Fatigue recovery and connected factors following paediatric concussion.

OBJECTIVE: Using a biopsychosocial framework and the three-factor fatigue model, we aimed to (1) plot recovery of fatigue over the 3 months following paediatric concussion and (2) explore factors associated with persisting fatigue during the first 3 months postconcussion. METHODS: 240 children and adolescents aged 5-18 years (M=11.64, SD=3.16) completed assessments from time of injury to 3 months postinjury. Separate linear mixed effects models were conducted for child and parent ratings on the PedsQL-Multidimensional Fatigue Scale to plot recovery across domains (General, Cognitive, Sleep/Rest) and Total fatigue, from 1 week to 3 months postinjury. Two-block hierarchical regression analyses were then conducted for parent and child ratings of fatigue at each time point, with age, sex and acute symptoms in block 1 and child and parent mental health variables added to block 2. RESULTS: There was a significant reduction in both child and parent ratings across the 3 months postinjury for all fatigue domains (all p<0.001). For both child and parent fatigue ratings, child mental health was the most significant factor associated with fatigue at all time points. Adding child and parent mental health variables in the second block of the regression substantially increased the variance explained for both child and parent ratings of fatigue. CONCLUSION: Our findings confirm that fatigue improves during the first 3 months postconcussion and highlights the importance of considering child and parent mental health screening when assessing patients with persisting postconcussive symptoms.

Arthroscopic treatment of type II superior labral anterior to posterior (SLAP) lesions in a younger population: minimum 2-year outcomes are similar between SLAP repair and biceps tenodesis.

PURPOSE: Compared to a relatively older population over 30-40 years of age, the efficacy of biceps tenodesis for type II SLAP lesions in a younger population is not well studied. The purpose of this study was to compare outcomes between biceps tenodesis and labral repair for type II SLAP lesions in a young active population. METHODS: Patients aged 15-40 who underwent primary arthroscopic biceps tenodesis or SLAP repair for type II SLAP tears between 2009 and 2016 were included. Shoulders with intraarticular chondral damage, full thickness rotator cuff tear, rotator cuff repair, labral repair outside of the superior labrum, bony subacromial decompression, and acromioclavicular joint resection were excluded. Patient-reported outcomes were evaluated using the American Shoulder and Elbow Surgeons (ASES) score, Disabilities of the Arm, Shoulder, and Hand Sports/Performing Arts Module (DASH-sport), visual analog scale (VAS) for pain, and satisfaction. Return to sport rates were also recorded. RESULTS: Fifty-three patients (20 tenodesis, 33 repair) were available for minimum 2-year follow-up. Postoperatively, there were no significant differences in mean ASES, DASH-sport, VAS, and satisfaction between groups [ASES: tenodesis 86.3 vs. repair 86.4 (n.s.); DASH-sport: 11.0 vs. 22.5 (n.s.); VAS: 1.85 vs. 1.64 (n.s.); satisfaction: 8.50 vs. 8.00 (n.s.)]. Rate of return to pre-injury level of performance/competition in sport/physical activity was also similar between groups [tenodesis 63% vs. repair 50% (n.s.)]. CONCLUSIONS: In a young active population, primary arthroscopic biceps tenodesis is a viable surgical alternative to labral repair for type II SLAP lesions. The results of this study suggest that indications for arthroscopic tenodesis can safely be expanded to a younger patient group than has previously been demonstrated in the literature. LEVEL OF EVIDENCE: III.

Use of the sport concussion assessment tools in the emergency department to predict persistent post-concussive symptoms in children.

AIM: The Sport Concussion Assessment Tool v3 (SCAT3) and its child version (ChildSCAT3) are composite tools including a symptom scale, a rapid cognitive assessment (standardised assessment of concussion (SAC)) and the modified Balance Error Scoring System (mBESS). It is unclear whether their use for the acute assessment of paediatric concussion in the emergency department (ED) may help predict persistent post-concussive symptoms (PPCS). We aim to assess the predictive value of the main SCAT3/ChildSCAT3 components for PPCS when applied in the ED. METHODS: A single-site, prospective longitudinal cohort study of children aged 5-18 years assessed within 48 h of their concussion at the ED of a state-wide tertiary paediatric hospital and followed up at the affiliated concussion clinic, between November 2013 and August 2017. PPCS was defined as ≥2 new or worsening symptoms at 1 month post-injury using the Post-Concussive Symptom Inventory. RESULTS: Of the 370 children enrolled, 213 (57.7% <13 years old) provided complete data. Of these, 34.7% had PPCS at 1 month post-injury (38.2% of children <13 years and 30.0% ≥13 years of age, P = 0.272). The adjusted ORs from multiple logistic regression models, for number and severity of symptoms, and for the SAC and mBESS performance in both the ChildSCAT3/SCAT3, were all not significant. The area under the curve of receiver operator characteristic curves for all analysed ChildSCAT3/SCAT3 components was below 0.6. CONCLUSIONS: Although SCAT3 and ChildSCAT3 are recommended tools to assist with concussion diagnosis and monitoring of patient recovery, their use in the ED does not seem to help predict PPCS.

