Research Appraisals
Evidence-based critical appraisals of the latest medical research, systematically evaluated using Oxford CEBM methodology.
Showing 10 appraisals
Pediatric surgery international
Early vs. delayed feeding after pediatric gastrointestinal surgery: a systematic review and meta-analysis
BACKGROUND: The adoption of early feeding after pediatric gastrointestinal surgery remains inconsistent due to concerns regarding anastomotic safety. METHODS: A systematic review and meta-analysis of randomized controlled trials was conducted comparing early enteral feeding (initiation within 48 h) with delayed feeding in patients < 18 years undergoing intestinal anastomosis or stoma reversal. RESULTS: Eight trials comprising 704 patients (323 early feeding, 381 delayed) were included across neonatal and pediatric elective surgical populations. Early feeding significantly shortened hospital length of stay (mean difference - 3.53 days; 95% CI - 4.35 to - 2.71) and reduced time to full feeds (mean difference - 3.15 days; 95% CI - 3.89 to - 2.40). There was no significant difference in anastomotic leakage (log risk ratio - 0.36; 95% CI - 1.23 to 0.51; I²=0%) or postoperative vomiting (log risk ratio - 0.02; 95% CI - 0.41 to 0.38). Early feeding was also associated with fewer wound infections (log risk ratio - 0.85; 95% CI - 1.48 to - 0.22). CONCLUSIONS: Overall, early enteral feeding after pediatric gastrointestinal surgery appears safe and confers clinically meaningful benefits by accelerating nutritional recovery, reducing infectious complications, and shortening hospitalization, supporting its incorporation into pediatric postoperative care pathways.
13 June 2026
Read appraisal →Neurosurgical review
Bilateral decompressive craniectomy in pediatric patients: A systematic review.
Traumatic brain injury (TBI) and other acute neurological insults remain leading causes of pediatric morbidity and mortality. In cases where elevated intracranial pressure (ICP) is refractory to maximal medical therapy, decompressive craniectomy (DC) may be considered as a salvage intervention. Although bilateral, bifrontal, bitemporal, and cruciate decompressive approaches are used in selected patients with diffuse cerebral edema or bihemispheric swelling, their role, timing, complications, and outcomes remain poorly defined in pediatric populations. Following PRISMA guidelines, PubMed, Scopus, Embase, and PubMed Central were searched for English-language studies reporting bifrontal, bitemporal, bilateral, or cruciate decompressive craniectomy in pediatric or young adult patients, defined a priori as age ≤ 21 years, with refractory intracranial hypertension from traumatic or non-traumatic etiologies. Studies were included only if the cohort met this age criterion or if pediatric/young adult outcomes could be separately extracted. Mixed-age studies without extractable pediatric/young adult data were excluded from the primary synthesis. Data regarding demographics, operative technique, timing, mortality, complications, ICP response, and functional outcomes were extracted and synthesized qualitatively because of clinical and methodological heterogeneity. Five studies met eligibility criteria for the primary pediatric/young adult synthesis, including one small randomized pilot trial and four observational cohorts. The available evidence was heterogeneous with respect to indication, ICP threshold, timing of surgery, operative technique, and outcome measurement. Bitemporal, bifrontal, bilateral, and cruciate decompressive strategies were reported primarily in selected patients with severe traumatic brain injury or diffuse cerebral swelling. Several larger pediatric decompressive craniectomy cohorts included only small bilateral or bifrontal subgroups, and outcomes were not always stratified by technique. Reported mortality, functional recovery, hydrocephalus, subgaleal collections, and need for reoperation varied across studies. Early decompression was associated with ICP reduction and favorable outcomes in limited reports, including one small randomized trial, but the evidence remains insufficient to determine comparative efficacy, optimal timing, or superiority of one bilateral decompressive approach. Bilateral, bifrontal, bitemporal, and cruciate decompressive craniectomy have been reported as feasible salvage strategies for carefully selected pediatric and young adult patients with refractory intracranial hypertension. However, current evidence is sparse, heterogeneous, and often not technique-specific. Therefore, definitive conclusions regarding efficacy, optimal timing, or superiority of one bilateral approach cannot be made. Prospective multicenter studies with standardized age definitions, ICP thresholds, operative taxonomy, complication reporting, and long-term neurocognitive outcomes are needed.
