Brain Function and Upper Limb Outcome in Stroke: A Cross-Sectional fMRI Study

Objective

The nature of changes in brain activation related to good recovery of arm function after stroke is still unclear. While the notion that this is a reflection of neuronal plasticity has gained much support, confounding by compensatory strategies cannot be ruled out. We address this issue by comparing brain activity in recovered patients 6 months after stroke with healthy controls.

Methods

We included 20 patients with upper limb paresis due to ischemic stroke and 15 controls. We measured brain activation during a finger flexion-extension task with functional MRI, and the relationship between brain activation and hand function. Patients exhibited various levels of recovery, but all were able to perform the task.

Results

Comparison between patients and controls with voxel-wise whole-brain analysis failed to reveal significant differences in brain activation. Equally, a region of interest analysis constrained to the motor network to optimize statistical power, failed to yield any differences. Finally, no significant relationship between brain activation and hand function was found in patients. Patients and controls performed scanner task equally well.

Conclusion

Brain activation and behavioral performance during finger flexion-extensions in (moderately) well recovered patients seems normal. The absence of significant differences in brain activity even in patients with a residual impairment may suggest that infarcts do not necessarily induce reorganization of motor function. While brain activity could be abnormal with higher task demands, this may also introduce performance confounds. It is thus still uncertain to what extent capacity for true neuronal repair after stroke exists.     

Neuronox versus BOTOX in the Treatment of Post-Stroke Upper Limb Spasticity: A Multicenter Randomized Controlled Trial

Background

Botulinum toxin type A is widely used for treating spasticity. Neuronox (Neu-BoNT/A), a newly manufactured botulinum toxin a, has not yet been investigated for its efficacy and safety in the treatment of post-stroke upper limb spasticity.

Objective

We evaluated the efficacy and safety of Neuronox (Neu-BoNT/A) compared with BOTOX (onabotulinum toxin A) for treating post-stroke upper limb spasticity.

Methods

In total, 196 stroke patients with moderate to severe upper limb spasticity were randomly assigned to either Neuronox or BOTOX intervention. The wrist flexors were mandatory and elbow, finger, and thumb flexors were optional muscles to be injected. Assessments were performed at baseline and 4, 8, and 12 weeks after the intervention. The primary outcome measure was the change from baseline of the Modified Ashworth Scale (MAS) at the wrist flexors at week 4. Secondary outcome measures included the change of MAS at each visit, response rate, Disability Assessment Scale (DAS), Carer Burden Scale, and Global Assessment of treatment benefit.

Results

Primary outcome measures were -1.39±0.79 and -1.56±0.81 in the Neuronox and BOTOX groups, respectively. The difference was within the noninferiority margin of 0.45 (95% upper limit=0.40). There were no significant differences between the groups in the secondary outcome and safety measures, except the change of the MAS at the elbow flexors at week 12 (-0.88±0.75 in the Neuronox group, -0.65±0.74 in the BOTOX group; P=0.0429). Both groups showed significant improvements in the MAS, DAS, and Carer Burden Scale at weeks 4, 8, and 12.

Conclusion

Neuronox showed equivalent efficacy and safety compared with BOTOX for treating post-stroke upper limb spasticity.

Trial Registration

ClinicalTrials.gov NCT01313767     

The addition of synchronous whole-body vibration to battling rope exercise increases skeletal muscle activity

Objectives:

To evaluate the effects of performing battling rope exercise with and without the addition of whole-body vibration (WBV) on muscle activity of the leg, trunk, and upper body.

Methods:

Twenty-eight recreationally active university students completed 20-s of battling rope undulation for 6 separate conditions: 1) alternating arm motion no WBV -Alt_NoWBV; 2) alternating arm motion 30 Hz low amplitude WBV -Alt_30 Hz-L; 3) alternating arm motion 50 Hz high amplitude -Alt_50 Hz-H; 4) double arm motion no WBV -Double_NoWBV; 5) double arm motion 30Hz low amplitude WBV -Double_30Hz-L; 6) double arm motion 50 `Hz high amplitude -Double_50 Hz-H. Electromyography (EMG) was measured for the gastrocnemius medialis (GM), vastus medialis oblique (VMO), vastus lateralis (VL), rectus abdominis (RA), multifidus (MF), biceps brachii (BB), and triceps brachii (TB) muscles.

