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PURPOSE Genomic tests improve accuracy of risk prediction for early breast cancers but these are expensive. This study evaluated the clinical utility of EndoPredict®, in terms of impact on adjuvant therapy recommendations and identification of parameters to guide selective application. METHODS Patients with ER-positive, HER2-negative, and early-stage invasive breast cancer were tested with EndoPredict®. Two cohorts were recruited: one consecutively and another at clinical team discretion. Systemic treatment recommendations were recorded before and after EndoPredict® results were revealed to the multidisciplinary team. RESULTS 233 patients were recruited across five sites: 123 consecutive and 110 at clinical team discretion. In the consecutive cohort 50.6% (62/123) cases were classified high risk of recurrence by EndoPredict®, compared with 62.7% (69/110) in the selective cohort. A change in treatment recommendation was significantly more likely (p

Contact sports players frequently sustain head impacts, most of which are mild impacts exhibiting 10-30 g peak head center-of-gravity (CG) linear acceleration. Wearable head impact sensors are commonly used to measure exposure and typically detect impacts using a linear acceleration threshold. However, linear acceleration across the head can substantially vary during 6-degree-of-freedom motion, leading to triggering biases that depend on sensor location and impact condition. We conducted an analytical investigation with impact characteristics extracted from on-field American football and soccer data. We assumed typical mouthguard sensor locations and evaluated whether simulated multi-directional impacts would trigger recording based on per-axis or resultant acceleration thresholding. Across 1387 impact directions, a 10g peak CG linear acceleration impact would trigger at only 24.7% and 31.8% of directions based on a 10 g per-axis and resultant acceleration threshold, respectively. Anterior impact locations had lower trigger rates and even a 30 g impact would not trigger recording in some directions. Such triggering biases also varied by sensor location and linear-rotational head kinematics coupling. Our results show that linear acceleration-based impact triggering could lead to considerable bias in head impact exposure measurements. We propose a set of recommendations to consider for sensor manufacturers and researchers to mitigate this potential exposure measurement bias.

In this retrospective study, we have explored the anatomical factors that lead to the development of radiation necrosis (RN) in the setting of stereotactic radiosurgery (SRS) for melanoma brain metastases (MBM). Between 2014 and 2018, 137 patients underwent SRS for 311 MBM. Lesions were assessed according to anatomical zones: zone 1—peripheral grey-white matter junction and cortical mantle, zone 2—deep white matter, including tumours located at base of sulci, zone 3—tumours adjacent to ependymal lining or in deep locations such as brainstem, basal ganglia and thalamus. Other anatomical factors including lobes, medial-peripheral, supra or infratentorial locations were also recorded. In all, 12.4% (n = 17) of patients and 6.1% (n = 20) of lesions developed RN, actuarial incidence of RN at 12 and 24 months was 10% and 14.2% respectively. Zone 2 lesions recorded the highest rate of development of RN (n = 7/19; 36%), zone 3 (N = 4/24; 16%) and zone 1 (n = 9/268; 3%). Five of 17 patients developed symptomatic RN and 7/17 patients underwent surgery for RN. This study raises awareness of the increased likelihood of deep lesions particularly in white matter structures to develop RN after SRS. Further studies including larger cohorts would be useful in identifying statistical differences in the rate of development of RN in different anatomical zones.

Background Stereotactic Ablative Body Radiotherapy (SABR) is a non-invasive treatment which allows delivery of an ablative radiation dose with high accuracy and precision. SABR is an established treatment for both primary and secondary liver malignancies, and technological advances have improved its efficacy and safety. Respiratory motion management to reduce tumour motion and image guidance to achieve targeting accuracy are crucial elements of liver SABR. This phase II multi-institutional TROG 17.03 study, Liver Ablative Radiotherapy using Kilovoltage intrafraction monitoring (LARK), aims to investigate and assess the dosimetric impact of the KIM real-time image guidance technology. KIM utilises standard linear accelerator equipment and therefore has the potential to be a widely available real-time image guidance technology for liver SABR. Methods Forty-six patients with either hepatocellular carcinoma or oligometastatic disease to the liver suitable for and treated with SABR using Kilovoltage Intrafraction Monitoring (KIM) guidance will be included in the study. The dosimetric impact will be assessed by quantifying accumulated patient dose distribution with or without the KIM intervention. The patient treatment outcomes of local control, toxicity and quality of life will be measured. Discussion Liver SABR is a highly effective treatment, but precise dose delivery is challenging due to organ motion. Currently, there is a lack of widely available options for performing real-time tumour localisation to assist with accurate delivery of liver SABR. This study will provide an assessment of the impact of KIM as a potential solution for real-time image guidance in liver SABR. Trial registration This trial was registered on December 7th 2016 on ClinicalTrials.gov under the trial-ID NCT02984566.

