Δευτέρα, 26 Νοεμβρίου 2018

Preoperative continuation of aspirin administration in patients undergoing major abdominal malignancy surgery

Abstract

Purpose

In contrast to that in a nonoperative setting, it has been shown that perioperative administration of aspirin did not decrease the rate of death or myocardial infarction but increased major bleeding risk. Since these conflicting results might be due to concurrent use of anticoagulants and a lower thrombotic risk of patients, this cohort study was carried out for patients at a high thrombotic risk without concurrent use of anticoagulants.

Methods

Medical records for patients who underwent major abdominal malignancy surgery and who were on a preoperative antiplatelet regimen were reviewed. The patients were divided into two groups according to perioperative antiplatelet management: administration of all preoperative antiplatelet agent-suspended (no aspirin) group and only aspirin administration-continued (aspirin) group. The incidence of symptomatic thromboembolic events, frequency of exogenous blood transfusion within 30 days after surgery and the amount of intraoperative bleeding were compared between the two groups.

Results

After propensity score matching, 105 patients of each group were matched. The incidence of perioperative thromboembolic events in the no-aspirin group was significantly higher than that in the aspirin group [7/105 (6.7%) vs 0/105 (0%), 95% CI 1.44–∞, P = 0.016]. In contrast, neither the frequency of exogenous transfusion [21.0% vs 11.4%, 95% CI 0.88–4.38 P = 0.110] nor the amount of intraoperative bleeding [median (interquartile range), ml: 230 (70–500) vs 208 (50–500), P = 0.325] was different between the two groups.

Conclusion

Although the sample size is relatively small, our findings suggest that continuation of aspirin administration is likely to reduce the thrombotic risk but unlikely to increase the bleeding risk of patients who undergo major abdominal surgery for malignancy.



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Virtual reality experiences, embodiment, videogames and their dimensions in neurorehabilitation

In the context of stroke rehabilitation, new training approaches mediated by virtual reality and videogames are usually discussed and evaluated together in reviews and meta-analyses. This represents a serious ...

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Conditional Inactivation of Nf1 and Pten in Schwann Cells Results in Abnormal Neuromuscular Junction Maturation

The neuromuscular junction (NMJ) consists of three components, namely presynaptic motor neurons, postsynaptic muscle fibers and perisynaptic Schwann cells (PSCs). The role of Schwann cells (SCs) in regulating NMJ structural and functional development remains unclear. In this study, mice with conditional inactivation of neurofibromin 1 (Nf1) and phosphatase and tensin homolog (Pten), specifically in SCs, resulted in delayed NMJ maturation that led to delayed muscle growth, recapitulating the muscular dystrophy condition observed in human neurofibromatosis type I syndrome (NF1) patients. Expression levels of NMJ development related molecules such as cholinergic receptor, nicotinic, alpha polypeptide 1 (Chrna1), agrin (Agrn), dystrophin, muscular dystrophy (Dmd), laminin, beta 2 (Lamb2) and dystroglycan 1 (Dag1) were also downregulated. To further explore the molecular alterations in these SCs, NF1- and PTEN-related pathways were analyzed in mutant sciatic nerves. As expected, hyperactive RAS/PI3K/AKT/mTOR signaling pathways were identified, suggesting the importance of these pathways for NMJ development, and subsequent muscle maturation.



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Bi‐allelic recessive loss‐of‐function mutations in FIGLA cause premature ovarian insufficiency with short stature

Clinical Genetics Bi‐allelic recessive loss‐of‐function mutations in FIGLA cause premature ovarian insufficiency with short stature

Premature ovarian insufficiency (POI) is a group of heterogeneous disorders characterized by decreased ovarian reserve and increased follicle stimulating hormone (FSH) levels. It is rarely associated with short stature. FIGLA mutations with POI are identified with regards to heterozygosity; till date, only one affected family has been identified with homozygous mutations in FIGLA but without functional evaluation. Here, we described two POI patients from a consanguineous family from China. An 18‐year‐old girl and her sister presented with primary amenorrhea and increased FSH and luteinizing hormone levels, but the sister also presented with short stature and bone age delay. Whole‐genome sequencing analysis identified a recurrent homozygous mutation in the FIGLA gene, c.2T>C (p.Met1Thr), in this family member with POI; this variant was segregated within the pedigree. This change was absent in 382 control subjects, and we did not detect any mutations in 39 other idiopathic POI patients. In vitro functional analysis indicates that the p.Met1Thr mutation does not affect the transcription of the FIGLA gene, but blocks the synthesis of the full‐length FIGLA protein. Our results support the notion that bi‐allelic recessive loss‐of‐function effects of FIGLA contribute to POI patients with short stature and expand the FIGLA‐related phenotypic spectrum.

This article is protected by copyright. All rights reserved.



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Prospective study of clinical, neurophysiological and urodynamic findings in multiple scleosis patients undergoing percutaneous transluminal venous angioplasty

Multiple Sclerosis (MS) is a multifactorial disease (Lucchinetti et al. 2000; Compston and Cole 2008): perivenular inflammation in the white matter followed by demyelination of central nervous fibers, together with axonal loss and neurodegeneration, contribute to affect sensory (somatic, visual, auditory) motor, cognitive and urinary system functions, leading to increase of disability over time. In animal models, demyelination slows down conduction properties of neural pathways and reduces the ability to transmit neural impulses at high frequency; when combined with axonal degeneration, partial or complete conduction blocks may also occur (McDonald and Sears 1970), leading to functional impairment in virtually all sensory and motor domains.

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De novo temporal intermittent rhythmic delta activity after laser interstitial thermal therapy for mesial temporal lobe epilepsy predicts poor seizure outcome

Temporal intermittent rhythmic delta activity (TIRDA) is an EEG pattern characterized by intermittent rhythmic sinusoidal bursts and trains of delta activity localized over the temporal regions (Cobb, 1945). Unlike other intermittent rhythmic delta activities such as occipital intermittent rhythmic delta activity (OIRDA) and frontal intermittent rhythmic delta activity (FIRDA), TIRDA represents a pre-operative EEG pattern that predicts focal seizures in patients with temporal lobe epilepsy (TLE) (Reiher et al., 1989).