Results:

The double arm motion during undulation resulted in greater (p<0.05) muscle activity in the VMO, VL, RA, and MF muscles while the GM was more active during the alternating arm motion. WBV at 50Hz increased EMG in all muscles measured vs NoWBV and the 30 Hz condition.

Conclusion:

These results are the first to demonstrate that the exercise stimulus of performing battling rope exercise can be augmented by completing the exercise while being exposed to WBV from a ground-based platform.     

Muscles in "concert": study of primary motor cortex upper limb functional topography

Background

Previous studies with Transcranial Magnetic Stimulation (TMS) have focused on the cortical representation of limited group of muscles. No attempts have been carried out so far to get simultaneous recordings from hand, forearm and arm with TMS in order to disentangle a ‘functional’ map providing information on the rules orchestrating muscle coupling and overlap. The aim of the present study is to disentangle functional associations between 12 upper limb muscles using two measures: cortical overlapping and cortical covariation of each pair of muscles. Interhemispheric differences and the influence of posture were evaluated as well.

Methodology/Principal Findings

TMS mapping studies of 12 muscles belonging to hand, forearm and arm were performed. Findings demonstrate significant differences between the 66 pairs of muscles in terms of cortical overlapping: extremely high for hand-forearm muscles and very low for arm vs hand/forearm muscles. When right and left hemispheres were compared, overlapping between all possible pairs of muscles in the left hemisphere (62.5%) was significantly higher than in the right one (53.5% ).The arm/hand posture influenced both measures of cortical association, the effect of Position being significant [p = .021] on overlapping, resulting in 59.5% with prone vs 53.2% with supine hand, but only for pairs of muscles belonging to hand and forearm, while no changes occurred in the overlapping of proximal muscles with those of more distal districts.

Conclusions/Significance

Larger overlapping in the left hemisphere could be related to its lifetime higher training of all twelve muscles studied with respect to the right hemisphere, resulting in larger intra-cortical connectivity within primary motor cortex. Altogether, findings with prone hand might be ascribed to mechanisms facilitating coupling of muscles for object grasping and lifting -with more proximal involvement for joint stabilization- compared to supine hand facilitating actions like catching. TMS multiple-muscle mapping studies permit a better understanding of motor control and ‘plastic’ reorganization of motor system.     

Muscle Recruitment and Coordination following Constraint-Induced Movement Therapy with Electrical Stimulation on Children with Hemiplegic Cerebral Palsy: A Randomized Controlled Trial

Objective

To investigate changes of muscle recruitment and coordination following constraint-induced movement therapy, constraint-induced movement therapy plus electrical stimulation, and traditional occupational therapy in treating hand dysfunction.

Methods

In a randomized, single-blind, controlled trial, children with hemiplegic cerebral palsy were randomly assigned to receive constraint-induced movement therapy (n = 22), constraint-induced movement therapy plus electrical stimulation (n = 23), or traditional occupational therapy (n = 23). Three groups received a 2-week hospital-based intervention and a 6-month home-based exercise program following hospital-based intervention. Constraint-induced movement therapy involved intensive functional training of the involved hand during which the uninvolved hand was constrained. Electrical stimulation was applied on wrist extensors of the involved hand. Traditional occupational therapy involved functional unimanual and bimanual training. All children underwent clinical assessments and surface electromyography (EMG) at baseline, 2 weeks, 3 and 6 months after treatment. Surface myoelectric signals were integrated EMG, root mean square and cocontraction ratio. Clinical measures were grip strength and upper extremity functional test.

