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Abstract Background Modeling patient data, particularly electronic health records (EHR), is one of the major focuses of machine learning studies in healthcare, as these records provide clinicians with valuable information that can potentially assist them in disease diagnosis and decision-making. Methods In this study, we present a multi-level graph-based framework called MedMGF, which models both patient medical profiles extracted from EHR data and their relationship network of health profiles in a single architecture. The medical profiles consist of several layers of data embedding derived from interval records obtained during hospitalization, and the patient-patient network is created by measuring the similarities between these profiles. We also propose a modification to the Focal Loss (FL) function to improve classification performance in imbalanced datasets without the need to imputate the data. MedMGF’s performance was evaluated against several Graphical Convolutional Network (GCN) baseline models implemented with Binary Cross Entropy (BCE), FL, class balancing parameter $$\alpha$$ α , and Synthetic Minority Oversampling Technique (SMOTE). Results Our proposed framework achieved high classification performance (AUC: 0.8098, ACC: 0.7503, SEN: 0.8750, SPE: 0.7445, NPV: 0.9923, PPV: 0.1367) on an extreme imbalanced pediatric sepsis dataset (n=3,014, imbalance ratio of 0.047). It yielded a classification improvement of 3.81% for AUC, 15% for SEN compared to the baseline GCN+ $$\alpha$$ α FL (AUC: 0.7717, ACC: 0.8144, SEN: 0.7250, SPE: 0.8185, PPV: 0.1559, NPV: 0.9847), and an improvement of 5.88% in AUC and 22.5% compared to GCN+FL+SMOTE (AUC: 0.7510, ACC: 0.8431, SEN: 0.6500, SPE: 0.8520, PPV: 0.1688, NPV: 0.9814). It also showed a classification improvement of 3.86% for AUC, 15% for SEN compared to the baseline GCN+ $$\alpha$$ α BCE (AUC: 0.7712, ACC: 0.8133, SEN: 0.7250, SPE: 0.8173, PPV: 0.1551, NPV: 0.9847), and an improvement of 14.33% in AUC and 27.5% in comparison to GCN+BCE+SMOTE (AUC: 0.6665, ACC: 0.7271, SEN: 0.6000, SPE: 0.7329, PPV: 0.0941, NPV: 0.9754). Conclusion When compared to all baseline models, MedMGF achieved the highest SEN and AUC results, demonstrating the potential for several healthcare applications.

Abstract Background Pediatric sepsis remains a leading cause of childhood morbidity and mortality worldwide. Despite advancements in modern medicine, it accounts for more than 3 million childhood deaths per year. Multiple studies have emphasized that sex and gender have an impact on the treatment and outcome of various diseases. Adult studies have revealed sex differences in pathophysiological responses to septic shock, as well as a possible protective effect of estrogens on critical illness. Sex-specific maturational and developmental differences in host immunology have been previously demonstrated for neonatal and pediatric age groups. At present, there are no studies assessing the impact of sex on outcomes of children with sepsis. Methods The goal of this study is to assess sex-specific differences in childhood sepsis survival outcomes. We will systematically assess associations of sex and gender with outcomes in pediatric sepsis in the literature by performing a systematic search of MEDLINE and Embase databases. We will include all English language randomized trials and cohort studies. The study population will include children > 37 weeks gestational age and

Abstract Introduction Sepsis is associated with neurocognitive impairment among preterm neonates but less is known about term neonates with sepsis. This systematic review and meta-analysis aims to provide an update of neurocognitive outcomes including cognitive delay, visual impairment, auditory impairment, and cerebral palsy, among neonates with sepsis. Methods We performed a systematic review of PubMed, Embase, CENTRAL and Web of Science for eligible studies published between January 2011 and March 2023. We included case–control, cohort studies and cross-sectional studies. Case reports and articles not in English language were excluded. Using the adjusted estimates, we performed random effects model meta-analysis to evaluate the risk of developing neurocognitive impairment among neonates with sepsis. Results Of 7,909 studies, 24 studies (n = 121,645) were included. Majority of studies were conducted in the United States (n = 7, 29.2%), and all studies were performed among neonates. 17 (70.8%) studies provided follow-up till 30 months. Sepsis was associated with increased risk of cognitive delay [adjusted odds ratio, aOR 1.14 (95% CI: 1.01—1.28)], visual impairment [aOR 2.57 (95%CI: 1.14- 5.82)], hearing impairment [aOR 1.70 (95% CI: 1.02–2.81)] and cerebral palsy [aOR 2.48 (95% CI: 1.03–5.99)]. Conclusion Neonates surviving sepsis are at a higher risk of poorer neurodevelopment. Current evidence is limited by significant heterogeneity across studies, lack of data related to long-term neurodevelopmental outcomes and term infants.

