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BACKGROUND Most distal radius fractures can be treated with closed reduction and casting in pediatric patients. These skills are traditionally developed treating real patients, however, there is growing interest in the use of simulation training to supplement traditional learning strategies. METHODS Seventy-eight children with distal radius fractures that underwent closed reduction and casting by novice orthopaedic surgery residents were retrospectively reviewed. Radiographic measures of patients treated by simulation-trained residents were compared with patients treated by residents without simulation training. RESULTS Patients treated by simulation-trained residents had less residual angulation in the anteroposterior radiograph (3.7 vs. 6.3 degrees, P=0.006) and translation on the lateral (14% vs. 21%, P=0.040) and anteroposterior radiograph (10% vs. 16%, P=0.029). Patients treated by simulation-trained residents also had lower rates of redisplacement (50% vs. 79%, P=0.016). CONCLUSIONS Loss of reduction is common, particularly when novice trainees perform their first independent reductions. Residents who underwent simulation training had lower rates of loss of reduction, thus simulation training has potential as a supplement to the traditional apprentice model of medical education. LEVEL OF EVIDENCE Level III.

"Insomnia is highly comorbid with other mental health and medical conditions and adversely affects quality of life and daytime functioning. Cognitive behavioral therapy for insomnia (CBT-I) is a safe and efficacious treatment for insomnia in the context of various comorbid conditions. In this article, the authors outline considerations for delivering CBT-I in patients with the most common co-occurring medical and mental health conditions, review the evidence for CBT-I in these populations as well as special considerations for its application, and highlight future areas for research in the area of CBT-I for comorbid medical and psychiatric conditions."

BACKGROUND Following anterior cruciate ligament (ACL) reconstruction, children are at significant risk for complications, including contralateral ACL rupture. The purpose of this study is to determine which children are at risk for a contralateral ACL tear after ipsilateral reconstruction. METHODS After review of medical records, we contacted patients who underwent primary ACL reconstruction between 2009 and 2016. Patients were included in the study if they were able to provide follow-up data either in person or remotely at least 2 years after surgery. Demographic data, sports participation, and intraoperative findings and techniques were recorded. All patients were also asked to confirm returning to sport information and postoperative complications (including contralateral ACL tear). Univariate analysis consisted of χ and independent samples t tests. Purposeful entry logistic regression was then conducted to control for confounding factors. Kaplan-Meier analysis was performed to assess contralateral ACL survival. RESULTS A total of 498 children with average follow-up of 4.3±2.1 years were included in the analysis. The mean age was 15.0±2.3 years and 262 patients (52.6%) were female. Thirty-five subjects (7.0%) sustained a contralateral ACL tear at a mean of 2.7±1.7 years following index reconstruction. Kaplan-Meier analysis revealed the median contralateral ACL survival time to be 8.9 years [95% confidence interval (CI): 8.3, 9.5 y]. In univariate analysis, 11.5% of female patients had a contralateral rupture compared with 2.1% of male patient (P

Background: Arthroscopic drilling is a well-established treatment for stable intact OCDs of the knee in children when non-operative treatment fails. The decision to proceed to operative treatment requires a discussion regarding the risks and benefits of surgical intervention. While there is abundant data suggesting that OCD drilling is a highly effective treatment strategy, there is little data specifically evaluating the risks and complications of this procedure. Purpose: The goal of this study was to assess the complications of drilling of stable OCDs of the knee, and the risk factors for developing complications. Methods: In a retrospective chart review from 2009-2017, data from patients Results: 139 knees in 131 patients were evaluated, of which 102 (73%) were male. The mean age was 12.7years. 108 knees (77%) had an open physis at the time of operation. Patients were managed conservatively for a mean of 6.76 months pre-operatively (SD=6.6). Average follow-up was 14.8 months after the initial surgery (SD=13.25). 53 patients (38%) were obese or overweight at the time of surgery. All patients regained full ROM within 5° of the contralateral knee at a mean 12.9 weeks post-op (SD=3.2), with all but 7 (5 %) returning to activities of daily living at the 3-month visit. No cases of infection, stiffness, arthrofibrosis, or other procedure-related complications were recorded. 6 knees (4.3%) underwent 7 additional surgeries during the follow-up period, all of which were for treatment failure in non-healing lesions (loose body removals, chondroplasty, or repeat drilling). In a multiple logistic regression model, age, gender, status of the physis at the time of surgery, BMI percentile, and OCD size were not predictive of the need for additional surgeries. Discussion: Our findings suggest that arthroscopic drilling for OCDs of the knee is a safe procedure with minimal risk of complications. The majority of patients return to their pre-operative daily activity level with full ROM by 3 months after surgery. Complications, including reoperation, were related to the progression of the OCD, rather than the surgical procedure.

The COVID-19 pandemic has led to a reduced colonoscopy capacity in the UK resulting in increased waiting times for investigation. To increase diagnostic capacity and reduce the risk of diagnostic delay, CT colonography (CTC) and colon capsule endoscopy (CCE) are increasingly being relied upon. Endoscopic assessment and treatment will be required for those patients with large colonic polyps or malignant tumours detected by CTC or CCE, provided they are fit enough to undergo further investigation. The management of patients with intermediate (6-9mm) and diminutive (

BACKGROUND Operative treatment of medial epicondyle fractures can be performed in either a supine or prone position. In the supine position, fracture visualization is sometimes difficult due to the posterior position of the medial epicondyle. However, the prone position requires extensive patient repositioning but may improve visualization. The purpose of this study was to compare the results and complications between the supine and prone position when treating medial epicondyle fractures. METHODS In a retrospective chart review, patients below 18 who underwent open reduction and internal fixation of an acute medial epicondyle fracture from January 2011 to August 2019 were identified. Patients with

Background: In adults, anterior glenohumeral instability has been associated with a tall and narrow glenoid morphology, assessed using the glenoid index (GI; glenoid height-to-width ratio) on magnetic resonance imaging (MRI). This morphological association has not been assessed in children and adolescents. Purpose/Hypothesis: To examine the association of GI and other MRI measurements of interest supported in studies on adults with anterior glenohumeral dislocation in patients aged ≤19 years. We hypothesized that these patients would have a significantly greater GI (relatively taller and narrower glenoid morphology) compared with healthy controls. Study Design: Case-control study; Level of evidence, 3. Methods: An institutional radiology database was queried over a 10-year period to identify patients aged ≤19 years who had been diagnosed with radiographically confirmed anterior shoulder dislocation and who underwent glenohumeral magnetic resonance arthrography as well as those without dislocation with normal shoulder arthrogram studies (controls). Patients with bony Bankart lesions were excluded. The following glenohumeral dimensions were measured on shoulder arthrogram: GI, glenoid version, coracohumeral interval, and rotator interval width/depth. Comparative analysis between the 2 groups was performed using the Student t test for each variable, followed by receiver operating characteristic (ROC) analysis to determine discriminative ability when statistically significant. Results: Overall, 55 participants (33 male and 22 female patients; mean age, 15.4 ± 2.1 years) were enrolled; 22 patients were in included in the dislocator group and 33 patients comprised the control group. The mean GI in the dislocator group was significantly greater than the control group (1.55 ± 0.14 vs. 1.38 ± 0.08; P < .001). ROC analysis revealed adequate discrimination of GI in predicting glenohumeral dislocation (area under the curve = 0.88). A GI ≥1.45 was 83% sensitive and 79% specific for predicting dislocation in the study cohort. Conclusion: Patients with anterior glenohumeral dislocation had increased GI (taller and narrower glenoid morphology) than controls. This useful MRI measurement may help identify patients at risk for primary or recurrent anterior glenohumeral instability events and may therefore help with guiding treatment and prevention.

Radial neck fractures are the third most common elbow fracture in children. Open reduction may be required if closed or mini-open techniques are not successful in reducing the fracture. Previous reports on open reduction have noted poor outcomes and complications with this treatment approach. However, it is unknown whether it is the open procedure itself or the severity of the initial injury that leads to the poor results. The purpose of this study was to evaluate the correlation between intraoperative findings at the time of open reduction of radial neck fractures and the clinical and radiographic outcomes.Data from patients who underwent open reduction for an acute radial neck fracture between January 2009 and December 2018 were abstracted and reviewed. Patients undergoing open treatment for a nonunion or malunion and those with inadequate follow-up were excluded. Demographic data, injury characteristics, treatment strategies, intraoperative findings, and clinical and radiographic outcomes were assessed.Twenty-two patients met the inclusion criteria. Of these patients, 14 were girls. The mean age was 9.7 ± 3 years, and the mean follow-up period was 15.8 months. Fifteen patients had a Judet grade IV displacement. Fair or poor outcomes were observed in 12 patients (55%). Ten reoperations were recorded during the study period. Age, weight, and associated injuries were not predictive of poor outcomes. Intraoperative findings of soft-tissue stripping and radial head comminution were the only significant predictors of fair or poor clinical outcomes (P.001) and subsequent radiographic changes including fragmentation and collapse of the radial head and arthritic changes (P.001). The quality of reduction and the choice of hardware were not significantly associated with either clinical or radiographic outcomes.Our findings support the notion that the outcomes of open reduction of radial neck fractures are most closely correlated with the injury severity, with the intraoperative findings of complete soft-tissue stripping or comminution of the radial head fragment being significant predictors of poor clinical and radiographic outcomes. The choice of hardware and the quality of reduction achieved at the time of surgery have less significance than injury severity.