Acute cognitive postconcussive symptoms follow longer recovery trajectories than somatic postconcussive symptoms in young children.

Objective: To investigate somatic and cognitive postconcussive symptoms (PCS) using the symptom evaluation subtest (cSCAT3-SE) of the Child Sports Concussion Assessment Tool 3 (Child SCAT) in tracking PCS up to 2 weeks postinjury.Methods: A total of 96 participants aged 5 to 12 years (Mage = 9.55, SD = 2.20) completed three assessment time points: 48 h postinjury (T0), 2 to 4 days postinjury (T1), and 2 weeks postinjury (T2). The Wilcoxon signed-rank test was used to analyze differences between cognitive and somatic symptoms over time, while the Friedman test was used to analyze differences within symptom type over time.Results: Cognitive PCS were found to be significantly higher than somatic PCS at all assessment time points and were also found to significantly decline from 4 days onwards postinjury; in contrast, somatic PCS significantly declined as early as 48 hpostinjury.Discussion: Differences between cognitive and somatic PCS emerge as early as a few days postinjury, with cognitive PCS being more persistent than somatic PCS across 2 weeks. Research in symptom-specific interventions may be of benefit in helping young children manage severe PCS as early as 2 weeks postinjury.

What Factors Predict Conversion to THA After Arthroscopy?

BACKGROUND: Failure of hip preservation to alleviate symptoms potentially subjects the patient to reoperation or conversion surgery to THA, adding recovery time, risk, and cost. A risk calculator using an algorithm that can predict the likelihood that a patient who undergoes arthroscopic hip surgery will undergo THA within 2 years would be helpful, but to our knowledge, no such tool exists. QUESTIONS: (1) Are there preoperative and intraoperative variables at the time of hip arthroscopy associated with subsequent conversion to THA? (2) Can these variables be used to develop a predictive tool for conversion to THA? MATERIALS AND METHODS: All patients undergoing arthroscopy from January 2009 through December 2011 were registered in our longitudinal database. Inclusion criteria for the study group were patients undergoing hip arthroscopy for a labral tear, who eventually had conversion surgery to THA. Patients were compared with a control group of patients who underwent hip arthroscopy for a labral tear but who did not undergo conversion surgery to THA during the same study period. Of the 893 who underwent surgery during that time, 792 (88.7%) were available for followup at a minimum of 2 years (mean, 31.1 ± 8.1 years) and so were considered in this analysis. Multivariate regression analyses of 41 preoperative and intraoperative variables were performed. Using the results of the multivariate regression, we developed a simplified calculator that may be helpful in counseling a patient regarding the risk of conversion to THA after hip arthroscopy. RESULTS: Variables simultaneously associated with conversion to THA in this model were older age (rate ratio, 1.06; 95% CI, 1.03-1.08; p < 0.0001), lower preoperative modified Harris hip score (rate ratio [RR], 0.98; 95% CI, 0.96-0.99; p = 0.0003), decreased femoral anteversion (RR, 0.97; 95% CI, 0.94-0.99; p = 0.0111), revision surgery (RR, 2.4; 95% CI, 1.15-5.01; p = 0.0193), femoral Outerbridge Grades II to IV (Grade II: RR, 2.23 [95% CI, 1.11-4.46], p = 0.023; Grade III: RR, 2.17, [95% CI, 1.11-4.23], p = 0.024; Grade IV: RR, 2.96 [95% CI, 1.34-6.52], p = 0.007), performance of acetabuloplasty (RR, 1.83; 95% CI, 1.03-3.24; p = 0.038), and lack of performance of femoral osteoplasty (RR, 0.62; 95% CI, 0.36-1.06; p = 0.081). Using the results of the multivariate regression, we developed a simplified calculator that may be helpful in counseling a patient regarding the risk of conversion surgery to THA after hip arthroscopy. CONCLUSION: Multiple risk factors have been identified as possible risk factors for conversion to THA after hip arthroscopy. A weighted calculator based on our data is presented here and may be useful for predicting failure after hip arthroscopy for labral treatment. Determining the best candidates for hip preservation remains challenging; careful attention to long-term followup and identifying characteristics associated with successful outcomes should be the focus of further study. LEVEL OF EVIDENCE: Level III, therapeutic study.

