Med-MGF: multi-level graph-based framework for handling medical data imbalance and representation.

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 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+ 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+ 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.

Physical, Cognitive, Emotional, and Social Health Outcomes of Parents in the First Six Months after Childhood Critical Illness: A Prospective Single Centre Study.

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.

Daily Sedation Interruption vs Continuous Sedation in Pediatric Patients Receiving Mechanical Ventilation: A Systematic Review and Meta-analysis.

Importance: The effectiveness of daily sedation interruption (DSI, defined as temporary interruption of sedation) has yet to be demonstrated in critically ill pediatric patients. Objective: To compare the clinical outcomes of DSI vs continuous intravenous (IV) sedation in patients receiving invasive mechanical ventilation (MV) support in the pediatric intensive care unit (PICU). Data Sources: A systematic search for studies was conducted using predefined keywords and Medical Subject Headings in 5 major databases (PubMed, Embase, Web of Science, CINAHL [Cumulated Index to Nursing and Allied Health Literature], and Cochrane Central Register of Controlled Trials) from database inception to October 31, 2023. Study Selection: Retrospective and prospective observational studies, randomized clinical trials (RCTs), and systematic reviews were assessed for inclusion. Studies were eligible if they compared DSI to continuous IV sedation in patients aged 18 years or younger requiring MV in the PICU. Data Extraction and Synthesis: Study characteristics, including the types of sedation, sedation protocols, and clinical outcomes, were extracted. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) reporting guideline was followed. A random-effects model was used to pool results from articles for the meta-analysis. Main Outcomes and Measures: The primary outcomes of interest were duration of MV and length of PICU stay. Secondary outcomes included total sedative dose requirement, adverse events (eg, complications associated with MV, withdrawal, and delirium), and mortality. Results: A total of 6 RCTs with 2810 pediatric patients (1569 males [55.8%]; mean age, 26.5 [95% CI, 15.0-37.9] months) were included in the final analysis; patients had a mean PRISM (Pediatric Risk of Mortality) score of 13.68 (95% CI, 10.75-16.61). Compared with continuous IV sedation, DSI was associated with a reduction in length of PICU stay (5 studies, n = 2770; mean difference [MD], -1.45 [95% CI, -2.75 to -0.15] days; P = .03]. There was no difference in MV duration (5 studies, n = 2750; MD, -0.93 [95% CI, -1.89 to 0.04] days; P = .06), total doses of midazolam (3 studies, n = 191; MD, -1.66 [95% CI, -3.95 to 0.63] mg/kg) and morphine used (2 studies, n = 189; MD, -2.63 [95% CI, -7.01 to 1.75] mg/kg), or adverse events (risk ratio [RR], 1.03 [95% CI, 0.74-1.42]; P = .88). There was no difference in mortality between patients exposed vs not exposed to DSI (RR, 0.89 [95% CI, 0.55-1.46]; P = .65). Conclusions and Relevance: This systematic review and meta-analysis found that use of DSI in pediatric patients was associated with reduced length of PICU stay with no increase in adverse events. Further research is needed to ascertain whether this strategy is associated with improved neurodevelopmental outcomes in PICU survivors.

Impact of neonatal sepsis on neurocognitive outcomes: a systematic review and meta-analysis.

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.

Establishment of a protocol for rapidly expanding Epstein-Barr-virus-specific cytotoxic T cells with enhanced cytotoxicity.

BACKGROUND: Lytic Epstein-Barr virus (EBV) infection plays a major role in the pathogenesis of nasopharyngeal carcinoma (NPC). For patients with recurrent or metastatic NPC and resistant to conventional therapies, adoptive cell therapy using EBV-specific cytotoxic T cells (EBV-CTLs) is a promising option. However, the long production period (around 3 to 4 weeks) and low EBV-CTL purity (approximately 40% of total CD8 T cells) in the cell product limits the application of EBV-CTLs in clinics. Thus, this study aimed to establish a protocol for the rapid production of EBV-CTLs. METHODS: By culturing peripheral blood mononuclear cells (PBMCs) from EBV-seropositive donors with EBV-specific peptides and interleukin (IL)-2, IL-15, and interferon α (IFN-α) for 9 days, we identified that IL-15 can enhance IL-2-mediated CTL activation and significantly increase the yield of CTLs. RESULTS: When IFN-α was used in IL-2/IL-15-mediated CTL production from days 0 to 6, the productivity of EBV-CTLs and EBV-specific cytotoxicity significantly were reinforced relative to EBV-CTLs from IL-2/IL-15 treatment. Additionally, IFN-α-induced production improvement of virus-specific CTLs was not only the case for EBV-CTLs but also for cytomegalovirus-specific CTLs. CONCLUSION: We established a novel protocol to rapidly expand highly pure EBV-CTLs from PBMCs, which can produce EBV-CTLs in 9 days and does not require feeder cells during cultivation.

