Midtrimester preterm prelabour rupture of membranes (PPROM):expectant management or amnioinfusion for improving perinatal outcomes (PPROMEXIL - III trial)

BACKGROUND: Babies born after midtrimester preterm prelabour rupture of membranes (PPROM) are at risk to develop neonatal pulmonary hypoplasia. Perinatal mortality and morbidity after this complication is high. Oligohydramnios in the midtrimester following PPROM is considered to cause a delay in lung development. Repeated transabdominal amnioinfusion with the objective to alleviate oligohydramnios might prevent this complication and might improve neonatal outcome. METHODS/DESIGN: Women with PPROM and persisting oligohydramnios between 16 and 24 weeks gestational age will be asked to participate in a multi-centre randomised controlled trial. Intervention: random allocation to (repeated) abdominal amnioinfusion (intervention) or expectant management (control). The primary outcome is perinatal mortality. Secondary outcomes are lethal pulmonary hypoplasia, non-lethal pulmonary hypoplasia, survival till discharge from NICU, neonatal mortality, chronic lung disease (CLD), number of days ventilatory support, necrotizing enterocolitis (NEC), periventricular leucomalacia (PVL) more than grade I, severe intraventricular hemorrhage (IVH) more than grade II, proven neonatal sepsis, gestational age at delivery, time to delivery, indication for delivery, successful amnioinfusion, placental abruption, cord prolapse, chorioamnionitis, fetal trauma due to puncture. The study will be evaluated according to intention to treat. To show a decrease in perinatal mortality from 70% to 35%, we need to randomise two groups of 28 women (two sided test, β-error 0.2 and α-error 0.05). DISCUSSION: This study will answer the question if (repeated) abdominal amnioinfusion after midtrimester PPROM with associated oligohydramnios improves perinatal survival and prevents pulmonary hypoplasia and other neonatal morbidities. Moreover, it will assess the risks associated with this procedure. TRIAL REGISTRATION: NTR3492 Dutch Trial Register (http://www.trialregister.nl)

Genotyping a second growth coast redwood forest : a high throughput methodology

The idea that excitonic (electronic) coherences are of fundamental importance to natural photosynthesis gained popularity when slowly dephasing quantum beats (QBs) were observed in the two-dimensional electronic spectra of the Fenna–Matthews–Olson (FMO) complex at 77 K. These were assigned to superpositions of excitonic states, a controversial interpretation, as the strong chromophore–environment interactions in the complex suggest fast dephasing. Although it has been pointed out that vibrational motion produces similar spectral signatures, a concrete assignment of these oscillatory signals to distinct physical processes is still lacking. Here we revisit the coherence dynamics of the FMO complex using polarization-controlled two-dimensional electronic spectroscopy, supported by theoretical modelling. We show that the long-lived QBs are exclusively vibrational in origin, whereas the dephasing of the electronic coherences is completed within 240 fs even at 77 K. We further find that specific vibrational coherences are produced via vibronically coupled excited states. The presence of such states suggests that vibronic coupling is relevant for photosynthetic energy transfer

Clinical management of the most common extra-intestinal manifestations in patients with inflammatory bowel disease focused on the joints, skin and eyes

Extra-intestinal manifestations (EIMs) of inflammatory bowel disease (IBD) occur frequently and contribute to morbidity and reduced quality of life. The musculoskeletal, ocular and cutaneous organ systems are frequently involved in IBD-related EIMs. By focusing on manifestations involving the joints, skin and eyes, this review will discuss the most common clinically relevant and burdensome EIMs that affect IBD patients, and strives for early recognition, adequate treatment and timely referral. For this purpose, we aimed to create a comprehensive overview on this topic, with the main focus on the treatment of reactive and associated EIMs, including spondyloarthropathies, pyoderma gangrenosum, erythema nodosum, psoriasis and anterior uveitis. The recently developed biologicals enable simultaneous treatment of inflammatory disorders. This review can be used as a helpful guide in daily clinical practice for physicians who are involved in the treatment of IBD patients

Effect of Daily Intake of Lactobacillus casei on Microbial Diversity and Dynamics in a Healthy Pediatric Population

