bluuebunny/crossref_metadata_2025 huggingface dataset:
Rationale and design of a single-blind, randomised controlled trial of exercise training for managing learning and memory impairment in persons with multiple sclerosis
Authors: Sandroff Brian M , Motl Robert W , Bamman Marcus , Cutter Gary R , Bolding Mark , Rinker John R , Wylie Glenn R , Genova Helen , DeLuca John
Published: December 2018

Introduction

This randomised controlled trial (RCT) examines treadmill walking exercise training effects on learning and memory performance, hippocampal volume, and hippocampal resting-state functional connectivity in persons with multiple sclerosis (MS) who have objective impairments in learning new information.

Methods and analysis

Forty fully ambulatory persons with MS who demonstrate objective learning and memory impairments will be randomly assigned into either the intervention or active control study conditions. The intervention condition involves supervised, progressive treadmill walking exercise training three times per week for a 3-month period. The active control condition involves supervised, progressive low-intensity resistive exercise that will be delivered at the same frequency as the intervention condition. The primary outcome will involve composite performance on neuropsychological learning and memory tests, and the secondary outcomes involve MRI measures of hippocampal volume and resting-state functional connectivity administered before and after the 3-month study period. Outcomes will be administered by treatment-blinded assessors using alternate test forms to minimise practice effects, and MRI data processing will be performed by blinded data analysts.

Ethics and dissemination

This study has been approved by a university institutional review board. The primary results will be disseminated via peer-reviewed publications and the final data will be made available to third parties in applicable data repositories. If successful, the results from this study will eventually inform subsequent RCTs for developing physical rehabilitation interventions (ie, treadmill walking exercise training) for improving learning and memory and its relationship with hippocampal outcomes in larger samples of cognitively impaired persons with MS. The results from this early-phase RCT will further lay preliminary groundwork for ultimately providing clinicians and patients with guidelines for better using chronic treadmill walking exercise for improving cognition and brain health. This approach is paramount as learning and memory impairment is common, burdensome and poorly managed in MS.

Trial registration number

NCT03319771; Pre-results.
Study protocol for a randomised controlled trial of humanoid robot-based distraction for venipuncture pain in children
Authors: Ali Samina , Sivakumar Mithra , Beran Tanya , Scott Shannon D , Vandermeer Ben , Curtis Sarah , Jou Hsing , Hartling Lisa
Published: December 2018

Introduction

Intravenous insertion (IVI) is a very common procedure in the emergency department (ED). IVI is often painful and stressful for both children and their families. Currently, distraction therapy is not used as a standard of care for IVI in North America. We propose that interaction with a humanoid robot may effectively distract children during IVI thereby reducing their pain and distress.

Methods and analysis

This randomised controlled superiority trial will be conducted in a Canadian paediatric ED. We plan to recruit 80 patients. Children will be eligible if they (1) are 6 to 11 years of age, (2) need an IVI, (3) are fully conscious and alert, (4) have sufficient knowledge of the English language to understand and complete the study assessments and (5) are accompanied by a legal guardian. Our primary objective is to compare patient-reported pain and distress with the use of distraction (via a humanoid robot) versus standard care in children. The primary outcomes will be (1) self-reported pain, as measured by the Faces Pain Scale—Revised and (2) observed distress, as measured by the Observational Scale of Behavioural Distress—Revised. Secondary outcomes will include (1) measuring parental anxiety, (2) examining the association between parental anxiety and child outcomes and (3) children’s degree of engagement with the humanoid robot via the Intrinsic Motivation Inventory tool. First enrolment occurred in April 2017 and is ongoing.

Ethics and dissemination

This study has been approved by the Health Research Ethics Board (University of Alberta). Informed consent to participate will be obtained from all participants’ parents/guardian, in conjunction with assent from the participant themselves. This study data will be submitted for publication regardless of results. Purchase of the robot was facilitated through a Stollery Children’s Hospital Foundation donation. Recruitment costs are supported by the Women and Children’s Health Research Institute.

Trial registration number

NCT02997631; Pre-results.
How is the audit of therapy intensity influencing rehabilitation in inpatient stroke units in the UK? An ethnographic study
Authors: Taylor Elizabeth , Jones Fiona , McKevitt Christopher
Published: December 2018

Objectives

Occupational therapy, physiotherapy and speech and language therapy are central to rehabilitation after a stroke. The UK has introduced an audited performance target: that 45 min of each therapy should be provided to patients deemed appropriate. We sought to understand how this has influenced delivery of stroke unit therapy.

