Trunk movement compensations and corresponding core muscle demand during step ambulation in people with unilateral transtibial amputation

Publication date: April 2018
Source:Journal of Electromyography and Kinesiology, Volume 39
Author(s): Brecca M.M. Gaffney, Cory L. Christiansen, Amanda M. Murray, Bradley S. Davidson
The objective of this investigation was to identify demands from core muscles that corresponded with trunk movement compensations during bilateral step ambulation in people with unilateral transtibial amputation (TTA). Trunk rotational angular momentum (RAM) was measured using motion capture and bilateral surface EMG was measured from four bilateral core muscles during step ascent and descent tasks in people with TTA and healthy controls. During step ascent, the TTA group generated larger mediolateral (P = 0.01) and axial (P = 0.01) trunk RAM toward the leading limb when stepping onto the intact limb than the control group, which corresponded with high demand from the bilateral erector spinae and oblique muscles. During step descent, the TTA group generated larger trunk RAM in the sagittal (P < 0.01), frontal (P < 0.01), and transverse planes (P = 0.01) than the control group, which was an effect of falling onto the intact limb. To maintain balance and arrest trunk RAM, core muscle demand was larger throughout the loading period of step descent in the TTA group. However, asymmetric trunk movement compensations did not correspond to asymmetric core muscle demand during either task, indicating a difference in motor control compensations dependent on the leading limb.



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A strong linear relationship between Turns/Amplitude peak ratio and ratio at maximal effort

Publication date: April 2018
Source:Journal of Electromyography and Kinesiology, Volume 39
Author(s): Christos Moschovos, Apostolia Ghika, Nikolaos Karandreas, Andreas Kyrozis
In EMG interference pattern analysis, the peak value of turns to mean amplitude ratio [peak(T/A)] is an established clinically significant marker, but its calculation requires specific software available only in few EMG apparatuses. On the contrary, the turns to mean amplitude ratio obtained at maximal muscle contraction (T/Amax) is easily calculated but less well standardized. We aimed to quantitatively assess the association between T/Amax and peak(T/A). Data were derived from 642 muscle contractions (Nc) from 270 consecutive patients (Np) who underwent EMG at our laboratory (software Dantec Keypoint, QEMG) from May 2015 to September 2016 and had interference patterns obtained from at least one of the following muscles: triceps-lateral head, brachioradialis, extensor digitorum communis and biceps. Statistics were calculated separately for normal and neurogenic muscles. Peak(T/A) was calculated by the built-in "peak ratio" function. T/Amax was calculated by the built-in Interference Pattern analysis function. The ratio with the highest amplitude was selected as T/Amax. Linear regression models provided high Pearson correlation coeffficientscoefficients (R) between peak(T/A) and T/Amax for all 4 muscles, normal or neurogenic, except a subgroup of biceps in patients aged <40y. Specifically, R were: (A) triceps normal 0.79 (Nc = 99), neurogenic 0.83 (Nc = 50) (B) brachioradialis normal 0.81 (Nc = 84), neurogenic 0.78 (Nc = 66) (C) extensor digitorum communis normal 0.72 (Nc = 92), neurogenic 0.73 (Nc = 61) (D) biceps (age > 40y) normal 0.77 (Nc = 77), neurogenic 0.67 (Nc = 62). We conclude that T/Amax has a strong linear association with peak(T/A) and, therefore, the former may be further investigated as a potentially useful quantitative diagnostic marker, especially in cases where the latter is not available.



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The effects of short-term and long-term experiences on co-contraction of lower extremity postural control muscles during continuous, multi-directional support-surface perturbations

Publication date: April 2018
Source:Journal of Electromyography and Kinesiology, Volume 39
Author(s): Alison Schinkel-Ivy, Carolyn A. Duncan
While reactive balance control in response to single perturbations in quiet standing is relatively well understood, some occupational environments (e.g. maritime environments) expose workers to continuous, multi-directional challenges to balance and postural control, which require workers to respond to the current perturbation, as well as anticipate coming perturbations. Investigation of muscle activation patterns during continuous, multi-directional perturbations, and the role of previous experience, is warranted to better understand postural control strategies in these types of environments. This study aimed to identify changes in co-contraction in the lower extremity postural control muscles during multi-directional support-surface perturbations as a result of short-term and long-term experience. Twenty-five participants (12 with minimal experience (novice), 13 with ≥6 months experience working in moving maritime environments (experienced)) were exposed to five 5-minute trials of continuous support-surface perturbations. Muscle activity was recorded from six muscles bilaterally. Co-contraction indices were calculated for selected muscle pairings and compared between groups and trials. Co-contraction decreased across trials, and was lower in the experienced group relative to the novice group. These findings provide insight into the influence of previous experience on muscle activation during reactive balance control, and suggest that increased co-contraction may be a potential mechanism of the increased risk of workplace fatigue, falls, and injury in novice maritime workers. The development and refinement of training programs targeting novice workers may be a potential avenue to reduce fall and injury risk in maritime environments.



