Two pediatric cases of multisystem inflammatory-like syndrome following COVID-19 vaccination.

Multisystem inflammatory syndrome in children (MIS-C) is a novel post-infectious disease occurring in the context of SARS-CoV2 infection. COVID-19 vaccines have been authorized since December 2020, and adverse events including myocarditis have been reported following vaccination. We describe the cases of two pediatric patients presenting with clinical and laboratory features suggestive of MIS-C a few days after receiving their first dose of the Pfizer BNT162b2 vaccine. The outcome was favorable for both patients (after corticosteroid and immunoglobulin administration for one patient). These cases suggest an association between the COVID-19 vaccine and the occurrence of MIS-C.

Diagnostic accuracy of a calibrated abdominal compression to predict fluid responsiveness in children.

BACKGROUND: Fluid administration to increase stroke volume index (SVi) is a cornerstone of haemodynamic resuscitation. We assessed the accuracy of SVi variation during a calibrated abdominal compression manoeuvre (ΔSVi-CAC) to predict fluid responsiveness in children. METHODS: Patients younger than 8 yr with acute circulatory failure, regardless of their ventilation status, were selected. SVi, calculated as the average of five velocity-time integrals multiplied by the left ventricular outflow tract surface area, was recorded at four different steps: baseline, after an abdominal compression with a calibrated pressure of 25 mm Hg, after return to baseline, and then after a volume expansion (VE) of 10 ml kg-1 lactated Ringer solution over 10 min. Patients were classified as responders if SVi variation after volume expansion (ΔSVi-VE) increased by at least 15%. RESULTS: The 39 children included had a median [inter-quartile range (IQR)] age of 9 [5-31] months. Twenty patients were fluid responders and 19 were non-responders. ΔSVi-CAC correlated with ΔSVi-VE (r=0.829; P<0.001). The area under the receiver operating characteristic curve (ROCAUC) was 0.94 [95% confidence interval (CI), 0.85-0.99]. The best threshold for ΔSVi-CAC was 11% with a specificity of 95% [95% CI, 84-100] and a sensitivity of 75% [95% CI, 55-95]. ROCAUC of respiratory variation of IVC diameter (ΔIVC) was 0.53 [95% CI, 0.32-0.72]. CONCLUSION: ΔSVi-CAC during abdominal compression was a reliable method to predict fluid responsiveness in children with acute circulatory failure regardless of their ventilation status. CLINICAL TRIALS REGISTRATION: CPP Lyon sud est II: n° ANSM 2015-A00388-41 Clinicaltrial.gov: NCT02505646.

Eculizumab and thrombotic microangiopathy after hematopoietic stem cell transplantation: A report on its efficacy and safety in two pediatric patients.

BACKGROUND: Thrombotic microangiopathy (TMA) is a severe complication after hematopoietic stem cell transplantation (HSCT), with the reported mortality rate in such cases usually reaching 90%. CASES: We report on two pediatric cases of patients successfully treated by eculizumab for severe HSCT-TMA, occurring in two girls (8.4 and 3.6 years). The first patient developed TMA with hematologic abnormalities and renal/pulmonary lesions after allogeneic HSCT for Philadelphia-positive acute lymphoblastic leukemia; she received eculizumab 7 months after HSCT, with a dramatic improvement of renal function. The second patient developed severe TMA (cardiac tamponade, renal failure requiring dialysis, gastritis) after autologous HSCT for metastatic neuroblastoma. She received eculizumab for 7 months, with a dramatic improvement of renal function. No side effects were observed. CONCLUSION: The use of eculizumab as first-line therapy in pediatric patients with severe HSCT-TMA with multisystemic lesions appears promising. Larger international studies are required to confirm its benefit and safety for this specific indication.

A systematic review of interventions and performance measures for antifungal stewardship programmes.

