Integrating Machine Learning with Biomedical Signal Processing and Systems Analysis: An Applications-based Course.

The growing importance of data analytics in biomedicine is increasingly becoming recognized in biomedical engineering curricula through the introduction of machine learning classes that generally run in parallel to, but separately from, more traditional engineering courses, such as signal and systems analysis. We propose a new approach that systematically integrates signal processing and systems analysis with key techniques in machine learning. In the proposed course, the student obtains hands-on experience in applying algorithms that can be applied to practical problems of physiological signal conditioning, analysis and interpretation. This is achieved by exposing the student to a sequence of 4 applications-based modules that represent different biomedical engineering problems: human activity recognition from wearable devices, epileptic seizure detection, quantification of dynamic respiratory-cardiac coupling in humans under different conditions, and detection of sleep apnea episodes from heart rate variability data. Within each module, the student gains the experience of working with the data in question "from the ground up". We also introduce a general plan for assessment of student learning, and discuss the expected outcomes and limitations of this integrative approach to teaching.Clinical Relevance- The proposed course is targeted at biomedical engineering students at the senior undergraduate or first-year graduate level who are interested in learning how to analyze physiological signals. The course would also be suitable for clinician-scientists who have prior training in statistics with some exposure to engineering mathematics.

Magnetic Resonance Imaging Features and Prognostic Indicators of Local Recurrence after Curettage and Cementation of Atypical Cartilaginous Tumour in the Appendicular Skeleton.

Objective: The aim of this study is to determine MRI features that may be prognostic indicators of local recurrence (LR) in patients treated with curettage and cementation of atypical cartilaginous tumours (ACTs) in the appendicular skeleton. Materials and Methods: This study is a retrospective review of adult patients with histologically confirmed appendicular ACT. The data collected included age, sex, skeletal location and histology from curettage, the presence of LR and oncological outcomes. The pre-operative MRI characteristics of the ACT reviewed by a specialist MSK radiologist included lesion location, lesion length, degree of medullary filling, bone expansion, cortical status and the presence of soft tissue extension. Results: A total of 43 patients were included, including 9 males and 34 females with a mean age of 42.8 years (range: 25-76 years). Tumours were located in the femur (n = 19), humerus (n = 15), tibia (n = 5), fibula (n = 2) and radius and ulna (n = 1 each). A total of 19 lesions were located in the diaphysis, 12 in the metadiaphysis, 6 in the metaphysis and 6 in the epiphysis. The mean tumour length was 61.0 mm (range: 12-134 mm). The mean follow up was 97.7 months (range: 20-157 months), during which 10 (23.3%) patients developed LR, 7 (70%) of which were asymptomatic and 3 (30%) of which presented with pain. Four patients required repeat surgery with no associated death or evidence of metastatic disease. LR was significantly commoner with tumours arising in the epiphysis or metadiaphysis, but no MRI features were predictive of LR. Conclusions: No relationship was found between the apparent 'aggressiveness' of an ACT of the appendicular skeleton on MRI and the development of LR following treatment with curettage and cementation.

McDAPS: A multi-channel physiological signals display and analysis system for clinical researchers.

We introduce McDAPS, an interactive software for assessing autonomic imbalance from non-invasive multi-channel physiological recordings. McDAPS provides a graphical user interface for data visualization, beat-to-beat processing and interactive analyses. The software extracts beat-to-beat RR interval systolic blood pressure, diastolic blood pressure, the pulse amplitude of photoplethysmogram and the pulse-to-pulse interval. The analysis modules include stationary and time-varying power spectral analyses, moving-correlation analysis and univariate analyses. Analyses can also be performed in batch mode if multiple datasets have to be processed in the same way. The program exports results in standard CSV format. McDAPS runs in MATLAB, and is supported on MS Windows and MAC OS systems. The MATLAB source code is available at https://github.com/thuptimd/McDAPS.git.

Functional near-infrared spectroscopy-based prefrontal cortex oxygenation during working memory tasks in sickle cell disease.

