bluuebunny/crossref_metadata_2025 huggingface dataset:
Does Computed Tomography–Based Muscle Density Predict Muscle Function and Health‐Related Quality of Life in Patients With Idiopathic Inflammatory Myopathies?
Authors: Cleary Laura C. , Crofford Leslie J. , Long Douglas , Charnigo Richard , Clasey Jody , Beaman Francesca , Jenkins Kirk A. , Fraser Natasha , Srinivas Archana , Dhaon Nicole , Hanaoka Beatriz Y.
Published: January 2015

Objective

To investigate the association of low‐density (lipid‐rich) muscle measured by computed tomography (CT) with skeletal muscle function and health‐related quality of life in idiopathic inflammatory myopathies (IIMs).

Methods

Seventeen patients and 10 healthy controls underwent CT of the midthigh to quantify high‐ (30–100 HU) and low‐density (0–29 HU) skeletal muscle areas. Anthropometric measures, body composition, physical activity level, health‐related quality of life, skeletal muscle strength, endurance, and fatigue were assessed. Patients were compared against controls. The relationship of anthropometric, body composition, and disease variables with measures of muscle function were examined using Spearman's test on the patient group. Linear regression was used to assess the age‐ and disease‐adjusted relationship of muscle quality to physical function and muscle strength.

Results

Patients had higher body fat percentage (P = 0.042), trunk fat mass (P = 0.042), android:gynoid fat (P = 0.033), and midthigh low‐density muscle/total muscle area (P < 0.001) compared to controls. Midthigh low‐density muscle/total muscle area was negatively correlated with self‐reported physical function, strength, and endurance (the Short Form 36 [SF‐36] health survey physical functioning [P = 0.004], manual muscle testing [P = 0.020], knee maximal voluntary isometric contraction/thigh mineral‐free lean mass [P < 0.001], and the endurance step test [P < 0.001]), suggesting that muscle quality impacts function in IIM. Using multiple linear regression adjusted for age, global disease damage, and total fat mass, poor muscle quality as measured by midthigh low‐density muscle/total muscle area was negatively associated with SF‐36 physical functioning (P = 0.009).

Conclusion

Midthigh low‐density muscle/total muscle area is a good predictor of muscle strength, endurance, and health‐related quality of life as it pertains to physical functioning in patients with IIMs.
Influence of Biomechanical Characteristics on Pain and Function Outcomes From Exercise in Medial Knee Osteoarthritis and Varus Malalignment: Exploratory Analyses From a Randomized Controlled Trial
Authors: Bennell Kim L. , Dobson Fiona , Roos Ewa M. , Skou Søren T. , Hodges Paul , Wrigley Tim V. , Kyriakides Mary , Metcalf Ben , Hunt Michael A. , Hinman Rana S.
Published: January 2015

Objective

To investigate whether selected biomechanical characteristics influence changes in pain and physical function with exercise in people with medial knee osteoarthritis (OA) and varus malalignment.

Methods

We conducted post hoc exploratory analyses from a randomized controlled trial involving 100 people with medial knee OA and varus malalignment who were randomly allocated to one of two 12‐week exercise programs (quadriceps strengthening [QS] or neuromuscular exercise [NEXA]). The outcome measures were change in overall average knee pain (visual analog scale) and self‐reported physical function (Western Ontario and McMaster Universities Osteoarthritis Index). Candidate biomechanical characteristics measured at baseline were visually observed varus thrust during walking, obesity (determined by body mass index), static varus alignment, and isometric quadriceps strength. Data were analyzed with separate two‐way analyses of covariance using the interaction term of exercise group by biomechanical characteristic.

Results

Ninety‐two participants were analyzed for each characteristic except varus thrust, for which 85 participants were included. For change in pain, there was a significant interaction effect between type of exercise and both varus thrust (P = 0.001) and obesity (P = 0.023). NEXA was more effective for nonobese participants (mean change 29.5 mm [95% confidence interval (95% CI) 20.5, 38.5]) and for those with varus thrust (mean change 28.7 mm [95% CI 19.4, 38.1]), whereas QS was more effective for obese people (mean change 24.7 mm [95% CI 14.9, 34.4]) and for those without varus thrust (mean change 29.4 mm [95% CI 21.2, 37.7]). Biomechanical characteristics did not influence the effect of exercise on physical function (P > 0.05).

Conclusion

These preliminary findings suggest that varus thrust and obesity influence the pain‐relieving effects of 2 different types of exercise. Further research is needed to confirm whether or not exercise that is prescribed according to specific biomechanical characteristics optimizes knee OA outcomes.
Effect of Aerobic Exercise Training on Fatigue in Rheumatoid Arthritis: A Meta‐Analysis
Authors: Rongen‐van Dartel S. A. A. , Repping‐Wuts H. , Flendrie M. , Bleijenberg G. , Metsios G. S. , van den Hout W. B. , van den Ende C. H. M. , Neuberger G. , Reid A. , van Riel P. L. C. M. , Fransen J.
Published: January 2015

Objective

Rheumatoid arthritis (RA) fatigue is not being well‐managed currently, and evidence of effective interventions is limited. Aerobic exercise may provide benefit to treat fatigue in RA. Therefore, the purpose of this meta‐analysis is to analyze the effect of aerobic land‐based exercise on fatigue in RA.

Methods

A literature search was conducted using PubMed, Cochrane Library, Embase, and trial registers to identify randomized controlled trials (RCTs) with a supervised land‐based aerobic exercise program performed with an intensity between 50% and 90% of maximal heart rate, of at least 15 minutes' duration, performed at least 2 times a week, and lasting for a time period of at least 4 consecutive weeks. Risk of bias was assessed using the Cochrane tool. A meta‐analysis of fatigue outcomes was performed by calculating the standardized mean difference (SMD) using a random‐effects model.