INTRODUCTION: Though musculoskeletal complaints account for roughly one-quarter of primary care and emergency department visits, only 2% of US medical school curriculum is devoted to musculoskeletal disease. Many graduating students demonstrate poor knowledge and report low confidence in treating musculoskeletal disorders. This study defines the current state of musculoskeletal curriculum of medical schools in detail to identify variations and potential shortcomings. METHODS: All eleven medical schools in California were invited to participate in an in-depth survey detailing the design and content of their musculoskeletal curriculum. RESULTS: A response rate of 100% was achieved. Overall, schools devoted an average of 58.7 h to musculoskeletal medicine, of which more than half was spent covering anatomy. The primary instructor for musculoskeletal medicine was a clinician in four schools (36.4%). Six schools offered a dedicated musculoskeletal physical exam course. No schools required students to complete a clinical rotation in musculoskeletal medicine. There was high variability among institutions when evaluating core subject coverage. DISCUSSION: There is large variation in the content and structure of musculoskeletal instruction among California medical schools. Increased curricular time, integration of preclinical and clinical experiences, greater specialist participation, and standardized objectives may provide more consistent and comprehensive musculoskeletal education. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s40670-020-01144-3.

Purpose The purpose of this study was to determine the (1) reoperation rate and (2) 30-day complication rate in a large insurance database. Methods The Truven Database was queried for subjects that underwent meniscus allograft transplantation (Current Procedural Terminology code 29868) in the outpatient setting with minimal 2-year follow-up. Patients without confirmed laterality and patients that underwent concomitant ligament reconstruction were excluded. Reoperation was defined by ipsilateral knee procedure after the index surgery. The 30-day postoperative complication rates were assessed using International Classification of Diseases, 9th Revision, Clinical Modification codes. Results A total of 284 patients (mean age of 26.2 ± 10.4 years; 49.6% females) were included in this study with mean follow up of 43.2 ± 19.2 months. One hundred and sixty-seven subjects (58.8%) undergoing meniscus allograft transplantation underwent reoperation at an average of 11.9 ± 12.2 months postoperatively. There was a low number of subjects that required ipsilateral unicompartmental knee arthroplasty and total knee arthroplasty postoperatively (0.7% and 1.1%, respectively). The overall 30-day complication rate following meniscus allograft transplantation was 1.4%. Conclusions Patients undergoing meniscus allograft transplantation have a 58.8% reoperation rate at final follow up with low (1.4%) 30-day complication rates in a large insurance database. Level of Evidence Level IV, case series.

The International Integrated Reporting Council (IIRC) and the South African King III Report on Governance emphasize the role of corporate governance in preparing a high-quality integrated report an...

The advent of Hyperscale Networks with the internet infrastructure has pushed digital data rates to the highest levels of performance. Emerging applications using 56Gbps and above are requiring new methods of validation, compared to the traditional metrics of BER and eye diagrams, to avoid throwing channel margin away unnecessarily. The Channel Operating Margin (COM) figure-of-merit along with measurement/simulation correlation is becoming a critical part of the design cycle. The analysis of the test cases proposed herein will present an extensive validation of a high speed connector for differential interconnects working up to 112 Gbps, by providing an in-depth analysis of such component, as a critical portion of the channel. A comprehensive correlation of the connector model to experimental results in terms of thru and crosstalk responses in both time and frequency domains provides a reliable connector model for the subsequent channel design. Comparison of new test methodologies will be shown to accurately predict how to optimize channel performance at today’s ultra-fast data rates.

Revision hip arthroplasty in the setting of periacetabular bone loss presents a significant challenge, as options for restoring bone loss are limited. Recombinant human bone morphogenetic protein-2 may offer a solution by promoting bone growth to restore bone stock before implant reimplantation. Here we present a case of a patient with a periprosthetic acetabulum fracture, resulting in pelvic discontinuity as the result of significant periacetabular bone loss. Using a staged approach, periacetabular bone stock was nearly entirely reconstituted using recombinant BMPs and allograft, which resulted in stable fixation, but with abundant heterotopic bone formation. Recombinant BMP-2 offers a useful tool for restoring bone stock in complex hip arthroplasty revision cases with periacetabular bone loss; however, caution must be used as overabundant bone growth as heterotopic ossification may result.

The study assesses the use of non‐financial information in predicting financial distress in private companies by developing credit risk models tailored to Italian private companies. The in‐sample and out‐of‐sample prediction test results are indicative of the incremental predictive ability of the two new non‐financial variables, that is, number of shareholders and number of subsidiaries, over accounting ratios and other widely used non‐financial information, including firm age and industry dummies. To be more specific, number of shareholders and number of subsidiaries are negatively associated with private company failures, and the models augmented by the two non‐financial variables improve forecasting performance from acceptable discrimination to excellent discrimination over one‐ to three‐year time horizons.