Purpose To evaluate the cost-effectiveness of a trial of nonoperative management versus early drilling in the treatment of skeletally immature patients with stable osteochondritis dissecans (OCD) of the knee. Methods A decision tree model was used to compare the cost-effectiveness of a trial of nonoperative management versus early drilling (within 6 weeks of the first office visit) from payer and societal perspectives over a 3-year time horizon. Relevant transition probabilities, costs (in 2019 US dollars based on Medicare reimbursement), health state utilities, and times to healing were derived from the literature. The principal outcome measure was the incremental cost-effectiveness ratio (ICER). One- and 2-way sensitivity analyses were performed on pertinent model parameters to validate the robustness of the base-case results using a conservative willingness-to-pay (WTP) threshold of $50,000 per quality-adjusted life-year (QALY). The Consolidated Health Economic Evaluation Reporting Standards checklist for reporting economic evaluations was used. Results In the base-case analysis from a payer perspective, early drilling was more effective (2.51 versus 2.27 QALYs), more costly ($4,655 versus $3,212), and overall more cost-effective (ICER $5,839/QALY) relative to nonoperative management. In the base-case analysis from a societal perspective, early drilling dominated nonoperative management owing to its increased effectiveness (2.51 versus 2.27 QALYs) and decreased cost ($13,098 versus $18,149). These results were stable across broad ranges on sensitivity analysis. Based on 1-way threshold analyses from a payer perspective, early drilling remained cost-effective as long it cost less than $19,840, the disutility of surgery was greater than –0.40, or the probability of successful early drilling was greater than 0.62. Conclusions Although the traditional approach to stable OCD lesions of the knee in skeletally immature patients has been a trial of nonoperative management, our data suggest that early drilling may be cost-effective from both payer and societal perspectives. Level of Evidence III, economic and decision analysis.

BACKGROUND Clinical consequences of an interplay between dysfunction/injury of different end-organs in acute heart failure (AHF) remain unknown. METHODS AND RESULTS In 284 consecutive AHF patients, end-organ dysfunction/injury was defined as cardiac [troponin I level above the upper reference limit (URL, > 0.056 ng/mL)], kidney (estimated glomerular filtration rate 3 times the URL (> 114 IU/L and > 105 IU/L for AST and ALT, respectively), bilirubin above the URL (> 1.3 mg/mL), albumin below the lower reference limit ( 1 end-organ dysfunction/injury identifies patients at the highest risk of poor outcomes.

Background Cardiovascular safety of marathon running in recreational runners remains unclear. We set up this study to comprehensively evaluate the effects of a marathon run on the profile of cardiovascular stress biomarkers in connection with transthoracic echocardiography. Design and methods Thirty-three healthy male amateur runners, aged ≥50 years (mean age 57 ± 7) were enrolled. Venous blood samples were obtained before the marathon, just after the race, 2–4 and seven days after the marathon. Using novel single molecule counting technology we measured: plasma concentrations of high-sensitivity cardiac troponin I (hs-cTnI) and endothelin-1. N-terminal pro B-type natriuretic peptide was measured using electrochemiluminescence. Each participant had transthoracic echocardiography before and immediately after the race. Results We observed a sharp rise in the levels of all biomarkers after the race (all p 169 km/month, a median for the studied group) had lower hs-cTnI leak after the race (median 15.11 ng/ml and 31.2 ng/ml, respectively; p Conclusions Marathon run is associated with sharp and significant rises in the biomarkers of cardiovascular stress. The profile of these changes, however, along with echocardiographic parameters, does not suggest irreversible myocardial damage.

Background Greater frequency and intensity level of sports participation may be contributing to an increasing incidence of anterior cruciate ligament (ACL) tears in skeletally immature athletes. Prior studies have assessed the functional outcomes of physeal-respecting ACL reconstruction in this patient population based on adult functional outcomes scoring systems; however, there is only sparse literature evaluating functional outcomes of this specific patient population. This study aimed to retrospectively evaluate a cohort of pediatric patients who had undergone all-epiphyseal ACL reconstruction (AEACLR) with a set of clinically validated, pediatric-specific patient-reported functional outcomes scores (PRFOS). We hypothesized that patients who had rerupture would have significantly lower outcomes scores compared with those who did not rerupture. Methods This was a retrospective evaluation of AEACLR patients at a single, tertiary care, children's hospital within a period of 2 years and had >6 months of initial clinical postoperative follow-up. Those who consented to participation were provided an online combined survey including questions relating to demographics and rerupture as well as 3 validated pediatric PRFOS. Statistical analysis of the cohort demographics, PRFOS, and subgroup analysis of the rerupture group compared with the ACL intact patients was performed. Results The mean functional outcome scores at a mean of 48.6 months from surgery demonstrated excellent return to functional activity (Mean International Knee Documentation Committee, 93.8; Pedi-Patient-Reported Outcomes Measurement Information System, 98.8; Pedi- Functional Activity Brief Score, 21.6). There was a 13% rerupture rate and rerupture patients had a significantly decreased Pedi-International Knee Documentation Committee (94.9 intact vs. 86.0 rerupture; P=0.001) and Pedi-Patient-Reported Outcomes Measurement Information System (99.4 intact vs. 95.4 rupture; P=0.001) scores. Conclusions AEACLR patients have excellent outcomes based on pediatric-specific PRFOS. Rerupture patients demonstrated a decrease in functional outcomes scores compared with intact ACL patients. The results demonstrate the efficacy of AEACLR as measured by pediatric-specific functional outcome scores for the treatment of ACL rupture in skeletally immature athletes. Level of evidence Level III-retrospective comparative study.

AIMS Despite attempts to improve the management of patients with acute heart failure (HF), virtually all therapeutic agents investigated in large clinical trials failed to show any consistent reduction in mortality and morbidity. Complexity of the clinical syndrome of acute HF seems to be likely an underlying explanation. Traditionally, clinical trials studied mixed patient populations with acute HF, and only recently, better clinical characterization of patients has been proposed. Dyspnoea is the most common presenting symptom related to hospital admission for acute HF. Whether in patients with acute HF, the pattern of symptoms onset preceding hospital admission is associated with clinical characteristics, and the outcomes have not yet been established. METHODS AND RESULTS We investigated 137 patients (mean age: 65 ± 13 years; 80% men) hospitalized due to acute HF with dyspnoea as major reported symptom, who were divided according to the time of its onset into those with acute (n = 98) vs. subacute (n = 39) onset (i.e. within 7 days vs. >7 days preceding hospital admission, respectively). On admission, the former group presented higher blood pressure (138 ± 33 vs. 121 ± 32 mmHg), more often moderate-severe pulmonary congestion (33 vs. 8%), and lower bilirubin level [1.07 (0.72-1.60) vs. 1.27 (0.87-2.06); P

Patients with RA display greater occult coronary atherosclerosis burden and experience higher cardiovascular morbidity and mortality compared with controls. We here explored whether pro-inflammatory cytokines and high-sensitivity cardiac troponin I (hs-cTnI), a biomarker of myocardial injury, correlated with plaque burden and cardiovascular events (CVEs) in RA.We evaluated 150 patients with 64-slice coronary CT angiography. Coronary artery calcium, number of segments with plaque (segment involvement score), stenotic severity and plaque burden were assessed. Lesions were described as non-calcified, mixed or fully calcified. Blood levels of hs-cTnI and pro-inflammatory cytokines were assessed during coronary CT angiography. Subjects were followed over 60 (s.d. 26) months for both ischaemic [cardiac death, non-fatal myocardial infarction (MI), stroke, peripheral arterial ischaemia] and non-ischaemic (new-onset heart failure hospitalization) CVEs.Plasma hs-cTnI correlated with all coronary plaque outcomes (P < 0.01). Elevated hs-cTnI (⩾1.5 pg/ml) further associated with significant calcification, extensive atherosclerosis, obstructive plaque and any advanced mixed or calcified plaques after adjustments for cardiac risk factors or Framingham D'Agostino scores (all P < 0.05). Eleven patients suffered a CVE (1.54/100 patient-years), eight ischaemic and three non-ischaemic. Elevated hs-cTnI predicted all CVE risk independent of demographics, cardiac risk factors and prednisone use (P = 0.03). Conversely, low hs-cTnI presaged a lower risk for both extensive atherosclerosis (P < 0.05) and incident CVEs (P = 0.037).Plasma hs-cTnI independently associated with occult coronary plaque burden, composition and long-term incident CVEs in patients with RA. Low hs-cTnI forecasted a lower risk for both extensive atherosclerosis as well as CVEs. hs-cTnI may therefore optimize cardiovascular risk stratification in RA.