Design

Ethnographic study, including observation and interviews. The theoretical framework drew on the work of Lipsky and Power, framing therapists as ‘street level bureaucrats’ in an ‘audit society’.

Setting

Stroke units in three English hospitals.

Participants

Forty-three participants were interviewed, including patients, therapists and other staff.

Results

There was wide variation in how therapy time was recorded and in decision-making regarding which patients were ‘appropriate for therapy’ or auditable. Therapists interpreted their roles differently in each stroke unit. Therapists doubted the validity of the audit results and did not believe their results reflected the quality of services they provided. Some assumed their audit results would inform commissioning decisions. Senior therapy leaders shaped priorities and practices in each therapy team. Patients were inactive outside therapy sessions. Patients differed regarding the quantity of therapy they felt they needed but consistently wanted to be more involved in decisions and treated as individuals.

Conclusions and implications

Stroke unit therapy has different meanings in different hospitals. Measuring therapy time is problematic due to varied interpretations of ‘what counts’ and variation in reporting practices. Although stroke policy, guidelines and audit are potential tools of improvement, their benefits are not automatic. Their actual effects depend largely on the attitudes and values of local influential ‘street level leaders’. More work is needed to promote an integrated whole team approach to rehabilitation. Further research into contextual and human factors, including the roles and views of therapy leaders, would enable a better understanding of implementation of guidelines and service improvement.
Exploring patient safety in Swedish specialised home healthcare: an interview study with multidisciplinary teams and clinical managers
Authors: Lindblad Marléne , Flink Maria , Ekstedt Mirjam
Published: December 2018

Objective

Home healthcare is the fastest growing arena in the healthcare system but patient safety research in this context is limited. The aim was to explore how patient safety in Swedish specialised home healthcare is described and adressed from multidisciplinary teams’ and clinical managers’ perspectives.

Design

An explorative qualitative study.

Setting

Multidisciplinary teams and clinical managers were recruited from three specialised home healthcare organisations in Sweden.

Methods

Nine focus group interviews with multidisciplinary teams and six individual interviews with clinical managers were conducted, in total 51 participants. The data were transcribed verbatim and analysed using qualitative content analysis.

Results

Patient safety was inherent in the well-established care ideology which shaped a common mindset between members in the multidisciplinary teams and clinical managers. This patient safety culture was challenged by the emerging complexity in which priority had to be given to standardised guidelines, quality assessments and management of information in maladapted communication systems and demands for required competence and skills. The multiple guidelines and quality assessments that aimed to promote patient safety from a macro-perspective, constrained the freedom, on a meso-level and micro-level, to adapt to challenges based on the care ideology.

Conclusion

Patient safety in home healthcare is dependent on adaptability at the management level; the team members’ ability to adapt to the varying conditions and on patients being capable of adjusting their homes and behaviours to reduce safety risks. A strong culture related to a patient’s value as a person where patients’ and families’ active participation and preferences guide the decisions, could be both a facilitator and a barrier to patient safety, depending on which value is given highest priority.
Reasons to stop drinking alcohol among patients with rheumatoid arthritis in Sweden: a mixed-methods study
Authors: Larsson Ingrid , Andersson Maria L E
Published: December 2018

Objectives

The aims were to identify patients with rheumatoid arthritis (RA) who had stopped drinking alcohol and compare them with patients drinking alcohol, and to explore reasons for stopping drinking alcohol.

Design

A sequential explanatory mixed methods design was used.

Setting

Six rheumatology clinics in Southern Sweden Better Anti-Rheumatic FarmacOTherapy cohort.

Participants

A total of 1509 patients completed the questions about alcohol and were included in the study. 86 of these had stopped drinking alcohol and 72 responded to the open question and their answers were analysed with qualitative content analysis.

Outcome measures

The quantitative data were from a cross-sectional survey assessing disease severity, physical function (Health Assessment Questionnaire, HAQ) and health-related quality of life (EuroQol five dimensions, EQ5D), pain, fatigue, patient global assessment (PatGA) and lifestyle factors, for example, alcohol. The questions assessing alcohol included an open question ‘Why have you stopped drinking alcohol?’