Significance: Sickle cell disease (SCD), characterized by painful vaso-occlusive crises, is associated with cognitive decline. However, objective quantification of cognitive decline in SCD remains a challenge, and the associated hemodynamics are unknown. Aim: To address this, we utilized functional near-infrared spectroscopy (fNIRS) to measure prefrontal cortex (PFC) oxygenation responses to N-back working memory tasks in SCD patients and compared them with healthy controls. Approach: We quantified the PFC oxygenation rate as an index of cognitive activity in each group and compared them. In half of the participants, a Stroop test was administered before they started N-back to elevate their baseline stress level. Results: In SCD compared to healthy controls, we found that (1) under a high baseline stress level, there were significantly greater oxygenation responses during the 2-back task, further elevated with histories of stroke; (2) there was a marginally slower N-back response time, and it was even slower with a history of stroke; and (3) the task accuracy was not different. Conclusions: Additional requirements for processing time, PFC resources, and PFC oxygenation in SCD patients offer an important basis for understanding their cognitive decline and highlight the potential of fNIRS for evaluating cognitive functions.

A 30-Minute Spontaneous Breathing Trial Misses Many Children Who Go On to Fail a 120-Minute Spontaneous Breathing Trial.

BACKGROUND: The optimal length of spontaneous breathing trials (SBTs) in children is unknown. RESEARCH QUESTIONS: What are the most common reasons for SBT failure in children, and when do they occur? Can clinical parameters at the 30-min mark of a 120-min SBT predict outcome? STUDY DESIGN AND METHODS: We performed a secondary analysis of a clinical trial in pediatric ARDS, in which 2-h SBTs are conducted daily. SBT failure is based on objective criteria, including esophageal manometry for effort of breathing, categorized as passage, early failure (≤ 30 min), or late failure (30-120 min). Spirometry was used to calculate respiratory rate (RR), tidal volume (Vt), and rapid shallow breathing index (RSBI), in addition to pulse oximetry and capnography. Predictive models evaluated parameters at 30 min against SBT outcome, using receiver operating characteristic plots and area under the curve. RESULTS: We included 100 children and 305 SBTs, with 42% of SBTs being successful, 32% failing within 30 min, and 25% failing between 30 and 120 min. Of the patients passing SBTs at 30 min, 40% went on to fail by 120 min. High respiratory effort (esophageal manometry) was present in > 80% of failed SBTs. At the 30-min mark, there were no clear thresholds for RR, Vt, RSBI, Fio2, oxygen saturation, or capnography that could reliably predict SBT outcome. Multivariable modeling identified RR (P < .001) and RSBI > 7 (P = .034) at 30 min, pre-SBT inspiratory pressure level (P = .009), and pre-SBT retractions (P = .042) as predictors for SBT failure, but this model performed poorly in an independent validation set with the receiver operating characteristic plot crossing the reference line (area under the curve, 0.67). INTERPRETATION: A 30-min SBT may be too short in children recovering from pediatric ARDS because many go on to fail between 30 and 120 min. Reassuring values of Vt, RR, and gas exchange at 30 min do not reliably predict SBT passage at 2 h, likely because they do not capture the effort of breathing. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov; No.: NCT03266016; URL: www. CLINICALTRIALS: gov.

Total Ankle Replacement Versus Arthrodesis for End-Stage Ankle Osteoarthritis: A Randomized Controlled Trial.