1 June 2026
Read appraisal →Critical care explorations
Linking the Virtual Pediatric System and Pediatric Hospital Information System Databases to Create Novel PICU Research Datasets
BACKGROUND: Lack of a robust, national PICU database hinders epidemiologic and quasi-experimental research of PICU care. Combining the virtual pediatric system (VPS) and pediatric health information system (PHIS) databases would overcome this data gap. However, limits on the use of variables containing protected health information (PHI) have prevented prior large-scale VPS-PHIS linkage. We sought to link VPS and PHIS records from 31 hospitals without using PHI. METHODS: We performed a database linkage study utilizing a sequential direct + probabilistic linkage approach with records from 31 hospitals contributing to VPS and PHIS for patients discharged between January 1, 2017 and December 31, 2022. Using directly linked records as a reference, we assessed the accuracy of probabilistically linked pairs with data from four hospitals by describing the percent of false-negative and false-positive links. We also compared demographic and clinical variables between linked and unlinked records using Cohen's Effect size (CES). RESULTS: We obtained 337,836 VPS and 3,515,595 PHIS records without PHI. In total, we linked 319,955 of 337,836 (94.7%) VPS records. Direct linkage contributed 274,345 of 319,955 (85.7%) of all record linkages. Probabilistic linkage contributed 45,610 of 319,955 (14.3%) of all record linkages. Assessment of the probabilistic linkage found 0.21% false-negative links and no false-positive links. We found negligible imbalance by CES for gender (% female in linked vs. unlinked: 44.8% vs. 43.6%, CES 0.024), age in years (median [interquartile range (IQR)]: 5.1 [1.21-13.22] vs. 5.53 [1.53-13.38], CES 0.054), Pediatric Risk of Mortality 3 score (median [IQR]: 0.44 [0.3-0.9] vs. 0.37 [0.29-1.02], CES 0.096), or days in PICU (median [IQR]: 1.55 [0.8-3.47] vs. 1.33 [0.79-3.45], CES 0.031). CONCLUSIONS: Using a combined direct and probabilistic linkage approach, we created a highly accurate linkage VPS and PHIS database records from 31 hospitals without using PHI. This combined database can be used to create novel datasets for PICU research.
31 May 2026
Read appraisal →Blood advances
Refining busulfan exposure enhances pediatric ALL HSCT outcomes: insights from the International FORUM study
The optimal busulfan exposure window in pediatric patients with acute lymphoblastic leukemia (ALL) undergoing allogeneic hematopoietic stem cell transplantation (HSCT) remains to be defined. We identify this window for patients receiving busulfan within the prospective international, randomized controlled phase 3 ALLSCTped 2012 FORUM trial. We included 145 participants receiving fludarabine-busulfan-thiotepa conditioning, with available busulfan plasma levels. Busulfan exposure was estimated using a validated pediatric population pharmacokinetic model. Primary outcomes were event-free survival (EFS) and graft-versus-host disease-free relapse-free survival (GRFS). Patients were aged between 0.5 and 19.5 years, with a median follow-up of 5.0 years. The optimal busulfan exposure was defined as area under busulfan concentration curve (cAUC) of 73.3 to 98.0 mg.h/L based on EFS and GRFS. Patients with nonoptimal exposure had lower EFS (hazard ratio [HR], 1.93; p = 0.008) and GRFS (HR, 2.01; p = 0.002). Underexposure (cAUC <73.3 mg.h/L) was associated with higher relapse rates (HR, 1.93; p = 0.019), and overexposure (cAUC >98.0 mg.h/L) with an increased risk of treatment-related toxicities and graft-versus-host disease. Patients with optimal busulfan exposure showed no differences in EFS, GRFS, overall survival, or relapse with post hoc matched total-body irradiation (TBI) recipients (n = 51 in each group). This study identifies a favorable busulfan exposure window for pediatric patients with ALL undergoing HSCT from an HLA-matched donor. Therapeutic drug monitoring for optimized personalized busulfan dosing improves HSCT outcomes and might be validated for use as an alternative to irradiation. This trial was registered at EudraCT as 2012-003032-22 and on www.ClinicalTrials.gov as NCT01949129.
