Crew awareness as key to optimizing habitability standards onboard naval platforms: A ‘back-to-basics’ approach

Publication date: Available online 18 December 2016
Source:Medical Journal Armed Forces India
Author(s): Anand Neelakantan, Mookkiah Ilankumaran, Sougat Ray
BackgroundA healthy habitable environment onboard warships is vital to operational fleet efficiency and fit sea-warrier force. Unique man-machine-armament interface issues and consequent constraints on habitability necessitate a multi-disciplinary approach toward optimizing habitability standards. Study of the basic 'human factor', including crew awareness on what determines shipboard habitability, and its association with habitation specifications is an essential step in such an approach. The aim of this study was to assess crew awareness on shipboard habitability and the association between awareness and maintenance of optimal habitability as per specifications.MethodsA cross-sectional descriptive study was carried out among 552 naval personnel onboard warships in Mumbai. Data on crew awareness on habitability was collected using a standardized questionnaire, and correlated with basic habitability requirement specifications. Data was analyzed using Microsoft Excel, Epi-info, and SPSS version 17.ResultsAwareness level on basic habitability aspects was very good in 65.3% of crew. Area-specific awareness was maximum with respect to living area (95.3%). Knowledge levels on waste management were among the lowest (65.2%) in the category of aspect-wise awareness. Statistically significant association was found between awareness levels and habitability standards (OR=7.27).ConclusionThe new benchmarks set in the form of high crew awareness levels on basic shipboard habitability specifications and its significant association with standards needs to be sustained. It entails re-iteration of healthy habitation essentials into training; and holds the key to a fit fighting force.



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Direct induction of neural progenitor cells transiently passes through a partially reprogrammed state

Publication date: March 2017
Source:Biomaterials, Volume 119
Author(s): Rui Gao, Wenchao Xiu, Linfeng Zhang, Ruge Zang, Lei Yang, Chenfei Wang, Min Wang, Mingzhu Wang, Li Yi, Yuanyuan Tang, Yawei Gao, Hong Wang, Jiajie Xi, Wenqiang Liu, Yixuan Wang, Xuejun Wen, Yongchun Yu, Yong Zhang, Liang Chen, Jiayu Chen, Shaorong Gao
The generation of functional neural progenitor cells (NPCs) holds great promise for both research and clinical applications in neurodegenerative diseases. Traditionally, NPCs are derived from embryonic stem cells (ESCs) and induced pluripotent stem cells (iPSCs), or NPCs can be directly converted from somatic cells by sets of transcription factors or by a combination of chemical cocktails and/or hypoxia. However, the ethical issues of ESCs, the risk of tumorigenesis from iPSCs and transgenic integration from exogenous genes as well as complicated manipulation and time-consuming of chemical induced NPCs (ciNPCs) limit the applications of these strategies. Here, we describe a novel method for generating growth factor-induced neural progenitor cells (giNPCs) from mouse embryonic and adult fibroblasts by using inductive and/or permissive signaling culture conditions. These giNPCs closely resemble brain-derived NPCs in terms of transcription networks and neural lineage differentiation potentials. Moreover, this somatic cell to NPC induction is a gradual process that includes initiation, intermediate, maturation and stabilization stages. Importantly, gene expression and histone modification analyses further indicate a partially reprogrammed state during the generation process of induced NPCs, in which lineage specific genes and pluripotency associated genes are transiently activated. Our study therefore describes the potential safety problems that also exist in the transgene-free direct induction strategy and highlights the importance of excluding the possibility of residual partially reprogrammed and/or teratoma-like cells from the generated NPCs for future clinical trials.



