Management options for pediatric venous thromboembolic disease: Beyond anticoagulation with endovascular therapies.

Venous thromboembolism (VTE) in pediatric patients is an uncommon but serious diagnosis that has an array of therapeutic options and challenges. An assessment of the existing literature on management of pediatric patients with VTE was conducted. The interventions reviewed include anticoagulation, thrombolysis, thrombectomy, inferior vena cava (IVC) filters, and venous stenting. For each intervention, a discussion of mechanism of action, indications, contraindications, and potential complications was performed. While anticoagulants are considered the first-line pediatric VTE treatment, many drugs remain investigational in this patient population and treatment recommendations are extrapolated from adult practice. Thrombolysis may be indicated in cases of acute thrombosis requiring more rapid clot resolution but presents a greater bleeding risk than anticoagulation. Similarly, thrombectomy also provides rapid clot resolution and offers a larger therapeutic window and usage in more mature thrombi than thrombolysis. In select patient groups, IVC filters may be indicated in the prevention of PE but present with inherent thrombogenicity and risk of migration. The data regarding pediatric VTE treatment options, monitoring, and long term outcomes is limited compared to the adult population. The relatively few clinical trials including pediatric patients have a relatively small sample size and are heterogenous with regards to predisposing factors that further exacerbate generalizability. Additional research is needed to help construct and evaluate a robust treatment algorithm for pediatric patients with VTE.

Modifying loading during gait leads to biochemical changes in serum cartilage oligomeric matrix protein concentrations in a subgroup of individuals with anterior cruciate ligament reconstruction.

PURPOSE: Strong observational evidence has linked changes in limb loading during walking following anterior cruciate ligament reconstruction (ACLR) to posttraumatic osteoarthritis (PTOA). It remains unknown if manipulating peak loading influences joint tissue biochemistry. Thus, the purpose of this study is to determine whether manipulating peak vertical ground reaction force (vGRF) during gait influences changes in serum cartilage oligomeric matrix protein (sCOMP) concentrations in ACLR participants. METHODS: Forty ACLR individuals participated in this randomized crossover study (48% female, age = 21.0 ± 4.4 years, BMI = 24.6 ± 3.1). Participants attended four sessions, wherein they completed one of four biofeedback conditions (habitual loading (no biofeedback), high loading (5% increase in vGRF), low loading (5% decrease in vGRF), and symmetrical loading (between-limb symmetry in vGRF)) while walking on a treadmill for 3000 steps. Serum was collected before (baseline), immediately (acute post), 1 h (1 h post), and 3.5 h (3.5 h post) following each condition. A comprehensive general linear mixed model was constructed to address the differences in sCOMP across all conditions and timepoints in all participants and a subgroup of sCOMP Increasers. RESULTS: No sCOMP differences were found across the entire cohort. In the sCOMP Increasers, a significant time × condition interaction was found (F9,206 = 2.6, p = 0.009). sCOMP was lower during high loading than low loading (p = 0.009) acutely (acute post). At 3.5 h post, sCOMP was higher during habitual loading than symmetrical loading (p = 0.001). CONCLUSION: These data suggest that manipulating lower limb loading in ACLR patients who habitually exhibit an acute increase in sCOMP following walking results in improved biochemical changes linked to cartilage health. Key Points • This study assesses the mechanistic link between lower limb load modification and joint tissue biochemistry at acute and delayed timepoints. • Real-time biofeedback provides a paradigm to experimentally assess the mechanistic link between loading and serum biomarkers. • Manipulating peak loading during gait resulted in a metabolic effect of lower sCOMP concentrations in a subgroup of ACLR individuals. • Peak loading modifications may provide an intervention strategy to mitigate the development of PTOA following ACLR.

Sustained Limb-Level Loading: A Ground Reaction Force Phenotype Common to Individuals at High Risk for and Those With Knee Osteoarthritis.

