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Background The sepsis-induced immunodepression contributes to impaired clinical outcomes of various stress conditions. This syndrome is well documented and characterized by attenuated function of innate and adaptive immune cells. Several pharmacological interventions aimed to restore the immune response are emerging of which interferon-gamma (IFNγ) is one. It is of paramount relevance to obtain clinical information on optimal timing of the IFNγ-treatment, −tolerance, −effectiveness and outcome before performing a RCT. We describe the effects of IFNγ in a cohort of 18 adult and 2 pediatric sepsis patients. Methods In this open-label prospective multi-center case-series, IFNγ treatment was initiated in patients selected on clinical and immunological criteria early (< 4 days) or late (> 7 days) following the onset of sepsis. The data collected in 18 adults and 2 liver transplanted pediatric patients were: clinical scores, monocyte expression of HLA-DR (flow cytometry), lymphocyte immune-phenotyping (flow cytometry), IL-6 and IL-10 plasma levels (ELISA), bacterial cultures, disease severity, and mortality. Results In 15 out of 18 patients IFNγ treatment was associated with an increase of median HLA-DR expression from 2666 [IQ 1547; 4991] to 12,451 [IQ 4166; 19,707], while the absolute number of lymphocyte subpopulations were not affected, except for the decrease number of NK cells 94.5 [23; 136] to 32.5 [13; 90.8] (0.0625)]. Plasma levels of IL-6 464 [201–770] to 108 (89–140) ng/mL ( p  = 0.04) and IL-10 from IL-10 from 29 [12–59] to 9 [1–15] pg/mL decreased significantly. Three patients who received IFNγ early after ICU admission (<4 days) died. The other patients had a rapid clinical improvement assessed by the SOFA score and bacterial cultures that were repeatedly positive became negative. The 2 pediatric cases improved rapidly, but 1 died for hemorrhagic complication. Conclusion Guided by clinical and immunological monitoring, adjunctive immunotherapy with IFNγ appears well-tolerated in our cases and improves immune host defense in sepsis induced immuno suppression. Randomized clinical studies to assess its potential clinical benefit are warranted.

Nirsevimab, a monoclonal antibody targeting RSV, led to decreased hospitalizations for RSV-associated lower respiratory tract infection in infants during their first RSV season, in an open-label, pragmatic trial.

Recent paediatric cases of acute myocarditis following a SARS-CoV-2 infection have raised the possibility of post-infective complications of COVID-19. This short editorial is reviewing current understanding of this new complication, its pathophysiology, diagnosis and therapeutic strategy.

According to the current understanding of the pathophysiology of sepsis, key host dysregulated responses leading to organ failure are mediated by innate immunity, through interactions between pathogen-associated molecular patterns (PAMPs) and damaged-associated molecular patterns (DAMPs) binding to four types of pattern recognition receptors (PRRs). PRRs activation triggers the protein kinase cascade, initiating the cellular response seen during sepsis. Pancreatic stone protein (PSP), a C-type lectin protein, is a well-defined biomarker of sepsis. Studies have shown that stressed and immune-activated pancreatic β-cells secrete PSP. Animal studies have shown that PSP injection aggravates sepsis, and that the disease severity score and mortality were directly correlated with the doses of PSP injected. In humans, studies have shown that PSP activates polymorphonuclear neutrophils (PMNs) and aggravates multiple organ dysfunction syndrome. Clinical studies have shown that PSP levels are correlated with disease severity, vasopressor support, progression to organ failure, mechanical ventilation, renal replacement therapy, length of stay, and mortality. As PSP is a C-type lectin protein, it may have a role in activating innate immunity through the C-type lectin receptors (CLRs), which is one of the four PRRs. Herein, we review the literature on PSP and its possible role in the pathophysiology of sepsis, and we discuss its potential therapeutic role.

