COVID-19 admissions: Trying to define the real impact of infection in hospitalized patients.

INTRODUCTION AND OBJECTIVE: Several studies have suggested that the hospitalization rate for COVID-19 in children and adolescents may reflect the prevalence of the infection rather than the severity of the disease. The aim of this study was to describe the clinical features of hospitalised paediatric patients with SARS-CoV-2 infection in order to understand if the infection was the reason for admission. METHODS: Retrospective cohort study including patients aged 0-18 years with SARS-CoV-2 infection or multisystem inflammatory syndrome in children (MIS-C) admitted to a tertiary care children's hospital in Spain between 01/01/2020 and 12/31/2021. RESULTS: 228 patients were included, corresponding to 150 cases of COVID-related admission (SARS-CoV-2 infection as main cause of hospitalization) and 78 of non-COVID-related admission (SARS-CoV-2 infection unrelated to the hospitalization). In the group of COVID-related admissions, 58 patients had comorbidities. Forty-nine patients had acute respiratory disease (pneumonia, bronchospasm or bronchiolitis). Multisystem inflammatory syndrome in children was diagnosed in 27 and was significantly more frequent in the first year of the pandemic (wild type virus). Eighty percent of patients with acute respiratory disease needed respiratory support, mostly low-flow oxygen therapy. The severity of the disease was similar in all virus variants. Two patients (both with severe comorbidities) died from COVID-related conditions. CONCLUSIONS: In our study, one third of the patients were admitted with SARS-CoV-2 infection but not because of it. Acute respiratory disease was less frequent and had a better prognosis compared to the adult population, while MIS-C was a major cause of morbidity and hospitalization. The fatality rate was extremely low.

Pleural Effusion and Chylothorax in Congenital Diaphragmatic Hernia-Risk Factors, Management and Outcome.

Background: Pleural effusion and chylothorax are common complications in the treatment of congenital diaphragmatic hernia (CDH). We set out to identify risk factors for chylothorax development in patients with CDH and to investigate the association of pleural effusion and chylothorax with neonatal morbidity and mortality. Methods: In this retrospective cohort study, we included 396 neonates with CDH treated at our institution between January 2013 and June 2019. Preoperative and postoperative chest radiographs and clinical data were evaluated and correlated with morbidity, complications and mortality. Results: Laboratory-confirmed chylothorax occurred in 58 (18.6%) of all CDH cases. Pleural effusion was frequently observed as a postoperative complication but also occurred as a pre-existing condition. Neonates with large defects of size C and D, patch repair, the need for presurgical and/or postsurgical ECMO support, pulmonary hypertension, liver-up phenomenon and lower relative fetal lung volume were associated with higher occurrences of chylothorax. After stepwise logistic regression, larger CDH defects (p < 0.0001) and the need for postsurgical ECMO (p = 0.0158) remained significant risk factors for CTX to occur (AUC 0.71). The same potential risk factors were used to assess their association with both presurgical and postsurgical pleural effusion. After stepwise logistic regression, only the need for presurgical ECMO remained significantly associated with presurgical PE (p < 0.01, AUC 0.65) and patch repair as the therapeutic intervention remained significantly associated with the occurrence of postsurgical PE (p < 0.0001, AUC 0.80). Patients with CTX had longer durations of both MV (p < 0.0001) and subsequent ventilatory assistance with spontaneous breathing (p = 0.0004), increased total lengths of hospitalization (p < 0.0001), increased durations of ECMO (p < 0.01) and increased incidences of CLD (p < 0.0001) compared to patients without CTX. No significant difference could be found for survival in both groups (p = 0.12). Conclusions: Our data suggest that the incidence of chylothorax is associated with large diaphragmatic defects, the need for postsurgical ECMO and the development of chronic lung disease, but not with survival.

Fetoscopic endoluminal tracheal occlusion vs expectant management for fetuses with severe left-sided congenital diaphragmatic hernia.

