Search

Purpose: Uncertainties remain about the safety and efficacy of therapies for managing intracranial hypertension in acute brain injured (ABI) patients. This study aims to describe the therapeutical approaches used in ABI, with/without intracranial pressure (ICP) monitoring, among different pathologies and across different countries, and their association with sixmonths mortality and neurological outcome. Methods: A preplanned subanalysis of the SYNAPSE-ICU study, a multicentre, prospective, international, observational cohort study, describing the ICP treatment, graded according to Therapy Intensity Level (TIL) scale, in patients with ABI during the first week of intensive care unit (ICU) admission. Results: 2320 patients were included in the analysis. The median age was 55 (I-III quartiles = 39-69) years, and 800 (34.5%) were female. During the first week from ICU admission, no-basic TIL was used in 382 (16.5%) patients, mild-moderate in 1643 (70.8%), and extreme in 295 cases (eTIL, 12.7%). Patients who received eTIL were younger (median age 49 (I-III quartiles = 35-62) vs 56 (40-69) years, p

Objective The purpose of this study was to assess feasibility, reliability, and validity of a new performance-based test, the Shoulder Performance Activity Test (SPAT). Methods People with shoulder pain (n = 93) and without shoulder pain (n = 43) were included. The SPAT consists of overhead reach, hand behind head, and hand behind back tasks, each performed with 20 repetitions and rated by time, pain, and effort. The SPAT scores were summed for time, pain, and effort, and a total score across the 3 tasks. Feasibility was assessed by the percentage of SPAT task completion, test–retest reliability by intraclass correlation coefficient (ICC), standard error measurement, minimal detectable change, and known-groups construct validity by comparing between groups (shoulder pain and no pain) and between shoulders in those with pain. Results All participants performed the 3 SPAT tasks. The ICC was 0.74–0.91, and the minimal detectable change was 3.1–4.7 for task scores and 10.0 points for the total score. Individuals with pain presented higher tasks and total scores compared with those without pain. The moderate/severe pain group had higher scores than the low pain and no shoulder pain groups, and the low pain group had higher scores than the no pain group. Scores were higher in the involved shoulder compared with the uninvolved shoulder. Conclusion The SPAT is a feasible and reliable performance-based test for use in patients with shoulder pain and can differentiate between individuals with and without pain, among different levels of pain, and between involved and uninvolved shoulders. Impact The SPAT provides a standardized method for clinicians to assess shoulder functional performance tasks, which can enable a comprehensive assessment of shoulder disability and clinical decision making. The error metrics can be used to determine meaningful changes in performance.

Anatomic total shoulder arthroplasty is the gold standard shoulder replacement procedure for patients with an intact rotator cuff and sufficient glenoid bone to accommodate prosthetic glenoid implant and offers reliable patient satisfaction, excellent implant longevity, and a low incidence of complications. Disparity exists in the literature regarding rehabilitation strategies following anatomic total shoulder arthroplasty. This article presents a consensus statement from experts in the field on rehabilitation following anatomic total shoulder arthroplasty. The goal of this consensus statement is to provide a current evidence–based foundation to inform the rehabilitation process after anatomic total shoulder arthroplasty. These guidelines apply to anatomic total shoulder arthroplasty (replacement of the humeral head and glenoid), hemiarthroplasty (replacing only the humeral head), and hemiarthroplasty with glenoid reaming or resurfacing. The consensus statement integrates an extensive literature review, as well as survey results of the practice patterns of members of the American Society of Shoulder and Elbow Therapists and the American Shoulder and Elbow Surgeons. Three stages of recovery are proposed, which initially protect and then gradually load soft tissue affected by the surgical procedure, such as the subscapularis, for optimal patient outcomes. The proposed guidelines should be used in collaboration with surgeon preferences and patient-specific factors. LEVEL OF EVIDENCE: Level IV; Expert Opinion

ObjectiveTo characterise whether preseason screening of shoulder range of motion (ROM) is associated with the risk of shoulder and elbow injuries in overhead athletes.DesignSystematic review and meta-analysis.Data sourcesSix electronic databases up to 22 September 2018.Eligibility criteriaInclusion criteria were (1) overhead athletes from Olympic or college sports, (2) preseason measures of shoulder ROM, (3) tracked in-season injuries at the shoulder and elbow, and (4) prospective cohort design. Exclusion criteria were (1) included contact injuries, (2) lower extremity, spine and hand injuries, and (3) full report not published in English.ResultsFifteen studies were identified, and they included 3314 overhead athletes (baseball (74.6%), softball (3.1%), handball (16.1%), tennis (2.0%), volleyball (2.0%) and swimming (2.2%)). Female athletes are unrepresented (12% of the overall sample). Study quality ranged from 11 to 18 points on a modified Downs and Black checklist (maximum score 21, better quality). In one study, swimmers with low (100°) shoulder external rotation were at higher risk of injuries. Using data pooled from three studies of professional baseball pitchers, we showed in the meta-analysis that shoulder external rotation insufficiency (throwing arm ConclusionPreseason screening of shoulder external rotation ROM may identify professional baseball pitchers and swimmers at risk of injury. Shoulder ROM screening may not be effective to identify handball, softball, volleyball and tennis players at risk of injuries. The results of this systematic review and meta-analysis should be interpreted with caution due to the limited number of studies and their high degree of heterogeneity.PROSPERO registration numberCRD42017072895.

BackgroundBehavioral and psychological symptoms of dementia (BPSD) have a high prevalence, and their presence is associated with a severe impact in terms of social costs. However, dedicated clinical tools or biomarkers to detect these symptoms are lacking. Thus, BPSD management in clinical settings is challenging. The aim of this study was to investigate the perception and the treatment strategies for BPSD in Italian centers working in the dementia field.MethodsA multicenter, national survey was developed by BPSD Study Group of the Italian Neurological Society for Dementia (SINDEM). The survey consisted of a semi-structured questionnaire that was e-mailed to SINDEM members, dementia centers part of the national network of memory clinics (Centers for Cognitive Deterioration and Dementia [CDCD]), and clinicians working in dementia care settings. The questions were focused on (1) perceived global frequency and relevance of BPSD; (2) tools used to assess BPSD; (3) pharmacological treatment for psychosis, apathy, agitation, aggression, depression, anxiety, sleep, and nutrition disturbances; (4) non-pharmacological treatments; (5) drugs side effects.ResultsOne-hundred and thirty-six clinicians participated in this study. Seventy-nine participants worked in a CDCD and 57 in other settings. The perceived frequency of BPSD was 74%. BPSD are detected by means of a clinical assessment for 96.3% or a caregiver interview for 97%. For psychosis treatment the first choice was atypical antipsychotics (83.3%), followed by typical antipsychotic (8.9%) and antidepressants (4.8%). For agitation, atypical antipsychotics were the first-choice treatment in 64% of cases and antidepressants in 16.1%. For aggression, the most used drugs were atypical antipsychotics (82.9%). For anxiety, 55.2% use antidepressants, 17.9% use atypical antipsychotics, and 16.9% use benzodiazepines. Interestingly, most of the centers apply non-pharmacological treatments for BPSD. Some differences emerged comparing the responses from CDCD and other care settings.ConclusionThe survey results revealed many differences in BPSD perception, treatment options, and observed side effect according to the clinical setting. This variability can be explained by the absence of clear guidelines, by differences in patients' characteristics, and by clinical practice based on subjective experience. These results suggest that producing guidelines for the pharmacological treatment of BPSD is a major need.