Results

Five RCTs were included. None of the trials selected patients with RA for having fatigue. Risk of bias was low in 3 RCTs and unclear in 2. Land‐based aerobic exercise programs had a positive effect on fatigue in RA compared to no exercise at 12 weeks, SMD −0.31 (95% confidence interval [95% CI] −0.55, −0.06). At 24 weeks, the effect of aerobic land‐based exercise was smaller and not statistically significant: SMD −0.15 (95% CI −0.33, 0.02).

Conclusion

There is evidence with low risk of bias that an aerobic exercise program is effective in reducing fatigue among patients with RA, especially in the short term; however, effects are small. To substantiate the evidence, RCTs should be performed in patients with RA selected for having fatigue.
Racial and Ethnic Differences in Mortality and Cardiovascular Events Among Patients With End‐Stage Renal Disease Due to Lupus Nephritis
Authors: Gómez‐Puerta Jose A. , Feldman Candace H. , Alarcón Graciela S. , Guan Hongshu , Winkelmayer Wolfgang C. , Costenbader Karen H.
Published: January 2015

Objective

To identify racial and ethnic differences in mortality and cardiovascular (CV) risk among patients with end‐stage renal disease (ESRD) due to lupus nephritis (LN).

Methods

Within the US ESRD registry (1995–2008), we identified individuals ages >17 years with incident ESRD due to systemic lupus erythematosus. We ascertained demographics, clinical factors, and deaths from registry patient files and CV events (myocardial infarction, heart failure, and hemorrhagic and ischemic strokes) from inpatient Medicare claims. We calculated incidence rates (95% confidence intervals [95% CIs]) per 1,000 person‐years for study events, stratified by race and ethnicity. We compared probabilities of the events among racial and ethnic groups using cumulative incidence function curves and multivariable‐adjusted subdistribution proportional hazard ratios (HRsd), taking into account the competing events of kidney transplantation and death (for nonfatal CV events).

Results

Of 12,533 patients with LN‐associated ESRD, the mean ± SD age was 40.7 ± 14.9 years, 82% were women, and 49% were African American. The overall mortality rate was 98.1/1,000 person‐years (95% CI 95.3–100.9). In multivariable models, Asian and Hispanic LN‐associated ESRD patients had lower mortality than whites (HRsd 0.70 [95% CI 0.58–0.84] and 0.79 [95% CI 0.71–0.88], respectively), whereas African Americans had higher mortality (HRsd 1.27 [95% CI 1.18–1.36]). African American patients >40 years old had higher mortality than their white counterparts (HRsd 1.67 [95% CI 1.44–1.93]). African Americans were more likely to be admitted for heart failure or hemorrhagic stroke.

Conclusion

Among patients with LN‐associated ESRD, Asians and Hispanics experienced lower mortality and CV event risks than whites, and African Americans had higher mortality and CV event risks than whites.
Perforation of a nasoseptal flap does not increase the rate of postoperative cerebrospinal fluid leak
Authors: Huntley Colin , Iloreta Alfred Marc Calo , Nyquist Gurston G. , Otten Marc , Garcia Hermes , Farrell Christopher , Rosen Marc R. , Evans James J.
Published: January 2015

Background

The nasoseptal flap (NSF) has been shown to be a valuable addition to the reconstructive armamentarium of the endoscopic skull‐base surgeon. We aimed to evaluate the rate of postoperative cerebrospinal fluid (CSF) leak after use of a NSF that had a small tear during harvest.

Methods

After Institutional Review Board (IRB) approval, we analyzed our database of patients undergoing skull‐base resection. We included all patients who had a NSF reconstruction, septoplasty, and/or spur on preoperative computed tomography (CT) imaging. We then evaluated video of each procedure to determine if a tear occurred in the NSF during harvest. Patient records were reviewed to determine if a postoperative CSF leak occurred.

Results

We evaluated video of 21 patients who underwent a skull‐base resection, were reconstructed with a NSF, and had either a septoplasty or evidence of a septal spur on CT imaging. Of these 21 cases, 11 small tears occurred during harvest of the NSF flap and none of the patients with a torn NSF had a postoperative CSF leak.

Conclusion

Our series shows a 0% postoperative CSF leak rate in patients undergoing skull‐base reconstruction with a NSF that was torn during harvest. Small tears in the NSF do not seem to affect postoperative CSF leak rates.
The impact of sinus surgery on sleep outcomes
Authors: Rotenberg Brian W. , Pang Kenny P.
Published: January 2015

Background

Functional endoscopic sinus surgery (FESS) is standard for patients who fail medical management of chronic sinusitis (CRS). The beneficial impact of surgery on CRS is well known. However, patients often note that their sleep is improved after FESS even without simultaneous correction of nasal obstruction. Sleep outcomes after FESS are significantly understudied. Hence in the current study we look to characterize patient sleep quality following sinus surgery.

Methods

Data was gathered from 2 sites (Western University [Canada] and the Asia Sleep Center [Singapore]). Patients meeting diagnostic criteria for CRS without nasal polyposis (CRSsNP) were included. Cases with polyposis and those who needed a septoplasty were excluded so as to purely analyze the impact of the sinus surgery on sleep. Sleep outcomes recorded at baseline just prior to surgery and 6 months after surgery were the Epworth Sleepiness Scale (EpSS) and the Pittsburgh Sleep Quality Index (PSQI). We also recorded 22‐item Sino‐Nasal Outcome Test (SNOT‐22) scores and Nasal Obstruction Symptom Evaluation (NOSE) scores. Comparisons were made with paired t tests.