Sex differences in pediatric sepsis-a systematic review protocol.

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 < 18 years of age. Exposure will be sepsis, severe sepsis, and septic shock and the main comparison will be between male and female sex. The primary outcome will be hospital mortality. Secondary outcomes will be the pediatric intensive care unit and hospital length of stay. DISCUSSION: Results from this review are expected to provide important information on the association of sex with the outcomes of pediatric sepsis. If an association is noted, this study may serve as a foundation for further research evaluating the pathophysiological aspects as well as potential socioeconomic factors responsible for the clinically detected sex differences. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42022315753.

Severe Pneumonia in PICU Admissions: The Pediatric Acute and Critical Care Medicine Asian Network (PACCMAN) Observational Cohort Study, 2020-2022.

OBJECTIVES: Mortality from pneumonia is three times higher in Asia compared with industrialized countries. We aimed to determine the epidemiology, microbiology, and outcome of severe pneumonia in PICUs across the Pediatric Acute and Critical Care Medicine Asian Network (PACCMAN). DESIGN: Prospective multicenter observational study from June 2020 to September 2022. SETTING: Fifteen PICUs in PACCMAN. PATIENTS: All children younger than 18 years old diagnosed with pneumonia and admitted to the PICU. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Clinical, microbiologic, and outcome data were recorded. The primary outcome was PICU mortality. Univariate and multivariable logistic regression was performed to investigate associations between PICU mortality and explanatory risk factors on presentation to the PICU. Among patients screened, 846 of 11,778 PICU patients (7.2%) with a median age of 1.2 years (interquartile range, 0.4-3.7 yr) had pneumonia. Respiratory syncytial virus was detected in 111 of 846 cases (13.1%). The most common bacteria were Staphylococcus species (71/846 [8.4%]) followed by Pseudomonas species (60/846 [7.1%]). Second-generation cephalosporins (322/846 [38.1%]) were the most common broad-spectrum antibiotics prescribed, followed by carbapenems (174/846 [20.6%]). Invasive mechanical ventilation and noninvasive respiratory support was provided in 438 of 846 (51.8%) and 500 of 846 (59.1%) patients, respectively. PICU mortality was 65 of 846 (7.7%). In the multivariable logistic regression model, age (adjusted odds ratio [aOR], 1.08; 95% CI, 1.00-1.16), Pediatric Index of Mortality 3 score (aOR, 1.03; 95% CI, 1.02-1.05), and drowsiness (aOR, 2.73; 95% CI, 1.24-6.00) were associated with greater odds of mortality. CONCLUSIONS: In the PACCMAN contributing PICUs, pneumonia is a frequent cause for admission (7%) and is associated with a greater odds of mortality.

Lung-Protective Ventilation for Pediatric Acute Respiratory Distress Syndrome: A Nonrandomized Controlled Trial.