BACKGROUND: The paucity of longitudinal clinical studies limits our understanding of the development of shoulder pain with repetitive shoulder tasks, and its association with underlying mind and body mechanisms. Tendon thickening characterizes painful shoulder supraspinatus tendinopathy, and the perception of pain can be affected by the presence of psychological factors such as anxiety and depression. This study determined the incidence of shoulder pain in novice individuals exposed to repetitive shoulder tasks, and the associated change in outcomes of supraspinatus tendon morphology and measures of anxiety and depression. METHODS: We recruited dental hygiene (DH) students (n = 45, novice and exposed to shoulder repetitive tasks) and occupational therapy (OT) students (n = 52, novice, but not exposed to shoulder repetitive tasks), following them over their first year of training. We measured shoulder pain, supraspinatus morphology via ultrasonography, and psychosocial distress via the Hospital Anxiety and Depression Scale. We compared the incidence of shoulder pain (defined as a change of visual analog scale for pain score greater than the minimal clinically important difference) between DH and OT students using Fisher exact test. We used mixed effects models to longitudinally compare the change in outcomes between 3 groups: DH students who develop and did not develop shoulder pain, and OT students. RESULTS: The incidence of shoulder pain is higher in DH students (relative risk = 4.0, 95% confidence interval [CI] 1.4, 11.4). After 1 year, DH students with pain had the greatest thickening of the supraspinatus (0.7 mm, 95% CI 0.4, 0.9). The change in supraspinatus thickness of DH students with pain was greater than both DH students with no pain (0.4 mm, 95% CI 0.1, 0.8) and OT students (0.9 mm, 95% CI 0.5, 1.2). Anxiety score increased 3.8 points (95% CI 1.6, 5.1) in DH students with pain, and 43% of DH students with pain had abnormal anxiety score at 1 year (relative risk = 2.9, 95% CI 1.0, 8.6). CONCLUSION: Our results provide support for the theoretical model of repetitive load as a mechanism of tendinopathy. The supraspinatus tendon thickens in the presence of repetitive tasks, and it thickens the most in those who develop shoulder pain. Concurrently, anxiety develops with shoulder pain, indicating a potential maladaptive central mechanism that may impact the perception of pain. LEVEL OF EVIDENCE: Level I; Prospective Cohort Design; Prognosis Study

Recent works have demonstrated a linear relationship between muscle activation and shear modulus in various superficial muscles. As such, it may be possible to overcome limitations of traditional electromyography (EMG) methods by assessing activation using shear wave elastography. However, the relationship has not been wholly validated in deep muscles. This study measured the association between squared shear wave velocity, which is related to shear modulus, and activation within superficial and deep muscles. This relationship was also compared between surface and intramuscular EMG electrodes. We simultaneously recorded EMG and shear wave velocity in one deep (brachialis) and one superficial (brachioradialis) muscle in ten healthy individuals during isometric elbow flexion across a wide range of contraction intensities. Muscle activation and squared shear wave velocity demonstrated good reliability (ICC > 0.75) and showed a linear relationship (P < 0.05) for all muscle/EMG electrode type combinations (study conditions) after down-sampling. Study condition was not a significant within-subject factor to the slope or intercept of the relationship (P > 0.05). This work demonstrates that activation of both superficial and deep muscles can be assessed noninvasively using ultrasound shear wave elastography and is a critical step toward demonstrating elastography’s utility as an alternative to EMG.

Background: The indications for intracranial pressure (ICP) monitoring in patients with acute brain injury and the effects of ICP on patients’ outcomes are uncertain. The aims of this study were to describe current ICP monitoring practises for patients with acute brain injury at centres around the world and to assess variations in indications for ICP monitoring and interventions, and their association with long-term patient outcomes. Methods: We did a prospective, observational cohort study at 146 intensive care units (ICUs) in 42 countries. We assessed for eligibility all patients aged 18 years or older who were admitted to the ICU with either acute brain injury due to primary haemorrhagic stroke (including intracranial haemorrhage or subarachnoid haemorrhage) or traumatic brain injury. We included patients with altered levels of consciousness at ICU admission or within the first 48 h after the brain injury, as defined by the Glasgow Coma Scale (GCS) eye response score of 1 (no eye opening) and a GCS motor response score of at least 5 (not obeying commands). Patients not admitted to the ICU or with other forms of acute brain injury were excluded from the study. Between-centre differences in use of ICP monitoring were quantified by using the median odds ratio (MOR). We used the therapy intensity level (TIL) to quantify practice variations in ICP interventions. Primary endpoints were 6 month mortality and 6 month Glasgow Outcome Scale Extended (GOSE) score. A propensity score method with inverse probability of treatment weighting was used to estimate the association between use of ICP monitoring and these 6 month outcomes, independently of measured baseline covariates. This study is registered with ClinicalTrial.gov, NCT03257904. Findings: Between March 15, 2018, and April 30, 2019, 4776 patients were assessed for eligibility and 2395 patients were included in the study, including 1287 (54%) with traumatic brain injury, 587 (25%) with intracranial haemorrhage, and 521 (22%) with subarachnoid haemorrhage. The median age of patients was 55 years (IQR 39–69) and 1567 (65%) patients were male. Considerable variability was recorded in the use of ICP monitoring across centres (MOR 4·5, 95% CI 3·8–4·9 between two randomly selected centres for patients with similar covariates). 6 month mortality was lower in patients who had ICP monitoring (441/1318 [34%]) than in those who were not monitored (517/1049 [49%]; p

Background Lombardy was the epicenter in Italy of the first wave of COVID-19 pandemic. To face the contagion growth, from March 8 to May 8 2020, a regional law re-designed the hub-and-spoke system for time-dependent diseases to better allocate resources for COVID-19 patients. Methods We report the reorganization of the major hospital in Lombardy during COVID-19 pandemic, including the rearrangement of its ICU beds to face COVID-19 pandemic and fulfill its role as extended hub for time-dependent diseases while preserving transplant activity. To highlight the impact of the emergently planned hub-and-spoke system, all patients admitted to a COVID-19-free ICU hub for trauma, neurosurgical emergencies and stroke during the two-month period were retrospectively collected and compared to 2019 cohort. Regional data on organ procurement was retrieved. Observed-to-expected (OE) in-ICU mortality ratios were computed to test the impact of the pandemic on patients affected by time-dependent diseases. Results Dynamic changes in ICU resource allocation occurred according to local COVID-19 epidemiology/trends of patients referred for time-dependent diseases. The absolute increase of admissions for trauma, neurosurgical emergencies and stroke was roughly two-fold. Patients referred to the hub were older and characterized by more severe conditions. An increase in crude mortality was observed, though OE ratios for in-ICU mortality were not statistically different when comparing 2020 vs. 2019. An increase in local organ procurement was observed, limiting the debacle of regional transplant activity. Conclusions We described the effects of a regional emergently planned hub-and-spoke system for time-dependent diseases settled in the epicenter of COVID-19 pandemic in Italy.