Objectives: Antifungal resistance is a significant and emerging threat. Stewardship programmes (SPs) have been proposed as an opportunity to optimize antifungal use. While examples of antifungal SP implementation have been recently described, there is yet to be an overview of interventions and their impacts on performance measures. Methods: We systematically reviewed published articles using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses check-list 2009. MEDLINE was searched using the term 'antifungal stewardship' on 15 February 2017. Eligible studies were those that described an antifungal SP and included an intervention and an evaluation of performance measures. Results: A total of 97 studies were identified and 14 were included. Only five studies reported an antifungal stewardship team composed of all the recommended members. The main intervention was the formulation of recommendations to change treatment (12 of 14). The main performance measure collected was antifungal consumption (10 of 14), followed by antifungal expenditure (7 of 14), adherence to therapeutic advice (4 of 14) and impact on mortality (4 of 14). Antifungal consumption was reduced by 11.8% to 71% and antifungal expenditure by as much as 50%. Adherence to therapeutic advice ranged from 40% to 88%, whereas antifungal SPs had no impact on mortality. Conclusions: All antifungal SPs had an impact, in particular on antifungal consumption and antifungal expenditure. Active intervention including a review of prescriptions seems to have more impact than implementation of treatment guidelines only. According to available published studies, antifungal consumption appears to be the most achievable performance measure to evaluate the impact of an antifungal SP.

[Effectiveness of management of children with severe trauma in a pediatric trauma center and in an adult trauma center: A before-after study]. / Efficacité de la prise en charge des traumatismes graves de l'enfant en salle d'accueil des urgences vitales adulte ou pédiatrique : une étude avant-après.

OBJECTIVE: To compare management of injured children in an adult trauma center (TC) with competencies in pediatric trauma care (2005-2007) and in a pediatric-only trauma center (2010-2012). STUDY DESIGN: A before-after retrospective study. PATIENTS AND METHODS: Fifty-nine children between 1 and 15 years of age admitted to the adult TC (2005-2007) were compared to 56 children admitted to the pediatric TC (2010-2012). Epidemiological data, severity scores, early outcome, and care duration in trauma resuscitation before whole-body CT were collected and compared between the two periods. RESULTS: This study found no significant differences between the two periods in terms of care duration before the whole-body CT scan (28 min [18-40] vs 26.5 min [21-36], P=0.89) and early mortality (eight children [13.5%] vs ten children [17.8%], P=0.35). CONCLUSION: With no differences in early management of injured children demonstrated, this study validates the organization within our pediatric trauma center. The effectiveness of management of children between 1 and 15 years of age with severe trauma seems to be similar in the two contexts.

[Nutritional status in pediatric intermediate care: Assessment at admission, progression during the stay and after discharge]. / État nutritionnel en unité de surveillance continue pédiatrique : évaluation à l'admission, en cours de séjour et à distance.

INTRODUCTION: Malnutrition, known as a cause of morbidity, has not been studied in children admitted to pediatric intermediate care units. This study aimed to describe the association between patients' nutritional status and the relative severity of illness that characterizes this population. PATIENTS AND METHODS: In this prospective longitudinal study, a dedicated nutrition support team assessed the nutritional status of all children, aged 5 days to 18 years, admitted to our university pediatric intermediate care unit (Hôpital Femme-Mère-Enfants, Lyon, France) over one year (2012-2013). Weight, height, body mass index, weight-for-age ratio, height-for-age ratio, and the analysis of growth curves were collected at admission. We monitored patients' weight, which allowed us to detect malnutrition occurrence during the stay, and its progression up to 3 months after discharge. RESULTS: A total of 459 patients were enrolled. Based on the analysis integrating all nutritional indices and the progression of growth curves, malnutrition at admission was detected in 23.8% of children (20.5% and 6.8% suffered from acute and chronic malnutrition, respectively). Based only on the body mass index, malnutrition was detected in 15.5% of children. Chronic disease appeared as a risk factor for malnutrition at admission (P=0.0001) and young age for acute malnutrition (P=0.04). The incidence of acquired malnutrition during the stay (in children with a length of stay > 5 days) was up to 26%, and dyspnea was the only risk factor identified. This population recovered with a normal nutritional status late (66% after 2 months and 16% after 3 months). CONCLUSIONS: The prevalence of malnutrition is high in our pediatric intermediate care unit. The occurrence of acquired malnutrition during the stay is frequent. All children should benefit from systematic nutritional assessment at admission as well as careful monitoring during the stay and after discharge, to adapt early and individualized nutritional support.

Decompressive craniectomy in the treatment of post-traumatic intracranial hypertension in children: our philosophy and indications.