BACKGROUND: The treatment of fetuses with a congenital diaphragmatic hernia is challenging, but there is evidence that fetoscopic endoluminal tracheal occlusion has a benefit over expectant care. In addition, standardization and expertism have a great impact on survival and are probably crucial in centers that rely on expectant management with extracorporeal membrane oxygenation after birth. OBJECTIVE: This study aimed to examine the survival and morbidity rates of fetuses with a severe isolated left-sided congenital diaphragmatic hernia who underwent fetoscopic endoluminal tracheal occlusion vs expectant management in high-volume centers. STUDY DESIGN: This was a multicenter, retrospective study that included all consecutive fetuses with severe isolated left-sided congenital diaphragmatic hernia who were expectantly managed in a German center or who underwent fetoscopic endoluminal tracheal occlusion in 3 other European centers (Belgium, France, and Italy). Severe congenital diaphragmatic hernia was defined as having an observed to expected total fetal lung volume ≤35% with intrathoracic position of the liver diagnosed with magnetic resonance imaging. All magnetic resonance images were centralized, and lung volumes were measured by 2 experienced operators who were blinded to the pre- and postnatal data. Multiple logistic regression analyses were performed to examine the effect of the management strategy in the 2 groups on the short- and long-term outcomes. RESULTS: A total of 147 patients who were managed expectantly and 47 patients who underwent fetoscopic endoluminal tracheal occlusion were analyzed. Fetuses who were managed expectantly had lower observed to expected total fetal lung volumes (20.6%±7.5% vs 23.7%±6.8%; P=.013), higher gestational age at delivery (median weeks of gestation, 37.4; interquartile range, 36.6-38.00 vs 35.1; interquartile range, 33.1-37.2; P<.001), and more frequent use of extracorporeal membrane oxygenation (55.8% vs 4.3%; P<.001) than the fetuses who underwent fetoscopic endoluminal tracheal occlusion. The survival rates at discharge and at 2 years of age in the expectant management group were higher than the survival rates of the fetoscopic endoluminal tracheal occlusion group (74.3% vs 44.7%; P=.001 and 72.8% vs 42.5%; P=.001, respectively). After adjustment for maternal age, gestational age at birth, observed to expected total fetal lung volume, and birth weight Z-score, the odds ratios were 4.65 (95% confidence interval, 1.9-11.9; P=.001) and 4.37 (95% confidence interval, 1.8-11.0; P=.001), respectively. CONCLUSION: Fetuses with a severe isolated left-sided congenital diaphragmatic hernia had a higher survival rate when treated in an experienced center in Germany with antenatal expectant management and frequent use of extracorporeal membrane oxygenation during the postnatal period than fetuses who were treated with fetoscopic endoluminal tracheal occlusion in 3 centers in Belgium, France, and Italy.

aCGH Analysis Reveals Novel Mutations Associated with Congenital Diaphragmatic Hernia Plus (CDH+).

Congenital diaphragmatic hernia (CDH) is a major birth anomaly that often occurs with additional non-hernia-related malformations, and is then referred to as CDH+. While the impact of genetic alterations does not play a major role in isolated CDH, patients with CDH+ display mutations that are usually determined via array-based comparative genomic hybridization (aCGH). We analyzed 43 patients with CDH+ between 2012 and 2021 to identify novel specific mutations via aCGH associated with CDH+ and its outcome. Deletions (n = 32) and duplications (n = 29) classified as either pathological or variants of unknown significance (VUS) could be detected. We determined a heterozygous deletion of approximately 3.75 Mb located at 8p23.1 involving several genes including GATA4, NEIL2, SOX7, and MSRA, which was consequently evaluated as pathological. Another heterozygous deletion within the region of 9p23 (9,972,017-10,034,230 kb) encompassing the Protein Tyrosine Phosphatase Receptor Type Delta gene (PTPRD) was identified in 2 patients. This work expands the knowledge of genetic alterations associated with CDH+ and proposes two novel candidate genes discovered via aCGH.

Characteristics and Risk Factors Associated with SARS-CoV-2 Pneumonias in Hospitalized Pediatric Patients: A Pilot Study.