This study addresses the challenge of accurately identifying diabetes mellitus in individuals. Utilizing accessible online and real-world diagnostic data, we employ machine learning models, including Support Vector Machine, Random Forest, Naïve Bayes, eXtreme Gradient Boosting, and Deep Neural Network, on the PIMA Indian Diabetes and NHANES 1999-2016 datasets. Rigorous data pre-processing steps were conducted, handling null values, outliers, and imbalanced data together with data normalization. Our results reveal that the RF model achieves a 79% accuracy for binary classification on the PIMA Indian Diabetes dataset, using a 60:40 train-test split with BORUTA selected features. Meanwhile, the XGBoost model excels on the NHANES 1999-2016 dataset, achieving 92% accuracy for binary and 91% for multiclass classification respectively.

The BOOST (Booster promotion for older outpatients using SMS text reminders) program at Taipei Veterans General Hospital assessed the effectiveness of text message reminders in enhancing COVID-19 booster vaccination rates among the elderly, guided by the Health Belief Model (HBM). Targeting patients aged 65 and above, eligible yet unvaccinated for a COVID-19 booster, this cohort study sent personalized reminders a week prior to their scheduled appointments between April 18, 2022, and May 12, 2022, acting as cues to action to enhance vaccination uptake by overcoming perceived barriers and raising awareness of benefits. Over 5 weeks, the study observed a 38% increase in vaccination rate among 3,500 eligible patients, markedly surpassing the concurrent national rate increase of 4% for the same demographic. The majority of vaccinations occurred within two weeks after the reminder, illustrating the effectiveness of the strategy. Cox regression analysis identified age and time since last vaccination as significant predictors of responsiveness, with those aged 65–74 and 75–84 showing higher uptake, particularly when reminders were sent within 4 months after the last dose. A single reminder proved to be effective. The findings of this study demonstrate the potential of SMS reminders to promote COVID-19 vaccination among the elderly through the strategic use of HBM principles, suggesting a feasible and effective approach to public health communication.

OBJECTIVES:. In critically ill children with severe sepsis, septic cardiomyopathy (SCM) denotes the subset of patients who have myocardial dysfunction with poor response to fluid and inotropic support, and higher mortality risk. The objective of this review was to evaluate the role of speckle-tracking echocardiography (STE) in the diagnosis and prognosis of pediatric SCM in the PICU setting. DATA SOURCES:. We performed detailed searches using PubMed, Scopus, Web of Science, and Google Scholar. Reference lists of all included studies were also examined for further identification of potentially relevant studies. STUDY SELECTION:. Studies with the following medical subject headings and keywords were selected: speckle-tracking echocardiography, strain imaging, global longitudinal strain, echocardiography, sepsis, severe sepsis, septic shock, septic cardiomyopathy, and myocardial dysfunction. DATA EXTRACTION:. The following data were extracted from all included studies: demographics, diagnoses, echocardiographic parameters, severity of illness, PICU management, and outcomes. DATA SYNTHESIS:. STE is a relatively new echocardiographic technique that directly quantifies myocardial contractility. It has high sensitivity in diagnosing SCM, correlates well with illness severity, and has good prognosticating value as compared with conventional echocardiographic parameters. Further studies are required to establish its role in evaluating biventricular systolic and diastolic dysfunction, and to investigate whether it has a role in individualizing treatment and improving treatment outcomes in this group of patients. CONCLUSIONS:. STE is a useful adjunct to conventional measures of cardiac function on 2D-echocardiography in the assessment of pediatric SCM in the PICU.

