Randomized Trial of Fetal Surgery for Severe Left Diaphragmatic Hernia.

BACKGROUND: Observational studies have shown that fetoscopic endoluminal tracheal occlusion (FETO) has been associated with increased survival among infants with severe pulmonary hypoplasia due to isolated congenital diaphragmatic hernia on the left side, but data from randomized trials are lacking. METHODS: In this open-label trial conducted at centers with experience in FETO and other types of prenatal surgery, we randomly assigned, in a 1:1 ratio, women carrying singleton fetuses with severe isolated congenital diaphragmatic hernia on the left side to FETO at 27 to 29 weeks of gestation or expectant care. Both treatments were followed by standardized postnatal care. The primary outcome was infant survival to discharge from the neonatal intensive care unit. We used a group-sequential design with five prespecified interim analyses for superiority, with a maximum sample size of 116 women. RESULTS: The trial was stopped early for efficacy after the third interim analysis. In an intention-to-treat analysis that included 80 women, 40% of infants (16 of 40) in the FETO group survived to discharge, as compared with 15% (6 of 40) in the expectant care group (relative risk, 2.67; 95% confidence interval [CI], 1.22 to 6.11; two-sided P = 0.009). Survival to 6 months of age was identical to the survival to discharge (relative risk, 2.67; 95% CI, 1.22 to 6.11). The incidence of preterm, prelabor rupture of membranes was higher among women in the FETO group than among those in the expectant care group (47% vs. 11%; relative risk, 4.51; 95% CI, 1.83 to 11.9), as was the incidence of preterm birth (75% vs. 29%; relative risk, 2.59; 95% CI, 1.59 to 4.52). One neonatal death occurred after emergency delivery for placental laceration from fetoscopic balloon removal, and one neonatal death occurred because of failed balloon removal. In an analysis that included 11 additional participants with data that were available after the trial was stopped, survival to discharge was 36% among infants in the FETO group and 14% among those in the expectant care group (relative risk, 2.65; 95% CI, 1.21 to 6.09). CONCLUSIONS: In fetuses with isolated severe congenital diaphragmatic hernia on the left side, FETO performed at 27 to 29 weeks of gestation resulted in a significant benefit over expectant care with respect to survival to discharge, and this benefit was sustained to 6 months of age. FETO increased the risks of preterm, prelabor rupture of membranes and preterm birth. (Funded by the European Commission and others; TOTAL ClinicalTrials.gov number, NCT01240057.).

On the Electrochemical Growth of a Crystalline p-n Junction From Aqueous Solutions.

Our society largely relies on inorganic semiconductor devices which are, so far, fabricated using expensive and complex processes requiring ultra-high vacuum equipment. Here we report on the possibility of growing a p-n junction taking advantage of electrochemical processes based on the use of aqueous solutions. The growth of the junction has been carried out using the Electrochemical Atomic Layer Deposition (E-ALD) technique, which allowed to sequentially deposit two different semiconductors, CdS and Cu2S, on an Ag(111) substrate, in a single procedure. The growth process was monitored in situ by Surface X-Ray Diffraction (SXRD) and resulted in the fabrication of a thin double-layer structure with a high degree of crystallographic order and a well-defined interface. The high-performance electrical characteristics of the device were analysed ex-situ and show the characteristic feature of a diode.

Self-reported respiratory and gastrointestinal outcomes in children with isolated congenital diaphragmatic hernia: A prospective multicentre study.

