Radiological pulmonary sequelae after COVID-19 and correlation with clinical and functional pulmonary evaluation: results of a prospective cohort.

OBJECTIVES: Whether COVID-19 leads to long-term pulmonary sequelae or not remains unknown. The aim of this study was to assess the prevalence of persisting radiological pulmonary fibrotic lesions in patients hospitalized for COVID-19. MATERIALS AND METHODS: We conducted a prospective single-center study among patients hospitalized for COVID-19 between March and May 2020. Patients with residual symptoms or admitted into intensive care units were investigated 4 months after discharge by a chest CT (CCT) and pulmonary function tests (PFTs). The primary endpoint was the rate of persistent radiological fibrotic lesions after 4 months. Secondary endpoints included further CCT evaluation at 9 and 16 months, correlation of fibrotic lesions with clinical and PFT evaluation, and assessment of predictive factors. RESULTS: Among the 1151 patients hospitalized for COVID-19, 169 patients performed a CCT at 4 months. CCTs showed pulmonary fibrotic lesions in 19% of the patients (32/169). These lesions were persistent at 9 months and 16 months in 97% (29/30) and 95% of patients (18/19) respectively. There was no significant clinical difference based on dyspnea scale in patients with pulmonary fibrosis. However, PFT evaluation showed significantly decreased diffusing lung capacity for carbon monoxide (p < 0.001) and total lung capacity (p < 0.001) in patients with radiological lesions. In multivariate analysis, the predictive factors of radiological pulmonary fibrotic lesions were pulmonary embolism (OR = 9.0), high-flow oxygen (OR = 6.37), and mechanical ventilation (OR = 3.49). CONCLUSION: At 4 months, 19% of patients investigated after hospitalization for COVID-19 had radiological pulmonary fibrotic lesions; they persisted up to 16 months. CLINICAL RELEVANCE STATEMENT: Whether COVID-19 leads to long-term pulmonary sequelae or not remains unknown. The aim of this study was to assess the prevalence of persisting radiological pulmonary fibrotic lesions in patients hospitalized for COVID-19. The prevalence of persisting lesions after COVID-19 remains unclear. We assessed this prevalence and predictive factors leading to fibrotic lesions in a large cohort. The respiratory clinical impact of these lesions was also assessed. KEY POINTS: • Nineteen percent of patients hospitalized for COVID-19 had radiological fibrotic lesions at 4 months, remaining stable at 16 months. • COVID-19 fibrotic lesions did not match any infiltrative lung disease pattern. • COVID-19 fibrotic lesions were associated with pulmonary function test abnormalities but did not lead to clinical respiratory manifestation.

Integrating virtual patients into undergraduate health professions curricula: a framework synthesis of stakeholders' opinions based on a systematic literature review.

BACKGROUND: Virtual patients (VPs) are widely used in health professions education. When they are well integrated into curricula, they are considered to be more effective than loosely coupled add-ons. However, it is unclear what constitutes their successful integration. The aim of this study was to identify and synthesise the themes found in the literature that stakeholders perceive as important for successful implementation of VPs in curricula. METHODS: We searched five databases from 2000 to September 25, 2023. We included qualitative, quantitative, mixed-methods and descriptive case studies that defined, identified, explored, or evaluated a set of factors that, in the perception of students, teachers, course directors and researchers, were crucial for VP implementation. We excluded effectiveness studies that did not consider implementation characteristics, and studies that focused on VP design factors. We included English-language full-text reports and excluded conference abstracts, short opinion papers and editorials. Synthesis of results was performed using the framework synthesis method with Kern's six-step model as the initial framework. We appraised the quality of the studies using the QuADS tool. RESULTS: Our search yielded a total of 4808 items, from which 21 studies met the inclusion criteria. We identified 14 themes that formed an integration framework. The themes were: goal in the curriculum; phase of the curriculum when to implement VPs; effective use of resources; VP alignment with curricular learning objectives; prioritisation of use; relation to other learning modalities; learning activities around VPs; time allocation; group setting; presence mode; VPs orientation for students and faculty; technical infrastructure; quality assurance, maintenance, and sustainability; assessment of VP learning outcomes and learning analytics. We investigated the occurrence of themes across studies to demonstrate the relevance of the framework. The quality of the studies did not influence the coverage of the themes. CONCLUSIONS: The resulting framework can be used to structure plans and discussions around implementation of VPs in curricula. It has already been used to organise the curriculum implementation guidelines of a European project. We expect it will direct further research to deepen our knowledge on individual integration themes.

