Scottish Rite Hospital

An overview of the evolving role of microfluidics within clinical laboratories and diagnostic settings. It explores how microfluidic technologies, initially envisioned to replace traditional lab practices, are instead integrating into established workflows. This integration is driven by advancements in miniaturization and automation, enhancing efficiency and expanding testing capabilities. Regulatory frameworks such as CLIA and FDA oversight shape the landscape for microfluidic adoption, emphasizing the need for rigorous validation and compliance. The total testing process (TTP) framework underscores the critical phases-pre-analytical, analytical, and post-analytical-where microfluidics must conform with to ensure accuracy and reliability in diagnostic outcomes. Automation emerges as pivotal by streamlining workflows and reducing errors, particularly in sample handling and result interpretation. Challenges persist including the complex categorization of tests and the push for tighter regulation of laboratory developed tests (LDTs). The challenges necessitate collaboration between researchers, clinicians, and regulatory bodies. This review highlights how automation and integration of microfluidic technologies in point-of-care settings are reshaping clinical diagnostics, offering rapid, personalized testing options while maintaining high standards of patient care. Despite advancements, mitigating diagnostic errors remains paramount, requiring continuous refinement of technologies and adherence to established clinical protocols. Ultimately, the successful integration of microfluidics into clinical laboratories hinges on balancing innovation with regulatory compliance, ensuring seamless usability and consistent diagnostic accuracy within existing healthcare infrastructures.

Introduction: This study aimed to examine if acute caffeine consumption influenced substrate utilization between recreationally trained males and females during submaximal aerobic exercise.Methods: Implementing a counter-balanced, crossover design study, 14 recreationally trained males (n = 7) and females (n = 7) consumed either 4 mg/kg of caffeine in 8 oz of water (CAFF) 60 min prior to aerobic exercise at varying submaximal intensities or the solitary consumption of 8 oz of water (CON). Substrate utilization was assessed via indirect calorimetry by measuring the respiratory exchange ratio. Results: There were no significant main effects for substrate utilization between sexes for the CAFF (p = .265) or CON (p = .253) trial. There were also no significant main effects for independent sex analysis between the two conditions (males, p = .917; females, p = .869).Conclusions: This study suggests no significant difference in substrate utilization between sexes when consuming caffeine. Although previous literature has indicated caffeine has the potential to increase fat utilization during moderate-intensity aerobic exercise, the current results revealed that caffeine also had no impact on substrate utilization when independently analyzing males and females.

Background and PurposeThe Expanded Cutting Alignment Scoring Tool (E-CAST) is a two-dimensional qualitative scoring system that has demonstrated moderate inter-rater and good intra-rater reliability for the assessment of trunk and lower extremity alignment during a 45-degree sidestep cut. The primary purpose of this study was to examine the reliability of the quantitative version of the E-CAST among physical therapists and to compare the reliability of the quantitative E-CAST to the original qualitative E-CAST. The hypothesis was that the quantitative version of the E-CAST would demonstrate greater inter-rater and intra-rater reliability compared to the qualitative E-CAST.Study DesignObservational cohort, repeated measures reliability studyMethodsTwenty-five healthy female athletes (age 13.8±1.4 years) performed three sidestep cuts with two-dimensional video capturing frontal and sagittal views. Two physical therapist raters independently scored a single trial using both views on two separate occasions. Based on the E-CAST criteria, select kinematic measurements were extracted using a motion analysis phone application. Intraclass correlation coefficients and 95% confident intervals were calculated for the total score, and kappa coefficients were calculated per kinematic variable. Correlations were converted to z-scores and compared to the six original criteria for significance (α<0.05).ResultsCumulative intra- and inter-rater reliability were both good (ICC=0.821, 95% CI 0.687-0.898 and ICC=0.752, 95% CI 0.565-0.859). Cumulative intra-rater kappa coefficients ranged from moderate to almost perfect, and cumulative inter-rater kappa coefficients ranged from slight to good. No significant differences were observed between the quantitative and qualitative criteria for either inter- or intra-rater reliability (Zobs(intra)= -0.38, p=0.352 and Zobs(inter)= -0.30, p=0.382).ConclusionThe quantitative E-CAST is a reliable tool to assess trunk and lower extremity alignment during a 45-degree sidestep cut. No significant differences were observed in reliability of the quantitative versus qualitative assessment.Level of evidence3b