OBJECTIVE: To evaluate medium-term self-reported respiratory and gastrointestinal (GI) outcomes in children with congenital diaphragmatic hernia (CDH). DESIGN: Self-reported respiratory and GI outcomes correlated with prenatal severity indicators. SETTING: Prospective study at three fetal medicine units. POPULATION: Families of children prenatally diagnosed with isolated, left-sided CDH surviving for >1 year. METHODS: Families received validated questionnaires for GI outcomes (Infant Gastroesophageal Reflux Questionnaire Revised, I-GERQ-R, for infants aged <2 years, or Paediatric Gastro-oesophageal Symptom and Quality of Life Questionnaire, PGSQ, for children aged aged 2-8 years or >9 years) and respiratory outcomes (preschool respiratory outcome questionnaire, for children aged ≤5 years, or the International Study of Asthma and Allergies in Childhood asthma questionnaire, for children aged 6-8 years or ≥9 years). Prenatal data collected from the medical records included lung size (percentage observed/expected lung-to-head ratio, O/E LHR %), liver position, fetal endoluminal tracheal occlusion (FETO) gestational age (GA) at delivery, and perinatal data included birthweight, location, patch repair and respiratory support. MAIN OUTCOME MEASURES: The GI and respiratory scores were correlated with O/E LHR using linear and logistic regression models. Univariate analysis was used to evaluate associations with perinatal variables. RESULTS: We obtained 142 responses from 342 families (representing a response rate of 45%). The baseline characteristics of participants and non-participants were comparable. No correlations between perinatal variables and respiratory or GI scores were identified. Children aged ≤5 years with lower O/E LHR values reported higher respiratory scores (P = 0.0175); this finding was not reported in older children. Overall, the children who underwent FETO (n = 51) had GI (P = 0.290) and respiratory (P = 0.052) scores that were comparable with those of children who were expectantly managed. CONCLUSIONS: Families and children with prenatally diagnosed CDH reported fewer respiratory symptoms with increasing age. There was no correlation between O/E LHR or the use of FETO and self-reported outcomes.

Predicting Matrix Test Effectiveness for Evaluating Auditory Performance in Noise Using Pure-Tone Audiometry and Speech Recognition in Quiet in Cochlear Implant Recipients.

INTRODUCTION: Auditory performance in noise of cochlear implant recipients can be assessed with the adaptive Matrix test (MT); however, when the speech-to-noise ratio (SNR) exceeds 15 dB, the background noise has any negative impact on the speech recognition. Here, we aim to evaluate the predictive power of aided pure-tone audiometry and speech recognition in quiet and establish cut-off values for both tests that indicate whether auditory performance in noise can be assessed using the Matrix sentence test in a diffuse noise environment. METHODS: Here, we assessed the power of pure-tone audiometry and speech recognition in quiet to predict the response to the MT. Ninety-eight cochlear implant recipients were assessed using different sound processors from Advanced Bionics (n = 56) and CochlearTM (n = 42). Auditory tests were performed at least 1 year after cochlear implantation or upgrading the sound processor to ensure the best benefit of the implant. Auditory assessment of the implanted ear in free-field conditions included: pure-tone average (PTA), speech discrimination score (SDS) in quiet at 65 dB, and speech recognition threshold (SRT) in noise that is the SNR at which the patient can correctly recognize 50% of the words using the MT in a diffuse sound field. RESULTS: The SRT in noise was determined in 60 patients (61%) and undetermined in 38 (39%) using the MT. When cut-off values for PTA <36 dB and SDS >41% were used separately, they were able to predict a positive response to the MT in 83% of recipients; using both cut-off values together, the predictive value reached 92%. DISCUSSION: As the pure-tone audiometry is standardized universally and the speech recognition in quiet could vary depending on the language used; we propose that the MT should be performed in recipients with PTA <36 dB, and in recipients with PTA >36 dB, a list of Matrix sentences at a fixed SNR should be presented to determine the percentage of words understood. This approach should enable clinicians to obtain information about auditory performance in noise whenever possible.

Association of perfluoroalkyl substances (PFAS) with liver function biomarkers in the highly exposed population of the Veneto Region.

INTRODUCTION: Epidemiological studies highlight the presence of associations between per- and polyfluoroalkyl substances (PFAS) exposure with liver damage. In 2013, PFAS contamination was discovered in Veneto (Italy), leading to the implementation of a Surveillance Program (SP). Our objective is to investigate the association between PFAS exposure and biomarkers of liver function using single-pollutant and mixture approaches, while exploring the sex-specific differences and the mediating role of obesity in the association. METHODS: The study included 42,094 subjects aged ≥20 years participating in the SP. We used generalized additive models to investigate the association between several PFAS and alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels, adjusting for possible confounders and stratifying by sex. Results were back-transformed to show predicted percentage changes in outcomes per ln-unit increase in PFAS levels; furthermore, we explored the role of BMI in the abovementioned causal pathway, considering it as a potential confounder or mediator PFAS joint effect was investigated using Quantile G-computation. RESULTS: One ln-unit increase in PFHxS concentrations was associated with a 1.49% (95%CI: 0.87, 2.12) and a 0.84% (95% CI: 0.27, 1.40) increase in ALT levels, in males and females respectively; one ln-unit increase in PFOA concentrations was associated with a 1.03% (95%CI: 0.50, 1.55) increase in ALT levels in males, and a 0.52% (95% CI: 0.22, 0.82) and a 0.60% (95% CI: 0.25, 0.96) increase in AST levels in females and males. PFOS showed no association with ALT and AST levels. Quantile G-computation revealed that an interquartile increase in the PFAS mixture was associated with a 3.02% increase (95% CI: 1.65, 4.43) and a 1.65% (95% CI: 0.77, 2.5) increase in ALT levels, in females and males. Mediation analysis suggested that BMI suppressed the association between PFAS and ALT levels, with positive direct effects higher than the total effects. CONCLUSION: Our findings suggest sex-specific associations between PFAS exposure and liver function biomarkers and underscore the need for additional studies on potential mediators.