Vein of Galen aneurysmal malformation: rationalizing medical management of neonatal heart failure.

Neonates who present in high output heart failure secondary to vein of Galen aneurysmal malformation can be difficult to manage medically due to the complex physiology that results from the large shunt through the malformation. Though the cardiac function is often normal, right ventricular dilation, severe pulmonary hypertension, and systemic steal can result in inadequate organ perfusion and shock. This report recommends medical management for stabilization of neonates prior to definitive management with endovascular embolization. IMPACT: Vein of Galen aneurysmal malformation (VGAM) is a rare intracranial arteriovenous malformation, which can present in the neonatal period with high output heart failure. Heart failure secondary to VGAM is often difficult to manage and is associated with high mortality and morbidity. Despite optimal medical management, many patients require urgent endovascular embolization for stabilization of their heart failure. This report offers discrete recommendations that can be used by clinicians as guidelines for the medical management of heart failure in newborns with VGAM.

Blood Purification with oXiris© in Critically Ill Children with Vasoplegic Shock.

INTRODUCTION: Sepsis is a life-threatening organ dysfunction caused by a dysregulated host response to infection. As such, circulating cytokines and danger- and pathogen-associated molecular patterns (such as endotoxins) are recognized as central in the pathogenesis of sepsis and organ dysfunction. Removing these compounds by extracorporeal blood filtration, commonly considered blood purification, may improve the septic patients' condition. This study aimed to assess the vaso-inotropic support evolution over time in pediatric patients with vasoplegic shock treated with oXiris©. METHODS: All patients aged below 18 years admitted at the Paris Saclay University Quaternary Pediatric Intensive Care Unit with vasoplegic shock and acute kidney injury and treated with oXiris© between October 2017 and January 2020 were included. The vaso-inotropic score and the 28-day mortality were assessed. Improvement under treatment was defined as a 50% decrease in the vaso-inotropic score following 24 h of oXiris© therapy. RESULTS: Eleven pediatric patients aged 2-15 years and weighing 11-60 kg were admitted with vasoplegic shock and acute kidney injury. They received thirteen sessions of oXiris© therapy for septic shock (N = 7) and liver failure (N = 6). Eight patients did not improve their condition during the session, and five ultimately died (37.5% survival). Five patients improved, decreasing their inotropic support by >50% in 24 h. Among them, four survived (80%). CONCLUSION: Hemofiltration and extracorporeal blood purification with oXiris© can be used in pediatric patients with vasoplegic shock with rapid improvement in hemodynamics in selected patients.

Comorbidity of long COVID and psychiatric disorders after a hospitalisation for COVID-19: a cross-sectional study.

OBJECTIVES: Long COVID is a major public health issue. Whether long COVID is comorbid with psychiatric disorders remains unclear. Here, we investigate the association between long COVID, psychiatric symptoms and psychiatric disorders. DESIGN: Cross-sectional. SETTINGS: Bicêtre Hospital, France, secondary care. PARTICIPANTS: One hundred seventy-seven patients admitted in intensive care unit during acute phase and/or reporting long COVID complaints were assessed 4 months after hospitalisation for an acute COVID. MAIN OUTCOME MEASURES: Eight long COVID complaints were investigated: fatigue, respiratory and cognitive complaints, muscle weakness, pain, headache, paraesthesia and anosmia. The number of complaints, the presence/absence of each COVID-19 complaint as well as lung CT scan abnormalities and objective cognitive impairment) were considered. Self-reported psychiatric symptoms were assessed with questionnaires. Experienced psychiatrists assessed Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition-based diagnoses of psychiatric disorders. RESULTS: One hundred and fifteen (65%) patients had at least one long COVID complaint. The number of long COVID complaints was associated with psychiatric symptoms. The number of long COVID complaints was higher in patients with psychiatric disorders (mean (m) (SD)=2.47 (1.30), p<0.05), new-onset psychiatric disorders (m (SD)=2.41 (1.32), p<0.05) and significant suicide risk (m (SD)=2.67 (1.32), p<0.05) than in patients without any psychiatric disorder (m (SD)=1.43 (1.48)). Respiratory complaints were associated with a higher risk of psychiatric disorder and new-onset psychiatric disorder, and cognitive complaints were associated with a higher risk of psychiatric disorder. CONCLUSIONS: Long COVID is associated with psychiatric disorders, new-onset psychiatric disorders and suicide risk. Psychiatric disorders and suicide risk should be systematically assessed in patients with long COVID.