Results

The patients who stopped drinking alcohol were older (median (min-max) 69 (36–90) vs 66 (23–95), p=0.011), had worse HAQ (1.00 (0–2.75) vs 0.50 (0–3.00), p<0.001), worse EQ5D (0.69 (−0.02–1.00) vs 0.76 (−0.58–1.00), p<0.001) worse PatGA (5 (0–10) vs 3 (0–10), p<0.001), more pain (5 (0–10) vs 3 (0–10), p<0.001) and more fatigue (6 (0–10) vs 4 (0–10), p<0.001 compared with patients drinking alcohol. The qualitative content analysis revealed five categories describing reasons for patients with RA to stop drinking alcohol: illness and treatment; health and well-being; work and family; faith and belief; and dependences and abuse.

Conclusions

The patients who had stopped drinking had worse physical functioning and higher levels in pain-related variables. Most stopped drinking due to their illness or a desire to improve health.
Behaviour change interventions for the management of Raynaud’s phenomenon: a systematic literature review
Authors: Daniels Jo , Pauling John D , Eccleston Christopher
Published: December 2018

Objectives

Raynaud’s phenomenon (RP) is a significant cause of morbidity. Vasodilator medications cause unwanted adverse effects, with behavioural and lifestyle changes forming the mainstay of self-management; this is difficult to implement successfully. The objectives of this study were to evaluate the efficacy of behaviour change interventions for RP and identify learning points for future treatment development.

Design

Systematic literature review and narrative synthesis of findings.

Data sources

EMBASE, MEDLINE, Cochrane and PsycINFO were searched for eligible studies on 22 August 2017.

Eligibility criteria

Randomised controlled trials (RCTs) of behaviour change interventions with at least one control comparator arm.

Data extraction and synthesis

Study selection, data extraction and risk of bias were assessed independently by two reviewers, reaching consensus with a third when necessary. Primary outcomes of interest included severity/impact, frequency and duration of RP episodes, pain, disability, adverse events and study withdrawal.

Results

Of 638 articles retrieved, eight studies fulfilled criteria for inclusion. Biofeedback was the active behaviour change treatment arm for seven studies, with one study reporting a behavioural intervention. Studies were published 1978–2002; six were USA-based studies, one German and one Swedish. Using Cochrane Risk of Bias assessment, studies were assessed to be overall at high risk of bias, with the exception of one large RCT. The total sample included 495 participants (study median=29), with a median age of 39.5 years and preponderance towards females (73%). Five studies reported significant effects in primary outcomes of interest; however, due to missing data, relative efficacy of interventions could not be reliably assessed.

Conclusions

There is no evidence to support or refute claims of the efficacy of behaviour change interventions for the management of RP. There remains a strong case for developing and testing behaviour change interventions that focus on self-management; however, theoretical development and advancement in trial quality is imperative to underpin future work.

PROSPERO registration number

CRD42017049643.
Effectiveness of cognitive–behavioural therapy: a protocol for an overview of systematic reviews and meta-analyses
Authors: Fordham Beth , Sugavanam Thavapriya , Hopewell Sally , Hemming Karla , Howick Jeremy , Kirtley Shona , das Nair Roshan , Hamer-Hunt Julia , Lamb Sarah E
Published: December 2018

Introduction

Cognitive–behavioural therapy (CBT) is a psychological therapy that has been used to improve patient well-being across multiple mental and physical health problems. Its effectiveness has been examined in thousands of randomised control trials that have been synthesised into hundreds of systematic reviews. The aim of this overview is to map, synthesise and assess the reliability of evidence generated from these systematic reviews of the effectiveness of CBT across all health conditions, patient groups and settings.

Methods and analysis

We will run our search strategy, to identify systematic reviews of CBT, within the Database of Abstracts of Reviews of Effects, the Cochrane Library of Systematic Reviews, MEDLINE, Embase, PsycInfo, CINAHL, Child Development and Adolescent Studies, and OpenGrey between January 1992 and 25 April 2018. Independent reviewers will sift, perform data extraction in duplicate and assess the quality of the reviews using the Assessing the Methodological Quality of Systematic Reviews (V.2) tool. The outcomes of interest include: health-related quality of life, depression, anxiety, psychosis and physical/physiological outcomes prioritised in the individual reviews. The evidence will be mapped and synthesised where appropriate by health problem, patient subgroups, intervention type, context and outcome.

Ethics and dissemination

Ethical approval is not required as this is an overview of published systematic reviews. We plan to publish results in peer-reviewed journals and present at international and national academic, clinical and patient conferences.

