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Background Gut colonization with multidrug-resistant organisms (MDRO) frequently precedes infection among patients in the intensive care unit (ICU), although the dynamics of colonization are not completely understood. We performed a systematic review and meta-analysis of ICU studies which described the cumulative incidence and rates of MDRO gut acquisition. Methods We systematically searched PubMed, Embase, and Web of Science for studies published from 2010 to 2023 reporting on gut acquisition of MDRO in the ICU. MDRO were defined as multidrug resistant non- Pseudomonas Gram-negative bacteria (NP-GN), Pseudomonas spp., and vancomycin-resistant Enterococcus ( VRE). We included observational studies which obtained perianal or rectal swabs at ICU admission (within 48 h) and at one or more subsequent timepoints. Our primary outcome was the incidence rate of gut acquisition of MDRO, defined as any MDRO newly detected after ICU admission (i.e., not present at baseline) for all patient-time at risk. The study was registered with PROSPERO, CRD42023481569. Results Of 482 studies initially identified, 14 studies with 37,305 patients met criteria for inclusion. The pooled incidence of gut acquisition of MDRO during ICU hospitalization was 5% (range: 1–43%) with a pooled incidence rate of 12.2 (95% CI 8.1–18.6) per 1000 patient-days. Median time to acquisition ranged from 4 to 26 days after ICU admission. Results were similar for NP-GN and Pseudomonas spp., with insufficient data to assess VRE. Among six studies which provided sufficient data to perform curve fitting, there was a quasi-linear increase in gut MDRO colonization of 1.41% per day which was stable through 30 days of ICU hospitalization (R 2  = 0.50, p  < 0.01). Conclusions Acquisition of gut MDRO was common in the ICU and increases with days spent in ICU through 30 days of follow-up. These data may guide future interventions seeking to prevent gut acquisition of MDRO in the ICU.

Background: The close proximity of the popliteal neurovascular bundle to the posterior horn of the lateral meniscus puts it at risk of compromise during lateral meniscal repair. This is particularly important in smaller pediatric patients, who are commonly treated for lateral meniscal abnormalities in isolation (discoid meniscus) or concomitantly with anterior cruciate ligament reconstruction. Purpose: To quantify the distance between the posterior horn of the lateral meniscus and the popliteal neurovascular bundle along the path of meniscal repair and to investigate for associations with age, sex, height, weight, body mass index (BMI), and skeletal maturity. Study Design: Cross-sectional study; Level of evidence, 3. Methods: A total of 144 magnetic resonance imaging scans were evaluated in a cohort of patients aged 10 to 18 years without meniscal or ligament abnormalities. Measurements were made along a line from the anterolateral portal between the popliteal neurovascular bundle and the free edge, midpoint, and meniscocapsular junctions of the posterior horn of the lateral meniscus. In addition to descriptive statistics of these distances by age and sex, analyses of variance and linear regression analyses were performed to investigate for associations with age, sex, height, weight, BMI, and skeletal maturity. Results: Male participants had a significantly larger mean free edge distance (14.4 ± 2.5 vs 13.1 ± 2.5 mm, respectively; P = .005) and midpoint distance (9.6 ± 2.2 vs 8.9 ± 1.8 mm, respectively; P = .011) than female participants but not a significantly larger meniscocapsular distance (5.2 ± 1.6 vs 4.6 ± 1.4 mm, respectively; P = .096). Linear regression analyses revealed significant associations between these distances and age, height, weight, and BMI (P < .001 for all). There were statistically significant pairwise differences for free edge and midpoint distances to the neurovascular bundle between patients with open and closed physes. Conclusion: The distance between the posterior horn of the lateral meniscus and the popliteal vasculature along a trajectory from the standard anterolateral arthroscopic portal increases linearly throughout development between the ages of 10 and 18 years. There were also significant associations between height, weight, BMI, and skeletal maturity and these anatomic distances. Knowing the safe distance to the popliteal vasculature will increase the safety of arthroscopic lateral meniscal repair in children, especially with all-inside devices that require setting the penetration depth for the advancement of a sharp delivery device beyond the posterior capsule.