Caring for Critically Ill Children With Suspected or Proven Coronavirus Disease 2019 Infection: Recommendations by the Scientific Sections' Collaborative of the European Society of Pediatric and Neonatal Intensive Care.

OBJECTIVES: In children, coronavirus disease 2019 is usually mild but can develop severe hypoxemic failure or a severe multisystem inflammatory syndrome, the latter considered to be a postinfectious syndrome, with cardiac involvement alone or together with a toxic shock like-presentation. Given the novelty of severe acute respiratory syndrome coronavirus 2, the causative agent of the recent coronavirus disease 2019 pandemic, little is known about the pathophysiology and phenotypic expressions of this new infectious disease nor the optimal treatment approach. STUDY SELECTION: From inception to July 10, 2020, repeated PubMed and open Web searches have been done by the scientific section collaborative group members of the European Society of Pediatric and Neonatal Intensive Care. DATA EXTRACTION: There is little in the way of clinical research in children affected by coronavirus disease 2019, apart from descriptive data and epidemiology. DATA SYNTHESIS: Even though basic treatment and organ support considerations seem not to differ much from other critical illness, such as pediatric septic shock and multiple organ failure, seen in PICUs, some specific issues must be considered when caring for children with severe coronavirus disease 2019 disease. CONCLUSIONS: In this clinical guidance article, we review the current clinical knowledge of coronavirus disease 2019 disease in critically ill children and discuss some specific treatment concepts based mainly on expert opinion based on limited experience and the lack of any completed controlled trials in children at this time.

Four-Month Clinical Status of a Cohort of Patients After Hospitalization for COVID-19.

Importance: Little is known about long-term sequelae of COVID-19. Objective: To describe the consequences at 4 months in patients hospitalized for COVID-19. Design, Setting, and Participants: In a prospective uncontrolled cohort study, survivors of COVID-19 who had been hospitalized in a university hospital in France between March 1 and May 29, 2020, underwent a telephone assessment 4 months after discharge, between July 15 and September 18, 2020. Patients with relevant symptoms and all patients hospitalized in an intensive care unit (ICU) were invited for further assessment at an ambulatory care visit. Exposures: Survival of hospitalization for COVID-19. Main Outcomes and Measures: Respiratory, cognitive, and functional symptoms were assessed by telephone with the Q3PC cognitive screening questionnaire and a checklist of symptoms. At the ambulatory care visit, patients underwent pulmonary function tests, lung computed tomographic scan, psychometric and cognitive tests (including the 36-Item Short-Form Health Survey and 20-item Multidimensional Fatigue Inventory), and, for patients who had been hospitalized in the ICU or reported ongoing symptoms, echocardiography. Results: Among 834 eligible patients, 478 were evaluated by telephone (mean age, 61 years [SD, 16 years]; 201 men, 277 women). During the telephone interview, 244 patients (51%) declared at least 1 symptom that did not exist before COVID-19: fatigue in 31%, cognitive symptoms in 21%, and new-onset dyspnea in 16%. There was further evaluation in 177 patients (37%), including 97 of 142 former ICU patients. The median 20-item Multidimensional Fatigue Inventory score (n = 130) was 4.5 (interquartile range, 3.0-5.0) for reduced motivation and 3.7 (interquartile range, 3.0-4.5) for mental fatigue (possible range, 1 [best] to 5 [worst]). The median 36-Item Short-Form Health Survey score (n = 145) was 25 (interquartile range, 25.0-75.0) for the subscale "role limited owing to physical problems" (possible range, 0 [best] to 100 [worst]). Computed tomographic lung-scan abnormalities were found in 108 of 171 patients (63%), mainly subtle ground-glass opacities. Fibrotic lesions were observed in 33 of 171 patients (19%), involving less than 25% of parenchyma in all but 1 patient. Fibrotic lesions were observed in 19 of 49 survivors (39%) with acute respiratory distress syndrome. Among 94 former ICU patients, anxiety, depression, and posttraumatic symptoms were observed in 23%, 18%, and 7%, respectively. The left ventricular ejection fraction was less than 50% in 8 of 83 ICU patients (10%). New-onset chronic kidney disease was observed in 2 ICU patients. Serology was positive in 172 of 177 outpatients (97%). Conclusions and Relevance: Four months after hospitalization for COVID-19, a cohort of patients frequently reported symptoms not previously present, and lung-scan abnormalities were common among those who were tested. These findings are limited by the absence of a control group and of pre-COVID assessments in this cohort. Further research is needed to understand longer-term outcomes and whether these findings reflect associations with the disease.