Objective To characterize patients with acute ischemic stroke related to SARS-CoV-2 infection and assess the classification performance of clinical and laboratory parameters in predicting in-hospital outcome of these patients. Methods In the setting of the STROKOVID study including patients with acute ischemic stroke consecutively admitted to the ten hub hospitals in Lombardy, Italy, between March 8 and April 30, 2020, we compared clinical features of patients with confirmed infection and non-infected patients by logistic regression models and survival analysis. Then, we trained and tested a random forest (RF) binary classifier for the prediction of in-hospital death among patients with COVID-19. Results Among 1013 patients, 160 (15.8%) had SARS-CoV-2 infection. Male sex (OR 1.53; 95% CI 1.06–2.27) and atrial fibrillation (OR 1.60; 95% CI 1.05–2.43) were independently associated with COVID-19 status. Patients with COVID-19 had increased stroke severity at admission [median NIHSS score, 9 (25th to75th percentile, 13) vs 6 (25th to75th percentile, 9)] and increased risk of in-hospital death (38.1% deaths vs 7.2%; HR 3.30; 95% CI 2.17–5.02). The RF model based on six clinical and laboratory parameters exhibited high cross-validated classification accuracy (0.86) and precision (0.87), good recall (0.72) and F1-score (0.79) in predicting in-hospital death. Conclusions Ischemic strokes in COVID-19 patients have distinctive risk factor profile and etiology, increased clinical severity and higher in-hospital mortality rate compared to non-COVID-19 patients. A simple model based on clinical and routine laboratory parameters may be useful in identifying ischemic stroke patients with SARS-CoV-2 infection who are unlikely to survive the acute phase.

Background Wearable devices validly assess spatiotemporal running parameters (cadence, vertical oscillation and ground contact time), but the relationship between these parameters and lower limb loading parameters (loading rate, peak vertical ground reaction force [vGRF] and braking impulse) is unknown. Purpose To characterize changes in lower limb loading parameters in runners instructed to run with increased cadence or low vertical oscillation, and to determine whether the change in spatiotemporal parameters predicted the changes in lower limb loading parameters. Study Design Cross Sectional Cohort Study. Methods Twenty healthy runners completed three running trials in three conditions: baseline, high cadence, and low vertical oscillation. Spatiotemporal parameters were measured with a wearable device and lower limb loading was measured using an instrumented treadmill. Spatiotemporal and loading parameters were analyzed between running conditions via a repeated measure ANOVA. A hierarchical regression model was used to determine if changes in spatiotemporal parameters predicted the change of loading parameters during conditions. Results High cadence and low oscillation conditions reduced average vertical loading rate (p = 0.013 and p = 0.002, respectively), instantaneous vertical loading rate (p = 0.022 and p = 0.001, respectively), and peak vGRF (p = 0.025 and p

For kinematic studies of the shoulder, electromagnetic sensors are commonly placed on the humerus, scapula, and trunk. The trunk sensor is used to describe humeral and scapular kinematics with respect to the trunk. There are two common trunk sensor placements, the sternum or third thoracic vertebrae (T3). It is currently unclear if placement of the trunk sensor affects kinematics, making it difficult to compare data across studies. The purpose of this study was to compare two trunk sensor placements (T3 and sternum) on trunk and scapular kinematics during arm elevation. An electromagnetic tracking system was used to collect kinematic data during five consecutive repetitions of ascending and descending arm elevation in the sagittal plane. The results indicate that trunk sensor placement had no significant effect on trunk kinematics or scapular upward/downward rotation and internal/external rotation. Scapular anterior/posterior tilt was significantly greater when the trunk sensor was on the sternum compared to the T3 vertebrae during ascending 30°–120°: mean difference = −3.51° (95%CI: −5.61, −1.40), and descending 120°–30°: mean difference = −3.27° (95%CI: −6.07, −0.48). However, the difference in anterior/posterior tilt did not exceed the error (minimal detectable change), and thus is likely not a meaningful difference. These results indicate the trunk sensors can be affixed on T3 or the sternum, depending on the needs of the study.

Study Design Cross-sectional. Background The scapular dyskinesis test (SDT) has demonstrated reliability and validity, but its utility for clinical decision making is unclear. Objectives To characterize the prevalence of scapular dyskinesis in participants with and without shoulder pain, and to determine the influence of blinding to the presence of shoulder pain on prevalence of scapular dyskinesis. Methods Participants (n = 135), 67 with shoulder pain and 68 healthy controls, were included in this study. The SDT was performed by 2 examiners, from a total of 21 physical therapists. The second examiner was blinded to the participant's presence of shoulder pain. The SDT involved participants performing 5 repetitions of shoulder flexion and abduction, while the clinician observed for scapular dyskinesis, as characterized by scapular winging or dysrhythmia. Dyskinesis was rated as normal, subtle, or obvious. Ratings were collapsed into 2 groups, dyskinesis (subtle and obvious) and no dyskinesis (normal), as recommended by expert consensus. Results There were no significant differences for scapular dyskinesis prevalence between the shoulder pain group and control group during the SDT in abduction (shoulder pain, 67.2%; 95% confidence interval [CI]: 0.55, 0.77 and control group, 52.9%; 95% CI: 0.41, 0.64; P = .09) or flexion (shoulder pain, 67.2%; 95% CI: 0.55, 0.77 and control group, 61.8%; 95% CI: 0.50, 0.72; P = .51). There were significant differences (P ≤001) between the examiners' SDT ratings in the shoulder pain group. The unblinded examiner reported a higher prevalence when testing the involved shoulder for dyskinesis in flexion (blinded, 67.7%; 95% CI: 0.56, 0.78 and unblinded, 80%; 95% CI: 0.69, 0.88) and during abduction (blinded, 66.2%; 95% CI: 0.54, 0.76 and unblinded, 78.5%; 95% CI: 0.67, 0.87). Conclusion Scapular dyskinesis as assessed with the SDT is not more prevalent in those with shoulder pain. Rating was influenced by an examiner's knowledge of shoulder pain presence. Scapular dyskinesis may represent normal movement variability. Level of Evidence Diagnosis, level 4. J Orthop Sports Phys Ther 2017;47(8):530-537. Epub 6 Jul 2017. doi:10.2519/jospt.2017.7268.

Background Weight-bearing asymmetry is common in individuals with hip osteoarthritis and after total hip arthroplasty. Including symmetry training to the rehabilitation programs may normalize movement strategies during dynamic tasks. The purpose of this study was to evaluate the immediate influences of real-time visual feedback of weight distribution on the interlimb movement symmetry during the sit-to-stand task, before and after total hip arthroplasty, and to determine whether physical impairments affect the response to visual feedback. Methods Subjects before and after total hip arthroplasty participated in three- dimensional motion analysis. Subjects completed 3 trials of sit-to-stand task in two conditions; “without visual feedback” and “with visual feedback”. Outcome measures were the interlimb symmetry of vertical ground reaction force, and joint kinematics and kinetics. Pain and strength of lower limbs were assessed. Findings Compared to “without visual feedback” condition, subjects moved with greater symmetry of vertical ground reaction force and joint kinetics when visual feedback was received. However, subjects continued to demonstrate interlimb difference for joint kinetics and vertical ground reaction force in the visual feedback condition. The increase in symmetry was not strongly influenced by physical impairments and subjects before and after total hip arthroplasty responded similarly to the feedback. Interpretations We concluded that in a single session, the visual feedback of weight bearing distribution had a positive immediate effect on movement symmetry during the sit-to-stand task. Future studies that assess long-term retention and functional benefits are warranted before visual feedback is incorporated in rehabilitation for this patient population.