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Disruption of Function: Neurophysiological markers of cognitive deficits in retired football players

An estimated 1.6-3.8 million sports-related traumatic brain injuries (TBIs) occur every year in the United States alone (Langlois et al., 2006a; 2006b). An uncomplicated mild-traumatic brain injury (MTBI), more commonly referred to as concussion (Maroon et al., 2000; McCrory et al., 2009; Guskiewicz and Mihalik, 2011; Iverson et al., 2012; Zetterberg and Blennow, 2016), has been described as a serious public health concern (Ommaya and Gennarelli, 1974; Gronwall, 1977; McCrory et al., 2009). Concussion, a "complex pathophysiological process affecting the brain, induced by traumatic biomechanical forces" (McCrory et al., 2009), has been shown to negatively affect cognition, social functioning, emotional wellbeing, and neurologic function years after initial diagnosis (Collins et al., 1991; Dekosky et al., 2010; Kraus et al., 2016).

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Cortical networks are disturbed in people with cirrhosis even in the absence of neuropsychometric impairment

The term 'hepatic encephalopathy' is used to describe the spectrum of neuropsychiatric change which commonly complicates the course of cirrhosis (Vilstrup et al., 2014). People with cirrhosis with clinically apparent impairment in mental and motor performance, for which there is no other discernible cause, are classified as having overt hepatic encephalopathy. Those with no apparent clinical neuropsychiatric deficits who nevertheless show neuropsychometric or neurophysiological abnormalities are classified as having minimal hepatic encephalopathy (Vilstrup et al., 2014).

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Simultaneously recorded intracranial and scalp high frequency oscillations help identify patients with poor postsurgical seizure outcome

Around one third of patients with focal epilepsy continue to have seizures even after therapy with several different antiepileptic drugs (Kwan and Brodie 2000). In these patients epilepsy surgery aiming to remove the epileptic focus is a very effective treatment to stop seizures permanently (Rosenow and Lüders 2001). In some patients non-invasive diagnostic such as MRI and long-term EEG do not lead to conclusive results regarding the epileptic focus. In these patients intracranial chronic EEG recording may be used to delineate the seizure onset zone (SOZ) and define which brain areas have to be removed to have a good postsurgical seizure outcome (Diehl and Lüders 2000).

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Micturition and startle-induced reflex seizures in a patient with focal cortical dysplasia in the middle frontal gyrus

Reflex seizures arise from hyperexcitable cortex within the areas physiologically activated during specific sensory stimulations, and cognitive or motor activities. Micturition-induced seizures are rare, only a few clinical cases have been reported, all with normal neuroimaging findings, and EEG indicative of fronto-central onset (Whitney and Callen, 2013; Jang et al., 2018). Startle seizures are induced by sudden and unexpected stimuli, usually noise. Most of the patients have widespread structural brain abnormalities, predominantly in the frontal, temporal and perisylvian cortices (Palmini et al., 2005; Yang 2010).

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Gain‐of‐function variants in the ODC1 gene cause a syndromic neurodevelopmental disorder associated with macrocephaly, alopecia, dysmorphic features, and neuroimaging abnormalities

Polyamines serve a number of vital functions in humans, including regulation of cellular proliferation, intracellular signaling, and modulation of ion channels. Ornithine decarboxylase 1 (ODC1) is the rate‐limiting enzyme in endogenous polyamine synthesis. In this report, we present four patients with a distinct neurometabolic disorder associated with de novo heterozygous, gain‐of‐function variants in the ODC1 gene. This disorder presents with global developmental delay, ectodermal abnormalities including alopecia, absolute or relative macrocephaly, and characteristic facial dysmorphisms. Neuroimaging variably demonstrates white matter abnormalities, prominent Virchow–Robin spaces, periventricular cysts, and abnormalities of the corpus callosum. Plasma clinical metabolomics analysis demonstrates elevation of N‐acetylputrescine, the acetylated form of putrescine, with otherwise normal polyamine levels. Therapies aimed at reducing putrescine levels, including ODC1 inhibitors, dietary interventions, and antibiotics to reduce polyamine production by gastrointestinal flora could be considered as disease‐modifying therapies. As the ODC1 gene has been implicated in neoplasia, cancer surveillance may be important in this disorder.



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The accuracy of computer‐based diagnostic tools for the identification of concurrent genetic disorders

The increasing use of next‐generation sequencing, especially clinical exome sequencing, has revealed that individuals having two coexisting genetic conditions are not uncommon occurrences. This pilot study evaluates the efficacy of two methodologically distinct computational differential diagnosis generating tools—FindZebra and SimulConsult—in identifying multiple genetic conditions in a single patient. Clinical query terms were generated for each of 15 monogenic disorders that were effective in resulting in the top 10 list of differential diagnoses for each of the 15 monogenic conditions when entered into these bioinformatics tools. Then, the terms of over 125 pairings of these conditions were entered using each tool and the resulting list of diagnoses evaluated to determine how often both diagnoses of a pair were represented in that list. Neither tool was successful in identifying both members of a pair of conditions in greater than 40% of test cases. Disorder detection sensitivity was not homogeneous within a tool, with each tool favoring the identification of a subset of genetic conditions. In view of recent exome sequencing data showing an unexpectedly high prevalence of coexistent monogenic conditions, the results from this pilot study highlight a need for the development of computational tools designed to effectively generate differential diagnoses with consideration of the possibility of coexisting conditions.



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Colonoscopy-related complications in a nationwide immunochemical fecal occult blood test-based colorectal cancer screening program

Clinical Epidemiology

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Development of microsatellite markers and analysis of genetic diversity of Barbatia virescens in the southern coasts of China

Abstract

Background

The blood clam Barbatia virescens is an ecologically and economically important species in the southern coast of China. Understanding of the genetic structure of B. virescens populations is vital to breeding strategies and conservation programs.

Objective

To develop and characterize a set of microsatellites loci primers for B. virescens, and provide helpful information for reasonable utilization and protection of B. virescens natural resources.

Methods

The microsatellites of B. virescens were detected using a RAD-seq approach based on an Illumina sequencing platform. For the test of microsatellite development, we calculated the number of alleles (Na), observed heterozygosities (Ho), expected heterozygosities (He) and exact tests for deviations from Hardy–Weinberg equilibrium (HWE). Twelve polymorphic loci were used to access the genetic diversity and population structure of four B. virescens populations.

Results

In this study, 50,729 microsatellites of B. virescens were detected. Twenty-two polymorphic microsatellite loci were developed for B. virescens. The number of alleles per locus ranged from 6 to 15, and expected heterozygosities varied from 0. 567 to 0.911. All the PIC values of the 22 loci were greater than 0.5, indicating that these markers were highly informative for further genetic analysis. Twelve loci were selected to analyze genetic diversity and population structure of four B. virescens populations collected from different geographical regions along the southern coast of China. The results showed moderate to high levels of genetic diversity in the four populations (mean Ar = 7.756–8.133; mean Ho = 0.575–0.639; mean He = 0.754–0.775). Pairwise FST estimates indicated that there was significant divergence among the four populations.