Results

Constraint-induced movement therapy plus electrical stimulation group showed both a greater rate of improvement in integrated EMG of the involved wrist extensors and cocontraction ratio compared to the other two groups at 3 and 6 months, as well as improving in root mean square of the involved wrist extensors than traditional occupational therapy group (p<0.05). Positive correlations were found between both upper extremity functional test scores and integrated EMG of the involved wrist as well as grip strength and integrated EMG of the involved wrist extensors (p<0.05).

Conclusions

Constraint-induced movement therapy plus electrical stimulation is likely to produce the best outcome in improving muscle recruitment and coordination in children with hemiplegic cerebral palsy compared to constraint-induced movement therapy alone or traditional occupational therapy.

Trial registration

chictr.org ChiCTR-TRC-13004041     

Influence of Cervical Muscle Fatigue on Musculo-Tendinous Stiffness of the Head-Neck Segment during Cervical Flexion

Aim

The aim of this study is to determine if the fatigue of cervical muscles has a significant influence on the head-neck segment musculo-tendinous stiffness.

Methods

Ten men (aged 21.2 ± 1.9 years) performed four quick-release trials of flexion at 30 and 50% MVC before and after the induction of muscular fatigue on cervical flexors. Electromyographic activity was recorded on the sternocleidomastoids (SCM) and spinal erectors (SE), bilaterally. Musculo-tendinous stiffness was calculated through the quick-release method adapted to the head-neck segment.

Results

We noticed a significant linear increase of the head-neck segment musculo-tendinous stiffness with the increase of exertion level both before (P < 0.0001) and after the fatigue procedure (P < 0.0001). However, this linear relationship was not different before and after the fatigue procedure. EMG analysis revealed a significant increase of the root mean square for the right SCM (P = 0.0002), the left SCM (P < 0.0001), the right SE (P < 0.0001), and the left SE (P < 0.0001) and a significant decrease of the median power frequency only for the right (P = 0.0006) and the left (P = 0.0003) SCM with muscular fatigue.

Discussion

We did not find significant changes in the head-neck segment musculo-tendinous stiffness with fatigue of cervical muscles. We found a significant increase in EMG activity in the SCM and the SE after the induction of fatigue of the SCM. Our findings suggest that with fatigue of cervical flexors, neck muscle activity is modulated in order to maintain the musculo-tendinous stiffness at a steady state.     

Association between body mass index and muscularity in healthy older Japanese women and men

Background

Body mass index (BMI), expressed as the ratio of body mass to height squared (kg/m²), involves not only fat but also lean mass. The present study aimed to clarify how BMI is associated with total muscle mass (TMM) in older Japanese women and men.

Findings

Using a B-mode ultrasound apparatus, muscle thickness was measured at nine sites (forearm, upper arm anterior and posterior, thigh anterior and posterior, lower leg anterior and posterior, abdomen, and subscapular) for 346 women (BMI 16.40 to 33.11 kg/m²) and 286 men (BMI 16.86 to 31.18 kg/m²) aged 60.0 to 79.5 yrs. TMM was estimated using the product of the sum of the muscle thicknesses at the nine sites with height as an independent variable. For both sexes, the estimated TMM relative to height squared was significantly correlated with BMI (r = 0.688, P<0.0001 for women; r = 0.696, P<0.0001 for men), but the percentage of the estimated TMM in body mass was not.

Conclusion

These results indicate that, for older Japanese women and men, BMI is a simple and convenient index for assessing total muscularity.     

Feasibility and Preliminary Efficacy of Visual Cue Training to Improve Adaptability of Walking after Stroke: Multi-Centre,Single-Blind Randomised Control Pilot Trial

Objectives

Given the importance of vision in the control of walking and evidence indicating varied practice of walking improves mobility outcomes, this study sought to examine the feasibility and preliminary efficacy of varied walking practice in response to visual cues, for the rehabilitation of walking following stroke.

Design

This 3 arm parallel, multi-centre, assessor blind, randomised control trial was conducted within outpatient neurorehabilitation services

Participants

Community dwelling stroke survivors with walking speed <0.8m/s, lower limb paresis and no severe visual impairments

Intervention

Over-ground visual cue training (O-VCT), Treadmill based visual cue training (T-VCT), and Usual care (UC) delivered by physiotherapists twice weekly for 8 weeks.Main outcome measures: Participants were randomised using computer generated random permutated balanced blocks of randomly varying size. Recruitment, retention, adherence, adverse events and mobility and balance were measured before randomisation, post-intervention and at four weeks follow-up.