Emerging evidence exists that an altered gut microbiota is a key factor in the pathophysiology of a variety of diseases. Consequently, microbiota-targeted interventions, including administration of probiotics, have increasingly been evaluated. Mechanisms on how probiotics contribute to homeostasis or reverse (effects of) dysbiosis remain yet to be elucidated. In the current study, we assessed the effects of daily Lactobacillus casei strain Shirota (LcS) ingestion in healthy children aged from 12–18 years on gut microbiota compositional diversity and stability. Results were compared to healthy children without LcS exposure. For a period of 6 weeks, fecal samples were collected weekly by both groups. In total, 18 children were included (6 probiotics; 12 non-probiotics). At 1-week intervals, no differences in diversity and stability were observed in children exposed to LcS versus controls. LcS ingestion by healthy children does not result in a more diverse and stable gut microbiota composition. Large double-blind placebo-controlled randomized clinical trials in children should be performed to gain more insight on potential beneficial health consequences

A low incidence of preoperative neurosonographic abnormalities in neonates with heart defects

Background and aim: To investigate whether neonates with prenatally detected congenital heart defects (CHD) demonstrate cerebral abnormalities on early preoperative cranial ultrasound (CUS), compared to healthy neonates, and to measure brain structures to assess brain growth and development in both groups. Study design, subjects and outcome measures: Prospective cohort study with controls. Between September 2013 and May 2016 consecutive cases of prenatally detected severe isolated CHD were included. Neonatal CUS was performed shortly after birth, before surgery and in a healthy control group. Blinded images were reviewed for brain abnormalities and various measurements of intracranial structures were compared. Results: CUS was performed in 59 healthy controls and 50 CHD cases. Physiological CUS variants were present in 54% of controls and in 52% of CHD cases. Abnormalities requiring additional monitoring (both significant and minor) were identified in four controls (7%) and five CHD neonates (10%). Significant abnormalities were only identified in four CHD neonates (8%) and never in controls. A separate analysis of an additional 8 CHD neonates after endovascular intervention demonstrated arterial stroke in two cases that underwent balloon atrioseptostomy (BAS). Cerebral measurements were smaller in CHD neonates, except for the cerebrospinal fluid measurements, which were similar to the controls. Conclusions: The prevalence of significant preoperative CUS abnormalities in CHD cases was lower than previously reported, which may be partially caused by a guarding effect of a prenatal diagnosis. Arterial stroke occurred only in cases after BAS. As expected, neonates with CHD display slightly smaller head size and cerebral growth

Feasibility of Reduced Clinical Monitoring in Patients with Inflammatory Bowel Disease Treated with Thiopurine Therapy

Background: Outpatient visits and laboratory assessments are routinely scheduled every 3 to 4 months in thiopurine-treated patients with inflammatory bowel disease (IBD) to timely detect thiopurine-related adverse events (AEs). AEs that require therapy adjustment beyond 12 months of treatment are rare. Aim and Methods: This single-center prospective cohort study evaluated the safety of a reduced 6-monthly monitoring strategy in steroid-free patients with quiescent IBD on stable dose of azathioprine, mercaptopurine, or thioguanine monotherapy. The primary outcome was thiopurine-related AEs requiring therapy adjustments during a follow-up period of 24 months. Secondary outcomes included all AEs including laboratory toxicity, disease flares until 12 months, and the net monetary benefit from this strategy concerning IBD-related health care use. Results: We enrolled 85 patients with IBD (median age 42 years, 61% Crohn’s disease, 62% female), with a median disease duration of 12.5 years and median thiopurine treatment duration of 6.7 years. During follow-up, 3 patients (4%) ceased thiopurines due to AEs: recurrent infections, non-melanoma skin cancer, and gastrointestinal complaints (nausea, vomiting). At 12 months, 25 laboratory toxicities were observed (including 13% myelotoxicity, 17% hepatotoxicity); none required therapy adjustments and all were transient. A reduced monitoring strategy had a net benefit of €136 per patient. Conclusion: Three patients (4%) ceased thiopurine therapy due to thiopurine-related AEs, while no laboratory toxicity required therapy adjustments. Monitoring frequency of every 6 months seems feasible in patients with stable IBD on long-term (median duration > 6 years) maintenance thiopurine therapy and may contribute to reduced patient-burden and health care costs

Composition and stability of intestinal microbiota of healthy children within a Dutch population