Conclusion

This study not only provides a large scale of sequence information of microsatellites which are valuable for future genetic mapping, trait association and kinship among B. virescens, but also offers useful information for the sustainable management of natural stocks and the development of breeding industry of B. virescens.



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Ultra-deep amplicon sequencing indicates absence of low-grade mosaicism with normal cells in patients with type-1 NF1 deletions

Abstract

Different types of large NF1 deletion are distinguishable by breakpoint location and potentially also by the frequency of mosaicism with normal cells lacking the deletion. However, low-grade mosaicism with fewer than 10% normal cells has not yet been excluded for all NF1 deletion types since it is impossible to assess by the standard techniques used to identify such deletions, including MLPA and array analysis. Here, we used ultra-deep amplicon sequencing to investigate the presence of normal cells in the blood of 20 patients with type-1 NF1 deletions lacking mosaicism according to MLPA. The ultra-deep sequencing entailed the screening of 96 amplicons for heterozygous SNVs located within the NF1 deletion region. DNA samples from three previously identified patients with type-2 NF1 deletions and low-grade mosaicism with normal cells as determined by FISH or microsatellite marker analysis were used to validate our methodology. In these type-2 NF1 deletion samples, proportions of 5.3%, 6.6% and 15.0% normal cells, respectively, were detected by ultra-deep amplicon sequencing. However, using this highly sensitive method, none of the 20 patients with type-1 NF1 deletions included in our analysis exhibited low-grade mosaicism with normal cells in blood, thereby supporting the view that the vast majority of type-1 deletions are germline deletions.



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Cortical networks are disturbed in people with cirrhosis even in the absence of neuropsychometric impairment

Publication date: Available online 26 November 2018

Source: Clinical Neurophysiology

Author(s): Søren S. Olesen, Clive D. Jackson, Mikkel Gram, Harry D. Zacharias, Meike Dirks, Karin Weissenborn, Asbjørn M. Drewes, Marsha Y. Morgan

Abstract
Objective

Hepatic encephalopathy is a common complication of cirrhosis; it is characterised by neuropsychometric/neurophysiological abnormalities. Its pathophysiology is complex but glial neuronal communication is likely to be disrupted and to impact on oscillatory networks and cortical connectivity. The aim of this study was to use multichannel electroencephalography (EEG) to investigate functional connectivity, as a surrogate for cortical networks, in patients with cirrhosis.

Methods

Resting EEGs were recorded in 98 healthy controls and in 264 patients with cirrhosis characterised psychometrically using the Psychometric Hepatic Encephalopathy Score (PHES). Functional connectivity was calculated using the phase-lag index with stratification into standard EEG frequency bands. The findings were validated in a further cohort of 39 healthy controls and 106 patients with cirrhosis.

Results

Widespread disruption in functional connectivity was observed in the patients compared with the controls; connectivity was increased in the theta (4-8 Hz) band and decreased in the delta (1–3.5 Hz), alpha (8.5–13 Hz) and beta (13.5–26.5 Hz) bands. Changes were apparent even in patients who were psychometrically unimpaired compared with healthy controls viz mean ± SEM theta 0.107±0.001 vs. 0.103±0.002 (p<0.05) and alpha.0.139±0.003 vs. 0.154±0.003 (p<0.01); more pronounced changes were observed with increasing neuropsychometric impairment. Findings were replicated in the second cohort.

Conclusions

Cortical networks are disturbed in patients with cirrhosis even in the absence of psychometric impairment.

Significance

These findings will facilitate further exploration of the pathophysiology of this condition and provide a robust means for assessing treatment effects in research settings.



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Micturition and startle-induced reflex seizures in a patient with focal cortical dysplasia in the middle frontal gyrus

Publication date: Available online 26 November 2018

Source: Clinical Neurophysiology

Author(s): Cvetkovska Emilija, Babunovska Marija, Kuzmanovski Igor, Boskovski Bojan, Trencevska Kiteva Gordana



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Disruption of Function: Neurophysiological markers of cognitive deficits in retired football players

Publication date: Available online 26 November 2018

Source: Clinical Neurophysiology

Author(s): Kyle I. Ruiter, Rober Boshra, Mitchell Doughty, Michael Noseworthy, John F. Connolly

Abstract
Objective

Recent studies demonstrate that sports-related concussions can have negative consequences on long-term brain health. The goal of the present study was to determine whether retired Canadian Football League (CFL) athletes with a history of concussions exhibit alterations in neurocognitive functioning, along with changes in physical, social, and psychological health.

Methods

Our study compared twenty retired CFL athletes' concussion histories to eighteen healthy age-matched controls with no history of concussion. Self-report inventories were used to assess depression, memory, attention, and general health. Neurophysiological markers of cognitive function were evaluated with event-related brain potentials (ERPs) as measured in two protocols: 1) A Mismatch Negativity (MMN) protocol for assessing the automatic early attentional brain mechanism; and, 2) a P300 auditory oddball task for assessing consciously controlled attention.

Results

Relative to controls, CFL players exhibited: response delays and reduced amplitudes in neurophysiological responses; overall decreases in cognitive function; and poorer scores on self-reports of physical, social, and psychological health; reflecting problems in all three categories.

Conclusion

Our findings demonstrate that multiple concussions sustained over several years can lead to altered cognitive and psychosocial function.

Significance

Neurophysiological markers of conscious and pre-conscious attention provide an objective assessment for evaluating long-term cognitive consequences of concussion.



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Simultaneously recorded intracranial and scalp high frequency oscillations help identify patients with poor postsurgical seizure outcome

Publication date: Available online 26 November 2018

Source: Clinical Neurophysiology

Author(s): N. Kuhnke, C. Klus, M. Dümpelmann, A. Schulze-Bonhage, J. Jacobs

Abstract
Objective

High frequency oscillations (HFO) between 80-500 Hz are markers of epileptic areas in intracranial and maybe also scalp EEG. We investigate simultaneous recordings of scalp and intracranial EEG and hypothesize that scalp HFOs provide important additional clinical information in the presurgical setting. Methods: Spikes and HFOs were visually identified in all intracranial scalp EEG channels. Analysis of correlation of event location between intracranial and scalp EEG as well as relationship between events and the SOZ and zone of surgical removal was performed.

Results

24 patients could be included, 23 showed spikes and 19 HFOs on scalp recordings. In 15/19 patients highest scalp HFO rate was located over the implantation side, with 13 patients having the highest scalp and intracranial HFO rate over the same region. 17 patients underwent surgery, 7 became seizure free. Patients with poor post-operative outcome showed significantly more regions with HFO than those with seizure free outcome.