28 May 2026
Read appraisal →European journal of pediatrics
Pediatric Trauma Score (PTS) combined with blood lactate measurement provides clinical treatment guidance and prognosis prediction for children with compound injuries: a prospective study
UNLABELLED: Compound injuries in children are the leading cause of death and disability, and early and accurate assessment is crucial to optimize treatment. This study aimed to explore the clinical value of Pediatric Trauma Score (PTS) combined with blood lactate measurement in the triage, treatment guidance and prognosis prediction of pediatric compound injuries. From January 2023 to December 2024, a randomized, single-blind controlled trial was conducted in the emergency department of Hebei Provincial Children's Hospital (the only tertiary pediatric medical center in Hebei Province), China. A total of 546 children with compound injuries who presented to the hospital were included and randomly divided into the intervention group (n = 273, managed by PTS combined with dynamic monitoring of blood lactate) and the control group (n = 273, managed by PTS only). The main outcomes were the timeliness of rescue (time to critical intervention) and the accuracy of prognosis prediction (predictive effectiveness of mortality and major complications). Secondary outcomes included emergency department length of stay, unplanned Intensive Care Unit (ICU) admission, and 30-day complication rate. The median time from admission to initiation of key interventions was significantly shorter in the intervention group compared with the control group (45 [interquartile range (IQR): 30-65] min vs. 68 [IQR: 45-95] min, P < 0.001). The area under the receiver operating characteristic (ROC) curve (AUC) of the combined indicator (PTS + initial lactate) to predict 30-day mortality was 0.936 (95% CI: 0.902-0.970), which was significantly higher than PTS alone (AUC: 0.812, P < 0.001) or initial lactate (AUC: 0.855, P = 0.002). The emergency department length of stay, unplanned ICU admission rate and 30-day complication rate of the intervention group were significantly lower than those of the control group (all P < 0.05). Dynamic monitoring showed that 6-h lactate clearance < 30% was a strong independent predictor of the occurrence of multiple organ dysfunction syndrome (MODS) (odds ratio (OR) = 5.42, 95% CI: 2.88-10.21,P < 0.001. CONCLUSION: The combined application of PTS and blood lactate integrates physiological status and metabolic information, which can significantly improve the accuracy of early triage of pediatric compound injuries, guide the implementation of rescue measures, and effectively predict prognosis through dynamic monitoring, providing a reliable basis for precise personalized management. WHAT IS KNOWN: • Compound injuries in children are the leading cause of death and disability, and early and accurate assessment is crucial to optimize treatment. WHAT IS NEW: • The combined application of the Pediatric Trauma Score (PTS) and blood lactate signifi cantly improves the accuracy of early triage and 30-day mortality prediction, shortens the time to critical intervention, and reduces unplanned ICU admission and 30-day complication rates in pediatric compound injuries. • Dynamic monitoring shows that 6-hour lactate clearance 30% is a strong independent predictor of multiple organ dysfunction syndrome (MODS).
25 May 2026
Read appraisal →Child's nervous system : ChNS : official journal of the International Society for Pediatric Neurosurgery
The relation between cerebral arteriovenous malformations and heart diseases in the pediatric population: a systematic review and meta-analysis
Cerebral arteriovenous malformations (AVMs) and congenital heart diseases (CHDs) are rare, complex conditions that often present diagnostic and therapeutic challenges-especially when they coexist in pediatric patients. Though individually uncommon, their association raises important questions about shared developmental origins, systemic implications, and long-term outcomes. Understanding this relationship is crucial for improving early recognition, tailoring treatment strategies, and reducing morbidity and mortality in affected children. This systematic review and meta-analysis explored the relationship between AVMs and CHDs in the pediatric population, analyzing 139 studies published between 1971 and 2023. Together, these studies included data from 1042 patients. The co-occurrence of these two conditions highlights a potential interplay between cerebral and cardiac vascular development. By clarifying their association, this study aims to support earlier recognition, improve multidisciplinary management, and ultimately enhance clinical outcomes. The results revealed important patterns in how specific types and locations of AVMs relate to different forms of heart disease. AVMs located in infratentorial regions-such as the brainstem and cerebellum-were generally associated with lower risks of complications, while those in deep cerebral areas showed stronger links to adverse outcomes. Among the heart conditions evaluated, atrial septal defects (ASDs), cardiomyopathies, and high-output cardiac failure were most frequently associated with AVMs, suggesting overlapping embryologic and hemodynamic mechanisms. The most commonly reported complications included hydrocephalus, hemorrhage, and mortality. ROC curve analysis showed that mortality had the highest predictive value (AUC 0.62), followed by hydrocephalus (0.53) and hemorrhage (0.48). A composite risk model (AUC 0.59) suggested that combining clinical variables could improve prognostication. Neurological sequelae such as seizures, developmental delay, and microcephaly were frequent, particularly in hemorrhagic cases. Interestingly, in some patients, AVM treatment led to improvement in cardiac symptoms, suggesting a bidirectional relationship between cerebral and cardiac function. Despite variability in study quality, results were consistent across analyses, even when lower-quality studies were excluded. Most studies were rated moderate to high quality, though classification challenges were noted. Overall, the findings support a meaningful association between specific AVM and CHD subtypes and highlight the importance of early diagnosis and collaborative care involving multidisciplinary approach.