Abstract Background Children with acute hematogenous osteomyelitis (AHO) and methicillin-resistant Staphylococcus aureus (MRSA) bacteremia are often treated with vancomycin (vanc) with risk of nephrotoxicity. This study evaluates resources used, and outcomes, of children with or without acute kidney injury (AKI) when vanc is used in this setting. Methods Children with AHO and MRSA bacteremia treated with vanc from 2009 to 2019 were retrospectively studied. AKI was assessed by chart review, for clinical diagnosis and by Kidney Disease Improving Global Outcomes (KDIGO) criteria. Cohorts of children with or without KDIGO AKI were compared for differences of illness severity, treatment, resource utilization, and outcomes. Multivariate logistic regression analysis was accomplished to identify factors associated with risk for AKI. Cost analysis was performed using Pediatric Health Information System (PHIS) and Healthcare Cost and Utilization Project (HCUP) databases. Results Among 631 children with AHO, 85 children with MRSA bacteremia were treated with vanc for a sufficient duration to allow trough measurements. Of these, 14 (16.5%) had chart-diagnosed AKI, whereas 24 (28.2%) children met KDIGO criteria. Children with AKI had more febrile days and higher rates of thrombosis. They had longer duration of vanc treatment (8 vs 5 d) and higher troughs (27.8 vs 17.5 mg/L). The AKI group had more blood cultures, vanc troughs, creatinine levels, and longer length of stay (LOS; 19.9 vs 11.1 days). Multivariate analysis revealed that maximum vanc trough level (odds ratio 1.05) with a cutoff of 21.7 mg/L was a significant predictor of AKI. PHIS data of 3,133 children with AHO treated with vanc identified 75 (2.4%) with AKI who had significantly longer LOS (13 vs 7 d) and higher billed charges ($117K vs $51K) than children without AKI. HCUP data of 13,223 children with AHO identified 384 (2.9%) with AKI who had longer LOS (27 vs 6 d) and higher billed charges ($317K vs $37K) than those without. Conclusion Clinical diagnosis of AKI (16.5%) grossly underestimated the KDIGO occurrence (28.2%) in our population. This study showed vanc associated AKI results in significant increases in resource utilization and healthcare costs. A high vanc trough &amp;gt;21.7 mg/dL is a significant contributing factor to AKI. Disclosures All Authors: No reported disclosures.

Objectives:The HSS Pedi-FABS activity scale has become increasingly used in children age10-18 since its development in 2013. Research reports on the utility of themeasure in general youth athletes with knee injuries, however limitedinformation is available regarding use in evaluating a variety of jointinjuries, athletes who participate in sports with disparate biomechanics, orspecialized competitive athletes. This study assessed the sensitivity anddistribution of Pedi-FABS in an athletic youth population. Secondarily, thisstudy evaluated Pedi-FABS association with PROMIS® Pediatric Global Health7(PGH7) with Pain Interference(PGHPI) and Fatigue(PGHF) components.Methods:A retrospective review of youth athletes age 10-18 presenting for evaluationat a single pediatric sports medicine clinic between 4/2016-7/2020 wasperformed. Participants were included if they completed a pre-visit intakequestionnaire and Pedi-FABS. Descriptive statistics were used to analyzePedi-FABS for normal distribution and the presence of a floor or ceilingeffect in subgroups determined by demographics, injury characteristics, andsports participation. A floor or ceiling effect was determined to be presentif more than 15% of respondents scored the lowest or highest possible score.A Kruskal-Wallis test used to compare average scores in each subgroup.Spearman’s Correlations were calculated to assess the association of PGHwith Pedi-FABS scores.Results:2274 sports medicine patients (14.6±2.1 years; 53.0% females) were included.Of these, 2010 youth athletes reported participating in sports for 9.6±7.9hours per week during 32.3±15.7 weeks per year with 6.2±3.4 years ofparticipation in 21 distinct primary sports. 80.3% of patients reportedparticipation in only one sport. Pedi-FABS Score differences were foundacross demographic(Table 1) and sport participation(Table 2) subgroups.Broad distribution was seen in each subgroup with no floor or ceilingeffects. Pedi-FABS score correlated with hours per week(r=0.20), days perweek(r=0.28), weeks per year(r=0.12), and years ofparticipation(r=0.16/p<0.01). An inverse correlation was observed betweenPedi-FABS and Days from Injury to Presentation(r=-0.21/p<0.01). Anassociation between general health and activity level was noted as all threePGH components correlated with Pedi-FABS(PGH7: r=0.28/PGHF: r=-0.16/PGHPI:r=-0.12, p<0.01).Conclusions:Correlations with multiple forms of self-reported activity without floor orceiling effects demonstrates the validity and sensitivity of Pedi-FABS foruse in athletes with a variety of primary sports and injury types.Additionally, mean differences between demographic and sport participationsubgroups, as well as associations with days to presentation and a commonlyused patient reported outcome measure, may demonstrate the utility ofPedi-FABS for sports medicine clinicians.Table 1.HSS Pedi-FABS Score Distributions by Study Cohort Demographics andInjury CharacteristicsTable 2.HSS Pedi-FABS Score Distributions by Sports ParticipationCharacteristics Among Self-Reported Athletes in Study Cohort