Results

Fifty‐three patients met inclusion/exclusion criteria. Sleep outcomes showed a clinically and statistically significant improvement (EpSS before FESS = 14.7 ± 3.1, EpSS after FESS = 9.1 ± 1.1, p < 0.01; PSQI before FESS = 10.9 ± 2.8, PSQI after FESS = 5.3 ± 2.2, p < 0.01). CRS‐specific outcomes were improved as well. Nasal obstruction scores did not change significantly.

Conclusion

FESS improved sleep outcomes for the patients in our study. This was independent of correction of nasal obstruction. Sinus surgery for CRSsNP has a beneficial impact on sleep; this novel information can be used during patient counseling and for justification to third‐party payers.
The Somatosensory Link in Fibromyalgia: Functional Connectivity of the Primary Somatosensory Cortex Is Altered by Sustained Pain and Is Associated With Clinical/Autonomic Dysfunction
Authors: Kim Jieun , Loggia Marco L. , Cahalan Christine M. , Harris Richard E. , Beissner Florian , Garcia Ronald G. , Kim Hyungjun , Barbieri Riccardo , Wasan Ajay D. , Edwards Robert R. , Napadow Vitaly
Published: January 2015

Objective

Fibromyalgia (FM) is a chronic functional pain syndrome characterized by widespread pain, significant pain catastrophizing, sympathovagal dysfunction, and amplified temporal summation for evoked pain. While several studies have demonstrated altered resting brain connectivity in FM, studies have not specifically probed the somatosensory system and its role in both somatic and nonsomatic FM symptoms. Our objective was to evaluate resting primary somatosensory cortex (S1) connectivity and to explore how sustained, evoked deep tissue pain modulates this connectivity.

Methods

We acquired functional magnetic resonance imaging and electrocardiography data on FM patients and healthy controls during rest (the rest phase) and during sustained mechanical pressure–induced pain over the lower leg (the pain phase). Functional connectivity associated with different S1 subregions was calculated, while S1leg connectivity (representation of the leg in the primary somatosensory cortex) was contrasted between the rest phase and the pain phase and was correlated with clinically relevant measures in FM.

Results

During the rest phase, FM patients showed decreased connectivity between multiple ipsilateral and cross‐hemispheric S1 subregions, which was correlated with clinical pain severity. Compared to the rest phase, the pain phase produced increased S1leg connectivity to the bilateral anterior insula in FM patients, but not in healthy controls. Moreover, in FM patients, sustained pain–altered S1leg connectivity to the anterior insula was correlated with clinical/behavioral pain measures and autonomic responses.

Conclusion

Our study demonstrates that both somatic and nonsomatic dysfunction in FM, including clinical pain, pain catastrophizing, autonomic dysfunction, and amplified temporal summation, are closely linked with the degree to which evoked deep tissue pain alters S1 connectivity to salience/affective pain‐processing regions. Additionally, diminished connectivity between S1 subregions during the rest phase in FM may result from ongoing widespread clinical pain.
Predominant Glandular Cholinergic Dysautonomia in Patients With Primary Sjögren's Syndrome
Authors: Imrich Richard , Alevizos Ilias , Bebris Lolita , Goldstein David S. , Holmes Courtney S. , Illei Gabor G. , Nikolov Nikolay P.
Published: January 2015

Objective

The autonomic nervous system (ANS) modulates exocrine gland function. Available data show poor correlation between the degree of function and destruction of the exocrine glands in primary Sjögren's syndrome (SS), suggesting that other mechanisms, such as autonomic dysfunction, may be important in these patients. The aim of this study was to perform a comprehensive analysis of sympathoneural and sympathetic cholinergic function in well‐characterized patients with primary SS.

Methods

Twenty‐one patients with primary SS (mean ± SEM age 44.2 ± 2.8 years) and 13 healthy control subjects (mean ± SEM age 50.8 ± 1.9 years) were assessed during orthostasis and intravenous injection of edrophonium (10 mg). The postganglionic sympathetic cholinergic system was evaluated by assessing sweat production by means of the Quantitative Sudomotor Axon Reflex Test (QSART). Tests of gastric emptying were used to assess the gastrointestinal ANS in primary SS patients.

Results

The velocity index and the acceleration index were significantly higher (P < 0.05) in patients with primary SS as compared to controls, both before and during the orthostatic and edrophonium tests. Findings of other hemodynamic and neurochemical parameters did not differ between primary SS patients and controls during the orthostasis and edrophonium test; however, the edrophonium‐induced saliva increment was lower in primary SS patients (P = 0.002). Abnormally low sweat production was found in 4 primary SS patients but in none of the controls, as determined by the QSART. Gastric emptying was delayed in 53% of primary SS patients.

Conclusion

We observed subtle differences in several ANS domains, including the gastrointestinal and sympathocholinergic systems, suggesting the presence of a complex ANS dysfunction in primary SS. The impact was greatest on the exocrine glands, with subtle differences in the cardiac parasympathetic function that were independent of glandular inflammation and atrophy, suggesting an alternative mechanism of disease pathogenesis in primary SS.
Cognitive–Behavioral Therapy for Insomnia in Knee Osteoarthritis: A Randomized, Double‐Blind, Active Placebo–Controlled Clinical Trial
Authors: Smith Michael T. , Finan Patrick H. , Buenaver Luis F. , Robinson Mercedes , Haque Uzma , Quain Angela , McInrue Erin , Han Dingfen , Leoutsakis Jeannie , Haythornthwaite Jennifer A.
Published: January 2015

Objective

Insomnia is prevalent among patients with knee osteoarthritis (OA). Research indicates that sleep disruption may amplify clinical pain by altering central pain modulation, suggesting that treatment of insomnia may improve pain. The aims of this study were to evaluate the efficacy of cognitive–behavioral therapy for insomnia (CBT‐I) in patients with knee OA, to determine whether improvements in sleep predict reduced pain, and to determine whether alterations in pain modulation mediate improvements in clinical pain.