Results

Fifty-six participants participated (18 T-VCT, 19 O-VCT, 19 UC). Thirty-four completed treatment and follow-up assessments. Of the participants that completed, adherence was good with 16 treatments provided over (median of) 8.4, 7.5 and 9 weeks for T-VCT, O-VCT and UC respectively. No adverse events were reported. Post-treatment improvements in walking speed, symmetry, balance and functional mobility were seen in all treatment arms.

Conclusions

Outpatient based treadmill and over-ground walking adaptability practice using visual cues are feasible and may improve mobility and balance. Future studies should continue a carefully phased approach using identified methods to improve retention.

Trial Registration

Clinicaltrials.gov NCT01600391     

Effects of Body Mass Index on Risks for Ischemic Stroke,Thromboembolism, and Mortality in Chinese Atrial Fibrillation Patients: A Single-Center Experience

Background

Obesity is considered to be related to recurrence of atrial fibrillation (AF), left atrial thrombus formation, and atrial remodeling. However, whether obesity is an independent risk factor for stroke and other thromboembolic events is still controversial.

Objective

This study aimed to investigate the effects of body mass index (BMI) on the risks of stroke, thromboembolism, and mortality in AF patients.

Methods

Patients who were diagnosed with nonvalvular AF were included in this observational, retrospective study. The study population was stratified by BMI at baseline. The Cox proportional hazard model was adopted to calculate adjusted hazard ratios of risk factors for adverse clinical events (stroke, thromboembolism, and mortality).

Results

A total of 1286 AF patients (males, 78.30%; mean age, 74.50 years; 94.48% paroxysmal AF) were followed up for a median of 2.1 years (IQR: 1.5–2.9 years). Overall, 159 patients died. A total of 84 strokes and 35 thromboembolic events occurred. Multivariate analysis showed that overweight (25.0≤BMI<30.0 kg/m²) and age ≥75 years were independent risk factors for ischemic stroke (both P<0.01). Obesity (BMI ≥30.0 kg/m²), age ≥75 years, persistent/permanent AF, and prior thromboembolism were independent risk factors for thromboembolism (all P<0.05). Underweight (BMI <18.5 kg/m²), age ≥75 years, prior ischemic stroke/transient ischemic attack, renal dysfunction, and heart failure were independent risk factors for all-cause deaths (all P<0.05).

Conclusions

Overweight or obesity may be a risk factor of ischemic stroke and thromboembolism in AF patients. Excessive low weight is significantly associated with increased all-cause mortality.     

Muscle hypertrophy in prepubescent tennis players: a segmentation MRI study

Purpose

To asses if tennis at prepubertal age elicits the hypertrophy of dominant arm muscles.

Methods

The volume of the muscles of both arms was determined using magnetic resonance imaging (MRI) in 7 male prepubertal tennis players (TP) and 7 non-active control subjects (CG) (mean age 11.0±0.8 years, Tanner 1–2).

Results

TP had 13% greater total muscle volume in the dominant than in the contralateral arm. The magnitude of inter-arm asymmetry was greater in TP than in CG (13 vs 3%, P<0.001). The dominant arm of TP was 16% greater than the dominant arm of CG (P<0.01), whilst non-dominant arms had similar total muscle volumes in both groups (P = 0.25), after accounting for height as covariate. In TP, dominant deltoid (11%), forearm supinator (55%) and forearm flexors (21%) and extensors (25%) were hypertrophied compared to the contralateral arm (P<0.05). In CG, the dominant supinator muscle was bigger than its contralateral homonimous (63%, P<0.05).