Experimental Induction of Complex Gastroschisis in the Fetal Lamb: Systematic Review.

We systematically reviewed experiments in the fetal lamb model of gastroschisis using PubMed, Embase, Web of Science, and Scopus, seeking for standardized surgical techniques to obtain complex gastroschisis. Eligible were studies where an abdominal wall defect was surgically induced and gross anatomical findings at birth were available. The primary outcome was complex gastroschisis, defined by the presence of bowel stenosis, atresia, volvulus, perforation, and/or necrosis. Secondary outcomes were fetal death and additional readouts reported. Of ten eligible studies, six included lambs that had no additional prenatal manipulations and were assessed at term (35 lambs). Gastroschisis was induced at day 70-80 (term = 140-145), typically (n = 4/6 studies) in the left lower abdomen with defect size ranging from 0.5 to 4.0 cm. Only one study, in which a 1.5 cm diameter silicone ring was utilized, resulted in complex gastroschisis in 100% of term survivors. Fetal loss was more frequent in studies where a silicone ring and/or a right-sided defect were used. No changes unique to complex gastroschisis were identified in additional readouts, including bowel histology. When gastroschisis becomes "complex" following induction is uncertain. This knowledge is essential in studying potential prenatal interventions that may change the natural course.

Development and validation of a novel fetal vesico-amniotic shunt, the vortex shunt.

Fetal lower urinary tract obstruction (LUTO) is a severe malformation associated with an up to 80% mortality risk as well as significant renal and pulmonary morbidity in survivors. Fetal vesico-amniotic shunts (VAS) bypass the bladder obstruction, improve amniotic fluid volume and enhance in-utero pulmonary development. VAS has been shown to reduce respiratory morbidity and mortality in the neonatal period without proven benefit on long-term renal and bladder function. Clinically available shunts are associated with an up to 80% dislodgement rate, leading to repeat invasive procedures which increase fetal and maternal risks. We developed a novel "Vortex" shunt, which incorporates enhanced fixation to reduce dislodgement, a one-way valve to optimize in-utero bladder function, and enhanced sonographic echogenicity that optimizes the accurate deployment. Following the validation of these characteristics in initial benchtop experiments we have moved to feasibility studies in the fetal lamb model. We hope that the Vortex shunt may ultimately facilitate shunt deployment, reduce dislodgement risk, improve neonatal morbidity and mortality, and decrease the significant healthcare expenditures associated with long-term morbidity in LUTO survivors. In this manuscript, we review the natural history of LUTO, the risks and benefits of clinically available fetal shunts, and our development and early validation experiments.

Parental Management Choices and Discordant Ultrasound Findings in Referrals for Fetal Spina Bifida.

OBJECTIVE: The severity of spina bifida aperta can be assessed prenatally by ultrasound. Morphological findings assist parents in choosing between management options. We aimed to document those management choices since the introduction of fetal surgery, and compare initial ultrasound findings prior to referral to findings in a fetal surgery center. METHOD: Single center cohort study of 245 consecutive fetuses with a second-trimester diagnosis of SBA. Data included nature of referral (for assessment or for surgery), condition-specific findings on ultrasound, and further management. We compared the reported findings on the initial ultrasound to ours for the presence of hindbrain herniation, lesion level, ventricular width, kyphosis, leg movement, and club feet. RESULTS: Seventy-two percent (n = 177) of fetuses met the eligibility criteria for surgery; in 60% (n = 106) parents opted for fetal surgery. Of 136 patients specifically referred for surgery, 27 were ineligible (20%). Of the others, 93 proceeded with surgery. In up to 28% (n = 30) of surgery referrals, eligibility criteria such as lesion level (n = 30, 28%) or leg movement (72%, n = 78) as severity indicators were not reported. CONCLUSION: Fetal surgery uptake was high in patients referred for surgery. Second assessment in a fetal surgery center often reveals additional relevant information.