Conclusions

Scalp HFOs are mostly located over the SOZ. Widespread scalp HFOs are indicative of a larger epileptic network and associated with poor postsurgical outcome.

Significance

Analysis of scalp HFO add clinically important information about the extent of epileptic areas during presurgical simultaneous scalp and intracranial EEG recordings.



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Prospective study of clinical, neurophysiological and urodynamic findings in multiple scleosis patients undergoing percutaneous transluminal venous angioplasty

Publication date: Available online 26 November 2018

Source: Clinical Neurophysiology

Author(s): Monica Ulivelli, Lucia Monti, Michele Ballerini, Sabina Bartalini, Alfonso Cerase, Filippo Cecconi, Gerardo Pizzirusso, Daiana Bezzini, Alessandro Rossi, Simone Rossi

Abstract
Objective

verify whether Percutaneous Transluminal Angioplasty (PTA) may affect neural conduction properties in Multiple Sclerosis (MS) patients, thereby modifying patients' disability, with prospective neurophysiological, urodynamic, clinical and subjective well-being evaluations.

Methods

in 55 out of 72 consecutively screened MS patients, the following procedures were carried out before (T0), at 2-6 months (T1) and at 6-15 months (T2) after a diagnostic phlebography, eventually followed by the PTA intervention if chronic cerebrospinal venous insufficiency (CCSVI) was diagnosed: clinical/objective evaluation (Expanded Disability Status Scale, EDSS), ratings of subjective well-being, evaluation of urodynamic functions and multimodal EPs (visual, acoustic, upper and lower limbs somatosensory and motor evoked potentials).

Results

the number of dropouts was relatively high, and a complete set of neurophysiological and clinical data remained available for 37 patients (19 for urological investigations). The subjective well-being score significantly increased at T1 and returned close to basal values at T2, but their degree of objective disability did not change. Nevertheless, global EP-scores (indexing the impairment in conductivity of central pathways in multiple functional domains) significantly increased from T0 (7.9 ± 6.0) to T1 (9.2 ± 6.3) and from T0 to T2 (9.8 ± 6.3), but not from T1 and T2 (p>0.05). Neurogenic urological lower tract dysfunctions slightly increased throughout the study.

Conclusions

The PTA intervention did not induce significant changes in disability in the present cohort of MS patients, in line with recent evidence of clinical inefficacy of this procedure.

Significance

absence of multimodal neurophysiological and functional testing changes in the first 15 months following PTA suggests that conduction properties of neural pathways are unaffected by PTA. Current findings suggest that the short-lived (2-6 months), post-PTA, beneficial effect on subjective well-being measures experienced by MS patients is likely related to a placebo effect.



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De novo temporal intermittent rhythmic delta activity after laser interstitial thermal therapy for mesial temporal lobe epilepsy predicts poor seizure outcome

Publication date: Available online 26 November 2018

Source: Clinical Neurophysiology

Author(s): William O. Tatum, Neeharika Thottempudi, V. Gupta, A.M. Feyissa, Sanjeet S. Grewal, Robert Wharen, Michael A. Pizzi

Abstract
Objective

To evaluate EEG abnormalities, particularly development of temporal intermittent rhythmic delta activity (TIRDA) after laser interstitial thermal therapy (LITT) and assess the role of further surgery after LITT.

Methods

We retrospectively identified consecutive cases of LITT for the prevalence of post-operative TIRDA. We assessed baseline demographics, clinical variables including age of seizure onset, age at surgery, pre-operative and post-operative EEG changes.

Results

40 patients underwent LITT for drug-resistant temporal lobe epilepsy (TLE), 29 met inclusion criteria. Median duration of follow-up was 15 months. Ten patients had post-LITT ipsilateral TIRDA, another two demonstrated post-operative TIRDA but they occurred contralateral to the side of ablation. None of the patients with TIRDA on their post-LITT EEG became seizure-free. Six out of 29 patients (21%) eventually required anterior temporal lobectomy (ATL), and of those 6 patients 4 (66%) had evidence of TIRDA on their post-LITT follow up EEG. The sensitivity and specificity of post-LITT TIRDA in predicting surgical failure was 57.14 % and 100% respectively.

Conclusions

Post-LITT TIRDA may serve as a biomarker to predict unsuccessful seizure outcome following LITT and be an early indicator for ATL.

Significance

The presence of TIRDA following LITT should prompt early consideration for reoperation.



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Genetic Diversity of Norovirus Infections, Coinfections, and Undernutrition in Children From Brazilian Semiarid Region

imageBackground and Objective: Norovirus (NoV) infections are known to have high-morbidity and mortality rates and are a major health problem globally. The impact of NoV on child development is, however, poorly understood. We evaluated the distribution of NoV genotypes in children from a low-income Brazilian semiarid region, in relation with their clinical symptoms, nutritional status, and co-pathogens. Methods: The test population included children aged 2 to 36 months from 6 cities of the Brazilian semiarid region. Fecal samples were collected from each child, along with the information regarding their socioeconomic/clinical conditions using a standardized questionnaire. Detection and quantification of NoV were performed by reverse-transcription quantitative polymerase chain reaction, followed by molecular and phylogenetic analyses. Results: The NoV detection rate was 45.2%. Presence of NoV was associated with lower z scores for weight-for-age (P = 0.03), weight-for-height (P = 0.03), and body mass index-for-age (P = 0.03). NoV infection was associated with more frequent respiratory illnesses (P 

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Osseous Metaplasia in a Juvenile Rectal Polyp

imageNo abstract available

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ESPGHAN Distinguished Service Award 2018 to Professor Markku Mäki

imageNo abstract available

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Classification and Nutrition Management of Acute Pancreatitis in the Pediatric Intensive Care Unit

imageThe aims of this retrospective cohort study were to classify the severity of patients admitted to the pediatric intensive care unit (PICU) with acute pancreatitis (AP) and to identify how many patients received appropriate nutritional management in accordance with more recent guidelines and the outcomes of those patients. Of the 54 children with AP, 12 (22.2%) had a primary diagnosis of AP (50% severe, 17% moderate) whereas 42 (77.8%) had a secondary diagnosis of AP (81% severe, 11.9% moderate). Just under half of the patients (48.1%) had enteral nutrition commenced before the third day of admission (50% with primary AP, 47.6% with secondary AP). The average time to initiation of enteral feeds was 2.3 days for those that received enteral nutrition. 51.8% of patients received parenteral nutrition (25% with primary AP, 59.5% with secondary AP). Most patients received enteral nutrition late and parenteral nutrition was overused in patients with AP admitted to the PICU.