OBJECTIVES: Despite the recommendation for lung-protective mechanical ventilation (LPMV) in pediatric acute respiratory distress syndrome (PARDS), there is a lack of robust supporting data and variable adherence in clinical practice. This study evaluates the impact of an LPMV protocol vs. standard care and adherence to LPMV elements on mortality. We hypothesized that LPMV strategies deployed as a pragmatic protocol reduces mortality in PARDS. DESIGN: Multicenter prospective before-and-after comparison design study. SETTING: Twenty-one PICUs. PATIENTS: Patients fulfilled the Pediatric Acute Lung Injury Consensus Conference 2015 definition of PARDS and were on invasive mechanical ventilation. INTERVENTIONS: The LPMV protocol included a limit on peak inspiratory pressure (PIP), delta/driving pressure (DP), tidal volume, positive end-expiratory pressure (PEEP) to F io2 combinations of the low PEEP acute respiratory distress syndrome network table, permissive hypercarbia, and conservative oxygen targets. MEASUREMENTS AND MAIN RESULTS: There were 285 of 693 (41·1%) and 408 of 693 (58·9%) patients treated with and without the LPMV protocol, respectively. Median age and oxygenation index was 1.5 years (0.4-5.3 yr) and 10.9 years (7.0-18.6 yr), respectively. There was no difference in 60-day mortality between LPMV and non-LPMV protocol groups (65/285 [22.8%] vs. 115/406 [28.3%]; p = 0.104). However, total adherence score did improve in the LPMV compared to non-LPMV group (57.1 [40.0-66.7] vs. 47.6 [31.0-58.3]; p < 0·001). After adjusting for confounders, adherence to LPMV strategies (adjusted hazard ratio, 0.98; 95% CI, 0.97-0.99; p = 0.004) but not the LPMV protocol itself was associated with a reduced risk of 60-day mortality. Adherence to PIP, DP, and PEEP/F io2 combinations were associated with reduced mortality. CONCLUSIONS: Adherence to LPMV elements over the first week of PARDS was associated with reduced mortality. Future work is needed to improve implementation of LPMV in order to improve adherence.

Psychological Outcomes in Families of PICU Survivors: A Meta-Analysis.

BACKGROUND: Pediatric critical illness exposes family members to stressful experiences that may lead to subsequent psychological repercussions. OBJECTIVE: To systematically review psychological outcomes among PICU survivors' family members. DATA SOURCES: Four medical databases (PubMed, Embase, CINAHL and PsycInfo) were searched from inception till October 2023. STUDY SELECTION: Studies reporting psychological disorders in family members of PICU patients with at least 3 months follow-up were included. Family members of nonsurvivors and palliative care patients were excluded. DATA EXTRACTION: Screening and data extraction was performed according to PRISMA guidelines. Data were pooled using a random-effects model. RESULTS: Of 5360 articles identified, 4 randomized controlled trials, 16 cohort studies, and 2 cross-sectional studies were included (total patients = 55 597; total family members = 97 506). Psychological distress was reported in 35.2% to 64.3% and 40.9% to 53% of family members 3 to 6 months and 1 year after their child's PICU admission, respectively. Post-traumatic stress disorder was diagnosed in 10% to 48% of parents 3 to 9 months later. Parents that experienced moderate to severe anxiety and depression 3 to 6 months later was 20.9% to 42% and 6.1% to 42.6%, respectively. Uptake of mental counseling among parents was disproportionately low at 0.7% to 29%. Risk factors for psychiatric morbidity include mothers, parents of younger children, and longer duration of PICU stay. LIMITATIONS: The majority of studies were on parents with limited data on siblings and second degree relatives. CONCLUSIONS: There is a high burden of psychological sequelae in family members of PICU survivors. Risk stratification to identify high-risk groups and early interventions are needed.

Use of Speckle-Tracking Echocardiography in Septic Cardiomyopathy in Critically Ill Children: A Narrative Review.

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.

Parental emotional, social and transitional health in the first 6 months after childhood critical illness: A longitudinal qualitative study.

AIM: To explore the experiences and support needs of parents in the first 6 months after paediatric critical care. DESIGN: Longitudinal qualitative design. METHODS: Sequential semi-structured qualitative interviews were conducted with a sample of 28 parents in succession at 1 month and at 6 months (n = 22) after their child's discharge from paediatric critical care using purposive sampling. Data were analysed using the adapted five-stage framework analysis. RESULTS: Data were developed into eight synthesized themes, three domains and an overarching theme: Regaining Normalcy. Families of children requiring medical treatment at 6 months showed signs of adaption to daily care routines. The two domains were Parental Emotional Health and Parental Social Health. Parental Transitional Health, a third domain, was added to the Post Intensive Care Syndrome-paediatric framework. Parents were forward-looking and discussed emotional health, relating to current caregiving issues. Emotional attention was related to present challenges and concerns about current health and possible readmission to the hospital. In terms of Parental Social Health, families isolated themselves for infection control while remaining connected with families using chat applications. Parents were selective to whom they allowed access to their lives. The impact of parental transitional health was evident and emphasized the daily challenges associated with integration back to home life. Flexible work arrangements allowed working parents to support caregiving needs in the first 6 months after discharge. CONCLUSION: In the first 6 months after paediatric critical illness, most families reported having moved past the experiences while having provoking memories of the admission period. Parents viewed the point of normalcy as child returned to school or when all medications were discontinued. Extension of transitional support can facilitate discharge experiences between paediatric critical care and normalcy. The findings highlight the importance of understanding the medium- and longer-term impact of paediatric critical care. IMPACT: What problem did the study address? ○ Limited understanding of long-term parental experiences and support needs after PICU discharge. What were the main findings? ○ Most families regained normalcy when child returns to school or when medications were discontinued. Some families continued to show signs of adaptations at 6 months after PICU discharge. Where and on whom did the research have an impact? ○ The research has an impact on improving the understanding of long-term parental experiences and support needs after PICU discharge, informing clinical practice, guiding policy development and shaping parental support programs. REPORTING METHOD: We reported this study using the COREQ guidelines. PATIENT OR PUBLIC CONTRIBUTION: Prior to confirming the interview guide, three parents of critically ill children actively participated by reviewing and providing feedback on its content. They provided suggestions to refine the wording and ensure clarity to enhance the participants' understanding. By including the perspectives of these parents, we aimed to improve the overall quality and relevance of the interview guide.

