Cancer Genomics Proteomics Table of Contents for Volume 14 November-December 2017; Vol. 14, No. 6

Cancer Genomics & Proteomics
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Cancer Genomics & Proteomics
Volume 14
November-December 2017; 14 (6)
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A clinical predictive score for postoperative myasthenic crisis

ABSTRACT

Objective: Myasthenia gravis (MG) is an autoimmune disease mostly caused by autoantibodies against acetylcholine receptor (AChR) associated with thymus abnormalities. Thymectomy has been proven to be an efficacious treatment for patients with MG, but postoperative myasthenic crisis often occurs and is a major complication. We aimed to develop and validate a simple scoring system based on clinical characteristics in the preoperative status to predict the risk of postoperative myasthenic crisis.

Methods: We studied 393 patients with MG who underwent thymectomy at six tertiary centers in Japan (275 patients for derivation and 118 for validation). Clinical characteristics, such as gender, age at onset and operation, body mass index, disease duration, MG subtype, severity, symptoms, preoperative therapy, operative data, and laboratory data, were reviewed retrospectively. A multivariate logistic regression with LASSO penalties was used to determine the factors associated with postoperative myasthenic crisis and score was assigned. Finally, the predictive score was evaluated using bootstrapping technique in the derivation and validation group.

Results: Multivariate logistic regression identified three clinical factors for predicting postoperative myasthenic crisis risk: (1) vital capacity < 80%, (2) disease duration < 3 months, and (3) bulbar symptoms immediately before thymectomy. The postoperative myasthenic crisis predictive score, ranging from 0 to 6 points, had areas under the curve of 0.84 (0.66 – 0.96) in the derivation group and 0.80 (0.62 – 0.95) in the validation group.

Interpretation: A simple scoring system based on three preoperative clinical characteristics can predict the possibility of postoperative myasthenic crisis. This article is protected by copyright. All rights reserved.

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Curative and palliative MRI-guided laser ablation for drug-resistant epilepsy

Epilepsy is a common neurological disorder occurring in 3% of the US adult population. It is characterised by seizures resulting from aberrant hypersynchronous neural activity. Approximately one-third of newly diagnosed epilepsy cases fail to become seizure-free in response to antiseizure drugs. Optimal seizure control, in cases of drug-resistant epilepsy, often requires neurosurgical intervention targeting seizure foci, such as the temporal lobe. Advances in minimally invasive ablative surgical approaches have led to the development of MRI-guided laser interstitial thermal therapy (LITT). For refractory epilepsy, this surgical intervention offers many advantages over traditional approaches, including real-time lesion monitoring, reduced morbidity, and in some reports increased preservation of cognitive and language processes. We review the use of LITT for epileptic indications in the context of its application as a curative (seizure freedom) or palliative (seizure reduction) measure for both lesional and non-lesional forms of epilepsy. Furthermore, we address the use of LITT for a variety of extratemporal lobe epilepsies. Finally, we describe clinical outcomes, limitations and future applications of LITT for epilepsy.

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Early intravenous immunoglobulin treatment in paraneoplastic neurological syndromes with onconeural antibodies

Introduction

Paraneoplastic neurological syndromes (PNS) are immune-mediated complications of cancer, characterised by relentless progression. The mainstay of PNS treatment is the achievement of tumour remission,1 while immunotherapy provides only little additional benefit.2 3 However, in historical series, immunotherapy was initiated over 6 months after neurological onset and, at that stage, neuronal loss is already extensive and irreversible.

Among available immunotherapies, intravenous immunoglobulin (IVIg) has been used in single cases4 and in one retrospective series,3 showing some efficacy when administered timely.4 Based on these findings, we designed a prospective study to assess the efficacy and safety of early IVIg treatment in patients with PNS.

MethodsStudy design

This prospective, multicentre, non-comparative, phase II clinical study was performed by the ‘Centre de Reference Francais des Syndromes Neurologiques Paranéoplasiques’. Written informed consent was obtained from all participants. This trial is registered at ClinicalTrials.gov (NCT02343211).