SARS-CoV-2 pneumonia in children has a lower incidence and severity compared to adults. Risk factors are adolescence and comorbidities. Our aims were to describe the characteristics of children admitted with SARS-CoV-2 pneumonia, identify risk factors associated with severity and compare the cases according to the variant of SARS-CoV-2. This was a descriptive and retrospective study, including patients aged 0-18 years hospitalized in a tertiary-care hospital between 1 March 2020 and 1 March 2022. Epidemiological, clinical, diagnostic and therapeutic data were analyzed. Forty-four patients were admitted; twenty-six (59%) were male and twenty-seven (61%) were older than 12 years. Thirty-six (82%) had comorbidities, the most frequent of which were obesity and asthma. Seven (15.9%) patients required high-flow oxygen, eleven (25%) non-invasive ventilation and four (9.1%) conventional mechanical ventilation. In critically ill patients, higher levels of anemia, lymphopenia, procalcitonin, lactate dehydrogenase (LDH) and hypoalbuminemia and lower levels of HDL-cholesterol were detected (all p < 0.05). Prematurity (p = 0.022) was associated with intensive care unit admission. Patients were younger during the Omicron wave (p < 0.01); no variant was associated with greater severity. In conclusion, pediatric patients with a history of prematurity or with anemia, lymphopenia, elevated procalcitonin, elevated LDH levels, hypoalbuminemia and low HDL-cholesterol levels may require admission and present more severe forms. Apart from age, no notable differences between SARS-CoV-2 variant periods were found.

Novel customized age-dependent corneal membranes and interactions with biodegradable nanoparticles loaded with dexibuprofen.

Ocular inflammation is one of the most prevalent diseases in ophthalmology and it is currently treated using eye drops of nonsteroidal antiinflammatory drugs such as dexibuprofen (DXI). However, their bioavailability is low and therefore, PLGA nanoparticles constitute a suitable approach to be administered as eyedrops. Therefore, DXI has been encapsulated into PLGA nanoparticles (DXI-NPs). Although the eye, and specifically the cornea, suffers from age-related changes in its composition, current medications are not focused on these variations. Therefore, to elucidate the interaction mechanism of DXI-NPs with the cornea in relation with age, two different corneal membrane models have been developed (corresponding to adult and elder population) using lipid monolayers, large and giant unilamellar vesicles. Interactions of both DXI and DXI-NPs were studied with these models by means of Langmuir balance technique, dipole potential, anisotropy and confocal microscopy. In addition, fluorescently labelled nanoparticles were administered to mice in order to corroborate these data obtained in vitro. It was observed that DXI-NPs interact with lipid membranes through an adhesion process, mainly in the rigid regions and afterwards DXI-NPs are internalized by a wrapping process. Furthermore, differences on the dipole potential caused by DXI-NPs in each corneal membrane have been obtained due to the increase of membrane rigidity on the ECMM. Additionally, it can be confirmed that DXI-NPs adhere to Lo phase and also inside the lipid membrane. Finally, in vitro and in vivo results corroborate that DXI-NPs are adhered to the more ordered phase. Finally, differences between interactions of DXI-NPs with the elder and adult corneal tissue were observed.

Determinación de viabilidad, vigor y banco de semillas de retamo espinoso (Ulex europaeus L.) en un Andisol de un ecosistema de Páramo

El retamo espinoso (Ulex europaeus L.) es una planta introducida invasora de rápido crecimiento y diseminación, con producción de semillas, que permanecen latentes en los primeros 5 cm de profundidad del suelo; esta planta altera espacios ecológicos nativos, áreas de producción agropecuaria y su control y erradicación no es exitosa. Conocer ciertas características de las semillas del retamo facilitará su control. Así, el objetivo de este trabajo, fue determinar el vigor, la viabilidad y el banco de semillas de retamo espinoso, en zonas del páramo de Sumapaz. Para las pruebas, se colectaron semillas en tres sitios: Delicias, Usabá y Laguna. La prueba de vigor, se llevó a cabo mediante conductividad eléctrica y la de viabilidad, por ensayo topográfico de tetrazolio; en cada prueba, se realizó cuatro repeticiones, cada una con 100 semillas; el diseño estadístico fue completamente al azar. Para el banco de semillas, se tomaron muestras de suelo, a profundidades 0-5, 5-10 y 10-20 cm y se dispusieron en bandejas de aluminio. La prueba de vigor mostró que, después de 6 horas de hidratación, la cantidad de iones lixiviados se estabilizó, con un valor de 38,51 µs.cm -1 g-1, a las diez horas, afirmando alto vigor de semillas. La prueba de viabilidad presentó un 98 % y el banco de semillas registró mayor cantidad en el horizonte de 10-20 cm, con 950 semillas.m2, en la Laguna. Este estudio demuestra que las semillas de retamo tienen altos valores de vigor, viabilidad y un abundante banco de semillas distribuidas a diferentes profundidades.