Background The interpretation and clinical usefulness of elevated levels of cardiac troponins in acute heart failure (AHF) remain controversial. We aimed to characterize the relationship between changes in cardiac troponin I (measured using a new high-sensitive immunoassay by single-molecule counting technology, Singulex, Alameda, USA; hs-TnI) during first 48h of hospital stay and patients' characteristics and the outcomes. Methods and results We measured hs-TnI at baseline, after 24 and 48h in 130 AHF patients (mean age: 65±13years, 77% men). The percentage of patients with elevated hs-TnI (i.e., above the upper reference limit [URL]>10.19pg/mL) were: on admission – 59%, after 24h – 61%, and after 48h – 58%. Elevated baseline level of hs-TnI was associated with more severe dyspnoea on admission but neither peak level nor changes in hs-TnI during first 48h were related to the dyspnoea severity or magnitude of dyspnoea relief. During 1-year follow-up there were 32 (25%) cardiovascular deaths. Neither absolute baseline nor peak values of hs-TnI predicted cardiovascular mortality. Only changes in hs-TnI were independently associated with cardiovascular mortality with the strongest relationship seen in peak change in hs-TnI: patients with an increase vs. remaining patients - hazard ratio (95% confidence interval): 3.22 (1.52–6.82) p =0.002. Conclusions Using the new assay (proved to be more sensitive that the other available troponin assays) we observed that approximately 60% of patients with AHF presented elevated hs-TnI above URL during first 48h of hospital stay. Only significant increase in hs-TnI predicted cardiovascular mortality.

Mycobacterial heat shock protein 65 gene (Hsp65) has been widely used for classification of Mycobacterial species, and detection of Mycobacterial genes by molecular methods and has proven useful in identification of Mycobacterial infection in various clinical conditions. Circulating antibody against Mycobacterial hsp65 has been found in many clinical diseases including autoimmune diseases (Crohn&rsquo, s disease, lupus erythematosus, multiple sclerosis, diabetes, etc.), atherosclerosis and cancers. The prevalence of anti-Hsp65 antibody in the normal healthy population is unknown. We determined the blood levels of antibody against Mycobacterial hsp65 in the normal population represented by 288 blood donors of the American Red Cross and tested the blood of 109 patients with Crohn&rsquo, s disease and 28 patients with Sjogren&rsquo, s syndrome for comparison. The seroprevalence of anti-Hsp65 IgG in the normal population of Red Cross donors was 2.8% (8 of 288 positive). The Hsp65 antibody levels were significantly elevated in patients with Crohn&rsquo, s disease and Sjogren&rsquo, s syndrome. The prevalence of Hsp65 antibody in Crohn&rsquo, s disease patients was 67.9% (74 of 109 patients), and 85.7% for Sjogren&rsquo, s patients (24 of 28 patients). Our data indicate that anti-Hsp65 antibody is rare in the normal population, but frequent in chronic diseases. The presence of circulating Hsp65 antibody reflects an abnormal immune (adaptive) response to Mycobacterial exposure in patients with chronic diseases, thus differentiating the patients with chronic diseases from those clinical mimics.

BACKGROUND Simulation-based training is one way to improve basic competence for surgical trainees and thus improve patient safety. Closed reduction and percutaneous pinning of a supracondylar humerus fracture is a common procedure that encompasses many basic orthopaedic skills and has been identified as a residency milestone. Despite this, no quantitative tools exist to help learners attain this basic skill. This study seeks to validate a quantitative, low-cost simulation-based training tool for teaching orthopaedic surgery trainees the fundamentals of fracture stabilization with pins. METHODS Two low-cost models were developed with simulated cancellous bone blocks and cortical bone sheets: a pinning agility tool to teach pin placement and redirection, and a low-cost construct stability tool to replicate pinning. A high-cost construct stability tool was cut using a pediatric supracondylar humerus model to simulate pinning a real fracture. Construct stability was assessed by adding weight until ∼1.6 mm of displacement was observed. Participants were tested naively on all 3 models and then completed a training session using only the low-cost models. Performance following training was then assessed and compared with fellowship-trained pediatric orthopaedic surgeons. Participants also rated their preintervention and postintervention confidence, skill, and knowledgeability. RESULTS A total of 18 novice trainees participated (10 PGY1 and PGY2 orthopaedic surgery residents and 8 medical student members of the orthopaedic surgery interest club), whereas the reference group consisted of 7 orthopaedic surgery attendings. The subjects significantly improved their scores on both the low-cost (P=0.002) and high-cost (P

Background: We recently reported that serum levels of highly-sensitive cardiac troponin-I (hs-cTnI)- a specific structural myocardial biomarker- associated with occult coronary plaque presence, burden and long-term cardiovascular events in patients with rheumatoid arthritis (RA). We further demonstrated that presence of IgA antibodies against beta2-glycoprotein-1 (a-b2GPI-IgA, an apolipoprotein readily expressed in human atherosclerotic plaque) associated with baseline coronary artery calcium (CAC) scores and independently predicted CAC progression in patients with RA. Objectives: We here explored whether baseline evaluation of both hs-cTnI and a-b2GPI-IgA better predicts CAC progression than either of them in isolation. Methods: Ninety five participants with a baseline plaque evaluation by coronary computed tomography angiography (CCTA) underwent follow-up assessment within 6.9±0.3 years. Coronary artery calcium (CAC) was quantified by the Agatston method. Hs-cTnI and a-b2GPI IgA Ab were assessed on the day of baseline CCTA; the latter were reconfirmed 12 weeks later, if positive. CAC change was evaluated with the MESA method as the natural logarithm plus 25 difference [(ln CAC(follow-up)+ 25) – (ln CAC(baseline) + 25)]. Generalized linear models evaluated the effect of hs-cTnI, a-b2GPI-IgA and their interaction on CAC change. Models were adjusted for age, hypertension, waist-to height ratio (obesity indicator), cumulative inflammatory burden (time-averaged C-Reactive protein), total prednisone dose and duration of statin exposure from baseline to follow-up scan. Results: Baseline hs-cTnI was higher in a-b2GPI-IgA positive compared to negative patients [median (IQR) of 1.9 (1.6-2.6) vs. 1.4 (1.3-1.7) respectively, p=0.043]. Hs-cTnI alone did not independently predict CAC change (β=0.214, p=0.132) in the multivariable model whereas a-b2GPI-IgA presence did (β=0.454, p=0.003). There was a significant interaction between hs-cTnI and a-b2GPI-IgA on CAC progression (Wald Chi-square=4.19, p=0.041); high hs-cTnI (>1.5pg/ml) predicted significantly greater CAC change in a-b2GPI-IgA positive patients but not in negative ones [estimated marginal mean difference (IQR)=0.36 (0.12-0.59), p=0.003) and figure 1]. Conclusion: Baseline hs-cTnI in isolation is not predictive of CAC progression in patients with RA; however, in the context of a-b2GPI-IgA presence, high hs-cTnI independently predicts significant increase in coronary atherosclerosis burden. Disclosure of Interests: George Karpouzas Grant/research support from: Pfizer, Consultant for: Sanofi-Genzyme-Regeneron, Janssen, Roche-Genentech, Pfizer, Speakers bureau: BMS, Sanofi-Genzyme-Regeneron, Janssen, Roche-Genentech, Sarah Ormseth: None declared, Elizabeth Hernandez: None declared, Joel Estis Employee of: Singulex, John Todd Employee of: Singulex, Matthew Budoff: None declared

Background: The use of a washer to supplement screw fixation can prevent fragmentation and penetration during the surgical treatment of medial epicondyle fractures. However, concerns may arise regarding screw prominence and the need for subsequent implant removal. The purpose of this study is to evaluate the impact of washer utilization on the need for hardware removal and elbow range of motion (ROM). Methods: All surgically-treated pediatric medial epicondyle fractures over a 7-year period were queried for this retrospective case-control study. Patients were only included if their fracture was fixed with a single screw with or without a washer. Per institutional protocol, implants were not routinely removed after fracture healing. Hardware removal was performed only if the patient experienced a complication or implant-related symptoms that were refractory to non-operative management. Full ROM was considered flexion beyond 130 degrees and less than a 10-degree loss of extension. Univariate analysis was followed by creation of Kaplan-Meier (one minus survival) curves in order to analyze the time until full ROM was regained after surgery. Curves between patients with and without a washer were compared with a log rank test. Results: Of the 137 patients included in the study, the mean age was 12.2±2.3 years and 85 (62%) were male. A total of 31 (23%) patients ultimately underwent hardware removal. A washer was utilized in 90 (66%) cases overall. There was not an increased need for subsequent implant removal in these patients compared to those that underwent screw fixation alone (p=0.11). The mean BMI of patients that underwent hardware removal (19.1±2.5) was similar to that of children who did not (20.4±3.5, p=0.06). When analyzing a subgroup of 102 athletes only, there was similarly no difference in the rate of implant removal if a washer was used (p=0.64). Overall, 107 (78%) patients regained full ROM at a mean of 13.9±9.7 weeks after surgery (Figure 1). There was no statistically significant difference in the proportions of patients with and without a washer that achieved full ROM (p=0.46). Full ROM was achieved at a mean of 14.1±11.0 weeks in those with a washer compared to 13.6±6.2 weeks in those without one (p=0.21). Conclusions: Use of a washer did not affect the need for subsequent implant removal or elbow ROM after fixation of pediatric medial epicondyle fractures, even in thinner patients or competitive athletes. If there is concern for fracture fragmentation or penetration, a washer can be included without concern that future unplanned surgeries may be required.