OBJECTIVE: The objective of this study was to compare the vertical (vGRF), anterior-posterior (apGRF), and medial-lateral (mlGRF) ground reaction force (GRF) profiles throughout the stance phase of gait (1) between individuals 6 to 12 months post-anterior cruciate ligament reconstruction (ACLR) and uninjured matched controls and (2) between ACLR and individuals with differing radiographic severities of knee osteoarthritis (KOA), defined as Kellgren and Lawrence (KL) grades KL2, KL3, and KL4. METHODS: A total of 196 participants were included in this retrospective cross-sectional analysis. Gait biomechanics were collected from individuals 6 to 12 months post-ACLR (n = 36), uninjured controls matched to the ACLR group (n = 36), and individuals with KL2 (n = 31), KL3 (n = 67), and KL4 osteoarthritis (OA) (n = 26). Between-group differences in vGRF, apGRF, and mlGRF were assessed in reference to the ACLR group throughout each percentage of stance phase using a functional linear model. RESULTS: The ACLR group demonstrated lower vGRF and apGRF in early and late stance compared to the uninjured controls, with large effects (Cohen's d range: 1.35-1.66). Conversely, the ACLR group exhibited greater vGRF (87%-90%; 4.88% body weight [BW]; d = 0.75) and apGRF (84%-94%; 2.41% BW; d = 0.79) than the KL2 group in a small portion of late stance. No differences in mlGRF profiles were observed between the ACLR and either the uninjured controls or the KL2 group. The magnitude of difference in GRF profiles between the ACLR and OA groups increased with OA disease severity. CONCLUSION: Individuals 6 to 12 months post-ACLR exhibit strikingly similar GRF profiles as individuals with KL2 KOA, suggesting both patient groups may benefit from targeted interventions to address aberrant GRF profiles.

Physical Activity Associates with T1rho MRI of Femoral Cartilage After Anterior Cruciate Ligament Reconstruction.

PURPOSE: Less physical activity has been associated with systemic biomarkers of cartilage breakdown after anterior cruciate ligament reconstruction (ACLR). However, previous research lacks analysis of deleterious cartilage compositional changes and objective physical activity after ACLR. The purpose of this study was to determine the association between physical activity quantified via accelerometer-based measures of daily steps and time in moderate-to-vigorous physical activity (MVPA), and T1rho magnetic resonance imaging (MRI) of the femoral articular cartilage, a marker of proteoglycan density in individuals with ACLR. METHODS: Daily steps and MVPA were assessed over 7 d using an accelerometer worn on the hip in 26 individuals between 6 and 12 months after primary unilateral ACLR. Resting T1rho MRI was collected bilaterally, and T1rho MRI interlimb ratios (ILR: ACLR limb/contralateral limb) were calculated for lateral and medial femoral condyle regions of interest. We conducted univariate linear regression analyses to determine associations between T1rho MRI ILRs and daily steps and MVPA with and without controlling for sex. RESULTS: Greater T1rho MRI ILR of the central lateral femoral condyle, indicative of less proteoglycan density in the ACLR limb, was associated with greater time in MVPA ( R2 = 0.178, P = 0.032). Sex-adjusted models showed significant interaction terms between daily steps and sex in the anterior ( P = 0.025), central ( P = 0.002), and posterior ( P = 0.002) medial femoral condyle. CONCLUSIONS: Lesser physical activity may be a risk factor for maintaining cartilage health after ACLR; additionally, the relationship between physical activity and cartilage health may be different between males and females.

Daily steps and stepping cadence increase one-year following prosthesis osseointegration in people with lower-limb amputation.

PURPOSE: People with lower-limb loss participate in less physical activity than able-bodied individuals, which increases the mortality risk and incidence of metabolic syndromes. This study evaluated the effect of lower-limb prosthesis osseointegration on physical activity, including daily steps and stepping cadence. METHODS: Free-living walking activity was assessed from 14 patients scheduled to undergo prosthesis osseointegration at two time points (within 2 weeks prior to osseointegration surgery and 12-months following). Daily step count, stepping time, number of walking bouts, average step cadence per bout, maximum step cadence per bout, and time spent in bands of step cadence were compared before and after osseointegration. RESULTS: Twelve months after prosthesis osseointegration, participants increased daily steps, daily stepping time, average step cadence, and maximum cadence per walking bout compared to pre-osseointegration. CONCLUSIONS: Participants engaged in more daily steps, higher stepping cadence, and longer bouts at higher cadence one year following osseointegration compared to when using a socket prosthesis. As a novel intervention that is becoming more common, it is important to understand walking activity outcomes as these are critical for long-term health.