Etiology of hospital mortality in children living in low- and middle-income countries: a systematic review and meta-analysis.

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.

A two-phased study on the use of remote photoplethysmography (rPPG) in paediatric care.

Background: Advancements in medical technologies have led to the development of contact-free methods of haemodynamic monitoring such as remote photoplethysmography (rPPG). rPPG uses video cameras to interpret variations in skin colour related to blood flow, which are analysed to generate vital signs readings. rPPG potentially ameliorates problems like fretfulness and fragile skin contact associated with conventional probes in children. While rPPG has been validated in adults, no prior validation has been performed in children. Methods: A two-phased prospective cross-sectional single-centre study was conducted from January to April 2023 to evaluate the feasibility, acceptability, and accuracy of obtaining heart rate (HR), respiratory rate (RR) and oxygen saturation (SpO2) using rPPG in children, compared to the current standard of care. In Phase 1, we recruited patients ≤16 years from the neonatal and paediatric wards. We excluded preterm neonates with gestational age <35 weeks and newborns <24 hours old. The rPPG webcam was positioned 30 cm from the face. After 1 minute of facial scanning, readings generated were compared with pulse oximetry for HR and SpO2, and manual counting for RR. Correlation and Bland-Altman analyses were performed. In Phase 2, we focused on the population in whom there was potential correlation between rPPG and the actual vital signs. Results: Ten neonates and 28 children aged 5 to 16 years were recruited for Phase 1 (765 datapoints). All patients were haemodynamically stable and normothermic. Patients and caregivers showed high acceptability to rPPG. rPPG values were clinically discrepant for children <10 years. For those ≥10 years, moderate correlation was observed for HR, with Spearman's correlation coefficient (Rs) of 0.50 [95% confidence intervals (CI): 0.42, 0.57]. We performed Phase 2 on 23 patients aged 12 to 16 years (559 datapoints). Strong correlation was observed for HR with Rs=0.82 (95% CI: 0.78, 0.85). There was weak correlation for SpO2 and RR (Rs=-0.25 and -0.02, respectively). Conclusions: Our study showed that rPPG is acceptable and feasible for neonates and children aged 5 to 16 years, and HR values in older children aged 12 to 16 years correlated well with the current standard. The rPPG algorithms need to be further refined for younger children, and for obtaining RR and SpO2 in all children. If successful, rPPG will provide a viable contact-free alternative for assessing paediatric vital signs, with potential use in remote monitoring and telemedicine.

Characterization of unique pattern of immune cell profile in patients with nasopharyngeal carcinoma through flow cytometry and machine learning.

In patients with nasopharyngeal carcinoma (NPC), the alteration of immune responses in peripheral blood remains unclear. In this study, we established an immune cell profile for patients with NPC and used flow cytometry and machine learning (ML) to identify the characteristics of this profile. After isolation of circulating leukocytes, the proportions of 104 immune cell subsets were compared between NPC group and the healthy control group (HC). Data obtained from the immune cell profile were subjected to ML training to differentiate between the immune cell profiles of the NPC and HC groups. We observed that subjects in the NPC group presented higher proportions of T cells, memory B cells, short-lived plasma cells, IgG-positive B cells, regulatory T cells, MHC II+ T cells, CTLA4+ T cells and PD-1+ T cells than subjects in the HC group, indicating weaker and compromised cellular and humoral immune responses. ML revealed that monocytes, PD-1+ CD4 T cells, memory B cells, CTLA4+ CD4 Treg cells and PD-1+ CD8 T cells were strongly contributed to the difference in immune cell profiles between the NPC and HC groups. This alteration can be fundamental in developing novel immunotherapies for NPC.