Background: Operative treatment of medial epicondyle (ME) fractures can be performed in either supine or prone position. In the supine position, visualization and fixation of the fracture is difficult. However, the prone position requires extensive patient repositioning but may improve visualization. Purpose: The purpose of this study was to compare the results of ORIF of ME fractures between supine and prone positions. Methods: In a retrospective review, patients Results: 204 patients were included, with a mean age of 11.7 years. 133(65.1%) were sports injuries, and 67(32.8%) had concomitant dislocation, with 17(8.3%) having an incarcerated fracture. 122(60%) patients were in the supine group, and 82(40%) in prone. The mean wheels in-wheels out time was 113 minutes in the supine group, and 141 minutes in the prone group (PConclusion: With the largest study population in the literature, the results of our study show that surgical stabilization of medial epicondyle fractures is safe, with minimal complications. While the prone position requires additional time in the operating room, presumably for positioning, the surgical procedure takes the same time and the prone position allows for a more accurate reduction. While the clinical significance of a 1mm difference in reduction quality is unknown, the observation that no surgeon that has tried the prone position had ever gone back to the supine position suggests that the surgical procedure is technically easier in this position.

Aims Recent studies indicate the need to redefine worsening renal function (WRF) in acute heart failure (AHF), linking a rise in creatinine with clinical status to identify patients who develop ‘true WRF’. We evaluated the usefulness of serial assessment of urinary levels of neutrophil gelatinase-associated lipocalin (uNGAL), kidney injury molecule-1 (uKIM-1), and cystatin C (uCysC) for prediction of ‘true WRF’. Methods and results In 132 patients with AHF, uNGAL, uKIM-1, and uCysC were measured using a highly sensitive immunoassay based on a single-molecule counting technology (Singulex, Alameda, CA, USA) at baseline, day 2, and day 3. Patients who developed WRF (a ≥0.3 mg/dL increase in serum creatinine or a >25% decrease in the estimated glomerular filtration rate from the baseline value) were differentiated into those ‘true WRF’ (presence of deterioration/no improvement in clinical status during hospitalization) vs. ‘pseudo-WRF’ (uneventful clinical course). ‘True WRF’ occurred in 13 (10%), ‘pseudo-WRF’ in 15 (11%), whereas the remaining 104 (79%) patients did not develop WRF. Patients with ‘true WRF’ were more often females, had higher levels of NT-proBNP, creatinine, and urea on admission, higher urine albumin to creatinine ratio at day 2, higher uNGAL at baseline, day 2, and day 3, and higher KIM-1 at day 2 (vs. pseudo-WRF vs. without WRF, all P < 0.05). Patients with pseudo-WRF did not differ from those without WRF. In the multivariable model, elevated uNGAL at all time points and uKIM-1 at day 2 remained independent predictors of ‘true WRF’. Conclusion Elevated levels of uNGAL and uKIM-1 may predict development of ‘true WRF’ in AHF.

Background & Aims Vedolizumab is an anti-a4b7 monoclonal antibody that is licensed for the treatment of moderate to severe Crohn’s disease and ulcerative colitis. The aims of this study were to establish the real-world effectiveness and safety of vedolizumab for the treatment of inflammatory bowel disease. Methods This was a retrospective study involving seven NHS health boards in Scotland between June 2015 and November 2017. Inclusion criteria included: a diagnosis of ulcerative colitis or Crohn’s disease with objective evidence of active inflammation at baseline (Harvey–Bradshaw Index[HBI] ≥5/Partial Mayo ≥2 plus C-reactive protein [CRP] >5 mg/L or faecal calprotectin ≥250 µg/g or inflammation on endoscopy/magnetic resonance imaging [MRI]); completion of induction; and at least one clinical follow-up by 12 months. Kaplan–Meier survival analysis was used to establish 12-month cumulative rates of clinical remission, mucosal healing, and deep remission [clinical remission plus mucosal healing]. Rates of serious adverse events were described quantitatively. Results Our cohort consisted of 180 patients with ulcerative colitis and 260 with Crohn’s disease. Combined median follow-up was 52 weeks (interquartile range [IQR] 26–52 weeks). In ulcerative colitis, 12-month cumulative rates of clinical remission, mucosal healing, and deep remission were 57.4%, 47.3%, and 38.5%, respectively. In Crohn’s disease, 12-month cumulative rates of clinical remission, mucosal healing, and deep remission were 58.4%, 38.9%, and 28.3% respectively. The serious adverse event rate was 15.6 per 100 patient-years of follow-up. Conclusions Vedolizumab is a safe and effective treatment for achieving both clinical remission and mucosal healing in ulcerative colitis and Crohn’s disease.

BACKGROUND The early diagnosis of urgent abdominal pain (UAP) is challenging. Most causes of UAP are associated with extensive inflammation. Therefore, we hypothesized that quantifying inflammation using interleukin-6 and/or procalcitonin would provide incremental value in the emergency diagnosis of UAP. METHODS This was an investigator-initiated prospective, multicenter diagnostic study enrolling patients presenting to the emergency department (ED) with acute abdominal pain. Clinical judgment of the treating physician regarding the presence of UAP was quantified using a visual analog scale after initial clinical and physician-directed laboratory assessment, and again after imaging. Two independent specialists adjudicated the final diagnosis and the classification as UAP (life-threatening, needing urgent surgery and/or hospitalization for acute medical reasons) using all information including histology and follow-up. Interleukin-6 and procalcitonin were measured blinded in a central laboratory. RESULTS UAP was adjudicated in 376 of 1038 (36%) patients. Diagnostic accuracy for UAP was higher for interleukin-6 [area under the ROC curve (AUC), 0.80; 95% CI, 0.77–0.82] vs procalcitonin (AUC, 0.65; 95% CI, 0.62–0.68) and clinical judgment (AUC, 0.69; 95% CI, 0.65–0.72; both P < 0.001). Combined assessment of interleukin-6 and clinical judgment increased the AUC at presentation to 0.83 (95% CI, 0.80–0.85) and after imaging to 0.87 (95% CI, 0.84–0.89) and improved the correct identification of patients with and without UAP (net improvement in mean predicted probability: presentation, +19%; after imaging, +15%; P < 0.001). Decision curve analysis documented incremental value across the full range of pretest probabilities. A clinical judgment/interleukin-6 algorithm ruled out UAP with a sensitivity of 97% and ruled in UAP with a specificity of 93%. CONCLUSIONS Interleukin-6 significantly improves the early diagnosis of UAP in the ED.

AIMS The clinical significance of the measurement of urine sodium concentration (UNa+ ) in response to loop diuretic administration in patients with acute heart failure (AHF) is still unsettled. We studied the association of serial measurements of spot UNa+ during the first 48 h of AHF treatment with the indices of decongestion, renal function, and prognosis. METHODS AND RESULTS We enrolled 111 AHF patients, all of whom received intravenous furosemide on admission. The mean spot UNa+ significantly increased in the 6 h sample (P

BackgroundCancer survivors with fatigue often experience depressive symptoms, anxiety, and pain. Previously, we reported that self-acupressure improved fatigue; however, its impact on other co-occurring symptoms and their involvement in treatment action has not been explored.MethodsChanges in depressive symptoms, anxiety, and pain were examined prior to and following two formulas of self-acupressure and usual care using linear mixed models in 288 women from a previously reported clinical trial. Participants were categorized by random assignment into one of three groups: 1) relaxing acupressure, 2) stimulating acupressure, or 3) usual care. Moderators investigated were body mass index, age, depressive symptoms, anxiety, sleep and pain, and mediators were change in these symptoms.ResultsFollowing treatment, depressive symptoms improved statistically significantly for the relaxing acupressure group (41.5%) compared with stimulating acupressure (25%) and usual care (7.7%). Both acupressure groups were associated with greater improvements in anxiety than usual care, but only relaxing acupressure was associated with greater reductions in pain severity, and only stimulating acupressure was associated with greater reductions in pain interference. There were no statistically significant moderators of sleep quality, anxiety, or depressive symptoms. Fatigue statistically significantly moderated pain, and age statistically significantly modified fatigue. Changes in depressive symptoms and sleep quality statistically significantly mediated the relationship between relaxing acupressure and usual care on fatigue; however, the effect was small.ConclusionsAcupressure was associated with greater improvements than usual care in anxiety, pain, and symptoms of depression in breast cancer survivors with troublesome fatigue. These findings warrant further evaluation in suitably controlled randomized trials.