People with lower-limb loss participate in less physical activity than able-bodied individuals, which increases the mortality risk and incidence of metabolic syndromes.Daily step count, walking bouts, and step cadence during free-living walking activity are promising measures to capture physical functional performance in patients with lower-limb amputation.This study shows that patients with osseointegrated prostheses increase their stepping activity, including daily steps, number of bouts, and stepping cadence compared to when using a socket prosthesis, which has positive implications on overall patient health.As a novel intervention that is becoming more common, it is important for clinicians, patients, and researchers to understand expectations for walking activity outcomes as a critical factor in long-term patient health after prosthesis osseointegration.

Protein S antibody as an adjunct therapy for hemophilia B.

ABSTRACT: Hemophilia B (HB) is caused by an inherited deficiency of plasma coagulation factor IX (FIX). Approximately 60% of pediatric patients with HB possess a severe form of FIX deficiency (<1% FIX activity). Treatment typically requires replacement therapy through the administration of FIX. However, exogenous FIX has a limited functional half-life, and the natural anticoagulant protein S (PS) inhibits activated FIX (FIXa). PS ultimately limits thrombin formation, which limits plasma coagulation. This regulation of FIXa activity by PS led us to test whether inhibiting PS would extend the functional half-life of FIX and thereby prolong FIX-based HB therapy. We assayed clotting times and thrombin generation to measure the efficacy of a PS antibody for increasing FIX activity in commercially obtained plasma and plasma from pediatric patients with HB. We included 11 pediatric patients who lacked additional comorbidities and coagulopathies. In vivo, we assessed thrombus formation in HB mice in the presence of the FIXa ± PS antibody. We found an accelerated rate of clotting in the presence of PS antibody. Similarly, the peak thrombin formed was significantly greater in the presence of the PS antibody, even in plasma from patients with severe HB. Furthermore, HB mice injected with PS antibody and FIX had a 4.5-fold higher accumulation of fibrin at the thrombus induction site compared with mice injected with FIX alone. Our findings imply that a PS antibody would be a valuable adjunct to increase the effectiveness of FIX replacement therapy in pediatric patients who have mild, moderate, and severe HB.

Corrigendum to ' Recurrent venous thromboembolism in hospitalized children with a history of prior venous thromboembolism: a report from the Children's Hospital-Acquired Thrombosis Consortium' [Research and Practice in Thrombosis and Haemostasis Volume 7, Issue 5, July 2023, 102139].

[This corrects the article DOI: 10.1016/j.rpth.2023.102139.].

Maximal daily stepping cadence partially explains functional capacity of individuals with end-stage knee osteoarthritis.

BACKGROUND: Individuals with end-stage knee osteoarthritis (OA) walk at a lower intensity (ie, slower step cadence) contributing to worse physical function. Previous literature reports daily step counts and sedentary time, with little information regarding stepping bouts or cadence. Determining relationships between daily higher stepping cadence duration and clinical outcomes can move the field toward optimal daily stepping prescription. OBJECTIVE: To quantify daily physical activity patterns of individuals with end-stage knee OA and determine the contribution of high stepping cadence to explain functional capacity variability. DESIGN: Cross-sectional analysis. SETTING: Veterans Administration medical center. PARTICIPANTS: U.S. military veterans (n = 104; age: 67.1 years [7.2]; mean [SD]; male [89.3%]) with end-stage knee OA were enrolled. INTERVENTION: Not applicable. MAIN OUTCOME MEASURE: Functional capacity (6-Minute Walk Test [6MWT]). Physical activity (activPAL wearable sensor; cadence and time sitting, standing, and stepping), pain (Western Ontario and McMaster Universities Osteoarthritis Index-pain subscale) sociodemographic variables, and comorbidities (body mass index and Functional Comorbidity Index) are the main explanatory variables. RESULTS: Participants' wake time was mainly sitting (11.0 h/day) in ≥60-minute bouts (29.7% ± 12.7 of sitting time). Standing (3.4 hours/day) and stepping (1.4 h/day) primarily occurred in 0-5 minute bouts (standing: 87.7% ± 14.4 of standing time, stepping: 98.7% ± 12.7 of stepping time) and stepping cadence was predominantly incidental (1-19 spm; 52.9% ± 9.6 of total stepping time). Backward elimination model results indicated shorter medium-to-brisk cadence bout duration, older age, and higher pain significantly explained shorter 6MWT distance (Adj R2 =0.24, p < .01). CONCLUSIONS: Individuals with knee OA spend most of their waking hours sitting, while standing and stepping occurs in short bouts at very low stepping cadence. Decreased time in high stepping cadence is associated with lower functional capacity. Future studies should explore if increasing the daily time spent in higher step cadence can improve functional capacity in this population.