Survey mode influence on patient-reported outcome scores in orthopaedic surgery: telephone results may be positively biased.

PURPOSE: Patient-reported outcome (PRO) scores are used to evaluate treatment modalities in orthopaedic surgery. The method of PRO collection may introduce bias to reported surgical outcomes due to the presence of an interviewer. This study evaluates post-operative PROs for variation of outcomes between survey methods-in-person, online, or telephone. METHODS: From 2008 to 2011, 456 patients underwent arthroscopic surgical treatment for acetabular labral tears. All pre-operative surveys were completed in the clinic during pre-operative visit. Two-year follow-up questionnaires were completed by 385 (84 %) patients. The PRO data were prospectively collected pre- and post-operatively using five tools: modified Harris Hip Score (mHHS), Hip Outcome Score Activities of Daily Living (HOS-ADLS), Hip Outcome Score Sports-Specific Subscale (HOS-SSS), Non-Arthritic Hip Score (NAHS), and visual analog scale. Patients were grouped according to method of 2-year follow-up: in-person during follow-up visit (102 patients, 26 %), online by email prompt (138 patients, 36 %), or telephone with an interviewer (145 patients, 38 %). RESULTS: Pre-operative baseline PRO scores demonstrated no statistically significant difference between groups for mHHS, HOS-ADLS, HOS-SSS, and NAHS. Two-year post-operative PRO scores obtained by telephone were statistically greater than scores obtained in-person or online for mHHS (p < 0.001), HOS-ADLS (p < 0.001), and HOS-SSS (p < 0.01). CONCLUSION: This study demonstrates higher patient-reported outcome scores and greater improvement by telephone surveys compared to in-person or online. The variation of results between collection methods is indicative of a confounding variable. Clinically, it is important to understand these confounding variables in order to assess patient responses and guide treatment. LEVEL OF EVIDENCE: IV.

Outcomes of Revision Hip Arthroscopy: 2-Year Clinical Follow-up.

PURPOSE: To evaluate clinical outcomes, pain, and patient satisfaction following revision hip arthroscopy with a minimum 2-year follow-up. METHODS: From April 2008 to October 2011, data were prospectively collected on all patients undergoing revision hip arthroscopy. All patients were assessed pre- and postoperatively with 4 patient-reported outcome (PRO) measures: the modified Harris hip score (mHHS), nonarthritic hip score (NAHS), hip outcome score-activities of daily living (HOS-ADL), and hip outcome score-sport-specific subscales (HOS-SSS). Pain was estimated on the visual analog scale (VAS). Patient satisfaction was measured on a scale from 0 to 10. The number of patients who underwent subsequent revision arthroscopy or total hip arthroplasty during the study period is also reported. RESULTS: Eighty-seven patients underwent revision hip arthroscopy during the study period. Seventy (80.5%) patients were included in our study. Average follow-up time was 28 months (range, 20 to 47.4 months). In terms of residual femoroacetabular impingement morphology, 45.7% of patients had preoperative alpha angles ≥ 55°, and 7.14% of patients had a lateral center-edge angle ≥ 40°. The score improvement from preoperative to 2-year follow-up was 57.84 to 73.65 for mHHS, 62.79 to 83.04 for HOS-ADL, 37.33 to 54.93 for HOS-SSS, and 55.65 to 70.79 for NAHS. VAS decreased from 6.72 to 4.08. All scores demonstrated statistically significant improvement (P < .001). Overall patient satisfaction was 7.67. Our success rate was 74.58%. Ten (14.29%) patients underwent total hip arthroplasty during the study period. Our hip survivorship was 85.7%. Five (7.14%) patients underwent secondary revision hip arthroscopy during the study period. We found an overall minor complication rate of 10%. CONCLUSIONS: Revision hip arthroscopy for all procedures performed on aggregate has improved clinical outcomes for all PROs, high survivorship, and high patient satisfaction scores at short-term follow-up. Patients should be counseled regarding the potential progression of degenerative change leading to arthroplasty and the potential for revision surgery. LEVEL OF EVIDENCE: Level IV retrospective case series.

Labral injury: radiographic predictors at the time of hip arthroscopy.