Background: Studies on pediatric anterior cruciate ligament reconstructions (ACLRs) often focus on graft choice, as rates of these injuries have risen in recent years. Large multicenter studies have found younger age and smaller graft size to be risk factors for graft failure and contralateral tears, but despite large sample sizes these studies have not looked specifically at graft strand number. Therefore the purpose of this study was to use a large sample size to ask whether ACLR graft strand number affects long-term outcomes. Hypothesis/Purpose: Examine long-term effects of ACLR graft strand number using a large cohort. Methods: This was a retrospective comparison study of all patients presenting between 1/1/2008 and 12/31/16 for a first-time ACLR at a single pediatric hospital. After querying medical records for all ACLRs using CPT codes, graft strand number, graft diameter, and other variables were abstracted. Long-term outcomes on graft rupture, contralateral ACL tear, and subsequent meniscus injury were collected via phone calls and REDCap emails. Patient groups were compared for differences in graft strand number and diameter using bivariate analyses, and differences in long-term outcomes were analyzed using multivariate regression. Results: 436 patients met the inclusion criteria also completed the long-term follow-up on outcomes. Long-term follow-up ranged from 18 months post surgery to 10 years post surgery. Patients with larger graft diameter were significantly less likely to suffer a complication (graft rupture, contralateral ACL tear, or subsequent meniscus injury) in multivariate regression (p=0.03), while strand number, sex, weight, and age showed no significant difference. Transphyseal reconstructions had larger graft diameters (8.8mm) than partial hybrid (8.6mm) and all-epiphyseal reconstructions (8.3mm) (pConclusion: This data supports the existing literature that pediatric ACLR patients with larger graft diameters are less likely to suffer long-term complications. Using both a large patient cohort and long-term follow-up, this data also showed that graft strand number was not significantly correlated with outcomes. This suggests that strand number is not important when constructing ACLR grafts, as long as sufficient graft diameter can be achieved.

BACKGROUND: Oesophageal adenocarcinoma is the sixth most common cause of cancer death worldwide and Barrett's oesophagus is the biggest risk factor. We aimed to evaluate the efficacy of high-dose esomeprazole proton-pump inhibitor (PPI) and aspirin for improving outcomes in patients with Barrett's oesophagus.METHODS: The Aspirin and Esomeprazole Chemoprevention in Barrett's metaplasia Trial had a 2 × 2 factorial design and was done at 84 centres in the UK and one in Canada. Patients with Barrett's oesophagus of 1 cm or more were randomised 1:1:1:1 using a computer-generated schedule held in a central trials unit to receive high-dose (40 mg twice-daily) or low-dose (20 mg once-daily) PPI, with or without aspirin (300 mg per day in the UK, 325 mg per day in Canada) for at least 8 years, in an unblinded manner. Reporting pathologists were masked to treatment allocation. The primary composite endpoint was time to all-cause mortality, oesophageal adenocarcinoma, or high-grade dysplasia, which was analysed with accelerated failure time modelling adjusted for minimisation factors (age, Barrett's oesophagus length, intestinal metaplasia) in all patients in the intention-to-treat population. This trial is registered with EudraCT, number 2004-003836-77.FINDINGS: Between March 10, 2005, and March 1, 2009, 2557 patients were recruited. 705 patients were assigned to low-dose PPI and no aspirin, 704 to high-dose PPI and no aspirin, 571 to low-dose PPI and aspirin, and 577 to high-dose PPI and aspirin. Median follow-up and treatment duration was 8·9 years (IQR 8·2-9·8), and we collected 20 095 follow-up years and 99·9% of planned data. 313 primary events occurred. High-dose PPI (139 events in 1270 patients) was superior to low-dose PPI (174 events in 1265 patients; time ratio [TR] 1·27, 95% CI 1·01-1·58, p=0·038). Aspirin (127 events in 1138 patients) was not significantly better than no aspirin (154 events in 1142 patients; TR 1·24, 0·98-1·57, p=0·068). If patients using non-steroidal anti-inflammatory drugs were censored at the time of first use, aspirin was significantly better than no aspirin (TR 1·29, 1·01-1·66, p=0·043; n=2236). Combining high-dose PPI with aspirin had the strongest effect compared with low-dose PPI without aspirin (TR 1·59, 1·14-2·23, p=0·0068). The numbers needed to treat were 34 for PPI and 43 for aspirin. Only 28 (1%) participants reported study-treatment-related serious adverse events.INTERPRETATION: High-dose PPI and aspirin chemoprevention therapy, especially in combination, significantly and safely improved outcomes in patients with Barrett's oesophagus.FUNDING: Cancer Research UK, AstraZeneca, Wellcome Trust, and Health Technology Assessment.

OBJECTIVES We sought to evaluate diagnostic accuracy of a high-sensitivity cardiac troponin I (hs-cTnI) assay for acute coronary syndromes (ACS) in the emergency department (ED). The assay has high precision at low concentrations and can detect cTnI in 96.8% of healthy individuals. METHODS In successive prospective multicenter studies (“testing” and “validation”), we included ED patients with suspected ACS. We drew blood for hs-cTnI [Singulex Clarity® cTnI; 99th percentile, 8.67 ng/L; limit of detection (LoD), 0.08 ng/L] on arrival. Patients also underwent hs-cTnT (Roche Elecsys) testing over ≥3 h. The primary outcome was an adjudicated diagnosis of ACS, defined as acute myocardial infarction (AMI; prevalent or incident), death, or revascularization within 30 days. RESULTS The testing and validation studies included 665 and 2470 patients, respectively, of which 94 (14.1%) and 565 (22.9%) had ACS. At a 1.5-ng/L cutoff, hs-cTnI had good sensitivity for AMI in both studies (98.7% and 98.1%, respectively) and would have “ruled out” 40.1% and 48.9% patients. However, sensitivity was lower for ACS (95.7% and 90.6%, respectively). At a 0.8-ng/L cutoff, sensitivity for ACS was higher (97.5% and 97.9%, ruling out 28.6% patients in each cohort). The hs-cTnT assay had similar performance at the LoD (24.6% ruled out; 97.2% sensitivity for ACS). CONCLUSIONS The hs-cTnI assay could immediately rule out AMI in 40% of patients and ACS in >25%, with similar accuracy to hs-cTnT at the LoD. Because of its high precision at low concentrations, this hs-cTnI assay has favorable characteristics for this clinical application.

Objectives: Rates of healing following treatment of juvenile osteochondritis dissecans (OCD) of the talus remain scarce. Additionally, there is a paucity of research into the outcomes associated with the treatment of these lesions. The purpose of this study was to evaluate radiographic healing of talar dome OCDs in adolescents. Methods: This was a retrospective review of patients ≤18 years of age with talar OCD from a single pediatric institution within a 12-year period. Charts and radiographs were reviewed for demographics and clinical data, lesion’s location and dimensions, and physeal status. The final radiologic healing was evaluated at 1-year follow-up. Complete and incomplete healing groups were compared using multivariable logistic regression models to examine the predictive effects for the independent variables. A nomogram was produced from the study sample to allow predictions to be made in individual patients. Results: Ninety-two lesions in 74 patients with mean age of 13.1 years (range 7.1 to 18.0 years) were analyzed. 60.8% of the patients were female. Thirty-three (41.8%) lesions were treated conservatively, and 59 (58.2%) were treated surgically (drilling, debridement, microfracture, bone grafting, or loose body removal). Thirty-nine (42.4%) lesions demonstrated complete healing. Patients with complete healing were younger (p 0.032) and had lower BMIs (p 0.006) compared to those with incomplete healing. In a multivariate regression model, the factors that correlated significantly were the age, BMI, Berndt and Harty’s stage at presentation and type of treatment (observation vs. surgical). Location and dimension of the lesion, physeal status (open vs. closed), presenting symptoms, and type of surgical procedure showed no association with likelihood of healing. A nomogram was developed using the independent variables that correlated significantly with the likelihood of complete radiographic healing (Figure 1). Conclusion: Complete radiologic healing of juvenile OCDs was more likely in patients with younger age and lower BMI. Although the difference in outcome between various surgical treatment types was not statistically significant, initial management with surgery was more likely to result in a complete healing compared to observation alone. To our knowledge, this is the first time a nomogram predicting outcome in terms of complete radiographic healing has been developed for juvenile OCD lesions of the talus. Besides its potential role in treatment decision making process, this nomogram can be used to counsel patients and their families with regard to the prognosis for healing. Figure 1. Nomogram for predicting outcome of juvenile osteochondritis dissecans (OCDs) lesion of the talus. To use the nomogram, one should place a straight edge vertically so that it touches the designated variable on the axis for each predictor and then should record the value that each of predictor provides on the “Score”. All of the recorded “points” are then summed, and this value is located on the “total score” line with a straight edge. A vertical line drawn down from the “total score” line to the “Prob” line will identify the probability that the patient will demonstrate healing or progression toward healing after 12 months of treatment.