Background: There are few non-invasive treatment options to slow the progression of osteoarthritis (OA). Recently, a novel knee unloader brace with knee extension assist has become commercially available. Therefore, the purpose of this study was to evaluate the preliminary effectiveness of using a novel unloader brace with extension assist to improve pain and functional outcomes for patients with knee OA. Methods: Thirty subjects (17 control group, 13 brace group) completed baseline and 6-week follow up testing with no brace. Patients were randomized into a Brace or No Brace group after baseline testing. Functional tests [timed up and go (TUG), stair climbing test (SCT) and six-minute walk (6MW)], self-reported measures [Knee Outcome Survey (KOS), pain, Patient Specific Functional Scale (PSFS)] and isometric knee extension strength were assessed. Repeated measure ANOVAs were used to identify differences in group and time. Pearson correlation coefficients were calculated for both average number of steps in the brace and exercises compliance compared to change in clinical scores for each group. Results: There was a significant interaction effect for “worst pain” (P=0.002), the brace group improved from a 7.3/10 to 4.7/10 at follow-up (P=0.006) while the control group had no change. There was an effect of time for the SCT (P=0.02), “best knee pain” (P=0.050), and knee extension range of motion (ROM) (P=0.041). There were no significant correlations between exercise compliance and change in outcomes, but when the groups were collapsed there was a significant correlation between compliance and change in knee extension ROM (r=0.526; P=0.025). Conclusions: The extension assist pneumatic unloader brace group demonstrated a significant and important reduction in the “worst knee pain”. This may indicate that wearing the brace was able to reduce painful flares. Both groups improved over time for the SCT, “best knee pain”, and knee extension ROM, which can be attributed to the stretching protocol. This unloader brace is a promising non-invasive treatment option for patients with knee OA when combined with a stretching program.

Thoracic spine thrust manipulation has been shown to improve patient-rated outcomes for individuals with neck pain. However, there is limited evidence of its effectiveness in patients with cervical radiculopathy.To compare the immediate and short-term effects of thoracic manipulation to those of a sham thoracic manipulation in patients with cervical radiculopathy.In this multicenter randomized controlled trial, participants with cervical radiculopathy were randomized to receive either manipulation (n = 22) or sham manipulation (n = 21) of the thoracic spine. Outcomes were measured at baseline, immediately after treatment, and at a follow-up 48 to 72 hours after manipulation. A repeated-measures analysis of variance was used to analyze neck and upper extremity pain (numeric pain-rating scale), disability (Neck Disability Index), cervical range of motion (ROM), and endurance (deep neck flexor endurance test). The chi-square test was used to analyze changes in neck and upper extremity pain, centralization of symptoms, and beliefs about receiving the active manipulation treatment using a global rating of change scale.Neck and upper extremity pain, cervical ROM, disability, and deep neck flexor endurance all showed significant interactions between group and time (One session of thoracic manipulation resulted in improvements in pain, disability, cervical ROM, and deep neck flexor endurance in patients with cervical radiculopathy. Patients treated with manipulation were more likely to report at least moderate change in their neck and upper extremity symptoms up to 48 to 72 hours following treatment.Therapy, level 2.

Background: Gymnastics is a demanding sport that places unique forces on the upper extremity. The repetitive nature of the sport and the high-impact forces involved may predispose the gymnast to overuse injuries. Risk factors for injuries in gymnastics are not well understood. Purpose/Hypothesis: The purpose of this study was to ascertain whether preseason upper extremity range of motion (ROM) and strength differ between National Collegiate Athletic Association (NCAA) Division I collegiate gymnasts who sustain an in-season upper extremity injury and those who do not. We hypothesized that gymnasts who sustain an upper extremity injury would demonstrate reduced ROM and strength compared with noninjured gymnasts. Study Design: Cohort study; Level of evidence, 3. Methods: Over 4 seasons, from 2014 to 2018, a total of 15 female NCAA Division I collegiate gymnasts underwent preseason upper extremity ROM (shoulder: flexion, internal and external rotation; elbow: extension; wrist: extension) and strength (shoulder: internal and external rotation, and middle and lower trapezius) testing. Overuse upper extremity injuries were tracked in each subsequent season. Gymnasts were dichotomized into injured and noninjured groups, and a 2 × 2 analysis of variance was used to measure differences in preseason measures between the groups as well as within arms (injured vs noninjured arm for the injured group; dominant vs nondominant arm for the noninjured group). Results: A total of 12 overuse upper extremity injuries (10 shoulders; 2 wrist/forearm) occurred during 31 gymnast-seasons. There were no significant interactions for preseason ROM and strength measurements between groups (injured vs noninjured) or within arms (injured and noninjured arm for the injured group; dominant and nondominant arm for the noninjured group; P = .07). Conclusion: Preseason upper extremity ROM and strength were not different between gymnasts who sustained an in-season upper extremity overuse injury and those who did not. It is possible that ROM and strength measures used to screen other overhead athletes may not capture the unique features and requirements of gymnastics. Further, it may be challenging to discern differences in clinical measures of ROM and strength in gymnastics populations owing to the bilateral nature of the sport.

The purpose of this study was to assess the ankle, knee, and hip joint contributions to the total support moment (TSM) and the activation patterns of muscles in the lower leg in patients after total knee arthroplasty (TKA) and healthy older adults during the step up and over task. Moreover, the relationship between quadriceps strength and knee contribution to TSM was measured. Twenty patients six-months after TKA and twenty healthy controls were recruited for this study. Motion and surface electromyographic (EMG) analyses were performed during a step up and over task. Biomechanics and EMG variables were compared between groups using ANCOVA models with movement speed as covariate. Patients after TKA had reduced contribution to the TSM from the knee joint, and greater contribution from the hip and ankle joints, possibly to compensate for the reduced contribution at the knee. No consistent differences of EMG activation or co-contraction were found between groups. Patients with stronger quadriceps had significantly higher knee contribution to TSM during the lowering phase of the task. The results of this study suggest that patients after TKA may use compensatory strategies at the hip and ankle joints to safely perform the step up and over task. Patients may rely on the force generating ability of the quadriceps during the lowering phase as they are not able to compensate with other joints of the lower extremity during this phase of the task.

Study Design Validity and reliability study. Background Providing feedback on running mechanics is a common intervention to decrease the risk of injury or to restore running after an injury. Commercially available devices are able to measure running dynamics, such as cadence, ground contact time (GCT), and vertical oscillation (VO), but there is limited evidence on the validity and reliability of these measures. Objective To determine the validity and reliability of measures of cadence, GCT, and VO with a fitness watch compared to a motion-analysis system. Methods Twenty runners ran in 3 conditions: (1) baseline (self-selected speed and cadence), (2) higher cadence, and (3) decreased vertical motion (minimal oscillation). Ten runners also performed an additional baseline running session to measure intrasession reliability. For each condition, the average cadence, GCT, and VO were collected from a watch and from a motion-capture system. Intraclass correlation coefficients (ICCs) were used to assess validity between devices. An analysis of variance with 2 repeated measures was used to determine the ability of the watch and motion analysis to detect change in running dynamics. Results The ICCs between the 2 measuring systems were 0.931, 0.963, and 0.749 for cadence, VO, and GCT, respectively (P.01). The minimal detectable changes at the 95% confidence interval for cadence, VO, and GCT were 2.53 steps per minute, 0.45 cm, and 0.01 seconds, respectively, for the watch. There were no interaction effects, but there was a main effect for condition; both devices detected changes in running dynamics. Conclusion The watch is a valid and reliable tool for detecting changes in cadence, VO, and GCT. J Orthop Sports Phys Ther 2016;46(6):471-476. Epub 26 Apr 2016. doi:10.2519/jospt.2016.6391.