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Clarifying the Definition of Breast-Milk Substitutes

No abstract available

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Parent-child Agreement on Health-Related Quality of Life in Children With Functional Constipation in Primary Care

imageObjective: Functional constipation (FC) has a major impact on the health-related quality of life (HRQoL) of children. The aim of this study was to evaluate parent-child agreement on HRQoL in children (8–17 years) with FC in primary care. Methods: Children diagnosed with FC by their clinician were eligible. HRQoL was measured with the Defecation Disorder List (DDL, score 0–100), and the EuroQol-5-Dimension-Youth Visual Analogue Scale (EQ-5D-Y-VAS, scale 0–100). Parent-child agreement was examined with discrepancy scores, intraclass correlation coefficients and Bland-Altman plots. Results: Fifty-six children, median age of 10 years (IQR 8–12) and their parents were included. Parent-child agreement at a group level was good, with an intraclass correlation coefficient of 0.80 (95% confidence interval 0.67 to 0.88) for the DDL, and 0.78 (95% confidence interval 0.65 to 0.87) for the EQ-5D-Y-VAS. Mean discrepancy scores for the DDL and EQ-5D-Y-VAS were small: −2.6 and −2.9, implying that parents were slightly more positive about the HRQoL than their children. Bland-Altman plots showed considerable discordance between individual parent-child pairs. Limits of agreement were −19.7 and 14.6 for the DDL and −27.6 and 21.8 for the EQ-5D-Y-VAS. Conclusions: There is good parent-child agreement on HRQoL in children with FC at group level. However, a substantial number of parent-child pairs differed considerably on their rating of the HRQoL of the child. Therefore, we recommend clinicians, if they want to have an impression of the impact of the FC on the HRQoL of the child, to ask both the child and the parent(s).

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There Is No Excuse for Mortality Due to Lack of Competency and Training of Paediatric Endoscopists in Gastrointestinal Bleeding Therapy in 2018

imageAcute upper gastrointestinal bleeding in children is possibly the last medical emergency which continues to lead to the death of a child due to the lack of competency/clinical judgement of the doctor, as opposed to the disease itself, leading to mortality despite optimum medical intervention. This is unacceptable in any circumstances in 2018. It occurs due to a number of conspiring factors including lack of appreciation of the clinical presentation requiring urgent endoscopic intervention; misapprehension of the urgency of timing required of such an intervention predicated on the severity of the gastrointestinal (GI) bleed; lack of application of a paediatric-specific validated score predicting for such endoscopic intervention; lack of skill in endo-haemostatic intervention techniques by paediatric endoscopists; poor training in such techniques among paediatric endoscopists; paucity of cases with lack of exposure of the paediatric endoscopist regularly to enable skills to be maintained, once acquired; reluctance of adult endoscopists in many centres to support paediatric GI bleeding services. In essence then the paediatric GI community urgently needs to identify centres of excellence to whom these children should be transferred. Transfer is safe in all but the most critical cases once stabilised with transfusion, octreotide/terlipressin and iv proton pump inhibitors. The resources are country-dependent but this is really no excuse. We must not let this parlous state of affairs continue. Solutions are explored in this article and please let this serve as a call to action for all those involved in this continuing debacle in order to save "save-able" lives.

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Switching From Originator to Biosimilar Infliximab in Paediatric Inflammatory Bowel Disease Is Feasible and Uneventful

imageThe safety, clinical efficacy, and cost-effectiveness of biosimilar infliximab in adult inflammatory bowel disease (IBD) have now been extensively shown. Limited data have been collected in the paediatric setting. We report nationwide, prospective, clinical safety and effectiveness data for patients from all 3 Scottish paediatric inflammatory bowel disease networks switching from originator to biosimilar infliximab. Prospective clinical data were collected for 33 patients. Information was collected from electronic patient records, laboratory reports, and patient case notes. There were no clinically significant changes to disease activity, biomarkers, antidrug antibodies, or trough drug levels (P > 0.1) within a 12-month follow-up period; in addition, there were no significant adverse events reported. No infusion reactions were seen in the 264 infusions delivered. Switching from originator infliximab to the biosimilar (CT-P13) appears to be associated with neither an increase in infusion reactions nor significant loss of effectiveness in the short term.

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Prognosis of Biliary Atresia After 2-year Survival With Native Liver: A Nationwide Cohort Analysis

imageObjectives: The aim of the study is to determine the prognosis of patients with biliary atresia after 2 years of native liver survival (NLS) and to identify prognostic factors for continued NLS after 2 years of age. Methods: We retrospectively analyzed perioperative, laboratory, and outcome parameters of all biliary atresia patients in The Netherlands between January 1987 and June 2015 with NLS of at least 2 years. We compared parameters between patients who continued to have their native liver (NLS+) to those who did not, either by transplant or death (NLS−). Results: We included 100 patients. Upon a median follow-up of 16.4 years, NLS ended in 37% by liver transplantation (LTx) and in 6% by (pre-transplant) mortality. NLS rates at 5, 10, 15, 18 years of age were 89%, 72%, 60%, 54%, respectively. Corresponding overall survival rates were 98%, 90%, 87%, 87%, respectively. Six months post-Kasai, NLS+ patients had higher clearance of jaundice (COJ) rate, significantly lower total and direct serum bilirubin, aspartate-aminotransferase and alkaline phosphatase levels, compared with NLS− patients (each P 

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Lack of Benefit of Lactobacillus reuteri DSM 17938 as an Addition to the Treatment of Functional Constipation

imageThe aim of this study was to investigate the role of Lactobacillus reuteri DSM 17983 in the treatment of functional constipation in children. The trial was a single-center randomized, double-blind, placebo-controlled study. Patients were allocated into the 2 groups; intervention group which received L reuteri DSM 17983 and lactulose and placebo group which received placebo and lactulose. Due to small recruitment rate study was terminated prematurely; therefore, only 33 children (12 girls, median age 4.5 years, range 2–16) were randomized. There was no difference between groups in the stool frequency, stool consistency, pain, soiling rate and dose of the lactulose. This study found that L reuteri DSM 17938 adds no benefit to the treatment of constipation in children. Due to small sample size, these results, however, should be interpreted with caution.

