Employing machine learning to enhance fracture recovery insights through gait analysis.

This study aimed to explore the potential of gait analysis coupled with supervised machine learning models as a predictive tool for assessing post-injury complications such as infection, malunion, or hardware irritation among individuals with lower extremity fractures. We prospectively identified participants with lower extremity fractures at a tertiary academic center. These participants underwent gait analysis with a chest-mounted inertial measurement unit device. Using customized software, the raw gait data were preprocessed, emphasizing 12 essential gait variables. The data were standardized, and several machine learning models, including XGBoost, logistic regression, support vector machine, LightGBM, and Random Forest, were trained, tested, and evaluated. Special attention was given to class imbalance, addressed using the synthetic minority oversampling technique (SMOTE). Additionally, we introduced a novel methodology to compute the post-injury recovery rate for gait variables, which operates independently of the time difference between the gait analyses of different participants. XGBoost was identified as the optimal model both before and after the application of SMOTE. Before using SMOTE, the model achieved an average test area under the ROC curve (AUC) of 0.90, with a 95% confidence interval (CI) of [0.79, 1.00], and an average test accuracy of 86%, with a 95% CI of [75%, 97%]. Through feature importance analysis, a pivotal role was attributed to the duration between the occurrence of the injury and the initial gait analysis. Data patterns over time revealed early aggressive physiological compensations, followed by stabilization phases, underscoring the importance of prompt gait analysis. χ2 analysis indicated a statistically significant higher readmission rate among participants with underlying medical conditions (p = 0.04). Although the complication rate was also higher in this group, the association did not reach statistical significance (p = 0.06), suggesting a more pronounced impact of medical conditions on readmission rates rather than on complications. This study highlights the transformative potential of integrating advanced machine learning techniques like XGBoost with gait analysis for orthopedic care. The findings underscore a shift toward a data-informed, proactive approach in orthopedics, enhancing patient outcomes through early detection and intervention. The χ2 analysis added crucial insights into the broader clinical implications, advocating for a comprehensive treatment strategy that accounts for the patient's overall health profile. The research paves the way for personalized, predictive medical care in orthopedics, emphasizing the importance of timely and tailored patient assessments.

Are Orthopaedic Trauma Surgeons Appropriately Compensated for Treating Acetabular Fractures? An Analysis of Operative Times and Relative Value Units.

OBJECTIVES: To evaluate the work relative value units (RVUs) attributed per minute of operative time (wRVU/min) in fixation of acetabular fractures, evaluate surgical factors that influence wRVU/min, and compare wRVU/min with other procedures. DESIGN: Retrospective. SETTING: Level 1 academic center. PATIENT SELECTION CRITERIA: Two hundred fifty-one operative acetabular fractures (62 A, B, C) from 2015 to 2021. OUTCOME MEASURES AND COMPARISONS: Work relative value unit per minute of operative time for each acetabular current procedural terminology (CPT) code. Surgical approach, patient positioning, total room time, and surgeon experience were collected. Comparison wRVU/min were collected from the literature. RESULTS: The mean wRVU per surgical minute for each CPT code was (1) CPT 27226 (isolated wall fracture): 0.091 wRVU/min, (2) CPT 27227 (isolated column or transverse fracture): 0.120 wRVU/min, and (3) CPT 27228 (associated fracture types): 0.120 wRVU/min. Of fractures with single approaches, anterior approaches generated the least wRVU/min (0.091 wRVU/min, P = 0.0001). Average nonsurgical room time was 82.1 minutes. Surgeon experience ranged from 3 to 26 years with operative time decreasing as surgeon experience increased ( P = 0.03). As a comparison, the wRVU/min for primary and revision hip arthroplasty have been reported as 0.26 and 0.249 wRVU/min, respectively. CONCLUSIONS: The wRVUs allocated per minute of operative time for acetabular fractures is less than half of other reported hip procedures and lowest for isolated wall fractures. There was a significant amount of nonsurgical room time that should be accounted for in compensation models. This information should be used to ensure that orthopaedic trauma surgeons are being appropriately supported for managing these fractures. LEVEL OF EVIDENCE: Economic Level IV. See Instructions for Authors for a complete description of levels of evidence.