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Monitoring disease progression with plasma creatinine in amyotrophic lateral sclerosis clinical trials

Objectives

Plasma creatinine is a predictor of survival in amyotrophic lateral sclerosis (ALS). It remains, however, to be established whether it can monitor disease progression and serve as surrogate endpoint in clinical trials.

Methods

We used clinical trial data from three cohorts of clinical trial participants in the LITRA, EMPOWER and PROACT studies. Longitudinal associations between functional decline, muscle strength and survival with plasma creatinine were assessed. Results were translated to trial design in terms of sample size and power.

Results

A total of 13 564 measurements were obtained for 1241 patients. The variability between patients in rate of decline was lower in plasma creatinine than in ALS functional rating scale–Revised (ALSFRS-R; p<0.001). The average rate of decline was faster in the ALSFRS-R, with less between-patient variability at baseline (p<0.001). Plasma creatinine had strong longitudinal correlations with the ALSFRS-R (0.43 (0.39–0.46), p<0.001), muscle strength (0.55 (0.51–0.58), p<0.001) and overall mortality (HR 0.88 (0.86–0.91, p<0.001)). Using plasma creatinine as outcome could reduce the sample size in trials by 21.5% at 18 months. For trials up to 10 months, the ALSFRS-R required a lower sample size.

Conclusions

Plasma creatinine is an inexpensive and easily accessible biomarker that exhibits less variability between patients with ALS over time and is predictive for the patient’s functional status, muscle strength and mortality risk. Plasma creatinine may, therefore, increase the power to detect treatment effects and could be incorporated in future ALS clinical trials as potential surrogate outcome.

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Clinical implications from daily physiotherapy examination of 131 acute hamstring injuries and their association with running speed and rehabilitation progression

Aim

To investigate the association of daily clinical measures and the progression of rehabilitation and perceived running effort.

Methods

A cohort of 131 athletes with an MRI-confirmed acute hamstring injury underwent a standardised criteria-based rehabilitation protocol. Descriptive and inferential statistics were used to investigate the association between daily clinical subjective and objective measures and both the progression of rehabilitation and perceived running effort. These measures included different strength, palpation, flexibility and functional tests. Inter-rater and intrarater reliability and minimal detectable change were established for the clinical measures of strength and flexibility by examining measures taken on consecutive days for the uninjured leg.

Results

The progression of the daily measures was seen to be non-linear and varied according to the measure. Intra-rater reliability for the strength and flexibility measures were excellent (95% CI ≥0.85 for all measures). Strength (in the outer range position) and flexibility (in maximum hip flexion with active knee extension (MHFAKE) in supine) were best associated with rehabilitation progression and perceived running effort. Additionally, length of pain on palpation was usefully associated with rehabilitation progression. At lower perceived running effort there was a large variation in actual running speed.

Conclusion

Daily physical measures of palpation pain, outer range strength, MHFAKE and reported pain during daily activity are useful to inform the progression of rehabilitation.

Trial registration number

NCT01812564 and NCT02104258.

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How can we implement exercise therapy for patellofemoral pain if we dont know what was prescribed? A systematic review

Objective

To evaluate the completeness of exercise prescription in randomised controlled trials (RCTs) for patellofemoral pain (PFP), identify which elements are most frequently missing and supplement recommendations based on additional data from authors.

Design

Systematic review.

Data sources

All studies included in the most recent Cochrane review were evaluated. Additionally, the Cochrane search was updated in June 2016 in Cochrane, MEDLINE, EMBASE, PEDro, CINAHL and AMED databases. Two raters independently assessed completeness of reporting using the Toigo and Boutellier mechanobiological exercise descriptors, and Template for Intervention Description and Replication (TIDieR) checklist. Authors were also contacted to provide additional information.

Eligibility criteria for selecting studies

RCTs of exercise interventions for PFP.

Results

We included 38 RCTs. The level of exercise prescription detail was low, with no study providing complete information. The most commonly reported exercise descriptors were the ’duration of the experimental period’ (n=38/38) and ’number of exercise interventions’ (n=35). From TIDieR, the most commonly reported items were the ’intervention name’ (n=38) and ’rationale’ (n=36).