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Lower 6-MMP/6-TG Ratio May Be a Therapeutic Target in Pediatric Autoimmune Hepatitis

imageBackground: Azathioprine (AZA) is the mainstay of maintenance therapy in pediatric autoimmune hepatitis (AIH). The use of thiopurines metabolites to individualize therapy and avoid toxicity has not, however, been clearly defined. Methods: Retrospective analysis of children ≤18 years diagnosed with AIH between January 2001 and 2016. Standard definitions were used for treatment response and disease flare. Thiopurine metabolite levels were correlated with the corresponding liver function test. Results: A total of 56 children (32 girls) were diagnosed with AIH at a median age of 11 years (interquartile range [IQR] 9). No difference in 6-thioguanine-nucleotide (6-TG) levels (271[IQR 251] pmol/8 × 108 red blood cell vs 224 [IQR 147] pmol/8 × 108 red blood cell, P = 0.06) was observed in children in remission when compared with those who were not in remission. No correlation was observed between the 6-TG and alanine aminotransferase levels (r = −0.179, P = 0.109) or between 6-methyl-mercaptopurine (6-MMP) and alanine aminotransferase levels (r = 0.139, P = 0.213). The 6-MMP/6-TG ratio was significantly lower in patients who were in remission (2[7] vs 5 (10), P = 0.04). Using a quartile analysis, we found that having a ratio of

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2018 Reviewer Acknowledgment

No abstract available

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Incidence and Clinical Features of Autoimmune Hepatitis in the Province of Santa Fe (Argentina)

imageObjetives: The aim of the study is to investigate the incidence and clinical features of autoimmune hepatitis (AIH) in children from the province of Santa Fe, Argentina, for 10 years. Methods: From the records of all of the pediatric hepatologists in the province of Santa Fe, Argentina, we reviewed the clinical charts of patients 6 points) and followed between January 2003 and December 2013. Population data were extracted from the 2010 national census. Values were expressed as percentages and median ± interquartile range. Mann-Whitney U test was used for comparison between the groups. Results: Sixty-seven patients fulfilled inclusion criteria, from which 11 (16%) were later reclassified as having "autoimmune sclerosing cholangitis" according to biochemical, histological, and radiological findings. A final sample of 56 patients (39 F) with AIH was analyzed, giving an annual incidence of 0.56/100,000. Median age at presentation was 8 (5.7–11) years, and the median follow-up was 4 (2–7) years. Type 1 AIH was diagnosed in 89%. An acute presentation was observed in 53%, while 13 (23%) showed cirrhosis on initial biopsy. Prednisone (87%) and azathioprine (60%) were the most common drugs prescribed. At the end of follow-up, 53/56 (95%) were alive, including 4 patients (7%) who underwent liver transplantation. Conclusions: AIH has an estimated incidence of 0.56/100,000 per year in children from the province of Santa Fe (Argentina). Overall survival rate was 95%. A subgroup of patients diagnosed as AIH develops predominant biliary disease and should be better classified as autoimmune sclerosing cholangitis.

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Polyethylene Glycol Maintenance Treatment for Childhood Functional Constipation: A Randomized, Placebo-controlled Trial

imageObjective: The aim of this study was to investigate the long-term efficacy of polyethylene glycol (PEG) during maintenance treatment of childhood functional constipation (FC) in a randomized, double-blinded, placebo-controlled trial. Methods: Children (2–16 years) with FC according to the Rome III criteria were randomly assigned to maintenance treatment with PEG or placebo for 24 weeks. Children reporting treatment failure before 24 weeks were switched to conventional treatment. Primary outcome was successful treatment, defined as absence of any Rome III criteria with or without use of medication after 24 weeks. Results: A total of 102 children were included: PEG/placebo: 49/53. At 24 weeks, significantly more patients in the PEG group, compared to the placebo group, were successfully treated (33 [67%] vs 19 [36%] hazard ratio (95% confidence intervals) = 3.21 [1.73–5.94]). Significantly fewer children in the PEG group switched to rescue medication (2 [4%] vs 30 [57%], P 

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Approach and Safety of Esophageal Dilation for Treatment of Strictures in Children With Epidermolysis Bullosa

imageObjective: The aim of the study is to analyze a large series of esophageal balloon dilations in patients with epidermolysis bullosa (EB) to determine procedural approach and frequency of post-endoscopic adverse events (AEs). Methods: Retrospective chart review for AE occurrence and clinical outcomes in children and adolescents with EB, age 1 to 19, who underwent esophageal dilation for esophageal stricture(s) from January 2003 to April 2016 at an academic, tertiary care, free-standing children's hospital. The primary outcome measure was occurrence of procedural AEs (defined as events occurring within 72 hours after endoscopic dilation procedure). Results: A total of 231 fluoroscopy-guided esophageal balloon dilation procedures (209 anterograde, 20 retrograde, 2 both) were performed in 24 patients. Strictures were more common in the proximal portion of the esophagus with median stricture location 13 cm from the lips. From 2003 to 2012, 4.1% of dilations were retrograde. From 2013 to 2016, 20.2% of dilations were retrograde. AEs attributable to dilation occurred after 10.0% of procedures, and the most common AEs were vomiting, pain, and fever. No esophageal perforations, serious bleeding events, or deaths occurred secondary to dilation. The rate of post-dilation hospitalization was 6.9%. Dilation approach (anterograde vs retrograde) did not impact the likelihood of AEs. Conclusions: The characteristic esophageal lesion in EB is a single, proximal esophageal stricture. EB patients can safely undergo repeat pneumatic esophageal balloon dilations with minimal risk for severe complication. We observed a trend towards increased use of retrograde esophageal dilation.

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Persistence of Muscle-bone Deficits Following Anti-tumour Necrosis Factor Therapy in Adolescents With Crohn Disease

imageObjectives: The aim of the study is to assess change in the muscle-bone unit in adolescents with Crohn disease (CD) on anti-tumour necrosis factor (anti-TNFα). Methods: Prospective study following anti-TNFα in 19 adolescents with CD with a median age (range) of 15.1 years (11.2, 17.2). At baseline, 6 and 12 months, subjects had a biochemical assessment of insulin growth factor axis, bone turnover and muscle-bone health by dual energy absorptiometry (DXA), peripheral quantitative computed tomography (pQCT), and dynamic isometry. Results: Significant clinical improvement in disease activity was observed by 2 weeks (P = 0.004 vs baseline) and maintained at 12 months (P = 0.038 vs baseline). Median bone specific alkaline phosphatase standard deviation score (SDS) increased from −1.7 (−3.6 to −1.0) to −1.2 (−3.6 to −0.5) by 6 weeks (P = 0.01). At baseline, DXA total body and lumbar spine bone mineral density (BMD) SDS was −0.9 (−2.3 to 0.5) and −1.1 (−2.9 to 0.4), respectively. At baseline, pQCT trabecular BMD SDS at 4% tibia and muscle cross-sectional area SDS at 66% radius was −1.6 (−3.2 to 1.1) and −2.4 (−4.3 to −0.3), respectively. At baseline, maximal isometric grip force (MIGF) of the non-dominant hand adjusted for height was −1.5 (−4.5 to 0.49). All these deficits in muscle-bone persisted at 6 and 12 months. Conclusions: Despite improvement in disease and osteoblast activity, bone and muscle deficits, as assessed by DXA, pQCT, and grip strength in adolescents with CD did not improve following twelve months of anti-TNFα.