Inflammation plays a major role in the pathogenesis of coronary artery disease (CAD).We hypothesized, that quantifying inflammation by measuring circulating interleukin-6 concentrations help in the diagnosis and/or prediction of functionally relevant CAD. Among consecutive patients with symptoms suggestive of CAD, functionally relevant CAD was adjudicated in two domains: first, diagnosis according to myocardial perfusion single photon emission tomography (MPI-SPECT) and coronary angiography; second, cardiovascular death and all-cause death during 2-years follow-up. Adjudication was done blinded to the interleukin-6 concentrations.Among 1553 patients, symptoms were adjudicated to be causally related to CAD in 43% (665/1553). Interleukin-6 concentrations were higher in patients with functionally relevant CAD as compared to those without (1.56 pg/mL versus 1.30 pg/mL, p 0.001), but overall had only low-to-modest diagnostic accuracy (area under the curve [AUC]: 0.57, 95%CI 0.55-0.61) and were no independent predictor of functionally relevant CAD after multivariable adjustment (p = 0.068). Interleukin-6 concentrations had moderate-to-high accuracy in the prediction of cardiovascular death (AUC 0.75, 95%CI 0.69-0.82) and all-cause death (AUC 0.72, 95%CI 0.66-0.78) at 2-years, and remained a significant predictor after multivariable adjustment (p 0.001). Compared to patients with interleukin-6 concentrations below the median (1.41 pg/mL), patients with concentrations above the median had a significantly higher cumulative incidence of cardiovascular death (1% vs. 4%, log-rank p 0.001) and all-cause death (2% vs. 8%, log-rank p 0.001) at 2 years.Interleukin-6 concentrations are strong and independent predictors of cardiovascular death and all-cause death.

Objective To assess the risk of glove perforation during common maneuvers or events in trauma-related orthopaedic surgical procedures. Methods Four investigators executed 6 high-risk maneuvers in a simulated laboratory setting. Alternative techniques were also performed for most maneuvers. Glove integrity was examined by 2 standard methods of fluid leak testing. The rates of perforation were compared between techniques using χ and Fisher exact tests. Results Investigators were only able to identify 14.3% of perforations. Cleaning drill bit flutes by hand had the highest overall tear rate (85%). Catching a glove along the guide wire when passing a cannulated drill bit resulted in a 50% perforation rate. Catching a glove around a rotating drill shaft had a tear rate of 40%. Palpating the end of a flexible nail cut with a wire cutter had a significantly higher perforation rate than a nail cut with a proprietary, nail-specific tool (35% vs. 5%, P = 0.022). Blind digital fracture reduction had a tear rate that was not statistically different than directly visualizing the reduction (20% vs. 15%, P = 0.5). Inserting screws while stabilizing the threads with one's fingers resulted in a perforation rate of 15%. Conclusions Orthopaedic surgeons should be aware that microperforation of surgical gloves often goes undetected and should consider modifying or using alternative techniques when performing certain surgical maneuvers. The results of this study can be used by orthopaedic and surgical first assist training programs to promote safe surgical practice.

Introduction The GEMINI trials and an increasing body of real-world data have demonstrated the effectiveness and safety of vedolizumab (VDZ) in IBD. However, there is limited available data about its effect on hospitalisations and steroid use. Our aim was to address this in a large real-world cohort of IBD patients from across Scotland. Methods A multicenter retrospective cohort analysis of medical records was performed across 7 Scottish healthcare trusts. Primary outcomes were hospitalisation rates and overall steroid use in patients remaining on VDZ. Secondary outcomes were safety and intention to treat steroid free remission rates in patients with active disease. All data were prospectively collected as part of routine clinical care. Baseline demographics, clinical scores (HBI or Partial Mayo), faecal calprotectin (FC), endoscopy and radiology at 3, 6 and 12 months was recorded where available. Active disease was defined as endoscopic or radiographic evidence of disease or FC >200 mcg/g. Clinical remission was defined as HBI Results 340 (137 UC and 203 CD) patients were included in the primary analysis with a median follow-up of 9.4 months. Hospitalisation rates per patient-year were 0.60, 0.67, 0.36 and 0.16 at baseline, 3, 6 and 12 months of treatment respectively. Total number of hospitalisations reduced by 52.5% from 204 (12 months prior to VDZ) to 97 (12 months after VDZ). Proportion of patients on concomitant steroids reduced from 39.7% to 16.7% (n=332), 8.1% (n=270), 9.3% (n=194) at 3, 6 and 12 months respectively. In patients with active CD (n=153, 75.4%) steroid free clinical and steroid free biochemical remission rates were; 54.4% and 30.2% at 3 months; 47.7% and 32.1% at 6 months; 28.6% and 33.9% at 12 months. In patients with active UC (n=112, 81.8%) steroid free clinical and steroid free biochemical remission rates were; 57.4% and 40.9% at 3 months; 51.6% and 39.1% at 6 months; 37.5% and 41.2% at 12 months. Our cohort received >2066 VDZ infusions, 2 (0.6%) patients developed infusion reactions, 9 (2.6%) patients developed serious infections and 17 (5.0%) serious adverse events. Conclusions VDZ is associated with reduced hospitalisation and steroid use over 1 year. Steroid free remission rates and safety profile is in keeping with the published literature.

Background Commercially available enzyme immunoassays (EIAs) for detection of norovirus antigen have poor sensitivity and are limited to use in investigations of a gastroenteritis outbreak. Hence, there remains a need for a standalone high-sensitivity assay that enables rapid and accurate detection of norovirus antigen. Methods The Singulex Clarity norovirus assay is currently in development for use on the Singulex Clarity® system (Singulex Inc., Alameda, CA, USA), a fully-automated platform powered by Single Molecule Counting technology (registered with the FDA and CE marked). The assay uses paramagnetic microparticles bound to capture antibody and a fluorescently labeled reporter antibody to detect virion capsid protein of norovirus genogroups I (GI) and II (GII) in the stool. For the development of Clarity Norovirus assay, diagnostic performance of 4 antibody pairs (as Capture and Detection reagent) were evaluated by testing 137 stool samples from patients with suspected norovirus infection. Samples were sourced from three providers: (1) 90 genotyped samples of which 75 were positive (19 different genotypes) and 15 were negative by the CDC assay, (2) 3 samples positive and 5 samples negative by the BioFire® FilmArray® Gastrointestinal Panel, and (3) 39 samples negative by a lab-developed test using Cepheid reagents (SmartCycler®). Results From all the antibody pairs tested, one of the pairs had best performance with the area under the receiver operating characteristic (AuROC) curve demonstrating a C-Statistic of 0.959 (95% CI 0.921–0.997), compared with AuROC C-statistic of 0.943 (95% CI 0.896–0.990), 0.871 (95% CI 0.807–0.936), and 0.914 (95% CI 0.863–0.964) for the three other pairs. The Clarity assay detected all 19 different genotypes tested (figures). Conclusion The ultrasensitive and rapid Clarity norovirus assay (in development) for detection of GI and GII demonstrated excellent performance with one of the antibody pairs tested and detected all 19 tested genotypes. The Clarity assay may offer a standalone solution for norovirus diagnostics. Disclosures All authors: No reported disclosures.