Focal white matter lesions are the defining pathological and imaging hallmark of the multiple sclerosis. Until recently, elucidation of the pathophysiology of lesion formation, progression and repair has relied on point neuropathological observations. Here, we review current and emerging concepts of the MRI-defined multiple sclerosis lesion phenotype, advanced longitudinal imaging techniques that permit in-vivo exploration of dynamic microstructural change within lesions and emerging MRI measures of lesion repair.Novel MRI techniques have elucidated dynamic features of the active multiple sclerosis lesion, defined imaging surrogates for chronic active lesions and revealed progressive microstructural change within chronic inactive lesions. Lesion-related anterograde, retrograde and trans-synaptic neurodegenerative mechanisms are being unravelled in vivo through MRI. An array of myelin-imaging techniques have emerged and in some cases have already been integrated into Phase 2 remyelination trials.MRI has shed new light on dynamic processes that occur over the lifespan of the multiple sclerosis lesion, and reaffirms the critical role of focal pathology as a determinant of disease progression. The development of robust, longitudinal biomarkers of lesion microstructure, such as advanced diffusion imaging, will be especially important as the era of neurorepair trials in multiple sclerosis dawns.

The study assesses the use of non-financial information in predicting financial distress in private companies by developing credit risk models tailored to Italian private companies. The in-sample and out-of-sample prediction test results are indicative of the incremental predictive ability of the two new non-financial variables, that is, number of shareholders and number of subsidiaries, over accounting ratios and other widely used non-financial information, including firm age and industry dummies. To be more specific, number of shareholders and number of subsidiaries are negatively associated with private company failures, and the models augmented by the two non-financial variables improve forecasting performance from acceptable discrimination to excellent discrimination over one- to-three year time horizons.

Fresh osteochondral allograft transplantation is an appealing option to address a failed cartilage repair surgical procedure, given the ability to treat large lesions and to address the subchondral osseous changes commonly seen in the revision setting. We hypothesized that osteochondral allograft transplantation after failed cartilage repair would result in low failure rates and improved function and that improved graft incorporation on postoperative magnetic resonance imaging (MRI) would correlate with a superior clinical outcome.A retrospective review of prospectively collected data was used to identify 43 patients treated with fresh osteochondral allograft transplantation after a previous cartilage repair surgical procedure and having a minimum follow-up of 2 years. Clinical outcomes were evaluated using the Short Form-36 (SF-36) score, International Knee Documentation Committee (IKDC) Subjective Knee Score, Marx Activity Scale, Knee Outcome Survey-Activities of Daily Living (KOS-ADL) Questionnaire, Cincinnati Sports Activity Score, and Cincinnati Overall Symptom Assessment. Postoperative MRI scans were obtained at a mean time of 19.7 months and were independently reviewed by a musculoskeletal radiologist using the Osteochondral Allograft MRI Scoring System (OCAMRISS).At a mean 3.5-year follow-up after osteochondral allograft transplantation, significant improvements (p0.05) in SF-36 Physical Function, SF-36 Pain, KOS-ADL, IKDC Subjective Knee Score, and Cincinnati Overall Symptom Assessment were seen. Over 90% of grafts remained in situ at the time of the latest follow-up, although 17 knees (40%) underwent reoperation, the majority for arthroscopic debridement or manipulation for stiffness. Body mass index (BMI) of30 kg/m was associated with worse clinical outcomes. The mean total OCAMRISS score demonstrated poorer allograft integration in patients with graft failure, but the total score did not meaningfully correlate with clinical outcome scores. However, better individual articular cartilage appearance and osseous integration subscores were associated with better clinical outcome scores.Significant improvements in pain and function were seen following fresh osteochondral allograft transplantation after failed cartilage repair, with an overall graft survival rate of90%. Patients with greater bone and cartilage incorporation on MRI had superior clinical outcomes, although persistent osseous edema was frequently seen. We concluded that osteochondral allograft transplantation is an effective salvage treatment after failed cartilage repair and recommend further evaluation of techniques to optimize graft integration.Therapeutic Level IV. See Instructions for Authors for a complete description of levels of evidence.

Background: Alemtuzumab is a highly effective treatment for relapsing-remitting multiple sclerosis (MS) but requires ongoing pathology monitoring for autoimmune adverse effects. The Alemtuzumab in MS Safety Systems (AMS3) study evaluated the implementation of an automated pathology-monitoring system. Objectives: To develop an efficient automated clinical decision support system (CDSS) to electronically prompt and track pathology collection and to provide prescribers and patients with customised alerts of abnormal results for identified risks. Methods: A total of 10 patients with relapsing-remitting MS treated with alemtuzumab were enrolled to test the system. Standard care laboratory monitoring was performed and compared to the performance of the CDSS. Results: The automated CDSS, an integrated patient smartphone application and an additional pre-screening tool were all successfully developed. Compliance with pathology monitoring was 96.7%. The automated analysis of pathology results was significantly faster than standard care neurologist review ( p Conclusion: We successfully developed automated pathology monitoring with a CDSS, demonstrating real-world benefits of high compliance and timely alerting of important results.