BACKGROUND: To compare the activation of shoulder and trunk muscles between six pairs of closed (CC) and open chain (OC) exercises for the upper extremity, matched for performance characteristics. The secondary aims were to compare shoulder and trunk muscle activation and shoulder activation ratios during each pair of CC and OC exercise. METHODS: Twenty-two healthy young adults were recruited. During visit 1, the 5-repetition maximum resistance was established for each CC and OC exercise. During visit 2, electromyography activation from the infraspinatus (INF), deltoid (DEL), serratus anterior (SA), upper, middle and lower trapezius (UT, MT, LT), erector spinae (ES) and external oblique (EO) muscles was collected during 5-repetition max of each exercise. Average activation was calculated during the concentric and eccentric phases of each exercises. Activation ratios (DEL/INF, UT/LT, UT/MT, UT/SA) were also calculated. Linear mixed models compared the activation by muscle collapsed across CC and OC exercises. A paired t-test compared the activation of each muscle and the activation ratios (DEL/INF, UT/LT, UT/MT, UT/SA) between each pair of CC and OC exercises. RESULTS: The INF, LT, ES, and EO had greater activation during both concentric (p = 0.03) and eccentric (p < 0.01) phases of CC versus OC exercises. Activation ratios were lower in CC exercises compared to OC exercises (DEL/INF, 3 pairs; UT/LT, 2 pairs; UT/MT, 1 pair; UT/SA, 3 pairs). CONCLUSION: Upper extremity CC exercises generated greater activation of shoulder and trunk muscles compared to OC exercises. Some of the CC exercises produced lower activation ratios compared to OC exercises.

Wearable devices validly assess spatiotemporal running parameters (cadence, vertical oscillation and ground contact time), but the relationship between these parameters and lower limb loading parameters (loading rate, peak vertical ground reaction force [vGRF] and braking impulse) is unknown.To characterize changes in lower limb loading parameters in runners instructed to run with increased cadence or low vertical oscillation, and to determine whether the change in spatiotemporal parameters predicted the changes in lower limb loading parameters.Cross Sectional Cohort Study.Twenty healthy runners completed three running trials in three conditions: baseline, high cadence, and low vertical oscillation. Spatiotemporal parameters were measured with a wearable device and lower limb loading was measured using an instrumented treadmill. Spatiotemporal and loading parameters were analyzed between running conditions via a repeated measure ANOVA. A hierarchical regression model was used to determine if changes in spatiotemporal parameters predicted the change of loading parameters during conditions.High cadence and low oscillation conditions reduced average vertical loading rate (p = 0.013 and p = 0.002, respectively), instantaneous vertical loading rate (p = 0.022 and p = 0.001, respectively), and peak vGRF (p = 0.025 and p 0.001, respectively). Braking impulse was significantly lower in the high cadence condition compared to baseline (p 0.001), but not during the low oscillation (p = 1.000). The increase in cadence during the high cadence condition predicted the reduction of instantaneous vertical loading rate (rWhile both higher cadence and lower vertical oscillation resulted in reduced loading rates during running, cueing to reduce vertical oscillation was more successful in reducing peak vGRF and only the higher cadence condition reduced braking impulse. These findings will inform clinicians who wish to use wearable devices for running gait modification to select injury-specific gait retraining cues.Level 3.

OBJECTIVE: The purpose of this study is to compare the functional status of patients 12 months after total knee arthroplasty (TKA) who underwent progressive strengthening or standard of care rehabilitation to older adults without knee joint pain. METHODS: This cross-sectional design study included 165 participants in the progressive strengthening group, 40 participants in the standard of care group, and 88 older adults (control group). The Knee Outcome Survey – Activity of Daily Living, knee active range of motion (ROM), quadriceps strength, and performance tests were compared between groups using a one-way ANOVA. The proportions of participants in both TKA groups who achieved the lower bound of the 95% confidence interval of the control group were compared using a Fisher’s exact test. RESULTS: Significant between-group effects were found for all variables (p < 0.001). The control group had better outcomes than both the progressive strengthening and standard of care groups (p < 0.001). Compared to the standard of care group, a higher proportion of participants in the progressive strengthening group achieved the lower bound cutoff for active knee extension ROM (p = 0.042), quadriceps strength (p = 0.032), and stair climbing time (p = 0.029). CONCLUSION: More participants in the progressive strengthening group had physical function that was similar to the healthy control group, when compared to the standard of care group. Progressive strengthening rehabilitation may be more effective in restoring normative levels of function after TKA than standard of care.

The purpose of this study was to evaluate changes in movement patterns during a sit-to-stand (STS) task before and after total hip arthroplasty (THA), and to compare biomechanical outcomes after THA to a control group. Forty-five subjects who underwent THA and twenty-three healthy control subjects participated in three-dimensional motion analysis. Pre-operatively, subjects exhibited inter-limb movement asymmetries with lower vertical ground reaction force (VGRF) and smaller moments on the operated limb. Although there were significant improvements in movement symmetry 3 months after THA, patients continued to demonstrate lower VGRF and smaller moments on the operated limb compared to non-operated and to control limbs. Future studies should identify the contributions of physical impairments and the influence of surgical approach on STS biomechanics.

Patients six months after total knee arthroplasty (TKA) demonstrate movement asymmetries and functional deficits, which may be related to poor functional performance. The aims of this study were to 1) compare biomechanical variables between subjects 6 months after TKA and an age-matched healthy control group during a step up and over task and 2) determine the relationship between quadriceps strength, movement patterns and stair climbing performance.Twenty patients 6 months following unilateral TKA and twenty healthy controls were enrolled. Participants completed questionnaires, isometric quadriceps strength testing and performance based tests to quantify functional performance. Motion analysis was performed during a step up and over task. Functional and biomechanical variables were analyzed using a 2 × 2 ANOVA. The symmetry ratios (operated/non-operated limb*100) for biomechanical variables were analyzed using independent t-tests. Pearson correlations were performed to determine the relationships between biomechanical variables, strength and stair climbing performance.In the TKA group, subjects had lower peak moments, power and sagittal plane excursion in the operated knee compared to the contralateral knee (P0.05), while the hip on the operated side had greater power generation (P = 0.014). Compared to the control group, all symmetry ratios were significantly lower in the surgical group (P0.05). Stair climbing time was correlated with quadriceps strength of the operated limb (R = -0.762, P0.001).Individuals 6 months after TKA had worse performance with respect to biomechanics, quadriceps strength, and performance-based tests. Biomechanical asymmetries after TKA reduce the demand on the operated knee and increase reliance on the contralateral limb and ipsilateral hip.