Objectives:For patients with significant growth remaining, the Micheli (iliotibial band) ACL reconstruction technique has proven to be a reliable procedure with minimal risk for growth disturbance. Recent cadaveric studies have demonstrated that graft passage over the top of the femur may bring the graft and surgical instrument close to the critical neurovascular structures. The purpose of this study was to evaluate the Micheli over-the-top, graft passage technique for ACL reconstruction using pediatric cadaveric knees, and measure the distance between surgical instrument tip and the peroneal nerve, tibial nerve, and popliteal artery.Methods:Gross dissection was performed on seventeen skeletally immature cadaveric knees (12 male and 5 female) between the ages of 4 and 12 years old. A 5.5” curved-tip hemostat clamp was used to create a path through the posterior capsule, after the posterior neurovascular structures were identified. The tip of the clamp was passed from an anterior medial portal through the notch postero-superiorly, towards the proximal lateral capsule, with the knee flexed to 90-100 degrees or more. Once passed, the clamp was positioned in the popliteal fossa and clinical photographs were taken from the posterior aspect of the dissected knee, visualizing the tip of the clamp and the neurovascular structures. A metric ruler was included in all photographs. Digital imaging software was used to measure the distance in centimeters from clamp tip to peroneal nerve laterally, and the popliteal artery and tibial nerve medially for all specimens, FIGURE 1. Distances were averaged and stratified to assess differences in age and sex FIGURE 2.Results:The average distances from clamp to neurovascular bundle were 0.875cm (range: 0.468-1.737cm), 0.968cm (range: 0.312-1.819cm), and 1.149cm (range: 0.202-2.409cm) for tibial nerve, popliteal artery and peroneal nerve, respectfully. Means were further calculated for age groups ≤8, 9-10, and 11-12 years old. The average distance from clamp tip to peroneal nerve was 1.400cm larger for 11–12-year-old patients vs. patients ≤8 after adjusting for sex (95% CI=[0.6, 2.2], p=0.005).Conclusions:Iliotibial band graft ACL reconstruction is one of the best options in the skeletally immature, as it has the lowest risk of growth plate complications and growth arrest. The neurovascular structures are very close to the path for over-the-top graft clamp placement with distances <1 cm in many subjects. When passing the graft through the posterior knee there may be greater accessibility on the lateral cortex of the knee among older patients who are closer in age to physeal closure. The current study provides detailed measurements of instrument proximity to the neurovascular bundle in the posterior compartment of the knee. This knowledge is important to help surgeons who perform the Micheli pediatric ACL reconstruction avoid damage to the nerves and vessels in this region. Careful instrument and graft passage, with awareness of proximity to critical structures, are important to reduce the risk of neurovascular injury.Figure 1.Measurements (cm) from clamp tip to neurovascular bundle structures in right Knee model.Figure 2.Average distance from clamp from tip to neurovascular bundle by age Error bars represent 95%CI,**p<0.01