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Iron nanomedicines induce Toll-like receptor activation, cytokine production and complement activation

Publication date: March 2017
Source:Biomaterials, Volume 119
Author(s): Johan J.F. Verhoef, A. Marit de Groot, Marc van Moorsel, Jeffrey Ritsema, Nataliia Beztsinna, Coen Maas, Huub Schellekens
Approximately a dozen of intravenous iron nanomedicines gained marketing authorization in the last two decades. These products are generally considered as safe, but have been associated with an increased risk for hypersensitivity-like reactions of which the underlying mechanisms are unknown. We hypothesized that iron nanomedicines can trigger the innate immune system. We hereto investigated the physico-chemical properties of ferric gluconate, iron sucrose, ferric carboxymaltose and iron isomaltoside 1000 and comparatively studied their interaction with Toll-like receptors, the complement system and peripheral blood mononuclear cells. Two out of four formulations appeared as aggregates by Scanning Transmission Electron Microscopy analysis and were actively taken up by HEK293T- and peripheral blood mononuclear cells in a cholesterol-dependent manner. These formulations triggered in vitro activation of intracellular Toll-like receptors 3, -7 and -9 in a dose- and serum-dependent manner. In parallel experiments, we determined that these compounds activated the complement system. Finally, we found that uptake of aggregation-prone iron nanomedicines by peripheral blood mononuclear cells in whole blood induced production of the proinflammatory cytokine IL-1β, but not IL-6.



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Editorial board

Publication date: February 2017
Source:Biomaterials, Volume 117





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Polydrug use among urban adolescent cigarette smokers

Publication date: March 2017
Source:Addictive Behaviors, Volume 66
Author(s): Karma L. McKelvey, Danielle E. Ramo, Kevin Delucchi, Mark L. Rubinstein
PurposeAdolescent smokers are at increased risk for polydrug use, which is associated with more consequences than use of a single drug. Here we classified subgroups of polydrug use among urban adolescent cigarette-smokers; described the sociodemographic, smoking, and depression correlates; and identified three-year outcomes associated with subgroup membership.MethodsAdolescent cigarette smokers (N=176; Mage=16.1; 35% male; 27% white) completed surveys assessing drug use, smoking characteristics, demographics, and depressive symptoms at baseline and 12, 24, and 36months follow-up.ResultsAlmost all participants (96%) reported using, on average, two (SD=0.97) substances (including other tobacco products) in addition to cigarettes. Latent class analysis revealed two distinct classes of polydrug users. "Limited Range Use" (84%) class members reported current use of other tobacco, alcohol, and marijuana, as did "Extended Range Use" class members (16%) who also reported current use of "harder drugs" (i.e., cocaine/crack, hallucinogens, ecstasy, and misused prescriptions). The classes did not differ on demographics or baseline likelihood of marijuana (χ²=0.25; p<0.62) or alcohol use (χ²=3.3; p<0.07). At baseline, a larger proportion of Extended Range Use class members reported both smoking the entire cigarette and symptoms of clinical depression. Extended Range Use class membership at baseline predicted higher mean depression scores at 24 and 36months.ConclusionAdolescent cigarette-smokers who reported extended range use (18%) also reported symptoms of clinical depression at baseline and follow-up. These findings indicate a need for early monitoring of depression symptoms and prevention and cessation interventions targeting this high-risk group.



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Editorial Board

Publication date: March 2017
Source:Addictive Behaviors, Volume 66





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Altered visual contrast gain control is sensitive for idiopathic generalized epilepsies

Publication date: Available online 18 December 2016
Source:Clinical Neurophysiology
Author(s): Daehan Won, Wonsuk Kim, W. Art Chaovalitwongse, Jeffrey J. Tsai
ObjectiveVisual hyperexcitability in the form of abnormal contrast gain control has been shown in photosensitive epilepsy and idiopathic generalized epilepsies. We assessed the accuracy and reliability of measures of visual contrast gain control in discerning individuals with idiopathic generalized epilepsies from healthy controls.MethodsTwenty-four adult patients with idiopathic generalized epilepsy and 32 neurotypical control subjects from two study sites participated in a prospective, cross-sectional study. We recorded steady-state visual evoked potentials to a wide range of contrasts of a flickering grating stimulus. The resultant response magnitude vs. contrast curves were fitted to a standard model of contrast response function, and the model parameters were used as input features to a linear classifier to separate patients from controls. Additionally we compared the relative contribution of model parameters towards the classification using a sparse feature-selection approach.ResultsClassification accuracy was 80% or better. Sensitivity and specificity both were 80-85%. Cross validation confirmed robust classifier performance generalizable across the data from the two samples. Patients' relative lack of gain control at high contrasts was the most important information distinguishing patients from controls.ConclusionsIndividuals with idiopathic generalized epilepsy were distinguishable from the neurotypical with a high degree of accuracy and reliability by a reduction in gain control at high contrasts.SignificanceGain control is an essential neural operation that regulates neuronal sensitivity to stimuli and may represent a novel biomarker of hyperexcitability.