Patients with hip osteoarthritis demonstrate limited range of motion, muscle weakness and altered biomechanics; however, few studies have evaluated the relationships between physical impairments and movement asymmetries. The purpose of this study was to identify the physical impairments related to movement abnormalities in patients awaiting total hip arthroplasty. We hypothesized that muscle weakness and pain would be related to greater movement asymmetries. Fifty-six subjects who were awaiting total hip arthroplasty were enrolled. Pain was assessed using a 0 to 10 scale, range of motion was assessed with the Harris Hip Score and isometric hip abductor strength was tested using a hand-held dynamometer. Trunk, pelvis and hip angles and moments in the frontal and sagittal planes were measured during walking using three dimensional motion analysis. During gait, subjects had 3.49 degrees less peak hip flexion and 8.82 degrees less extension angles (p

Most rehabilitation interventions after total hip arthroplasty (THA) are not designed to return patients to high-levels of physical activity and, thus, low levels of physical activity and residual weakness are common. The purpose of this case series was to describe the feasibility and preliminary efficacy of an exercise and education intervention for patients after THA who have already completed formal outpatient physical therapy.Case series.Two participants underwent unilateral THA seven (case A) or eight (case B) months prior to the intervention. Individuals participated in 18 treatment sessions that included progressive aerobic and strengthening exercises and meetings with a health coach. Change in function, strength, and self-reported physical activity were measured. Outcomes 12 months after surgery were compared to a historical cohort of patients after THA.There were no adverse events during the intervention. At the end of the intervention, hip and knee strength on the surgical side increased approximately 30% compared to baseline in both cases. Activity level, and recreational performance, including walking up stairs and hiking uphill (case A), and running and golfing (case B), improved by the end of the intervention. Most changes were maintained at follow-up, although hip strength for case B decreased 27% after discharge from the intervention. Outcomes for both cases exceeded historical averages for patients 12 months after THA, with the exception of strength in case B.The exercise intervention was well tolerated and without negative effects in two participants. Both participants increased their ability to complete demanding recreational and sports-related activities, physical activity, and demonstrated improved hip abductor and knee extensor strength. Further research is needed to evaluate the implementation and effectiveness of similar interventions after THA.Level 4.

Objective Performance tests and self-reported questionnaires capture different domains of function in patients with lower extremity osteoarthritis, but the impairments related to each of these domains have not been elucidated. The purpose of this study was to determine how strength and joint pain influence performance-based tests and self-reported questionnaires of functional ability of individuals with end-stage hip osteoarthritis. Methods Fifty-six patients scheduled to undergo unilateral total hip arthroplasty were included in this cross-sectional analysis. Subjects completed the Hip Outcome Survey (HOS) and pain in the affected hip was quantified on a scale from 0–10. Performance-based tests included the Six-Minute Walk Test (6MWT), the Timed Up & Go (TUG), and the Stair Climbing Test (SCT). Isometric strength of the hip abductors and knee extensors was tested and recorded. Hierarchical linear regressions were created to determine the contributions of pain, knee extensor strength, and hip strength for each outcome measure (TUG, 6MWT, SCT, and HOS). Height and body mass index were entered first, followed by pain, then knee extensor strength, and then hip abduction strength. Results Greater pain significantly predicted lower HOS scores, but hip strength did not significantly improve the model. Hip pain was also significantly related to TUG, SCT, and 6MWT values, but hip and knee strength explained additional variance for these performance-based measures. Conclusion Self-report and performance-based measures capture different aspects of disability and are influenced by different underlying impairments. Both types of outcome measures should be used in studies that evaluate functional changes in patients with hip osteoarthritis.

Ankle sprains are a common injury and those affected are at a risk of developing chronic ankle instability (CAI). Complications of an acute sprain include increased risk of re-injury and persistent disability; however, the exact link between ankle sprains and chronic instability has yet to be elucidated. The purpose of this study was to investigate neuromuscular control (including kinematics, kinetics and EMG) during stepping down from a curb, a common yet challenging daily activity, in persons with ankle instability (n = 11), those with a history of ankle sprain without persistent instability, called ankle sprain "copers" (CPRs) (n = 9) and uninjured controls (CTLs) (n = 13). A significant group difference was noted as the CPR group demonstrated increased tibialis anterior activity in both the preparatory (pre-touchdown) and reactive (post-touchdown) phases when compared to healthy and unstable groups (P0.05). It follows that the CPR group also demonstrated a significantly less plantar-flexed position at touchdown than the other two groups (P0.05). This is a more stable position to load the ankle and this strategy differed from that used by participants with CAI and uninjured CTLs. These findings provide insight into the neuromuscular control strategies of CPRs, which may allow them to more appropriately control ankle stability following sprains.

Study Design Cross-sectional cohort. Introduction Tendon collagen organization can be estimated by peak spatial frequency radius (PSFR) on ultrasound images. Characterizing PSFR can define the contribution of collagen disruption to shoulder symptoms. Purpose of the Study The purpose of this was to characterize the (1) supraspinatus tendon PSFR in participants with subacromial pain syndrome (SPS) and healthy controls; (2) PSFR between participants grouped on a tendon visual quality score; and (3) relationship between PSFR with patient-reported pain, function, and shoulder strength. Methods Participants with SPS ( n = 20) and age, sex, and arm-dominance–matched healthy controls ( n = 20) completed strength testing in scaption and external rotation, and patient-reported pain, and functional outcomes. Supraspinatus tendon ultrasound images were acquired, and PSFR was calculated for a region of interest 15 mm medial to the supraspinatus footprint. PSFR was compared between groups using an independent t -test and an analysis of variance to compare between 3 groups for visually qualitatively rated tendon abnormalities. Relationships between PSFR with pain, function, and strength were assessed using Pearson correlation coefficient. Results Supraspinatus tendon PSFR was not different between groups ( P = .190) or tendon qualitative ratings ( P = .556). No relationship was found between PSFR and pain, functional loss, and strength ( P > .05). Conclusions Collagen disruption (PSFR) measured via ultrasound images of the supraspinatus tendon was not different between participants with SPS or in those with visually rated tendon defects. PSFR is not related to shoulder pain, function, and strength, suggesting that supraspinatus tendon collagen disorganization may not be a contributing factor to shoulder SPS. However, collagen disruption may not be isolated to a single region of interest. Level of Evidence 3b: case-control study.

The purpose of this study was to characterize the magnitude and distribution of the total support moment during single-limb drop landings in individuals after anterior cruciate ligament reconstruction compared to a control group.Twenty participants after reconstruction and twenty control participants matched on sex, limb dominance and activity level were recruited. Motion analysis was performed during a single-limb drop landing task. Total support moment was determined by summing the internal extensor moments at the ankle, knee, and hip. Each relative joint contribution to the total support moment was calculated by dividing each individual contribution by the total support moment. Data were captured during a landing interval that started at initial contact and ended at the lowest vertical position of the pelvis. Data were then time-normalized and indexed at 25, 50, 75, and 100% of the landing interval.No between-group differences for total support moment magnitude were observed. At both 75% and 100% of the landing, the relative contribution of the knee joint was lower in those with a history of surgery (p0.001). At the same instances, the relative contribution to the total support moment by the hip joint was greater in those with a history of surgery (p=0.004).In active participants after anterior cruciate ligament reconstruction, relative contributions to anti-gravity support of the center of mass shifted from the knee to the hip joint during single-limb landing, which became evident towards the end of the landing interval.