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Reliability of ultrasound shear-wave elastography in assessing low back musculature elasticity in asymptomatic individuals

Publication date: April 2018
Source:Journal of Electromyography and Kinesiology, Volume 39
Author(s): Shane Koppenhaver, Joshua Kniss, Daniel Lilley, Michael Oates, Cesar Fernández-de-las-Peñas, Ruth Maher, Theodore Croy, Minoru Shinohara
Patients with low back pain commonly exhibit impaired morphology and function of spinal musculature that may be quantifiable using shear-wave elastography (SWE). The purpose of this study was to assess the intra-rater and test-retest reliability of SWE elasticity measures of the lumbar erector spinae and multifidus muscles during rest and differing levels of contraction in asymptomatic individuals. This single-group repeated-measures design involved a baseline measurement session and a follow-up session 3 days later. The lumbar multifidus was imaged at rest and during three levels of contraction (minimal, moderate, and maximum). The lumbar erector spinae (illiocostalis and longissimus muscles) were imaged at rest only. Overall reliability estimates were fair to excellent with ICCs ranging from 0.44 to 0.92. Reliability was higher in the lumbar multifidus muscles than the erector spinae muscles, slightly higher during contraction than during rest, and substantially improved by using the mean of 3 measurements. By reliably quantifying impaired spinal musculature, SWE may facilitate an improved understanding of the etiology and treatment of low back pain and other muscle pain-related conditions such as trigger points and fibromyalgia.



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Improving the test-retest and inter-rater reliability for stretch reflex measurements using an isokinetic device in stroke patients with mild to moderate elbow spasticity

Publication date: Available online 3 February 2018
Source:Journal of Electromyography and Kinesiology
Author(s): Minki Sin, Won-Seok Kim, Kyujin Cho, Sungmin Cho, Nam-Jong Paik
The conventional tools to measure spasticity exhibited insufficient test-retest or inter-rater reliability. Therefore, the spasticity measurement using an isokinetic device has been proposed to improve these reliabilities of the angle of catch (AoC) measurements; however, this proposal has not been investigated in a standardized manner.In this study, the comparison of the AoC measurement was performed using two modes (isokinetic and manual motion) to investigate whether the standardized isokinetic motion could increase the reliabilities. Motion consistency was calculated using a newly developed index. To analyze the effect of the motion standardization, AoC were estimated using EMG data for both modes, and to compare the measurement reliability, AoC for isokinetic mode was estimated using both EMG and torque data.Although the test-retest reliability for manual motion was excellent, the use of isokinetic motion improved it to the level of extremely excellent. Intraclass correlation coefficient (ICC) for the inter-rater reliability of manual motion was 0.788, which was near the lower limit of the excellent. Isokinetic motion improved it to the ICC of 0.890 and 0.931 based on the EMG and torque, respectively.These improvements in reliabilities reduced the measurement errors, sample size, and need for the same rater in clinical trials.



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Occurrence of bifid median nerve in healthy and carpal tunnel syndrome patients

Publication date: Available online 3 February 2018
Source:Journal of Electromyography and Kinesiology
Author(s): Eftychia Trachani, Aspasia Rigopoulou, Dimitra Veltsista, Evangelia Gavanozi, Athina Chrysanthopoulou, Elisabeth Chroni
We investigated the possible association between median nerve morphology and carpal tunnel size, hand side and nerve conduction measurements. The study included a patient group (n=58; 44 women) with idiopathic carpal tunnel syndrome (CTS) in 100 hands and a control group of healthy volunteers (n=56, 112 hands; 44 women). The following data were recorded: (1) median and ulnar motor and sensory nerve conduction parameters (2) ultrasonographic dimensions of the carpal tunnel inlet area (CTAin) and inlet area of the median nerve. The prevalence of bifid median nerve was 19% in the CTS hands and 13.3 % in the control group. Bilateral bifid nerve was detected in 7 subjects and unilateral in 23, with no side or sex preponderance. The median nerve area was larger in the participants with single than those with bifid median nerve. No correlation was found between CTAin and median nerve area for single or bifid nerves in controls or patients. It was concluded that bifid median nerve was not a rare variation. We could not, however, support its etiological relation to CTS. Ultrasonographic examination of the carpal tunnel region supplementing neurophysiology provided a reliable means to detect median nerve size and morphology.Clinical trial registration number: 84; 5/3/15



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STING-dependent interferon-λ1 induction in HT29 cells, a human colorectal cancer cell line following gamma-radiation