The gorse (Ulex europaeus L.) is an invasive introduced plant of rapid growth and spread, with seeds production that remain dormant in the first 5 cm of soil depth, this plant alters native ecological spaces, areas of agricultural production, and its control and eradication is not successful. Know certain characteristics of gorse seeds will facilitate its control. Thus, the purpose of this work was to determine the vigor, viability and seed bank of gorse in areas of the Sumapaz paramo. For the tests, seeds were collected in three sites: Delicias, Usabá and Laguna. The vigor test was carried out by means of electrical conductivity and the viability test by tetrazolium topographic assay, in each test four repetitions were carried out, each with 100 seeds, the statistical design was completely random. For the seed bank, soil samples were taken at depths of 0-5, 5-10 and 10-20 cm, and placed in aluminium trays. The vigor test showed that after 6 hours of hydration, the amount of leached ions stabilized with a value of 38.51 µs.cm -1 g-1 at ten hours, confirming high seed vigor. The viability test presented 98 % and the seed bank registered a greater quantity in the 10-20 cm horizon with 950 seeds.m2 in the Laguna. This study shows that gorse seeds have high values of vigor, viability, and an abundant seed bank distributed at different depths.

Chronic Lung Disease Following Neonatal Extracorporeal Membrane Oxygenation: A Single-Center Experience.

Objective: To assess the incidence and severity of chronic lung disease (CLD) after neonatal extracorporeal membrane oxygenation (ECMO) and to identify factors associated with its development. Methods: A retrospective observational study in a neonatal ECMO center was conducted. All neonates who received support with ECMO in our institution between January 2019 and October 2021 were included and their pulmonary outcome was investigated. Results: A total of 91 patients [60 with congenital diaphragmatic hernia (CDH), 26 with meconium aspiration syndrome, and 5 with other diagnoses] were included in this study. Sixty-eight (75%) neonates survived. Fifty-two (76%) ECMO survivors developed CLD. There was no statistical difference between patients with and without CLD with regard to gender or gestational age. Patients with CLD had lower birth weight, were younger at the initiation of ECMO, and required longer ECMO runs. Patients with CDH developed CLD more often than infants with other underlying diseases (94 vs. 60%). Seventeen ECMO survivors (25%) developed severe CLD. Conclusion: The incidence of CLD after neonatal ECMO is substantial. Risk factors for its development include CDH as an underlying condition, the necessity for early initiation of ECMO, and the need for ECMO over 7 days.

Impact of Time Point of Extracorporeal Membrane Oxygenation on Mortality and Morbidity in Congenital Diaphragmatic Hernia: A Single-Center Case Series.

Since there are no data available on the influence of the time point of ECMO initiation on morbidity and mortality in patients with congenital diaphragmatic hernia (CDH), we investigated whether early initiation of ECMO after birth is associated with a beneficial outcome in severe forms of CDH. All neonates with CDH admitted to our institution between 2010 until 2020 and undergoing ECMO treatment were included in this study and divided into four different groups: (1) ECMO initiation < 12 h after birth (n = 143), (2) ECMO initiation between 12−24 h after birth (n = 31), (3) ECMO initiation between 24−120 h after birth (n = 48) and (4) ECMO initiation > 120 h after birth (n = 14). The mortality rate in the first (34%) and fourth group (43%) was high and in the second group (23%) and third group (12%) rather low. The morbidity, characterized by chronic lung disease (CLD), did not differ significantly in the three groups; only patients in which ECMO was initiated >120 h after birth had an increased rate of severe CLD. Our data, although not randomized and limited due to small study groups, suggest that very early need for ECMO and ECMO initiation > 120 h after birth is associated with increased mortality.