Unilateral transfemoral osseointegrated prostheses improve joint loading during walking.

People with unilateral transfemoral amputation using socket prostheses are at increased risk for developing osteoarthritis in both the residual hip and intact lower-limb joints. Osseointegrated prostheses are a surgical alternative to socket prostheses that directly attach to the residual femur via a bone-anchored implant, however their multi-joint loading effect is largely unknown. Our objective was to establish how osseointegrated prostheses influence joint loading during walking. Motion capture data (kinematics, ground reaction forces) were collected from 12 participants at baseline, with socket prostheses, and 12-months after prosthesis osseointegration during overground walking at self-selected speeds. Subject-specific musculoskeletal models were developed at each timepoint relative to osseointegration. Internal joint moments were calculated using inverse dynamics, muscle and joint reaction forces (JRFs) were estimated with static optimization. Changes in internal joint moments, JRFs, and joint loading-symmetry were compared using statistical parametric mapping (p≤ 0.05) before and after osseointegration. Amputated limb hip flexion moments and anterior JRFs decreased during terminal stance (p = 0.002, <0.001; respectively), while amputated limb hip abduction moments increased during mid-stance (p < 0.001), amputated hip rotation moment changed from internal to external throughout early stance (p < 0.001). Intact limb hip extension and knee flexion moments (p = 0.028, 0.032; respectively), superior and resultant knee JRFs (p = 0.046, 0.049; respectively) decreased during the loading response following prosthesis osseointegration. These results may indicate that the direct loading transmission of these novel prostheses create a more typical mechanical environment in bilateral joints, which is comparable with loading observed in able-bodied individuals and could decrease the risk of development or progression of osteoarthritis.

Delayed cartilage oligomeric matrix protein response to loading is associated with femoral cartilage composition post-ACLR.

PURPOSE: To determine associations between immediate and delayed response of serum cartilage oligomeric matrix protein (sCOMP) to loading (i.e., 3000 walking steps) and femoral cartilage interlimb T1ρ relaxation times in individual's post-anterior cruciate ligament reconstruction (ACLR). METHODS: This cross-sectional study included 20 individuals 6-12 months following primary ACLR (65% female, 20.5 ± 4.0 years old, 24.9 ± 3.0 kg/m2, 7.3 ± 1.5 months post-ACLR). Serum samples were collected prior to, immediately following, and 3.5 h following walking 3000 steps on a treadmill at habitual walking speed. sCOMP concentrations were processed using enzyme-linked immunosorbent assays. Immediate and delayed absolute sCOMP responses to loading were evaluated immediately and 3.5 h post-walking, respectively. Participants underwent bilateral magnetic resonance imaging with T1ρ sequences to calculate resting femoral cartilage interlimb T1ρ relaxation time ratios between limbs (i.e., ACLR/Uninjured limb). Linear regression models were fitted to determine associations between sCOMP response to loading and femoral cartilage T1ρ outcomes controlling for pre-loading sCOMP concentrations. RESULTS: Greater increases in delayed sCOMP response to loading were associated with greater lateral (∆R2 = 0.29, p = 0.02) but not medial (∆R2 < 0.01, p = 0.99) femoral cartilage interlimb T1ρ ratios. Associations between immediate sCOMP response to loading with femoral cartilage interlimb T1ρ ratios were weak and non-significant (∆R2 range = 0.02-0.09, p range = 0.21-0.58). CONCLUSION: Greater delayed sCOMP response to loading, a biomarker of cartilage breakdown, is associated with worse lateral femoral cartilage composition in the ACLR limb compared to the uninjured limb. Delayed sCOMP response to loading may be a more indicative metabolic indicator linked to deleterious changes in composition than immediate sCOMP response.