In this work we report on process development for Al-BSF and PERC solar cells applying a texturing approach for an inline equipment based on Metal Catalyst Chemical Etching (MCCE). The texturing process can be varied in a wide parameter range resulting in average reflectivity in the range of 12% up to 25%. PERC solar cells were processed on DWS multicrystalline wafers in an industrial production line at Solartech with average efficiencies of 20.23% and peak efficiencies of 20.6%. The PERC solar cells demonstrated an increase of >0.6%abs. compared to solar cells textured with additives. An optimization of the front surface has been carried out on MCCE textured wafer with varying reflectivity by applying different POCl 3 diffusions as well as including PSG as passivation layer.

Adequate coverage of sites harbouring potential microscopic disease is paramount, where the clinical decision has been made to include regional lymph node radiotherapy for patients with breast cancer. This must be achieved in balance with minimising dose to normal tissues. Several international consensus guidelines detailing clinical target volumes (CTVs) are available, but there is currently no agreement as to which is most appropriate for a given clinical situation. Contouring guidelines are beneficial for routine practice and essential for clinical trial quality assurance. The aims of this study were as follows: to provide a single point of comparison of four commonly used contouring guidelines, including one used in a current Trans-Tasman Radiation Oncology Group trial; and to undertake a systematic review of existing studies which map sites of breast cancer recurrence against contouring guidelines. Two international consensus guidelines (European Society for Radiotherapy and Oncology, and Radiation Therapy Oncology Group) were compared with two clinical trial guidelines (TROG 12.02 PET LABRADOR and the Proton/Photon trial NCT02603341 RADCOMP). Comprehensive literature search for patterns of failure studies was undertaken using Embase and Pubmed. We detail the small but significant differences between the breast consensus guidelines, particularly the supraclavicular (SCF) and internal mammary chain CTVs. Seven series were found mapping recurrence patterns. These results are discussed in the context of the contouring guidelines. Several studies found the SCF CTV is the area at greatest risk of geographical 'miss'. This review will facilitate further discussion about guideline selection and modification, particularly for future clinical trials in Australia and New Zealand.

The purpose of this article is to review the recent literature concerning modern repair techniques related to partial- and full-thickness rotator cuff tears. The understanding of rotator cuff pathology and healing continues to evolve, beginning with emerging descriptions of the anatomic footprint and natural history of rotator cuff tears. Significant controversy remains in treatment indications for partial-thickness rotator cuff lesions as well as optimal surgical repair techniques for both partial- and full-thickness tears. Techniques such as margin convergence and reduction of the so-called “comma” tissue have improved the ability to anatomically reduce large and retracted tears. Repair strength and contact pressures are improved with double-row repairs and transosseus-equivalent techniques compared to traditional single-row repairs. Future work is directed towards obtaining reliable radiographic healing and demonstrating clinical superiority and cost-effectiveness of a single technique. Much recent work regarding rotator cuff anatomy and pathology has been reported. Newer techniques improve repair strength. Despite these advances, significant questions remain concerning surgical indications and clinical outcomes.

Background There has been increasing interest in using the lumbosacral spinous processes for fixation as a less invasive alternative to transpedicular instrumentation. Alhough prior studies have described the appearance and biomechanics of lumbar spinous processes, few have evaluated the dimensions, morphology, or strength of the sacral spinous processes. Purpose The goals of this study were to characterize the morphology of the S1 spinous process and biomechanical strength of the S1 spinous process when loaded in a cranial direction. Study Design This study was performed as both an analysis of radiographic data and biomechanical testing of cadaveric specimens. Methods Lumbosacral spine radiographs and computed tomography scans of 20 patients were evaluated for visibility and morphology of the S1 spinous process. S1 spinous process length, height, and size of the L5–S1 segment were measured. Additionally, 13 cadaveric lumbosacral spinal segments were obtained for biomechanical testing and morphologic analysis. Specimens were loaded at the S1 spinous process in a cranial direction via a strap, simulating resistance to a flexion moment applied across the L5–S1 segment. Peak load to failure, displacement, and mode of failure were recorded. Results The S1 spinous process was clearly visible on lateral radiographs in only 10% of patients. Mean spinous process length (anterior-posterior) was 11.6 mm while mean spinous process height (cranial-caudal) was 23.1 mm. We identified six different morphologic subtypes of the S1 spinous process: fin, lumbar type, fenestrated, fused, tubercle, and spina bifida occulta. During tension loading of the S1 spinous process in the cephalad direction, mean peak load to failure was 439N, with 92% of specimens failing by fracture through the spinous process. Conclusions This is the first study evaluating sacral spinous process morphology, visibility, and biomechanical strength for potential instrumentation. Compared with lumbar spinous processes, sacral spinous processes are smaller with more variable morphology but have similar peak load to failure. For ideal visualization of morphology and suitability for interspinous fixation,preoperative three-dimensional imaging may be a valuable tool over plain radiographs.