Background Despite widespread vaccination programs, pertussis continues circulating within populations and remains a life-threatening infection in infants. While several mortality risk factors have been described, a comprehensive synthesis is lacking. We conducted a meta-analysis of studies investigating mortality risk factors in Pertussis infections and validated those factors in a large cohort. Methods Observational studies published in English were systematically searched in PubMed, EMBASE, and LiSSa databases from 01/2000 to 06/2024. The search yielded 816 unique citations. The primary outcome was mortality before discharge from the Pediatric Intensive Care Unit (PICU). Two independent reviewers assessed the risk of bias and extracted data. A REML-random effect model was used to calculate pooled prevalence and conduct the analysis. The identified risk factors were subsequently evaluated in a monocentric cohort of patients admitted to a tertiary hospital’s PICU for severe pertussis between January 1996 and December 2020. Data analysis was conducted between June and August 2024. Results Seventeen studies, including 2,725 patients, met the inclusion criteria. The pooled prevalence of mechanical ventilation, continuous renal replacement therapy, and Extracorporeal Membrane Oxygenation support were 55% (95% CI: 40–70; I 2  = 98), 15% (95% CI: 3–27; I 2  = 95), and 8% (95% CI: 3–12; I 2  = 93), respectively. The pooled mortality incidence was 19% (95% CI:12–26; I 2  = 96). Identified mortality risk factors included elevated heart rate, presence of pulmonary hypertension, presence of seizures, and elevated white blood cell (WBC) count. Validation in an 83-patient cohort (median age: 45 days, IQR: 30–55) revealed a mortality rate of 12%. Risk factors identified in the meta-analysis were significantly associated with non-survival in the cohort. A mortality prediction score was developed incorporating age < 30 days, heart rate > 200/min, and WBC > 30 G/l, achieving an area under the curve of 0.92 (95% CI: 0.86–0.99). Conclusion This meta-analysis identified a simple yet effective score to assess the severity of pertussis infection in infants admitted to PICU. Accurate risk stratification may enable timely treatment of critically ill patients, potentially improving outcomes. Trial registration : The study protocol was registered on PROSPERO: CRD42024582057. Graphic abstract

BackgroundDe-regulated host response to severe coronavirus disease 2019 (COVID-19), directly referring to the concept of sepsis-associated immunological dysregulation, seems to be a strong signature of severe COVID-19. Myeloid cells phenotyping is well recognized to diagnose critical illness-induced immunodepression in sepsis and has not been well characterized in COVID-19. The aim of this study is to review phenotypic characteristics of myeloid cells and evaluate their relations with the occurrence of secondary infection and mortality in patients with COVID-19 admitted in an intensive care unit.MethodsRetrospective analysis of the circulating myeloid cells phenotypes of adult COVID-19 critically ill patients. Phenotyping circulating immune cells was performed by flow cytometry daily for routine analysis and twice weekly for lymphocytes and monocytes subpopulations analysis, as well as monocyte human leukocyte antigen (mHLA)-DR expression.ResultsOut of the 29 critically ill adult patients with severe COVID-19 analyzed, 12 (41.4%) developed secondary infection and six patients died during their stay. Monocyte HLA-DR kinetics was significantly different between patients developing secondary infection and those without, respectively, at day 5–7 and 8–10 following admission. The monocytes myeloid-derived suppressor cells to total monocytes ratio was associated with 28- and 60-day mortality. Those myeloid characteristics suggest three phenotypes: hyperactivated monocyte/macrophage is significantly associated with mortality, whereas persistent immunodepression is associated with secondary infection occurrence compared to transient immunodepression.ConclusionsMyeloid phenotypes of critically ill COVID-19 patients may be associated with development of secondary infection, 28- and 60-day mortality.