Spontaneous Pneumomediastinum in Children with Viral Infections: Report of Three Cases Related to Rhinovirus or Respiratory Syncytial Virus Infection.

BACKGROUND: Spontaneous pneumomediastinum (SP) is generally a benign condition which can have various etiologies. Data on SP related to respiratory viral infections in children are rare and there are currently no official guidelines or consistent treatment recommendations for these patients. AIM: To discuss treatment options considering the recommendations for SP with different etiologies. METHODS: We report three cases of SP, which were related to rhinovirus or respiratory syncytial virus (RSV) infection. RESULTS: All three patients presented with typical symptoms of a respiratory tract infection and required oxygen supplementation during the hospital stay. All children benefited from a conservative, supportive therapy, and bed rest, and could be discharged after seven days or less without remaining symptoms. CONCLUSION: Surveillance and monitoring might be reasonable to detect and treat potential complications in children with SP due to viral infections, as one child developed an increasing pneumothorax, which had to be treated with a thoracic drainage.

Neurocardiovascular coupling in congenital diaphragmatic hernia patients undergoing different types of surgical treatment.

BACKGROUND: The effect of peri-operative management on the neonatal brain is largely unknown. Triggers for perioperative brain injury might be revealed by studying changes in neonatal physiology peri-operatively. OBJECTIVE: To study neonatal pathophysiology and cerebral blood flow regulation peri-operatively using the neuro-cardiovascular graph. DESIGN: Observational, prospective cohort study on perioperative neuromonitoring. Neonates were included between July 2018 and April 2020. SETTING: Multicentre study in two high-volume tertiary university hospitals. PATIENTS: Neonates with congenital diaphragmatic hernia were eligible if they received surgical treatment within the first 28 days of life. Exclusion criteria were major cardiac or chromosomal anomalies, or syndromes associated with altered cerebral perfusion or major neurodevelopmental impairment. The neonates were stratified into different groups by type of peri-operative management. INTERVENTION: Each patient was monitored using near-infrared spectroscopy and EEG in addition to the routine peri-operative monitoring. Neurocardiovascular graphs were computed off-line. MAIN OUTCOME MEASURES: The primary endpoint was the difference in neurocardiovascular graph connectivity in the groups over time. RESULTS: Thirty-six patients were included. The intraoperative graph connectivity decreased in all patients operated upon in the operation room (OR) with sevoflurane-based anaesthesia ( P  < 0.001) but remained stable in all patients operated upon in the neonatal intensive care unit (NICU) with midazolam-based anaesthesia. Thoracoscopic surgery in the OR was associated with the largest median connectivity reduction (0.33 to 0.12, P  < 0.001) and a loss of baroreflex and neurovascular coupling. During open surgery in the OR, all regulation mechanisms remained intact. Open surgery in the NICU was associated with the highest neurovascular coupling values. CONCLUSION: Neurocardiovascular graphs provided more insight into the effect of the peri-operative management on the pathophysiology of neonates undergoing surgery. The neonate's clinical condition as well as the surgical and the anaesthesiological approach affected the neonatal physiology and CBF regulation mechanisms at different levels. TRIAL REGISTRATION: NL6972, URL: https://www.trialre-gister.nl/trial/6972 .

Assessing Anticoagulation in Neonates With Congenital Diaphragmatic Hernia During Extracorporeal Membrane Oxygenation: Does Anti-Factor Xa or Thromboelastometry Provide Additional Benefit?