INTRODUCTION: For slim patients eligible to breast reconstruction, clinical concerns exist on availability of adequate amount of donor tissue to restore breast volume and challenges in donor-site c ...

Background: Treatment of large chondral defects of the knee among patients aged ≥40 years remains a difficult clinical challenge owing to preexisting joint degeneration and the lack of treatment options short of arthroplasty. Purpose: To characterize the survivorship, predictors of failure, and clinical outcomes of osteochondral allograft transplantation (OCA) of the knee among patients aged ≥40 years. Study Design: Case series; Level of evidence, 4. Methods: Prospectively collected data were reviewed for 54 consecutive patients aged ≥40 years who were treated with OCA. Preoperative levels of osteoarthritis (according to Kellgren-Lawrence classification) and meniscal volume and quality were graded from review of radiographs and magnetic resonance imaging. Complications, reoperations, and patient responses to validated outcome measures were reviewed. A minimum follow-up of 2 years was required for analysis. Failure was defined by any removal or revision of the allograft or conversion to arthroplasty. Results: Among 51 patients (mean age, 48 years; range, 40-63 years; 65% male), a total of 52 knees had symptomatic focal cartilage lesions (up to 2 affected areas) that were classified as Outerbridge grade 4 at the time of OCA and did not involve substantial bone loss requiring shell allografts or additional bone grafting. Mean duration of follow-up was 3.6 years (range, 2-11 years). After OCA, 21 knees (40%) underwent reoperation, including 14 failures (27%) consisting of revision OCA (n = 1), unicompartmental knee arthroplasty (n = 5), and total knee arthroplasty (n = 8). Mean time to failure was 33 months, and 2- and 4-year survivorship rates were 88% and 73%, respectively. Male sex (hazard ratio = 4.18, 95% CI = 1.12-27.13) and a higher number of previous ipsilateral knee operations (hazard ratio = 1.70 per increase in 1 surgical procedure, 95% CI = 1.03-2.83) were predictors of failure. A higher Kellgren-Lawrence osteoarthritis grade on preoperative radiographs was associated with higher failure rates in the Kaplan-Meier analysis but not the multivariate model. At final follow-up, clinically significant improvements were noted in the pain (mean score, 47.8 to 67.6) and physical functioning (56.8 to 79.1) subscales of the Short Form-36, as well as the International Knee Documentation Committee subjective form (45.0 to 63.6), Knee Outcome Survey–Activities of Daily Living (64.5 to 80.1), and overall condition statement (4.5 to 6.8) ( P < .001). No significant changes were noted for the Marx Activity Rating Scale (5.1 to 3.9, P = .789). Conclusion: A higher failure rate was found in this series of patients aged ≥40 years who were treated with OCA as compared with other studies of younger populations. However, for select older patients, OCA can be a good midterm treatment option for cartilage defects of the knee.

To analyze the functional outcomes of patients treated with particulated juvenile articular cartilage (PJAC) for symptomatic articular cartilage lesions in the patellofemoral joint, correlates clinical outcomes with magnetic resonance imaging (MRI) appearance of the repair tissue using cartilage-sensitive quantitative T2-mapping.All patients treated with PJAC for patellofemoral lesions were identified and prospectively followed with clinical outcome scores (International Knee Documentation Committee [IKDC], Knee Outcome Survey-Activities of Daily Living [KOS-ADL], and Marx Activity Scale [MAS]). Postoperative MRI scans using quantitative T2 mapping were obtained and interpreted by an independent musculoskeletal radiologist.Twenty-seven patients treated with PJAC for 30 full-thickness patellofemoral cartilage lesions were identified; mean postoperative follow-up was 3.84 years. Improvements from pre- to postoperative mean IKDC (45.9 vs 71.2, P.001) and KOS-ADL (60.7 vs 78.8, P.001) scores were observed; no significant change in MAS was seen (7.04 vs 7.17, P = .97). Advanced age, history of previous surgery, lesion location (patella vs trochlea), or concomitant tibial tubercle osteotomy did not affect outcome scores. Greater body mass index was associated with less improvement in KOS-ADL score. No patients required reoperation for graft-related issues. Lesion fill exceeding 67% by MRI assessment was noted in 69.2% of lesions; depth of lesion fill did not correlate with clinical outcomes. Quantitative T2-mapping revealed prolonged relaxation time at the graft site compared with adjacent normal cartilage at both deep and superficial zones.This study found significantly improved pain and function in patients treated with PJAC for symptomatic patellofemoral articular cartilage defects. No patients required reoperation for graft-related issues. Postoperative MRI revealed majority lesion fill in more than 69% of patients, but persistent morphologic differences between graft site and normal adjacent cartilage remain. Though we support PJAC use in this setting to improve patient subjective outcomes, improved appearance on postoperative imaging was not found to provide additional clinical benefit.Level IV, case series.