Decompressive craniotomy (DC) in children is a life-saving procedure for the treatment of refractory intracranial hypertension related to traumatic, ischemic and infectious lesions. Different surgical procedures have been proposed including uni or bilateral hemicraniectomy, bi-frontal, bi-temporal, or bi-parietal craniotomies. DC can avoid the cascade of events related to tissue hypoxia, brain perfusion reduction, hypotension and the evolution of brain edema that can be responsible for brain herniation. The monitoring of intracranial pressure (ICP) is very important to take a decision as well as the value of Trans cranial Doppler (TCD). Repeated TCD in the intensive care unit give important information about the decrease of the cerebral perfusion pressure (CPP) and facilitates the decision making. The important question is about how long time we have to wait before to perform the DC. Three conditions can be distinguished: 1) ICP stable and TCD with good parameters: the decision can be postponed; 2) ICP>20 mmHg with good TCD and without clinical signs of deterioration: the decision can be postponed; 3) ICP>20 mmHg with altered CPP and degraded TCD value and clinical signs of brain herniation: the surgical procedure is indicated. The decision of a ventricular drainage can also be discussed but in cases of slit ventricles it is preferable to realize a DC to avoid the problems of multiple taps without finding the ventricular system. In some very specific situations, DC has to be contraindicated. The first one is a prolonged cardiopulmonary arrest with a no-flow longer than 15 minutes and irreversible lesions on the TCD or on the CT-scan. The second most common situation is a patient with GCS of 3 on admission associated with bilaterally fixed dilated pupils. In this case TCD is very useful to document the decrease or the absence of diastolic flux that indicates a very poor cerebral perfusion. In case of severe polytraumatism with multiorgan failure, especially in very severe hemorrhagic shock with incontrollable coagulopathy, the realization of DC is definitely hazardous with y a high risk of cardiac arrest during the surgical procedure. The decision to realize a hemicraniectomy or a bi-frontal craniotomy is related to the presence or not of associated traumatic lesions as hemorrhagic contusions or a sub-dural or extradural hematoma. In cases of diffuse cerebral edema the bi-frontal bone flap is indicated. In all cases a closure of the dura mater with a large dural patch has to be performed avoiding compression of the nervous system. Our results showed a mortality rate of 18%. Eighty percent of the survivors have a good quality of life but only 43% in a scholar age could attend a normal program. Patients treated with DC need a long follow-up and an important rehabilitation program to improve their quality of life. Our report shows that DC in children is effective to control the post-traumatic intracranial hypertension but a long follow-up is recommended to access the sequels and quality of life of these patients.

[Severe local anesthetic intoxication in an infant undergoing circumcision]. / Intoxication grave aux anesthésiques locaux lors d'une circoncision.

Local anesthetic intoxication is an uncommon complication of regional anesthesia. We report the case of a 4-month-old infant who presented with generalized tonic-clonic seizure complicated by cardiac arrest secondary to a severe intoxication to local anesthesia. These complications were observed after a bilateral dorsal penile nerve block with lidocaine for circumcision in a non-hospital setting. This report emphasizes the potential risk of local anesthetic systemic toxicity in such circumstances and describes its treatment.

[Deep vein thrombosis revealing myeloproliferative syndrome in two adolescents]. / Thrombose splanchnique révélatrice d'un syndrome myéloprolifératif chez deux adolescentes.

Deep vein thrombosis occurs in 30% of patients with essential thrombocythemia, but rarely at initial diagnosis. We report two pediatric patients with essential thrombocythemia revealed by atypical deep vein thrombosis. First, a 16-year-old girl presented Budd-Chiari syndrome revealed by a hemorrhagic shock. Clinical exam revealed isolated splenomegaly. A search for thrombophilia found a factor V Leiden homozygous mutation and a Jak2 mutation. Bone marrow biopsy confirmed the diagnosis of a myeloproliferative disorder. The second case, a 17-year-old girl, had a routine examination by her physician that revealed splenomegaly. Ultrasonography displayed thrombus in the splenic and portal vein. An isolated Jak2 mutation was found and a myeloproliferative disorder was confirmed by bone marrow biopsy. The diagnosis of myeloproliferative disorder was made in both patients presenting atypical venous thrombosis with a Jak2 mutation and confirmed by bone marrow biopsy. These initial presentations of myeloproliferative disorders are rare in childhood and possibly underdiagnosed.