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Endoscopic Esophageal Vacuum Therapy: A Novel Therapy for Esophageal Perforations in Pediatric Patients

imageBackground: Esophageal perforation is a potentially life-threatening problem if not quickly diagnosed and treated appropriately. Negative-pressure wound therapy, commercially known as V.A.C. therapy, was developed in the early 1990s and is now standard of care for chronic surface wounds, ulcers, and burns. Adapting vacuum sponge therapy for use intraluminally for perforations of the esophagus was first reported in 2008. We report the first pediatric experience on a customized esophageal vacuum–assisted closure (EVAC) device for closure of esophageal perforations. Aim: To evaluate the technical feasibility, safety, and efficacy of EVAC in a pediatric population with esophageal perforations and compare efficacy to a cohort of patients who underwent stenting for esophageal perforation. Methods: We performed an institutional review board–approved retrospective chart review on all patients who underwent EVAC for esophageal perforations (October 2013–September 2017) and who underwent externally removable stent placement for esophageal perforation (January 2010–December 2017) at our institution. Our primary aim was to evaluate technical feasibility, efficacy, and safety in the treatment of pediatric esophageal perforations. A secondary aim was to compare the efficacy of EVAC to esophageal stenting in healing esophageal perforations in our pediatric population. Results: A total of 17 patients with esophageal atresia underwent therapy for esophageal perforation. Eight sponges were placed for surgical perforation and 9 were placed after endoscopic therapy perforation. The median age of patients was 24 months with the youngest patient being 3 months of age. The success rate of EVAC to seal all esophageal perforations was 88% (15/17). The success rate was similar in both subgroups: surgical anastomotic leaks at 88% (7/8) and endoscopic therapy leaks at 89% (8/9). There were no technical failures with placement. The stent group had a total of 24 patients: 19 were placed secondary to perforations from endoscopic therapy and 5 were placed secondary to surgical anastomotic perforations. The success rate of stents to seal all esophageal perforations was 63% (15/24). The success rate in the subgroups was 74% (14/19) for endoscopic therapy leaks and 20% (1/5) for surgical anastomotic leaks. In comparing success of EVAC and stent therapy, we found a statistically significant difference in favor of EVAC in healing surgical anastomotic perforations (P = 0.032). There was, however, no statistical difference in healing endoscopic therapy perforations (P = 0.360). Conclusions: EVAC is a novel, promising technique for the treatment of esophageal perforations in a pediatric population. This treatment is comparable to esophageal stenting in iatrogenic endoscopic therapy perforations and superior to stenting surgical perforations. Further prospective studies are needed to compare the effectiveness of EVAC to esophageal stenting. Improvement in device design and customization could further improve success and ease of placement.

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Prospective Evaluation of the ESPGHAN Guidelines for Diagnosis of Celiac Disease in New Zealand Children

imageObjective: The 2012 European Society of Pediatric Gastroenterology, Hepatology and Nutrition (ESPGHAN) guideline for diagnosis of celiac disease (CD) questioned the requirement for intestinal biopsy to confirm the diagnosis. The guideline recommends that in symptomatic patients with consistent human leukocyte antigen (HLA) subtypes, the diagnostic accuracy of strongly positive serology is sufficient to confirm the diagnosis. We prospectively assessed these guidelines in a "real-life" clinical setting. Methods: One hundred and four children referred for evaluation of possible CD were prospectively recruited. Following informed consent, blood was drawn for serological testing and HLA analysis at upper gastrointestinal endoscopy. Histological findings according to Marsh criteria were correlated with blood results and the accuracy of the guideline analyzed. The study also examined the role of deamidated gliadin peptide (DGP) in the diagnosis of CD. Results: For symptomatic patients with consistent HLA subtypes, strongly positive serology (as described in the ESPGHAN guidelines) accurately predicted biopsy-proven CD in >95% of cases. DGP was positive in fewer patients than anti-TG2 or EMA. Incorporation of DGP as a second confirmatory serological test in place of EMA was associated with maintained predictive value of guideline, but fewer patients fulfilling criteria for biopsy-free diagnosis. Conclusions: The ESPGHAN guideline performs well in our population. Adoption of the guideline would reduce the number of patients requiring endoscopy without compromise in diagnostic accuracy. The involvement of pediatric gastroenterological expertise, however, remains key to diagnosis of CD.

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Piecemeal Deglutition and the Implications for Pressure Impedance Dysphagia Assessment in Pediatrics

imageObjectives: High-resolution impedance manometry (HRIM) enables biomechanical swallow assessment. Piecemeal deglutition (PD) defines swallowing of a single bolus in 2 or more portions. We investigated PD sequences on HRIM recordings to ascertain appropriate swallow selection for analysis and to determine the impact of PD on swallow function measures. Methods: Pharyngo-esophageal motility and bolus flow were assessed in 27 children (19 M, mean age 15 months) with repaired esophageal atresia and trachea-esophageal fistula, but who were asymptomatic of oropharyngeal dysphagia. A consistent volume of between 2 and 5 mL saline boluses was given to each patient. Retrospectively, PD sequences were defined based on the number of swallows required to clear the bolus from the oral cavity: pattern A = 1–2 swallows; pattern B = 3 swallows; and pattern C = 4+ swallows. The largest bolus volume swallowed was noted as the dominant swallow in each pattern. Pressure Flow Analysis defined contractility, distension and flow timing metrics. Data were averaged for each PD pattern, and compared with dominant swallows from each pattern. Results: PD pattern B (43.7%) was the most prevalent across the cohort. PD patterns were similarly distributed across age groups (G1:

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Is the WHO Creating Unnecessary Confusion Over Breast Milk Substitutes?

A recent statement by WHO that "breast milk substitutes should be understood to include any milks …that are specifically marketed for feeding infants and young children up to the age of 3 years" differs significantly from the definition in the International Code which states "a breast milk substitute is any food being marketed or otherwise presented as a partial or total replacement for breast milk, whether or not suitable for that purpose." The new interpretation, which lacks consultation and endorsement, is also ambiguous, with the boundaries between breast milk substitutes and complementary foods being blurred during the first 3 years of life. The logical definitions of breast milk substitutes and complementary foods contained within the Code should be maintained and inappropriate promotion of foods and fluids for infants and young children should be addressed through effective regulation of composition and labelling standards.