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Congenital Zika virus infection: the tropical Asian perspective

Publication date: Available online 18 December 2016
Source:Clinical Neurophysiology
Author(s): Beuy Joob, Viroj Wiwanitkit




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Clinical implication of cervical vestibular evoked myogenic potentials in benign paroxysmal positional vertigo

Publication date: Available online 18 December 2016
Source:Clinical Neurophysiology
Author(s): Mun Young Chang, Ji Ho Shin, Kyung Hyun Oh, Young Ho Hong, Seog-Kyun Mun
ObjectivesTo evaluate the value of cervical vestibular evoked myogenic potential (cVEMP) as a prognostic factor for benign paroxysmal positional vertigo (BPPV).MethodsWe reviewed 65 patients with BPPV who underwent cVEMP. Patients were divided into two groups according to resistance to the repositioning maneuver. Univariable and multivariable analyses were performed with age, gender, affected semicircular canal, affected side and cVEMP parameters to find the associated factors for resistance to the repositioning maneuver.ResultsFrom univariable analysis, cVEMP interaural amplitude difference (IAD) ratio, the affected semicircular canal and the affected side showed a better association (p<0.10) with resistance to the repositioning maneuver. With multivariable analysis, decreased cVEMP IAD ratio at the affected side (⩽-25%) (p=0.043, OR=4.934) and the posterior semicircular canal (p=0.049, OR=3.780) remained as associated factors.ConclusionsDecreased cVEMP IAD ratio at the affected side is associated with resistance to the repositioning maneuver. BPPV patients with decreased cVEMP IAD ratio at the affected side have a higher likelihood of their BPPV persisting after a single repositioning maneuver.SignificancecVEMP test may provide a prognosis of BPPV. A decreased cVEMP IAD ratio at the affected side may be prognostic of BPPV not resolving after a single repositioning maneuver.



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Inhibitory control in euthymic bipolar disorder: event related potentials during a Go/NoGo task

Publication date: Available online 18 December 2016
Source:Clinical Neurophysiology
Author(s): A.M. Morsel, M. Dhar, W. Hulstijn, A. Temmerman, M. Morrens, B. Sabbe
ObjectivesPatients with bipolar disorder (BD) are reported to have difficulties with inhibition, even in a euthymic state. However, the literature on cortical activity associated with response inhibition in BD remains ambiguous. This study investigates inhibition in euthymic BD using electrophysiological measures, while controlling for effects of specific medications.MethodsTwenty patients with BD were compared with eighteen healthy controls on a Go/NoGo task while electroencephalogram was recorded. Behavioral and event-related potential (ERP) measurements were analyzed for the two groups. Medication effects were controlled for in the analysis.ResultsPatients with BD had marginally reduced NoGo N2 amplitudes and increased NoGo P3 amplitudes compared with healthy controls when patients using benzodiazepines were excluded from the study. No behavioural differences between the groups were found.ConclusionsReduced NoGo N2 amplitudes in BD reflect aberrant conflict detection, an early stage of the inhibition process. In addition, increased NoGo P3 amplitudes in BD despite normal task performance reflect an overactive cortical system during a simple inhibition task.SignificanceDifficulties in early stages of inhibition in BD appear to have been compensated by increased cortical activation. This study extends current knowledge regarding cortical activations relating to inhibition in BD.