[Nuclear magnetic resonance based metabolic phenotyping for patient evaluations in operating rooms and intensive care units]. / Phénotypage métabolique par résonance magnétique nucléaire pour l'évaluation périopératoire et en réanimation.

Metabolic phenotyping consists in the identification of subtle and coordinated metabolic variations associated with various pathophysiological stimuli. Different analytical methods, such as nuclear magnetic resonance, allow the simultaneous quantification of a large number of metabolites. Statistical analyses of these spectra thus lead to the discrimination between samples and the identification of a metabolic phenotype corresponding to the effect under study. This approach allows the extraction of candidate biomarkers and the recovery of perturbed metabolic networks, driving to the generation of biochemical hypotheses (pathophysiological mechanisms, diagnostic tests, therapeutic targets…). Metabolic phenotyping could be useful in anaesthesiology and intensive care medicine for the evaluation, monitoring or diagnosis of life-threatening situations, to optimise patient managements. This review introduces the physical and statistical fundamentals of NMR-based metabolic phenotyping, describes the work already achieved by this approach in anaesthesiology and intensive care medicine. Finally, potential areas of interest are discussed for the perioperative and intensive management of patients, from newborns to adults.

Complications and factors associated with severity of influenza in hospitalized children and adults during the pandemic wave of A(H1N1)pdm2009 infections--the Fluco French cohort.

BACKGROUND: The emergence of novel A(H1N1)pdm2009 virus threatened to lead to frequent severe manifestations. OBJECTIVES: To describe the clinical, virological, and biological characteristics of the disease and identify the factors associated with severe presentations. STUDY DESIGN: This prospective multicenter study recruited consecutive hospitalized patients with confirmed A(H1N1)pdm2009 disease. Clinical, virological and biological assessments were carried out at inclusion and 30 days post-inclusion. Disease manifestations were assessed by an adjudication committee using pre-identified definitions of complications and severity scores. RESULTS: The study analyzed from November 30th, 2009 to February 8th, 2010, 40 hospitalized patients, 21 children and 19 adults. Eighteen (45%) were considered to have severe presentations. Except age, main characteristics in children and adults did not differ. The majority (18/21) of children and all adults had a respiratory presentation; extra-respiratory manifestations tended to be more frequent in children (12 vs. 6, P=0.10). Two children against 5 adults presented acute respiratory distress syndrome (ARDS, P=0.23), but more children suffered respiratory failure (7 vs. 1, P=0.046) without ARDS. At day 30, one death had occurred in each group. The main factor associated with non-severe presentation was an early (<48 h) implementation of oseltamivir treatment (P=0.038). CONCLUSIONS: Although the study failed to achieve its main objective, due mainly to the difficulty of carrying a study of this nature in the midst of a pandemic, it allowed the description of a panel of unusual and complicated forms and confirmed the added value of early oseltamivir treatment in limiting severity in hospitalized children and adults.

[Epidemiology and evaluation of withdrawing and withholding of treatment procedure in a pediatric intensive care unit]. / Épidémiologie et évaluation des procédures de limitation et d'arrêt des traitements de maintien des fonctions vitales en réanimation pédiatrique.

OBJECTIVES: Leonetti Law of 2005 concerns procedures for questioning about the appropriateness of initiating or maintaining life-sustaining treatments. Decision of withdrawing and withholding treatment has long been practiced by neonatologists, adult and pediatricians intensivists. In this regard, the recommendations of societies encourage medical teams to assess their practices to improve them. Our evaluation is based on the document of the Ethics Committee of SRLF edited in 2010. TYPE OF STUDY: We achieved a retrospective evaluation of professional practices of the transcription of our decisions of withdrawing and withholding treatment. PATIENTS AND METHODS: This study included all children (95 patients) who have had a questioning about life-sustaining treatment of ICU between March 2008 and August 2011 in the pediatric intensive care unit of Children's Hospital of Lyon. Our evaluation is based on the document of the Ethics Committee of French Society of intensive care (SRLF) edited in 2010. We collected epidemiological data on children concerned by questioning about the appropriateness of initiating or maintaining LST and an evaluation of the transcription of our procedures for LST in our folders. Evaluation included 40 cases: 20 folders randomly selected prior an information meeting (January 2011) which were compared with 20 cases occurred consecutively after this information. This meeting was intended to remind recommendations of good practice and principal points of the law. The main assessment measure was the improvement of the practices respecting criteria of the document of the Ethics Committee of SRLF modified for pediatric care. MAIN RESULTS: Epidemiological data on procedures are comparable to literature data. Concerning the evaluation of our practices before/after a briefing and highlighted a tendency to the improvement without statistically significance. The transcription of reflection and the arguments of decision of withdrawing and withholding treatment and evaluation of pain was the points who need improvement. Finally, despite the positive developments in the therapeutic use of analgesics and sedatives, pain continues to be undervalued. CONCLUSION: The evaluation of professional practices is recommended to improve the procedures of questioning about life-sustaining treatments have become an area of expertise in intensive care.