Publication date: Available online 3 February 2018
Source:International Journal of Radiation Oncology*Biology*Physics
Author(s): Jianzhou Chen, Bostjan Markelc, Jakob Kaeppler, Vivian M.L. Ogundipe, Yunhong Cao, W. Gillies McKenna, Ruth J. Muschel
PurposeIonizing radiation augments anti-tumor immune responses with interferons (IFN) acting as mediators. Of the three types of IFNs, type I and II IFNs are induced in irradiated tumors with induction of type III IFNs (IFNLs) currently not reported. Here, we investigated the induction of type III IFNs in human cancer cells by gamma-rays and its mechanisms.Methods and MaterialsType III IFN expression in human cancer cell lines following gamma-ray irradiation in vitro was assessed by RT-qPCR and ELISA. Signaling pathways mediating type III IFN induction were examined by a variety of means, including immunoblotting, flow cytometry, confocal imaging and RT-qPCR. Key mediators in these pathways were further explored and validated using gene CRISPR knockout or shRNA knockdown.ResultsExposure to gamma-rays directly induced type III IFNs (mainly IFNL1) in human cancer cell lines in dose- and time-dependent fashions. The induction of IFNL1 was primarily mediated by the cytosolic DNA sensors-STING-TBK1-IRF1 signaling axis with a lesser contribution from NF-κB signaling in HT29 cells. In addition, type III IFN signaling through its receptors serves as a positive feedback loop further enhancing IFN expression via upregulation of the kinases in the STING-TBK1 signaling axis.ConclusionsOur results suggest that IFNL1 can be upregulated in human cancer cell lines following gamma-rays treatment. In HT29 cells this induction occurs via the STING pathway adding another layer of complexity to the understanding of radiation-induced anti-tumor immunity and may provide novel insights into IFN-based cancer treatment.



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Ki67 is an independent predictor of recurrence in the largest randomised trial of 3 radiation fractionation schedules in localised prostate cancer

Publication date: Available online 3 February 2018
Source:International Journal of Radiation Oncology*Biology*Physics
Author(s): Anna C. Wilkins, Barry Gusterson, Zsolt Szijgyarto, Joanne Haviland, Clare Griffin, Christine Stuttle, Frances Daley, Catherine M. Corbishley, David P. Dearnaley, Emma Hall, Navita Somaiah
BackgroundExternal beam radiotherapy is delivered using a uniform fractionation schedule for localised prostate tumours, individualising fractionation according to tumour biology could improve outcomes. Additionally recurrence rates following radiotherapy vary considerably, better prognostic markers could improve treatment stratification. This study assessed if the cellular proliferation marker Ki67 provides prognostic information and predicts response to radiotherapy fractionation in patients participating in ", a randomised trial of three radiotherapy fractionation schedules (74Gy/37f vs 60Gy/20f vs 57Gy/19f).MethodsA matched case:control study design was used, patients with biochemical/clinical failure >2 years after radiotherapy (BCR) were matched 1:1 to patients without recurrence using established prognostic factors (Gleason score, PSA, tumour-stage) and fractionation schedule. Immunohistochemistry was used to stain diagnostic biopsy specimens for Ki67, which were scored using the unweighted global method. Conditional logistic regression models estimated the prognostic value of mean and maximum Ki67 scores on BCR risk. Biomarker-fractionation interaction terms determined whether Ki67 was predictive of BCR by fractionation.ResultsUsing 173 matched pairs, the median for mean and maximum Ki67 scores were 6.6% (IQR:3.9-9.8) and 11.0% (IQR:7.0-15.0) respectively. Both scores were significant predictors of BCR in models adjusted for established prognostic factors. Conditioning on matching variables and age, the odds of BCR was estimated to increase by 9% per 1% increase in mean Ki67 score (OR=1.09, 95%CI:1.04–1.15,p=0.001). Interaction terms between Ki67 and fractionation schedules were not statistically significant.ConclusionsDiagnostic Ki67 did not predict BCR according to fractionation schedule in ", however it was a strong independent prognostic factor for BCR.



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Relationship Between Citation-Based Scholarly Activity of United States Radiation Oncology Residents and Subsequent Choice of Academic versus Private Practice Career

Publication date: Available online 3 February 2018
Source:International Journal of Radiation Oncology*Biology*Physics
Author(s): Shearwood McClelland, Timur Mitin, Lynn D. Wilson, Charles R. Thomas, Jerry J. Jaboin
IntroductionCitation-based scholarly activity of physicians has become increasingly evaluated via the Hirsch index (h-index), which assesses the number of manuscripts (h) cited at least h times. However, such evaluation involving Radiation Oncology residents is lacking in the peer-reviewed literature. The objective of this study was to assess h-index data and its association with resident choice of academic versus private practice career.MethodsA list of 2016 radiation oncology resident graduates (163 residents from 76 Accreditation Council for Graduate Medical Education-certified programs) and their post-residency career choice (academic versus private practice) was compiled as previously described (McClelland et al., Practical Radiation Oncology 2017). The SCOPUS bibliometric citation database was then searched to collect h-index data for each resident. Demographics included in analyses were gender and PhD degree status.ResultsMean h-index score for all resident graduates was 4.15. Residents with a PhD had significantly higher h-index scores (6.75 versus 3.42; p<0.01), while there was no statistically significant difference in h-index scores between male and female residents (4.38 versus 3.36; p=0.06). With regard to career choice, residents choosing academic careers had higher h-index scores than those choosing private practice (5.41 versus 2.96; p<0.01). There was no significant difference in mean h-index scores between male and female residents regardless of private practice (3.15 versus 2.19; p=0.25) or academic (5.80 versus 4.30; p=0.13) career choice.ConclusionThe average radiation oncology resident graduate published a minimum of four manuscripts cited at least four times. Graduates with a PhD are significantly more likely to have higher h-index scores, as are residents who choose academic over private practice careers. There is no significant difference in h-index score between male and female residents regardless of career choice. These results offer up-to-date benchmarks for evaluating radiation oncology resident productivity and have potential utility in predicting career choices post-residency.