In 2019, 80% of the 7.4 million global child deaths occurred in low- and middle-income countries (LMICs). Global and regional estimates of cause of hospital death and admission in LMIC children are needed to guide global and local priority setting and resource allocation but are currently lacking. The study objective was to estimate global and regional prevalence for common causes of pediatric hospital mortality and admission in LMICs. We performed a systematic review and meta-analysis to identify LMIC observational studies published January 1, 2005-February 26, 2021. Eligible studies included: a general pediatric admission population, a cause of admission or death, and total admissions. We excluded studies with data before 2,000 or without a full text. Two authors independently screened and extracted data. We performed methodological assessment using domains adapted from the Quality in Prognosis Studies tool. Data were pooled using random-effects models where possible. We reported prevalence as a proportion of cause of death or admission per 1,000 admissions with 95% confidence intervals (95% CI). Our search identified 29,637 texts. After duplicate removal and screening, we analyzed 253 studies representing 21.8 million pediatric hospitalizations in 59 LMICs. All-cause pediatric hospital mortality was 4.1% [95% CI 3.4%–4.7%]. The most common causes of mortality (deaths/1,000 admissions) were infectious [12 (95% CI 9–14)]; respiratory [9 (95% CI 5–13)]; and gastrointestinal [9 (95% CI 6–11)]. Common causes of admission (cases/1,000 admissions) were respiratory [255 (95% CI 231–280)]; infectious [214 (95% CI 193–234)]; and gastrointestinal [166 (95% CI 143–190)]. We observed regional variation in estimates. Pediatric hospital mortality remains high in LMICs. Global child health efforts must include measures to reduce hospital mortality including basic emergency and critical care services tailored to the local disease burden. Resources are urgently needed to promote equity in child health research, support researchers, and collect high-quality data in LMICs to further guide priority setting and resource allocation.

Abstract We aimed to derive the Febrile Infants Risk Score at Triage (FIRST) to quantify risk for serious bacterial infections (SBIs), defined as bacteremia, meningitis and urinary tract infections. We performed a prospective observational study on febrile infants

Childhood critical illness can have long-term effects on families, but the extent and trajectory of recovery for parents are unknown. Using prospective longitudinal design, we describe the health outcomes of parents and their trajectory six months after paediatric intensive care unit (PICU) discharge. Parents reported health outcomes at PICU discharge (baseline), and 1-, 3-, and 6-months post-discharge. We used the Pediatric Quality-of-Life Family Impact Module, Patient Health Questionnaire-4, and post-traumatic stress disorder (PTSD) Checklist for DSM-5. The group-based trajectory model was used to identify recovery patterns. We included 128 parents of children aged 1 month to 18 years, admitted to the PICU for ≥48 h. Three post-discharge composite health trajectory groups were classified: 54 mild (42%), 68 moderate (53%), and 6 severe (4%). Parents in the mild and moderate groups returned to baseline health within the first 3 months, but those in the severe group exhibited worse outcomes at 6-months. The mean (SD) PICU stay durations for mild, moderate, and severe groups were 9 (16), 7 (10), and 38 (61) days; days of mechanical ventilation were 4 (5), 4 (7), and 18 (25) days; and readmission rates were 12 (22%), 23 (34%), and 4 (66%), respectively. Identifying these trajectories enables novel, targeted interventions for at-risk parents, underscoring the significance of integrated PICU follow-up care.

IntroductionLiterature on parental experiences after childhood critical illness has limited representation from diverse ethnic backgrounds. Parents from global ethnic majority groups have reported worst psychological outcomes and required more social support after childhood critical illness.AimTo explore the experiences of Chinese, Malay, and Indian parents in the first six months after Pediatric Intensive Care Unit (PICU) discharge of their child in Singapore.MethodsSequential semi-structured qualitative interviews were conducted to collect data from a convenience sample of 28 parents at one month (n = 28) and at six months (n = 22) after their child's discharge from a multidisciplinary PICU. Framework Analysis was adopted as the qualitative analysis strategy. The PICS-p framework was applied a priori in the Framework Analysis.FindingsThree interdependent domains and seven themes framed the 28 accounts in which ethnically diverse parents reported psychological stressors (PICS-p: emotional health), support received (PICS-p: social health) and practical challenges (transitional health) in the first six months after childhood critical illness. In the emotional health domain, parents were affected by different stressors and had different priorities over their child's survivorship. Only Indian parents reported experiences of stress symptoms, at six months post discharge. Malay parents sought solace from their religion more than Chinese and Indian parents. In the social health domain, parents reported various sources and degree of support received. Familial supports were strong across all groups, while community support was more prominent in Malay as compared to Chinese and Indian parents. A third domain, transitional health, was introduced to capture the difficulties parents faced during the transition from PICU survival to home. Parents from non-Chinese families were more likely to report financial challenges and more involvement of spouses after discharge. Complementary medicine or commercial health products were utilized by Chinese and Malay families.ConclusionThese findings reveal preferred strategies that parents from a global ethnic employ to address the emotional, social and transitional health impacts of their child's critical illness. Future care delivery may consider tailored care plans, communication strategies, and emotional support in PICUs that address the unique ethnic needs of parents during the critical six-months post their child's illness.