SummaryObjective Glucagon-like peptide 1 (GLP-1)-related pathways may partially explain the strong relationship between obesity and type 2 diabetes. We therefore aimed to evaluate the relationships between fasting GLP-1 levels, body fat mass and other obesity markers in a large sample of young and healthy adults. Design and Patients Our population-based study included 2096 individuals aged 24–44. Exclusion criteria were prevalent cardiovascular disease, diabetes or a body mass index (BMI) >35 kg/m2. Body fat mass was obtained by bioelectrical impedance analysis. Multivariable linear regression models were constructed to assess the relationships of GLP-1 with various measures of body composition. Results Median age of our population was 37 years, median BMI 24·1 kg/m2 and median body fat 25·1%. A strong positive correlation was observed in age-adjusted models between GLP-1 and fat mass in men (β (95% confidence interval) 1·38 (0·69; 2·07), P

Aims: \ud Lactate is produced by anaerobic metabolism and may reflect inadequate tissue perfusion in conditions such as acute heart failure (AHF). We evaluated the prevalence and clinical significance of elevated blood lactate on admission in patients with AHF.\ud \ud Methods and results: \ud We enrolled 237 patients with AHF (mean age 67 ± 12 years; 70% men) presenting without overt clinical evidence of peripheral hypoperfusion (‘warm haemodynamic profile’). Median (upper and lower quartiles) blood lactate on admission was 1.8 (1.5; 2.4) mmol/L; 103 (43%) patients had an elevated blood lactate (≥2 mmol/L). Patients with an elevated lactate had higher blood high-sensitivity troponin I [15.4 (8.5; 26.1) vs. 9.9 (4.3; 19.6) pg/mL], aspartate aminotransferase [28 (20; 44) vs 24 (19; 36) IU/L] and endothelin-1 (12.1 ± 6.2 vs. 9.3 ± 3.9 pg/mL) (all P

Purpose: Most studies examining the safety and efficacy of transphyseal ACL reconstruction for skeletally immature patients have utilized transtibial drilling. Independent femoral tunnel drilling may impart a different pattern of distal femoral physeal involvement. The purpose of this study was to radiographically assess differences in distal femoral physeal disruption between transtibial and independent femoral tunnel drilling, paying particular attention to tunnel angle in relation to the physis. We hypothesized that more oblique tunnels associated with independent drilling involve a significantly larger area of physeal disruption compared to vertically oriented tunnels. Methods: Skeletally immature patients between 10 …

Purpose: In the adult population, anterior glenohumeral instability has been associated with a tall and narrow glenoid morphology, assessed as glenoid index (GI). This morphological association has not been assessed in children and adolescents. This study was designed to examine the association of GI with anterior glenohumeral dislocation in patients 19 years old and younger using a case-control study design. Methods: An institutional radiology database was queried over a 10-year period to …

Background: Fibroblast growth factor 23 (FGF-23), an osteocyte hormone involved in the regulation of phosphate metabolism, is associated with incident and progressive chronic kidney disease. We aimed to assess the association of FGF-23 with renal parameters, vascular function and phosphate metabolism in a large cohort of young and healthy individuals. Methods: Healthy individuals aged 25–41 years were included in a prospective population-based study. Fasting venous blood and morning urinary samples were used to measure plasma creatinine, cystatin C, endothelin-1, phosphate and plasma FGF-23 as well as urinary creatinine and phosphate. Multivariable regression models were constructed to assess the relationship of FGF-23 with parameters of renal function, endothelin-1 and fractional phosphate excretion. Results: The median age of 2077 participants was 37 years, 46% were males. The mean estimated glomerular filtration rate (eGFR – CKD-EPI creatinine-cystatin C equation) and fractional phosphate excretion were 110 mL/min/1.73 m2 and 8.7%, respectively. After multivariable adjustment, there was a significant inverse relationship of FGF-23 with eGFR (β per 1 log-unit increase −3.81; 95% CI [−5.42; −2.20]; p Conclusions: Increasing plasma FGF-23 levels are strongly associated with decreasing eGFR and increasing urinary phosphate excretion, suggesting an important role of FGF-23 in the regulation of kidney function in young and healthy adults.

Background: Diseases associated with coal mine dust continue to affect coal miners. Elucidation of initial pathological changes as a precursor of coal dust-related diffuse fibrosis and emphysema, may have a role in treatment and prevention. Objective: To identify the precursor of dust-related diffuse fibrosis and emphysema. Methods: Birefringent silica/silicate particles were counted by standard microscope under polarized light in the alveolar macrophages and fibrous tissue in 25 consecutive autopsy cases of complicated coal worker's pneumoconiosis and in 21 patients with tobacco-related respiratory bronchiolitis. Results: Coal miners had 331 birefringent particles/high power field while smokers had 4 (p

Background This study evaluated an anterior cruciate ligament (ACL) graft preparation simulation learning model for use by orthopaedic surgery trainees. Methods A simulation model for ACL graft preparation was constructed using shoelace as graft material and a wooden graft preparation board that matched the dimensions of existing products. A 12-minute instructional video targeted at novice learners was created to accompany the simulation model. A prospective randomized controlled trial was conducted on orthopaedic surgery residents divided into 2 groups with equal distributions of postgraduate year (PGY) status. The intervention group learned ACL graft preparation via the Shoelace ACL Simulation Guide, whereas a control group viewed a standard instructional video. All participants then prepared an 8-strand ACL graft using allograft materials and were evaluated via a checklist of critical steps and a global assessment rating as provided by an expert blinded to group allocation. Participants' preintervention and postintervention self-assessment scores were also collected. Results Ten orthopaedic surgery residents from a single institution participated in the study, with even distributions across study groups of PGY-1, PGY-3, and PGY-4 residents. Preintervention self-assessments of knowledge and technical ability were similar between participant groups. The mean overall performance score was significantly greater in the shoelace simulation intervention group (22.6±1.5) than in the instructional video only control group (16.0±5.1) (P=0.043). Participants in the intervention group showed greater improvement in self-confidence in their technical ability than those in the control group (P=0.012). Groups demonstrated similar postintervention improvements in self-reported knowledge of ACL graft preparation (P=0.128). All participants who learned via the Shoelace ACL Simulation Guide strongly agreed that they would use the learning tool to prepare for ACL reconstruction surgery. Conclusions A self-directed low-cost simulation model for soft tissue ACL graft preparation utilizing shoelaces resulted in improved performance metrics compared with standard video instruction. The teaching model may be incorporated easily and inexpensively into simulation curricula at other training programs. Level of evidence Level II-therapeutic study.

Background: Tibial spine fractures, although relatively rare, account for a substantial proportion of pediatric knee injuries with effusions and can have significant complications. Meyers and McKeever type II fractures are displaced anteriorly with an intact posterior hinge. Whether this subtype of pediatric tibial spine fracture should be treated operatively or nonoperatively remains controversial. Surgical delay is associated with an increased risk of arthrofibrosis; thus, prompt treatment decision making is imperative. Purpose: To assess for variability among pediatric orthopaedic surgeons when treating pediatric type II tibial spine fractures. Study Design: Cross-sectional study. Methods: A discrete choice experiment was conducted to determine the patient and injury attributes that influence the management choice. A convenience sample of 20 pediatric orthopaedic surgeons reviewed 40 case vignettes, including physis-blinded radiographs displaying displaced fractures and a description of the patient’s sex, age, mechanism of injury, and predominant sport. Surgeons were asked whether they would treat the fracture operatively or nonoperatively. A mixed-effects model was then used to determine the patient attributes most likely to influence the surgeon’s decision, as well as surgeon training background, years in practice, and risk-taking behavior. Results: The majority of respondents selected operative treatment for 85% of the presented cases. The degree of fracture displacement was the only attribute significantly associated with treatment choice ( P < .001). Surgeons were 28% more likely to treat the fracture operatively with each additional millimeter of displacement of fracture fragment. Over 64% of surgeons chose to treat operatively when the fracture fragment was displaced by ≥3.5 mm. Significant variation in surgeon’s propensity for operative treatment of this fracture was observed ( P = .01). Surgeon training, years in practice, and risk-taking scores were not associated with the respondent’s preference for surgical treatment. Conclusion: There was substantial variation among pediatric orthopaedic surgeons when treating type II tibial spine fractures. The decision to operate was based on the degree of fracture displacement. Identifying current treatment preferences among surgeons given different patient factors can highlight current variation in practice patterns and direct efforts toward promoting the most optimal treatment strategies for controversial type II tibial spine fractures.