Pediatric neurological complications associated with the A(H1N1)pdm09 influenza infection.

BACKGROUND: Influenza-related neurological complications (INC) have been reported during seasonal flu in children. OBJECTIVES: To investigate the types, outcomes and incidence of INC occurring during the 2009 A(H1N1) pandemic, a retrospective analyze was conducted in the single French pediatric hospital of Lyon from October 2009 to February 2010. STUDY DESIGN: All children presenting with fever, influenza-like illness, respiratory distress or neurological symptoms were tested for influenza A(H1N1)pdm09 infection from respiratory specimens using real time RT-PCR. RESULTS: INC occurred in 14 A(H1N1)pdm09 positive children (7.7% of A(H1N1)pdm09 positive children admitted to hospital) with a median age of 5.1 years. Admission to the intensive care unit (ICU) was required for nine children (64.3%). Half of the children with INC had comorbidity and three had coinfection, both characteristics mainly found in children requiring the ICU. All children received oral oseltamivir treatment. Febrile seizures were observed in eight children, half of them having a chronic comorbidity (2 epilepsy, 1 nonketotic hyperglycinemia, 1 anoxic encephalopathy). Other INC, less commonly reported, included 2 cases of encephalitis, 1 encephalopathy, 1 basilar artery thrombosis, 1 myasthenic crisis and 1 coma. Eleven of the 14 children (78.6%) recovered, one had a minor disability, one child developed a locked-in syndrome and one died from complications of an acute necrotizing encephalopathy. DISCUSSION: INC can be observed even in children with no underlying disorder. It may lead to dramatic issue in a significant number of cases.

Pragmatic management of Panton-Valentine leukocidin-associated staphylococcal diseases.

Panton-Valentine leukocidin (PVL)-producing Staphylococcus aureus is associated with a broad spectrum of diseases, ranging from common uncomplicated soft tissue infections to severe diseases such as complicated soft tissue infections, extensive bone and joint infections, and necrotising pneumonia. Specialised management of infection based on the presence of PVL may not be required for mild infections, whereas it could be lifesaving in other settings. Moreover, most severe PVL diseases are recently identified entities and a 'gold standard' treatment from comparatives studies of different therapeutic options is lacking. Thus, recommendations are based on expert opinions, which are elaborated based on theory, in vitro data and analogies with other toxin-mediated diseases. In this review, we consider the potential need for specialised PVL-based management and, if required, which tools should be used to achieve optimal management.

[Varicella-associated purpura fulminans and deep vein thrombosis: a pediatric case report]. / Purpura fulminans post-varicelleux et thrombose veineuse : à propos d'un cas pédiatrique.

Purpura fulminans (PF) and deep vein thrombosis are rare complications secondary to chicken pox disease. The presence of antibodies reflects an ongoing immunological process and requires specialized management. The present study reports a 4-year-old boy with no medical history who presented with purpura on the legs 10 days after chicken pox eruption. Laboratory tests showed a disseminated intravascular coagulation associated with low plasma protein C and S activities, and the presence of anti-protein S antibodies. A replacement therapy with protein C infusions and fresh frozen plasma was prescribed. The patient also underwent regular sessions of hyperbaric oxygen followed by the surgery. Fourteen days after the beginning of the purpuric lesions, he presented deep vein thrombosis (DVT) of the lower limbs and was treated with unfractionated heparin. This case report illustrates the pathophysiology of DVT occurring in a patient with chicken pox disease (i.e., acquired protein C and S deficiencies and anti-protein S autoantibodies) and emphasizes the utility of thrombophilia testing in order to better adapt treatment.