PURPOSE: The purpose of this study was to investigate the influence of multiple demographic and radiographic findings on the size of labral tears identified at the time of hip arthroscopy. METHODS: Data were prospectively collected for patients treated with arthroscopic labral repair or debridement from February 2008 to August 2011. Preoperative radiographic and demographic data were collected for 392 patients during the study period. Exclusion criteria included revision surgery and previous hip conditions. An anteroposterior pelvic view, 45° Dunn view, and false-profile view were used to measure Tönnis grade, neck-shaft angle, alpha angle, lateral center edge angle (LCEA), anterior center edge angle (ACEA), acetabular inclination, and the extent of crossover sign when present. At the time of surgery, labral tear size and location were documented for all patients, using traditional acetabular clock face nomenclature for sizing. A multiple linear regression analysis was then performed to assess the correlation of radiographic and demographic findings with the size of the labral tear. RESULTS: Regression analysis displayed statistical significance for sex (P < .0001), age (P < .0001), and alpha angle (P = .005) with labral tear size. For female patients, Tönnis grade (P = .0004) and neck-shaft angle (P = .004) correlated with labral tear size. This model accounted for only 26% of variation in labral tear size. CONCLUSIONS: Preoperative risk factors for the extent of labral tear size are male sex, increasing age, and increasing alpha angle. Labral tears were larger in female patients with higher Tönnis grades and lower neck-shaft angles. Measurements of acetabular coverage and version showed no correlation with labral tear size. The majority of labral tear size variation was not accounted for in this model. LEVEL OF EVIDENCE: Level IV, therapeutic case series.

A matched-pair controlled study of microfracture of the hip with average 2-year follow-up: do full-thickness chondral defects portend an inferior prognosis in hip arthroscopy?

PURPOSE: This study compared 2-year clinical outcomes in hip arthroscopy patients treated with microfracture to a matched control group without full-thickness chondral damage. METHODS: During the study period between June 2008 and July 2011, data were collected on all patients treated with hip arthroscopy who underwent microfracture. All patients were assessed pre- and postoperatively with 4 patient-reported outcome (PRO) measures. Pain was estimated on the visual analog scale (VAS), and satisfaction was measured on a scale from 0 to 10. A matched-pair group of patients who did not undergo microfracture was selected in a 1:2 ratio. Matching criteria were age within 5 years, sex, surgical procedures, and radiographic findings. RESULTS: Average follow-up for the study was 26.66 months (17.29 to 48.89 months). Forty-nine hips were included in the microfracture group and 98 hips were in entered in the nonmicrofracture group, with no significant difference in PRO scores preoperatively between the groups. Both groups had statistically significant postoperative improvement in all scores, and the average amount of change from preoperative to postoperative scores between the 2 groups was not statistically significantly different for any of the PRO scores. Most importantly, there was no statistically significant difference in postoperative PRO scores between the microfracture and control groups. Patient satisfaction was 6.9 for the microfracture group and 7.84 for the nonmicrofracture group, which was statistically significant (P < .05). When comparing patients who received acetabular microfracture to those who received femoral microfracture, both groups had similar preoperative and postoperative PRO scores, with no significant difference in the magnitude of change (delta) at final follow-up. CONCLUSIONS: Our study found that patients undergoing microfracture during hip arthroscopy did not show a statistically significant difference in PRO scores when compared with a matched-pair control group at an average of 2 years of follow-up. Both groups showed significant improvement in all PRO scores. LEVEL OF EVIDENCE: Level III, matched case-control study.

The role of subcutaneous fat and BMI in predicting surgical outcomes and patient reported outcomes in robotic-assisted total hip arthroplasty.