Management and Outcomes of Neonatal Arteriovenous Brain Malformations with Cardiac Failure: A 17 Years' Experience in a Tertiary Referral Center.

OBJECTIVES: To assess the management and outcomes of neonatal arteriovenous brain malformations (mostly vein of Galen malformations) complicated by cardiac failure in the era of prenatal diagnosis and endovascular treatment in a tertiary referral center. STUDY DESIGN: This observational study included 77 living newborn infants with arteriovenous brain malformations with cardiac failure, admitted to our referral center from 2001 to 2017. All infants underwent cardiovascular evaluation including echocardiogram and brain magnetic resonance imaging. Long-term survivors had standard neurocognitive assessments. RESULTS: Infants were admitted to the neonatal intensive care unit at a median of 5 days of age (including 18 inborn patients since 2009). Sixty transarterial shunt embolizations were performed in 46 patients during their first month (at a median age of 7.5 days) or postponed beyond the first month in another 10 long-term survivors. Embolization was not performed in 21 infants, including 19 nonsurvivors with severe brain injury, uncontrolled cardiac failure, or multiple organ failure. Cardiac failure requiring vasopressor infusion occurred in 48 patients (64%) during the hospitalization. Infants who survived the first month underwent a median of 3 embolization sessions. Among the 51 survivors, 21 had a good outcome and 19 had a poor outcome at follow-up (median age, 5.3 years); 11 children were lost to follow-up. CONCLUSIONS: In the era of multidisciplinary prenatal diagnosis, using a standardized care protocol, 47% of liveborn infants with an arteriovenous shunt malformation with cardiac failure experienced a favorable outcome.

Different response to antiepileptic drugs according to the type of epileptic events in a neonatal ischemia-reperfusion model.

Perinatal arterial stroke is the most frequent form of cerebral infarction in children. Neonatal seizures are the most frequent symptom during the neonatal period. The current management of perinatal stroke is based on supportive care. It is currently unknown if treatment of the seizures modifies the outcome, and no clinical studies have focused on seizures during neonatal stroke. We studied the effect of phenobarbital and levetiracetam on an ischemic-reperfusion stroke model in P7 rats using prolonged electroencephalographic recordings and a histologic analysis of the brain (24h after injury). The following two types of epileptic events were observed: 1) bursts of high amplitude spikes during ischemia and the first hours of reperfusion and 2) organized seizures consisting in discharges of a 1-2Hz spike-and-wave. Both phenobarbital and levetiracetam decreased the total duration of the bursts of high amplitude spikes. Phenobarbital also delayed the start of seizures without changing the total duration of epileptic discharges. The markedly limited efficacy of the antiepileptic drugs studied in our neonatal stroke rat model is frequently observed in human neonatal seizures. Both drugs did not modify the stroke volume, which suggests that the modification of the quantity of bursts of high amplitude spikes does not influence the infarct size. In the absence of a reduction in seizure burden by the antiepileptic drugs, we increased the seizure burden and stroke volume by combining our neonatal stroke model with a lithium-pilocarpine-induced status epilepticus. Our data suggest that the reduction of burst of spikes did not influence the stroke volume. The presence of organized seizure with a pattern close to what is observed in human newborns seems related to the presence of the infarct. Further research is required to determine the relationship between seizure burden and infarct volume.