25 May 2026
Read appraisal →European journal of pediatrics
Piperacillin-tazobactam versus cefepime monotherapy in pediatric patients with febrile neutropenia: a systematic review and meta-analysis
UNLABELLED: The purpose of this study is to evaluate whether piperacillin-tazobactam therapy, compared with cefepime monotherapy, results in significant difference in treatment success, mortality, and duration outcomes in pediatric patients with febrile neutropenia (FN). A systematic review and meta-analysis of randomized controlled trials (RCTs) was conducted following PRISMA guidelines. PubMed, Embase, Scopus, Web of Science, and Cochrane CENTRAL were searched up to February 3. No starting limits for dates were used. We only included studies of pediatric patients with FN comparing piperacillin-tazobactam to cefepime monotherapy. Risk of bias was assessed using Cochrane RoB 2 tool. Meta-analysis was performed using random-effects model to calculate risk ratios (RR) and mean differences (MD). Five RCTs involving 470 episodes were included. The pooled analysis for treatment success showed no statistically significant difference between groups (RR = 1.02; 95% CI [0.89; 1.18]; P = 0.76) with low heterogeneity (I2 = 0.0%). No significant differences for mortality (RR = 2.09; 95% CI [0.62; 7.03]; P = 0.23; I2 = 0.0%). Duration of treatment was 0.9 day shorter for cefepime group (MD = 0.9 day; 95% CI [0.2; 1.6]; P < 0.1; I2 = 0%). CONCLUSION: No statistically significant difference was found in treatment success or mortality between the groups. Patients receiving cefepime had a treatment duration 0.9 days shorter than those receiving piperacillin-tazobactam, although this finding should be interpreted with caution. The available evidence remains limited. Further RCTs are needed to elucidate potential differences in treatment success, mortality, and duration between the drugs. REGISTRATION: PROSPERO (CRD420261296621). WHAT IS KNOWN: • Cefepime and piperacillin-tazobactam are widely utilized as empirical monotherapy for febrile neutropenia, but evidence regarding their comparative clinical efficacy and safety in children remains inconclusive. WHAT IS NEW: • This meta-analysis quantifies differences in treatment success, mortality and duration of treatment outcomes in pediatric patients with febrile neutropenia.
12 May 2026
Read appraisal →European journal of pediatrics
Impact of protocolized restrictive versus liberal/usual maintenance fluid strategy on fluid overload among mechanically ventilated children: an open-label randomized trial (ReLiSCh-II trial)
UNLABELLED: Fluid overload (FO) is associated with poor clinical outcomes among critically ill children. The objective of this trial was to assess the impact of a protocolized restrictive maintenance fluid strategy on FO among mechanically ventilated children. This open-label randomized controlled trial was conducted in the pediatric intensive care unit (PICU) of a tertiary care hospital in North India over 13 months (November 2023-November 2024). Hemodynamically stable mechanically ventilated children were randomized to protocolized restrictive (n = 64) (40-50% of maintenance fluids with diuretic infusion if FO% > 10%); and liberal/usual (n = 66) (70-80% of maintenance fluid) groups. The primary outcome was the proportion of children with cumulative FO% > 10% through day 5. Secondary outcomes were daily cumulative FO%; inferior vena cava variability index (∆IVC) and N-terminal pro-brain natriuretic peptide (NT-proBNP) levels at 48 h; safety parameters (requirement of fluid boluses or vasoactive drugs); 28-day ventilator and PICU-free days (VFDs and PFDs), and mortality. Significantly fewer children in the protocolized restrictive group had cumulative FO% > 10% than in the liberal/usual group (22% vs. 47%, p = 0.003). Also, the restrictive group had significantly lower daily cumulative FO% on the first 5 days. ∆IVC and NT-proBNP levels at 48 h, as well as safety parameters, were similar between the two groups. Protocolized restrictive and liberal/usual groups had similar VFDs [20 (8-24) vs. 16 (0-23), p = 0.076], PFDs [16 (3-21) vs. 13 (0-19), p = 0.071], and mortality (14% vs. 24%, p = 0.14). CONCLUSION: A protocolized restrictive maintenance fluid strategy resulted in significantly lower FO among hemodynamically stable, mechanically ventilated children without a measurable impact on short-term clinical outcomes. WHAT IS KNOWN: • Fluid overload (FO) is associated with poor clinical outcomes among critically ill mechanically ventilated children. WHAT IS NEW: • Among hemodynamically stable, mechanically ventilated children, a restrictive maintenance fluid strategy may be a useful intervention to limit FO and improve clinical outcomes in LMICs.