Background: The purpose of this study was to assess if subcutaneous fat (SCF) or BMI is a predictor of surgical complications and patient reported outcomes in patients undergoing robotic-assisted total hip arthroplasty (THA). Methods: Patients who underwent robotic-assisted primary THAs at one institution between 2018 and 2020 were included in this retrospective cohort study. Prior to surgery, computed tomography (CT) was used to measure SCF in the posterolateral quadrant of the hip. SCF was measured 3 centimeters (cm) proximal to the greater trochanter (PGT) and 3 cm inferior to the distal tip of the greater trochanter (DGT).Measurements were normalized to the size of the patient's bony anatomy by dividing the subcutaneous fat area measurement by the transverse diameter of the femur 10 cm inferior to the tip of the greater trochanter. Patients were divided into quintiles determined by SCF distribution around the mean (groups 1-5) and BMI (BMI<25, BMI 25-29.9, BMI 30-34.9, BMI 35-39.9, and >40). Ninety day outcomes and PROMIS (Patient Reported Outcome Measures Information System) scores were acquired from the Michigan Arthroplasty Registry Collaborative Quality Initiative (MARCQI) database preoperatively, at 14-112 days post-operative and at the latest follow up. Results: There were 175 patients identified with a mean age of 63.83 years (range 27-89) and a mean BMI of 30.73kg/m2 (range 18.2-48.4). Interclass correlation coefficient was greater than 0.9 in all PGT, DGT, and GT measurements. Analysis of Variance (ANOVA) found there was a significantly shorter time from incision to closure in quintiles 1 and 3 when compared to the SCF quintile 5 (p<0.05) and that there was a significantly shorter time from incision to closure in BMI categories 1, 2, and 3 when compared to BMI category 5 (BMI > 40). There were no differences between SCF and BMI as predictive of length of stay, transfusion status, infection, or PROMIS scores. Conclusion: It can be concluded that hip SCF on axial CT images can reliably measure SCF and is predictive of time from incision to closure, but it does not show a significant difference in predicting the length of stay, infection, or PROMIS scores when compared to BMI.

White matter fiber morphology in persisting postconcussive symptoms and posttraumatic headache after pediatric concussion: a fixel-based analysis.

OBJECTIVE: Posttraumatic headache (PTH) represents the most common acute and persistent postconcussive symptom (PCS) in children after concussion, yet there remains a lack of valid and objective biomarkers to facilitate risk stratification and early intervention in this patient population. Fixel-based analysis of diffusion-weighted imaging, which overcomes constraints of traditional diffusion tensor imaging analyses, can improve the sensitivity and specificity of detecting white matter changes postconcussion. The aim of this study was to investigate whole-brain and tract-based differences in white matter morphology, including fiber density (FD) and fiber bundle cross-section (FC) area in children with PCSs and PTH at 2 weeks after concussion. METHODS: This prospective longitudinal study recruited children aged 5-18 years who presented to the emergency department of a tertiary pediatric hospital with a concussion sustained within the previous 48 hours. Participants underwent diffusion-weighted MRI at 2 weeks postinjury. Whole-brain white matter statistical analysis was performed at the level of each individual fiber population within an image voxel (fixel) to compute FD, FC, and a combined metric (FD and bundle cross-section [FDC]) using connectivity-based fixel enhancement. Tract-based Bayesian analysis was performed to examine FD in 23 major white matter tracts. RESULTS: Comparisons of 1) recovered (n = 27) and symptomatic (n = 16) children, and those with 2) PTH (n = 13) and non-PTH (n = 30; overall mean age 12.99 ± 2.70 years, 74% male) found no fiber-specific white matter microstructural differences in FD, FC, or FDC at 2 weeks postconcussion, when adjusting for age and sex (family-wise error rate corrected p value > 0.05). Tract-based Bayesian analysis showed evidence of no effect of PTH on FD in 10 major white matter tracts, and evidence of no effect of recovery group on FD in 3 white matter tracts (Bayes factor < 1/3). CONCLUSIONS: Using whole-brain fixel-wise and tract-based analyses, these findings indicate that fiber-specific properties of white matter microstructure are not different between children with persisting PCSs compared with recovered children 2 weeks after concussion. These data extend the limited research on white matter fiber-specific morphology while overcoming limitations inherent to traditional diffusion models. Further validation of our findings with a large-scale cohort is warranted.

Psychological Predictors of Mental Health Difficulties After Pediatric Concussion.

Children often experience mental health difficulties after a concussion. Yet, the extent to which a concussion precipitates or exacerbates mental health difficulties remains unclear. This study aimed to examine psychological predictors of mental health difficulties after pediatric concussion. Children (5 to <18 years of age, M = 11.7, SD = 3.3) with concussion were recruited in a single-site longitudinal prospective cohort study conducted at a tertiary children's hospital (n = 115, 73.9% male). The primary outcomes included internalizing (anxious, depressed, withdrawn behaviors), externalizing (risk-taking, aggression, attention difficulties), and total mental health problems, as measured by the Child Behavior Checklist at 2 weeks (acute) and 3 months (post-acute) after concussion. Predictors included parents' retrospective reports of premorbid concussive symptoms (Post-Concussion Symptom Inventory; PCSI), the child and their family's psychiatric history, child-rated perfectionism (Adaptive-Maladaptive Perfectionism Scale), and child-rated resilience (Youth Resilience Measure). Higher premorbid PCSI ratings consistently predicted acute and post-acute mental health difficulties. This relationship was significantly moderated by child psychiatric history. Furthermore, pre-injury learning difficulties, child psychiatric diagnoses, family psychiatric history, lower resilience, previous concussions, female sex, and older age at injury were associated with greater mental health difficulties after concussion. Pre-injury factors accounted for 23.4-39.9% of acute mental health outcomes, and 32.3-37.8% of post-acute mental health outcomes. When acute mental health was factored into the model, a total of 47.0-68.8% of variance was explained by the model. Overall, in this sample of children, several pre-injury demographic and psychological factors were observed to predict mental health difficulties after a concussion. These findings need to be validated in future research involving larger, multi-site studies that include a broader cohort of children after concussion.