Pediatric Intensive Care Unit follow-up: thinking before acting.

OBJECTIVE: It is now well established that post-intensive care syndrome is frequent in critically ill children after discharge from the Pediatric Intensive Care Unit (PICU). Nevertheless, post-intensive care follow-up is highly heterogenous worldwide and is not considered routine care in many countries. The purpose of this viewpoint was to report the reflections of the French PICU society working group on how to implement post-PICU follow-up. METHODS: A working group was set up within the Groupe Francophone de Reanimation et d'Urgences Pédiatriques (GFRUP) to provide conceptual and practical guidance for developing post-PICU follow-up. The working group included psychologists, PICU physicians, physiotherapists, and nurses, from different French PICUs. Five virtual meetings have been held. RESULTS: First, we described in this work the objectives of the follow-up program and the population to be targeted. We also provided a framework to implement post-PICU follow-up in clinical practice. Finally, we detailed the potential obstacles and challenges to consider. CONCLUSION: Although implementing a post-PICU follow-up program is a challenge, the benefits could be significant for both patient and relatives, as well as for the health care professionals involved.

Four- and sixteen-month clinical status of a cohort of patients following hospitalization for COVID-19.

BACKGROUND AND OBJECTIVES: Although many symptoms of post-COVID syndrome have been described, a comprehensive evaluation of their prevalence is lacking. We aimed to describe symptoms at 16 months from hospitalization for COVID-19. METHODS: A telephone assessment was performed one year later in a cohort of COVID-19 survivors hospitalized between March and May 2020 and already evaluated four months after discharge. Patients with relevant symptoms at 16 months, patients who presented symptoms at four months, and all intensive care unit patients were invited for assessment at an outpatient facility. At telephone consultation, respiratory, cognitive, and functional symptoms were assessed. Patients underwent pulmonary function tests, lung CT scans, and psychometric and cognitive tests at the outpatient facility. RESULTS: Among 478 patients evaluated four months after discharge, 317 (67 %) were assessed at telephone consultation and 124 at ambulatory assessment. At telephone assessment, ≥1 new symptom was reported by 216 patients (68 %), mainly fatigue (53 %), dyspnea (37 %), and memory difficulties (24 %). Seventy-nine patients (25 %) were asymptomatic at four months but declared ≥1 symptom one year later. In patients evaluated twice, the prevalence of cognitive impairment was 45 % at four months and 40 % at 16 months. Depression and post-traumatic symptoms prevalence remained stable, and the prevalence of anxiety significantly decreased. Dysfunctional breathing was detected in 32 % of patients. At 16 months after discharge, lung CT-scan exhibited abnormalities in 30/80 patients (38 %), compared to 52/85 patients (61 %) at four months. CONCLUSION: At 16 months after hospitalization for COVID-19, 68 % of patients declared symptoms, including patients whose symptoms appeared between 4 and 16 months. TRIAL REGISTRATION: ClinicalTrials.gov, NCT04704388.

Ultrasound guided percutaneous catheterization of the brachiocephalic vein by small caliber catheter: An alternative to epicutaneo-caval catheter in newborn and premature infants.