Disorders of the Gut‐Brain Interaction (DGBI) are highly prevalent conditions that all gastroenterologists encounter in clinical practice. Differences between men and women in the prevalence and symptom burden of DGBI have been well documented in numerous epidemiological and observational studies. Few have identified how DGBI are affected by hormonal changes in women through the lifespan or comorbid conditions and ultimately if and how treatment pathways should differ. This review aims to synthesize current evidence on women's health in the context of DGBI and suggest future directions for clinical studies and trials. Improving women's health in DGBI will require clinical trials that intentionally account for hormonal influences on symptoms and treatment outcomes, inclusion of sex‐specific comorbidities, and collaborative, cross‐disciplinary trial designs that address overlapping symptoms.

Background: Running analysis is an essential component of evaluation of both injured runners and uninjured runners seeking advice on injury prevention. Reliability of two-dimensional (2D) video analysis has been reported in the adult running population. However, these findings may not apply to youth runners given their unique state during growth and development. The reliability of quantitative and qualitative video-based running gait analysis in the adolescent population is unknown. Purpose: The purpose of this study was to determine the intra-rater and inter-rater reliability of sagittal and frontal plane kinematics using 2D video analysis in healthy adolescent runners. Methods: High-definition videos were recorded of 10 healthy runners between 14-18 years old running on a treadmill at self-selected speed with markers attached to the thoracic spine, pelvis, and lower extremities. Kinematic variables in the sagittal and frontal planes were measured using Dartfish Motion Analysis Software™ (Fribourg, Switzerland) by three raters. Intra- and inter-rater reliability were calculated using Intraclass Correlation Coefficients (ICCs). Results: Of the 10 runners, 4 (40%) were male and the mean age was 16 ± 1.5 years. The intra-rater ICC for all kinematic variables ranged from 0.574 to 0.999 for the primary sports physical therapist, and 0.367 to 0.973 for the inexperienced research assistant. The inter-rater ICC for all raters ranged from -0.01 to 0.941. Eleven kinematic variables showed substantial agreement and 4 showed almost perfect agreement. Step width and foot progression showed fair and poor agreement, respectively. Conclusion: The results of this study demonstrate that a 2D video-based running analysis can be reliably performed in an adolescent population on all kinematic variables except for step width and foot progression. Inexperienced raters can be properly trained in the video analysis of running kinematics using Dartfish Software in order to consistently assess the same runner.

Background: Quality of motion and neuromuscular balance are noted predictors of acute injury risk. Early sports specialization and extremely high activity levels have been linked to high risk of injury, especially overuse injury. Purpose: The purpose of this study is to investigate for any relationships between quality of physical movement, quantity of physical activity, and degree of sports specialization in a healthy cohort of children and adolescents. Methods: Healthy children between the ages 10 and 18 completed the HSS Pedi-FABS to assess quantity of physical activity and the Jayanthi scale to assess degree of sports specialization. Quality of motion was assessed using motion analysis sensors (DorsaVi, Kew, Australia) during 5 repetitions of 4 different jumping and squatting motions (Table 1). For each repetition, one point was given for low risk of injury anterior or medial/lateral motion, for a maximum score of 2 per leg. Quality of motion scores were summed for a maximum score of 100 per participant. Specialization level was dichotomized as high specialization with a Jayanthi scale score of 2 or 3 and low specialization with a score of 1 or 2. Independent samples t-tests were used to compare high vs. low specialization participants on physical activity quantity and overall quality of motion. A Pearson correlation was used to determine the relationship between quantity of physical activity and quality of motion. Results: Final analyses included 147 participants (72% male) with a mean age of 13.4 ± 2.2 years. For the entire cohort, the mean Pedi-FABS score was 22.9 ± 6.8, the mean quality score was 25.5 ± 13.5 and 73% were highly specialized. Participants that were highly specialized displayed low risk motion more frequently than participants with low sport specialization (27.6 ± 14.0 vs 19.8 ± 10.1, p < 0.01; Table 2). Highly specialized participants had significantly higher activity levels (24.6 ± 5.9 vs 18.1 ± 6.9, p < 0.001). Additionally, quality of motion was moderately correlated with physical activity level (r = 0.349, p < 0.001). Conclusion: Overall quality of motion as in jump-landing tasks in healthy children was better in highly specialized participants. Taken together with existing literature, although early specialization may put young athletes at risk for overuse injuries, highly sports specialized youth athletes may be at lower risk for acute injury. Future research should explore associations between sports specialization, physical activity, save movement patterns, and athletic injuries.