Gliomas are the most common primary brain tumors in adults. Despite multidisciplinary treatment approaches, the survival rates for patients with malignant glioma have only improved marginally, and few prognostic biomarkers have been identified. Peroxisome proliferator-activated receptor γ (PPARγ) coactivator-1α (PGC-1α) is a crucial regulator of cancer metabolism, playing a vital role in cancer cell adaptation to fluctuating energy demands. In this study, the clinicopathological roles of PGC-1α in gliomas were evaluated. Employing immunohistochemistry, cell culture, siRNA transfection, cell viability assays, western blot analyses, and in vitro and in vivo invasion and migration assays, we explored the functions of PGC-1α in glioma progression. High PGC-1α expression was significantly associated with an advanced pathological stage in patients with glioma and with poorer overall survival. The downregulation of PGC-1α inhibited glioma cell proliferation, invasion, and migration and altered the expression of oncogenic markers. These results conclusively demonstrated that PGC-1α plays a critical role in maintaining the malignant phenotype of glioma cells and indicated that targeting PGC-1α could be an effective strategy to curb glioma progression and improve patient survival outcomes.

Glioblastoma (GBM), the most aggressive form of brain cancer, is characterized by rapid growth and resistance to conventional therapies. Current treatments offer limited effectiveness, leading to poor survival rates and the need for novel therapeutic strategies. Arylquin 1 has emerged as a potential therapeutic candidate because of its unique mechanism of inducing apoptosis in cancer cells without affecting normal cells. This study investigated the efficacy of Arylquin 1 against GBM using the GBM8401 and A172 cells by assessing its dose-dependent cytotoxicity, apoptosis induction, and synergy with radiotherapy. In vitro assays demonstrated a significant reduction in cell viability and increased apoptosis, particularly at high concentrations of Arylquin 1. Migration and invasion analyses revealed notable inhibition of cellular motility. In vivo experiments on NU/NU nude mice with intracranially implanted GBM cells revealed that Arylquin 1 substantially reduced tumor growth, an effect magnified by concurrent radiotherapy. These findings indicate that by promoting apoptosis and enhancing radiosensitivity, Arylquin 1 is a potent therapeutic option for GBM treatment.

Abstract Introduction There is lack of consensus on what constitutes best practice when assessing extubation readiness in children. This systematic review aims to synthesize data from existing literature on pre-extubation assessments and evaluate their diagnostic accuracies in predicting extubation failure (EF) in children. Methods A systematic search in PubMed, EMBASE, Web of Science, CINAHL, and Cochrane was performed from inception of each database to 15 July 2021. Randomized controlled trials or observational studies that studied the association between pre-extubation assessments and extubation outcome in the pediatric intensive care unit population were included. Meta-analysis was performed for studies that report diagnostic tests results of a combination of parameters. Results In total, 41 of 11,663 publications screened were included (total patients, n = 8111). Definition of EF across studies was heterogeneous. Fifty-five unique pre-extubation assessments were identified. Parameters most studied were: respiratory rate (RR) (13/41, n = 1945), partial pressure of arterial carbon dioxide (10/41, n = 1379), tidal volume (13/41, n = 1945), rapid shallow breathing index (RBSI) (9/41, n = 1400), and spontaneous breathing trials (SBT) (13/41, n = 5652). Meta-analysis shows that RSBI, compliance rate oxygenation pressure (CROP) index, and SBT had sensitivities ranging from 0.14 to 0.57. CROP index had the highest sensitivity [0.57, 95% confidence interval (CI) 0.4–0.73] and area under curve (AUC, 0.98). SBT had the highest specificity (0.93, 95% CI 0.92–0.94). Conclusions Pre-extubation assessments studied thus far remain poor predictors of EF. CROP index, having the highest AUC, should be further explored as a predictor of EF. Standardizing the EF definition will allow better comparison of pre-extubation assessments.