Methods

We conducted a randomized, double‐blind, active placebo–controlled clinical trial of CBT‐I in 100 patients with knee OA and insomnia (mean ± SD age 59.4 ± 9.5 years). Patients were randomized (1:1) to receive either 8 sessions of CBT‐I or behavioral desensitization (placebo). We conducted in‐home polysomnography (PSG), diary assessment, and sensory tests of pain modulation at baseline, posttreatment, 3 months, and 6 months.

Results

Intent‐to‐treat analyses demonstrated substantial improvement in sleep in both groups of patients. Patients in the CBT‐I group had significantly greater reductions in wake after sleep onset (WASO), as measured by patient diary and PSG. Patients in both groups reported significant and comparable reductions in pain over 6 months, with one‐third reporting a 30% reduction in pain severity. Baseline‐to‐posttreatment reductions in WASO as measured by diary and PSG predicted subsequent decreases in clinical pain. This effect was significantly greater for CBT‐I compared with behavioral desensitization. No significant changes in laboratory measures of pain modulation were observed.

Conclusion

Compared with active placebo, CBT‐I was efficacious in reducing sleep maintenance insomnia. CBT‐I decreased clinical pain, but not pain modulation, suggesting that it has the potential to augment pain management in knee OA. Future work is needed to identify the mechanisms by which improved sleep reduces clinical pain.
Adaptive Tracking Control for Nonlinear Systems with a Class of Input Nonlinearities
Authors: Liu Zongcheng , Dong Xinmin , Xue Jianping , Zhang Lipeng
Published: January 2015

An adaptive tracking control approach is presented for nonlinear systems with a class of input nonlinearities. A generalized model has been developed for a class of non‐smooth nonlinearities that include dead‐zone, backlash and ‘backlash‐like’ hysteresis. By using the developed model and Nussbaum‐gain technique, the problem of input nonlinearity is solved perfectly. The proposed method is available even when the designer is uncertain about the type of input nonlinearities mentioned above, and the knowledge on the bounds of these nonlinearity parameters is not required. Furthermore, it is proved that all closed‐loop signals are bounded and the tracking error converges to a small residual set asymptotically. Two simulation examples are provided to demonstrate the effectiveness of the proposed method.
Control of Discrete‐Time Systems Composed of Linear Blocks in Series with Saturation Components
Authors: Ghani D. , Giri F. , Chater E. , Chaoui F. Z. , Haloua M.
Published: January 2015

We consider the problem of controlling cascade systems consisting of two linear dynamic blocks and two saturation elements arranged according to the N‐L‐N‐L series configuration. A cascade controller is considered and its performances are formally analyzed using input–output stability tools. In addition to global boundedness of all signals of the closed‐loop system, the controller is formally shown to enjoy a l2 ‐tracking performance in presence of arbitrary‐shape inputs (i.e. reference signal, disturbance).
Eye Movements in Risky Choice
Authors: Stewart Neil , Hermens Frouke , Matthews William J.
Published: January 2015

We asked participants to make simple risky choices while we recorded their eye movements. We built a complete statistical model of the eye movements and found very little systematic variation in eye movements over the time course of a choice or across the different choices. The only exceptions were finding more (of the same) eye movements when choice options were similar, and an emerging gaze bias in which people looked more at the gamble they ultimately chose. These findings are inconsistent with prospect theory, the priority heuristic, or decision field theory. However, the eye movements made during a choice have a large relationship with the final choice, and this is mostly independent from the contribution of the actual attribute values in the choice options. That is, eye movements tell us not just about the processing of attribute values but also are independently associated with choice. The pattern is simple—people choose the gamble they look at more often, independently of the actual numbers they see—and this pattern is simpler than predicted by decision field theory, decision by sampling, and the parallel constraint satisfaction model. © 2015 The Authors. Journal of Behavioral Decision Making published by John Wiley & Sons Ltd.
A case study using the PrOACT‐URL and BRAT frameworks for structured benefit risk assessment
Authors: Nixon Richard , Dierig Christoph , Mt‐Isa Shahrul , Stöckert Isabelle , Tong Thaison , Kuhls Silvia , Hodgson Gemma , Pears John , Waddingham Ed , Hockley Kimberley , Thomson Andrew
Published: January 2015

While benefit‐risk assessment is a key component of the drug development and maintenance process, it is often described in a narrative. In contrast, structured benefit‐risk assessment builds on established ideas from decision analysis and comprises a qualitative framework and quantitative methodology. We compare two such frameworks, applying multi‐criteria decision‐analysis (MCDA) within the PrOACT‐URL framework and weighted net clinical benefit (wNCB), within the BRAT framework. These are applied to a case study of natalizumab for the treatment of relapsing remitting multiple sclerosis. We focus on the practical considerations of applying these methods and give recommendations for visual presentation of results. In the case study, we found structured benefit‐risk analysis to be a useful tool for structuring, quantifying, and communicating the relative benefit and safety profiles of drugs in a transparent, rational and consistent way. The two frameworks were similar. MCDA is a generic and flexible methodology that can be used to perform a structured benefit‐risk in any common context. wNCB is a special case of MCDA and is shown to be equivalent to an extension of the number needed to treat (NNT) principle. It is simpler to apply and understand than MCDA and can be applied when all outcomes are measured on a binary scale.
Spectrophotometric and spectrofluorimetric determination of indacaterol maleate in pure form and pharmaceutical preparations: application to content uniformity
Authors: El‐Ashry S. M. , El‐Wasseef D. R. , El‐Sherbiny D. T. , Salem Y. A.
Published: January 2015

