Antenatal and postnatal ultrasound in the evaluation of the risk of vesicoureteral reflux

Antenatal hydronephrosis (ANH) is a frequent anomaly detected on fetal ultrasound scans. There is no consensus recommendation for the postnatal follow-up and/or the necessity to perform a voiding cystourethrography (VCUG) to diagnose vesicoureteral reflux (VUR). We conducted a cohort/non-randomized trial of 121 patients with ANH, defined as an anterior posterior diameter (APD) ≥5mm after the 20th week of gestation, to evaluate the ability of the antenatal and postnatal ultrasonography results to predict VUR. All infants had two successive ultrasounds at 5days and 1month, respectively, after birth. A VCUG was performed at 6weeks in children with a persistent APD ≥5mm and/or an ureteral dilatation observed on at least one of two postnatal ultrasounds. In total, 88 patients had VCUG and nine had VUR, with five having high-grade reflux (>grade II). The risk of VUR increased significantly with the degree of APD detected on the postnatal ultrasound scan (p = 0.03). The odds ratios were 5.0 [95% confidence interval (CI) 0.5-51.2] for APD = 7-9mm and 9.1 (95% CI 1.0-80.9) for APD ≥10mm. The results of this study show that among our patient cohort antenatal ultrasound was not predictive of reflux. There was, however, a relation between the importance of the postnatal renal pelvis diameter and the risk of VUR. A cut-off of 7mm showed a fair ability of ultrasonography to predict VUR and a cut-off of 10mm enabled all severe refluxes in the 88 patients who had a VCUG to be diagnose

Best Practice Recommendations for the Diagnosis and Management of Children With Pediatric Inflammatory Multisystem Syndrome Temporally Associated With SARS-CoV-2 (PIMS-TS; Multisystem Inflammatory Syndrome in Children, MIS-C) in Switzerland.

Background: Following the spread of the coronavirus disease 2019 (COVID-19) pandemic a new disease entity emerged, defined as Pediatric Inflammatory Multisystem Syndrome temporally associated with COVID-19 (PIMS-TS), or Multisystem Inflammatory Syndrome in Children (MIS-C). In the absence of trials, evidence for treatment remains scarce. Purpose: To develop best practice recommendations for the diagnosis and treatment of children with PIMS-TS in Switzerland. It is acknowledged that the field is changing rapidly, and regular revisions in the coming months are pre-planned as evidence is increasing. Methods: Consensus guidelines for best practice were established by a multidisciplinary group of Swiss pediatric clinicians with expertise in intensive care, immunology/rheumatology, infectious diseases, hematology, and cardiology. Subsequent to literature review, four working groups established draft recommendations which were subsequently adapted in a modified Delphi process. Recommendations had to reach >80% agreement for acceptance. Results: The group achieved agreement on 26 recommendations, which specify diagnostic approaches and interventions across anti-inflammatory, anti-infectious, and support therapies, and follow-up for children with suspected PIMS-TS. A management algorithm was derived to guide treatment depending on the phenotype of presentation, categorized into PIMS-TS with (a) shock, (b) Kawasaki-disease like, and (c) undifferentiated inflammatory presentation. Conclusion: Available literature on PIMS-TS is limited to retrospective or prospective observational studies. Informed by these cohort studies and indirect evidence from other inflammatory conditions in children and adults, as well as guidelines from international health authorities, the Swiss PIMS-TS recommendations represent best practice guidelines based on currently available knowledge to standardize treatment of children with suspected PIMS-TS. Given the absence of high-grade evidence, regular updates of the recommendations will be warranted, and participation of patients in trials should be encouraged

Multicenter Randomized Trial of Methylprednisolone vs. Intravenous Immunoglobulins to Treat the Pediatric Inflammatory Multisystem Syndrome-Temporally Associated With SARS-CoV-2 (PIMS-TS): Protocol of the Swissped RECOVERY Trial.