Objective: The optimal management of anticoagulation in neonatal/pediatric patients during extracorporeal membrane oxygenation (ECMO) has not been established yet and varies greatly among ECMO centers worldwide. Therefore, we aimed to assess whether the use of anti-factor Xa assay and/or thromboelastometry correlate better than activated clotting time with heparin dose in newborns with congenital diaphragmatic hernia during ECMO. We also examined whether these coagulation assays correlate with thrombotic and/or hemorrhagic complications, when the management of anticoagulation is based only on activated clotting time values. Methods: A prospective observational study in a neonatal ECMO center was conducted. We included all neonates with congenital diaphragmatic hernia born in our institution between March 2018 and January 2019 and requiring support with venoarterial ECMO. A total of 26 ECMO runs were analyzed. During the study, the heparin dose was still adjusted according to activated clotting time values. Measurements of anti-factor Xa assay, activated partial thromboplastin time, and a thromboelastometry from the same blood specimen were performed twice a day. Results: Anti-factor Xa levels showed a moderate correlation with heparin dose, whereas the other tests showed a weak correlation. Four patients (17.4%) had thrombotic complications, 2 patients (8.7%) experienced life-threatening bleeding, and in 11 patients (47.8%) disseminated intravascular coagulation (DIC) occurred. Anti-factor Xa levels were lower in the group with thrombotic complications (0.23 vs. 0.27 IU/ml; p = 0.002), while activated partial thromboplastin time was higher in the group with hemorrhagic complications (69.4 s vs. 59.8 s; p = 0.01). In patients experiencing DIC, heparin dose and anti-factor Xa levels were lower, while no difference in activated clotting time and clotting time in INTEM and INTEM-HEPTEM were shown. Conclusions: Anti-factor Xa levels correlate better to heparin dose than activated clotting time. The use of anti-factor Xa assay instead of activated clotting time for dosing of unfractionated heparin could reduce thrombotic complications in neonates with congenital diaphragmatic hernia on ECMO support. The thromboelastometry showed no additional benefit for this purpose.

Severe Pneumonia in Neonates Associated with Legionella pneumophila: Case Report and Review of the Literature.

The causative agent of legionellosis is the Gram-negative intracellular bacteria Legionella spp. Its clinical presentation varies from a mild febrile illness called Pontiac fever to the severe and possible fatal pneumonia, Legionnaires' disease. Immunocompromised patients, in particular, are affected. Only a small number of infected neonates are described in the literature. Most of them have been associated with water birth or the use of air humidifiers. In the last five years, a growing number of cases have been reported in Germany by the national institute of disease surveillance and prevention (Robert-Koch Institute). Here, we describe a fatal case report of pulmonary legionellosis with acute respiratory distress syndrome (ARDS), sepsis, associated cutaneous manifestation, and extracorporeal membrane oxygenation in a full-term neonate. Moreover, we present a review of the literature discussing the epidemiology, risk factors, clinical features, diagnostics, treatment options, and prevention for this rare condition in neonates.

Psoriasis: From Pathogenesis to Pharmacological and Nano-Technological-Based Therapeutics.

Research in the pathogenesis of inflammatory skin diseases, such as skin dermatitis and psoriasis, has experienced some relevant breakthroughs in recent years. The understanding of age-related factors, gender, and genetic predisposition of these multifactorial diseases has been instrumental for the development of new pharmacological and technological treatment approaches. In this review, we discuss the molecular mechanisms behind the pathological features of psoriasis, also addressing the currently available treatments and novel therapies that are under clinical trials. Innovative therapies developed over the last 10 years have been researched. In this area, advantages of nanotechnological approaches to provide an effective drug concentration in the disease site are highlighted, together with microneedles as innovative candidates for drug delivery systems in psoriasis and other inflammatory chronic skin diseases.

The Chest Radiographic Thoracic Area Can Serve as a Prediction Marker for Morbidity and Mortality in Infants With Congenital Diaphragmatic Hernia.

Objective: Valid postnatal prediction parameters for neonates with congenital diaphragmatic hernia (CDH) are lacking, but recently, the chest radiographic thoracic area (CRTA) was proposed to predict survival with high sensitivity. Here, we evaluated whether the CRTA correlated with morbidity and mortality in neonates with CDH and was able to predict these with higher sensitivity and specificity than prenatal observed-to-expected (O/E) lung-to-head ratio (LHR). Methods: In this retrospective cohort study, all neonates with CDH admitted to our institution between 2013 and 2019 were included. The CRTA was measured using the software Horos (V. 3.3.5) and compared with O/E LHR diagnosed by fetal ultrasonography in relation to outcome parameters including survival, extracorporeal membrane oxygenation (ECMO) support, and chronic lung disease (CLD). Results: In this study 255 neonates were included with a survival to discharge of 84%, ECMO support in 46%, and 56% developing a CLD. Multiple regression analysis demonstrated that the CRTA correlates significantly with survival (p = 0.001), ECMO support (p < 0.0001), and development of CLD (p = 0.0193). The CRTA displayed a higher prognostic validity for survival [area under the curve (AUC) = 0.822], ECMO support (AUC = 0.802), and developing a CLD (AUC = 0.855) compared with the O/E LHR. Conclusions: Our data suggest that the postnatal CRTA might be a better prognostic parameter for morbidity and mortality than the prenatal O/E LHR.