Numerous diseases linked to microbial imbalance can be traced back to childhood, illustrating the impact of the juvenile microbiota development from infancy toward adulthood. However, knowledge on this subject is currently very limited. The primary aim of this study was to characterize composition and short- and long-term stability of the intestinal microbiota in healthy children. Between November 2011 and June 2014, 61 children 2 to 18 yr of age from different areas in The Netherlands were included and instructed to collect fecal samples weekly, for 6 wk, and a follow-up sample after 18 mo. The intergenic spacer profiling technique (IS-pro) was used to analyze all available fecal samples. Microbial diversity was calculated by the Shannon diversity index and individual compositional stability by comparing all collection time points. Microbial stability varied per phylum (P <0.0005), declined rapidly in a short time period, and subsequently stabilized on the long run with very gradual variation, leading to an overall compositional stability of 70% on average over a period of 18 mo. Higher species diversity was correlated to a higher overall compositional stability (P <0.001). We observed an age-independent bacterial shared core consisting of a limited number of species. In conclusion, in this study, we showed that microbial composition stability in children varied per phylum, at both short-term and long-term intervals. Healthy children seem to share a microbiome core consisting of a limited number of species.-De Meij, T. G. J., Budding, A. E., de Groot, E. F. J., Jansen, F. M., Kneepkens, C. M. F., Benninga, M. A., Penders, J., van Bodegraven, A. A., Savelkoul, P. H. M. Composition and stability of intestinal microbiota of healthy children within a Dutch populatio

The association between flow and oxygenation and cortical development in fetuses with congenital heart defects using a brain-age prediction algorithm

Objectives: Presumably, changes in fetal circulation contribute to the delay in maturation of the cortex in fetuses with congenital heart defect (CHD). The aim of the current study is to analyze fetal brain development based on hemodynamic differences, using novel brain-age prediction software. Methods: We have performed detailed neurosonography, including acquiring 3D volumes, prospectively in cases with isolated CHD from 20 weeks onwards. An algorithm that assesses the degree of fetal brain-age automatically was used to compare CHD cases to controls. We stratified CHD cases according to flow and oxygenation profiles by lesion physiology and performed subgroup analyses. Results: A total of 616 ultrasound volumes of 162 CHD cases and 75 controls were analyzed. Significant differences in maturation of the cortex were observed in cases with normal blood flow toward the brain (−3.8 days, 95%CI [−5.5; −2.0], P = <.001) and low (−4.0 days, 95% CI [−6.7; −1.2] P = <.05; hypoplastic left heart syndrome[HLHS]) and mixed (−4.4 days, 95%CI [−6.4; −2.5] p = <.001) oxygen saturation in the ascending aorta (TGA) and in cardiac mixing (eg, Fallot) cases. Conclusion: The current study shows significant delay in brain-age in TGA and Fallot cases as compared to control cases. However, the small differences found in this study questions the clinical relevance

Cortical development in fetuses with congenital heart defects using an automated brain-age prediction algorithm

Introduction: Congenital heart defects are associated with neurodevelopmental delay. It is hypothesized that fetuses affected by congenital heart defect have altered cerebral oxygen perfusion and are therefore prone to delay in cortical maturation. The aim of this study was to determine the difference in fetal brain age between consecutive congenital heart defect cases and controls in the second and third trimester using ultrasound. Material and methods: Since 2014, we have included 90 isolated severe congenital heart defect cases in the Heart And Neurodevelopment (HAND)-study. Every 4 weeks, detailed neurosonography was performed in these fetuses, including the recording of a 3D volume of the fetal brain, from 20 weeks onwards. In all, 75 healthy fetuses underwent the same protocol to serve as a control group. The volumes were analyzed by automated age prediction software which determines gestational age by the assessment of cortical maturation. Results: In total, 477 volumes were analyzed using the age prediction software (199 volumes of 90 congenital heart defect cases; 278 volumes of 75 controls). Of these, 16 (3.2%) volume recordings were excluded because of imaging quality. The age distribution was 19-33 weeks. Mixed model analysis showed that the age predicted by brain maturation was 3 days delayed compared with the control group (P =.002). Conclusions: This study shows that fetuses with isolated cases of congenital heart defects show some delay in cortical maturation as compared with healthy control cases. The clinical relevance of this small difference is debatable. This finding was consistent throughout pregnancy and did not progress during the third trimester