In 2001, Texas Scottish Rite Hospital for Children (TSRH) prospectively began a clubfoot database that included all of our patients with clubfeet who were willing to enroll. Nonoperative treatment, primarily the Ponseti method, was utilized. This article summarizes the experience from Dallas treating idiopathic clubfeet using the Ponseti technique, and is based on previously published studies utilizing information from the database. Patient clinical outcomes were defined as “good” (plantigrade foot achieved either with or without a percutaneous heel-cord tenotomy), “fair” (a plantigrade foot that required a limited procedure, such as tibialis anterior tendon transfer or posterior release), or “poor” (a plantigrade foot that required posteromedial release). Nearly 95% of idiopathic clubfeet obtained initial correction using the Ponseti technique, but relapses occurred and by age two years 24% needed some surgical intervention, usually limited procedures. Use of Dimeglio’s rating system before treatment strongly correlated with the probability of a “good” outcome at two years. Objective measurements of brace wear compliance (iButton) in those who reached age two years with “good” outcomes demonstrated an unexpected pattern of diminishing use of the foot abduction orthoses over the first two years of brace wear. By the 18-month period of brace wear, 1/3 patients wore the orthoses less than 6 hours per day, and nearly half of the patients wore the orthoses less than 8 hours per day. Between ages 2–5 years, nearly 21% of the corrected clubfeet at age two years needed limited procedures to maintain/regain plantigrade positioning. Lateral weight-bearing radiographs between 18–24 months were not helpful in predicting future relapse in these patients, and are no longer routinely obtained. Following these patients for normal development is important, as nearly 9% of infants initially presenting as idiopathic clubfeet were eventually found to have another disorder including neurological, syndromic, chromosomal, or spinal abnormalities. We continue to emphasize the need to devote great attention to detail when using the Ponseti method in an effort to optimize the clinical outcomes.

Despite the widespread use of the Ponseti method for treatment of clubfeet, there continue to be a significant number of patients who present with a severe, stiff clubfoot as a result of extensive intra-articular soft tissue release or lack of access to care. In such patients, circular external fixators can be utilized for deformity correction with distraction across soft tissues, joints, and osteotomies. Ilizarov or hexapod circular fixators may be utilized according to surgeon preference. Indications for soft tissue release and osteotomies to aid in correction of clubfoot deformity with Ilizarov and hexapod fixators are not standardized and are guided by patient age, joint congruity, soft tissue suppleness, and osseous deformity. Correction time varies according to clubfoot deformity severity. Following deformity correction, external fixators are left in place for several weeks to stabilize the soft tissues and allow for osteotomy healing. Complications range from relatively minor pin tract infections that resolve with oral antibiotics to tarsal tunnel syndrome, osteomyelitis, or disabling arthritis requiring revision procedures. At Scottish Rite Hospital for Children, we prefer to correct severe residual clubfoot deformity with a hexapod external fixator. Acute correction and gradual correction via distraction are considered for each segmental deformity and utilized to efficiently correct deformity while minimizing soft tissue trauma. The purpose of this article is to summarize the relevant literature related to circular external fixator treatment of recurrent clubfoot deformity and outline our approach to the segmental deformities of the foot and ankle in this patient population.

The carbohydrate response element binding protein (ChREBP) is a glucose-responsive transcription factor that plays a critical role in glucose-mediated induction of genes involved in hepatic glycolysis and lipogenesis. In response to fluctuating blood glucose levels ChREBP activity is regulated mainly by nucleocytoplasmic shuttling of ChREBP. Under high glucose ChREBP binds to importin α and importin β and translocates into the nucleus to initiate transcription. We have previously shown that the nuclear localization signal site (NLS) for ChREBP is bipartite with the NLS extending from Arg158 to Lys190. Here, we report the 2.5 Å crystal structure of the ChREBP-NLS peptide bound to importin α. The structure revealed that the NLS binding is monopartite, with the amino acid residues K171RRI174 from the ChREBP-NLS interacting with ARM2–ARM5 on importin α. We discovered that importin α also binds to the primary binding site of the 14-3-3 proteins with high affinity, which suggests that both importin α and 14-3-3 are each competing with the other for this broad-binding region (residues 117–196) on ChREBP. We screened a small compound library and identified two novel compounds that inhibit the ChREBP-NLS/importin α interaction, nuclear localization, and transcription activities of ChREBP. These candidate molecules support developing inhibitors of ChREBP that may be useful in treatment of obesity and the associated diseases.

This is the seventh article in a new series about evidence-based practice (EBP) that builds on AJN's award-winning previous series-Evidence-Based Practice, Step by Step-published between 2009 and 2011 (to access the series, go to http://links.lww.com/AJN/A133). This follow-up series features exemplars illustrating the various strategies that can be used to implement EBP changes-one of the most challenging steps in the EBP process.