Background: Idiopathic scoliosis has historically been considered a benign condition without significant functional limitations for the patient. However, as curves progress, patients may experience worsening pain, deformity, and quality of life. Patient reported outcome measures (PROMs) help assess functional limitations that may indicate treatment. Purpose: The objective of this study was to compare physical activity related PROM scores in three groups of patients with different severities of spinal curvature. Methods: Pediatric patients diagnosed with adolescent and juvenile idiopathic scoliosis, kyphoscoliosis, or spinal asymmetry completed the SRS-22R, HSS Pedi-FABS activity scale, and Patient-Reported Outcomes Management Information System (PROMIS) Pediatric Computer Adaptive Tests for Mobility and Physical Activity (PA) at a single institution from July 2018 to February 2019. Radiographic images were reviewed, and patients were grouped as Spinal Asymmetry (SA), Mild Deformity (MD), and Severe Deformity (SD) by major Cobb angle measuring less than 10°, between 10° and 40°, and greater than 40° respectively. One-way ANOVA with a Tukey post-hoc correction was used to determine differences between groups. Results: 206 pediatric patients (65% female) with a mean age 13.5 ± 2.2 years were included. The mean Cobb angles by group were 7.1° ± 2.1° in SA (n=51), 19.4° ± 7.8° in MD (n=130), and 50.2° ± 9.1° in SD (n=25). Compared to both SA and MD patients, SD patients scored lower on PROMIS Mobility (p<0.005). Compared to SA patients only, SD patients had lower scores on the HSS Pedi-FABS (p<0.01) and SRS-22R Function (p<0.05). PROMIS PA scores decreased with increasing spinal deformity, but these differences were not statistically significant. There was no significant difference between SA and MD for all PROMs administered. Conclusion: These findings suggest that mobility, function, and physical activity are affected by increasing severity of spinal curvature. Patients with severe spinal deformity reported lower PROMs compared to patients without clinical spinal deformity. Finally, patients with spinal asymmetry and mild deformity do not report significantly different PROMs. Tables: Table 1. Mean PROM scores by group. NS, nonsignificant. SA MD SD P value PROMIS Mobility 56.7 ± 5.4 54.6 ± 7.4 49.6 ± 9.0 <0.005 between SA & SD, MD & SD PROMIS PA 47.1 ± 7.4 45.2 ± 8.8 43.4 ± 10.5 NS SRS-22R Function 4.9 ± 0.3 4.7 ± 0.4 4.6 ± 0.4 <0.05 between SA & SD HSS Pedi-FABS 17.8 ± 7.5 15.0 ± 8.6 11.8 ± 6.3 <0.01 between SA & SD