Conclusions

Tennis at prepubertal age is associated with marked hypertrophy of the dominant arm, leading to a marked level of asymmetry (+13%), much greater than observed in non-active controls (+3%). Therefore, tennis particpation at prepubertal age is associated with increased muscle volumes in dominant compared to the non-dominant arm, likely due to selectively hypertrophy of the loaded muscles.     

Assessment of a Standardized Pre-Operative Telephone Checklist Designed to Avoid Late Cancellation of Ambulatory Surgery: The AMBUPROG Multicenter Randomized Controlled Trial

Objectives

To assess the impact of a standardized pre-operative telephone checklist on the rate of late cancellations of ambulatory surgery (AMBUPROG trial).

Design

Multicenter, two-arm, parallel-group, open-label randomized controlled trial.

Setting

11 university hospital ambulatory surgery units in Paris, France.

Participants

Patients scheduled for ambulatory surgery and able to be reached by telephone.

Intervention

A 7-item checklist designed to prevent late cancellation, available in five languages and two versions (for children and adults), was administered between 7 and 3 days before the planned date of surgery, by an automated phone system or a research assistant. The control group received standard management alone.

Main Outcome Measures

Rate of cancellation on the day of surgery or the day before.

Results

The study population comprised 3900 patients enrolled between November 2012 and September 2013: 1950 patients were randomized to the checklist arm and 1950 patients to the control arm. The checklist was administered to 68.8% of patients in the intervention arm, 1002 by the automated phone system and 340 by a research assistant. The rate of late cancellation did not differ significantly between the checklist and control arms (109 (5.6%) vs. 113 (5.8%), adjusted odds ratio [95% confidence interval] = 0.91 [0.65–1.29], (p = 0.57)). Checklist administration revealed that 355 patients (28.0%) had not undergone tests ordered by the surgeon or anesthetist, and that 254 patients (20.0%) still had questions concerning the fasting state.

Conclusions

A standardized pre-operative telephone checklist did not avoid late cancellations of ambulatory surgery but enabled us to identify several frequent causes.

Trial Registration

ClinicalTrials.gov {"type":"clinical-trial","attrs":{"text":"NCT01732159","term_id":"NCT01732159"}}NCT01732159     

Association between Diurnal Variation of Ozone Concentration and Stroke Occurrence: 24-Hour Time Series Study

Background and Purpose

Increasing ozone concentrations have been known to damage human health and ecosystems. Although ozone tends to display diurnal variation, most studies have reported only on the association between daily ozone concentrations and ischemic stroke occurrence on the same day, or with a 1-day lag. We investigated the effect of the diurnal variation of ozone on ischemic stroke occurrence during the same day.

Methods

We included a consecutive series of 1,734 patients from January 1, 2008, to December 31, 2014, at a single tertiary hospital in Seoul, South Korea. We evaluated differences between temperature and pollutants at the time of stroke onset for each time interval and averaged those parameters across the 7-year study period.

Results

During the interval from 13:00 to 16:59, we found a positive association between ischemic stroke occurrence and ozone concentration relative to other time periods. Upper median ozone levels from 13:00 to 16:59 were positively correlated with ischemic stroke (odds ratio, 1.550; 95% confidence intervals, 1.220 to 1.970; P = <0.001) when compared with lower median levels.

Conclusions

The results show diurnal patterns of ischemic stroke occurrence based on upper and lower median ozone levels for a 24-hour period, which extends understanding of the association between stroke occurrence and environmental influences.     

Endovascular Treatment with Stent-Retriever Devices for Acute Ischemic Stroke: A Meta-Analysis of Randomized Controlled Trials

Importance

Acute ischemic stroke is a leading cause of death and disability worldwide. Several recent clinical trials have shown that endovascular treatment improves clinical outcomes among patients with acute ischemic stroke.

Objective

To provide an overall and precise estimate of the efficacy of endovascular treatment predominantly using second-generation mechanical thrombectomy devices (stent-retriever devices) compared to medical management on clinical and functional outcomes among patients with acute ischemic stroke.

Data Sources

MEDLINE, EMBASE, Cochrane Collaboration Central Register of Controlled Clinical Trials, Web of Science, and NIH ClinicalTrials.gov were searched through November 2015.