BACKGROUND: Umbilical Venous Catheter (UVC) and Epicutaneo-Caval Catheters (ECC) are reference catheters in the neonatal period. However, many factors such as the corpulence of neonates, poor venous capital, and anatomical variants can complicate ECC insertion or make it impossible. In newborns with failed ECC insertion, we developed an hybrid technique that combines the insertion of a long-lasting silicone or polyurethane small caliber catheter, usually used as a ECC in newborns, with the ease and speed of ultrasound guided puncture of the brachiocephalic vein (BCV). METHODS: Three years retrospective single center experience of ultrasound guided BCV insertion of silicon or polyurethane small caliber central catheter in a tertiary neonatal intensive care in case of insertion fail of ECC. RESULTS: Twenty-one echo guided BCV-ECC insertions were performed in 20 newborns. Median age was 16 days (range: 0-110 days), median weight was 1700 g (range: 605-4960 g) at insertion. In most cases, insertion was on the left side (17/21). No failures were noted. Only one attempt was necessary in all cases. Insertion time, when noted, was always of <45 min. The median duration of use of these catheters was 11 days (range 3-35 days). No complication was noted during insertion or catheter use, including catheter-related infections and thrombosis. CONCLUSION: Echo guided percutaneous catheterization of the brachiocephalic vein with a long lasting silicone or polyurethane small caliber catheter is a safe alternative to the ECC if insertion has failed. However, it requires a mastery of ultrasound-guided insertion technique in term and premature neonates.

Risk of Admission to the Pediatric Intensive Care Unit for SARS-CoV-2 Delta and Omicron Infections.

BACKGROUND: The severity of SARS-CoV-2-related diseases in children remains unclear. This study aimed to describe the incidence of French pediatric intensive care units (PICUs) admissions with acute COVID-19, incidental positive SARS-CoV-2 test result, and multisystem inflammatory syndrome in children (MIS-C) during the delta and omicron variant periods. METHODS: This study used the French PICU registry to obtain data on all patients admitted to 41 French PICUs diagnosed with acute COVID-19, incidental positive SARS-CoV-2 test result, or MIS-C between August 30, 2021 and April 20, 2022. Data regarding the total number of positive SARS-CoV-2 polymerase chain reaction results according to the type of variants were obtained from the French National Public Health Agency. RESULTS: Of 745 children, 244 (32.8%) were admitted for acute COVID-19, 246 (33.0%) for incidental positive SARS-CoV-2 test results, and 255 (34.2%) for MIS-C. The incidence of each group was higher with delta than with omicron. The incidence rate ratios with the delta variant were 7.47 (95% CI, 4.22-13.26) for acute COVID-19, 4·78 (95% CI, 2.30-9.94) for incidental positive SARS-CoV-2 test results, and 10.46 (95% CI, 5.98-18.31) for MIS-C compared to the omicron variant. The median age was 66 (7.7-126.8) months; 314 (42%) patients had comorbidities. Patients with acute COVID-19 and incidental positive SARS-CoV-2 test results had similar proportions of comorbidities. No patient with MIS-C died, whereas the mortality rates in the acute COVID-19 and incidental positive SARS-CoV-2 test results groups were 6.8% and 3.8%, respectively. CONCLUSIONS: The incidence of acute COVID-19, incidental positive SARS-CoV-2 test results, and MIS-C admitted to the PICU were significantly higher with the delta variant than with the omicron variant.

Multisystem inflammatory syndrome in children during the COVID-19 waves: data from the Juvenile Inflammatory Rheumatism cohort.

Introduction: Multisystem inflammatory syndrome in children (MIS-C) is a new condition that first appeared in children and adolescents during the COVID-19 pandemic. We aimed to describe the diagnostic course, clinical and biological manifestations, and treatment of MIS-C during the first three COVID-19 waves. Methods: We extracted patient data from the Juvenile Inflammatory Rheumatism (JIR) cohort. We analyzed data for patients meeting the World Health Organization diagnostic criteria for MIS-C from the start of the COVID-19 pandemic from March 2020 to June 30, 2021. We then compared data for patients in wave one to those in waves two and three. Results: We identified 136 patients with MIS-C. The median age decreased but not significantly during the waves, from 9.9 years to 7.3 years (p = 0.105). Boys represented 52.2% (n = 71) of patients, and 46% (n = 41) of patients originated from sub-Saharan Africa (p < 0.001). Patients presented less diarrhea (p = 0.004), respiratory distress (p < 0.001), and myocarditis (p < 0.001) with progressive waves. Biological inflammation also decreased, namely, C-reactive protein level (p < 0.001), neutrophil count (p = 0.004), and albumin level (p < 0.001). Patients received more corticosteroids (p < 0.001) and required less ventilation support (p < 0.01) and less inotrope treatment (p < 0.001) in the later waves. The duration of hospitalization gradually decreased (p < 0.001), as did critical care unit admissions (p = 0.002). Conclusion: Over the three COVID-19 waves, with a change in the management of MIS-C, children in the JIR cohort in France showed a less severe disease course, in particular, a greater use of corticosteroids. This observation may reflect the impact of both improved management and different SARS-CoV-2 variant.