BACKGROUND: End-stage ankle osteoarthritis causes severe pain and disability. There are no randomized trials comparing the 2 main surgical treatments: total ankle replacement (TAR) and ankle fusion (AF). OBJECTIVE: To determine which treatment is superior in terms of clinical scores and adverse events. DESIGN: A multicenter, parallel-group, open-label randomized trial. (ISRCTN registry number: 60672307). SETTING: 17 National Health Service trusts across the United Kingdom. PATIENTS: Patients with end-stage ankle osteoarthritis, aged 50 to 85 years, and suitable for either procedure. INTERVENTION: Patients were randomly assigned to TAR or AF surgical treatment. MEASUREMENTS: The primary outcome was change in Manchester-Oxford Foot Questionnaire walking/standing (MOXFQ-W/S) domain scores between baseline and 52 weeks after surgery. No blinding was possible. RESULTS: Between 6 March 2015 and 10 January 2019, a total of 303 patients were randomly assigned; mean age was 68 years, and 71% were men. Twenty-one patients withdrew before surgery, and 281 clinical scores were analyzed. At 52 weeks, the mean MOXFQ-W/S scores improved for both groups. The adjusted difference in the change in MOXFQ-W/S scores from baseline was -5.6 (95% CI, -12.5 to 1.4), showing that TAR improved more than AF, but the difference was not considered clinically or statistically significant. The number of adverse events was similar between groups (109 vs. 104), but there were more wound healing issues in the TAR group and more thromboembolic events and nonunion in the AF group. The symptomatic nonunion rate for AF was 7%. A post hoc analysis suggested superiority of fixed-bearing TAR over AF (-11.1 [CI, -19.3 to -2.9]). LIMITATION: Only 52-week data; pragmatic design creates heterogeneity of implants and surgical techniques. CONCLUSION: Both TAR and AF improve MOXFQ-W/S and had similar clinical scores and number of harms. Total ankle replacement had greater wound healing complications and nerve injuries, whereas AF had greater thromboembolism and nonunion, with a symptomatic nonunion rate of 7%. PRIMARY FUNDING SOURCE: National Institute for Health and Care Research Heath Technology Assessment Programme.

Treatment of Cheyne-Stokes Respiration in Heart Failure with Adaptive Servo-Ventilation: An Integrative Model.

The SERVE-HF (Treatment of Predominant Central Sleep Apnea by Adaptive Servo Ventilation in Patients with Heart Failure) multicenter trial found a small but significant increase in all-cause and cardiovascular mortality in patients assigned to adaptive servo-ventilation (ASV) versus guideline-based medical treatment. To better understand the physiological underpinnings of this clinical outcome, we employ an integrative computer model to simulate congestive heart failure with Cheyne-Stokes respiration (CHF-CSR) in subjects with a broad spectrum of underlying pathogenetic mechanisms, as well as to determine the in silico changes in cardiopulmonary and autonomic physiology resulting from ASV. Our simulation results demonstrate that while the elimination of CSR through ASV can partially restore cardiorespiratory and autonomic physiology toward normality in the vast majority of CHF phenotypes, the degree of restoration can be highly variable, depending on the combination of CHF mechanisms in play. The group with the lowest left ventricular ejection fraction (LVEF) appears to be most vulnerable to the potentially adverse effects of ASV, but the level of pulmonary capillary wedge pressure (PCWP) plays an important role in determining the nature of these effects.

A side-sensitive synthetic chart for the multivariate coefficient of variation.

Control charts for the coefficient of variations (γ) are receiving increasing attention as it is able to monitor the stability in the ratio of the standard deviation (σ) over the mean (µ), unlike conventional charts that monitor the µ and/or σ separately. A side-sensitive synthetic (SS) chart for monitoring γ was recently developed for univariate processes. The chart outperforms the non-side-sensitive synthetic (NSS) γ chart. However, the SS chart monitoring γ for multivariate processes cannot be found. Thus, a SS chart for multivariate processes is proposed in this paper. A SS chart for multivariate processes is important as multiple quality characteristic that are correlated with each other are frequently encountered in practical scenarios. Based on numerical examples, the side-sensitivity feature that is included in the multivariate synthetic γ chart significantly improves the sensitivity of the chart based on the run length performance, particularly in detecting small shifts (τ), and for small sample size (n), as well as a large number of variables (p) and in-control γ (γ0). The multivariate SS chart also significantly outperforms the Shewhart γ chart, and marginally outperforms the Multivariate Exponentially Weighted Moving Average (MEWMA) γ chart when shift sizes are moderate and large. To show its implementation, the proposed multivariate SS chart is adopted to monitor investment risks.

Vasoconstriction Response to Mental Stress in Sickle Cell Disease: The Role of the Cardiac and Vascular Baroreflexes.