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Motor Unit Number Index (MUNIX) detects motor neuron loss in pre-symptomatic muscles in Amyotrophic lateral sclerosis

Publication date: Available online 18 December 2016
Source:Clinical Neurophysiology
Author(s): Christoph Neuwirth, Paul E. Barkhaus, Christian Burkhardt, José Castro, David Czell, Mamede de Carvalho, Sanjeev Nandedkar, Erik Stålberg, Markus Weber
ObjectiveMotor Unit Number Index (MUNIX) is a quantitative neurophysiological measure that provides an index of the number of lower motor neurons supplying a muscle. It reflects the loss of motor neurons in patients with Amyotrophic Lateral Sclerosis (ALS). However, it is unclear whether MUNIX also detects motor unit loss in strong, non-wasted muscles.MethodsThree centres measured MUNIX in 49 ALS patients every three months in six different muscles (abductor pollicis brevis, abductor digiti minimi, biceps brachii, tibialis anterior, extensor digitorum brevis, abductor hallucis) on the less affected side. The decline of MUNIX in initially non-wasted, clinically strong muscles (manual muscle testing, MMT grade 5) was analysed before and after onset of weakness.ResultsIn 49 subjects, 151 clinically strong muscles developed weakness and were included for analysis. The average monthly relative loss of MUNIX was 5.0% before and 5.6% after onset of weakness. This rate of change was significantly higher compared to ALS functional rating scale (ALSFRS-R) and compound muscle action potential (CMAP) change over 12 months prior to the onset of muscle weakness (p=0.024).ConclusionMUNIX is an electrophysiological marker that detects lower motor neuron loss in ALS, before clinical weakness becomes apparent by manual muscle testing.SignificanceThis makes MUNIX a good biomarker candidate for disease progression



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Auditory brainstem responses to stop consonants predict literacy

Publication date: Available online 18 December 2016
Source:Clinical Neurophysiology
Author(s): Nicole E. Neef, Gesa Schaadt, Angela D. Friederici
ObjectivePrecise temporal coding of speech plays a pivotal role for sound processing throughout the central auditory system which in turn influences literacy acquisition. The current study tests whether an electrophysiological measure of this precision predicts literacy skills.MethodsComplex auditory brainstem responses were analyzed from 62 native-German speaking children aged 11-13 years. We employed the cross-phaseogram approach to compute the quality of the electrophysiological stimulus contrast [da] and [ba]. Phase shifts were expected to vary with literacy.ResultsReceiver operating curves demonstrated a feasible sensitivity and specificity of the electrophysiological measure. A multiple regression analysis resulted in a significant prediction of literacy by delta cross-phase as well as phonological awareness. A further commonality analysis separated a unique variance explained by the physiological measure from a unique variance explained by the behavioral measure, and common effects of both.ConclusionsDespite multicollinearities between literacy, phonological awareness, and subcortical differentiation of stop consonants, a combined assessment of behavior and physiology strongly increases the ability to predict literacy skills.SignificanceThe strong link between the neurophysiological signature of sound encoding and literacy outcome suggests that the delta cross-phase could indicate the risk of dyslexia and thereby complement subjective psychometric measures for early diagnoses.



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Aberrant temporal behavior of mismatch negativity generators in schizophrenia patients and subjects at clinical high risk for psychosis

Publication date: Available online 18 December 2016
Source:Clinical Neurophysiology
Author(s): Minah Kim, Kang Ik Kevin Cho, Youngwoo Bryan Yoon, Tae Young Lee, Jun Soo Kwon
ObjectiveAlthough disconnection syndrome has been considered a core pathophysiologic mechanism of schizophrenia, little is known about the temporal behavior of mismatch negativity (MMN) generators in individuals with schizophrenia or clinical high risk (CHR) for psychosis.MethodsMMN was assessed in 29 schizophrenia patients, 40 CHR subjects, and 47 healthy controls (HCs). Individual realistic head models and the minimum L2 norm algorithm were used to generate a current source density (CSD) model of MMN. The strength and time course of MMN CSD activity were calculated separately for the frontal and temporal cortices and were compared across brain regions and groups.ResultsSchizophrenia patients and CHR subjects displayed lower MMN CSD strength than HCs in both the temporal and frontal cortices. We found a significant time delay in MMN generator activity in the frontal cortex relative to that in the temporal cortex in HCs. However, the sequential temporo-frontal activities of MMN generators were disrupted in both the schizophrenia and CHR groups.ConclusionsImpairments and altered temporal behavior of MMN multiple generators were observed even in individuals at risk for psychosis.SignificanceThese findings suggest that aberrant MMN generator activity might be helpful in revealing the pathophysiology of schizophrenia.