IMPORTANCE:. Quadriceps thickness (QT) and rectus femoris cross-sectional area (RFCSA) are both used to evaluate muscle changes in critically ill children. However, their correlation and association with physical function has not been compared. OBJECTIVES:. To compare QT with RFCSA changes, and their association with physical function in critically ill children. DESIGN, SETTING, AND PARTICIPANTS:. Secondary analysis of a prospective cohort study of children 0–18 years old admitted to a tertiary mixed PICU between January 2015 and October 2018 with PICU stay greater than 48 hours and greater than or equal to one organ dysfunction. MAIN OUTCOMES AND MEASURES:. Ultrasound QT and RFCSA were measured at PICU admission, PICU discharge, hospital discharge, and 6 months post-discharge. QT and RFCSA changes from baseline were compared with each other and with change in motor function, physical ability, and physical health-related quality of life (HRQOL). RESULTS:. Two hundred thirty-seven images from 66 subjects were analyzed. RFCSA change was not significantly different from QT change at PICU (–8.07% [interquartile range (IQR), –17.11% to 4.80%] vs –4.55% [IQR, –14.32% to 4.35%]; p = 0.927) or hospital discharge (–5.62% [IQR, –15.00% to 9.42%] vs –8.81% [IQR, –18.67% to 2.39%]; p = 0.238) but was significantly greater than QT change at 6 months (32.7% [IQR, 5.74–109.76%] vs 9.66% [IQR, –8.17% to 25.70%]; p < 0.001). Motor function change at PICU discharge was significantly associated with RFCSA change (adjusted β coefficient, 0.02 [95% CI, 0.01–0.03]; p = 0.013) but not QT change (adjusted β coefficient, –0.01 [95% CI, –0.02 to 0.01]; p = 0.415). Similar results were observed for physical HRQOL changes at hospital discharge (adjusted β coefficient for RFCSA change, 0.51 [95% CI, 0.10–0.92]; p = 0.017 and adjusted β coefficient for QT change, –0.21 [–0.76 to 0.35]; p = 0.458). Physical ability was not significantly associated with RFCSA or QT changes at 6 months post-discharge. CONCLUSIONS AND RELEVANCE:. Ultrasound derived RFCSA is associated with PICU motor function and hospital discharge physical HRQOL changes, unlike QT, and may be more useful for in-hospital muscle monitoring in critically ill children.

Edible bird’s nest (EBN) is a valuable and nutritious food tonic made from the saliva of swiftlet birds. EBN has been consumed for centuries due to its high nutritional value. Proteins are the main nutrient in EBN. However, studies investigating the functional proteins in EBN are still limited. Therefore, the present study aims to characterize the functional proteins from EBN using proteomic-based techniques. In addition, the molecular characteristics of the functional proteins were analyzed using sodium dodecyl sulfate–polyacrylamide gel electrophoresis (SDS-PAGE). The results showed that 0.951 ± 0.03 mg/mL of functional proteins were successfully extracted from the EBN. Several distinct protein bands in the range of 35–135 kDa were profiled from the EBN. Using ultrahigh-performance liquid chromatography coupled with quadrupole time-of-flight tandem mass spectrometry (UHPLC-Q-TOF-MS-MS), a total of 51 proteins were identified from the EBN. The protein sequences were processed in the BIOPEP database to predict the potential biological activity of EBN proteins. The prediction results suggest that EBN proteins potentially possess antioxidant, anti-inflammatory, immunostimulatory, antiamnestic, antihypertensive (angiotensin-converting enzyme (ACE) inhibitors), antidiabetic (alpha-glucosidase inhibitors, alpha-amylase inhibitors, dipeptidyl peptidase IV inhibitors), and antithrombotic properties. The antioxidant properties (DPPH-scavenging activity (20.84% ± 3.43) and ABTS-scavenging activity (31.49% ± 1.66)) and anti-inflammatory properties (inhibition of nitric oxide (NO) production (21.30% ± 4.41) and inhibition of albumin denaturation (25.30% ± 0.32)) were experimentally validated. In conclusion, the results suggest that functional proteins from EBN are potentially functional ingredients in the nutraceutical and food industries.