Patients with glenohumeral arthritis are more likely to be prescribed opioids in the emergency department or urgent care setting.

OBJECTIVE: The objective is to quantify the rate of opioid and benzodiazepine prescribing for the diagnosis of shoulder osteoarthritis across a large healthcare system and to describe the impact of a clinical decision support intervention on prescribing patterns. DESIGN: A prospective observational study. SETTING: One large healthcare system. PATIENTS AND PARTICIPANTS: Adult patients presenting with shoulder osteoarthritis. INTERVENTIONS: A clinical decision support intervention that presents an alert to prescribers when patients meet criteria for increased risk of opioid use disorder. MAIN OUTCOME MEASURE: The percentage of patients receiving an opioid or benzodiazepine, the percentage who had at least one risk factor for misuse, and the percent of encounters in which the prescribing decision was influenced by the alert were the main outcome measures. RESULTS: A total of 5,380 outpatient encounters with a diagnosis of shoulder osteoarthritis were included. Twenty-nine percent (n = 1,548) of these encounters resulted in an opioid or benzodiazepine prescription. One-third of those who received a prescription had at least one risk factor for prescription misuse. Patients were more likely to receive opioids from the emergency department or urgent care facilities (40 percent of encounters) compared to outpatient facilities (28 percent) (p < .0001). Forty-four percent of the opioid prescriptions were for "potent opioids" (morphine milliequivalent conversion factor > 1). Of the 612 encounters triggering an alert, the prescribing decision was influenced (modified or not prescribed) in 53 encounters (8.7 percent). All but four (0.65 percent) of these encounters resulted in an opioid prescription. CONCLUSION: Despite evidence against routine opioid use for osteoarthritis, one-third of patients with a primary diagnosis of glenohumeral osteoarthritis received an opioid prescription. Of those who received a prescription, over one-third had a risk factor for opioid misuse. An electronic clinic decision support tool influenced the prescription in less than 10 percent of encounters.

Comparison of the Neer classification to the 2018 update of the Orthopedic Trauma Association/AO fracture classification for classifying proximal humerus fractures.

Background: The classification of fractures is necessary to ensure a reliable means of communication for clinical interaction, education and research. The Neer classification is the most commonly used classification for proximal humerus fractures. In 2018 the Orthopedic Trauma Association (OTA) and the AO Foundation provided an update to the OTA/AO Fracture Classification Scheme addressing many of the concerns about the previous versions of the classification. The objective of the present study was to evaluate the rater reliability of the 2 classifications and if the classifications subjectively better characterized the fracture patterns. Methods: X-rays and CT scans of 24 proximal humerus fractures were given to 7 independent raters for classification according to the Neer and 2018 OTA/AO classification. Both full-forms and short-forms of the classifications were tested. The Fleiss Kappa statistic was used to assess inter-rater agreement and intra-rater consistency for the 2 classifications. For each case the raters subjectively commented on how well each classification was able to characterize the fracture pattern. Results: All raters graded the 2018 OTA/AO classification as good as or better than the Neer classification for an adequate description of the fracture patterns. The short-form 2018 OTA/AO classification had the most 4 rater and 5 rater agreement cases and the second most 6 rater agreement cases. The short-form Neer classification had the second most 4 rater and 5 rater agreement cases and the most 6 rater agreement cases. The full 2018 OTA/AO had the least 4, 5, or 6 rater agreement cases of all the classification systems. Inter-rater agreement was fair for the full and short form of both the Neer and 2018 OTA/AO classification. The full and short Neer classifications together with the short 2018 OTA/AO classification had moderate intra-rater consistency, while the full 2018 OTA/AO classification only had slight intra-rater consistency. Conclusions: The 2018 OTA/AO classification is equivalent in its short-form to the Neer classification in inter-rater reliability and intra-rater consistency; and is superior in its full form for characterizing specific fracture types. The low inter-rater reliability of the full 2018 OTA/AO classification is a concern that may need to be addressed in the future.