Introduction: In 2020, a new disease entitled Pediatric Inflammatory Multisystem Syndrome temporally associated with COVID-19 (PIMS-TS), or Multisystem Inflammatory Syndrome in Children (MIS-C), emerged, with thousands of children affected globally. There is no available evidence based on randomized controlled trials (RCT) to date on the two most commonly used immunomodulatory treatments, intravenous immunoglobulins (IVIG) and corticosteroids. Therefore, the Swissped RECOVERY trial was conducted to assess whether intravenous (IV) methylprednisolone shortens hospital length of stay compared with IVIG. Methods and Analysis: Swissped RECOVERY is an ongoing investigator-initiated, open-label, multicenter two-arm RCT in children and adolescents <18 years hospitalized with a diagnosis of PIMS-TS. The trial is recruiting at 10 sites across Switzerland. Patients diagnosed with PIMS-TS are randomized 1:1 to methylprednisolone IV (10 mg/kg/day for 3 days) or IVIG (2 g/kg as a single dose). The primary outcome is hospital length of stay censored at day 28, death, or discharge (whichever is first). The target total sample size is ~80 patients 1:1 randomized to each study arm. Ancillary and exploratory studies on inflammation, vaccination acceptance and coverage, long-term outcomes, and healthcare costs are pre-planned. Significance: Currently, robust trial evidence for the treatment of PIMS-TS is lacking, with a controversy surrounding the use of corticosteroids vs. IVIG. This trial will provide evidence for the effectiveness and safety of these two treatments. Ethics and Dissemination: The study protocol, which was designed based on the U.K. RECOVERY trial, the patient information and consent forms, and other study-specific study documents were approved by the local ethics committees (Project ID: 2021-00362). Registration Details: The study is registered on the Swiss National Clinical Trials Portal (SNCTP000004720) and Clinicaltrials.gov (NCT04826588)

Mitochondrial Damage-Associated Molecular Patterns: From Inflammatory Signaling to Human Diseases

Over the recent years, much has been unraveled about the pro-inflammatory properties of various mitochondrial molecules once they are leaving the mitochondrial compartment. On entering the cytoplasm or the extracellular space, mitochondrial DAMPs (also known as mitochondrial alarmins) can become pro-inflammatory and initiate innate and adaptive immune responses by activating cell surface and intracellular receptors. Current evidence indicates that uncontrolled and excessive release of mitochondrial DAMPs is associated with severity, has prognosis value in human diseases, and contributes to the dysregulated process observed in numerous inflammatory and autoimmune conditions, as well as in ischemic heart disease and cancer. Herein, we review that the expanding research field of mitochondrial DAMPs in innate immune responses and the current knowledge on the association between mitochondrial DAMPs and human diseases

Multisystem inflammatory syndrome in children related to COVID-19: What we have learned so far on this new pediatric inflammatory syndrome

Since the beginning of COVID-19 pandemic, a new post-infectious inflammatory manifestation of SARS-CoV-2 affecting children has been described. It was defined as Pediatric Inflammatory Multisystem Syndrome temporally associated with COVID-19 (PIMS/PIMS-TS) by the Royal College of Pediatrics and Child Health, or as Multisystem Inflammatory Syndrome in Children (MIS-C) by the World Health Organization and the Center for Disease Control and Prevention. MIS-C represents a late manifestation of SARS-CoV-2 infection affecting predominantly previously healthy school-age children presenting with moderate to severe multi-organ dysfunction associated with an exaggerated proinflammatory response and presence of elevated SARS-CoV-2 immunoglobulin G antibodies. Although MIS-C shares similarities with Kawasaki Disease (KD), children with MIS-C tend to be older and present with a more severe proinflammatory response and myocardial injury than children with KD. The pathophysiology of MIS-C remains largely unknown, and the current management of MIS-C is extrapolated from KD and focuses on restoring immune homeostasis with intravenous immunoglobulin, corticosteroids, and biologics as well as on the prevention of vascular complications with antiplatelet therapy and anticoagulation. Recent immunoprofile studies on MIS-C patients discovered the presence of a superantigenic-like motif on SARS-CoV-2 spike glycoprotein and an autoimmune signature targeting the various organs involved in MIS-C. This review provides an extensive update on the state of knowledge of this new post-infectious hyperinflammatory syndrome affecting children. This topic is important for two reasons. Firstly, SARS-CoV-2 continues to infect children worldwide who may therefore still be at risk of developing MIS-C. The additional knowledge brought by this review to the clinicians may help them in the care of MIS-C patients. Secondly, a better understanding of the immunopathogenesis of MIS-C and how its immunopathological signature is distinct from acute SARS-CoV-2 infection or KD will not only be useful to guide optimal treatment in MIS-C but may also help in the management of similar hyperinflammatory conditions affecting children such as KD or haemophagocytic lymphohistiocytosis.</p