Functional respiratory complaints among COVID-19 survivors: a prospective cohort study.

Background: Dyspnoea is a common persistent symptom after COVID-19. Whether it is associated with functional respiratory disorders remains unclear. Methods: We assessed the proportion and characteristics of patients with "functional respiratory complaints" (FRCs) (as defined by Nijmegen Questionnaire >22) among 177 post-COVID-19 individuals who benefited from outclinic evaluation in the COMEBAC study (i.e., symptomatic and/or intensive care unit (ICU) survivors at 4 months). In a distinct explanatory cohort of 21 consecutive individuals with unexplained post-COVID-19 dyspnoea after routine tests, we also analysed the physiological responses to incremental cardiopulmonary exercise testing (CPET). Findings: In the COMEBAC cohort, 37 patients had significant FRCs (20.9%, IC95: 14.9-26.9). The prevalence of FRCs ranged from 7.2% (ICU patients) to 37.5% (non-ICU patients). The presence of FRCs was significantly associated with more severe dyspnoea, lower 6-min walk distance, more frequent psychological and neurological symptoms (cognitive complaint, anxiety, depression, insomnia and post-traumatic stress disorders) and poorer quality of life (all p<0.01). In the explanatory cohort, seven out of 21 patients had significant FRCs. Based on CPET, dysfunctional breathing was identified in 12 out of 21 patients, five out of 21 had normal CPET, three out of 21 had deconditioning and one out of 21 had evidence of uncontrolled cardiovascular disease. Interpretation: FRCs are common during post-COVID-19 follow-up, especially among patients with unexplained dyspnoea. Diagnosis of dysfunctional breathing should be considered in those cases.

Multi-organ failure caused by lasagnas: A case report of Bacillus cereus food poisoning.

We report a Bacillus cereus, cereulide producing strain, food poisoning of two sisters. After eating a few bites of pasta cooked 3 days earlier, a 13-year-old girl developed mild symptoms. However, her 11-year-old sister suffered, 40 h after ingestion of the entire platter, a multi-organ failure including acute liver failure, rhabdomyolysis, disseminated intravascular coagulation, and acute kidney injury (AKI). She received supportive care in pediatric intensive care using mechanical ventilation, hemofiltration, and high-doses vasopressors. She was specifically treated for toxin-mediated disease using blood purification and further digestive decontamination. This report highlights the potential severity of B. cereus food poisoning but also a successful dual treatment including toxin removal and antimicrobial treatment to prevent toxin production.

Planning a Collection of Virtual Patients to Train Clinical Reasoning: A Blueprint Representative of the European Population.

BACKGROUND: Virtual patients (VPs) are a suitable method for students to train their clinical reasoning abilities. We describe a process of developing a blueprint for a diverse and realistic VP collection (prior to VP creation) that facilitates deliberate practice of clinical reasoning and meets educational requirements of medical schools. METHODS: An international and interdisciplinary partnership of five European countries developed a blueprint for a collection of 200 VPs in four steps: (1) Defining the criteria (e.g., key symptoms, age, sex) and categorizing them into disease-, patient-, encounter- and learner-related, (2) Identifying data sources for assessing the representativeness of the collection, (3) Populating the blueprint, and (4) Refining and reaching consensus. RESULTS: The blueprint is publicly available and covers 29 key symptoms and 176 final diagnoses including the most prevalent medical conditions in Europe. Moreover, our analyses showed that the blueprint appears to be representative of the European population. CONCLUSIONS: The development of the blueprint required a stepwise approach, which can be replicated for the creation of other VP or case collections. We consider the blueprint an appropriate starting point for the actual creation of the VPs, but constant updating and refining is needed.