Resident Education and Wellness: A Strategy for Future Pandemics.

The Coronavirus Disease 2019 (COVID-19) pandemic presented a novel challenge to modern healthcare systems and medical training. Resource allocation and risk mitigation dramatically affected resident training. The objective of this article is to develop new strategies to maintain a healthy, competent residency program while combating the unique challenges to resident education and wellness. In 2020, our institution implemented a revolving 3-Team system. While the "Inpatient-Team" delivered direct care, the "Back-up Team" and "Quarantine-Team" managed the telemedicine virtual clinic and education-wellness strategy, respectively. Our 3-Team system allowed delivery of safe, high-quality patient care while optimizing resident education, research, and wellness. The efficient use of technology led to both improved virtual education outside of the hospital and intentional wellness opportunities despite social distancing restrictions. Utilization of virtual platforms for patient care, education, research, and wellness grew out of necessity in this pandemic, yet represent an opportunity for lasting improvement. (Journal of Surgical Orthopaedic Advances 31(3):150-154, 2022).

A Randomized Trial of Preoperative Practice in a Simulated Operative Environment: 3D Printed Pilon Model Improves Resident Performance.

This study assessed the effect of preoperative planning using a 3D-printed periarticular fracture model on operative performance. A complex pilon fracture was 3D-printed, and a preoperative plan was developed. Orthopaedic surgery residents (n = 20) were randomized into two groups. Group 1 performed routine preoperative planning, while Group 2 was also practiced using a 3D-printed construct before performing fixation of the 3D-printed model. Resident performance was assessed using a video motion capture system and evaluated by blinded reviewers. Three residents (3D group) completed fixation within the allotted 45 minutes. The 3D group had less hand distance traveled for step 1 (89 m vs. 162 m, p = 0.04). The 3D group had better performance on three of the four components and more acceptable reductions (6 vs. 0, p = 0.009). Average global rating scale was higher in the 3D group (3.0 vs. 1.7, p = 0.0095). Use of 3D-printed models for preoperative planning improved resident performance. (Journal of Surgical Orthopaedic Advances 31(3):187-192, 2022).

Nonoperative Treatment of Select Lateral Compression Type II Pelvic Ring Injuries (OTA/AO 61B2.2) Results in a Low Rate of Radiographic Displacement.

OBJECTIVES: To quantify radiographic outcomes and to identify predictors of late displacement in the nonoperative treatment of lateral compression type II (LC-2) pelvic ring injuries. DESIGN: Retrospective review. SETTING: Two Level 1 trauma centers. PATIENTS/PARTICIPANTS: Thirty eight patients 18 years of age or older with LC-2 pelvic ring injuries were included in the study. INTERVENTION: Nonoperative treatment. MAIN OUTCOME MEASUREMENTS: Crescent fracture displacement (CFD) was measured on initial axial computed tomography scan. Change in pelvic ring alignment was measured by the deformity index, simple ratio, and inlet and outlet ratios on successive plain radiographs. RESULTS: Patients in this study had minimally displaced LC-2 pelvic ring injuries, with median initial CFD of 2 mm and median initial deformity index of 2%. No patients had a change of more than or equal to 10 percentage points in deformity index over the treatment period, but small amounts of displacement were seen on the other ratios. No patients initially selected for nonoperative treatment converted to operative treatment. No radiographic predictors of late displacement were identified. Bilateral pubic rami fractures and the presence of a complete sacral fracture ipsilateral to the crescent fracture were not associated with late displacement. CONCLUSIONS: A spectrum of injury severity and stability exists in the LC-2 pattern. Nonoperative treatment of LC-2 injuries with low initial deformity and CFD results in minimal subsequent displacement. LEVEL OF EVIDENCE: Therapeutic Level IV. See Instructions for Authors for a complete description of levels of evidence.

Opioid Prescribing Risk Factors in Nonoperative Ankle Fractures: The Impact of a Prospective Clinical Decision Support Intervention.