Two simple, rapid, sensitive and precise spectrophotometric and spectrofluorimetric methods were developed for the determination of indacaterol maleate in bulk powder and capsules. Both methods were based on the direct measurement of the drug in methanol. In the spectrophotometric merthod (Method I) the absorbance was measured at 259 nm. The absorbance‐concentration plot was rectilinear over the range 1.0–10.0 µg mL−1 with a lower detection limit (LOD) of 0.078 µg mL−1 and lower quantification limit (LOQ) of 0.238 µg mL−1. Meanwhile in the spectrofluorimetric method (Method II) the native fluorescence was measured at 358 nm after excitation at 258 nm. The fluorescence‐concentration plot was rectilinear over the range of 1.0–40.0 ng mL−1 with an LOD of 0.075 ng mL−1and an LOQ of 0.226 ng mL−1. The proposed methods were successfully applied to the determination of indacaterol maleate in capsules with average percent recoveries ± RSD% of 99.94 ± 0.96 for Method I and 99.97 ± 0.81 for Method II. In addition, the proposed methods were extended to a content uniformity test according to the United States Pharmacopoeia (USP) guidelines and were accurate, precise for the capsules studied with acceptance value 3.98 for Method I and 2.616 for Method II. Copyright © 2015 John Wiley & Sons, Ltd.
Oncological outcome following anastomotic leak in rectal surgery
Authors: Espín E , Ciga M A , Pera M , Ortiz H , Lujan J , Fraccalvieri D , Biondo S , Ciga M A , Espí A , Codina A , Ruiz M D , Espin E , Vallribera F , Palasí R , Parajo A , Camps I , Piñol M , Viciano V , Alonso E , Pera M , García T , Casal E , Garcia J , Rodríguez M , Reina Á , Roig J , Errasti J , Múgica J A , Gomez J , Rada R , Orelogio M
Published: January 2015

Background

The influence of anastomotic leak on local recurrence and survival remains debated in rectal cancer.

Methods

This was a multicentre observational study using data from the Spanish Rectal Cancer Project database. Demographics, American Society of Anesthesiologists classification, tumour location, stage, use of defunctioning stoma, administration of neoadjuvant and adjuvant treatment, invasion of circumferential resection margin, quality of mesorectal excision and anastomotic leakage were recorded. Anastomotic leak was defined as an anastomotic event requiring surgical intervention or interventional radiology, including pelvic abscesses without radiological evidence of leakage and early rectovaginal fistulas. Variables associated with oncological outcome were assessed by multivariable Cox regression analysis.

Results

A total of 1181 consecutive patients were included. Rates of anastomotic leak and 30-day postoperative mortality were 9·4 and 2·4 per cent respectively. Data from 1153 patients were analysed after a median follow-up of 5 years. Cumulative rates of local recurrence, overall recurrence, overall survival and cancer-specific survival were 4·9, 19·4, 77·5 and 84·7 per cent respectively. In the multivariable regression analysis, anastomotic leakage was not associated with local recurrence (hazard ratio (HR) 0·80, 95 per cent c.i. 0·28 to 2·26; P = 0·669), overall recurrence (HR 1·14, 0·70 to 1·85; P = 0·606), overall survival (HR 1·10, 0·73 to 1·65; P = 0·648) or cancer-specific survival (HR 1·23, 0·75 to 2·02; P = 0·421).

Conclusion

Anastomotic leak after low anterior resection did not affect oncological outcomes in these patients.
Simultaneous determination of senkyunolide I and senkyunolide H in rat plasma by LC‐MS: application to a comparative pharmacokinetic study in normal and migrainous rats after oral administration of Chuanxiong Rhizoma extract
Authors: Zhao Xu , Ma Tiancheng , Zhang Chenning , Shi Shaohuai , Cui Sijiao , Bi Kaishun , Jia Ying
Published: January 2015

A selective liquid chromatographic–mass spectrometric method has been developed and validated for simultaneous determination of senkyunolide I (SEI) and senkyunolide H (SEH) from Chuanxiong Rhizoma in rat plasma. Plasma samples were extracted by liquid–liquid extraction with ethyl acetate and separated on a Kromasil C18 column (250 × 4.6 mm, 5 µm), with methanol–water (55:45, v/v) as mobile phase. The linear range was 0.05–25 µg/mL for SEI and 0.01–5.0 µg/mL for SEH, with lower limits of quantitation of 0.05 and 0.01 µg/mL, respectively. Intra‐ and inter‐day precision were within 10.0 and 9.8%, and the accuracies (relative errors) were <9.6 and 5.9%, with the mean extraction recoveries 81.0–86.6 and 80.5–85.0% for the two anayltes, respectively. The validated method was successfully applied to a comparative pharmacokinetic study of SEI and SEH in normal and migrainous rats after oral administration of Chuanxiong Rhizoma extract. The results indicated that there were obvious differences between normal and migrainous rats in the pharmacokinetic behavior after oral administration of Chuanxiong Rhizoma extract. The absorption of SEI and SEH were significantly increased in migrainous rats compared with normal rats. Copyright © 2015 John Wiley & Sons, Ltd.
Epigenetic changes in the CDKN2A locus are associated with differential expression of P16INK4A and P14ARF in HPV‐positive oropharyngeal squamous cell carcinoma
Authors: Schlecht Nicolas F. , Ben‐Dayan Miriam , Anayannis Nicole , Lleras Roberto A. , Thomas Carlos , Wang Yanhua , Smith Richard V. , Burk Robert D. , Harris Thomas M. , Childs Geoffrey , Ow Thomas J. , Prystowsky Michael B. , Belbin Thomas J.
Published: January 2015