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Co-occurrence of high-frequency oscillations and delayed responses evoked by intracranial electrical stimulation in stereo-EEG studies

Publication date: Available online 18 December 2016
Source:Clinical Neurophysiology
Author(s): Cristian Donos, Ioana Mîndruţă, Mihai Dragoş Malîia, Alin Raşină, Jean Ciurea, Andrei Barborica
ObjectiveTo perform a side-by-side comparison of two epileptogenicity biomarkers, high frequency oscillations (HFOs) and delayed responses (DRs), as a result of single-pulse electrical stimulation.MethodsWe have recorded stimulation-evoked HFOs and DRs in 16 epileptic patients undergoing presurgical evaluation using the stereoelectroencephalographic method. To evaluate converging and complementary information provided by the biomarkers, we analyzed them individually and for logical "and"/"or" combinations between them. 3D maps of the biomarkers' distributions by recording location (inbound maps) and by stimulation location (outbound maps) were created to analyze their relationship with the epileptogenic structures.ResultsHFOs occur less frequently than DRs, by 18.7%, when counting by recording contacts, and more frequently, by 7.4%, when counting by stimulation contacts. 40.6% of the contacts exhibiting HFOs also exhibit DRs, and 44.1% of the contacts exhibiting DRs also exhibit HFOs. When combining biomarkers, there was a tradeoff between increased seizure onset zone (SOZ) sensitivity, from 21.3% to 73%, and decreased specificity, from 87.2% to 34.3%.ConclusionsThere is a moderate similarity in the information provided by the DRs and HFOs.SignificanceThe biomarkers complement each other, but there is a tradeoff between different metrics for SOZ localization.



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Saccades abnormalities in posterior cortical atrophy - A case report

Publication date: Available online 18 December 2016
Source:Clinical Neurophysiology
Author(s): Yasuo Terao, Fukuda Hideki, Shin-ichi Tokushige, Satomi Inomata-Terada, Masashi Hamada, Yoshikazu Ugawa




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Utility of Deep inspiration breath-hold for left sided breast radiation therapy in preventing early cardiac perfusion defects - A Prospective Study

Publication date: Available online 18 December 2016
Source:International Journal of Radiation Oncology*Biology*Physics
Author(s): Timothy Zagar, Orit Kaidar - Person, Xiaoli Tang, Ellen Jones, Jason Matney, Shiva Das, Rebecca L. Green, Arif Sheikh, Amir H. Khandani, William H. McCartney, Jorge Daniel Oldan, Terence Z. Wong, Lawrence Bruce Marks
PurposeTo evaluate early cardiac single photon computed tomography (SPECT) findings after left breast/chest wall postoperative radiation therapy (RT) in the setting of deep inspiration breath hold (DIBH).MethodsWe performed a prospective single-institution- single arm study of patients who were planned for tangential RT with DIBH to the left breast/chest wall (+/- internal mammary nodes). Deep inspiration breath hold was done utilizing a controlled surface monitoring technique (AlignRT, Vision RT Ltd., London, UK). Radiation therapy was given with tangential fields and a heart block. Radiation-induced cardiac perfusion and wall-motion changes were assessed using pre-RT and 6 month post-RT SPECT scans. A cumulative SPECT summed-rest score (SRS) was used to quantify perfusion in predefined left ventricle segments. The incidence of wall-motion abnormalities was assessed in each of these same segments.ResultsA total of 20 patients with normal pre-RT scans were studied; median age 56 years (range, 39-72). Seven (35%) patients were also irradiated to left internal mammary chain, and 5 (25%) had an additional RT field to supraclavicular nodes. Median heart dose 94cGy (range, 56-200), median V25Gy was zero (range, 0-0.1). None of the patients had post-RT perfusion or wall motion abnormalities.ConclusionsOur results suggest that DIBH and conformal cardiac blocking for patients receiving tangential RT for left-sided breast cancer is an effective means to avoid early RT-associated cardiac perfusion defects.