Opioids are frequently used for acute pain management of musculoskeletal injuries, which can lead to misuse and abuse. This study aimed to identify the opioid prescribing rate for ankle fractures treated nonoperatively in the ambulatory and emergency department setting across a single healthcare system and to identify patients considered at high risk for abuse, misuse, or diversion of prescription opioids that received an opioid. A retrospective cohort study was performed at a large healthcare system. The case list included nonoperatively treated emergency department, urgent care and outpatient clinic visits for ankle fracture and was merged with the Prescription Reporting With Immediate Medication Mapping (PRIMUM) database to identify encounters with prescription for opioids. Descriptive statistics characterize patient demographics, treatment location and prescriber type. Rates of prescribing among subgroups were calculated. There were 1,324 patient encounters identified, of which, 630 (47.6%) received a prescription opioid. The majority of patients were 18-64 years old (60.3%). Patients within this age range were more likely to receive an opioid prescription compared to other age groups (p < .0001). Patients treated in the emergency department were significantly more likely to receive an opioid medication (68.3%) compared to patients treated at urgent care (33.7%) or in the ambulatory setting (16.4%) (p < .0001). Utilizing the PRIMUM tool, 14.2% of prescriptions were provided to patients with at least one risk factor. Despite the recent emphasis on opioid stewardship, 14.2% of patients with risk factors for misuse, abuse, or diversion received opioid analgesics in this study, identifying an area of improvement for prescribers.

Age and socioeconomic status affect access to telemedicine at an urban level 1 trauma center.

OBJECTIVES: Despite clinical and economic advantages, routine utilization of telemedicine remains uncommon. The purpose of this study was to examine potential disparities in access and utilization of telehealth services during the rapid transition to virtual clinic during the coronavirus pandemic. DESIGN: Retrospective chart review. SETTING: Outpatient visits (in-person, telephone, virtual-Doxy.me) over a 7-week period at a Level I Trauma Center orthopaedic clinic. INTERVENTION: Virtual visits utilizing the Doxy.me platform. MAIN OUTCOME MEASURES: Accessing at least 1 virtual visit ("Virtual") or having telephone or in-person visits only ("No virtual"). METHODS: All outpatient visits (in-person, telephone, virtual) during a 7-week period were tracked. At the end of the 7-week period, the electronic medical record was queried for each of the 641 patients who had a visit during this period for the following variables: gender, ethnicity, race, age, payer source, home zip code. Data were analyzed for both the total number of visits (n = 785) and the total number of unique patients (n = 641). Patients were identified as accessing at least 1 virtual visit ("Virtual") or having telephone or in-person visits only ("No virtual"). RESULTS: Weekly totals demonstrated a rapid increase from 0 to greater than 50% virtual visits by the third week of quarantine with sustained high rates of virtual visits throughout the study period. Hispanic and Black/African American patients were able to access virtual care at similar rates to White/Caucasian patients. Patients of ages 65 to 74 and 75+ accessed virtual care at lower rates than patients ≤64 (P = .003). No difference was found in rates of virtual care between payer sources. A statistically significant difference was found between patients from different zip codes (P = .028). CONCLUSION: A rapid transition to virtual clinic can be performed at a level 1 trauma center, and high rates of virtual visits can be maintained. However, disparities in access exist and need to be addressed.

Effect of Intrawound Vancomycin Powder in Operatively Treated High-risk Tibia Fractures: A Randomized Clinical Trial.