Low-frequency pitch coding: relationships with speech-in-noise and music perception by pediatric populations with typical hearing and cochlear implants.

PURPOSE: This study aimed to investigate the effects of low frequency (LF) pitch perception on speech-in-noise and music perception performance by children with cochlear implants (CIC) and typical hearing (THC). Moreover, the relationships between speech-in-noise and music perception as well as the effects of demographic and audiological factors on present research outcomes were studied. METHODS: The sample consisted of 22 CIC and 20 THC (7-10 years). Harmonic intonation (HI) and disharmonic intonation (DI) tests were used to assess LF pitch perception. Speech perception in quiet (WRSq)/noise (WRSn + 10) were tested with the Italian bisyllabic words for pediatric populations. The Gordon test was used to evaluate music perception (rhythm, melody, harmony, and overall). RESULTS: CIC/THC performance comparisons for LF pitch, speech-in-noise, and all music measures except harmony revealed statistically significant differences with large effect sizes. For the CI group, HI showed statistically significant correlations with melody discrimination. Melody/total Gordon scores were significantly correlated with WRSn + 10. For the overall group, HI/DI showed significant correlations with all music perception measures and WRSn + 10. Hearing thresholds showed significant effects on HI/DI scores. Hearing thresholds and WRSn + 10 scores were significantly correlated; both revealed significant effects on all music perception scores. CI age had significant effects on WRSn + 10, harmony, and total Gordon scores (p < 0.05). CONCLUSION: Such findings confirmed the significant effects of LF pitch perception on complex listening performance. Significant speech-in-noise and music perception correlations were as promising as results from recent studies indicating significant positive effects of music training on speech-in-noise recognition in CIC.

Follow-up strategies in pediatric cholesteatoma: a systematic review.

PURPOSE: The aim of this article was to systematically review the literature on the pediatric population surgically treated for cholesteatoma and describe the applied post-operative follow-up strategies. METHODS: A systematic review was conducted following the Primary Reporting Items for Systematic Review and Meta-analysis (PRISMA) statement recommendations. After running the selected search string in PubMed, Scopus and Google Scholar, studies in English, reporting on surgically treated pediatric cholesteatoma patients (age younger or equal to 18 year-old) were retrieved. Both primary and revision cholesteatoma surgeries were included. Articles lacking specific data on post-surgical follow-up and case series with less than 10 patients were excluded. RESULTS: Nineteen papers, published between 2000 and 2023, were included for final analysis. Fourteen studies were retrospective and five prospective, for a total of 1319 patients and 1349 operated ears. Male to female ratio was 1.8:1, with a mean age at surgery of 10.4 years (range 1-18). The mean length of the follow-up after surgery was 4.4 ± 1.7 years (range 1-6.9). Clinical follow-up was detailed in 9 studies (47%) with otomicroscopy being the most common evaluation. In most articles (n = 8, 50%), MRI alone was utilized for radiological follow-up, while in 3 studies (19%), CT scans were employed exclusively. In 5 studies (31%), MRI was combined with CT scans. The timing of radiological investigations varied widely (ranging from 6 months to 3 years). A second-look strategy was reported in 14 studies (74%). CONCLUSION: This systematic review highlights the heterogeneity of the follow-up strategies applied to pediatric patients after cholesteatoma surgery, both in terms of timing and types of investigations.

The risk-based breast screening (RIBBS) study protocol: a personalized screening model for young women.

The optimal mammography screening strategy for women aged 45-49 years is a matter of debate. We present the RIBBS study protocol, a quasi-experimental, prospective, population-based study comparing a risk- and breast density-stratified screening model (interventional cohort) with annual digital mammography (DM) screening (observational control cohort) in a real-world setting. The interventional cohort consists of 10,269 women aged 45 years enrolled between 2020 and 2021 from two provinces of the Veneto Region (northen Italy). At baseline, participants underwent two-view digital breast tomosynthesis (DBT) and completed the Tyrer-Cuzick risk prediction model. Volumetric breast density (VBD) was calculated from DBT and the lifetime risk (LTR) was estimated by including VBD among the risk factors. Based on VBD and LTR, women were classified into five subgroups with specific screening protocols for subsequent screening rounds: (1) LTR ≤ 17% and nondense breast: biennial DBT; (2) LTR ≤ 17% and dense breast: biennial DBT and ultrasound; (3) LTR 17-30% or LTR > 30% without family history of BC, and nondense breast: annual DBT; (4) LTR 17-30% or > 30% without family history of BC, and dense breast: annual DBT and ultrasound; and (5) LTR > 30% and family history of BC: annual DBT and breast MRI. The interventional cohort is still ongoing. An observational, nonequivalent control cohort of 43,000 women aged 45 years participating in an annual DM screening programme was recruited in three provinces of the neighbouring Emilia-Romagna Region. Cumulative incidence rates of advanced BC at three, five, and ten years between the two cohorts will be compared, adjusting for the incidence difference at baseline.Trial registration This study is registered on Clinicaltrials.gov (NCT05675085).