Study Selection

Searches returned 3,045 articles. After removal of duplicates, two authors independently screened titles and abstracts to assess eligibility of 2,495 potentially relevant publications. From these, 38 full-text publications were more closely assessed. Finally, 5 randomized controlled trials of endovascular treatment with predominant use of retrievable stents were selected.

Data Extraction and Synthesis

Three authors independently extracted information on participant and trial characteristics and clinical events using a standardized protocol. Random effects models were used to pool endovascular treatment effects across outcomes.

Main Outcomes and Measures

The primary outcome was better functional outcome as measured on the modified Rankin Scale at 90 days of follow-up. Secondary outcomes included all-cause mortality and symptomatic intra-cerebral hemorrhage.

Results

Five trials representing 1,287 patients were included. Overall, patients randomized to endovascular therapy experienced 2.22 times greater odds of better functional outcome compared to those randomized to medical management (95% CI, 1.66 to 2.98; P < 0.0001). Endovascular therapy was not associated with mortality [OR (95% CI), 0.78 (0.54, 1.12); P = 0.1056] or symptomatic intracerebral hemorrhage [OR (95% CI), 1.19 (0.69, 2.05); P = 0.5348]. Meta-regression analysis suggested that shorter times from stroke onset to groin puncture and from stroke onset to reperfusion result in better functional outcomes in ischemic stroke patients (P = 0.0077 and P = 0.0089). There were no significant differences in the beneficial effects of endovascular treatment on functional outcomes across categories of gender, age, stroke severity, ischemic changes on computed tomography, or intravenous tissue plasminogen activator administration.

Conclusions and Relevance

This meta-analysis demonstrated superior functional outcomes in subjects receiving endovascular treatment compared to medical management. Further, this analysis showed that acute ischemic stroke patients may receive enhanced functional benefit from earlier endovascular treatment.     

The Cannabinoid Receptor 2 Q63R Variant Modulates the Relationship between Childhood Obesity and Age at Menarche

Background

The ovary is an important site where gene variants modulate pubertal timing. The cannabinoid receptor 2 (CB2) is expressed in the ovary, plays a role in folliculogenesis and ovulation, and can be modulated by estrogens. Obesity is strictly associated with early menarche and is characterized by sex hormone and endocannabinoid derangement.

Aim

In this study, we investigated the role of the CB2 receptor in determining the age at menarche in obese girls.

Methods

We studied a cohort of 240 obese girls (age 11.9±3 years; BMI z-score 2.8±0.8). The age at menarche (if it had already occurred) was recorded at the time of the visit or via phonecall. The CNR2 rs35761398 polymorphism, which leads to the CB2 Q63R variant, was detected by the TaqMan assay.

Results

In total, 105 patients were homozygous for the R63-coding allele (RR), 113 were QR and 22 were QQ. Variance analysis revealed a significantly earlier age of menarche in subjects carrying the Q63 allele, which was also found after adjusting for BMI z-score (11±1.2 vs. 11.6±1.2 years, p = 0.0003). Logistic regression analysis demonstrated that patients homozygous for the Q allele had a 2.2-fold higher risk (odds ratio = 2.2; CI1.1–3.4; p = 0.02) of presenting with an early menarche (age at menarche <12 years).

Conclusion

We demonstrated for the first time the association between the CB2 Q63R functional variant and the age at menarche in a cohort of Italian obese girls.     

Role of Brain-Derived Neurotrophic Factor in Beneficial Effects of Repetitive Transcranial Magnetic Stimulation for Upper Limb Hemiparesis after Stroke

Background

Repetitive transcranial magnetic stimulation (rTMS) can improve upper limb hemiparesis after stroke but the mechanism underlying its efficacy remains elusive. rTMS seems to alter brain-derived neurotrophic factor (BDNF) and such effect is influenced by BDNF gene polymorphism.

Objectives

To investigate the molecular effects of rTMS on serum levels of BDNF, its precursor proBDNF and matrix metalloproteinase-9 (MMP-9) in poststroke patients with upper limb hemiparesis.