Importance: Despite the widespread use of systemic antibiotics to prevent infections in surgically treated patients with fracture, high rates of surgical site infection persist. Objective: To examine the effect of intrawound vancomycin powder in reducing deep surgical site infections. Design, Setting, and Participants: This open-label randomized clinical trial enrolled adult patients with an operatively treated tibial plateau or pilon fracture who met the criteria for a high risk of infection from January 1, 2015, through June 30, 2017, with 12 months of follow-up (final follow-up assessments completed in April 2018) at 36 US trauma centers. Interventions: A standard infection prevention protocol with (n = 481) or without (n = 499) 1000 mg of intrawound vancomycin powder. Main Outcomes and Measures: The primary outcome was a deep surgical site infection within 182 days of definitive fracture fixation. A post hoc comparison assessed the treatment effect on gram-positive and gram-negative-only infections. Other secondary outcomes included superficial surgical site infection, nonunion, and wound dehiscence. Results: The analysis included 980 patients (mean [SD] age, 45.7 [13.7] years; 617 [63.0%] male) with 91% of the expected person-time of follow-up for the primary outcome. Within 182 days, deep surgical site infection was observed in 29 of 481 patients in the treatment group and 46 of 499 patients in the control group. The time-to-event estimated probability of deep infection by 182 days was 6.4% in the treatment group and 9.8% in the control group (risk difference, -3.4%; 95% CI, -6.9% to 0.1%; P = .06). A post hoc analysis of the effect of treatment on gram-positive (risk difference, -3.7%; 95% CI, -6.7% to -0.8%; P = .02) and gram-negative-only (risk difference, 0.3%; 95% CI, -1.6% to 2.1%; P = .78) infections found that the effect of vancomycin powder was a result of its reduction in gram-positive infections. Conclusions and Relevance: Among patients with operatively treated tibial articular fractures at a high risk of infection, intrawound vancomycin powder at the time of definitive fracture fixation reduced the risk of a gram-positive deep surgical site infection, consistent with the activity of vancomycin. Trial Registration: ClinicalTrials.gov Identifier: NCT02227446.

The Quadrilateral Plate in Acetabular Fracture Surgery: What Is It and When Should It Be Addressed?

The quadrilateral plate (QP) is the relatively flat surface of bone in the true pelvis lying directly medial to the acetabulum. This surface is frequently involved in acetabular fractures. Elderly individuals, in particular, commonly sustain anterior column fractures with incomplete or complete posterior hemitransverse fracture lines with associated QP comminution. If QP fracture lines propagate through the superior weight-bearing surface of the acetabulum, the femoral head may displace medially, leading to poor outcomes if not addressed. Fortunately, the collective work of many orthopaedic surgeons has resulted in numerous effective methods for approaching, reducing, and stabilizing the QP and the diverse family of fractures which affect it. A thorough understanding of the QP, its anatomy, radiology, and techniques for fixation, is required to optimize patient outcomes.

Why Make the Cut? Trochanteric Slide Osteotomy Can Improve Exposure to the Anterosuperior Acetabulum.

OBJECTIVE: To define relative increases in visual bony surface area and access to critical landmarks with the addition of a trochanteric slide osteotomy to a Kocher-Langenbeck approach. METHODS: A Kocher-Langenbeck approach followed by a trochanteric slide osteotomy was sequentially performed on 10, fresh-frozen, hemipelvectomy cadaveric specimens. Visual and palpable access to relevant surgical landmarks was recorded. Calibrated digital photographs were taken of each approach and analyzed using Image J. RESULTS: The acetabular surface area exposed was 27.66 (±6.67) cm2 for a Kocher-Langenbeck approach. This increased to and 41.82 (±7.97) cm2 with the addition of a trochanteric osteotomy. The exposed surface area was increased by 51.2% for the trochanteric osteotomy (P < 0.001). The superior margin of the acetabulum could be visualized and palpably accessed in both exposures. Access to the more anterosuperior portions of the acetabulum was consistently possible in the trochanteric osteotomy but not with the Kocher-Langenbeck approach. CONCLUSIONS: A trochanteric osteotomy may visually improve access to the most anterosuperior acetabulum but does not significantly improve surgical access to relevant portions of the superior acetabulum when compared with a Kocher-Langenbeck approach.

Supplemental Superior Buttress Plating for the Treatment of Posterosuperior Wall Acetabulum Fractures.

Posterosuperior wall acetabulum fractures are a unique and uncommon fracture pattern. Traditional plate fixation may not provide adequate fixation of these fracture fragments. This article presents a surgical technique and the results of a case series using a supplemental 1/3 tubular superior buttress plate to improve fracture reduction and better neutralize shear forces in the treatment of superior posterior wall fractures. Additionally, we compared failure rates of those posterior superior wall acetabular fractures treated with supplemental superior buttress plates to those treated with standard plate fixation and no supplemental superior buttress plates.