Recent studies have shown that individuals with sickle cell disease (SCD) exhibit greater vasoconstriction responses to physical autonomic stressors, such as heat pain and cold pain than normal individuals, but this is not the case for mental stress (MTS). We sought to determine whether this anomalous finding for MTS is related to inter-group differences in baseline cardiac and vascular autonomic function. Fifteen subjects with SCD and 15 healthy volunteers participated in three MTS tasks: N-back, Stroop, and pain anticipation (PA). R-R interval (RRI), arterial blood pressure and finger photoplethysmogram (PPG) were continuously monitored before and during these MTS tasks. The magnitude of vasoconstriction was quantified using change in PPG amplitude (PPGa) from the baseline period. To represent basal autonomic function, we assessed both cardiac and vascular arms of the baroreflex during the baseline period. Cardiac baroreflex sensitivity (BRSc) was estimated by applying both the "sequence" and "spectral" techniques to beat-to-beat measurements of systolic blood pressure and RRIs. The vascular baroreflex sensitivity (BRSv) was quantified using the same approaches, modified for application to beat-to-beat diastolic blood pressure and PPGa measurements. Baseline BRSc was not different between SCD and non-SCD subjects, was not correlated with BRSv, and was not associated with the vasoconstriction responses to MTS tasks. BRSv in both groups was correlated with mean PPGa, and since both baseline PPGa and BRSv were lower in SCD, these results suggested that the SCD subjects were in a basal state of higher sympathetically mediated vascular tone. In both groups, baseline BRSv was positively correlated with the vasoconstriction responses to N-back, Stroop, and PA. After adjusting for differences in BRSv within and between groups, we found no difference in the vasoconstriction responses to all three mental tasks between SCD and non-SCD subjects. The implications of these findings are significant in subjects with SCD since vasoconstriction reduces microvascular flow and prolongs capillary transit time, increasing the likelihood for vaso-occlusive crisis (VOC) to be triggered by exposure to stressful events.

Identifying elevated risk for future pain crises in sickle-cell disease using photoplethysmogram patterns measured during sleep: A machine learning approach.

Transient increases in peripheral vasoconstriction frequently occur in obstructive sleep apnea and periodic leg movement disorder, both of which are common in sickle cell disease (SCD). These events reduce microvascular blood flow and increase the likelihood of triggering painful vaso-occlusive crises (VOC) that are the hallmark of SCD. We recently reported a significant association between the magnitude of vasoconstriction, inferred from the finger photoplethysmogram (PPG) during sleep, and the frequency of future VOC in 212 children with SCD. In this study, we present an improved predictive model of VOC frequency by employing a two-level stacking machine learning (ML) model that incorporates detailed features extracted from the PPG signals in the same database. The first level contains seven different base ML algorithms predicting each subject's pain category based on the input PPG characteristics and other clinical information, while the second level is a meta model which uses the inputs to the first-level model along with the outputs of the base models to produce the final prediction. Model performance in predicting future VOC was significantly higher than in predicting VOC prior to each sleep study (F1-score of 0.43 vs 0.35, p-value < 0.0001), consistent with our hypothesis of a causal relationship between vasoconstriction and future pain incidence, rather than past pain leading to greater propensity for vasoconstriction. The model also performed much better than our previous conventional statistical model (F1=0.33), as well as all other algorithms that used only the base-models for predicting VOC without the second tier meta model. The modest F1 score of the present predictive model was due in part to the relatively small database with substantial imbalance (176:36) between low-pain and high-pain subjects, as well as other factors not captured by the sleep data alone. This report represents the first attempt ever to use noninvasive finger PPG measurements during sleep and a ML-based approach to predict increased propensity for VOC crises in SCD. The promising results suggest the future possibility of embedding an improved version of this model in a low-cost wearable system to assist clinicians in managing long-term therapy for SCD patients.

Pathological fracture in paediatric bone tumours and tumour-like lesions: A predictor of benign lesions?