Knee kinetics and the medial femoral cartilage cross-sectional area response to loading in indviduals with anterior cruciate ligament reconstruction.

BACKGROUND: Ultrasonography is capable of detecting morphological changes in femoral articular cartilage cross-sectional area in response to an acute bout of walking; yet, the response of femoral cartilage cross-sectional area varies between individuals. It is hypothesized that differences in joint kinetics may influence the response of cartilage to a standardized walking protocol. Therefore, the study purpose was to compare internal knee abduction and extension moments between individuals with anterior cruciate ligament reconstruction who demonstrate an acute increase, decrease, or unchanged medial femoral cross-sectional area response following 3000 steps. METHODS: The medial femoral cartilage in the anterior cruciate ligament reconstructed limb was assessed with ultrasonography before and immediately following 3000 steps of treadmill walking. Knee joint moments were calculated in the anterior cruciate ligament reconstructed limb and compared between groups throughout the stance phase of gait using linear regression and functional, mixed effects waveform analyses. FINDINGS: No associations between peak knee joint moments and the cross-sectional area response were observed. The group that demonstrated an acute cross-sectional area increase exhibited 1) lower knee abduction moments in early stance in comparison to the group that exhibited a decreased cross-sectional area response; and 2) greater knee extension moments in early stance in comparison to the group with an unchanged cross-sectional area response. INTERPRETATION: The propensity of femoral cartilage to acutely increase cross-sectional area in response to walking is consistent with less-dynamic knee abduction and knee extension moment profiles.

Changes in lower extremity joint moments one-year following osseointegration in individuals with Transfemoral lower-limb amputation: A case series.

BACKGROUND: Dissatisfaction with socket prostheses has led to the development of bone-anchored prostheses through osseointegration for people with transfemoral amputation, eliminating the need for a prosthetic socket. Gait deviations of transfemoral prosthesis users may be linked to increased risk of osteoarthritis, and it remains unknown if gait biomechanics change following osseointegration. The purpose of this case series was to evaluate the longitudinal changes in joint kinetics one year post-osseointegration in patients with transfemoral amputation during walking. METHODS: Knee, hip, and trunk internal moments were evaluated in the prosthetic and intact limbs during walking at a self-selected speed in four participants pre- and one-year post-osseointegration. Longitudinal changes were quantified using the percent change (%∆) in peak joint moments between the two time points and Cohen's d (d) effect size was used to determine the magnitude of effect on joint moments during walking one year following osseointegration. FINDINGS: Participants demonstrated increased peak knee extension moment (224 ± 308%∆, d = -1.31) in the prosthetic limb, while demonstrating reduced peak knee extension moment (-43 ± 34%∆, d = 1.82) in the intact limb post-osseointegration. Participants demonstrated bilateral reduction of peak hip extension moment (prosthetic: -22 ± 37%∆, d = 0.86; intact: -29 ± 10%∆, d = 1.27) and bilateral increase of peak hip abduction moment (prosthetic: 45 ± 40%∆, d = 1.20; intact: 23 ± 44%∆, d = 0.74) post-osseointegration. Participants demonstrated reduced peak trunk moments on both the prosthetic (extension: -31 ± 16%∆, d = 1.51; lateral flexion: -21 ± 20%∆, d = 0.63) and intact side (extension: -7 ± 22%∆, d = 0.38; lateral flexion: -22 ± 18%∆, d = 1.12) post-osseointegration. INTERPRETATION: This case series suggests improved gait symmetry in individuals with transfemoral amputation one year following osseointegration, justifying future investigation.

Gait Variability Structure Linked to Worse Cartilage Composition Post-ACL Reconstruction.