Nutritional Intake in Children with Septic Shock: A Retrospective Single-Center Study.

Nutritional practice in children with severe sepsis or septic shock remains poorly described. We aimed to describe nutrition received by children with severe sepsis or septic shock and explore the association of nutritional intake with clinical outcomes. This study was a retrospective study of children who required pediatric intensive care unit (PICU) admission from 2009 to 2016. Outcomes were mortality, ventilator-free days (VFDs), and PICU-free days (IFDs). A total of 74 patients with septic shock or severe sepsis were identified. Forty-one (55.4%) patients received enteral nutrition (EN) only, 6 (8.1%) patients received parental nutrition (PN) only, 15 (20.3%) patients received both EN and PN, and 12 (16.2%) patients received intravenous fluids alone. Eight of 74 (10.8%) and 4 of 74 (5.4%) had adequate energy and protein intake, respectively. Patients who received early EN had lower odds of 28-day mortality (adjusted hazard ratio [HR] = 0.09, 95% confidence interval [CI]: 0.02, 0.45, p = 0.03) more 28-day VFDs (adjusted ß-coefficient = 18.21 [95% CI: 11.11, 25.32], p < 0.001), and IFDs (adjusted ß-coefficient = 16.71 [95% CI: 9.86, 23.56], p < 0.001) than patients who did not receive EN. Late EN was also associated with lower odds of mortality, more VFDs, and IFDs compared with no EN (HR = 0.06, 95% CI: 0.02, 0.23; p < 0.001; adjusted ß coefficient = 15.66, 95% CI: 9.31, 22.02; p < 0.001; and 12.34 [95% CI: 6.22, 18.46], p < 0.001; respectively). Inadequate calories and protein were not associated with mortality. EN in children with septic shock or severe sepsis was associated with improved clinical outcomes. Future prospective studies are required to explore the impact of EN timing and optimal nutritional intake in these children.

Characterization of tumoricidal activities mediated by a novel immune cell regimen composing interferon-producing killer dendritic cells and tumor-specific cytotoxic T lymphocytes.

BACKGROUND: Although immune cell therapy has long been used for treating solid cancer, its efficacy remains limited. Interferon (IFN)-producing killer dendritic cells (IKDCs) exhibit cytotoxicity and present antigens to relevant cells; thus, they can selectively induce tumor-associated antigen (TAA)-specific CD8 T cells and may be useful in cancer treatment. Various protocols have been used to amplify human IKDCs from peripheral sources, but the complexity of the process has prevented their widespread clinical application. Additionally, the induction of TAA-specific CD8 T cells through the adoptive transfer of IKDCs to immunocompromised patients with cancer may be insufficient. Therefore, we developed a method for generating an immune cell-based regimen, Phyduxon-T, comprising a human IKDC counterpart (Phyduxon) and expanded TAA-specific CD8 T cells. METHODS: Peripheral blood mononuclear cells from ovarian cancer patients were cultured with human interleukin (hIL)-15, hIL-12, and hIL-18 to generate Phyduxon-T. Then, its phenotype, cytotoxicity, and antigen-presenting function were evaluated through flow cytometry using specific monoclonal antibodies. RESULTS: Phyduxon exhibited the characteristics of both natural killer and dendritic cells. This regimen also exhibited cytotoxicity against primary ovarian cancer cells and presented TAAs, thereby inducing TAA-specific CD8 T cells, as evidenced by the expression of 4-1BB and IFN-γ. Notably, the Phyduxon-T manufacturing protocol effectively expanded IFN-γ-producing 4-1BB+ TAA-specific CD8 T cells from peripheral sources; these cells exhibited cytotoxic activities against ovarian cancer cells. CONCLUSIONS: Phyduxon-T, which is a combination of natural killer cells, dendritic cells, and TAA-specific CD8 T cells, may enhance the efficacy of cancer immunotherapy.

Respiratory Support After Extubation in Children With Pediatric ARDS.