Respiratory viruses in children admitted to hospital intensive care units: evaluating the CLART® Pneumovir DNA array.

Viruses play a significant part in children's respiratory infections, sometimes leading to hospitalization in cases of severe respiratory distress. The aim of this study was to investigate respiratory infections in children treated in a hospital intensive care unit (ICU). Assays were performed using the CLART® Pneumovir DNA array assay (Genomica, Coslada, Madrid, Spain), which makes it possible to detect 11 genus of respiratory viruses simultaneously. During the winter of 2008-2009, 73 respiratory specimens collected from 53 children under 2 years of age and admitted to an ICU were tested. At least one virus was detected in 78% (57/73) of the samples. The virological diagnosis was based on single infections in 65% (37/57) and on multiple infections in 35% (20/57) of cases. The array assay revealed respiratory syncytial virus (RSV) in 73.6% (42/57) of the samples and rhinovirus in 24.6% (14/57), either on their own or in co-infections. All viruses identified in single and multiple infections were tested, taking into account clinical features, risk factors, and severity criteria. Children with no risk factors presented more multiple infections, up to 42% of cases, than children with at least one risk factor. RSV seemed to induce severe symptoms by itself as no difference in intubation needs was observed when RSV was detected on its own or in co-infection. The CLART® Pneumovir DNA array was useful for examining severe viral respiratory infections, when other viruses than those detected by conventional methods could be involved, particularly in an ICU.

[Cardiac tamponade by right atrial laceration due to blunt chest trauma in a 3-year-old child]. / Tamponnade cardiaque par plaie de l'oreillette droite liée à un traumatisme fermé du thorax chez une enfant de trois ans.

The case of 3-year-old girl severely injured, as restrained car passenger in a road crash, is reported. She presented with isolated circulatory failure, without specific clinical signs except skin contusions corresponding to seat belt. Because of mediastinum enlargement on systematic chest X-ray, a pericardial effusion was suspected, which was confirmed by echography, rapidly complicated by an acute tamponade without visible cause on CT-scan. The radiological assessment showed a moderate peritoneal haemorrhage related to a splenic injury. A persistent haemodynamic instability required a pericardial puncture, after rapid sequence tracheal intubation of the child, but without clinical improvement, despite fluid bolus, red-blood cell transfusion and epinephrine infusion. The child was rapidly transferred to the cardiac operating room for sternotomy, which showed a right atrial laceration. The injury was repaired, allowing the child to survive without disability. Tamponade due to traumatic cardiac injury is extremely rare in children. The clinical diagnosis is particularly difficult to establish in the context of polytrauma. The classical symptoms of cardiac tamponade are rarely complete. The association of chest injury, isolated circulatory failure and enlargement of mediastinum at chest X-ray should alert the physician. As the severity of these injuries is high, a rapid and multidisciplinary management is required, as well as specific anaesthetics precautions.

Pandemic A(H1N1)2009 influenza virus detection by real time RT-PCR: is viral quantification useful?

The emergence of the influenza A(H1N1) 2009 virus prompted the development of sensitive RT-PCR detection methods. Most are real time RT-PCRs which can provide viral quantification. In this manuscript, we describe a universal influenza A RT-PCR targeting the matrix (M) gene, combined with an RNaseP RT-PCR. These PCRs allow the detection of all influenza A virus subtypes, including A(H1N1)2009, together with a real-time assessment of the quality of the specimens tested. These PCR procedures were evaluated on 209 samples collected from paediatric patients. Viral loads determined through Ct values were corrected according to the RNaseP Ct value. The mean viral load in the collected samples was estimated to be 6.84 log RNA copies/mL. For poor quality samples (RNaseP Ct > 27), corrections resulted in +3 to +8 Ct values for the M gene RT-PCR. Corrected influenza Ct values were lower in late samples. No correlation was established between viral loads and clinical severity or duration of disease.This study shows that real time RT-PCR targeting the matrix gene is a reliable tool for quantification of type A influenza virus but emphasises the need for sample quality control assessment through cellular gene quantification for reliable estimation of the viral load. This method would be useful for disease management when repeated specimens are collected from an infected individual.