Teaser

The average radiation oncology resident graduate published a minimum of four manuscripts cited at least four times. Graduates with a PhD are significantly more likely to have higher h-index scores, as are residents who choose academic over private practice careers. There is no significant difference in h-index score between male and female residents regardless of career choice. These results offer up-to-date benchmarks for evaluating resident productivity and have potential utility in predicting career choices post-residency.


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Stereotactic Ablative Radiotherapy Versus Surgery in Early Lung Cancer: A Meta-Analysis of Propensity Score Studies

Publication date: Available online 3 February 2018
Source:International Journal of Radiation Oncology*Biology*Physics
Author(s): Hanbo Chen, Joanna M. Laba, R. Gabriel Boldt, Christopher D. Goodman, David A. Palma, Suresh Senan, Alexander V. Louie
BackgroundAs no completed randomized trials of surgery versus stereotactic ablative radiotherapy (SABR) in patients with early-stage non-small cell lung cancer are available, numerous propensity score studies have attempted to mimic the setting of clinical trials using non-randomized data. We performed a meta-analysis of propensity score studies comparing SABR and surgery.MethodsThe Medline and Embase databases were queried up to December 2016. Two authors independently reviewed the records for inclusion and extracted outcome measures. The study was conducted according to PRISMA and MOOSE guidelines. Primary meta-analysis and secondary analyses were carried out using R (v3.3.2) at a significance level of 0.05.ResultsSixteen studies were included in the meta-analysis. Overall survival favored surgery (SABR versus surgery hazard ratio = 1.48 [95% confidence interval: 1.26-1.72], I² = 80.5%). Lung cancer-specific survival was not significantly different between SABR and surgery (hazard ratio = 1.17 [0.92-1.50], I² = 18.6%). On stratification, overall survival favored both lobectomy and sublobar resection over SABR, though lung cancer-specific survival was again not significantly different. On secondary analysis, lymph node upstaging rate was 15.6% following surgery, with 11.4% of patients receiving chemotherapy. Propensity score-matching caliper distance and first author specialty was found to be associated with survival endpoints on regression.ConclusionsFor patients with early stage non-small cell lung cancer who are eligible for either treatment, better overall survivals were seen after surgery compared to SABR. However, lung cancer-specific survival was similar for both treatments. Prospective clinical trials are preferred to propensity analyses in evaluating the nature of non-cancer related mortality post-SABR.



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L’observance du traitement par pression positive continue : étude prospective de 103 patients suivis au service de pneumologie de Nabeul-Tunisie

Publication date: Available online 3 February 2018
Source:Revue des Maladies Respiratoires
Author(s): H. Ghrairi, I. Khalfallah, N. Abid, M. Loukil
IntroductionLe traitement de référence du syndrome d'apnées hypopnées obstructives du sommeil (SAHOS) est la pression positive continue (PPC). Ses effets bénéfiques sont certains si les indications sont respectées et l'observance thérapeutique est bonne.MéthodesÉtude prospective sur quatre ans incluant 103 patients ayant un SAHOS sévère et traités par PPC.RésultatsL'âge moyen de notre population était de 52 ans. Le taux du refus initial de la PPC était de 20 %. Le mode constant était prescrit chez 98 % des patients. Les effets indésirables de la PPC étaient observés chez 75,9 % des patients, dominés par l'intolérance nasale et les complications du masque. L'observance thérapeutique était bonne dans 76 % des cas. Le taux d'abandon secondaire était de 10,6 %. L'observance de la PPC était corrélée à la sévérité de la maladie, la somnolence diurne excessive initiale, un haut niveau de pression, l'éducation répétée au cours du suivi, l'efficacité clinique et des effets indésirables moindres. Sous PPC, il a été noté une amélioration significative des symptômes initiaux ainsi que de l'indice d'apnées-hypopnées résiduel.ConclusionLe suivi régulier des patients avec des consultations réalisées en présence du prestataire nous a permis d'obtenir des taux d'observance, de tolérance et d'efficacité satisfaisants.IntroductionContinuous positive airways pressure (CPAP) is the standard treatment for obstructive sleep apnea syndrome (OSAS). It produces substantial benefits if used for the appropriate indication and if patients adhere to treatment.MethodsWe conducted a prospective study of 103 patients treated with CPAP over four years follow-up.ResultsOur population had a mean age of 52 years with a sex ratio of 0.63. Face to face, individual education was provided in all cases. CPAP titration was performed by an unattended domiciliary autoadjusted CPAP device in 83.5% of patients for 15 days to one month. Twenty patients refused CPAP treatment after the period of titration. Eighty two patients (98.8%) were treated by constant CPAP. Seventy five percent of the patients complained of at least one side effect. The more common were nasal (56.6%) and mask related problems (40%). Seventy six percent of patients used CPAP for more than 4hours per day. Eleven patients stopped CPAP therapy because of intolerance (10 cases) and reluctance to instrumental therapy (one case). Adherence to CPAP therapy was associated with the severity of OSAS, the level of daytime sleepiness, higher pressures, repeated education during the course of follow up, clinical efficacy and the presence of fewer side-effects.ConclusionsWe obtained satisfactory rates of adherence and tolerance of CPAP assisted by regular medical and technical follow-up of patients.