Although real-time reverse transcriptase polymerase chain reaction (real-time RT-PCR) remains as a golden standard for detection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, it can not be easily expanded to large-scaled screening during outbreaks, and the positive results do not necessarily correlate with infectious status of the identified subjects. In this study, the performance of Vstrip® RV2 COVID-19 Antigen Rapid Test (RAT) and its correlation with virus infectivity was examined by virus culture using 163 sequential respiratory specimens collected from 26 SARS-CoV-2 infected patients. When the presence of cytopathic effects (CPE) in cell culture was used as a reference method for virus infectivity, the sensitivity, specificity and accuracy of Vstrip® RV2 COVID-19 Antigen Rapid Test was 96.43%, 89.63%, and 90.8%, respectively. The highest Ct value was 27.7 for RdRp gene and 25.79 for E gene within CPE-positive samples, and the highest Ct value was 31.9 for RdRp gene and 29.1 for E gene within RAT positive samples. When the Ct values of specimens were below 25, the CPE and RAT results had high degree of consistency. We concluded that the RAT could be a great alternative method for determining the infectious potential of individuals with high viral load.

Pyrolysis is a key technology that converts unrecyclable end-of-life plastics into value-added products. Nevertheless, the high energy consumption during plastic pyrolysis limits the economic feasibility of a scaled-up process. Development of an energy-efficient plastic pyrolysis process is necessary to realise its full potential in the circular economy. Catalysts derived from mesocellular foam possess high acidity and mesoporosity, and exhibit high catalytic activity in chemical reactions. Application of such catalyst in plastic pyrolysis has never been reported. This work presents the catalytic pyrolysis of low- and high-density polyethylene and polypropylene over maghemite-impregnated mesocellular foam (Fe@AlMCF). Fe@AlMCF has a BET surface area of 629.8 m2/g and a strong Brønsted acidity (677 µmol/gcat). The catalyst contains pentagonal and hexagonal packed mesostructure. Induction heating resulted in a rapid increase in reactor temperature (at 65 °C /min) and complete plastics conversion within 10 min. Catalytic pyrolysis produced gas products rich in C3 compounds. The liquid products were rich in alkenes (69.7-71.3 %) and alkanes, followed by aromatics (10.4-12.8 %). These observations indicate that the highly acidic Fe@AlMCF catalysed hydrocarbon aromatization within a short reaction time. Thermal analysis of the spent catalysts revealed considerably high coke yields (5.78 - 6.03 %), as the higher acidity of the original catalyst promoted coke precursor formation. Based on the research findings, induction heating can rapidly and effectively convert plastics into hydrocarbon feedstocks, and Fe@AlMCF is a valuable catalyst for plastic pyrolysis.

BackgroundThe longitudinal course of patients with pediatric acute respiratory distress syndrome (PARDS) is not well described. In this study, we describe the oxygenation index (OI) and oxygen saturation index (OSI) in mild, moderate, and severe PARDS over 28 days and provide pilot data for the time to resolution of PARDS (Tres), as a short-term respiratory-specific outcome, hypothesizing that it is associated with the severity of PARDS and clinical outcomes.MethodsThis prospective observational study recruited consecutive patients with PARDS. OI and OSI were trended daily over 28 days. Tres (defined as OI

Abstract The specific cytokines that regulate pediatric acute respiratory distress syndrome (PARDS) pathophysiology remains unclear. Here, we evaluated the respiratory cytokine profile in PARDS to identify the molecular signatures associated with severe disease. A multiplex suspension immunoassay was used to profile 45 cytokines, chemokines and growth factors. Cytokine concentrations were compared between severe and non-severe PARDS, and correlated with oxygenation index (OI). Partial least squares regression modelling and regression coefficient plots were used to identify a composite of key mediators that differentially segregated severe from non-severe disease. The mean (standard deviation) age and OI of this cohort was 5.2 (4.9) years and 17.8 (11.3), respectively. Early PARDS patients with severe disease exhibited a cytokine signature that was up-regulated for IL-12p70, IL-17A, MCP-1, IL-4, IL-1β, IL-6, MIP-1β, SCF, EGF and HGF. In particular, pro-inflammatory cytokines (IL-6, MCP-1, IP-10, IL-17A, IL-12p70) positively correlated with OI early in the disease. Whereas late PARDS was characterized by a differential lung cytokine signature consisting of both up-regulated (IL-8, IL-12p70, VEGF-D, IL-4, GM-CSF) and down-regulated (IL-1β, EGF, Eotaxin, IL-1RA, and PDGF-BB) profiles segregating non-severe and severe groups. This cytokine signature was associated with increased transcription, T cell activation and proliferation as well as activation of mitogen-activated protein kinase pathway that underpin PARDS severity.