10 May 2026
Read appraisal →European journal of pediatrics
Evaluating the impact of simulation on patient outcomes in pediatric and neonatal critical care: a systematic review and critical appraisal of the evidence
UNLABELLED: While the literature widely supports a positive relationship between simulation-based education (SBE) and learning outcomes, its impact on patient outcomes remains less clearly understood. Our aim was to comprehensively survey the landscape of simulation-based research (SBR) that evaluates patient outcomes (Kirkpatrick Level 4) in the context of pediatric and neonatal critical care. A systematic search of MEDLINE, Cochrane Library, CINAHL, and ERIC was conducted through December 2024. We included RCTs, non-RCTs, and before-after studies focusing on Kirkpatrick Level 4 outcomes. Quality was appraised using the RoB 2 and ROBINS-I tools. A total of 2481 articles were screened. Sixteen studies met the inclusion criteria. Most were prospective (63%) and single-center (69%), with only three RCTs (19%). All included studies (100%) reported Level 4 outcomes; however, a critical distinction emerged between system-level and patient-level results. While 75% (12/16) of studies reported positive impacts on Level 4a (system processes), such as protocol adherence or response times, only 50% (8/16) demonstrated significant improvements in Level 4b (direct patient outcomes), such as mortality or complication rates. In addition, all included studies were judged to have a high or critical risk of bias. CONCLUSIONS: Although SBE effectively optimizes clinical processes (Level 4a), a significant evidence gap remains regarding its direct impact on patient health (Level 4b). Current SBR often lacks the methodological rigor-specifically the use of randomized designs-needed to isolate SBE as the primary driver of clinical improvement. Future research must prioritize high-quality, multicenter trials targeting patient-oriented metrics to bridge this translational gap. WHAT IS KNOWN: • SBE has been extensively developed in pediatric and neonatal critical care settings; however, its impact on healthcare professional training and on patient outcomes remains less well understood. WHAT IS NEW: • There is a scarcity of rigorous Level 4 evidence linking SBE to patient outcomes in pediatric and neonatal critical care. • We provide a methodological roadmap advocating for mixed-methods and multicenter designs to bridge this clinical evidence gap.
1 May 2026
Read appraisal →Renal failure
Explainable machine learning using urinary metabolomics to predict pediatric sepsis-associated acute kidney injury: a two-center prospective observational study
Sepsis-induced acute kidney injury (S-AKI) is a common and serious complication in critically ill children with a poor prognosis, and its early and accurate prediction remains challenging due to the lack of reliable biomarkers. Urinary small-molecule metabolomics offers a promising approach to capture the dynamic metabolic changes during the progression of S-AKI. In this two-center prospective observational study, we enrolled 360 children from both centers. Urine samples were collected within 24h after hospitalized children diagnosed with sepsis, stored at -80 °C, and analyzed using gas chromatography-mass spectrometry (GC-MS). Based on urinary metabolic fingerprints (U-MF), we developed and validated a machine learning model for early prediction of S-AKI. The Shapley Additive Explanations (SHAP) algorithm was applied to visually explain the optimal model. A panel of 10 metabolites was selected as common discriminative features. Among the 4 machine learning models evaluated, the support vector machine (SVM) demonstrated the best performance in both the discovery cohort (AUC 0.94, 95% CI: 0.91-0.98) and the external validation cohort (AUC 0.89, 95% CI: 0.82-0.96), enabling early prediction of S-AKI within 24 h. Furthermore, the U-MF panel was integrated into an open-access online platform to facilitate clinical translation. Our findings suggest that U-MF combined with machine learning holds promise as a robust and noninvasive approach with potential utility for early prediction of S-AKI in pediatric patients.
24 Apr 2026
Read appraisal →