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Étude de la prévalence du syndrome d’apnées obstructives du sommeil au Vietnam

Publication date: Available online 3 February 2018
Source:Revue des Maladies Respiratoires
Author(s): S. Duong-Quy, K. Dang Thi Mai, N. Tran Van, H. Nguyen Xuan Bich, T. Hua-Huy, F. Chalumeau, A.T. Dinh-Xuan, F. Soyez, F. Martin
IntroductionLes études épidémiologiques sur le syndrome d'apnées obstructives du sommeil (SAOS) en Asie, notamment en Asie du Sud Est, sont peu nombreuses. L'étude EPSASIE vise à déterminer la prévalence du SAOS dans une population adulte vietnamienne et à décrire ses caractéristiques.MéthodesIl s'agit d'une étude prospective, multicentrique et observationnelle. Une polygraphie ventilatoire nocturne (PV) ou une polysomnographie (PSG) ont été pratiquées chez les sujets présentant des symptômes évocateurs de SAS et un index d'événements respiratoires (IER)>10/h ou>25 sur une heure, mesuré par RU Sleeping.RésultatsAu total, 667/750 questionnaires validés ont été reçus. L'âge moyen de la population étudiée était de 44±12 ans avec un indice de masse corporelle moyen de 21,6±5,2kg/m². Une PV ou PSG a été réalisée 93 fois après dépistage positif par RU Sleeping. Un SAOS avec un index d'apnées-hypopnées (IAH)>5 a été retrouvé chez 57 sujets (8,5 %) et chez 35 personnes pour un IAH>15 (5,2 % des cas).ConclusionsLa prévalence du SAOS est assez élevée au sein de la population vietnamienne et comparable aux données actuelles de la littérature.IntroductionEpidemiological studies on obstructive sleep apnoea syndrome (OSAS) in Asia, South East Asia in particular, are few. The EPSASIE study aimed to determine the prevalence of OSAS in an adult Vietnamese population and to describe its characteristics.MethodsThis is a prospective, observational, multicenter study. Nocturnal ventilatory polygraphy (PV) or polysomnography (PSG) were performed in patients having symptoms evocative of the SAS syndrome and an index of respiratory events (IER)>10/h or>25 in one hour, measured by RU Sleeping.ResultsA total of 667/750 validated questionnaires were received. The mean age of the study population was 44±12 years with a mean body mass index of 21.6±5.2kg/m². PV or PSG were performed on 93 subjects after positive screening by RU Sleeping. OSAS with an apnoea-hypopnoea index (AHI)>5 was found in 57 subjects (8.5%) and in 35 subjects with AHI>15 (5.2% of cases).ConclusionThe prevalence of OSAS is quite high in the Vietnamese population and comparable with current literature data.



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Emphysème, vous avez dit emphysème ?

Publication date: Available online 3 February 2018
Source:Revue des Maladies Respiratoires
Author(s): J. Benzaquen, J. Pradelli, B. Padovani, CH. Marquette, S. Leroy
IntroductionLa bronchopneumopathie chronique obstructive (BPCO) est une pathologie fréquente qui, bien que pouvant sembler banale, est susceptible de dissimuler d'autres diagnostics à même d'accélérer son histoire naturelle ou à même de la simuler. Nous présentons le cas de quatre patients, suivis pour BPCO emphysémateuse, mais dont certaines caractéristiques cliniques et radiologiques ont conduit à reconsidérer le diagnostic.ObservationsUne femme de 52 ans, non fumeuse et non ménopausée, suivie pour emphysème, qui présentait finalement une lymphangioléiomyomatose décelée par imagerie sous-diaphragmatique révélant des angiomyolipomes rénaux ; un homme de 44 ans, tabagique, suivi pour un emphysème très rapidement évolutif, présentant finalement une histiocytose langheransienne décelée sur un scanner réalisé quatre ans plus tôt révélant des « nodules troués » ; un ancien avitailleur d'aéroport de 73 ans, non-fumeur, présentant un emphysème sévère, révélant un déficit en alpha-1 antitrypsine ; un homme de 54 ans, non-fumeur, présentant un trouble ventilatoire obstructif sévère, une hypo-atténuation multilobaire et des bronchectasies de même topographie, révélant une forme sévère de syndrome de Swyer-James- MacLeod.ConclusionLes quatre observations présentées illustrent la nécessité de savoir remettre en question le diagnostic de BPCO lorsque certaines caractéristiques phénotypiques sont décelées.IntroductionChronic obstructive pulmonary disease (COPD) is a common condition that may initially look simple but may conceal other diseases capable of accelerating its natural history or even simulating it. We describe four cases presenting as COPD with emphysema that were reclassified on the basis of certain clinical characteristics and the radiological pattern.Case reportsA 52 year old never smoking woman presenting with emphysema was eventually diagnosed as having lymphangioleiomyomatosis on the basis of an abdominal CT scan showing kidney angiomyolipomas. A 44 years old smoker presenting with rapidly evolving emphysema was eventually diagnosed as having Langerhans cell histiocytosis on the basis of a previous chest CT (four years earlier) showing cavitating nodules. An airport refueler, 73 years old, with severe emphysema despite never having smoked, was eventually diagnosed as suffering from alpha-1 antitrypsin deficiency. The last patient was a 54 year old man, a never smoker, who presented with severe airflow limitation and multilobar hyperlucency, with bronchiectasis in the same areas. He was eventually diagnosed as having a severe form of the Swyer–James-MacLeod syndrome.ConclusionThese four case reports underline the importance of questioning the diagnosis of COPD when certain particular phenotypic characteristics are identified.