Human papillomavirus (HPV)‐positive oropharyngeal squamous cell carcinoma (OPSCC) is recognized as a distinct disease entity associated with improved survival. DNA hypermethylation profiles differ significantly by HPV status suggesting that a specific subset of methylated CpG loci could give mechanistic insight into HPV‐driven OPSCC. We analyzed genome‐wide DNA methylation of primary tumor samples and adjacent normal mucosa from 46 OPSCC patients undergoing treatment at Montefiore Medical Center, Bronx, NY using the Illumina HumanMethylation27 beadchip. For each matched tissue set, we measured differentially methylated CpG loci using a change in methylation level (M value). From these analyses, we identified a 22 CpG loci panel for HPV+ OPSCC that included four CDKN2A loci downstream of the p16(INK4A) and p14(ARF) transcription start sites. This panel was significantly associated with overall HPV detection (P < 0.05; ROC area under the curve = 0.96, 95% CI: 0.91–1.0) similar to the subset of four CDKN2A‐specific CpG loci (0.90, 95% CI: 0.82–0.99) with equivalence to the full 22 CpG panel. DNA hypermethylation correlated with a significant increase in alternative open reading frame (ARF) expression in HPV+ OPSCC primary tumors, but not to the other transcript variant encoded by the CDKN2A locus. Overall, this study provides evidence of epigenetic changes to the downstream region of the CDKN2A locus in HPV+ oropharyngeal cancer that are associated with changes in expression of the coded protein products.
Nab‐paclitaxel‐based compared to docetaxel‐based induction chemotherapy regimens for locally advanced squamous cell carcinoma of the head and neck
Authors: Schell Amy , Ley Jessica , Wu Ningying , Trinkaus Kathryn , Wildes Tanya Marya , Michel Loren , Thorstad Wade , Gay Hiram , Lewis James , Rich Jason , Diaz Jason , Paniello Randal C. , Nussenbaum Brian , Adkins Douglas R.
Published: January 2015

We previously reported that nab‐paclitaxel‐based induction chemotherapy (IC) and concurrent chemoradiotherapy resulted in low relapse rates (13%) and excellent survival in head and neck squamous cell carcinoma (HNSCC). We compare the disease‐specific survival (DSS) and overall survival (OS) between patients given nab‐paclitaxel, cisplatin, and fluorouracil with cetuximab (APF‐C) and historical controls given docetaxel, cisplatin, and fluorouracil with cetuximab (TPF‐C). Patients with locally advanced HNSCC were treated with APF‐C (n = 30) or TPF‐C (n = 38). After 3 cycles of IC, patients were scheduled to receive cisplatin concurrent with definitive radiotherapy. T and N classification and smoking history were similar between the two groups and within p16‐positive and p16‐negative subsets. The median duration of follow‐up for living patients in the APF‐C group was 43.5 (range: 30–58) months versus 52 (range: 13–84) months for TPF‐C. The 2‐year DSS for patients treated with APF‐C was 96.7% [95% Confidence Interval (CI): 85.2%, 99.8%] and with TPF‐C was 77.6% (CI: 62.6%, 89.7%) (P = 0.0004). Disease progression that resulted in death was more frequent in the TPF‐C group (39%) compared with the APF‐C group (3%) when adjusted for competing risks of death from other causes (Gray's test, P = 0.0004). In p16 positive OPSCC, the 2‐year DSS for APF‐C was 100% and for TPF‐C was 74.6% (CI: 47.4%, 94.6%) (P = 0.0019) and the 2‐year OS for APF‐C was 94.1% (CI: 65.0%, 99.2%) and for TPF‐C was 74.6% (CI: 39.8%, 91.1%) (P = 0.013). In p16 negative HNSCC, the 2‐year DSS for APF‐C was 91.7% (CI: 67.6%, 99.6%) and for TPF‐C was 82.6% (CI: 64.4%, 94.8%) (P = 0.092). A 2‐year DSS and OS were significantly better with a nab‐paclitaxel‐based IC regimen (APF‐C) compared to a docetaxel‐based IC regimen (TPF‐C) in p16‐positive OPSCC.
Spectrum of myeloid neoplasms and immune deficiency associated with germline GATA2 mutations
Authors: Mir Muhammad A. , Kochuparambil Samith T. , Abraham Roshini S. , Rodriguez Vilmarie , Howard Matthew , Hsu Amy P. , Jackson Amie E. , Holland Steven M. , Patnaik Mrinal M.
Published: January 2015

Guanine‐adenine‐thymine‐adenine 2 (GATA2) mutated disorders include the recently described MonoMAC syndrome (Monocytopenia and Mycobacterium avium complex infections), DCML (dendritic cell, monocyte, and lymphocyte deficiency), familial MDS/AML (myelodysplastic syndrome/acute myeloid leukemia) (myeloid neoplasms), congenital neutropenia, congenital lymphedema (Emberger's syndrome), sensorineural deafness, viral warts, and a spectrum of aggressive infections seen across all age groups. While considerable efforts have been made to identify the mutations that characterize this disorder, pathogenesis remains a work in progress with less than 100 patients described in current literature. Varying clinical presentations offer diagnostic challenges. Allogeneic stem cell transplant remains the treatment of choice. Morbidity, mortality, and social costs due to the familial nature of the disease are considerable. We describe our experience with the disorder in three affected families and a comprehensive review of current literature.
Xenograft assessment of predictive biomarkers for standard head and neck cancer therapies
Authors: Stein Andrew P. , Swick Adam D. , Smith Molly A. , Blitzer Grace C. , Yang Robert Z. , Saha Sandeep , Harari Paul M. , Lambert Paul F. , Liu Cheng Z. , Kimple Randall J.
Published: January 2015