Does formal vs home-based physical therapy predict outcomes after ankle fracture or ankle fracture-dislocation?

Background: Ankle fractures are among the most common injuries treated by orthopaedic surgeons. Various postoperative rehabilitation strategies have been promoted, but the ability to improve patient-reported functional outcome has not been clearly demonstrated. We aim to evaluate outcomes associated with clinic-based, physical therapist-supervised rehabilitation (Formal-PT) compared to surgeon-directed rehabilitation (Home-PT). Methods: This prospective observational study included patients with operative bimalleolar or trimalleolar ankle fractures with or without dislocation (n = 80) at a Level I trauma center. Patients were prescribed PT per the surgeon's practice pattern. Patient-reported functional outcomes at 6 months and complication rates were compared between groups. Results: Of the 80 patients, 38 (47.5%) patients received Formal-PT; the remaining received Home-PT. Thirty-four patients (89.5%) attended ≥1 PT session. Number of sessions attended ranged from 1 to 36 (mean = 16). Receipt of Formal-PT did not differ by injury characteristics or demographics. Of patients with private insurance, 57% were prescribed Formal-PT vs 7% of uninsured patients (P = .033). FAAM and Combination SMFA scores at 6 months were similar between groups (Formal-PT: 69.7, 20.1; Home-PT: 70.9, 24.4; P = .868, .454, respectively). Postoperative complications were rare and equivalent between groups. Conclusions: Comparison of outcomes between patients with operatively treated displaced ankle fractures/dislocations with Formal-PT vs Home-PT showed no difference in SMFA and FAAM scores. These findings suggest patients receiving supervised PT produced a similar outcome to those under routine physician-directed rehabilitation at 6 months. The cost for therapy averaged $2012.96 per patient receiving Formal-PT.

Electronically augmented gait abnormality assessment following lower extremity trauma.

BACKGROUND: Objective evaluation of patient outcomes has become an essential component of patient management. Along with patient-reported outcomes, performance-based measures (PBMs) such as gait analysis are an important part of this evaluation. The purpose of this study was to evaluate the validity of utilizing a wearable inertial measurement unit (IMU) in an outpatient clinic setting to assess its ability to provide clinically relevant data in patients with altered gait resulting from lower extremity trauma. METHODS: Five orthopaedic trauma patients with varying degrees of gait pathologies were compared to 5 healthy control subjects. Kinematic data were simultaneously recorded by the IMU and a gold standard Vicon video motion analysis system (Vicon Motion Systems Ltd, Oxford, UK) during a modified 10-m walk test. Raw data captured by the IMU were directly compared to Vicon data. Additionally, 5 objective gait parameters were compared for controls and the 5 trauma patients. RESULTS: The IMU data streams strongly correlated with Vicon data for measured variables used in the subsequent gait analysis: vertical acceleration, vertical displacement, pitch angular velocity, and roll angular velocity (Pearson r-value > 0.9 for all correlations). Quantitative kinematic data in post-trauma patients significantly differed from control data and correlated with observed gait pathology. CONCLUSIONS: When compared to the gold standard motion capture reference system (Vicon), an IMU can reliably and accurately measure clinically relevant gait parameters and differentiate between normal and pathologic gait patterns. This technology is easily integrated into clinical settings, requires minimal time, and represents a performance-based method for quantifiably assessing gait outcomes. LEVEL OF EVIDENCE: Diagnostic Level 1.

Association Between 6-Week Postdischarge Risk Classification and 12-Month Outcomes After Orthopedic Trauma.