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Impact of pemetrexed on intracranial disease control and radiation necrosis in patients with brain metastases from non-small cell lung cancer receiving stereotactic radiation

Publication date: Available online 3 February 2018
Source:Radiotherapy and Oncology
Author(s): Daniel N. Cagney, Allison M. Martin, Paul J. Catalano, Zachary J. Reitman, Gabrielle A. Mezochow, Eudocia Q. Lee, Patrick Y. Wen, Stephanie E. Weiss, Paul D. Brown, Manmeet S. Ahluwalia, Nils D. Arvold, Shyam K. Tanguturi, Daphne A. Haas-Kogan, Brian M. Alexander, Amanda J. Redig, Ayal A. Aizer
BackgroundPemetrexed is a folate antimetabolite used in the management of advanced adenocarcinoma of the lung. We sought to assess the impact of pemetrexed on intracranial disease control and radiation-related toxicity among patients with adenocarcinoma of the lung who received stereotactic radiation for brain metastases.Materials/MethodsWe identified 149 patients with adenocarcinoma of the lung and newly diagnosed brain metastases without a targetable mutation receiving stereotactic radiation. Kaplan–Meier plots and Cox regression were employed to assess whether use of pemetrexed was associated with intracranial disease control and radiation necrosis.ResultsAmong the entire cohort, 105 patients received pemetrexed while 44 did not. Among patients who were chemotherapy-naïve, use of pemetrexed (n = 43) versus alternative regimens after stereotactic radiation (n = 24) was associated with a reduced likelihood of developing new brain metastases (HR 0.42, 95% CI 0.22–0.79, p = 0.006) and a reduced need for salvage brain-directed radiation therapy (HR 0.36, 95% CI 0.18–0.73, p = 0.005). Pemetrexed use was associated with increased radiographic necrosis. (HR 2.70, 95% CI 1.09–6.70, p = 0.03).ConclusionsPatients receiving pemetrexed after brain-directed stereotactic radiation appear to benefit from improved intracranial disease control at the possible expense of radiation-related radiographic necrosis. Whether symptomatic radiation injury occurs more frequently in patients receiving pemetrexed requires further study.



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Evaluation of clinical and endoscopic toxicity after external beam radiotherapy and endorectal brachytherapy in elderly patients with rectal cancer treated in the HERBERT study

Publication date: Available online 3 February 2018
Source:Radiotherapy and Oncology
Author(s): E.C. Rijkmans, B. van Triest, R.A. Nout, E.M. Kerkhof, J. Buijsen, T. Rozema, J.H. Franssen, L.A. Velema, M.S. Laman, A. Cats, C.A.M. Marijnen
IntroductionThe HERBERT study evaluated a high-dose-rate endorectal brachytherapy boost (HDREBT) after EBRT in medically inoperable/elderly patients with rectal cancer. The response-rates are promising but not without risk of toxicity. The current analysis provides a comprehensive overview of patient reported, physician reported and endoscopically observed toxicity.Material and methodsA brachytherapy dose finding study was performed in 38 inoperable/elderly patients with T2-T4N0-1 rectal cancer. Patients received EBRT (13 × 3 Gy) followed by three weekly HDREBT applications (5–8 Gy). Toxicity was assessed via three methods: patient and physician (CTCAEv3) reported rectal symptoms and endoscopically. Wilcoxon's signed rank test, paired t-test and Spearman's correlation were used.ResultsPatient reported bowel symptoms showed a marked increase at the end of EBRT and two weeks after HDREBT. Acute grade 2 and 3 proctitis occurred in 68.4% and 13.2% respectively while late grade 2 and ≥3 proctitis occurred in 48% and 40%. Endoscopic evaluation mainly showed erythema and telangiectasia. In three patients frank haemorrhage or ulceration occurred. Most severe toxicity was observed 12–18 months after treatment.ConclusionFor elderly patients with rectal cancer, definitive radiotherapy can provide good tumour response but has a substantial risk of toxicity. The potential benefit and risks of a HDREBT boost above EBRT alone must be further evaluated.