The Current and Future State of Pediatric Sepsis Definitions: An International Survey.

BACKGROUND AND OBJECTIVES: Definitions for pediatric sepsis were established in 2005 without data-driven criteria. It is unknown whether the more recent adult Sepsis-3 definitions meet the needs of providers caring for children. We aimed to explore the use and applicability of criteria to diagnose sepsis and septic shock in children across the world. METHODS: This is an international electronic survey of clinicians distributed across international and national societies representing pediatric intensive care, emergency medicine, pediatrics, and pediatric infectious diseases. Respondents stated their preferences on a 5-point Likert scale. RESULTS: There were 2835 survey responses analyzed, of which 48% originated from upper-middle income countries, followed by high income countries (38%) and low or lower-middle income countries (14%). Abnormal vital signs, laboratory evidence of inflammation, and microbiologic diagnoses were the criteria most used for the diagnosis of "sepsis." The 2005 consensus definitions were perceived to be the most useful for sepsis recognition, while Sepsis-3 definitions were stated as more useful for benchmarking, disease classification, enrollment into trials, and prognostication. The World Health Organization definitions were perceived as least useful across all domains. Seventy one percent of respondents agreed that the term sepsis should be restricted to children with infection-associated organ dysfunction. CONCLUSIONS: Clinicians around the world apply a myriad of signs, symptoms, laboratory studies, and treatment factors when diagnosing sepsis. The concept of sepsis as infection with associated organ dysfunction is broadly supported. Currently available sepsis definitions fall short of the perceived needs. Future diagnostic algorithms should be pragmatic and sensitive to the clinical settings.

Respiratory symptoms and radiological findings in post-acute COVID-19 syndrome.

Rationale: The characteristics of patients with respiratory complaints and/or lung radiologic abnormalities after hospitalisation for coronavirus disease 2019 (COVID-19) are unknown. The objectives were to determine their characteristics and the relationships between dyspnoea, radiologic abnormalities and functional impairment. Methods: In the COMEBAC (Consultation Multi-Expertise de Bicêtre Après COVID-19) cohort study, 478 hospital survivors were evaluated by telephone 4 months after hospital discharge, and 177 who had been hospitalised in an intensive care unit (ICU) or presented relevant symptoms underwent an ambulatory evaluation. New-onset dyspnoea and cough were evaluated, and the results of pulmonary function tests and high-resolution computed tomography of the chest were collected. Results: Among the 478 patients, 78 (16.3%) reported new-onset dyspnoea, and 23 (4.8%) new-onset cough. The patients with new-onset dyspnoea were younger (56.1±12.3 versus 61.9±16.6 years), had more severe COVID-19 (ICU admission 56.4% versus 24.5%) and more frequent pulmonary embolism (18.0% versus 6.8%) (all p≤0.001) than patients without dyspnoea. Among the patients reassessed at the ambulatory care visit, the prevalence of fibrotic lung lesions was 19.3%, with extent <25% in 97% of the patients. The patients with fibrotic lesions were older (61±11 versus 56±14 years, p=0.03), more frequently managed in an ICU (87.9 versus 47.4%, p<0.001), had lower total lung capacity (74.1±13.7 versus 84.9±14.8% pred, p<0.001) and diffusing capacity of the lung for carbon monoxide (D LCO) (73.3±17.9 versus 89.7±22.8% pred, p<0.001). The combination of new-onset dyspnoea, fibrotic lesions and D LCO <70% pred was observed in eight out of 478 patients. Conclusions: New-onset dyspnoea and mild fibrotic lesions were frequent at 4 months, but the association of new-onset dyspnoea, fibrotic lesions and low D LCO was rare.