Background: Surgical decision making and preoperative planning for children and adolescents with patellofemoral instability rely heavily on a patient’s skeletal maturity. To be clinically useful, radiologic assessments of skeletal maturity must demonstrate acceptable interrater reliability and accuracy. Purpose: The purpose of this study was to examine the interrater reliability among surgeons of varying experience levels and specialty training backgrounds when evaluating the skeletal maturity of the distal femur and proximal tibia of children and adolescents with patellofemoral instability. Study Design: Cohort study (diagnosis); Level of evidence, 3. Methods: Six fellowship-trained orthopaedic surgeons (3 pediatric orthopaedic, 2 sports medicine, and 1 with both) who perform a high volume of patellofemoral instability surgery examined 20 blinded knee radiographs and magnetic resonance images in random order. They assessed these images for clinically relevant growth (open physis) or clinically insignificant growth (closing/closed physis) remaining in the distal femoral and proximal tibial physes. Fleiss’ kappa was calculated for each measurement. After initial ratings, raters discussed consensus methods to improve reliability and assessed the images again to determine if training and new criteria improved interrater reliability. Results: Reliability for initial assessments of distal femoral and proximal tibial physeal patency was poor (kappa range, 0.01-0.58). After consensus building, all assessments demonstrated almost-perfect interrater reliability (kappa, 0.99 for all measurements). Conclusion: Surgical decision making and preoperative planning for children and adolescents with patellofemoral instability rely heavily on radiologic assessment of skeletal maturity. This study found that initial interrater reliability of physeal patency and clinical decision making was unacceptably low. However, with the addition of new criteria, a consensus-building process, and training, these variables became highly reliable.

Background: The Marx Activity Rating Scale (MARS) and the Hospital for Special Surgery Pediatric Functional Activity Brief Scale (HSS Pedi-FABS) are both validated activity scales. While the MARS examines greatest physical activity level within the last year, the HSS Pedi-FABS assesses the greatest level of physical activity within the last month. Purpose: To determine whether the different time frames used in MARS and HSS Pedi-FABS affect scores on common items in both scales, and if so, to determine whether age or injury status affect this difference. Methods: The MARS and 4 analogous items on the HSS Pedi-FABS were administered sequentially in random order to patients being evaluated at two sports surgeons’ clinic for knee injuries in addition to their healthy companions in order to enroll an uninjured comparison group. Responses to each question were scored from 0-4 for a maximum overall score of 16. Participant demographics were also recorded. Paired and independent sample t-tests were used to determine mean differences between the two scales and between healthy and injured adults and children, respectively. Results: The final cohort included 88 participants of which 47% were children (ages 10-17) and 51% had a knee injury. All participants except for healthy adults scored significantly lower on the HSS Pedi-FABS than the MARS (p < 0.05, Table 1). On the HSS Pedi-FABS activity scale, healthy participants scored significantly higher than injured participants (p<0.01), but there were no significant differences based on age, Figure 1A. Conversely, on the MARS scale, children scored higher than adults (p≤0.001), but there were no significant differences based on injury, Figure 1B. Conclusion: Physical activity level is significantly different when evaluated by either MARS or its analogue portion of HSS Pedi-FABS. Because the only difference between the scales is the timeframe, the lower scores on the Pedi-FABS than the MARS are likely due to seasonal changes in activity which are not captured in the MARS. Because the Pedi-FABS analyzes a shorter window, it is more likely to capture acute changes in physical activity due to a recent injury than the MARS scale while the MARS scale is better suited for examining general physical activity unaffected by seasonality. Understating the differences between these scales can guide clinicians in using them appropriately when evaluating patient activity level. Tables: Table 1. Mean differences between the MARS and HSS Pedi-FABS scales based on adult vs. child and healthy vs. injured status. n MARS HSS Pedi-FABS Difference Mean ± SD Mean ± SD Mean ± SD p-value Healthy Child 22 12.5 ± 3.8 9.7 ± 5.0 2.7 ± 3.8 0.003 Adult 21 6.8 ± 4.4 7.0 ± 4.8 0.1 ± 1.3 0.614 Injured Child 19 12.4 ± 5.0 3.1 ± 4.5 9.3 ± 8.1 <0.001 Adult 26 6.4 ± 5.6 3.2 ± 4.4 3.2 ± 6.7 0.024 SD = Standard deviation Figures: Figure 1. Significant differences between injured and healthy adults and children on the A) HSS Pedi-FABS scale and B) MARS scale.