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A qualitative signature for predicting pathological response to neoadjuvant chemoradiation in locally advanced rectal cancers

Publication date: Available online 3 February 2018
Source:Radiotherapy and Oncology
Author(s): You Guo, Weizhong Jiang, Lu Ao, Kai Song, Huxing Chen, Qingzhou Guan, Qiao Gao, Jun Cheng, Huaping Liu, Xianlong Wang, Guoxian Guan, Zheng Guo
Background and purposeThe standard therapy for locally advanced rectal cancers (LARCs) is neoadjuvant chemoradiation (nCRT) followed by surgical resection. Pathological response to nCRT varies among patients, and it remains a challenge to predict pathological response to nCRT in LARCs.Material and methodsUsing 42 samples as the training cohort, we searched a signature by screening the gene pairs whose within-sample relative expression orderings are significantly correlated with the pathological response. The signature was validated in both a public cohort of 46 samples and a cohort of 33 samples measured at our laboratory.ResultsA signature consisting of 27 gene pairs was identified in the training cohort with an accuracy of 92.86% and an area under the receiver operating characteristic curve (AUC) of 0.95. The accuracy was 89.13% for the public test cohort and 90.91% for the private test cohort, with AUC being 0.95 and 0.91, respectively. Furthermore, the signature was used to predict disease-free survival benefits from 5Fu-based chemotherapy in 285 locally advanced colorectal cancers.ConclusionsThe signature consisting of 27 gene pairs can robustly predict clinical response of LARCs to nCRT.



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Differentiation between radiation-induced brain injury and glioma recurrence using 3D pCASL and dynamic susceptibility contrast-enhanced perfusion-weighted imaging

Publication date: Available online 2 February 2018
Source:Radiotherapy and Oncology
Author(s): Yu-Lin Wang, Si Chen, Hua-Feng Xiao, Ying Li, Yan Wang, Gang Liu, Xin Lou, Lin Ma
PurposeThis study was performed to validate the efficacy of three-dimensional pseudocontinuous arterial spin labeling (pCASL) compared with dynamic susceptibility contrast-enhanced perfusion-weighted imaging (DSC-PWI) in distinguishing radiation-induced brain injury from glioma recurrence in patients with glioma.MethodsBoth 3D pCASL and DSC-PWI were performed using a 3.0 Tesla scanner in 69 patients with previously resected and irradiated glioma who displayed newly developed abnormal contrast-enhanced lesions. The included patients were classified into a radiation-induced brain injury group (n = 34) and a glioma recurrence group (n = 35) based on subsequent pathologic analysis or clinical–radiological follow-up. Lesion perfusion parameter values (CBF and nCBF on pCASL, nrCBV and nrCBF on DSC-PWI) were measured and compared between the two groups using Student's t test. Pearson correlation analysis was performed to evaluate the correlation between pCASL (CBF and nCBF) and DSC-PWI (nrCBV and nrCBF) values in the contrast-enhanced lesions and in the perifocal edema regions.ResultsFor the contrast-enhanced lesions, the CBF, nCBF, nrCBV, and nrCBF (29.46 ± 15.08 ml/100 g/min, 1.11 ± 0.50, 1.39 ± 1.15, and 1.30 ± 0.74) in the radiation-induced brain injury group were significantly lower than those (64.52 ± 33.92 ml/100 g/min, 2.73 ± 1.71, 3.39 ± 2.12, and 3.20 ± 1.95) in the glioma recurrence group (P < 0.001). The CBF and nCBF demonstrated strong correlation with nrCBV and nrCBF in the contrast-enhanced lesions.ConclusionRadiation-induced brain injury and glioma recurrence can be reliably distinguished using both 3D pCASL and DSC-PWI. Contrast-free 3D pCASL is a suitable alternative to DSC-PWI for long-term follow-up in glioma patients with postoperative radiotherapy.



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Prognostic significance of pretreatment total lymphocyte count and neutrophil-to-lymphocyte ratio in extensive-stage small-cell lung cancer