Head and neck squamous cell carcinoma (HNSCC) remains a challenging cancer to treat with overall 5‐year survival on the order of 50–60%. Therefore, predictive biomarkers for this disease would be valuable to provide more effective and individualized therapeutic approaches for these patients. While prognostic biomarkers such as p16 expression correlate with outcome; to date, no predictive biomarkers have been clinically validated for HNSCC. We generated xenografts in immunocompromised mice from six established HNSCC cell lines and evaluated response to cisplatin, cetuximab, and radiation. Tissue microarrays were constructed from pre‐ and posttreatment tumor samples derived from each xenograft experiment. Quantitative immunohistochemistry was performed using a semiautomated imaging and analysis platform to determine the relative expression of five potential predictive biomarkers: epidermal growth factor receptor (EGFR), phospho‐EGFR, phospho‐Akt, phospho‐ERK, and excision repair cross‐complementation group 1 (ERCC1). Biomarker levels were compared between xenografts that were sensitive versus resistant to a specific therapy utilizing a two‐sample t‐test with equal standard deviations. Indeed the xenografts displayed heterogeneous responses to each treatment, and we linked a number of baseline biomarker levels to response. This included low ERCC1 being associated with cisplatin sensitivity, low phospho‐Akt correlated with cetuximab sensitivity, and high total EGFR was related to radiation resistance. Overall, we developed a systematic approach to identifying predictive biomarkers and demonstrated several connections between biomarker levels and treatment response. Despite these promising initial results, this work requires additional preclinical validation, likely involving the use of patient‐derived xenografts, prior to moving into the clinical realm for confirmation among patients with HNSCC.
Cutaneous squamous cell carcinoma in norway 1963–2011: increasing incidence and stable mortality
Authors: Robsahm Trude E. , Helsing Per , Veierød Marit B.
Published: January 2015

The incidence of cutaneous squamous cell carcinoma (SCC) is rapidly increasing in white populations, causing high morbidity and health‐care costs. Few studies, however, have described the trends forSCC, as population‐based data with a long follow‐up are limited. In Norway we have this opportunity and we aimed to describeSCCincidence, mortality and survival rates, according to sex, age, stage, primary anatomical location, and geographical region, for the period 1963–2011, for estimation of future health‐care needs. Data were retrieved from the Cancer Registry of Norway. Age‐adjustedSCCincidence and mortality rates and 5‐year relative survival (in percent) were calculated for 5‐year calendar periods. A joinpoint regression model identified the annual percentage change (APC) in rates over the 50‐year period. The age‐adjusted incidence rate increased ninefold in females and sixfold in males from 1963 to 2011, withAPCs of 5.6% (95% confidence interval,CI4.5, 7.3) and 3.3% (95%CI1.3, 5.3) in females and males, respectively.SCCincidence rose in all age groups, anatomical locations (except ears in females), and geographical regions, though restricted to localized tumors. Most striking increase was seen in the age group 70–79, in face and head locations and among residents in southern Norway.SCCmortality and survival rates remained relatively stable. Our findings underline an increasing need forSCCtreatment in Norway, especially considering the aging population. The findings also call for the creation of particular guidelines for primary prevention ofSCC.
Risk of second malignancies in patients with early‐stage classical Hodgkin's lymphoma treated in a modern era
Authors: LeMieux Melissa H. , Solanki Abhishek A. , Mahmood Usama , Chmura Steven J. , Koshy Matthew
Published: January 2015

Second malignancies remain an issue affecting morbidity and mortality in long‐term survivors of early stage Hodgkin's lymphoma (HL). We undertook this study to determine if treatment in the modern era resulted in decreased second malignancies. Patients diagnosed with stage I–II cHL between 1988 and 2009 who received radiation therapy (RT) were selected from the Surveillance, Epidemiology, and End Results (SEER) database. Freedom from second malignancy (FFSM) was estimated using the Kaplan–Meier method. Univariate analysis (UVA) was performed using the Log‐Rank test, and included age, gender, year of diagnosis, and stage. Multivariable analysis (MVA) was performed using Cox Proportional Hazards modeling. The study cohort included 8807 patients. The median age at diagnosis was 32 years (range: 2–85). The majority of patients had stage II disease (n = 6044, 69%), 597 (7%) had extranodal involvement (ENI), and 1925 (22%) had B symptoms. Median follow‐up for the entire cohort was 7.2 years (range: 0–22). Five hundred twenty‐three (6%) patients developed a second malignancy. Median latency to second malignancy was 5.8 years (range: 0.1–21.5). Of the 523 patients that developed a second malignancy, 228 (44%) occurred in the first 5 years, 139 (27%) were diagnosed between years 5–10, and 156 (30%) beyond 10 years. The 10 year FFSM for patients treated between 1988 and 1999 was 93.0% versus 95.1% for patients treated between 2000 and 2009 (P = 0.04), On MVA, treatment between 2000 and 2009 was associated with a HR for second malignancy of 0.77 (95% Confidence Interval: 0.62–0.96, P = 0.02) compared to the treatment between 1988 and 1999. Our analysis suggests that in patients treated with RT for stage I or II cHL, treatment prior to 2000 had a slightly higher risk of second malignancy compared to treatment in 2000 and later. Further studies, with longer follow‐up of patients treated in the modern era are needed to confirm these findings.
Rates of complete diagnostic testing for patients with acute myeloid leukemia
Authors: Lin Tara L. , Williams Travis , He Jianghua , Aljitawi Omar S. , Ganguly Siddhartha , Abhyankar Sunil , Fleming Allan , Male Heather , McGuirk Joseph P.
Published: January 2015