Importance: Numerous studies have demonstrated that long-term outcomes after orthopedic trauma are associated with psychosocial and behavioral health factors evident early in the patient's recovery. Little is known about how to identify clinically actionable subgroups within this population. Objectives: To examine whether risk and protective factors measured at 6 weeks after injury could classify individuals into risk clusters and evaluate whether these clusters explain variations in 12-month outcomes. Design, Setting, and Participants: A prospective observational study was conducted between July 16, 2013, and January 15, 2016, among 352 patients with severe orthopedic injuries at 6 US level I trauma centers. Statistical analysis was conducted from October 9, 2017, to July 13, 2018. Main Outcomes and Measures: At 6 weeks after discharge, patients completed standardized measures for 5 risk factors (pain intensity, depression, posttraumatic stress disorder, alcohol abuse, and tobacco use) and 4 protective factors (resilience, social support, self-efficacy for return to usual activity, and self-efficacy for managing the financial demands of recovery). Latent class analysis was used to classify participants into clusters, which were evaluated against measures of function, depression, posttraumatic stress disorder, and self-rated health collected at 12 months. Results: Among the 352 patients (121 women and 231 men; mean [SD] age, 37.6 [12.5] years), latent class analysis identified 6 distinct patient clusters as the optimal solution. For clinical use, these clusters can be collapsed into 4 groups, sorted from low risk and high protection (best) to high risk and low protection (worst). All outcomes worsened across the 4 clinical groupings. Bayesian analysis shows that the mean Short Musculoskeletal Function Assessment dysfunction scores at 12 months differed by 7.8 points (95% CI, 3.0-12.6) between the best and second groups, by 10.3 points (95% CI, 1.6-20.2) between the second and third groups, and by 18.4 points (95% CI, 7.7-28.0) between the third and worst groups. Conclusions and Relevance: This study demonstrates that during early recovery, patients with orthopedic trauma can be classified into risk and protective clusters that account for a substantial amount of the variance in 12-month functional and health outcomes. Early screening and classification may allow a personalized approach to postsurgical care that conserves resources and targets appropriate levels of care to more patients.

S-Nitrosylation of STIM1 by Neuronal Nitric Oxide Synthase Inhibits Store-Operated Ca2+ Entry.

Store-operated Ca2+ entry (SOCE) mediated by stromal interacting molecule-1 (STIM1) and Orai1 represents a major route of Ca2+ entry in mammalian cells and is initiated by STIM1 oligomerization in the endoplasmic or sarcoplasmic reticulum. However, the effects of nitric oxide (NO) on STIM1 function are unknown. Neuronal NO synthase is located in the sarcoplasmic reticulum of cardiomyocytes. Here, we show that STIM1 is susceptible to S-nitrosylation. Neuronal NO synthase deficiency or inhibition enhanced Ca2+ release-activated Ca2+ channel current (ICRAC) and SOCE in cardiomyocytes. Consistently, NO donor S-nitrosoglutathione inhibited STIM1 puncta formation and ICRAC in HEK293 cells, but this effect was absent in cells expressing the Cys49Ser/Cys56Ser STIM1 double mutant. Furthermore, NO donors caused Cys49- and Cys56-specific structural changes associated with reduced protein backbone mobility, increased thermal stability and suppressed Ca2+ depletion-dependent oligomerization of the luminal Ca2+-sensing region of STIM1. Collectively, our data show that S-nitrosylation of STIM1 suppresses oligomerization via enhanced luminal domain stability and rigidity and inhibits SOCE in cardiomyocytes.

Mortality After High-Energy Pelvic Fractures in Patients of Age 65 Years or Older.

