Treatment and mortality of hemophagocytic lymphohistiocytosis in critically ill children: A systematic review and meta-analysis.

OBJECTIVE: Risk factors of mortality in critically ill children with hemophagocytic lymphohistiocytosis (HLH) are not well described. This systematic review aims to determine overall mortality of critically ill children with HLH, and describes etiologies, treatment, and pediatric intensive care unit (PICU) support employed. DATA SOURCES: PubMed, Embase, Web of Science, CINAHL, and Cochrane Library from inception until February 28, 2022. STUDY SELECTION: Observational studies and randomized controlled trials reporting children aged 18 years or below, diagnosed with HLH and admitted to the PICU. DATA EXTRACTION: Etiologies, treatment modalities, PICU therapies, and mortality outcomes were summarized. Random-effects meta-analysis was performed. DATA SYNTHESIS: Total 36 studies (total patients = 493, mean age: 49.5 months [95% confidence interval (CI): 30.9-79.5]) were included. Pooled mortality rate was 32.6% (95% CI: 23.4-42.4). The most frequent etiologies for HLH were infections (53.3%) and primary HLH (12.8%), while the remaining cases were due to other causes of secondary HLH, including autoimmune diseases, malignancy, and drug-induced and idiopathic HLH. Pooled mortality rate was higher in primary than secondary HLH (72.2%, 95% CI: 57.8-84.5 vs. 23.9%, 95% CI: 14.4-35.02; p < .01). Univariate analysis found that treatment with etoposide was associated with higher mortality, while intravenous immunoglobulins (IVIGs) were associated with lower mortality. Conversely, multivariable analysis adjusted for etiology demonstrated no association between etoposide and IVIG use, and mortality. Twenty-one studies (total patients = 278) had detailed information on PICU therapies. Mechanical ventilation (MV), continuous renal replacement therapy, and inotropes were used in 107 (38.5%), 66 (23.7%), and 51 patients (18.3%), respectively. Need for MV was associated with increased risk of mortality (mean difference = 28%, 95% CI: 9-47). CONCLUSION: Critically ill children with HLH have high mortality rates and require substantial PICU support. Collaborative work between multiple centers with standardized data collection can potentially provide more robust data.

Biomechanical Effects of Prophylactic Knee Bracing on Anterior Cruciate Ligament Injury Risk: A Systematic Review.

OBJECTIVE: Prophylactic knee braces (PKBs) are widely used by athletes in pivoting and landing sports and have the potential to influence knee movement and alignment, thus modulating anterior cruciate ligament (ACL) injury risk. This systematic review analyses current evidence on the biomechanical effects that PKBs have in the prevention of ACL injuries. DATA SOURCES: The review was conducted in accordance with Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines. Searches were conducted on PubMed, Web of Science, Scopus, Ovid MEDLINE, EMBASE, Cochrane, and CINAHL for studies published from inception until May 31, 2021. Included studies assessed the effects of PKBs on biomechanical variables associated with ACL injuries in landing or pivoting tasks, comparing between braced and unbraced conditions. MAIN RESULTS: A total of 234 articles were identified; from which, 14 controlled, laboratory, biomechanical studies were included in this review. The effects of PKBs on knee biomechanics could be divided into kinematic variables in the coronal, sagittal, and transverse planes; and common kinetic variables, such as ground reaction force (GRF) and ACL load/strain. Also, PKBs were found to have protective effects in coronal and transverse plane kinematics, but results in the sagittal plane were inconclusive. Assessing knee kinetics, PKBs were advantageous in decreasing ACL load/strain but had no significant effect on GRF. CONCLUSIONS: Prophylactic knee braces may serve to reduce ACL injury risk by modulating knee coronal and transverse plane movements and ACL load/strain during high-risk maneuvres. Precise recommendations are limited by study heterogeneity. More prospective studies are needed to assess ACL injury risk during high-risk sports using specific PKBs.