INTRODUCTION: Aberrant gait variability has been observed after anterior cruciate ligament reconstruction (ACLR), yet it remains unknown if gait variability is associated with early changes in cartilage composition linked to osteoarthritis development. Our purpose was to determine the association between femoral articular cartilage T1ρ magnetic resonance imaging relaxation times and gait variability. METHODS: T1ρ magnetic resonance imaging and gait kinematics were collected in 22 ACLR participants (13 women; 21 ± 4 yr old; 7.52 ± 1.43 months post-ACLR). Femoral articular cartilage from the ACLR and uninjured limbs were segmented into anterior, central, and posterior regions from the weight-bearing portions of the medial and lateral condyles. Mean T1ρ relaxation times were extracted from each region and interlimb ratios (ILR) were calculated (i.e., ACLR/uninjured limb). Greater T1ρ ILR values were interpreted as less proteoglycan density (worse cartilage composition) in the injured limb compared with the uninjured limb. Knee kinematics were collected at a self-selected comfortable walking speed on a treadmill with an eight-camera three-dimensional motion capture system. Frontal and sagittal plane kinematics were extracted, and sample entropy was used to calculate kinematic variability structure (KV structure ). Pearson's product-moment correlations were conducted to determine the associations between T1ρ and KV structure variables. RESULTS: Lesser frontal plane KV structure was associated with greater mean T1ρ ILR in the anterior lateral ( r = - 0.44, P = 0.04) and anterior medial condyles ( r = - 0.47, P = 0 .03). Lesser sagittal plane KV structure was associated with greater mean T1ρ ILR in the anterior lateral condyle ( r = - 0.47, P = 0.03). CONCLUSIONS: The association between less KV structure and worse femoral articular cartilage proteoglycan density suggests a link between less variable knee kinematics and deleterious changes joint tissue changes. The findings suggest that less knee kinematic variability structure is a mechanism linking aberrant gait to early osteoarthritis development.

Improvements in disability and function in people with lower-limb amputation one year after prosthesis osseointegration.

BACKGROUND: People with lower-limb amputation (LLA) are routinely prescribed a socket prosthesis; however, many socket prosthesis users experience severe complications with the fit of their prosthesis including residual limb wounds and pain. Osseointegration is a procedure that creates a direct connection between the bone and prosthetic limb through a bone-anchored prosthesis, eliminating the need for a socket interface. It is offered as a secondary procedure to people with LLA who experience significant complications with socket prostheses. OBJECTIVES: To evaluate change in disability and function 1 year postosseointegration compared with preosseointegration in people with LLA. STUDY DESIGN: Single group, pretest, and post-test. METHODS: Twelve participants (9 transfemoral and 3 transtibial amputations, age: 44 ± 10 years, 7 female participants, 14 ± 12 years since amputation) with unilateral LLA underwent osseointegration with press-fit implants. Disability was measured with the World Health Organization Disability Assessment Schedule 2.0, and function was measured with both Prosthetic Limb Users Mobility Survey and the Activities-Specific Balance Confidence Scale. Questionnaires were administered preosseointegration and 1 year postosseointegration. Paired t tests assessed change in outcomes between time points. RESULTS: Postosseointegration, participants demonstrated reduced disability measured with World Health Organization Disability Assessment Schedule 2.0 (%Δ = -52.6, p = 0.01), improved mobility measured with Prosthetic Limb Users Mobility Survey (%Δ = 21.8, P < 0.01), and improved balance confidence measured with the Activities-Specific Balance Confidence Scale (%Δ = 28.4, P < 0.01). CONCLUSIONS: Participants report less disability and greater function in their prosthesis postosseointegration. Osseointegration is a novel procedure for people experiencing complications with their socket prosthesis, and this study is the first to show improvements in disability postosseointegration.

Immediate Effects of Walking With a Knee Brace After Anterior Cruciate Ligament Reconstruction: A Biomechanical, Biochemical, and Structural Approach.