Subsequent fertility, pregnancy, and gynaecological and psychological outcomes after maternal-fetal surgery for open spina bifida: A prospective cohort study.

OBJECTIVE: To determine the medium-term maternal impact of open fetal spina bifida repair. DESIGN: Prospective cohort study. SETTING: University Hospitals Leuven, Belgium. POPULATION: Mothers who had open maternal-fetal spina bifida repair between March 2012 and December 2021. METHODS: A patient-reported survey on subsequent fertility, pregnancy, and gynaecological and psychological outcomes. MAIN OUTCOME MEASURES: Complications during subsequent pregnancies, and gynaecological and psychological problems. RESULTS: Seventy-two out of 100 invited women completed the questionnaire (72%). Despite being advised not to, seven of 13 women attempting to conceive became pregnant within 2 years after fetal surgery and one woman delivered vaginally. Two of the 16 subsequent pregnancies were complicated by an open neural tube defect. One pregnancy was complicated by a placenta accreta and one pregnancy was complicated by a uterine rupture, both with good neonatal outcomes. Nearly half of respondents who did not attempt to conceive reported that this was because of their experience of the index pregnancy and caring for the index child. Three out of four respondents reported medium-term psychological problems, mostly anxiety for the health of the index child, fear for recurrence in subsequent pregnancies and feelings of guilt. CONCLUSIONS: Open maternal-fetal surgery for spina bifida did not appear to affect fertility in our cohort. Half of the attempts to conceive took place within 2 years. One uterine rupture and one placenta accreta occurred in 16 subsequent pregnancies. Most respondents reported psychological problems linked to the index pregnancy, which reinforces the need for long-term psychological support.

Survival in very preterm infants with congenital diaphragmatic hernia and association with prenatal imaging markers: A retrospective cohort study.

OBJECTIVES: To describe the outcomes of preterm born infants with congenital diaphragmatic hernia (CDH; ≤32.0 weeks of gestation) and the associations between prenatal imaging markers and survival. DESIGN: Retrospective cohort study. SETTING: Multicentre study in large referral centres. POPULATION: Infants with an isolated unilateral CDH, live born at 32.0 weeks or less of gestation, between January 2009 and January 2020. METHODS: Neonatal outcomes were evaluated for infants that were expectantly managed during pregnancy and infants that underwent fetoscopic endoluminal tracheal occlusion (FETO) therapy, separately. We evaluated the association between prenatal imaging markers and survival to discharge. Prenatal imaging markers included observed to expected lung-to-head ratio (o/e LHR), side of the defect, liver position, stomach position grade, and observed to expected total fetal lung volume (o/e TFLV). MAIN OUTCOME MEASURE: Survival to discharge. RESULTS: We included 53 infants born at 30+4 (interquartile range 29+1 -31+2 ) weeks. Survival in fetuses expectantly managed during pregnancy was 48% (13/27) in left-sided CDH and 33% (2/6) in right-sided CDH. Survival in fetuses that underwent FETO therapy was 50% (6/12) in left-sided CDH and 25% (2/8) in right-sided CDH. The o/e LHR at baseline was positively associated with survival in cases expectantly managed during pregnancy (odds ratio [OR] 1.20, 95% CI 1.07-1.42, p < 0.01), but not in cases that received FETO therapy (OR 1.01, 95% CI 0.88-1.15, p = 0.87). Stomach position grade (p = 0.03) and o/e TFLV were associated with survival (p = 0.02); liver position was not (p = 0.13). CONCLUSIONS: In infants with CDH born at or before 32 weeks of gestation, prenatal imaging markers of disease severity were associated with postnatal survival.

Exploring the effect on the environment of encapsulated micro- and nano-plastics into asphalt mastics for road pavement.