OBJECTIVE: To determine the incidence and causes of pathological fractures in paediatric bone tumours and tumour-like lesions, and to determine if they are predictive of benign lesions. METHODS AND MATERIALS: Retrospective review of children with suspected bone tumours referred to a specialist musculoskeletal oncology service between September 2019 and August 2020. Data recorded included patient age and gender, lesion location, the presence of a pathological fracture on the initial plain radiograph, and the final diagnosis made either by image-guided biopsy/curettage or based on typical imaging features. RESULTS: 231 patients were included with 233 lesions (138 males and 93 females with mean age 10.5 years, range 3 months-18 years). Final diagnosis was based on histology in 85 (36.5%) cases and imaging in 148 (63.5%) cases, 52 (22.3%) lesions classed as non-neoplastic, 139 (59.7%) as benign and 42 (18%) as malignant. Pathological fractures were seen in 41 cases (17.6%) at presentation, involving the humerus in 19 (46.3%), the femur in 14 (34.1%), the tibia in 3 (7.3%), the fibula and radius in two each (4.9%) and the second toe proximal phalanx in 1 (2.4%) (p < 0.001). The commonest underlying lesions included simple bone cyst (n = 17; 41.5%) and non-ossifying fibroma (n = 10; 24.4%). Only 4 cases (9.75%) were malignant, one case each of osteosarcoma, Ewing sarcoma, leukaemia and BCOR undifferentiated round cell sarcoma. Pathological fracture occurred in 27.7% of non-malignant lesions and 9.5% of malignant lesions, this difference being statistically significant (p < 0.001). CONCLUSION: Pathological fractures were seen in 17.6% of paediatric bone tumours, tumour-like lesions, being significantly associated with humeral location and non-malignant diagnosis. ADVANCES IN KNOWLEDGE: Demonstrates the frequency, location and underlying diagnosis of pathological fractures in paediatric bone tumour and tumour-like lesions.

MRI differentiation of low-grade and high-grade chondrosarcoma of the shoulder girdle, chest wall and pelvis: a pictorial review based on 111 consecutive cases.

Approximately 40% of conventional chondrosarcomas arise from the shoulder girdle, chest wall and pelvis. This pictorial review describes the MRI features which may aid in the differentiation of Grade 1 chondrosarcoma (Gd1-CS) from high-grade chondrosarcoma (HG-CS) and dedifferentiated chondrosarcoma (DD-CS) in these locations, based on literature review and assessment of 111 consecutive cases presenting to the senior authors institution over a 13-year period. Of the 111 patients reviewed (71 males and 40 females; mean age 54.3 years; range 17-92 years), 27 were Gd1-CS, 72 were HG-CS and 12 were DD-CS. Tumours arising from the scapula, acetabulum, pubis/ischium and sacrum were more likely to be HG-CS, as were intramedullary tumours. MRI features associated with HG-CS and DD-CS included cortical destruction, bone oedema, soft tissue oedema, tumour necrosis, intermediate T2W SI and joint invasion. The presence of a soft tissue mass became a significant differentiating feature for tumours arising within the medullary cavity, but this was location-specific and did not differentiate between Gd1-CS and HG-CS/DD-CS arising from the sternum or clavicle.

Natural history of the cervical high-intensity intramedullary lesion in achondroplasia.

STUDY DESIGN: Retrospective cohort study. OBJECTIVE: The cervical high-intensity intramedullary (CHII) lesion is a recognised finding in achondroplasia, manifesting as a focal area of increased T2W signal intensity in the upper cervical cord in the absence of cervical cord compression. The aim of this study is to determine the natural history of this abnormality. SETTING: Tertiary referral spinal and orthopaedic hospital, UK. METHODS: A retrospective review was undertaken of all patients with achondroplasia who had undergone at least one MRI study which included the cervical spine. Patient age at presentation was recorded and presence of the CHII lesion was determined on the sagittal T2W FSE sequence. For patients who had follow-up studies, presence of the CHII lesion was assessed for any change in morphology (resolution, partial resolution or enlargement). The development of new CHII lesions and presence of associated cord atrophy was also recorded. RESULTS: The study group consisted of 40 patients (20 males, 20 females: mean age at first MRI of 32.6 years (range 7-66 years). The CHII lesion was identified in 19 (47.5%) cases and was associated with focal cord atrophy in 17 (85%) cases. There was no change or resolution of these lesions nor any associated cord compression. No new CHII lesions developed but progressive cord atrophy was evident. CONCLUSION: The CHII lesion is seen in 47.5% of cases of achondroplasia. It appears to be a stable abnormality which does not progress or change its morphology. However, it does appear to be associated with progressive cord atrophy.

Introducing image-guided synovial aspiration and biopsy in assessing peri-prosthetic joint infection: an early single-centre experience.