CONTEXT: Individuals who undergo anterior cruciate ligament reconstruction (ACLR) are at higher risk of posttraumatic osteoarthritis. Altered joint tissue loading caused by aberrant gait biomechanics leads to deleterious changes in joint health linked to the onset of posttraumatic osteoarthritis. Knee braces have been used to modify joint tissue loading in individuals with joint injury, yet the effects of walking with a brace after ACLR on biomechanical, biochemical, and structural cartilage outcomes are unknown. OBJECTIVE: To compare biomechanical, biochemical, and structural outcomes between braced and nonbraced walking in individuals with ACLR. DESIGN: Crossover study. SETTING: Research laboratory. PATIENTS OR OTHER PARTICIPANTS: A total of 34 individuals with unilateral ACLR (18 females, 16 males; time since ACLR = 50.1 ± 36.8 months). INTERVENTION(S): Gait biomechanics were assessed during braced and unbraced conditions on separate days. MAIN OUTCOME MEASURE(S): Vertical ground reaction force, knee-flexion angle, and internal knee-extension moment waveforms were evaluated throughout the stance phase and compared between conditions. Percentage changes in serum cartilage oligomeric matrix protein (%ΔCOMP) and femoral cartilage cross-sectional area (%ΔCSA) measured via ultrasound were calculated after a 3000-step walking protocol. RESULTS: Braced walking increased the knee-flexion angle (largest difference = 3.56°; Cohen d effect size = 1.72) and knee-extension moment (largest difference = -0.48% body weight × height; Cohen d effect size = -1.14) compared with nonbraced walking but did not influence vertical ground reaction force. Whereas no difference (P = .20) in %ΔCOMP existed between the braced and nonbraced conditions in the entire cohort (n = 30 with complete blood data), a larger increase (P = .04) in %ΔCOMP was seen during nonbraced than braced walking in individuals who demonstrated increased COMP during nonbraced walking. No difference (P = .86) in %ΔCSA was present between the braced and nonbraced conditions. CONCLUSIONS: Braced walking may improve sagittal-plane gait biomechanics and %ΔCOMP in a subset of individuals who demonstrate a typical increased COMP response to load (ie, increase in COMP) after nonbraced walking.

Osseointegrated prostheses improve balance and balance confidence in individuals with unilateral transfemoral limb loss.

BACKGROUND: More than half of patients with lower-limb amputation who use socket prostheses experience at least one fall annually. These falls are primarily attributed to reduced proprioception which negatively affects balance. A promising alternative to socket prostheses are osseointegrated prostheses that involve direct fixation of the prosthetic limb to the residual limb through a bone-anchored implant, yet its effect on balance remains unknown. RESEARCH QUESTION: Do osseointegrated prostheses change static and dynamic balance, as well as patient reported measures of balance confidence, compared to a socket prosthesis? METHODS: A sample of 10 patients with unilateral transfemoral amputation scheduled to undergo prosthesis osseointegration were enrolled (6 F/4 M, BMI: 26.7 ± 2.9 kg/m2, Age: 46.1 ± 6.3 years). Motion capture data during quiet standing (eyes opened and eyes closed) and overground walking at a self-selected speed, and the Activities-Specific Balance Confidence (ABC) scale, were collected before (with socket prosthesis) and 12-months following osseointegration. Postural sway via the center of pressure (COP), variability of spatiotemporal parameters, and ABC scores were compared using a repeated measures design before and after osseointegration. RESULTS: Following prosthesis osseointegration, COP path length and 95 % confidence ellipse area were reduced during quiet standing (d = 0.75, P = 0.09; d = 0.52, P = 0.29, respectively) and the variability of step width and length were reduced during overground walking (d = 0.50, P = 0.06; d = 0.72, P = 0.06, respectively). Furthermore, patients reported significantly improved ABC scores with an osseointegrated prosthesis compared to a socket prosthesis (d = -1.36, P = 0.01). SIGNIFICANCE: Improvements in postural sway, reductions in gait variability, and greater balance confidence indicate that osseointegrated prostheses improve balance for people with unilateral transfemoral amputation.

Diagnosis and management of isolated neutropenia: A survey of pediatric hematologist oncologists.