A new environmental problem is represented by the huge transformation of plastic waste released into the environment into small fragments, the so called micro- and nano-plastics, due to atmospheric phenomena. The smaller the size of the plastic fragments, the more their spreading into environmental compartments. The aim of this study is to test encapsulation into asphalt mastics of waste plastic material (WPM) as sustainable strategy to obtain road flexible pavements and to evaluate the potential release in water of micro and nano plastics. A new mastic mixing method was developed to blend the WPM with the bitumen contained into a bitumen emulsion (BE60/40) by adopting low mixing temperatures. Three different WPM contents, equal to 5, 10 and 20% by the weight of the bitumen contained in the BE60/40, were adopted to produce the mastics; the mastics' rheological properties, obtained by frequency sweep and multiple stress creep and recovery tests, were compared to those of a traditional asphalt mastic containing limestone filler. The aging of asphalt mastics was analyzed by soaking them in water and gradually lowering and raising temperature between -10 and 60 °C at predefined intervals. The addition of WPM improved greatly the asphalt mastic performance; in particular, for a WPM content of 10%, the rheological response in terms of stiffness remained unchanged after the mastic underwent thermal excursions in water. Encapsulation of micro and nano plastics into mastics reduced of more than 99% their potential water release.

Have the results of the TOTAL-trials changed the attitude and practice of maternal-fetal medicine specialists?

OBJECTIVE: To explore the views and practices of maternal-fetal medicine specialists on offering fetoscopic endoluminal tracheal occlusion (FETO) for left- and right-sided congenital diaphragmatic hernia (LCDH, RCDH) in the post Tracheal Occlusion To Accelerate Lung growth (TOTAL)-trial era. METHOD: Cross-sectional knowledge, attitude and practice survey was conducted among 105 attendees of the 19th World Congress of Fetal Medicine. RESULTS: On average, respondents were knowledgeable about CDH, involved in research, and provided antenatal treatment options. Four out of five (82%) agreed that neonatal survival in LCDH can be reliably predicted in the prenatal period. Few respondents considered the exact risks and benefits of FETO for severe LCDH as being unclear (16%), yet half were uncertain about this for moderate LCDH (57%) and severe RCDH (45%). Most respondents offer FETO for severe LCDH (97%) and RCDH (79%), but only 59% offer it for moderate LCDH. However, half of respondents (58%) stated that not offering FETO for moderate LCDH would be a psychological burden for parents. CONCLUSION: Respondents consider the risk-benefit ratio of FETO for severe LCDH clear and consistently offer FETO, but not for moderate LDCH and severe RCDH. However, not offering the option of FETO to parents was considered a psychological burden.

Patient-reported outcomes for congenital diaphragmatic hernia: A qualitative study.

OBJECTIVE: To identify Patient-reported outcomes (PROs) for parents with a lived experience of a prenatal diagnosis of isolated congenital diaphragmatic hernia (CDH). METHOD: Thematic analysis of in-depth interview transcripts. RESULTS: Interviews (n = 26) identified 11 PROs for given time points throughout the CDH trajectory. At the time of diagnosis, acceptable quality of life was selected as relevant PRO to decide whether to continue or terminate the pregnancy. During pregnancy, (neonatal) survival chances and the eligibility for foetal therapy were prominent outcomes with foetal and maternal complications adding distress. After birth, postnatal management options became the next milestone. When survival was deemed likely, post-hospital discharge complications and future care for infant and child became important. In retrospect, impact on family, bonding, parental mental health, and parental satisfaction with care were reported as relevant outcomes. CONCLUSION: PROs are relevant in addition to hard medical outcomes, as they help parents to make decisions suiting their unique needs and personal situation. Given the knowledge inherently related to the parent's perspective, our findings provide relevant directions for clinicians to support parents and their family in facing challenging decisions in healthcare. The outcomes impacting parents are essential to prepare parents for the steep journey ahead.

Brain development is altered in rabbit fetuses with congenital diaphragmatic hernia.