AIM: Synovial sampling can be used in the diagnosis of peri-prosthetic joint infection (PJI). The purpose of this study was to establish the role of simultaneous image-guided synovial aspiration and biopsy (SAB) during an initial 2-year experience at our institution. METHODS: Retrospective review of consecutive SABs performed during 2014-2016 at a tertiary referral musculoskeletal centre. Radiological SAB microbiology culture results were compared with intra-operative surgical samples or multidisciplinary team (MDT) meeting outcome at 1-year follow-up if surgery was not undertaken. Sensitivity, specificity and accuracy of synovial aspiration (SA), synovial biopsy (SB) and simultaneous SAB were calculated. RESULTS: 103 patients (46 male, 57 female) totalling 111 procedures were analysed with mean age 65 years (range 31-83). Image-guided synovial procedures were performed on 52 (46.9%) hip and 59 (53.1%) knee joint prostheses. The mean combined sensitivity, specificity and accuracy for the entire cohort was 72.6%, 96.9% and 90%, respectively. When only SB was obtained, diagnostic accuracy (92.5%) was similar to SA alone (94.1%). In total, there were 21 (18.9%) true-positive, 80 (72.1%) true-negative, 2 (1.8%) false-positive and 8 (7.2%) false-negative cases (PPV 91.3% and NPV 90.9%). No post-procedural complications were recorded at 1-year follow-up. CONCLUSION: Percutaneous image-guided SAB is a valuable technique in assessing suspected PJI, with most samples indicative of infective status and causative organisms when validated against intra-operative results and specialist MDT evaluation. Image-guided SB is a safe and useful additional procedure following failed SA with equivalent levels of diagnostic accuracy.

Monitoring of three-phase variations in the mortality of COVID-19 pandemic using control charts: where does Pakistan stand?

BACKGROUND: At the end of December 2019, the world in general and Wuhan, the industrial hub of China, in particular, experienced the COVID-19 pandemic. Massive increment of cases and deaths occurred in China and 209 countries in Europe, America, Australia, Asia and Pakistan. Pakistan was first hit by COVID-19 when a case was reported in Karachi on 26 February 2020. Several methods were presented to model the death rate due to the COVID-19 pandemic and to forecast the pinnacle of reported deaths. Still, these methods were not used in identifying the first day when Pakistan enters or exits the early exponential growth phase. OBJECTIVE: The present study intends to monitor variations in deaths and identify the growth phases such as pre-growth, growth, and post-growth phases in Pakistan due to the COVID-19 pandemic. METHODS: New approaches are needed that display the death patterns and signal an alarming situation so that corrective actions can be taken before the condition worsens. To meet this purpose, secondary data on daily reported deaths due to the COVID-19 pandemic have been considered, and the $c$ and exponentially weighted moving average (EWMA) control charts are used To meet this purpose, secondary data on daily reported deaths in Pakistan due to the COVID-19 pandemic have been considered. The $ c$ and exponentially weighted moving average (EWMA) control charts have been used for monitoring variations. RESULTS: The chart shows that Pakistan switches from the pre-growth to the growth phase on 31 March 2020. The EWMA chart demonstrates that Pakistan remains in the growth phase from 31 March 2020 to 17 August 2020, with some indications signaling a decrease in deaths. It is found that Pakistan moved to a post-growth phase for a brief period from 27 July 2020 to 28 July 2020. Pakistan switches to re-growth phase with an alarm on 31/7/2020, right after the short-term post-growth phase. The number of deaths starts decreasing in August in that Pakistan may approach the post-growth phase shortly. CONCLUSION: This amalgamation of control charts illustrates a systematic implementation of the charts for government leaders and forefront medical teams to facilitate the rapid detection of daily reported deaths due to COVID-19. Besides government and public health officials, it is also the public's responsibility to follow the enforced standard operating procedures as a temporary remedy of this pandemic in ensuring public safety while awaiting a suitable vaccine to be discovered.

Comparison of lumbar degenerative disc disease using conventional fast spin echo T2W MRI and T2 fast spin echo dixon sequences.