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From Total Volume to Sequence Maps—Sophisticated Accelerometer Data Analysis

Purpose To date, epidemiological studies have focused on the potential health effects of total volume of physical activity (PA) or sedentary behaviour (SB). However, two persons may have the same volume of PA or SB but accumulated in a completely different sequence. The pattern of accumulating PA and SB might be more important for health effects than the total volume. Therefore the aim was to develop a sophisticated algorithm translating accelerometer data into detailed sequence maps considering how PA and SB are accumulated throughout the day. Methods We developed a novel algorithm to convert accelerometer counts into a sequence map based on behaviour states defined by a combination of intensity (SB, light, moderate, and vigorous intensity) and duration (sporadic accumulation or in bouts of different duration). Additionally, hierarchical cluster analysis was applied to identify clusters of children with similar behavioural sequence maps. Results Clustering resulted in seven clusters of children with similar PA and SB sequence maps: an average cluster (33% of children); a cluster with relatively more SB, light and moderate PA in bouts (SB and PA bouters, 31%); a cluster characterized by more sporadic SB and light PA (light activity breakers, 26%); and four smaller clusters with 7% of the children or less. Conclusion This novel algorithm is a next step in more sophisticated analyses of accelerometer data considering how PA and SB are accumulated throughout the day. The next step is identifying whether specific patterns of accumulating PA and SB are associated with improved health outcomes. *Mai Chinapaw and Xinhui Wang contributed equally to the paper. Corresponding author: M.J.M. Chinapaw, PhD, Department of Public and Occupational Health, Amsterdam Public Health research institute, VU University Medical Center, Van der Boechorststraat 7, 1081 BT Amsterdam, The Netherlands, ph: +31 20 444 8203, f: +31 20 444 8387, m.chinapaw@vumc.nl The contributions of Chinapaw, Wang, and Altenburg were funded by the Netherlands Organization for Health Research and Development (ZonMw projectnr 91211057). The CHAMPS-study was funded by: The TRYG Foundation, University College Lillebaelt, University of Southern Denmark, The Nordea Foundation, The IMK foundation, The Region of Southern Denmark, The Egmont Foundation, The A.J. Andersen Foundation, The Danish Rheumatism Association, Østifternes Foundation, Brd. Hartmann's Foundation, TEAM Denmark, The Danish Chiropractor Foundation, The Nordic Institute of Chiropractic and Clinical Biomechanics. Conflict of interest: The authors have no relevant conflicts of interest to disclose, the results of the present study do not constitute endorsement by ACSM and the results of the study are presented clearly, honestly, and without fabrication, falsification, or inappropriate data manipulation. Accepted for Publication: 14 November 2018. © 2018 American College of Sports Medicine

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Grounded Running Reduces Musculoskeletal Loading

Purpose Recent observations demonstrate that a sizeable proportion of the recreational running population runs at rather slow speeds and does not always show a clear flight phase. This study determined the key biomechanical and physiological characteristics of this running pattern, i.e. grounded running (GR), and compared these characteristics with slow aerial running (SAR) and reference data on walking at the same slow running speed. Methods Thirty male subjects performed instructed GR and SAR at 2.10 m·s-1 on a treadmill. Ground reaction forces, tibial accelerations and metabolic rate were measured to estimate general musculoskeletal loading (external power and maximal vertical ground reaction force), impact intensity (vertical instantaneous loading rate and tibial acceleration) and energy expenditure. More explicit measures of muscular loading (muscle stresses and peak eccentric power) were calculated based on a representative subsample, in which detailed kinematics and kinetics were recorded. We hypothesized that all measures would be lower for the GR condition. Results Subjects successfully altered their running pattern upon a simple instruction towards a GR pattern by increasing their duty factor from 41.5% to 51.2%. As hypothesized, impact intensity, general measures for musculoskeletal and the more explicit measures for muscular loading decreased by up to 35.0%, 20.3% and 34.0% respectively compared to SAR. Contrary to our hypothesis, metabolic rate showed an increase of 4.8%. Conclusion Changing running style from SAR to GR reduces musculoskeletal loading without lowering the metabolic energy requirements. As such, GR might be beneficial for most runners as it has the potential to reduce the risk of running related injuries while remaining a moderate-to-vigorous form of physical activity, contributing to fulfillment of the recommendations concerning physical activity and public health. Corresponding author: Dirk De Clercq; Watersportlaan 2, 9000 Gent, Belgium; +32 9 264 63 22; dirk.declercq@UGent.be Mizuno Corporation provided financial and product support for this study. All authors declare no conflict of interest. The results of the study are presented clearly, honestly and without fabrication, falsification, or inappropriate data manipulation. The results of the present study do not constitute endorsement by ACSM. Accepted for Publication: 18 October 2018. © 2018 American College of Sports Medicine

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Quantifying Brain White Matter Microstructure of People with Lateral Ankle Sprain

Purpose This study aimed to quantify differences in white matter microstructure and static postural control in individuals with and without a previous history of a lateral ankle sprain. Methods Ten participants with a history of a lateral ankle sprain and 10 controls performed 3, 20-second trials of single-leg static balance on a force platform under an eyes-open condition. Resultant sample entropy (SampEn) was used to assess static postural control performance. To assess white matter microstructure, fractional anisotropy (FA) of the superior cerebellar peduncles and corticospinal tracts was quantified using diffusion tensor imaging (DTI). In the case of statistically significant differences in FA, component diffusivities were evaluated, including mean diffusivity, radial diffusivity (RD), and axial diffusivity (AD). Results Significant differences between participants with and without a history of lateral ankle sprains were observed in superior cerebellar peduncle FA and RD. Participants with a history of lateral ankle sprains had significantly lower FA in the superior cerebellar peduncle compared to controls. Participants with a history of lateral ankle sprains also demonstrated higher RD values in the superior peduncle compared to control. Finally, participants with a history of lateral ankle sprains had lower resultant SampEn values compared to controls. Conclusion Findings suggest that microstructural changes in white matter tracts governing postural control, may be biomarkers of central nervous system dysfunction in individuals with a lateral ankle sprain history. Correspondence: Masafumi Terada, College of Sport and Health Science, Ritsumeikan University, Shiga, Japan. mterada@fc.ritsumei.ac.jp No funding was received for this current study. The results of the current study are presented clearly, honestly, and without fabrication, falsification, or inappropriate data manipulation. The results of the present study do not constitute endorsement by ACSM. CONFLICT OF INTEREST: All authors declare that they have no conflict of interest. Accepted for publication November 2018. © 2018 American College of Sports Medicine

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