Quantitative fetal fibronectin testing in combination with cervical length measurement in the prediction of spontaneous preterm delivery in symptomatic women.

OBJECTIVE: To evaluate whether in symptomatic women, the combination of quantitative fetal fibronectin (fFN) testing and cervical length (CL) improves the prediction of preterm delivery (PTD) within 7 days compared with qualitative fFN and CL. DESIGN: Post hoc analysis of frozen fFN samples of a nationwide cohort study. SETTING: Ten perinatal centres in the Netherlands. POPULATION: Symptomatic women between 24 and 34 weeks of gestation. METHODS: The risk of PTD <7 days was estimated in predefined CL and fFN strata. We used logistic regression to develop a model including quantitative fFN and CL, and one including qualitative fFN (threshold 50 ng/ml) and CL. We compared the models' capacity to identify women at low risk (<5%) for delivery within 7 days using a reclassification table. MAIN OUTCOME MEASURES: Spontaneous delivery within 7 days after study entry. RESULTS: We studied 350 women, of whom 69 (20%) delivered within 7 days. The risk of PTD in <7 days ranged from 2% in the lowest fFN group (<10 ng/ml) to 71% in the highest group (>500 ng/ml). Multivariable logistic regression showed an increasing risk of PTD in <7 days with rising fFN concentration [10-49 ng/ml: odds ratio (OR) 1.3, 95% confidence interval (95% CI) 0.23-7.0; 50-199 ng/ml: OR 3.2, 95% CI 0.79-13; 200-499 ng/ml: OR 9.0, 95% CI 2.3-35; >500 ng/ml: OR 39, 95% CI 9.4-164] and shortening of the CL (OR 0.86 per mm, 95% CI 0.82-0.90). Use of quantitative fFN instead of qualitative fFN resulted in reclassification of 18 (5%) women from high to low risk, of whom one (6%) woman delivered within 7 days. CONCLUSION: In symptomatic women, quantitative fFN testing does not improve the prediction of PTD within 7 days compared with qualitative fFN testing in combination with CL measurement in terms of reclassification from high to low (<5%) risk, but it adds value across the risk range. TWEETABLE ABSTRACT: Quantitative fFN testing adds value to qualitative fFN testing with CL measurement in the prediction of PTD.

Suboptimal bonding impairs hormonal, epigenetic and neuronal development in preterm infants, but these impairments can be reversed.

UNLABELLED: This review aimed to raise awareness of the consequences of suboptimal bonding caused by prematurity. In addition to hypoxia-ischaemia, infection and malnutrition, suboptimal bonding is one of the many unnatural stimuli that preterm infants are exposed to, compromising their physiological development. However, the physiological consequences of suboptimal bonding are less frequently addressed in the literature than those of other threatening unnatural stimuli. CONCLUSION: This review found that suboptimal bonding significantly impaired hormonal, epigenetic and neuronal development, but these impairments could be reversed by bonding interventions. This suggests that neonatal intensive care units should focus more on interventions that optimise bonding.

Helium-induced early preconditioning and postconditioning are abolished in obese Zucker rats in vivo.

Preconditioning is abolished in the prediabetic Zucker obese rat. It has been shown that prevention of mitochondrial permeability transition pore (mPTP) opening is involved in preconditioning by the noble gas helium. Here, we investigated: 1) whether helium induces pre- and postconditioning in Zucker rats and 2) whether possible regulators of the mPTP [i.e., mitochondrial respiration or the extracellular signal-regulated kinase (Erk) 1/2, Akt/glycogen synthase kinase (GSK)-3beta signaling pathway] are influenced. Anesthetized Zucker lean (ZL) and Zucker obese (ZO) rats were randomized to seven groups. Control animals were not treated (ZL-/ZO-Con). Preconditioning groups (ZL-/ZO-He-PC) inhaled 70% helium for 3 x 5 or 6 x 5 min, and postconditioning groups (ZL-/ZO-He-PostC) inhaled 70% helium for 15 min at the onset of reperfusion. Animals underwent 25 min of ischemia and 120 min of reperfusion. In additional experiments, hearts were excised after the third helium exposure for analysis of mitochondrial respiration and for Western blot analysis of Erk1/2, Akt, and GSK-3beta phosphorylation. Helium reduced infarct size from 52 +/- 3% (mean +/- S.E.) to 32 +/- 2% and 37 +/- 2% in ZL rats (ZL-HE-PC, ZL-He-PostC), respectively, but not in ZO rats [ZO-He-PC, 56 +/- 3%; ZO-He-PC (6x), 57 +/- 4%; and ZO-He-PostC, 51 +/- 3% versus ZO-Con, 54 +/- 3%]. Mitochondrial respiration analysis showed that helium causes mild uncoupling in ZL rats (2.27 +/- 0.03 versus 2.51 +/- 0.03) but not in ZO rats (2.52 +/- 0.04 versus 2.52 +/- 0.03). Helium had no effect on Erk1/2 and Akt phosphorylation. GSK-3beta phosphorylation during ischemia was reduced after helium application in ZL but not in ZO rats. Helium-induced preconditioning is abolished in obese Zucker rats in vivo, probably caused by a diminished effect of helium on mitochondrial respiration.