OBJECTIVES: To document in-hospital and 1-year mortality rates after high-energy pelvic fracture in patients 65 years of age or older as compared to a younger cohort. DESIGN: Retrospective review. SETTING: Urban Level 1 academic trauma center. PATIENTS: Seventy consecutive patients 65 years of age and older treated for pelvic fracture resulting from high-energy mechanism from 2008 to 2011. A total of 140 patients 18-64 years of age were matched to the study population based on mechanism of injury and OTA Code 61 subtype for comparison. INTERVENTION: Review of demographics, injury characteristics, hospital management, and mortality. MAIN OUTCOME MEASUREMENTS: Mortality. RESULTS: The overall inpatient mortality rate was 10%. The older cohort exhibited an inpatient mortality rate 3 times higher than the younger cohort (18.6% vs. 5.7%, P = 0.003). There was no difference in mortality 1 year post discharge (5.3% vs. 3.8%, P = 0.699). No significant differences in initial Glasgow Coma Scale or Injury Severity Score were identified (GCS 12.9 vs. 12.4, P = 0.363; ISS 24.7 vs. 23.4, P = 0.479). Multivariate analysis identified the Charlson Comorbidity Index (CCI) (P = 0.012) and Abbreviated Injury Scale (AIS)-chest (P = 0.005) as independent predictors of in-hospital mortality, and CCI (0.005) and AIS-abdomen (0.012) for 1-year mortality. CONCLUSIONS: After controlling for mechanism of injury and pelvic fracture classification, we found that adults ≥65 and those with multiple comorbidities were more likely to die in the hospital than younger adults. However, mortality within 1-year postdischarge was low and did not differ between groups. This is in sharp contrast to the high rates of postdischarge mortality observed in elderly patients with a hip fracture. LEVEL OF EVIDENCE: Prognostic Level III. See Instructions for Authors for a complete description of levels of evidence.

Practical fabrication of microfluidic platforms for live-cell microscopy.

We describe a simple fabrication technique - targeted towards non-specialists - that allows for the production of leak-proof polydimethylsiloxane (PDMS) microfluidic devices that are compatible with live-cell microscopy. Thin PDMS base membranes were spin-coated onto a glass-bottom cell culture dish and then partially cured via microwave irradiation. PDMS chips were generated using a replica molding technique, and then sealed to the PDMS base membrane by microwave irradiation. Once a mold was generated, devices could be rapidly fabricated within hours. Fibronectin pre-treatment of the PDMS improved cell attachment. Coupling the device to programmable pumps allowed application of precise fluid flow rates through the channels. The transparency and minimal thickness of the device enabled compatibility with inverted light microscopy techniques (e.g. phase-contrast, fluorescence imaging, etc.). The key benefits of this technique are the use of standard laboratory equipment during fabrication and ease of implementation, helping to extend applications in live-cell microfluidics for scientists outside the engineering and core microdevice communities.

Inhibition of Rac1 reduces store overload-induced calcium release and protects against ventricular arrhythmia.

Rac1 is a small GTPase and plays key roles in multiple cellular processes including the production of reactive oxygen species (ROS). However, whether Rac1 activation during myocardial ischaemia and reperfusion (I/R) contributes to arrhythmogenesis is not fully understood. We aimed to study the effects of Rac1 inhibition on store overload-induced Ca(2+) release (SOICR) and ventricular arrhythmia during myocardial I/R. Adult Rac1(f/f) and cardiac-specific Rac1 knockdown (Rac1(ckd) ) mice were subjected to myocardial I/R and their electrocardiograms (ECGs) were monitored for ventricular arrhythmia. Myocardial Rac1 activity was increased and ventricular arrhythmia was induced during I/R in Rac1(f/f) mice. Remarkably, I/R-induced ventricular arrhythmia was significantly decreased in Rac1(ckd) compared to Rac1(f/f) mice. Furthermore, treatment with Rac1 inhibitor NSC23766 decreased I/R-induced ventricular arrhythmia. Ca(2+) imaging analysis showed that in response to a 6 mM external Ca(2+) concentration challenge, SOICR was induced with characteristic spontaneous intracellular Ca(2+) waves in Rac1(f/f) cardiomyocytes. Notably, SOICR was diminished by pharmacological and genetic inhibition of Rac1 in adult cardiomyocytes. Moreover, I/R-induced ROS production and ryanodine receptor 2 (RyR2) oxidation were significantly inhibited in the myocardium of Rac1(ckd) mice. We conclude that Rac1 activation induces ventricular arrhythmia during myocardial I/R. Inhibition of Rac1 suppresses SOICR and protects against ventricular arrhythmia. Blockade of Rac1 activation may represent a new paradigm for the treatment of cardiac arrhythmia in ischaemic heart disease.