Rôle de l'ultrason anténatal et postnatal dans l'évaluation du risque de reflux vésico-urétéral

L'hydronéphrose anténatale se définit par une dilatation du système pyélocaliciel rénal et représente une des anomalies les plus fréquentes découverte à l'ultrason anténatal. Bien que les formes mineures soient la plupart du temps physiologiques et transitoires, la présence d'une dilatation du système pyélocaliciel peut néanmoins être associée à une uropathie obstructive ou à un reflux vésico-urétéral. L'importance de la dilatation se quantifie par la mesure en cm du diamètre antéro-postérieure (AP) de celle-ci. A l'heure actuelle, il n'existe aucun consensus dans la littérature concernant le diamètre AP à partir duquel il est indiqué d'effectuer un suivi postnatal et un dépistage systématique à la recherche d'un reflux vésico-urétéral lors de la découverte d'une hydronéphrose anténatale de forme mineure (diamètre antéro-postérieur du bassinet < 10mm). Cette situation engendre pour le nourrisson un nombre important d'examens invasifs et irradiants inutiles associés à un stress parental considérable. Le but de cette étude est d'évaluer de manière prospective l'habileté de l'échographie anténatale et postnatale à sélectionner les enfants à risque de présenter un reflux vésico-urétéral en fonction du diamètre AP à l'ultrason. Notre recherche a permis de démontrer que le risque de présenter un reflux vésico-urétéral était mieux corrélé avec le résultat des ultrasons postnataux que ceux des US anténataux et que ce risque augmente de manière significative en fonction du degré de dilatation pyélocalicielle présent sur l'ultrason postnatal. Ces données confirment l'utilité de l'ultrason postnatal comme examen de dépistage du reflux vésico-urétéral pour les enfants ayant présenté une hydronéphrose anténatale de forme mineure

Mitochondrial Damage-Associated Molecular Patterns: From Inflammatory Signaling to Human Diseases

Over the recent years, much has been unraveled about the pro-inflammatory properties of various mitochondrial molecules once they are leaving the mitochondrial compartment. On entering the cytoplasm or the extracellular space, mitochondrial DAMPs (also known as mitochondrial alarmins) can become pro-inflammatory and initiate innate and adaptive immune responses by activating cell surface and intracellular receptors. Current evidence indicates that uncontrolled and excessive release of mitochondrial DAMPs is associated with severity, has prognosis value in human diseases, and contributes to the dysregulated process observed in numerous inflammatory and autoimmune conditions, as well as in ischemic heart disease and cancer. Herein, we review that the expanding research field of mitochondrial DAMPs in innate immune responses and the current knowledge on the association between mitochondrial DAMPs and human diseases

New Generation Neonatal High Frequency Ventilators: Effect of Oscillatory Frequency and Working Principles on Performance

Several new generation neonatal ventilators that incorporate conventional as well as high frequency ventilation (HFOV) have appeared on the market. Most of them offer the possibility to use HFOV in a volume-targeted mode, despite absence of any preclinical data. With a bench test, we evaluated the performances of 4 new neonatal HFOV devices and compared them to the SensorMedics HFOV device