Background: Persistent fatigue is a common and debilitating symptom in breast cancer survivors (BCS), yet treatments remain limited. The purpose of this study was to examine the effect of two types of self-administered acupressure on fatigue versus usual care in BCS. Methods: This was a 10-week randomized trial that enrolled adult female BCS (stage 0-III), who had completed cancer treatments at least 12 months previously and who reported persistent mild-moderate fatigue (≥ 4 on the Brief Fatigue Inventory [BFI]). BCS were randomized equally into relaxation acupressure (RA), stimulating acupressure (SA) or usual care (UC). The primary endpoint was change in BFI from baseline to week 6 when acupressure was stopped and at week 10 to assess carryover effects of acupressure. Secondary analyses were conducted on sleep quality using the Pittsburgh Sleep Quality Index (PSQI) and 14-day sleep diaries; quality of life was assessed with the Long-Term Quality of Life in BCS (LTQL). Intent-to-treat analyses were conducted using linear mixed models. Results: 288 BCS were randomized (98 RA, 94 SA, and 96 UC). 228 BCS completed the 6-week visit and 223 the 10-week visit (71 RA, 69 SA, and 83 UC). There were no significant group differences on baseline sociodemographic, clinical characteristics, BFI, PSQI, sleep diary parameters, or LTQL. At week 6 the mean change in BFI from baseline was significantly lower in the RA and SA arms than UC (RA = -2.57 ± 1.5, SA = -1.98 ± 1.5, and UC = -1.07 ± 1.6; p < 0.001 for both RA and SA vs. UC), but there was no significant difference between acupressure arms (p = 0.29). At week 10 the mean change in BFI from baseline ± SD was maintained and continued to be lower in RA and SA arms than UC (RA = -2.27 ± 1.4, SA = -1.96 ± 1.5, and UC = -0.99 ± 1.5; p < 0.001 for both RA and SA vs. UC), but no significant difference between acupressure arms (p >0.99). At week 6 the mean change in PSQI from baseline mean ± SD for RA = -1.93 ± 3.3 was significantly different from UC = -0.46 ± 3.1 (p = 0.03) but not SA = -1.34 ± 3.2 (p = 0.96). At week10 there was no significant difference on the PSQI between arms (RA vs. UC, p = 0.40; SA vs. UC, p Conclusions: Both acupressure arms significantly reduced fatigue compared to UC, but only RA had a significant effect on improving sleep quality and quality of life in BCS. Improvements in fatigue, sleep, and quality of life continued to persist for 4 weeks after cessation of acupressure. Self-administered RA offers an inexpensive easy to learn method to manage fatigue, sleep quality and overall quality of life in BCS with persistent fatigue. Citation Format: Zick SM, Wyatt GK, Murphy SL, Arnedt JT, Sen A, Harris RE. Acupressure for persistent fatigue in breast cancer survivors. [abstract]. In: Proceedings of the Thirty-Eighth Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2015 Dec 8-12; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(4 Suppl):Abstract nr PD4-06.

Interleukin (IL)-6, and tissue necrosis factor alpha (TNF-α) are established biomarkers for clinical practice and use in clinical trials of patients with cardiovascular disease. IL-17A may be an emerging marker for atherosclerosis disease progression. We measured IL-6, TNF-α, and IL-17A using a high sensitivity immunoassay (Erenna, Singulex, Inc.) to determine the reference range and to calculate the weekly (25 subjects over 6 weeks) and monthly (17 subjects over 9 months) biological variation (BV) from apparently healthy subjects and those attending a cardiovascular disease clinic. As a validation for the experimental and statistical approach taken, the weekly BV for high sensitivity C-reactive protein was also determined and result compared to previous reports. The upper 95th percentile reference limit for IL-6, TNF-α, and IL17-A was 4.45, 2.53, and 1.93 pg/mL, respectively. The intra-individual variability ranged from 21% to 57% and the inter-individual variation ranged from 22% to 53%. The corresponding index of individuality was 0.65–1.6 and reference change values from 63% to 161%. The BV for IL-6 and TNF-α are similar to previous reports, documenting their diagnostic utility in clinical practice. Up until now, the biological variation of IL-17A and upper reference limit has not been previously reported, thereby limiting the use of this marker in clinical trials.

Introduction Recently, manufacturers have marketed alginate impression materials, claiming dimensional stability for up to 100 hours to allow shipping to a dental laboratory for digital model fabrication. The purpose of this study was to evaluate the dimensional changes of these newer materials after storage at different temperatures and times. Methods Two extended-pour alginates (claiming 100 hours of accuracy) (Kromopan; Lascod, Florence, Italy; and Triphasix; Parkell, Edgewood, NY), 2 traditional alginates (Jeltrate; Dentsply-Caulk, York, Pa; and Kromatica; Matech, Sylmar, Calif), and 1 vinyl polysiloxane (VP Mix; Henry Schein, Melville, NY) were used to impress a scored aluminum die. The distance between the score lines was measured on the impressions at 10 minutes, 24 hours, and 100 hours after mix, and the percentages of dimensional change were calculated. Temperature effects were studied by storage at cold (–9°C), room (22°C), or hot (46°C) temperatures for 8 hours. Results All alginates had statistically significant dimensional changes at 24 and 100 hours (0.69%-6.13%). VP Mix exhibited no statistically significant changes for any storage condition. The Kromopan (100 hour) and Kromatica (traditional) alginates were the most stable (0.85%-2.22% at 100 hours). Triphasix (100 hour) and Jeltrate (traditional) were the least stable (1.53%-4.73% at 100 hours). Cold-temperature storage resulted in the most dimensional changes (1.96%-4.73% at 100 hours). Room-temperature storage resulted in the least dimensional changes (0.97%-1.53% at 100 hours). Conclusions All alginate impression materials in the study had significant changes at 24 and 100 hours in all storage conditions tested.

Troponins are sensitive markers of myocardial injury and predictive of cardiovascular events, but conventional assays fail to detect slightly elevated troponins in a considerable proportion of the general population. Using a novel ultrasensitive assay, we explored the relationship of troponin levels with the incidence of coronary heart disease (CHD) in a case-cohort sample (mean age 52.5 ± 0.2 years, 51.5% women) comprising 803 CHD cases and 1942 non-cases. Ultrasensitive troponin I was detectable in 99.9% of available case-cohort samples. In an age- and sex-adjusted model, individuals in the highest quartile of the troponin distribution had a more than threefold increased risk for CHD events compared to those in the bottom quartile [hazard ratio, HR, 3.11; 95% confidence interval (CI) 2.15–4.49]. In a model adjusting for cardiovascular risk factors including C-reactive protein, cystatin C and N-terminal pro brain natriuretic peptide, individuals in the highest troponin I quartile still showed a hazard ratio of 2.58 (95% CI 1.66–4.00) for incident CHD as compared to those in the lowest quartile. Ultrasensitive troponin I was detectable in almost all individuals of a study sample reflecting middle-aged to elderly European general population. Ultrasensitive troponin concentrations exhibit an independent, graded, positive relation with incident CHD.

Aims: \ud \ud Urinary kidney injury molecule-1 (KIM-1) is a marker of tubular damage and associated with worse outcome in heart failure (HF). Plasma KIM-1 has not been described in HF.\ud Methods and results: \ud \ud In a renal mechanistic cohort of 120 chronic HF patients, we established the association between plasma KIM-1, renal invasive haemodynamic parameters {renal blood flow ([131I]hippuran clearance) and measured glomerular filtration rate (GFR; [125I]iothalamate)} and urinary tubular damage markers. The association between plasma KIM-1, plasma creatinine, and clinical outcome was further explored in a cohort of 2033 acute HF patients. Median plasma KIM-1 was 171.5 pg/mL (122.8–325.7) in chronic (n = 99) and 295.1 pg/mL (182.2–484.2) in acute HF (n = 1588). In chronic HF, plasma KIM-1 was associated with GFR (P < 0.001), creatinine, and cystatin C. Plasma KIM-1 was associated with urinary N-acetyl-β-d-glucosaminidase (NAG), but not with other urinary tubular damage markers. Log plasma KIM-1 predicted adverse clinical outcome after adjustment for age, gender, and GFR [hazard ratio (HR) 1.94, 95% confidence interval (CI) 1.07–3.53, P = 0.030]. Statistical significance was lost after correction for NT-proBNP (HR 1.61, 95% CI 0.81–3.20, P = 0.175). In acute HF, higher plasma KIM-1 levels were associated with higher creatinine, lower albumin, and presence of diabetes. Log plasma KIM-1 predicted 60-day HF rehospitalization (HR 1.27, 95% CI 1.03–1.55, P = 0.024), but not 180-day mortality or 60-day death or renal or cardiovascular rehospitalization.\ud Conclusions: \ud \ud Plasma KIM-1 is associated with glomerular filtration and urinary NAG, but not with other urinary tubular damage markers. Plasma KIM-1 does not predict outcome in chronic HF after correction for NT-proBNP. In acute HF, plasma KIM-1 predicts HF rehospitalization in multivariable analysis.

Cardiotoxicity was an unanticipated side effect elicited by the clinical use of imatinib (Imb). This toxicity has been examined in only a limited number of experimental studies. The present study sought, by a variety of approaches, to identify important characteristics of Imb-induced cardiac alterations. Male spontaneously hypertensive rats (SHRs) received oral doses of 10, 30, or 50 mg/kg Imb or water daily for 10 d. Cardiac lesions, detected at all doses, were characterized by cytoplasmic vacuolization and myofibrillar loss. In a second experiment, cardiac lesions were found in Sprague Dawley (SD) and SHR rats given 50 or 100 mg/kg Imb for 14 d. Mean cardiac lesion scores and serum levels of cardiac troponin I were higher in SHRs than in SD rats. Imb induced myocyte death by necrosis, autophagy, and apoptosis. Dose-related increases in cardiac expression were observed for several genes associated with endoplasmic reticulum stress response, protein folding, and vascular development and remodeling. Imb caused alterations in isolated myocytes (myofibrillar loss, highly disrupted and disorganized sarcomeric α-actinin, apoptosis, and increased lactate dehydrogenase release) at low concentrations (5 mM). The authors conclude that Imb exerts cardiotoxic effects that are manifest through a complex pattern of cellular alterations, the severity of which can be influenced by arterial blood pressure.