Teaser

To evaluate radiation induced cardiac toxicity after left breast/chest wall adjuvant radiation in the setting of Vision RT-based deep inspiration breath hold. We performed a prospective single-institution- single arm study. Our results suggest that Vision RT-based deep inspiration breath hold for patients receiving adjuvant tangential radiation for left-sided breast cancer is an effective means to avoid radiation-associated cardiac perfusion and motion defects.


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Nationwide multicenter retrospective study on high-dose-rate brachytherapy as monotherapy for prostate cancer

Publication date: Available online 18 December 2016
Source:International Journal of Radiation Oncology*Biology*Physics
Author(s): Yasuo Yoshioka, Tadayuki Kotsuma, Akira Komiya, Shinji Kariya, Koji Konishi, Norio Nonomura, Kazuhiko Ogawa, Eiichi Tanaka, Kensaku Nishimura, Yasuyoshi Fujiuchi, Hiroshi Kitamura, Takuji Yamagami, Ichiro Yamasaki, Kazuo Nishimura, Teruki Teshima, Katsumasa Nakamura, Jun Itami
PurposeTo present, analyze and discuss results of a nationwide multicenter retrospective study on high-dose-rate brachytherapy (HDR-BT) as monotherapy for low-, intermediate- and high-risk prostate cancer.Methods and materialsFrom 1995 through 2013, 524 patients, 73 (14%) with low-risk, 207 (40%) with intermediate-risk, and 244 (47%) with high-risk prostate cancer, were treated with HDR-BT as monotherapy at 5 institutions in XXXXX. Dose fractionations were 27 Gy/2 fractions for 69 patients (13%), 45.5 Gy/7 fractions for 168 (32%), 49 Gy/7 fractions for 149 (28%), 54 Gy/9 fractions for 130 (25%), and others for 8 (2%). Of these patients, 156 (30%) did not receive androgen deprivation therapy (ADT), 202 patients (39%) did receive ADT <1 year, 112 (21%) for 1-3 years, and 54 (10%) for >3 years. Median follow-up time was 5.9 years (range, 0.4-18.1 years), with a minimum of 2 years for surviving patients.ResultsAfter 5 years, respective actuarial rates of no biochemical evidence of disease (bNED), overall survival (OS), cause-specific survival (CSS), and metastasis-free survival (MFS) for all patients were 92%, 97%, 99%, and 94%. For low/intermediate/high-risk patients, the 5-year bNED rates were 95%/94%/89%, the 5-year OS rates were 98%/98%/94%, the 5-year CSS rates were 98%/100%/98%, and the 5-year MFS rates were 98%/95%/90%, respectively. The cumulative incidence of late Grade 2-3 genitourinary toxicity at 5 years was 19%, and that of late Grade 3 was 1%. The corresponding incidences of gastrointestinal toxicity were 3% and 0% (0.2%). No Grade 4 or 5 of either type of toxicity was detected.ConclusionsThe findings of this nationwide multicenter retrospective study demonstrate that HDR-BT as monotherapy was safe and effective for all patients with low-, intermediate- and high-risk prostate cancer.

Teaser

A nationwide multicenter retrospective study on high-dose-rate brachytherapy (HDR-BT) as monotherapy for prostate cancer was conducted. A total of 524 patients was treated at 5 institutions in Japan. Median follow-up time was 5.9 years. For low/intermediate/high-risk patients, 5-year rates for no biochemical evidence of disease were 95%/94%/89%, respectively. Late Grade 3 genitourinary/gastrointestinal toxicity rate was 1%/0.2% at 5 years. This study thus demonstrated that HDR-BT monotherapy was safe and effective for patients with prostate cancer.