OBJECTIVES: To compare the grading of lumbar degenerative disc disease (DDD), Modic end-plate changes (MEPC) and identification of high intensity zones (HIZ) on a combination of sagittal T1weighted turbo spin echo (T1W TSE), T2weighted fast spin echo (T2W FSE) and short tau inversion recovery (STIR) sequences (routine protocol) with a single sagittal T2W FSE Dixon MRI sequence which provides in-phase, opposed-phase, water only and fat only images in a single acquisition (Dixon protocol). METHODS: 50 patients underwent lumbar spine MRI using the routine protocol with the addition of a T2W FSE Dixon sequence. DDD grade, MEPC and HIZ for each disc level were assessed on the routine and Dixon protocols. Each protocol was reviewed independently by three readers (consultant musculoskeletal radiologists with 26-, 8- and 4 years' experience), allowing assessment of inter-reader agreement and inter protocol agreement for each assessed variable. RESULTS: The study included 17 males and 33 females (mean age 51 years; range 8-82 years). Inter-reader agreement for DDD grade on the routine protocol was 0.57 and for the Dixon protocol was 0.63 (p = 0.08). Inter-reader agreement for MEPC on the routine protocol was 0.45 and for the Dixon protocol was 0.53 (p = 0.02), and inter-reader agreement for identification of the HIZ on the routine protocol was 0.52 and for the Dixon protocol was 0.46 (p = 0.27). Intersequence agreement for DDD grade ranged from 0.61 to 0.97, for MEPC 0.46-0.62 and for HIZ 0.39-0.5. CONCLUSION: A single sagittal T2W FSE Dixon MRI sequence could potentially replace the routine three sagittal sequence protocol for assessment of lumbar DDD, MEPC and HIZ resulting in ~60% time saving. ADVANCES IN KNOWLEDGE: Grading of lumbar DDD, presence of Modic changes and high intensity zones were compared on sagittal T1W TSE, T2W FSE and STIR sequences with a T2W FSE Dixon sequence, with fair-to-good correlation suggesting that three conventional sequences could be replaced by a single Dixon sequence.

The differential diagnosis of trunk and extremity dermal and sub-dermal lesions referred to a musculoskeletal oncology service.

OBJECTIVES: To determine the differential diagnosis of dermal and sub-dermal soft tissue masses which do not extend to the deep fascia that are referred to a specialist musculoskeletal oncology service. MATERIALS AND METHODS: Review of all patients referred to a specialist musculoskeletal oncology service over a 13-month period with a dermal or sub-dermal soft tissue mass which did not extend to the deep fascia based on MRI appearances. Data collected included age, gender, site and maximal lesion size, and final histological diagnosis for biopsied and/or excised lesions. RESULTS: 56 patients were included, 21 (37.5%) males and 35 (62.5%) females with mean age 49.75 years (range 5-86 years). 3 patients had 2 lesions making a total of 59 lesions, 11 (18.6%) dermal and 48 (81.4%) sub-dermal. Histological diagnosis was available in 44 (74.6%) cases, of which 11 (25%) were non-neoplastic, 23 (52.3%) were benign neoplasms, and 10 (22.7%) were malignant neoplasms. Although older age at presentation and greater mean maximal tumour dimension were seen with malignant lesions, these did not reach statistical significance (p = 0.154 and 0.102 respectively). There was also no relationship between skin involvement from sub-dermal lesions and malignancy, but 5 of 6 dermal lesions which showed an exophytic growth pattern were malignant. CONCLUSIONS: The differential diagnosis of dermal and sub-dermal lesions which do not reach the deep fascia is wide with a malignant lesion being the cause in almost one-quarter of cases.

Loss of alpha-globin genes in human subjects is associated with improved nitric oxide-mediated vascular perfusion.