Cerebral Oxygenation and Activity During Surgical Repair of Neonates With Congenital Diaphragmatic Hernia: A Center Comparison Analysis.

Background and aim: Neonatal brain monitoring is increasingly used due to reports of brain injury perioperatively. Little is known about the effect of sedatives (midazolam) and anesthetics (sevoflurane) on cerebral oxygenation (rScO2) and cerebral activity. This study aims to determine these effects in the perioperative period. Methods: This is an observational, prospective study in two tertiary pediatric surgical centers. All neonates with a congenital diaphragmatic hernia received perioperative cerebral oxygenation and activity measurements. Patients were stratified based on intraoperatively administrated medication: the sevoflurane group (continuous sevoflurane, bolus fentanyl, bolus rocuronium) and the midazolam group (continuous midazolam, continuous fentanyl, and continuous vecuronium). Results: Intraoperatively, rScO2 was higher in the sevoflurane compared to the midazolam group (84%, IQR 77-95 vs. 65%, IQR 59-76, p = < 0.001), fractional tissue oxygen extraction was lower (14%, IQR 5-21 vs. 31%, IQR 29-40, p = < 0.001), the duration of hypoxia was shorter (2%, IQR 0.4-9.6 vs. 38.6%, IQR 4.9-70, p = 0.023), and cerebral activity decreased more: slow delta: 2.16 vs. 4.35 µV 2 (p = 0.0049), fast delta: 0.73 vs. 1.37 µV 2 (p = < 0.001). In the first 30 min of the surgical procedure, a 3-fold increase in fast delta (10.48-31.22 µV 2) and a 5-fold increase in gamma (1.42-7.58 µV 2) were observed in the midazolam group. Conclusion: Sevoflurane-based anesthesia resulted in increased cerebral oxygenation and decreased cerebral activity, suggesting adequate anesthesia. Midazolam-based anesthesia in neonates with a more severe CDH led to alarmingly low rScO2 values, below hypoxia threshold, and increased values of EEG power during the first 30 min of surgery. This might indicate conscious experience of pain. Integrating population-pharmacokinetic models and multimodal neuromonitoring are needed for personalized pharmacotherapy in these vulnerable patients. Trial Registration: https://www.trialregister.nl/trial/6972, identifier: NL6972.

Dexibuprofen Biodegradable Nanoparticles: One Step Closer towards a Better Ocular Interaction Study.

Ocular inflammation is one of the most prevalent diseases in ophthalmology, which can affect various parts of the eye or the surrounding tissues. Non-steroidal anti-inflammatory drugs (NSAIDs) such as ibuprofen, are commonly used to treat ocular inflammation in the form of eye-drops. However, their bioavailability in ocular tissues is very low (less than 5%). Therefore, drug delivery systems such as biodegradable polymeric PLGA nanoparticles constitute a suitable alternative to topical eye administration, as they can improve ocular bioavailability and simultaneously reduce drug induced side effects. Moreover, their prolonged drug release can enhance patient treatment adherence as they require fewer administrations. Therefore, several formulations of PLGA based nanoparticles encapsulating dexibuprofen (active enantiomer of Ibuprofen) were prepared using the solvent displacement method employing different surfactants. The formulations have been characterized and their interactions with a customized lipid corneal membrane model were studied. Ex vivo permeation through ocular tissues and in vivo anti-inflammatory efficacy have also been studied.

Metabolomic analysis of Shiga toxin 2a-induced injury in conditionally immortalized glomerular endothelial cells.