Introduction LAL deficiency (LALd) is a rare autosomal recessive condition of deficiency or underexpression of the enzyme LAL which leads to the excessive accumulation of cholesteryl esters and triglycerides in various organs especially the liver. Patients often present with hepatosplenomegaly, deranged liver function tests (LFTs), hyperlipidaemia, gastrointestinal symptoms, and hepatic failure. LALd is often misdiagnosed as non-alcoholic fatty liver disease (NAFLD), non-alcoholic steatohepatitis (NASH), cryptogenic cirrhosis or type IIa or b hyperlipoproteinaemia. Aim To develop a model for LALd testing in the hepatology and metabolic clinics using dried blood spotting (DBS). Method We carried out a systematic literature review and worked closely with paediatricians, hepatologists, metabolic consultants and endocrinologists to develop a screening algorithm for LALd. With the support of industry partners, we obtained DBS test kits and started testing suitable patients. The DBS tests were sent for processing to an external laboratory in Glasgow. Results To date we have tested 122 adult patients (M:F 2.4:1). The mean LAL levels were 0.56 nmol/punch/hour (range 0.08–1.26 nmol/punch/hour) (Figure 1). We identified 27 (22.5%) patients with LAL levels below the reference range (0.37–2.30 nmol/punch/hr). Almost half of these patients were eventually diagnosed with NAFLD/NASH (48.15%) (Figure 2). The control enzyme, beta galactosidase, was used on two occasions to test sample quality and one sample was regarded as of poor quality. Conclusion The genotype to phenotype presentation has not been clearly elucidated for LALd. More than 40 mutations have been identified each leading to variable enzymatic expression. Traditionally, if the LAL levels are less than 0.15, control enzymes are used to test sample quality. In good quality samples, levels of Disclosure of Interest None Declared

Purpose To compare failure rates and clinical outcomes of osteochondral allograft transplantation (OCA) in anterior cruciate ligament (ACL)-intact versus ACL-reconstructed knees at midterm follow-up. Methods After a priori power analysis, a prospective registry of patients treated with OCA for focal chondral lesions ≥2 cm 2 in size with minimum 2-year follow-up was used to match ACL-reconstructed knees with ACL-intact knees by age, sex, and primary chondral defect location. Exclusion criteria included meniscus transplantation, realignment osteotomy, or other ligamentous injury. Complications, reoperations, and patient responses to validated outcome measures were reviewed. Failure was defined by any procedure involving allograft removal/revision or conversion to arthroplasty. Kaplan-Meier analysis and multivariate Cox regression were performed to evaluate the association of ACL reconstruction (ACLR) with failure. Results A total of 50 ACL-intact and 25 ACL-reconstructed (18 prior, 7 concomitant) OCA patients were analyzed. The mean age was 36.2 years (range, 14-62 years). Mean follow-up was 3.9 years (range, 2-14 years). Patient demographics and chondral lesion characteristics were similar between groups. ACL-reconstructed patients averaged 2.2 ± 1.9 prior surgeries on the ipsilateral knee compared with 1.4 ± 1.4 surgeries for ACL-intact patients ( P = .014). Grafts used for the last ACLR included bone-patellar tendon-bone autograft, hamstring autograft, Achilles tendon allograft, and tibialis allograft (data available for only 11 of 25 patients). At final follow-up, 22% of ACL-intact and 32% of ACL-reconstructed patients had undergone reoperation. OCA survivorship was 90% and 96% at 2 years and 79% and 85% at 5 years in ACL-intact and ACL-reconstructed patients, respectively ( P = .774). ACLR was not independently associated with failure. Both groups demonstrated clinically significant improvements in the Short Form-36 pain and physical functioning, International Knee Documentation Committee subjective, and Knee Outcome Survey—Activities of Daily Living scores at final follow-up ( P Conclusions OCA in the setting of prior or concomitant ACLR does not portend higher failure rates or compromise clinical outcomes. Level of Evidence Level III, retrospective comparative study.

Summary Lysosomal acid lipase deficiency is a rare, autosomal recessive condition caused by mutations in the gene encoding lysosomal acid lipase ( LIPA ) that result in reduced or absent activity of this essential enzyme. The severity of the resulting disease depends on the nature of the underlying mutation and magnitude of its effect on enzymatic function. Wolman's disease is a severe disorder that presents during infancy, resulting in failure to thrive, hepatomegaly, and hepatic failure, and an average life expectancy of less than 4 months. Cholesteryl ester storage disorder arises later in life and is less severe, although the two diseases share many common features, including dyslipidaemia and transaminitis. The prevalence of these diseases has been estimated at one in 40 000 to 300 000, but many cases are undiagnosed and unreported, and awareness among clinicians is low. Lysosomal acid lipase deficiency—which can be diagnosed using dry blood spot testing—is often misdiagnosed as non-alcoholic fatty liver disease (NAFLD), non-alcoholic steatohepatitis (NASH), hereditary dyslipidaemia, or cryptogenic cirrhosis. There are no formal guidelines for treatment of these patients, and treatment options are limited. In this Review we appraise the existing literature on Wolman's disease and cholesteryl ester storage disease, and discuss available treatments, including enzyme replacement therapy, oral lipid-lowering therapy, stem-cell transplantation, and liver transplantation.