Oxytocin levels in the saliva of preterm infant twins during Kangaroo care.

BACKGROUND AND PURPOSE: To investigate whether Kangaroo care (KC) influences the salivary oxytocin (OT) concentration in preterm infants, and which correlates affect the OT response. METHODS: Eleven twin pairs participated in a study in which we collected saliva using cotton swabs twice a day, once during KC and once during baseline conditions (lying in bed or incubator). The total study duration was five days. The saliva of twin siblings were pooled to obtain vials with sufficient volumes of either saliva collected during KC or at baseline. OT levels were measured using a radio-immuno assay. The infants' state of comfort and parent-infant interaction were examined using previously developed Likert-scales, amongst other correlates such as the KC duration, gestational age and birth weight. RESULTS: During KC, OT was lower compared to baseline (mean 1.39 pg/ml (SD 0.58 pg/ml) versus 2.40 pg/ml (SD 1.64 pg/ml), p =  0.03). Comfort at baseline and parent-infant interaction seemed to influence OT responses. CONCLUSION: The OT concentration in the pooled saliva of preterm infant twins decreased during KC. This response of the OT system might be explained by stress during baseline.

Outcomes in pediatric patients with abdominal compartment syndrome following urgent exploratory laparotomy.

BACKGROUND/PURPOSE: Abdominal compartment syndrome (ACS) is a serious condition with high mortality in critically ill children. Our objectives were to characterize the incidence of ACS in pediatric patients who underwent urgent exploratory laparotomy and to compare outcomes of patients with and without ACS. METHODS: This retrospective review examined pediatric patients (0-18years) who underwent urgent exploratory laparotomy over a 2-year period. Primary outcome was mortality; secondary outcomes were achievement of primary fascial closure and necessity of bowel resection. RESULTS: One hundred nineteen patients were included, of which 33 (28%) had ACS, with 27 (23%) being primary ACS and 6 (5%) secondary ACS. Twenty-eight-day mortality was higher in the ACS versus non-ACS group (52% versus 0%, p<0.001) and overall hospitalization (64% versus 2%, p<0.001). Primary fascial closure was achieved less often in ACS compared to non-ACS patients (46% versus 98%, p<0.001). Bowel resection was more frequent in ACS versus non-ACS patients, approaching statistical significance (49% versus 30%, p 0.056). CONCLUSION: During the study period, almost one third of children who underwent urgent exploratory laparotomy had ACS and 64% died. Children undergoing evaluation for acute surgical abdomen may benefit from routine intraabdominal pressure measurement. LEVEL OF EVIDENCE: Level III retrospective comparative study.

Imbalanced presence of Borrelia burgdorferi s.l. multilocus sequence types in clinical manifestations of Lyme borreliosis.

In this study we used typing based on the eight multilocus sequence typing scheme housekeeping genes (MLST) and 5S-23S rDNA intergenic spacer (IGS) to explore the population structure of Borrelia burgdorferi sensu lato isolates from patients with Lyme borreliosis (LB) and to test the association between the B. burgdorferi s.l. sequence types (ST) and the clinical manifestations they cause in humans. Isolates of B. burgdorferi from 183 LB cases across Europe, with distinct clinical manifestations, and 257 Ixodes ricinus lysates from The Netherlands, were analyzed for this study alone. For completeness, we incorporated in our analysis also 335 European B. burgdorferi s.l. MLST profiles retrieved from literature. Borrelia afzelii and Borrelia bavariensis were associated with human cases of LB while Borrelia garinii, Borrelia lusitaniae and Borrelia valaisiana were associated with questing I. ricinus ticks. B. afzelii was associated with acrodermatitis chronica atrophicans, while B. garinii and B. bavariensis were associated with neuroborreliosis. The samples in our study belonged to 251 different STs, of which 94 are newly described, adding to the overall picture of the genetic diversity of Borrelia genospecies. The fraction of STs that were isolated from human samples was significantly higher for the genospecies that are known to be maintained in enzootic cycles by mammals (B. afzelii, B. bavariensis, and Borrelia spielmanii) than for genospecies that are maintained by birds (B. garinii and B. valaisiana) or lizards (B. lusitaniae). We found six multilocus sequence types that were significantly associated to clinical manifestations in humans and five IGS haplotypes that were associated with the human LB cases. While IGS could perform just as well as the housekeeping genes in the MLST scheme for predicting the infectivity of B. burgdorferi s.l., the advantage of MLST is that it can also capture the differential invasiveness of the various STs.