INTRODUCTION: Children with congenital diaphragmatic hernia (CDH) are at risk for neurodevelopmental delay. Some changes are already present prenatally. Herein, we further examined how the brain develops in fetal rabbits with surgically created DH. METHODS: Two fetuses underwent surgical DH creation on day 23 (term = d31). DH pups and littermate controls were harvested at term. Ten DH pups and 11 controls underwent transcardial perfusion for brain fixation and measurement of brain volume, brain folding, neuron and synaptic density, pre-oligodendrocyte count, proliferation, and vascularization. Twelve other DH and 11 controls had echocardiographic assessment of cardiac output and aortic and cerebral blood flow, magnetic resonance imaging (9.4 T) for cerebral volumetry, and molecular assessment of vascularization markers. RESULTS: DH pups had lower lung-to-body weight ratio (1.3 ± 0.3 vs. 2.4 ± 0.3%; p < 0.0001) and lower heart-to-body weight ratio (0.007 ± 0.001 vs. 0.009 ± 0.001; p = 0.0006) but comparable body weight and brain-to-body weight ratio. DH pups had a lower left ventricular ejection fraction, aortic and cerebral blood flow (39 ± 8 vs. 54 ± 15 mm/beat; p = 0.03) as compared to controls but similar left cardiac ventricular morphology. Fetal DH-brains were similar in volume but the cerebellum was less folded (perimeter/surface area: 25.5 ± 1.5 vs. 26.8 ± 1.2; p = 0.049). Furthermore, DH brains had a thinner cortex (143 ± 9 vs. 156 ± 13 µm; p = 0.02). Neuron densities in the white matter were higher in DH fetuses (124 ± 18 vs. 104 ± 14; p = 0.01) with comparable proliferation rates. Pre-oligodendrocyte count was lower, coinciding with the lower endothelial cell count. CONCLUSION: Rabbits with DH had altered brain development compared to controls prenatally, indicating that brain development is already altered prenatally in CDH.

Antimicrobial Performance of Innovative Functionalized Surfaces Based on Enamel Coatings: The Effect of Silver-Based Additives on the Antibacterial and Antifungal Activity.

Frequently touched surfaces (FTS) that are contaminated with pathogens are one of the main sources of nosocomial infections, which commonly include hospital-acquired and healthcare-associated infections (HAIs). HAIs are considered the most common adverse event that has a significant burden on the public's health worldwide currently. The persistence of pathogens on contaminated surfaces and the transmission of multi-drug resistant (MDR) pathogens by way of healthcare surfaces, which are frequently touched by healthcare workers, visitors, and patients increase the risk of acquiring infectious agents in hospital environments. Moreover, not only in hospitals but also in high-traffic public places, FTS play a major role in the spreading of pathogens. Consequently, attention has been devoted to developing novel and alternative methods to tackle this problem. This study planned to produce and characterize innovative functionalized enameled coated surfaces supplemented with 1% AgNO3 and 2% AgNO3. Thus, the antimicrobial properties of the enamels against relevant nosocomial pathogens including the Gram-positive Staphylococcus aureus and the Gram-negative Escherichia coli and the yeast Candida albicans were assessed using the ISO:22196:2011 norm.

Complementary Effect of Maternal Sildenafil and Fetal Tracheal Occlusion Improves Lung Development in the Rabbit Model of Congenital Diaphragmatic Hernia.

OBJECTIVE: To evaluate the effect of combining antenatal sildenafil with fetal tracheal occlusion (TO) in fetal rabbits with surgically induced congenital diaphragmatic hernia (CDH). BACKGROUND: Although antenatal sildenafil administration rescues vascular abnormalities in lungs of fetal rabbits with CDH, it only partially improves airway morphometry. We hypothesized that we could additionally stimulate lung growth by combining this medical treatment with fetal TO. METHODS: CDH was created on gestational day (GD)23 (n=54). Does were randomized to receive either sildenafil 10 mg/kg/d or placebo by subcutaneous injection from GD24 to GD30. On GD28, fetuses were randomly assigned to TO or sham neck dissection. At term (GD30) fetuses were delivered, ventilated, and finally harvested for histological and molecular analyses. Unoperated littermates served as controls. RESULTS: The lung-to-body-weight ratio was significantly reduced in sham-CDH fetuses either (1.2 ±â€Š0.3% vs 2.3 ±â€Š0.3% in controls, P=0.0003). Sildenafil had no effect on this parameter, while CDH fetuses undergoing TO had a lung-to-body-weight ratio comparable to that of controls (2.5 ±â€Š0.8%, P<0.0001). Sildenafil alone induced an improvement in the mean terminal bronchiolar density (2.5 ±â€Š0.8 br/mm2 vs 3.5 ±â€Š0.9 br/mm2, P=0.043) and lung mechanics (static elastance 61 ±â€Š36 cmH2O /mL vs 113 ±â€Š40 cmH2O/mL, P=0.008), but both effects were more pronounced in fetuses undergoing additional TO (2.1 ±â€Š0.8 br/mm2, P=0.001 and 31 ±â€Š9 cmH2O/mL, P<0.0001 respectively). Both CDH-sham and CDH-TO fetuses treated with placebo had an increased medial wall thickness of peripheral pulmonary vessels (41.9 ±â€Š2.9% and 41.8 ±â€Š3.2%, vs 24.0 ±â€Š2.9% in controls, P<0.0001). CDH fetuses treated with sildenafil, either with or without TO, had a medial thickness in the normal range (29.4% ±â€Š2.6%). Finally, TO reduced gene expression of vascular endothelial growth factor and surfactant protein A and B, but this effect was counteracted by sildenafil. CONCLUSION: In the rabbit model for CDH, the combination of maternal sildenafil and TO has a complementary effect on vascular and parenchymal lung development.