Caspase-2 is essential for proliferation and self-renewal of nucleophosmin-mutated acute myeloid leukemia.

Mutation in nucleophosmin (NPM1) causes relocalization of this normally nucleolar protein to the cytoplasm (NPM1c+). Despite NPM1 mutation being the most common driver mutation in cytogenetically normal adult acute myeloid leukemia (AML), the mechanisms of NPM1c+-induced leukemogenesis remain unclear. Caspase-2 is a proapoptotic protein activated by NPM1 in the nucleolus. Here, we show that caspase-2 is also activated by NPM1c+ in the cytoplasm and DNA damage-induced apoptosis is caspase-2 dependent in NPM1c+ but not in NPM1wt AML cells. Strikingly, in NPM1c+ cells, caspase-2 loss results in profound cell cycle arrest, differentiation, and down-regulation of stem cell pathways that regulate pluripotency including impairment of the AKT/mTORC1 pathways, and inhibition of Rictor cleavage. In contrast, there were minimal differences in proliferation, differentiation, or the transcriptional profile of NPM1wt cells lacking caspase-2. Our results show that caspase-2 is essential for proliferation and self-renewal of AML cells expressing mutated NPM1. This study demonstrates that caspase-2 is a major effector of NPM1c+ function.

Capillary blood protein markers of posttraumatic headache in children after concussion.

OBJECTIVE: Posttraumatic headache (PTH) represents the most common acute and persistent symptom in children after concussion, yet there is no blood protein signature to stratify the risk of PTH after concussion to facilitate early intervention. This discovery study aimed to identify capillary blood protein markers, at emergency department (ED) presentation within 48 hours of concussion, to predict children at risk of persisting PTH at 2 weeks postinjury. METHODS: Capillary blood was collected using the Mitra Clamshell device from children aged 8-17 years who presented to the ED of the Royal Children's Hospital, Melbourne, Australia, within 48 hours of sustaining a concussion. Participants were followed up at 2 weeks postinjury to determine PTH status. PTH was defined per clinical guidelines as a new or worsened headache compared with preinjury. An untargeted proteomics analysis using data-independent acquisition (DIA) was performed. Principal component analysis and hierarchical clustering were used to reduce the dimensionality of the protein dataset. RESULTS: A total of 907 proteins were reproducibly identified from 82 children within 48 hours of concussion. The mean participant age was 12.78 years (SD 2.54 years, range 8-17 years); 70% of patients were male. Eighty percent met criteria for acute PTH in the ED, while one-third of participants with follow-up experienced PTH at 2 weeks postinjury (range 8-16 days). Hemoglobin subunit zeta (HBZ), cystatin B (CSTB), beta-ala-his dipeptidase (CNDP1), hemoglobin subunit gamma-1 (HBG1), and zyxin (ZYX) were weakly associated with PTH at 2 weeks postinjury based on up to a 7% increase in the PTH group despite nonsignificant Benjamini-Hochberg adjusted p values. CONCLUSIONS: This discovery study determined that no capillary blood protein markers, measured at ED presentation within 48 hours of concussion, can predict children at risk of persisting PTH at 2 weeks postinjury. While HBZ, CSTB, CNDP1, HBG1, and ZYX were weakly associated with PTH at 2 weeks postinjury, there was no specific blood protein signature predictor of PTH in children after concussion. There is an urgent need to discover new blood biomarkers associated with PTH to facilitate risk stratification and improve clinical management of pediatric concussion.

Caspase-2 is essential for proliferation and self-renewal of nucleophosmin-mutated acute myeloid leukemia.