Alpha thalassemia is a hemoglobinopathy due to decreased production of the α-globin protein from loss of up to four α-globin genes, with one or two missing in the trait phenotype. Individuals with sickle cell disease who co-inherit the loss of one or two α-globin genes have been known to have reduced risk of morbid outcomes, but the underlying mechanism is unknown. While α-globin gene deletions affect sickle red cell deformability, the α-globin genes and protein are also present in the endothelial wall of human arterioles and participate in nitric oxide scavenging during vasoconstriction. Decreased production of α-globin due to α-thalassemia trait may thereby limit nitric oxide scavenging and promote vasodilation. To evaluate this potential mechanism, we performed flow-mediated dilation and microvascular post-occlusive reactive hyperemia in 27 human subjects (15 missing one or two α-globin genes and 12 healthy controls). Flow-mediated dilation was significantly higher in subjects with α-trait after controlling for age (P = .0357), but microvascular perfusion was not different between groups. As none of the subjects had anemia or hemolysis, the improvement in vascular function could be attributed to the difference in α-globin gene status. This may explain the beneficial effect of α-globin gene loss in sickle cell disease and suggests that α-globin gene status may play a role in other vascular diseases.

MRI-histopathological correlation in paediatric conventional central chondrosarcoma: a report of 17 cases.

OBJECTIVE: To describe the MRI features of paediatric conventional central chondrosarcoma (CC-CS) and correlate with histological grade. MATERIALS AND METHODS: A retrospective review of children/adolescents with histologically confirmed CC-CS. Data collected included age, sex, skeletal location, and histology from needle biopsy or resection, which was classified as atypical cartilaginous tumours/grade 1 CS (ACT/Gd 1 CS), high-grade chondrosarcoma (HGCS), and dedifferentiated chondrosarcoma (DD-CS). MRI studies were reviewed independently by 2 radiologists blinded to the histology grade, who graded the tumours as ACT/Gd 1 CS, HGCS, and DD-CS based on MRI features. RESULTS: The study included 7 males and 10 females with mean age 13.9 years (range 6-18 years). Tumours were located in the femur (n = 6), humerus (n = 3), tibia, ilium, scapula, and ulna (n = 1 each), and the small bones of the hands or feet (n = 4). Final histology grade was ACT/Gd 1 CS in 15 cases and HGCS in 2 (both grade 1 CS with focal transition to grade 2), 15 based on surgical specimens, 1 based on open biopsy, and 1 on needle biopsy alone. Predicted MRI grade for the 2 readers was ACT/Gd 1 CS in 11 cases each and HGCS in 6 cases each, indicating a mismatch between predicted MRI grade and histological grade in 8 (47%) cases (4 cases with one reader mismatch and 4 cases with both). CONCLUSIONS: MRI findings in paediatric CC-CS may be misleading, showing features suggestive of HGCS 7 of 17 (41.2%) of cases. This should be taken into consideration when planning surgical treatment.

Tricuspid regurgitant jet velocity and myocardial tissue Doppler parameters predict mortality in a cohort of patients with sickle cell disease spanning from pediatric to adult age groups - revisiting this controversial concept after 16 years of additional evidence.

Sickle cell disease (SCD) is a monogenic hemoglobinopathy associated with significant morbidity and mortality. Cardiopulmonary, vascular and sudden death are the reasons for the majority of young adult mortality in SCD. To better understand the clinical importance of multi-level vascular dysfunction, in 2009 we assessed cardiac function including tricuspid regurgitant jet velocity (TRV), tissue velocity in systole(S') and diastole (E'), inflammatory, rheologic and hemolytic biomarkers as predictors of mortality in patients with SCD. With up to 9 years of follow up, we determined survival in 95 children, adolescents and adults with SCD. Thirty-eight patients (40%) were less than 21 years old at initial evaluation. Survival and Cox proportional-hazards analysis were performed. There was 19% mortality in our cohort, with median age at death of 35 years. In the pediatric subset, there was 11% mortality during the follow up period. The causes of death included cardiovascular and pulmonary complications in addition to other end-organ failure. On Cox proportional-hazards analysis, our model predicts that a 0.1 m/s increase in TRV increases risk of mortality 3%, 1 cm/s increase in S' results in a 91% increase, and 1 cm/s decrease in E' results in a 43% increase in mortality. While excluding cardiac parameters, higher plasma free hemoglobin was significantly associated with risk of mortality (p=.049). In conclusion, elevated TRV and altered markers of cardiac systolic and diastolic function predict mortality in a cohort of adolescents and young adult patients with SCD. These predictors should be considered when counseling cardiovascular risk and therapeutic optimization at transition to adult providers.