Intestinal Enterococcus faecium colonization improves host defense during polymicrobial peritonitis.

BACKGROUND: Vancomycin-resistant (VR) Enterococcus faecium is increasingly found to colonize and infect hospitalized patients. Enterococci are frequently isolated from polymicrobial infections originating from the intestines. The impact of VR E. faecium on these infections and vice versa is not clear. METHODS: Mice were intestinally colonized with VR E. faecium during oral vancomycin treatment; control mice received oral vancomycin only. Fourteen days later, cecal ligation and puncture (CLP) was performed in all mice to induce polymicrobial peritonitis in the presence or absence of VR E. faecium colonization. RESULTS: VR E. faecium colonization per se was not associated with systemic dissemination of VR E. faecium. CLP resulted in systemic VR E. faecium infection in all VR E. faecium-colonized mice, with high VR E. faecium loads in peritoneal lavage fluid, blood, liver, and lungs. Forty-eight hours after CLP, mice infected with VR E. faecium had significantly lower bacterial loads in all organs tested than mice not infected with VR E. faecium. Additionally, lower inflammatory parameters were measured in VR E. faecium-infected mice. CLP induced transient liver and kidney damage, with a faster recovery in VR E. faecium-colonized mice. CONCLUSIONS: VR E. faecium infection, originating from a natural source (the intestinal tract), does not worsen the outcome of CLP-induced polymicrobial peritonitis and sepsis but rather facilitates bacterial clearance and attenuates host inflammatory responses.

Preferential protection of Borrelia burgdorferi sensu stricto by a Salp15 homologue in Ixodes ricinus saliva.

BACKGROUND: Ixodes ticks are the main vectors for Borrelia burgdorferi sensu lato. In the United States, B. burgdorferi is the sole causative agent of Lyme borreliosis and is transmitted by Ixodes scapularis. In Europe, 3 Borrelia species-B. burgdorferi, B. garinii, and B. afzelii-are prevalent, which are transmitted by Ixodes ricinus. The I. scapularis salivary protein Salp15 has been shown to bind to B. burgdorferi outer surface protein (Osp) C, protecting the spirochete from antibody-mediated killing. METHODS AND RESULTS: We recently identified a Salp15 homologue in I. ricinus, Salp15 Iric-1. Here, we have demonstrated, by solid-phase overlays, enzyme-linked immunosorbent assay, and surface plasmon resonance, that Salp15 Iric-1 binds to B. burgdorferi OspC. Importantly, this binding protected the spirochete from antibody-mediated killing in vitro and in vivo; immune mice rechallenged with B. burgdorferi preincubated with Salp15 Iric-1 displayed significantly higher Borrelia numbers and more severe carditis, compared with control mice. Furthermore, Salp15 Iric-1 was capable of binding to OspC from B. garinii and B. afzelii, but these Borrelia species were not protected from antibody-mediated killing. CONCLUSIONS: Salp15 Iric-1 interacts with all European Borrelia species but differentially protects B. burgdorferi from antibody-mediated killing, putatively giving this Borrelia species a survival advantage in nature.

Maternal ECG removal from non-invasive fetal ECG recordings.

Fetal monitoring during pregnancy is important to support medical decision making. The fetal electrocardiogram (fECG) is a valuable signal to diagnose fetal well-being. Non-invasive recording of the fECG is performed by positioning electrodes on the maternal abdomen. The signal-to-noise ratio of these recordings is relatively low and the main undesired signal is the maternal electrocardiogram (mECG). Existing methods to remove the mECG signal are not sufficiently accurate to extract the complete fECG signal. In this paper, a novel method for removal of the mECG signal from abdominal recordings is presented. It is an extension of the linear prediction method. Each mECG complex is segmented and these segments are separately estimated by linear prediction. Both the presented method and the standard linear prediction are applied to simulated abdominal recordings and evaluated by determining the rms errors between the estimated and the actual fECG signals. The ratio between the rms errors of the linear prediction method and the presented method varies between 0.4 dB and 2.3 dB. It can therefore be concluded that the presented method is capable of a more accurate removal of the mECG signal for all simulated abdominal recordings with respect to the linear prediction method.