Mutation in nucleophosmin (NPM1) causes relocalization of this normally nucleolar protein to the cytoplasm ( NPM1c+ ). Despite NPM1 mutation being the most common driver mutation in cytogenetically normal adult acute myeloid leukemia (AML), the mechanisms of NPM1c+-induced leukemogenesis remain unclear. Caspase-2 is a pro-apoptotic protein activated by NPM1 in the nucleolus. Here, we show that caspase-2 is also activated by NPM1c+ in the cytoplasm, and DNA damage-induced apoptosis is caspase-2-dependent in NPM1c+ AML but not in NPM1wt cells. Strikingly, in NPM1c+ cells, loss of caspase-2 results in profound cell cycle arrest, differentiation, and down-regulation of stem cell pathways that regulate pluripotency including impairment in the AKT/mTORC1 and Wnt signaling pathways. In contrast, there were minimal differences in proliferation, differentiation, or the transcriptional profile of NPM1wt cells with and without caspase-2. Together, these results show that caspase-2 is essential for proliferation and self-renewal of AML cells that have mutated NPM1. This study demonstrates that caspase-2 is a major effector of NPM1c+ function and may even be a druggable target to treat NPM1c+ AML and prevent relapse.

Cerebral blood flow in children with persisting postconcussive symptoms and posttraumatic headache at 2 weeks postconcussion.

OBJECTIVE: Persisting postconcussive symptoms (pPCS), particularly headache, can significantly disrupt children's recovery and functioning. However, the underlying pathophysiology of these symptoms remains unclear. The goal in this study was to determine whether pPCS are related to cerebral blood flow (CBF) at 2 weeks postconcussion. The authors also investigated whether variations in CBF can explain the increased risk of acute posttraumatic headache (PTH) in female children following concussion. METHODS: As part of a prospective, longitudinal study, the authors recruited children 5-18 years old who were admitted to the emergency department of a tertiary pediatric hospital with a concussion sustained within 48 hours of admission. Participants underwent pseudocontinuous arterial spin labeling MRI at 2 weeks postconcussion to quantify global mean gray and white matter perfusion (in ml/100 g/min). Conventional frequentist analysis and Bayesian analysis were performed. RESULTS: Comparison of recovered (n = 26) and symptomatic (n = 12) groups (mean age 13.15 years, SD 2.69 years; 28 male) found no differences in mean global gray and white matter perfusion at 2 weeks postconcussion (Bayes factors > 3). Although female sex was identified as a risk factor for PTH with migraine features (p = 0.003), there was no difference in CBF between female children with and without PTH. CONCLUSIONS: Global CBF was not associated with pPCS and female PTH at 2 weeks after pediatric concussion. These findings provide evidence against the use of CBF measured by arterial spin labeling as an acute biomarker for pediatric concussion recovery.

A randomized controlled trial of SAFMEDS to improve chest radiograph interpretation among medical students.

RATIONALE AND OBJECTIVES: Junior doctors find chest radiograph (CXR) interpretation challenging, and commonly make diagnostic errors. The aim of this study was to evaluate the effectiveness of SAFMEDS in teaching undergraduate medical students to identify important chest abnormalities in radiology imaging. MATERIALS AND METHODS: A pragmatic randomized controlled trial design was utilized. Third-year medical students were randomly assigned to an intervention group (n = 20), who received the SAFMEDS intervention, or a control group (n = 20), who did not receive the intervention. Three participants (one intervention, two control) withdrew from participation. Percentage accuracy in CXR interpretation was assessed at three timepoints (baseline, post-test, and retention). A series of one-way between-subjects' analyses of covariance, with percentage accuracy at the pre-test timepoint entered as the covariate, were conducted. RESULTS: Large effect sizes of the SAFMEDS intervention were observed at post-test and retention (η2 = 0.67, η2 = 0.58 respectively), with the intervention group demonstrating significantly higher percentage accuracy in CXR interpretation as compared to the control group at both timepoints. Intervention group performance decreased by 5.26% (SD = 9.80) from post-test to retention. Twelve intervention group participants (63.2%) met the fluency criteria. Despite large effect sizes, there were no significant differences in post-test or retention performance between fluent and non-fluent participants (η2 = 0.17 and η2 = 0.2 respectively). CONCLUSION: SAFMEDS offers an effective adjunct to usual teaching. Future research could focus on examining the effect of fluency with a larger sample, in addition the expansion of the SAFMEDS approach, and its' application to other health profession populations.

Improving subacute management of post concussion symptoms: a pilot study of the Melbourne Paediatric Concussion Scale parent report.