The anti-PD-1 antibodies nivolumab and pembrolizumab are active in metastatic melanoma; however, there is limited data on combining anti-PD-1 antibody and radiotherapy (RT). We sought to review clinical outcomes of patients receiving RT and anti-PD-1 therapy. All patients receiving anti-PD-1 antibody and RT for metastatic melanoma were identified. RT and systemic treatment, clinical outcome, and toxicity data were collected. Fifty-three patients were included; 35 patients received extracranial RT and/or intracranial stereotactic radiosurgery (SRS) and 21 received whole brain radiotherapy (WBRT) (three of whom also received SRS/extracranial RT). Patients treated with extracranial RT or SRS received treatment either sequentially (RT then anti-PD-1, n = 11), concurrently (n = 16), or concurrent “salvage” treatment to lesions progressing on anti-PD-1 therapy (n = 15). There was no excessive anti-PD-1 or RT toxicity observed in patients receiving extracranial RT. Of six patients receiving SRS, one patient developed grade 3 radiation necrosis. In 21 patients receiving WBRT, one patient developed Stevens–Johnson syndrome, one patient developed acute neurocognitive decline, and one patient developed significant cerebral edema in the setting of disease. Response in irradiated extracranial/intracranial SRS lesions was 44% for sequential treatment and 64% for concurrent treatment (p=0.448). Likewise there was no significant difference between sequential or concurrent treatment in lesional response of non-irradiated lesions. For progressing lesions subsequently irradiated, response rate was 45%. RT and anti-PD-1 antibodies can be safely combined, with no detectable excess toxicity in extracranial sites. WBRT and anti-PD-1 therapy is well tolerated, although there are rare toxicities and the role of either anti-PD-1 or WBRT in the etiology of these is uncertain.

Cancellous screws are designed to optimize fixation in metaphyseal bone environments; however, certain clinical situations may require the substitution of cortical screws for use in cancellous bone, such as anatomic constraints, fragment size, or available instrumentation. This study compares the biomechanical properties of commercially available cortical and cancellous screw designs in a synthetic model representing various bone densities. Commercially available, fully threaded, 4.0-mm outer-diameter cortical and cancellous screws were tested in terms of pullout strength and maximum insertion torque in standard-density and osteoporotic cancellous bone models. Pullout strength and maximum insertion torque were both found to be greater for cancellous screws than cortical screws in all synthetic densities tested. The magnitude of difference in pullout strength between cortical and cancellous screws increased with decreasing synthetic bone density. Screw displacement prior to failure and total energy absorbed during pullout strength testing were also significantly greater for cancellous screws in osteoporotic models. Stiffness was greater for cancellous screws in standard and osteoporotic models. Cancellous screws have biomechanical advantages over cortical screws when used in metaphyseal bone, implying the ability to both achieve greater compression and resist displacement at the screw-plate interface. Surgeons should preferentially use cancellous over cortical screws in metaphyseal environments where cortical bone is insufficient for fixation. [ Orthopedics. 2016; 39(5):e828–e832.]

Background Uncorrected glenoid retroversion during total shoulder arthroplasty may lead to an increased likelihood of glenoid prosthetic loosening. Augmented glenoid components seek to correct retroversion to address posterior glenoid bone loss, but few biomechanical studies have evaluated their performance.

Objective: Several female sub-populations of the healthcare industry, including radiologists, radiology technicians, and orthopedic surgeons, display an increased prevalence of breast cancer. Female plastic surgeons have a similar exposure to possible risk factors such as radiation exposure, late parturition, and overnight shifts. Therefore, this study aimed to evaluate the risk of breast cancer and overall cancer in female plastic surgeons. Methods: A two-page survey designed to collect data on respondent demographics, cancer incidence and exposure to social and occupational risk factors as identified in the current literature was mailed to 612 currently practicing female plastic surgeons identified by the American Society of Plastic Surgeons (ASPS). Prevalence rates for breast cancer and cancer in general were calculated. Only melanoma and internal cancers that were diagnosed within 15 years of the survey date were included, enabling us to compare the results with data from the National Institute’s Surveillance Epidemiology and End Results (SEER 11) Program. Standardized prevalence ratios (SPR), confidence intervals, and exact p-values were calculated. Results: Fourteen of the 352 respondents had been diagnosed with cancer, including three breast cancer cases, within 15 years preceeding the survey. These numbers are not signficantly lower than the expected prediction of 16 cancer and six breast cancer cases, based on the sex and race-specific prevalences in the general U.S. population. SPRs were 0.89 [95%CI: 0.49 to 1.5] for all cancers and 0.54 [95%CI: 0.11, 1.57] for breast cancer. Conclusion: Despite similarities to subpopulations with increased breast and overall cancer prevalence, the subpopulation of female plastic surgeons had no evdience of excess cancers compared to age and race-adjusted women in the general US population.