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Single nucleotide polymorphism TGFβ1 R25P correlates with acute toxicity during neoadjuvant chemoradiotherapy in rectal cancer patients

Publication date: Available online 18 December 2016
Source:International Journal of Radiation Oncology*Biology*Physics
Author(s): J. Joshua Smith, Isaac Wasserman, Sarah A. Milgrom, Oliver S. Chow, Chin-Tung Chen, Sujata Patil, Karyn A. Goodman, Julio Garcia-Aguilar
Purpose/Objective: Our group and others have identified an association between single nucleotide polymorphisms (SNPs) and toxicity during chemoradiotherapy (CRT) in rectal cancer patients. This study aimed to validate these findings in an independent population.Methods and MaterialsThe cohort consisted of 165 patients who received CRT for rectal cancer from 2006 to 2012. Prospectively recorded toxicity information, graded according to the Common Terminology Criteria for Adverse Events (CTCAE) version 3.0, was retrieved from the medical record. Additionally, a subset of 52 patients recorded their gastrointestinal symptoms weekly during CRT, using the 7-item Bowel Problems Scale. DNA was extracted from normal tissue in the proctectomy specimens and screened for 3 SNPs: XRCC1 R399Q, XPD K751Q, and TGFβ1 R25P. Univariable and multivariable logistic regression models were constructed.ResultsThe median radiation dose was 50.4 Gy, and all patients received concurrent chemotherapy. Toxicities measured by CTCAE were closely associated with patients reported outcomes for the patients who completed the 7-item Bowel Problems Scale. Grade ≥ 3 toxicity occurred during CRT in 14 patients (8%). All 14 patients had either XRCC1 R399Q or TGFβ1 R25P polymorphisms. The TGFβ1 R25P polymorphism was significantly associated with grade ≥3 toxicity (OR 3.47, p = 0.04) and, in patients who completed the Bowel Problems Scale, with grade ≥4 toxicity (OR 5.61, p = 0.02). The latter finding persisted in a multivariable logistic regression model controlling for ethnicity, age, and gender (adjusted OR 1.83, p = 0.02).ConclusionsWe have validated the correlation between the TGFβ1 R25P SNP and acute toxicity during CRT in an independent cohort using both clinician- and patient-reported toxicity. The information from our study could be used as a basis to formulate a prospective trial testing its utility as a biomarker of acute toxicity during neoadjuvant treatment in locally advanced rectal cancer.

Teaser

Our group and others have identified an association between single nucleotide polymorphisms and acute toxicity in patients receiving neoadjuvant chemoradiotherapy for rectal cancer. The current study validated these correlations in an independent cohort of 165 patients.


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Low dose radiotherapy for benign painful skeletal disorders –The typical treatment for the elderly patient?

Publication date: Available online 18 December 2016
Source:International Journal of Radiation Oncology*Biology*Physics
Author(s): Oliver Micke, M. Heinrich Seegenschmiedt, Irenaeus A. Adamietz, Guenter Kundt, Khashayar Fakhrian, Ulrich Schaefer, Ralph Muecke
PurposeThe aim of this prospective analysis was to evaluate the short-term and long-term efficacy of low dose radiotherapy (RT) for calcaneodynia, achillodynia, painful gonarthrosis, and painful bursitis trochanterica in eldely patients with an age of => 70 years.MethodsBetween October 2011 and October 2013, patients with an age of => 70 years with painful degenerative disorders of joints were recruited for a prospective trial. Single doses of 0.5 - 1.0 Gy and a total dose of 6.0 Gy per series were used. Pain was measured before and right after RT (early response) with a 10 scale visual analogue scale (VAS. Additionally, pain relief was measured with the four-scale pain score according to "von Pannewitz" (VPS) immediately on completion of RT and during follow-up. We defined a good response as complete pain relief and markedly improved.Results166 evaluable patients with a mean age of 76.6 years (70-90) with calcaneodynia (n=51), achillodynia (n=8), painful gonarthrosis (n=80), and painful bursitis trochanterica (n=27) were recruited. The mean VAS value before treatment was 6.38 and immediately on completion of RT 4.49(p<0.001). Concerning the VPS immediately on completion of RT, 6 patients were free of pain, 56 were much improved, 47 reported slight improvement, and 57 experienced no change. After a median follow-up of 29 months, 109 patients could be reached for evaluation of follow up results.33 patients were free of pain, 21 had marked improvement, 18 had some improvement, and 37 experienced no change. Therefore, a good response immediately on completion of RT could be achieved in 62/166 patients, and with the follow up in 54/109 patients(p=0.001).ConclusionsLow dose RT is a very effective treatment for the management of painful degenerative disorders of joints in the elderly. Low dose radiotherapy offers a low-risk, genuinely conservative, non-invasive therapeutic alternative for elderly patients.