BACKGROUND: Isolated neutropenia is a common referral to pediatric hematology oncology (PHO) physicians. There are no established consensus guidelines in the diagnosis and management of patients with isolated, asymptomatic, and incidentally discovered neutropenia. METHODS: A survey was distributed to PHO physicians on the American Society of Pediatric Hematology Oncology member discussion page to determine the common diagnostic and management decisions regarding patients with isolated neutropenia and to explore beliefs regarding the term "benign ethnic neutropenia." RESULTS: One hundred twenty-six PHO attending physicians completed the survey. The most common tests reportedly ordered for this patient population included complete blood cell count (CBC) (98%), peripheral smear (75%), antineutrophil antibody testing (29%), and immunoglobulins (24%). Providers were more likely to order an antineutrophil antibody in toddlers (p = .0085), and antinuclear antibody (ANA) panels in adolescents (p < .001). Half of providers do not request additional CBCs prior to their initial consultation, and most suggest referring patients with mild neutropenia after confirming a declining absolute neutrophil count (ANC) (51%). The three most important factors influencing ongoing follow-up included: history of recurrent/severe infections (98%), family history of blood disorders (98%), and more severe/progressively worsening neutropenia (97%). Seventy percent of respondents have diagnosed patients with "benign ethnic neutropenia," and 75% support replacement of the term to "typical neutrophil count with Fy(a-/b-) status," if confirmed with red cell phenotyping. CONCLUSION: We identified practice patterns of PHO physicians for the diagnosis and management of patients referred for asymptomatic and isolated neutropenia. These data provide the framework to conduct cost-effectiveness studies.

Evaluation for Bleeding Disorders in Suspected Child Abuse.

Bruising or bleeding in a child can raise the concern for child abuse. Assessing whether the findings are the result of trauma and/or whether the child has a bleeding disorder is critical. Many bleeding disorders are rare, and not every child with bruising/bleeding that may raise a concern for abuse requires an evaluation for bleeding disorders. However, in some instances, bleeding disorders can present in a manner similar to child abuse. Bleeding disorders cannot be ruled out solely on the basis of patient and family history, no matter how extensive. The history and clinical evaluation can be used to determine the necessity of an evaluation for a possible bleeding disorder, and prevalence and known clinical presentations of individual bleeding disorders can be used to guide the extent of laboratory testing. This clinical report provides guidance to pediatricians and other clinicians regarding the evaluation for bleeding disorders when child abuse is suspected.

Feasibility of repeated session error-augmentation gait training for people with nontraumatic transtibial amputation.

BACKGROUND: Spatiotemporal gait asymmetries are a persistent problem for people with non-traumatic lower-limb amputation. To date, there is limited knowledge of multi-session gait training interventions targeting step length symmetry after non-traumatic amputation. OBJECTIVE: The objective was to evaluate the feasibility and efficacy of an eight-session, treadmill-based error-augmentation gait training (EAT) protocol to improve spatiotemporal gait asymmetry in people with non-traumatic transtibial amputation (TTA). STUDY DESIGN: Pre-post, single group. Methods: The EAT protocol involved eight training sessions (twice per week, four weeks) of supervised split-belt treadmill walking with asymmetrical belt speeds for five, three-minute sets each session. Step length symmetry during overground walking at a self-selected gait speed was assessed prior to, weekly, and one-week after the EAT protocol. Feasibility outcomes included protocol fidelity, safety, participant acceptability, and efficacy. RESULTS: Seven of the eight participants (87.5%) completed the intervention at the prescribed dose. One participant developed a skin blister on their residual limb, which was possibly related to the intervention. No falls, musculoskeletal injuries, or increases in pain occurred. Participants rated EAT as acceptable based on scores on the Intrinsic Motivation Inventory - Interest/Enjoyment subscale (6.6 ± 0.5; mean ± SD). Average between-limb step length Normalized Symmetry Index improved (was reduced) one-week following EAT (2.41 ± 6.6) compared to baseline (5.47 ± 4.91) indicating a moderate effect size (d=0.53). CONCLUSIONS: An eight session EAT program delivered over four weeks using a split-belt treadmill is feasible for people with unilateral non-traumatic TTA and may reduce step length asymmetry up to a week after intervention.