The introduction of KRAS testing as a diagnostic tool to select patients for epidermal growth factor receptor (EGFR)-targeted cetuximab- or panitumumab-based therapies for metastatic colorectal cancer is widely regarded as a key advance in the field of personalized cancer medicine. Oncologists are now facing emerging issues in the treatment of metastatic colorectal cancer, including: (i) the identification of additional genetic determinants of primary resistance to EGFR-targeted therapy for further improving selection of patients; (ii) the explanation of rare cases of patients carrying KRAS-mutated tumors who have been reported to respond to either cetuximab or panitumumab and (iii) the discovery of mechanisms of secondary resistance to anti-EGFR antibody therapies. Here we discuss the potential role of comprehensive dissection of the key oncogenic nodes in the EGFR signaling cascade to predict resistance and sensitivity to EGFR monoclonal antibodies in metastatic colorectal cancer. Current data suggest that, together with KRAS mutations, the evaluation of BRAF and PIK3CA/PTEN alterations could also be useful for selecting patients with reduced chance to benefit from EGFR-targeted therapy. Furthermore, measuring EGFR gene copy number also appears relevant to positively identify responders. Up until now, each of these markers has been mainly assessed as a single event, often in retrospective analyses and patients' series. As these molecular alterations display overlapping patterns of occurrence, this adds considerable complexity to the drawing of an algorithm suitable for clinical decision-making. We suggest that in the near future comprehensive molecular analysis of the entire oncogenic pathway triggered by the EGFR should be performed, thus enhancing the prediction ability of individual markers.

s / Osteoarthritis and Cartilage 23 (2015) A82eA416 A349 568 RELATIONSHIP BETWEEN FUNCTIONAL PERFORMANCE AND FALLS IN FEMALE PATIENTS WITH END STAGE HIP OSTEOARTHRITIS F. Pozzi y, S. Abujaber z, S. Fenstermacher y, J. Zeni, Jr. y. yUniv. of Delaware, Newark, DE, USA; z The Univ. of Jordan, Amman, Jordan Purpose: To compare functional performance between women with end stage hip osteoarthritis (OA) who sustained a fall within the previous 6 months and women who did not. In addition, the relationship between functional performance and fall status (yes/no) will be explored. Methods: Thirty-one female individuals (age 65±8 years of age, 30.8±7.8Kg/m2 BMI) who were scheduled to undergo total hip arthroplasty were enrolled in this study. Patients underwent a functional evaluation with a physical therapist approximately 2 weeks before the surgery. Self-reported function was assessed using the Hip Harris Score (HHS) and the Hip Outcome Score (HOS). Total hip range of motion (ROM) was calculated as part of the HHS. Pain in the lower extremity joints and low back was measured using an analog scale (0, no pain; 10, worst pain imaginable). Isometric hip abductor strength was measured using a hand held dynamometer and knee extensor strength was measured using an electromechanical dynamometer. Both strength measures were normalized according to body weight. Functional performance was assessed with the Timed Up-and-Go (TUG), Stair climbing (SCT), and Six Minute Walk (6MW) tests. Fall status was assessed by asking patients whether they sustained a fall in the previous 6 months. The group was then divided into fall and no-fall groups based on the response to the fall question. An independent sample ttest was used to compare data between groups. Point-biserial correlation coefficient was then calculated to explore the relationship between functional variables and fall status. The quartile distribution of the performance on the functional tests (TUG, SCT, and 6MW) was built with the data from all subjects. The percentile value of the performance of the subjects in the fall group was then calculated. Results: Seven out of 31 patients (22.5%) reported sustaining at least one fall within 6 months from the evaluation session. Patients that fell were significantly older (þ8 years, p 1⁄4 0.01) and had significantly less total hip ROM (-21 , p 1⁄4 0.03) and quadriceps strength on both surgical and non-surgical side (-0.82 and -0.97 Nm/Kg, respectively, p 1⁄4 0.04). Additionally, patients in the fall group took longer time to complete the TUG (þ6.73s, p < 0.01) and SCT (þ18.76s, p < 0.01), and walk shorter distance in the 6MW test (-134.8m, p < 0.01, table 1). The correlation analysis revealed that older age and worse performance during functional tests were strongly related falls (Table 1). The percentile distribution of the performance during functional tests for subjects in the fall group revealed that most of the patients performed below the 25th percentile for each functional measures, although two subjects in the fall group were in the top quartile for TUG and SCT (Figure 1). Table 1 Demographic characteristics, range of motion, pain, strenght, performance tests, and sel

Background: The renin-angiotensin system (RAS) plays a role in the pathogenesis of ARDS, Angiotensin II (Ang-II) contributing to the pathogenesis of inflammation and fibrogenesis. Angiotensin-(1-7) (Ang-(1-7)) may antagonize the effects of Ang-II. This study was aimed at evaluating the potential for Ang-(1-7) to reduce injury, inflammation and fibrosis in an experimental model of ARDS in the acute and late phases. Methods: Male Sprague Dawley rats underwent an instillation of 0.1 M hydrochloric acid (HCl, 2.5 ml/kg) into the right bronchus. In an acute ARDS study, acid-injured rats were subjected to high stretch mechanical ventilation (18 ml/kg) for 5 h and randomized to receive an intravenous infusion of either vehicle (saline), Ang-(1-7) at low dose(0.27 μg/kg/h) (ALD), or high dose (60 μg/kg/h) (AHD) starting simultaneously with injury or 2 h afterwards. Arterial blood gas analysis and bronchoalveolar lavage (BAL) were performed to assess the injury. For the late ARDS study, after HCl instillation rats were randomized to either vehicle or high dose Ang-(1-7) (300 μg/kg/day) infused by mini osmotic pumps for two weeks, and lung hydroxyproline content measured. Results: In the acute ARDS study, Ang-(1-7) led to a significant improvement in oxygenation (PaO2/FiO2 : vehicle 359 ± 86; ALD 436 ± 72; AHD 44 442 ± 56; ANOVA p = 0.007) and reduced white blood cells counts (vehicle 4,519 ± 2,234; ALD 2,496 ± 621; AHD 2,744 ± 119/mm3; ANOVA p = 0.004). Only treatment with high dose Ang-(1-7) reduced inflammatory cell numbers in BAL (vehicle 127 ± 34; AHD 96 ± 34/ μl; p = 0.033). Interestingly also delayed administration of Ang-(1-7) was effective in reducing injury. In later ARDS, Ang-(1-7) decreased hydroxyproline content (649 ± 202 and 1,117 ± 297 μg/lung; p < 0.05). Conclusions: Angiotensin-(1-7), decreased the severity of acute lung injury and inflammation induced by combined acid aspiration and high stretch ventilation. Furthermore, continuous infusion of Ang-(1-7) reduced lung fibrosis 2 weeks following acid aspiration injury. These results call for further research on Ang-(1-7) as possible therapy for ARDS. The renin-angiotensin system (RAS) plays a role in the pathogenesis of ARDS, Angiotensin II (Ang-II) contributing to the pathogenesis of inflammation and fibrogenesis. Angiotensin-(1-7) (Ang-(1-7)) may antagonize the effects of Ang-II. This study was aimed at evaluating the potential for Ang-(1-7) to reduce injury, inflammation and fibrosis in an experimental model of ARDS in the acute and late phases. Methods Male Sprague Dawley rats underwent an instillation of 0.1 M hydrochloric acid (HCl, 2.5 ml/kg) into the right bronchus. In an acute ARDS study, acid-injured rats were subjected to high stretch mechanical ventilation (18 ml/kg) for 5 h and randomized to receive an intravenous infusion of either vehicle (saline), Ang-(1-7) at low dose(0.27 μg/kg/h) (ALD), or high dose (60 μg/kg/h) (AHD) starting simultaneously with injury or 2 h afterwards. Arterial blood gas analysis and bronchoalveolar lavage (BAL) were performed to assess the injury. For the late ARDS study, after HCl instillation rats were randomized to either vehicle or high dose Ang-(1-7) (300 μg/kg/day) infused by mini osmotic pumps for two weeks, and lung hydroxyproline content measured. Results In the acute ARDS study, Ang-(1-7) led to a significant improvement in oxygenation (PaO2/FiO2 : vehicle 359 ± 86; ALD 436 ± 72; AHD 44 442 ± 56; ANOVA p = 0.007) and reduced white blood cells counts (vehicle 4,519 ± 2,234; ALD 2,496 ± 621; AHD 2,744 ± 119/mm3; ANOVA p = 0.004). Only treatment with high dose Ang-(1-7) reduced inflammatory cell numbers in BAL (vehicle 127 ± 34; AHD 96 ± 34/ μl; p = 0.033). Interestingly also delayed administration of Ang-(1-7) was effective in reducing injury. In later ARDS, Ang-(1-7) decreased hydroxyproline content (649 ± 202 and 1,117 ± 297 μg/lung; p < 0.05). Conclusions Angiotensin-(1-7), decreased the severity of acute lung injury and inflammation induced by combined acid aspiration and high stretch ventilation. Furthermore, continuous infusion of Ang-(1-7) reduced lung fibrosis 2 weeks following acid aspiration injury. These results call for further research on Ang-(1-7) as possible therapy for ARDS.