INTRODUCTION: Shiga toxin 2a (Stx2a) induces hemolytic uremic syndrome (STEC HUS) by targeting glomerular endothelial cells (GEC). OBJECTIVES: We investigated in a metabolomic analysis the response of a conditionally immortalized, stable glomerular endothelial cell line (ciGEnC) to Stx2a stimulation as a cell culture model for STEC HUS. METHODS: CiGEnC were treated with tumor necrosis factor-(TNF)α, Stx2a or sequentially with TNFα and Stx2a. We performed a metabolomic high-throughput screening by lipid- or gas chromatography and subsequent mass spectrometry. Metabolite fold changes in stimulated ciGEnC compared to untreated cells were calculated. RESULTS: 320 metabolites were identified and investigated. In response to TNFα + Stx2a, there was a predominant increase in intracellular free fatty acids and amino acids. Furthermore, lipid- and protein derived pro-inflammatory mediators, oxidative stress and an augmented intracellular energy turnover were increased in ciGEnC. Levels of most biochemicals related to carbohydrate metabolism remained unchanged. CONCLUSION: Stimulation of ciGEnC with TNFα + Stx2a is associated with profound metabolic changes indicative of increased inflammation, oxidative stress and energy turnover.

Poly(benzyl ether) Dendrimers Functionalized at the Core with Palladium Bis(N-Heterocyclic Carbene) Complexes as Catalysts for the Heck Coupling Reaction.

Bis(imidazolylidene)palladium complexes 9-12 containing a sterically hindered aryl group (mesityl or 2,6-diisopropylphenyl) and a poly(benzyl ether) dendron as N-substituents of the NHC ligand are accessible up to the third generation by transmetalation of the corresponding silver complexes. Complexes 9-12 are soluble, active, and very stable catalysts under Heck reaction conditions. The NHC ligand appears to be stably coordinated to the Pd during catalysis. The catalytic activity increases with generation number, although irregularly. The palladium site is not significantly congested in the reaction solvent by the increasing size of the dendritic substituents, as corroborated by X-ray diffraction, fluorescence and DOSY-NMR spectroscopy, and MD simulation studies. This is a consequence of the conformational semiflexibility of the poly(benzyl ether) dendrons and the benzylic link between these dendrons and the N-heterocyclic ligands.

Early Initiation of Renal Replacement Therapy in Pediatric Heart Surgery Is Associated with Lower Mortality.

Acute kidney injury (AKI) is frequent in the postoperative period of pediatric heart surgery and leads to significant morbidity and mortality. Renal replacement therapies (RRTs) are often used to treat AKI; however, these therapies have also been associated with higher mortality rates. Earlier initiation of RRT might improve outcomes. This study aims to investigate the relationship between the RRT and morbidity and mortality after pediatric heart surgery. We performed a single-center retrospective study of all children undergoing pediatric heart surgery between April 2010 and December 2012 at a tertiary children's hospital. A total of 480 patients were included. Of those, 109 (23 %) were neonates and 126 patients (26 %) developed AKI within the first 72 postoperative hours. Patients who developed AKI had longer PICU admissions [12 days (4-37.75) vs. 4 (2-11); p < 0.001] and hospital length of stay [27 (11-53) vs. 14 (8-24) p < 0.001] and higher mortality [22/126 (17.5 %) vs. 13/354 (3.7 %); p < 0.001]. RRT techniques were used in 32 (6.6 %) patients [18/109 (16 %) neonates and 14/371 (3.8 %) infants and children; p < 0.01], with 25 (78 %) receiving peritoneal dialysis (PD) and 7 (22 %) continuous RRT (CRRT). Patients who received PD within the first 24 postoperative hours had lower mortality compared with those in whom PD was initiated later [4/16 (25 %) vs. 4/9 (44.4 %)]. Mortality among patients who received CRRT was 28.6 % (2/7). No deaths were reported in patients treated with CRRT within the first 24 postoperative hours. Postoperative AKI is associated with higher mortality in children undergoing cardiac surgery. Early initiation of RRT, both PD in neonates and CRRT in pediatric patients, might improve morbidity and mortality associated with AKI.