Methods

Poststroke patients with upper limb hemiparesis were studied. Sixty-two patients underwent rehabilitation plus rTMS combination therapy and 33 patients underwent rehabilitation monotherapy without rTMS for 14 days at our hospital. One Hz rTMS was applied over the motor representation of the first dorsal interosseous muscle on the non-lesional hemisphere. Fugl-Meyer Assessment and Wolf Motor Function (WMFT) were used to evaluate motor function on the affected upper limb before and after intervention. Blood samples were collected for analysis of BDNF polymorphism and measurement of BDNF, proBDNF and MMP-9 levels.

Results

Two-week combination therapy increased BDNF and MMP-9 serum levels, but not serum proBDNF. Serum BDNF and MMP-9 levels did not correlate with motor function improvement, though baseline serum proBDNF levels correlated negatively and significantly with improvement in WMFT (ρ = -0.422, p = 0.002). The outcome of rTMS therapy was not altered by BDNF gene polymorphism.

Conclusions

The combination therapy of rehabilitation plus low-frequency rTMS seems to improve motor function in the affected limb, by activating BDNF processing. BDNF and its precursor proBDNF could be potentially suitable biomarkers for poststroke motor recovery.     

Randomized Phase II Study of 5-Fluorouracil Hepatic Arterial Infusion with or without Antineoplastons as an Adjuvant Therapy after Hepatectomy for Liver Metastases from Colorectal Cancer

Background

Antineoplastons are naturally occurring peptides and amino acid derivatives found in human blood and urine. Antineoplaston A10 and AS2-1 reportedly control neoplastic growth and do not significantly inhibit normal cell growth. Antineoplastons contain 3-phenylacetylamino-2, 6-piperidinedione (A10), phenylacetylglutamine plus phenylacetylisoglutamine (A10-I), and phenylacetylglutamine plus phenylacetate (AS2-1). This open label, non- blinded randomized phase II study compared the efficacy of hepatic arterial infusion (HAI) with 5-fluorouracil,with or without antineoplastons as a postoperative therapy for colorectal metastasis to the liver.

Methods

Sixty-five patients with histologically confirmed metastatic colon adenocarcinoma in liver, who had undergone hepatectomy, and/or thermal ablation for liver metastases were enrolled between 1998- 2004 in Kurume University Hospital. Patients were randomly assigned to receive systemic antineoplastons (A10-I infusion followed by per-oral AS2-1) plus HAI (AN arm) or HAI alone (control arm) based on the number of metastases and presence/ absence of extra-hepatic metastasis at the time of surgery. Primary endpoint was cancer-specific survival (CSS); secondary endpoints were relapse-free survival (RFS), status and extent of recurrence, salvage surgery (rate) and toxicity.

Findings

Overall survival was not statistically improved (p=0.105) in the AN arm (n=32). RFS was not significant (p=0.343). Nevertheless, the CSS rate was significantly higher in the AN arm versus the control arm (n=33) with a median survival time 67 months (95%CI 43-not calculated) versus 39 months (95%CI 28-47) (p=0.037) and 5 year CSS rate 60% versus 32% respectively. Cancer recurred more often in a single organ than in multiple organs in the AN arm versus the control arm. The limited extent of recurrent tumours in the AN arm meant more patients remained eligible for salvage surgery. Major adverse effects of antineoplastons were fullness of the stomach and phlebitis. No serious toxicity, including bone marrow suppression, liver or renal dysfunction, were found in the AN arm.

Interpretation

Antineoplastons (A10 Injection and AS2-1) might be useful as adjunctive therapy in addition to HAI after hepatectomy in colorectal metastases to the liver.

Trial registration information

ClinicalTrials.gov UMIN000012099     

Gender,Age, and Education Level Modify the Association between Body Mass Index and Physical Activity: A Cross-Sectional Study in Hangzhou,China

Introduction

Numerous studies have reported a strong inverse association between BMI and physical activity in western populations. Recently, the association between BMI and physical activity has been considered bidirectional. This study aimed to examine the associations of body mass index (BMI) with physical activity and sedentary behavior and to explore whether those associations were modified by socio-demographic characteristics.