Abstract Extracorporeal membrane oxygenation (ECMO) is a life‐saving rescue therapy used in acute respiratory failure refractory to invasive mechanical ventilation. Recent studies on positive outcomes of extended ECMO therapy are promising. We describe a case of a 2‐year 8‐month‐old female child with necrotizing pneumonia secondary to Streptococcus pneumoniae, Influenza A, and Mycoplasma pneumoniae, who survived with intact neurological function and no long‐term adverse outcomes after a prolonged ECMO run of 86 days. To the best of our knowledge, this is one of the longer durations of ECMO with transplant‐free survival in a pediatric patient requiring respiratory support with good recovery and a good functional outcome. Allowing time for native lung recovery is pivotal for optimal recovery, despite significant lung injury due to the underlying disease process. With evolving ECMO experience, clinicians may need to re‐consider the conventional maximum duration of ECMO in children with severe respiratory failure on a case‐by‐case basis.

ObjectiveCurrent knowledge on the global burden of infant sepsis is limited to population-level data. We aimed to summarize global case fatality rates (CFRs) of young infants with sepsis, stratified by gross national income (GNI) status and patient-level risk factors.MethodsWe performed a systematic review and meta-analysis on CFRs among young infants < 90 days with sepsis. We searched PubMed, Cochrane Central, Embase, and Web of Science for studies published between January 2010 and September 2019. We obtained pooled CFRs estimates using the random effects model. We performed a univariate analysis at patient-level and a meta-regression to study the associations of gestational age, birth weight, onset of sepsis, GNI, age group and culture-proven sepsis with CFRs.ResultsThe search yielded 6314 publications, of which 240 studies (N = 437,796 patients) from 77 countries were included. Of 240 studies, 99 were conducted in high-income countries, 44 in upper-middle-income countries, 82 in lower-middle-income countries, 6 in low-income countries and 9 in multiple income-level countries. Overall pooled CFR was 18% (95% CI, 17–19%). The CFR was highest for low-income countries [25% (95% CI, 7–43%)], followed by lower-middle [25% (95% CI, 7–43%)], upper-middle [21% (95% CI, 18–24%)] and lowest for high-income countries [12% (95% CI, 11–13%)]. Factors associated with high CFRs included prematurity, low birth weight, age less than 28 days, early onset sepsis, hospital acquired infections and sepsis in middle- and low-income countries. Study setting in middle-income countries was an independent predictor of high CFRs. We found a widening disparity in CFRs between countries of different GNI over time.ConclusionYoung infant sepsis remains a major global health challenge. The widening disparity in young infant sepsis CFRs between GNI groups underscore the need to channel greater resources especially to the lower income regions.Systematic Review Registration[www.crd.york.ac.uk/prospero], identifier [CRD42020164321].

Palliative care (PC) is an integral component of optimal critical care (CC) practice for pediatric patients facing life-threatening illness. PC acts as an additional resource for patients and families as they navigate through critical illness. Although PC encompasses end of life care, it is most effective when integrated early alongside disease-directed and curative therapies. PC primarily focuses on improving quality of life for patients and families by anticipating, preventing and treating suffering throughout the continuum of illness. This includes addressing symptom distress and facilitating communication. Effective communication is vital to elicit value-based goals of care, and to guide parents through patient-focused and potentially difficult decision-making process which includes advanced care planning. A multidisciplinary approach is most favorable when providing support to both patient and family, whether it is from the psychosocial, practical, emotional, spiritual or cultural aspects. PC also ensures coordination and continuity of care across different care settings. Support for family carries on after death with grief and bereavement support. This narrative review aims to appraise the current evidence of integration of PC into pediatric CC and its impact on patient- and family-centered outcomes. We will also summarize the impact of integration of good PC into pediatric CC, including effective communication with families, advanced care planning, withholding or withdrawal of life sustaining measures and bereavement support. Finally, we will provide a framework on how best to integrate PC in PICU. These findings will provide insights on how PC can improve the quality of care of a critically ill child.

Abstract Fever of unknown origin (FUO) is a diagnostic challenge. Anti‐N‐methyl‐D‐aspartate receptor encephalitis should be considered in children with FUO and new‐onset neurological symptoms without significant encephalopathy.