Teaser

Low dose RT is a very effective treatment for the management of painful degenerative skeletal disorders in the elderly. Due to the delayed onset of analgesic effects low dose RT results in a significantly improved long-term efficacy in comparison to the results immediately after RT. In view of the ageing population and the corresponding increase in painful degenerative disorders of joints, low dose radiotherapy offers a low-risk, genuinely conservative, non-invasive therapeutic alternative for elderly patients.


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A Comparison between Low Dose-Rate Brachytherapy +/- Androgen Deprivation, External Beam Radiotherapy +/- Androgen Deprivation, and Radical Prostatectomy +/- Adjuvant or Salvage Radiotherapy for High-Risk Prostate Cancer

Publication date: Available online 18 December 2016
Source:International Journal of Radiation Oncology*Biology*Physics
Author(s): Jay P. Ciezki, Michael Weller, Chandana A. Reddy, Jeffrey Kittel, Harguneet Singh, Rahul Tendulkar, Kevin L. Stephans, James Ulchaker, Kenneth Angermeier, Andrew Stephenson, Steven Campbell, Georges-Pascal Haber, Eric A. Klein
PurposeWe compare the efficacy and toxicity among the three major modalities available used to treat high-risk prostate cancer (HRCaP).Methods and MaterialsFrom 1996-2012, 2557 HRCaP patients were treated: 734 external beam radiation (EBRT) +/- androgen deprivation therapy (ADT), 515 low-dose-rate prostate brachytherapy (LDR) +/- ADT, and 1308 radical prostatectomy (RP) +/- EBRT. Biochemical relapse-free survival (bRFS), clinical relapse-free survival (cRFS), and prostate cancer-specific mortality (PCSM) were assessed. Toxicity was assessed using the Common Terminology Criteria for Adverse Events, version 4.03 (CTCAE v4.03). The log-rank test compared bRFS and cRFS among the modalities, and Cox regression identified factors associated with bRFS and cRFS. Gray's test compared differences in late toxicity and PSCM among the modalities. Competing risk regression identified factors associated with PCSM.ResultsThe median follow-up and age were 63.5 months and 65 years, respectively. The bRFS at 5 and 10 years, respectively, was 74% and 53% for EBRT, 74% and 52% for LDR, and 65% and 47% for RP (p=0.0001). The cRFS at 5 and 10 years, respectively, was 85% and 73% for EBRT, 90% and 76% for LDR, and 89% and 75% for RP (p=0.121). The PCSM at 5 and 10 years, respectively, was 5.3% and 11.2% for EBRT, 3.2% and 3.6% for LDR, and 2.8% and 6.8% for RP (p=0.0004). The 10-year cumulative incidence of > grade 3 genitourinary toxicity was 8.1% for EBRT, 7.2% for LDR, and 16.4% for RP (p<0.0001). The 10-year cumulative incidence of > grade 3 gastrointestinal toxicity was 4.6% for EBRT, 1.1% for LDR, 1.0% for RP (p<0.0001).ConclusionHRCaP treated with EBRT, LDR, or RP yields efficacy showing better bRFS for LDR and EBRT relative to RP, equivalence for cRFS, and a PCSM advantage of LDR and RP over EBRT. The toxicity is lowest for LDR.

Teaser

There is no level I evidence defining a standard of care for patients with high-risk prostate cancer. Clinical trials comparing treatment variations within a modality exist but none compare outcomes among modalities. We present an inception cohort study in which we compare efficacy and toxicity among the three major therapeutic modalities for high-risk prostate cancer: radical prostatectomy plus/minus adjuvant or salvage radiotherapy, external beam radiotherapy plus/minus androgen deprivation, and low-dose-rate prostate brachytherapy plus/minus androgen deprivation therapy.


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