The randomized Tracheal Occlusion To Accelerate Lung growth (TOTAL)-trials on fetal surgery for congenital diaphragmatic hernia: reanalysis using pooled data.

BACKGROUND: Two randomized controlled trials compared the neonatal and infant outcomes after fetoscopic endoluminal tracheal occlusion with expectant prenatal management in fetuses with severe and moderate isolated congenital diaphragmatic hernia, respectively. Fetoscopic endoluminal tracheal occlusion was carried out at 27+0 to 29+6 weeks' gestation (referred to as "early") for severe and at 30+0 to 31+6 weeks ("late") for moderate hypoplasia. The reported absolute increase in the survival to discharge was 13% (95% confidence interval, -1 to 28; P=.059) and 25% (95% confidence interval, 6-46; P=.0091) for moderate and severe hypoplasia. OBJECTIVE: Data from the 2 trials were pooled to study the heterogeneity of the treatment effect by observed over expected lung-to-head ratio and explore the effect of gestational age at balloon insertion. STUDY DESIGN: Individual participant data from the 2 trials were reanalyzed. Women were assessed between 2008 and 2020 at 14 experienced fetoscopic endoluminal tracheal occlusion centers and were randomized in a 1:1 ratio to either expectant management or fetoscopic endoluminal tracheal occlusion. All received standardized postnatal management. The combined data involved 287 patients (196 with moderate hypoplasia and 91 with severe hypoplasia). The primary endpoint was survival to discharge from the neonatal intensive care unit. The secondary endpoints were survival to 6 months of age, survival to 6 months without oxygen supplementation, and gestational age at live birth. Penalized regression was used with the following covariates: intervention (fetoscopic endoluminal tracheal occlusion vs expectant), early balloon insertion (yes vs no), observed over expected lung-to-head ratio, liver herniation (yes vs no), and trial (severe vs moderate). The interaction between intervention and the observed over expected lung-to-head ratio was evaluated to study treatment effect heterogeneity. RESULTS: For survival to discharge, the adjusted odds ratio of fetoscopic endoluminal tracheal occlusion was 1.78 (95% confidence interval, 1.05-3.01; P=.031). The additional effect of early balloon insertion was highly uncertain (adjusted odds ratio, 1.53; 95% confidence interval, 0.60-3.91; P=.370). When combining these 2 effects, the adjusted odds ratio of fetoscopic endoluminal tracheal occlusion with early balloon insertion was 2.73 (95% confidence interval, 1.15-6.49). The results for survival to 6 months and survival to 6 months without oxygen dependence were comparable. The gestational age at delivery was on average 1.7 weeks earlier (95% confidence interval, 1.1-2.3) following fetoscopic endoluminal tracheal occlusion with late insertion and 3.2 weeks earlier (95% confidence interval, 2.3-4.1) following fetoscopic endoluminal tracheal occlusion with early insertion compared with expectant management. There was no evidence that the effect of fetoscopic endoluminal tracheal occlusion depended on the observed over expected lung-to-head ratio for any of the endpoints. CONCLUSION: This analysis suggests that fetoscopic endoluminal tracheal occlusion increases survival for both moderate and severe lung hypoplasia. The difference between the results for the Tracheal Occlusion To Accelerate Lung growth trials, when considered apart, may be because of the difference in the time point of balloon insertion. However, the effect of the time point of balloon insertion could not be robustly assessed because of a small sample size and the confounding effect of disease severity. Fetoscopic endoluminal tracheal occlusion with early balloon insertion in particular strongly increases the risk for preterm delivery.