High-frequency oscillatory ventilation (HFOV) is a type of invasive mechanical ventilation that employs supra-physiologic respiratory rates and low tidal volumes (VT) that approximate the anatomic deadspace. During HFOV, mean airway pressure is set and gas is then displaced towards and away from the patient through a piston. Carbon dioxide (CO2) is cleared based on the power (amplitude) setting and frequency, with lower frequencies resulting in higher VT and CO2 clearance. Airway pressure amplitude is significantly attenuated throughout the respiratory system and mechanical strain and stress on the alveoli are theoretically minimized. HFOV has been purported as a form of lung protective ventilation that minimizes volutrauma, atelectrauma, and biotrauma. Following two large randomized controlled trials showing no benefit and harm, respectively, HFOV has largely been abandoned in adults with ARDS. A multi-center clinical trial in children is ongoing. This article aims to review the physiologic rationale for the use of HFOV in patients with acute respiratory failure, summarize relevant bench and animal models, and discuss the potential use of HFOV as a primary and rescue mode in adults and children with severe respiratory failure.

IntroductionFear of missed serious bacterial infections (SBIs) results in many febrile young infants receiving antibiotics. We aimed to compare the time to antibiotics between infants with SBIs and those without.Materials and MethodsWe recruited febrile infants ≤ 90 days old seen in the emergency department (ED) between December 2017 and April 2021. SBI was defined as (1) urinary tract infection, (2) bacteremia or (3) bacterial meningitis. We compared the total time (median with interquartile range, IQR) from ED arrival to infusion of antibiotics, divided into (i) time from triage to decision for antibiotics and (ii) time from decision for antibiotics to administration of antibiotics.ResultsWe analyzed 81 and 266 infants with and without SBIs. Median age of those with and without SBIs were 44 (IQR 19–72) and 29 (IQR 7–56) days, respectively (p = 0.002). All infants with SBIs and 168/266 (63.2%) infants without SBIs received antibiotics. Among 249 infants who received antibiotics, the median total time from ED arrival to infusion of antibiotics was 277.0 (IQR 236.0–385.0) mins for infants with SBIs and 304.5 (IQR 238.5–404.0) mins for those without (p = 0.561). The median time to decision for antibiotics was 156.0 (IQR 115.0–255.0) mins and 144.0 (IQR 105.5–211.0) mins, respectively (p = 0.175). Following decision for antibiotics, infants with SBIs received antibiotics much faster compared to those without [107.0 (IQR 83.0–168.0) vs. 141.0 (94.0–209.5) mins, p = 0.017].ConclusionThere was no difference in total time taken to antibiotics between infants with SBIs and without SBIs. Both recognition and administration delays were observed. While all infants with SBIs were adequately treated, more than half of the infants without SBIs received unnecessary antibiotics. This highlights the challenge in managing young febrile infants at initial presentation, and demonstrates the need to examine various aspects of care to improve the overall timeliness to antibiotics.

BackgroundThe majority of childhood deaths occur in low- and middle-income countries (LMICs). Many of these deaths are avoidable with basic critical care interventions. Quantifying the burden of pediatric critical illness in LMICs is essential for targeting interventions to reduce childhood mortality.ObjectiveTo determine the burden of hospitalization and mortality associated with acute pediatric critical illness in LMICs through a systematic review and meta-analysis of the literature.Data Sources and Search StrategyWe will identify eligible studies by searching MEDLINE, EMBASE, CINAHL, and LILACS using MeSH terms and keywords. Results will be limited to infants or children (ages >28 days to 12 years) hospitalized in LMICs and publications in English, Spanish, or French. Publications with non-original data (e.g., comments, editorials, letters, notes, conference materials) will be excluded.Study SelectionWe will include observational studies published since January 1, 2005, that meet all eligibility criteria and for which a full text can be located.Data ExtractionData extraction will include information related to study characteristics, hospital characteristics, underlying population characteristics, patient population characteristics, and outcomes.Data SynthesisWe will extract and report data on study, hospital, and patient characteristics; outcomes; and risk of bias. We will report the causes of admission and mortality by region, country income level, and age. We will report or calculate the case fatality rate (CFR) for each diagnosis when data allow.ConclusionsBy understanding the burden of pediatric critical illness in LMICs, we can advocate for resources and inform resource allocation and investment decisions to improve the management and outcomes of children with acute pediatric critical illness in LMICs.