Purpose Severe bronchiolitis is the leading cause of admission to the pediatric intensive care unit (PICU). Nasal continuous positive airway pressure (nCPAP) has become the primary respiratory support, replacing invasive mechanical ventilation (MV). Our objective was to evaluate the economic and clinical consequences following implementation of this respiratory strategy in our unit. Methods This was a retrospective cohort analysis of 525 infants with bronchiolitis requiring respiratory support and successively treated during two distinct periods with invasive MV between 1996 and 2000, P1 ( n  = 193) and nCPAP between 2006 and 2010, P2 ( n  = 332). Costs were estimated using the hospital cost billing reports. Results Patients’ baseline characteristics were similar between the two periods. P2 is associated with a significant decrease in the length of ventilation (LOV) (4.1 ± 3.5 versus 6.9 ± 4.6 days, p  < 0.001), PICU length of stay (LOS) (6.2 ± 4.6 versus 9.7 ± 5.5 days, p  < 0.001) and hospital LOS. nCPAP was independently associated with a shorter duration of ventilatory support than MV (hazard ratio 1.8, 95 % CI 1.5–2.2, p  < 0.001). nCPAP was also associated with a significant decrease in ventilation-associated complications, and less invasive management. The mean cost of acute viral bronchiolitis-related PICU hospitalizations was significantly decreased, from 17,451 to 11,205 € ( p  < 0.001). Implementation of nCPAP led to a reduction of the total annual cost of acute viral bronchiolitis hospitalizations of 715,000 €. Conclusion nCPAP in severe bronchiolitis is associated with a significant improvement in patient management as shown by the reduction in invasive care, LOV, PICU LOS, hospital LOS, and economic burden.

Purpose To determine the optimal level of nasal continuous positive airway pressure (nCPAP) in infants with severe hypercapnic viral bronchiolitis as assessed by the maximal unloading of the respiratory muscles and improvement of breathing pattern and gas exchange. Methods A prospective physiological study in a tertiary paediatric intensive care unit (PICU). Breathing pattern, gas exchange, intrinsic end expiratory pressure (PEEPi) and respiratory muscle effort were measured in ten infants with severe hypercapnic viral bronchiolitis during spontaneous breathing (SB) and three increasing levels of nCPAP. Results During SB, median PEEPi was 6 cmH 2 O (range 3.9–9.2 cmH 2 O), median respiratory rate was 78 breaths/min (range 41–96), median inspiratory time/total duty cycle ( T i / T tot ) was 0.45 (range 0.40–0.48) and transcutaneous carbon dioxide pressure ( P tc CO 2 ) was 61.5 mmHg (range 50–78). In all the infants, an nCPAP level of 7 cmH 2 O was associated with the greatest reduction in respiratory effort with a mean reduction in oesophageal and diaphragmatic pressure swings of 48 and 46%, respectively, and of the oesophageal and diaphragmatic pressure time product of 49 and 56%, respectively. During nCPAP, median respiratory rate decreased to 56 breaths/min (range 39–108, p  < 0.05), median T i / T tot decreased to 0.40 (range 0.34–0.44, p  < 0.50) and P tc CO 2 decreased to 49 mmHg (range 35–65, p  < 0.05). Only one infant with associated bacterial pneumonia required intubation and all the infants were discharged alive from the PICU after a median stay of 5.5 (range 3–27 days). Conclusion In infants with hypercapnic respiratory failure due to acute viral bronchiolitis, an nCPAP level of 7 cmH 2 O is associated with the greatest unloading of the respiratory muscles and improvement of breathing pattern, as well as a favourable short-term clinical outcome.

Background Point-of-care ultrasound (POCUS) is nowadays an essential tool in critical care. Its role seems more important in neonates and children where other monitoring techniques may be unavailable. POCUS Working Group of the European Society of Paediatric and Neonatal Intensive Care (ESPNIC) aimed to provide evidence-based clinical guidelines for the use of POCUS in critically ill neonates and children. Methods Creation of an international Euro-American panel of paediatric and neonatal intensivists expert in POCUS and systematic review of relevant literature. A literature search was performed, and the level of evidence was assessed according to a GRADE method. Recommendations were developed through discussions managed following a Quaker-based consensus technique and evaluating appropriateness using a modified blind RAND/UCLA voting method. AGREE statement was followed to prepare this document. Results Panellists agreed on 39 out of 41 recommendations for the use of cardiac, lung, vascular, cerebral and abdominal POCUS in critically ill neonates and children. Recommendations were mostly (28 out of 39) based on moderate quality of evidence (B and C). Conclusions Evidence-based guidelines for the use of POCUS in critically ill neonates and children are now available. They will be useful to optimise the use of POCUS, training programs and further research, which are urgently needed given the weak quality of evidence available.