Acknowledgements: The authors would like to acknowledge Drs. Matthew Milewski, Yi-Meng Yen, and Adam Yanke for their contributions. Background: Surgical decision-making and pre-operative planning for children and adolescents with patellofemoral instability relies heavily on skeletal maturity status. In order to be clinically useful, radiologic assessments of skeletal maturity must demonstrate acceptable interrater reliability and accuracy. Purpose: The purpose of this study was to evaluate the interrater reliability among surgeons of varying experience levels and specialty training backgrounds when evaluating skeletal maturity in the distal femur and proximal tibia of children and adolescents with patellofemoral instability. Study Design: Cross-sectional study Methods: Six fellowship-trained orthopedic surgeons (4 pediatric orthopedic, 2 sports medicine) who perform a high volume of patellofemoral instability surgery examined 20 blinded and randomized knee radiographs and MR images. They assessed these images for clinically relevant growth (open physis) or clinically insignificant growth (closing/closed physis) remaining in the distal femoral and proximal tibial physes. Fleiss’s kappa was calculated for each measurement. After initial ratings, raters discussed consensus methods to improve reliability and assessed the images again in order to determine if training and new criteria improved interrater reliability. Results: Reliability for initial assessments of distal femoral and proximal tibial physeal status was poor (Kappa range: 0.01 – 0.58). After consensus building, all assessments demonstrated almost perfect interrater reliability (Kappa = 0.99 for all measurements). Conclusion: Surgical decision-making and pre-operative planning for children and adolescents with patellofemoral instability relies heavily on radiologic assessment of skeletal maturity. This study found that initial interrater reliability of physeal status and clinical decision making was unacceptably low. However, with the addition of new criteria, a consensus-building process, and training, these variables became highly reliable. Clinical Relevance: Lack of assessment reliability can jeopardize patient care, both when determining surgical indications as well as choosing an appropriate procedure based upon skeletal maturity. Surgeons should focus on using reliable imaging metrics in children and adolescents with patellofemoral instability, and measurements that remain unreliable after consensus building and training should be removed from clinical decision-making algorithms. What is known about the subject: Treatment of patellofemoral instability heavily relies on skeletal maturity status. Physeal assessments of the knee must be reliable and clinically relevant to ensure optimal patient care. What this study adds to existing knowledge: Physeal assessment of the knee without training can be unreliable among fellowship trained orthopedic surgeons. With consensus building and training in the use of the methods described in this manuscript, physeal assessments can demonstrate almost perfect reliability.

Epidermal growth factor receptor ( EGFR ) mutations typically occur in exons 18–21 and are established driver mutations in non-small cell lung cancer (NSCLC) 1 – 3 . Targeted therapies are approved for patients with ‘classical’ mutations and a small number of other mutations 4 – 6 . However, effective therapies have not been identified for additional EGFR mutations. Furthermore, the frequency and effects of atypical EGFR mutations on drug sensitivity are unknown 1 , 3 , 7 – 10 . Here we characterize the mutational landscape in 16,715 patients with EGFR -mutant NSCLC, and establish the structure–function relationship of EGFR mutations on drug sensitivity. We found that EGFR mutations can be separated into four distinct subgroups on the basis of sensitivity and structural changes that retrospectively predict patient outcomes following treatment with EGFR inhibitors better than traditional exon-based groups. Together, these data delineate a structure-based approach for defining functional groups of EGFR mutations that can effectively guide treatment and clinical trial choices for patients with EGFR -mutant NSCLC and suggest that a structure–function-based approach may improve the prediction of drug sensitivity to targeted therapies in oncogenes with diverse mutations. Structural classification of mutations in the epidermal growth factor receptor causing non-small cell lung cancer is a better predictor of patient outcomes following drug treatment than traditional exon-based classification.