Aim: To pilot a modification of the Post Concussion Symptom Inventory, the Melbourne Paediatric Concussion Scale (MPCS) and examine its clinical utility. Materials & methods: A total of 40 families of concussed children, aged 8-18 years, were recruited from the emergency department. Parent responses to the MPCS in the emergency department and 2-weeks post injury determined child symptomatic status. Association between MPCS symptom endorsement and symptomatic group status was examined. Results: All additional MPCS items were endorsed by at least 25% of the parents of symptomatic children at 2 weeks. MPCS items were classified into nine symptom domains, with most falling in mood, neurological, autonomic and vestibular domains. Conclusion: The additional items and domain classifications in the MPCS have the potential to improve subacute diagnostic precision, monitoring of clinical recovery and identification of appropriate interventions post pediatric concussion.

Evaluation of Genetic Polymorphisms of the Antioxidant Enzymes and Biomarkers of Oxidative Stress in Preterm Neonates With Respiratory Distress Syndrome Receiving External Surfactant.

Background: Preterm neonates, particularly extremely preterm, are susceptible to respiratory distress syndrome (RDS) due to surfactant deficiency. Single nucleotide polymorphisms (SNPs) in the antioxidant enzymes influence the balance between antioxidant and oxidative stress molecules. Objectives: To ascertain the role of SNPs of antioxidant enzymes and oxidative stress biomarkers in preterm neonates with RDS. Design: Observational, cross-sectional study. Methods: Preterm neonates diagnosed with RDS receiving external surfactant within 24 hours were considered as the cases and those without RDS were the control group. Umbilical cord blood and peripheral blood samples before administering surfactant (day 1), and on days 2 and 3 were collected. Plasma malondialdehyde, 8-hydroxy-2-deoxy guanosine (8-OH-dG), advanced oxidation protein products (AOPP), total antioxidant capacity (TAC), visfatin, reduced glutathione, and chaperonin 60 were evaluated using enzyme-linked immunosorbent assay. SNPs in manganese superoxide dismutase (MnSOD), copper/zinc superoxide dismutase (Cu/Zn SOD), glutathione peroxidase (GPX1 and GPX3), catalase (CAT), glutathione S-transferase (GSTP1) were evaluated using real-time polymerase-chain-reaction. The receiver-operating characteristics curve was used for predicting the accuracy of biomarkers using the area under the curve (AUC) and 95% confidence intervals (95% CI). Results: GSTP1, MnSOD, and eNOS (rs1799983) SNPs were observed to significantly influence the oxidative biomarker concentrations in the entire study population. SNPs in GSTP1, MnSOD, and eNOS (rs1799983) were significantly associated with differences in oxidative stress biomarkers. MnSOD (rs4880) significantly increased the risk of pulmonary complications in neonates with RDS. DNA damage product (8-OH-dG) concentrations before surfactant administration has the best predictive accuracy (AUC: 0.8; 95% CI: 0.7-1; P = .001) for pulmonary complications with a cut-off value of 5008.8 pg/mL. TAC concentrations are significantly greater on day 2 and day 3 amongst neonates receiving surfactant compared to the control group. AOPP in the umbilical cord blood was observed to significantly predict the severity of RDS (AUC: 0.8; 95% CI: 0.6-1; P = .01) with an optimal cut-off value of 88.78 µmol/L. Conclusion: We observed that SNPs in eNOS and MnSOD significantly influence the production of oxidative stress biomarkers in preterm neonates. Baseline 8-OH-dG concentrations best predict the risk of pulmonary complications and AOPP concentrations in the umbilical cord blood predict the risk of RDS severity.

Choosing the Right Lignin to Fully Replace Bisphenol A in Epoxy Resin Formulation.

Thirteen unmodified lignin samples from different biomass sources and isolation processes were characterized and used to entirely replace bisphenol A (BPA) in the formulation of solubilized epoxy resins using a developed novel method. The objective was to measure the reactivity of different lignins toward bio-based epichlorohydrin (ECH). The epoxy contents of various bio-based epoxidized lignins were measured by titration and 1 H NMR spectroscopy methods. A partial least square regression (PLS-R) model with 92 % fitting accuracy and 90 % prediction ability was developed to find correlations between lignin properties and their epoxy contents. The results showed that lignins with higher phenolic hydroxy content and lower molecular weights were more suitable for replacing 100 % of toxic BPA in the formulation of epoxy resins. Additionally, two epoxidized lignin samples (highest epoxy contents) cured by using a bio-based hardener (Cardolite GX-3090) were found to show comparable thermomechanical performances and thermal stabilities to a petroleum-based (DGEBA) epoxy system.