Publication date: Available online 2 February 2018
Source:Radiotherapy and Oncology
Author(s): Ryoko Suzuki, Steven H. Lin, Xiong Wei, Pamela K. Allen, James W. Welsh, Lauren A. Byers, Ritsuko Komaki
BackgroundWe evaluated pretreatment total lymphocyte count (TLC, marker of immunosuppression), neutrophil-to-lymphocyte ratio (NLR, marker of inflammation), and overall survival (OS) in patients with extensive-stage small-cell lung cancer (ES-SCLC).MethodsPretreatment blood characteristics, age, sex, performance status, race, stage (M1a vs. M1b), number and location of metastases, weight loss, smoking status, chemotherapy cycles (<4 vs. ≥4), thoracic radiotherapy dose (<45 vs. ≥45 Gy), and receipt of prophylactic cranial irradiation (PCI) were evaluated in 252 patients with ES-SCLC treated in 1998–2015. Factors significant in univariate analysis were selected as covariates for a multivariate Cox model.ResultsPretreatment TLC was below normal (<1.0 × 10³/µL) in 58 patients (23%). Median OS time was 11.0 months and was worse for those with TLC ≤ 1.5 × 10³/µL (9.8 vs. 12.0 months) and pretreatment NLR > 4.0 (9.4 vs. 13.9 months). Multivariate analysis identified low TLC (hazard ratio [HR] 0.734, 95% confidence interval [CI] 0.565–0.955, P = 0.021) and high NLR (HR 1.521, 95% CI 1.172–1.976, P = 0.002) as predicting inferior survival. Age (>63 y), sex (male), performance status (≥2), chemotherapy cycles (<4), radiation dose (<45 Gy), and no PCI also predicted worse OS (P < 0.05).ConclusionsPretreatment TLC and NLR may be useful for stratifying patients with ES-SCLC for treatment approaches.



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Radiotherapy for prostate cancer – Does daily image guidance with tighter margins improve patient reported outcomes compared to weekly orthogonal verified irradiation? Results from a randomized controlled trial

Publication date: Available online 3 February 2018
Source:Radiotherapy and Oncology
Author(s): Hanne Tøndel, Jo-Åsmund Lund, Stian Lydersen, Anne D. Wanderås, Bjørg Aksnessæther, Christer Andre Jensen, Stein Kaasa, Arne Solberg
BackgroundNovel cancer drugs are subject to strict scientific evaluation of safety and efficacy and usually undergo a cost effectiveness analysis before approval for use in clinical practice. For new techniques in radiotherapy (RT) such as image-guided radiotherapy (IGRT), this is often not the case. We performed a randomized controlled trial to compare daily cone beam computer tomography (CBCT) IGRT with reduced planning target volume (PTV) margins vs weekly orthogonal portal imaging with conventional PTV margins. The primary aim of the study was to investigate the effect of two different image guidance techniques on patient reported outcome (PRO) using early side effects as proxy outcome of late rectal side effects in patients receiving curative RT for prostate cancer.MethodsThis open label, phase 3 trial conducted at two RT centers in Norway enrolled men aged 18 years or older with previously untreated histologically proven intermediate or high-risk adenocarcinoma of the prostate. Patients eligible for radical RT received it after 3 months of total androgen blockage and were randomly assigned to 78 Gy in 39 fractions guided either by weekly offline orthogonal portal imaging (15 mm margins to PTV) or by daily online CBCT IGRT (7 mm margins to PTV). Based on previous results indicating that acute rectal side effects are a valid proxy outcome for late rectal side effects, the primary outcome was acute rectal toxicity at end of RT as evaluated by rectal bother scale (five of the items from PRO's QUFW94). The RIC-trial is registered with ClinicalTrials.gov, number NCT01550237.FindingsBetween October 2012 and June 2015, 257 patients were randomly assigned to weekly offline portal imaging (n = 129) or daily online CBCT IGRT (n = 128). Out of 250 evaluable patients, 96% completed PROs at baseline and 97% at end of RT. Baseline analyses demonstrated balance between groups for baseline characteristics as well as for PROs. In general, patients reported a small degree of side effects at end of RT, and there was no difference between groups for primary outcome (rectal bother scale of QUFW94 1.871 vs 1.884, p = 0.804). In addition, there were no significant differences between groups for any other gastrointestinal or urinary symptom as reported by QUFW94. Health related quality of life analyses (EORTC QLQ 30) demonstrated no differences between groups.InterpretationIn radical RT for prostate cancer, daily CBCT IGRT with reduced PTV margins demonstrated no advantage with respect to patient reported side effects at end of RT as compared to weekly orthogonal offline portal imaging with standard PTV margins.



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Anxiety and Threat-Related Attention: Cognitive-Motivational Framework and Treatment

Publication date: Available online 3 February 2018
Source:Trends in Cognitive Sciences
Author(s): Karin Mogg, Brendan P. Bradley
Research in experimental psychopathology and cognitive theories of anxiety highlight threat-related attention biases (ABs) and underpin the development of a computer-delivered treatment for anxiety disorders: attention-bias modification (ABM) training. Variable effects of ABM training on anxiety and ABs generate conflicting research recommendations, novel ABM training procedures, and theoretical controversy. This article summarises an updated cognitive-motivational framework, integrating proposals from cognitive models of anxiety and attention, as well as evidence of ABs. Interactions between motivational salience-driven and goal-directed influences on multiple cognitive processes (e.g., stimulus evaluation, inhibition, switching, orienting) underlie anxiety and the variable manifestations of ABs (orienting towards and away from threat; threat-distractor interference). This theoretical analysis also considers ABM training as cognitive skill training, describes a conceptual framework for evaluating/developing novel ABM training procedures, and complements network-based research on reciprocal anxiety–cognition relationships.



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