BACKGROUND: Postextubation respiratory support in pediatric ARDS may be used to support the recovering respiratory system and promote timely, successful liberation from mechanical ventilation. This study's aims were to (1) describe the use of postextubation respiratory support in pediatric ARDS from the time of extubation to hospital discharge, (2) identify potential risk factors for postextubation respiratory support, and (3) provide preliminary data for future larger studies. METHODS: This pilot single-center prospective cohort study recruited subjects with pediatric ARDS. Subjects' respiratory status up to hospital discharge, the use of postextubation respiratory support, and how it changed over time were recorded. Analysis was performed comparing subjects who received postextubation respiratory support versus those who did not and compared its use among pediatric ARDS severity categories. Multivariable logistic regression was used to determine variables associated with the use of postextubation respiratory support and included oxygenation index (OI), ventilator duration, and weight. RESULTS: Seventy-three subjects with pediatric ARDS, with median age and OI of 4 (0.6-10.5) y and 7.3 (4.9-12.7), respectively, were analyzed. Postextubation respiratory support was provided to 54/73 (74%) subjects: 28/45 (62.2%), 19/21 (90.5%), and 7/7 (100%) for mild, moderate, and severe pediatric ARDS, respectively, (P = .01). OI and mechanical ventilation duration were higher in subjects who received postextubation respiratory support (8.7 [5.4-14] vs 4.6 [3.7-7], P < .001 and 10 [7-17] d vs 4 [2-7] d, P < .001) compared to those who did not. At hospital discharge, 12/67 (18.2%) survivors received home respiratory support (6 subjects died prior to hospital discharge). In the multivariable model, ventilator duration (adjusted odds ratio 1.3 [95% CI 1.0-1.7], P = .050) and weight (adjusted odds ratio 0.95 [95% CI 0.91-0.99], P = .02) were associated with the use of postextubation respiratory support. CONCLUSIONS: The majority of intubated subjects with pediatric ARDS received respiratory support postextubation, and a substantial proportion continued to require it up to hospital discharge.

Initial dysnatremia and clinical outcomes in pediatric traumatic brain injury: a multicenter observational study.

PURPOSE: We aimed to investigate the association between initial dysnatremia (hyponatremia and hypernatremia) and in-hospital mortality, as well as between initial dysnatremia and functional outcomes, among children with traumatic brain injury (TBI). METHOD: We performed a multicenter observational study among 26 pediatric intensive care units from January 2014 to August 2022. We recruited children with TBI under 18 years of age who presented to participating sites within 24 h of injury. We compared demographics and clinical characteristics between children with initial hyponatremia and eu-natremia and between those with initial hypernatremia and eu-natremia. We defined poor functional outcome as a discharge Pediatric Cerebral Performance Category (PCPC) score of moderate, severe disability, coma, and death, or an increase of at least 2 categories from baseline. We performed multivariable logistic regression for mortality and poor PCPC outcome. RESULTS: Among 648 children, 84 (13.0%) and 42 (6.5%) presented with hyponatremia and hypernatremia, respectively. We observed fewer 14-day ventilation-free days between those with initial hyponatremia [7.0 (interquartile range (IQR) = 0.0-11.0)] and initial hypernatremia [0.0 (IQR = 0.0-10.0)], compared to eu-natremia [9.0 (IQR = 4.0-12.0); p = 0.006 and p < 0.001]. We observed fewer 14-day ICU-free days between those with initial hyponatremia [3.0 (IQR = 0.0-9.0)] and initial hypernatremia [0.0 (IQR = 0.0-3.0)], compared to eu-natremia [7.0 (IQR = 0.0-11.0); p = 0.006 and p < 0.001]. After adjusting for age, severity, and sex, presenting hyponatremia was associated with in-hospital mortality [adjusted odds ratio (aOR) = 2.47, 95% confidence interval (CI) = 1.31-4.66, p = 0.005] and poor outcome (aOR = 1.67, 95% CI = 1.01-2.76, p = 0.045). After adjustment, initial hypernatremia was associated with mortality (aOR = 5.91, 95% CI = 2.85-12.25, p < 0.001) and poor outcome (aOR = 3.00, 95% CI = 1.50-5.98, p = 0.002). CONCLUSION: Among children with TBI, presenting dysnatremia was associated with in-hospital mortality and poor functional outcome, particularly hypernatremia. Future research should investigate longitudinal sodium measurements in pediatric TBI and their association with clinical outcomes.