Patients with hip osteoarthritis demonstrate limited range of motion, muscle weakness, and altered biomechanics; however, few studies have evaluated the relationships between physical impairments and movement asymmetries. The purpose of this study was to identify the physical impairments related to movement abnormalities in patients awaiting total hip arthroplasty. We hypothesized that muscle weakness and pain would be related to greater movement asymmetries. Fifty-six subjects who were awaiting total hip arthroplasty were enrolled. Pain was assessed using a 0-10 scale, range of motion was assessed with the Harris Hip Score and isometric hip abductor strength was tested using a hand-held dynamometer. Trunk, pelvis and hip angles and moments in the frontal and sagittal planes were measured during walking using three dimensional motion analysis. During gait, subjects had 3.49 degrees less peak hip flexion and 8.82 degrees less extension angles (p 0.001) and had 0.03 Nm/k*m less hip adduction moment on the affected side (p = 0.043). Weaker hip muscles were related to greater pelvis (r = -0.291) and trunk (r = -0.332) rotations in the frontal plane. These findings suggest that hip weakness drives abnormal movement patterns at the pelvis and trunk in patients with hip osteoarthritis to a greater degree than hip pain.

Prospective analysis of a longitudinal cohort with an embedded comparison group at a single time point.To determine the feasibility and effectiveness of an outpatient rehabilitation protocol that includes movement symmetry biofeedback on functional and biomechanical outcomes after total knee arthroplasty (TKA).TKA reduces pain and improves functional ability, but many patients experience strength deficits and movement abnormalities in the operated limb, despite outpatient rehabilitation. These asymmetries increase load on the nonoperated limb, and greater asymmetry is related to worse functional outcomes.Biomechanical and functional metrics were assessed 2 to 3 weeks prior to TKA, at discharge from outpatient physical therapy, and 6 months after TKA in 11 patients (9 men, 2 women; mean ± SD age, 61.4 ± 5.8 years; body mass index, 33.1 ± 5.4 kg/m2) who received 6 to 8 weeks of outpatient physical therapy that included specialized symmetry training. Six-month outcomes were compared to a control group, matched by age, body mass index, and sex (9 men, 2 women; mean ± SD age, 61.8 ± 5 years; body mass index, 34.3 ± 5.1 kg/m2), that did not receive specialized symmetry retraining.Of the 11 patients who received added symmetry training, 9 demonstrated clinically meaningful improvements that exceeded the minimal detectable change for all performance-based functional tests at 6 months post-TKA compared to pre-TKA. Six months after TKA, when walking, patients who underwent symmetry retraining had greater knee extension during midstance and had mean sagittal knee moments that were more symmetrical, biphasic, and more representative of normal knee kinetics compared to patients who did not undergo symmetry training. No patients experienced adverse events as the result of the protocol.Adding symmetry retraining to postoperative protocols is clinically viable, safe, and may have additional benefits compared to rehabilitation protocols that focus on range of motion, strength, and return to independence.Therapy, level 4.

Personalized cancer medicine based on the genetic milieu of individual tumors has long been postulated but until recently this concept was not supported by clinical evidence. The advent of the EGFR-targeted monoclonal antibodies cetuximab and panitumumab has revolutionized the therapy of colorectal tumors and paved the way to the individualized treatment of this cancer type. From the initial observation that cetuximab or panitumumab as monotherapy are effective only in 10–20%, of mCRCs, knowledge has being gained on the molecular mechanisms underlying primary resistance to these agents. It has already been unequivocally established that KRAS mutations, which occur in 35–45% of colorectal cancers, preclude responsiveness to EGFR-targeted therapy. However, less than 20% patients displaying wild-type KRAS tumors achieve objective response. Alterations in other effectors downstream of the EGFR, such as BRAF, and deregulation of the PIK3CA/PTEN pathway have independently been suggested to give rise to resistance. Molecular profiling of tumor samples and functional analysis of cellular models were preformed to clarify the relative contribution of molecular alterations to resistance. We retrospectively analyzed objective tumor response, progression-free (PFS) and overall survival (OS) together with the mutational status of KRAS, BRAF, PIK3CA and expression of PTEN in 132 tumors from cetuximab or panitumumab treated mCRC patients. Among the 106 non responsive patients, 74 (70%) had tumors with at least one molecular alteration in the four markers. The probability of response was 51% (22/43) among patients with no alterations, 4% (2/47) among patients with 1 alteration, and 0% (0/24) for patients with ≥ 2 alterations (p When expression of PTEN and mutations of KRAS, BRAF and PIK3CA were concomitantly ascertained, up to 70% of mCRC patients unlikely to respond to anti-EGFR therapies can be identified. We propose to define as ‘quadruple negative’, the CRCs lacking alterations in KRAS, BRAF, PTEN and PIK3CA. The functional role of mutated KRAS, BRAF and PIK3CA alleles in modulating resistance to cetuximab was evaluated in multiple cellular models in the presence or absence of ligands of the EGF receptor. The introduction of these oncogenic alleles in colorectal cancer cells impaired the therapeutic effect of cetuximab. Accordingly, we propose a molecular mechanism whereby the occurrence of KRAS and BRAF mutations together with the availability of EGF receptor ligands modulate the response to anti EGFR monoclonal antibodies. Comprehensive molecular dissection of the EGFR signaling pathways should be considered to select mCRC patients for cetuximab- or panitumumab based therapies. The rapid and effective translation of these findings into predictive biomarkers to couple EGFR-targeted antibodies to the patients that benefit from them represent a paradigm of modern clinical oncology. Citation Information: Mol Cancer Ther 2009;8(12 Suppl):B229.