Trial registration number

CRD42017078690.
Born to be Wise: a population registry data linkage protocol to assess the impact of modifiable early-life environmental exposures on the health and development of children
Authors: van den Bosch Matilda , Brauer Michael , Burnett Rick , Davies Hugh W , Davis Zoe , Guhn Martin , Jarvis Ingrid , Nesbitt Lorien , Oberlander Tim , Rugel Emily , Sbihi Hind , Su Jason G , Jerrett Michael
Published: December 2018

Introduction

Deficiencies in childhood development is a major global issue and inequalities are large. The influence of environmental exposures on childhood development is currently insufficiently explored. This project will analyse the impact of various modifiable early life environmental exposures on different dimensions of childhood development.

Methods

Born to be Wise will study a Canadian cohort of approximately 34 000 children who have completed an early development test at the age of 5. Land use regression models of air pollution and spatially defined noise models will be linked to geocoded data on early development to analyse any harmful effects of these exposures. The potentially beneficial effect on early development of early life exposure to natural environments, as measured by fine-grained remote sensing data and various land use indexes, will also be explored. The project will use data linkages and analyse overall and age-specific impact, including variability depending on cumulative exposure by assigning time-weighted exposure estimates and by studying subsamples who have changed residence and exposure. Potentially moderating effects of natural environments on air pollution or noise exposures will be studied by mediation analyses. A matched case–control design will be applied to study moderating effects of natural environments on the association between low socioeconomic status and early development. The main statistical approach will be mixed effects models, applying a specific software to deal with multilevel random effects of nested data. Extensive confounding control will be achieved by including data on a range of detailed health and sociodemographic variables.

Ethics and dissemination

The study protocol has been ethically approved by the Behavioural Research Ethics Board at the University of British Columbia. The findings will be published in peer-reviewed journals and presented at scholarly conferences. Through stakeholder engagement, the results will also reach policy and a broader audience.
Stent-screw-assisted internal fixation: the SAIF technique to augment severe osteoporotic and neoplastic vertebral body fractures
Authors: Cianfoni Alessandro , Distefano Daniela , Isalberti Maurizio , Reinert Michael , Scarone Pietro , Kuhlen Dominique , Hirsch Joshua A , Bonaldi Giuseppe
Published: December 2018

Objectives

To describe a new technique to obtain minimally invasive but efficient vertebral body (VB) reconstruction, augmentation, and stabilization in severe osteoporotic and neoplastic fractures, combining two pre-existing procedures. The implant of vertebral body stents (VBS) is followed by insertion of percutaneous, fenestrated, cement-augmented pedicular screws that act as anchors to the posterior elements for the cement/stent complex. The screws reduce the risk of stent mobilization in a non-intact VB cortical shell and bridge middle column and pedicular fractures. This procedure results in a 360° non-fusion form of vertebral internal fixation that may empower vertebral augmentation and potentially avoid corpectomy in challenging fractures.

Procedure details

This report provides step-by-step procedural details, rationale, and proposed indications for this procedure. The procedure is entirely percutaneous under fluoroscopic guidance. Through transpedicular trocars the VBS are inserted, balloon-expanded and implanted in the VB. Over k-wire exchange the transpedicular screws are inserted inside the lumen of the stents and cement is injected through the screws to augment the stents and fuse the screws to the stents.

Applications

This technique may find appropriate applications for the most severe osteoporotic fractures with large clefts, high-degree fragmentation and collapse, middle column and pedicular involvement, and in extensive neoplastic lytic lesions.

Conclusions

Stent-Screw-Assisted Internal Fixation (SAIF) might represent a minimally invasive option to obtain VB reconstruction and restoration of axial load capability in severe osteoporotic and neoplastic fractures, potentially obviating the need for more invasive surgical interventions in situations that would pose significant challenges to standard vertebroplasty or balloon kyphoplasty.
Pseudo-Hermitian position and momentum operators, Hermitian Hamiltonian, and deformed oscillators
Authors: Gavrilik Alexandre , Kachurik Ivan
Published: December 2018

The recently introduced by us, two- and three-parameter (p, q)- and (p, q, [Formula: see text])-deformed extensions of the Heisenberg algebra were explored under the condition of their direct link with the respective (nonstandard) deformed quantum oscillator algebras. In this paper, we explore certain Hermitian Hamiltonians build in terms of non-Hermitian position and momentum operators obeying definite [Formula: see text](N)-pseudo-hermiticity properties. A generalized nonlinear (with the coefficients depending on the particle number operator N) one-mode Bogoliubov transformation is developed as main tool for the corresponding study. Its application enables to obtain the spectrum of “almost free” (but essentially nonlinear) Hamiltonian.
Generalization of optical solitons with dual dispersion in the presence of Kerr and quadratic-cubic law nonlinearities
Authors: Raza Nauman , Javid Ahmad
Published: December 2018