Materials and Methods

We conducted a multistage random sampling survey in three districts of Hangzhou, China, in 2012. The International Physical Activity Questionnaire long form was used to collect data regarding physical activity and sedentary behavior. A multilevel mixed-effects regression model was used to assess the associations of BMI with physical activity and sedentary behavior.

Results

A total of 1362 eligible people (624 men and 738 women, ages 23-59 years) completed the survey. People who are young or middle-aged and have the highest education level are the most inactive. Significant differences in the associations between physical activity and BMI across socio-demographic groups were identified (sex*BMI, P=0.018; age*BMI, P<0.001; education level*BMI, P=0.030). Women or individuals older than 50 had a higher level of physical activity with increasing BMI. There was no statistically significant association between BMI and sedentary behavior (P=0.450).

Conclusions

The associations between BMI and physical activity were modified by sex, age, and education level in Hangzhou, China.     

Correlation between Body Composition and Walking Capacity in Severe Obesity

Background

Obesity is associated with mobility reduction due to mechanical factors and excessive body fat. The six-minute walk test (6MWT) has been used to assess functional capacity in severe obesity.

Objective

To determine the association of BMI, total and segmental body composition with distance walked (6MWD) during the six-minute walk test (6MWT) according to gender and obesity grade.

Setting

University of São Paulo Medical School, Brazil; Public Practice.

Methods

Functional capacity was assessed by 6MWD and body composition (%) by bioelectrical impedance analysis in 90 patients.

Results

The mean 6MWD was 514.9 ± 50.3 m for both genders. The male group (M: 545.2 ± 46.9 m) showed a 6MWD higher (p = 0.002) than the female group (F: 505.6 ± 47.9 m). The morbid obese group (MO: 524.7 ± 44.0 m) also showed a 6MWD higher (p = 0.014) than the super obese group (SO: 494.2 ± 57.0 m). There was a positive relationship between 6MWD and fat free mass (FFM), FFM of upper limps (FFM_UL), trunk (FFM_TR) and lower limbs (FFM_LL). Female group presented a positive relationship between 6MWD and FFM, FFM_UL and FFM_LL and male group presented a positive relationship between 6MWD and FFM_TR. In morbid obese group there was a positive relationship between 6MWD with FFM, FFM_UL, FFM_TR and FFM_LL. The super obese group presented a positive relationship between 6MWD with FFM, FFM_TR and FFM_LL.

Conclusions

Total and segmental FFM is associated with a better walking capacity than BMI.     

Age-Related Macular Degeneration and Incident Stroke: A Systematic Review and Meta-Analysis

Background

Age-related macular degeneration (AMD) is the leading cause of vision loss and blindness in people over 65 years old in the United States and has been associated with cardiovascular risk and decreased survival. There is conflicting data, however, regarding the contribution of AMD to the prediction of stroke.

Aim

To determine whether AMD is a risk indicator for incident stroke in a meta-analysis of available prospective and retrospective cohort studies published in the English literature.

Methods

We performed a systematic literature search of all studies published in English with Pub Med and other databases from 1966 to August 2014, reporting stroke incidence in patients with macular degeneration. Two investigators independently extracted the data. A random effects model was used to report Odds ratios (OR), with corresponding 95% confidence intervals (CI). Meta-regression using a mixed linear model was used to understand potential heterogeneity amongst studies.

Results

We identified 9 studies that reported stroke incidence in patients with and without early AMD (N = 1,420,978). No significant association was found between early AMD with incident stroke. Combined, these 9 studies demonstrated random effects (OR, 1.12; CI, 0.86–1.47; I² = 96%). Meta-regression on baseline covariates of age, sex, and year of publication did not significantly relate to heterogeneity.

Conclusions

We found no significant relationship between AMD and incident stroke. Further studies are needed to clarify other causes of decreased survival in patients with AMD.