A mixed-mode university course, combining online learning and face-to-face meetings, can encourage students to formulate and express their own ideas more than would be the case in traditional classrooms. This article describes an experimental project at the University of British Columbia and explores connections between online learning and aspects of liberal humanism.

The heat resistance data on Listeria monocytogenes in culture media and foods are summarized. Most heat resistance data for foods have been obtained in dairy, meat, poultry, and egg products. Limited data have been published on seafood, fruits, and vegetables. The methodologies employed have evolved over time; hence data from earlier experiments are not directly comparable to more recent studies. Many factors influence the heat resistance of L. monocytogenes. Variation exists among different strains in their ability to withstand heat treatment. In addition, heat resistance is influenced by age of the culture, growth conditions, recovery media, and characteristics of foods such as salt content, a(w), acidity, and the presence of other inhibitors. Listeriae are more heat resistant than most other nonspore-forming foodborne pathogens, and thus, processing recommendations based on data from experiments with Salmonella spp. or pathogenic Escherichia coli may not be sufficient to eliminate similar numbers of L. monocytogenes. The data provided in this review may prove useful for food processors in determining appropriate times and temperatures for producing foods free of vegetative pathogens.

Many burns surgeons avoid excision and direct closure of acute burns owing to concerns over wound dehiscence, scarring and infection. There is no evidence in the literature to support this practice. We present outcomes of a prospective series of 100 patients who underwent excision and direct closure of 138 burns over a 2-year period, along with results from a survey sent to 33 senior burns surgeons to gauge attitudes towards direct closure in burns surgery. 47% of survey respondents never perform direct closure. Dehiscence was cited as the most common concern, followed by hypertrophic scarring (HTS). In our cohort, the superficial dehiscence rate was 12% and the HTS rate was 16%, with no scarring contractures. Patients with healing time greater than 14 days were more likely to develop HTS (p = 0.008), as were those with wound dehiscence (p = 0.014). Patients undergoing part-grafting in addition to direct closure took significantly longer to heal than those undergoing direct closure alone (p = 0.0002), with the donor site or graft delaying healing in the majority. Excision and direct closure of acute burn wounds avoids donor site morbidity and has an acceptable complication rate. It is a safe and effective treatment for full thickness burns in selected cases.

Conclusions: Updated OS analysis confirmed improvement in OS favoring D+T over Vem with medians of 25.6 versus 18 months. Two-year OS rates and additional efficacy and safety analysis will be presented. Conflict of interest: Ownership: J Legos reported equity ownership with GSK. B Mookerjee reported equity ownership with GSK, Incyte Corporation, and AstraZeneca. Advisory Board: P Rutkowski participated in an Advisory Committee for Novartis, Roche, BMS, and MSD. R Dummer participated in an Ad Board with Roche, BMS, GSK, MSD, Novartis. V Chiarion-Sileni participated in an Advisory Committee for BMS, GSK, Roche, and Merck. I Krajsova participated in an Advisory Committee for BMS. Board of Directors: P Rutkowski was a member of the board of directors for Novartis, Roche, BMS, and MSD. V Chiarion-Sileni was a member of the board of directors for BMS, GSK, Roche, and Merck. I was a member of the board of directors for BMS. Corporatesponsored Research: M Lichinitser received research funding from GSK. R Dummer received research funding from Roche, BMS, GSK, MSD, Novartis. K Drucis received research funding from GSK. A Hauschild received research funding from Amgen, BMS, Celgene, Eisai, GSK, MelaSciences, Merck Serono, MSD/Merck, Novartis, Oncosec, Roche Pharma. Other Substantive Relationships: C Robert acted as a consultant for GSK, Novartis, Merck, BMS, Amgen, and Roche. P Rutkowski received honoraria from Novartis, GSK, Roche, Amgen, Pfizer, BMS, MSD, and Bayer and participated in a speakers bureau for Novartis and Pfizer. L Mortier reports personal fees from GSK, during the conduct of the study. A Hauschild acted as a consultant for Amgen, BMS, Celgene, Eisai, GSK, MedImmune, MelaSciences, Merck Serono, MSD/Merck, Novartis, Oncosec, and Roche and received honoraria from Amgen, BMS, Celgene, Eisai, GSK, MedImmune, MelaSciences, Merck Serono, MSD/Merck, Novartis, Oncosec, and Roche. B Mookerjee and J Legos are employees of GSK. D Schadendorf acted as a consultant and received honoraria from, and participated in a speakers bureau for GSK, Novartis, Roche, Amgen, BMS, Boehringer Ingelheim, and Merck/MSD.