The least reported items from the exercise descriptors were ’volitional muscular failure’, ’temporal distribution of contraction modes’, ’time under tension’ and ’recovery between exercise sessions’ (all n=2/38). From TIDieR, the least reported item was ‘How well (fidelity and adherence)’ (n=3/38).

36 authors were contacted, with 22 replies and 13 providing additional exercise prescription details .

Conclusion

Exercise prescriptions in RCTs with proven efficacy for PFP are poorly reported, impairing their implementation in clinical practice.

PROSPERO registration number

CRD42016039138.

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Temporal trends in the cardiorespiratory fitness of children and adolescents representing 19 high-income and upper middle-income countries between 1981 and 2014

Objective

To estimate international and national temporal trends in the cardiorespiratory fitness (CRF) of children and adolescents and to examine relationships between temporal trends in CRF and temporal trends in broad socioeconomic and health-related indicators across countries.

Methods

Data were obtained from a systematic search of studies that explicitly reported 20 m shuttle run test (a validated measure of CRF) descriptive data on apparently healthy individuals aged 9–17 years. Following the estimation of relative peak oxygen uptake (mL/kg/min) as a measure of CRF, sample-weighted temporal trends were estimated at the country–sex–age level using best-fitting linear or polynomial regression models relating the year of testing to mean CRF. Poststratified population-weighted mean changes in absolute and per cent CRF were estimated. Pearson’s correlations were used to describe the association between linear temporal trends in CRF and linear temporal trends in broad socioeconomic and health-related indicators.

Results

Temporal trends were estimated from 965 264 children and adolescents from 19 high-income and upper middle-income countries between 1981 and 2014, using data from 137 studies. Collectively, there was a moderate decline in CRF of 3.3 mL/kg/min (95% CI –3.5 to –3.1), equivalent to a decline of 7.3% (95% CI –7.8% to –6.7%) over the 33-year time period. This international decline diminished with each decade and stabilised near zero around 2000. The decline was larger for boys than girls and was similar for children and adolescents. Trends also differed in magnitude and direction between countries, with most showing declines. There was a strong negative association between country-specific trends in income inequality (Gini index) and trends in CRF across 18 countries; meaning, countries approaching income equality had more favourable trends in CRF.

Conclusions

There has been a substantial decline in CRF since 1981, which is suggestive of a meaningful decline in population health. However, the international trend in CRF has not followed the anticipated trajectory, diminishing and stabilising with negligible change since 2000. CRF data are needed from children in low-income and middle-income countries to more confidently determine true international trends and determine whether temporal trends are similar to those observed in high-income and upper middle-income countries.

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Crash-test dummy and pendulum impact tests of ice hockey boards: greater displacement does not reduce impact

Background

One injury mechanism in ice hockey is impact with the boards. We investigated whether more flexible hockey boards would provide less biomechanical loading on impact than did existing (reference) boards.

Methods

We conducted impact tests with a dynamic pendulum (mass 60 kg) and with crash test dummies (ES-2 dummy, 4.76 m/s impact speed). Outcomes were biomechanical loading experienced by a player in terms of head acceleration, impact force to the shoulder, spine, abdomen and pelvis as well as compression of the thorax.

Results

The more flexible board designs featured substantial displacement at impact. Some so-called flexible boards were displaced four times more than the reference board. The new boards possessed less stiffness and up to 90 kg less effective mass, reducing the portion of the board mass a player experienced on impact, compared with boards with a conventional design. Flexible boards resulted in a similar or reduced loading for all body regions, apart from the shoulder. The displacement of a board system did not correlate directly with the biomechanical loading.

Conclusions

Flexible board systems can reduce the loading of a player on impact. However, we found no correlation between the displacement and the biomechanical loading; accordingly, displacement alone was insufficient to characterise the overall loading of a player and thus the risk of injury associated with board impact. Ideally, the performance of boards is assessed on the basis of parameters that show a good correlation to injury risk.

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