In addition to cytogenetics, additional molecular markers of prognosis have been identified and incorporated into the management of patients with acute myeloid leukemia (AML). We hypothesized that rates of molecular testing would be higher in an academic center versus community sites. A retrospective chart review included all de novo AML patients (excluding M3) at Kansas University Medical Center (KUMC) from January 2008 through April 2013. Records were evaluated for completeness of molecular testing as indicated by karyotype (FLT3, CEBPα, NPM1 in normal cytogenetics AML and c‐KIT in core binding factor [CBF] AML). 271 charts were reviewed: 98 with CN‐AML and 29 with CBF AML. Seventy were diagnosed at KUMC, 57 at a community site. Molecular testing was sent in 76/98 (77%) patients with CN‐AML. Patients diagnosed at KUMC had a significantly higher rate of molecular testing (51/55, 93%) as compared to those diagnosed at outside centers (18/43, 41%) (P < 0.001). Of 29 patients with CBF AML, c‐kit mutational analysis was performed more frequently at KUMC (14/15, 93%) than in community sites (8/14, 57%) (P = 0.035). There was a trend towards increased testing at both KUMC and community sites in later years. Rates of molecular testing in AML were higher in an academic center versus community sites in the 5 years following the World Health Organization revised classification of AML. All physicians who diagnose and treat AML must remain up to date on the latest recommendations and controversies in molecular testing in order to appropriately risk stratify patients and determine optimal therapy.
Racial/ethnic disparities in knowledge about one's breast cancer characteristics
Authors: Freedman Rachel A. , Kouri Elena M. , West Dee W. , Keating Nancy L.
Published: January 2015

BACKGROUND

Understanding tumor characteristics is likely important, but little is known about breast cancer patients' knowledge of their own disease. The authors assessed women's knowledge about their tumor characteristics, whether racial/ethnic disparities in knowledge exist, and whether education and health literacy influence associations.

METHODS

A population‐based cohort of women in Northern California with stage 0 through III breast cancers diagnosed from 2010 to 2011 (participation rate 68.5%) was surveyed. Among 500 respondents (222 non‐Hispanic white women, 142 non‐Hispanic black women, and 136 Hispanic women), racial/ethnic differences in knowledge about tumor characteristics (estrogen receptor [ER] status, human epidermal growth factor receptor 2 [HER2] status, stage, grade) and correctness of tumor information (with California Cancer Registry data for confirmation) were examined. Multivariate logistic regression was used to assess the probability of: 1) knowing tumor stage, receptor status, and grade; and 2) correctly answering questions about tumor information by race/ethnicity. The impact of education and health literacy on findings was examined in sequential models.

RESULTS

Overall, 32% to 82% of women reported knowing each of the 4 tumor characteristics of interest, and 20% to 58% correctly reported these characteristics. After adjustment, black and Hispanic women were less likely than white women to know and have correct responses for stage, ER status, and HER2 status (all P<.05). Education and health literacy were significantly associated with knowing and having correct information about some characteristics, but these variables did not eliminate most of the racial/ethnic differences observed.

CONCLUSIONS

Patient's knowledge about their own breast cancer was generally poor, particularly for minority women. Further study of how this knowledge may impact receipt of care and outcomes is warranted. Cancer 2015;121:724–732. © 2014 American Cancer Society.
Petri nets‐based model for the analysis of NORIA protocol
Authors: Macia H. , Ruiz M. C. , Mateo J. A. , Calleja J. L.
Published: January 2015

Network rOle‐based Routing Intelligent Algorithm is a novel routing algorithm for wireless sensor networks, which combine various effective techniques in order to reduce energy consumption and improve data routes. This algorithm uses role assignment for distributing tasks over the network nodes and fuzzy logic for making decisions. There is a clear need for the use of formal methods to validate the correctness of the protocols as well as performance and functionality prior to the deployment of such algorithms in a real environment. This paper presents a formal and rigorous study of Network rOle‐based Routing Intelligent Algorithm. Prioritised‐timed coloured petri nets (PTCPNs) have been chosen as an appropriate modelling language. In this way, PTCPNs have been used to describe complete and unambiguous specifications of system behaviour, whereas CPNTools is used to evaluate the correctness of the protocol using state space exploration and for performance evaluation using simulation. Copyright © 2015 John Wiley & Sons, Ltd.
User location prediction with energy efficiency model in the Long Term‐Evolution network
Authors: Qiao Yuanyuan , Yang Jie , He Haiyang , Cheng Yihang , Ma Zhanyu
Published: January 2015

Predicting users' next location/place allows us to anticipate their future movement. It provides additional time to be ready for that movement and react consequently. Furthermore, many industries, including Internet Service Providers, are still requiring low cost and simple location/place prediction methods that can be implemented on mobile device. This paper studies domain‐independent prediction algorithms and spatio‐temporal based prediction method using 20‐day‐long records in Long Term‐Evolution(LTE) network, which captures the mobility patterns of 3474 individuals. After examining the prediction accuracy and resource consumption of domain‐independent prediction algorithms, we find Markov provides the best tradeoff. Furthermore, Active LeZi outperforms Markov if enough consecutive parsed patterns of users' history movement are captured. In addition, we further group users according to their spatio‐temporal entropy profiles in order to predict not only user's future locations but also the place he or she most likely to appear within a specific period. By applying the simple spatio‐temporal based method to each group of user, 83.3% accuracy can be achieved for some users. Yet Markov and Active LeZi algorithms perform better for some other users. This implies that we should consider applying different prediction methods to users with distinct spatio‐temporal characteristics. Copyright © 2015 John Wiley & Sons, Ltd.