The images represent at least 75% of whole sections. Original magnification X 40; insets, X 400. n = 3–4.</p