In this work, nonlinear Schrödinger’s equation along with group velocity dispersion and spatio-temporal dispersion is considered in [Formula: see text] dimensions with Kerr and quadratic-cubic law nonlinearities which expose the propagation of light pulses in fiber optics. Dark, singular and periodic singular optical solitons in [Formula: see text] dimensions are retrieved and generalized through versatile modified simple equation method. The constraint conditions that righteously guarantee the perseverance of these soliton solutions are obtained as an outgrowth. The results presented in this paper are new and generalized which are already available in the literature.
PRACTICAL CONSIDERATIONS FOR STANDARDIZED RECORDING OF MUSCLE MECHANICAL PROPERTIES USING A MYOMETRIC DEVICE: RECORDING SITE, MUSCLE LENGTH, STATE OF CONTRACTION AND PRIOR ACTIVITY
Authors: Agyapong-Badu Sandra , Warner Martin , Samuel Dinesh , Stokes Maria
Published: December 2018

Purpose: This study aimed to systematically examine the influence of various muscle and experimental conditions on Myoton recordings. Methods: A cross-sectional, observational design was used to examine muscle conditions and experimental factors (different recording sites, muscle length, level of contraction and prior physical activity) that may influence reproducibility of Myoton recordings for biceps brachii (BB) and rectus femoris (RF). Fifty-three healthy adults (26 young, 27 older) aged 18–90 years were studied. Muscle stiffness, tone and elasticity were measured using the MyotonPRO device. Results: Statistically significant differences in Myoton parameters were found for aspects of all four muscle and experimental conditions compared with the control condition ([Formula: see text]). However, clinically relevant differences in tone, stiffness and elasticity were only found for contracted compared to resting muscle, with changes being greater than the minimal detectable change. Elasticity was not affected by prior activity. Conclusions: The conditions studied significantly altered Myoton parameters of BB and RF in healthy adults, but only changes in parameters during muscle contraction were clinically relevant. These findings provide evidence to support the need to consider muscle condition and experimental factors for improving the robustness of test protocols for assessing muscle mechanical properties using the MyotonPRO device.
A Tour of Reinforcement Learning: The View from Continuous Control
Authors: Recht Benjamin
Published: December 2018

This article surveys reinforcement learning from the perspective of optimization and control, with a focus on continuous control applications. It reviews the general formulation, terminology, and typical experimental implementations of reinforcement learning as well as competing solution paradigms. In order to compare the relative merits of various techniques, it presents a case study of the linear quadratic regulator (LQR) with unknown dynamics, perhaps the simplest and best-studied problem in optimal control. It also describes how merging techniques from learning theory and control can provide nonasymptotic characterizations of LQR performance and shows that these characterizations tend to match experimental behavior. In turn, when revisiting more complex applications, many of the observed phenomena in LQR persist. In particular, theory and experiment demonstrate the role and importance of models and the cost of generality in reinforcement learning algorithms. The article concludes with a discussion of some of the challenges in designing learning systems that safely and reliably interact with complex and uncertain environments and how tools from reinforcement learning and control might be combined to approach these challenges.
Losartan prevents the elevation of blood pressure in adipose-PRR deficient female mice while elevated circulating sPRR activates the renin-angiotensin system
Authors: Gatineau Eva , Cohn Dianne M. , Poglitsch Marko , Loria Analia S. , Gong Ming , Yiannikouris Frédérique
Published: December 2018

Deletion of the prorenin receptor (PRR) in adipose tissue elevates systolic blood pressure (SBP) and the circulating soluble form of PRR (sPRR) in male mice fed a high-fat (HF) diet. However, sex differences in the contribution of adipose-PRR and sPRR to the regulation of the renin-angiotensin system (RAS) in key organs for blood pressure control are undefined. Therefore, we assessed blood pressure and the systemic and intrarenal RAS status in adipose-PRR knockout (KO) female mice. Blockade of RAS with losartan blunted SBP elevation in HF diet-fed adipose-PRR KO mice. ANG II levels were significantly increased in the renal cortex of HF diet-fed adipose-PRR KO female mice, but not systemically. HF diet-fed adipose-PRR KO mice exhibited higher vasopressin levels, water retention, and lower urine output than wild-type (WT) mice. The results also showed that deletion of adipose-PRR increased circulating sPRR and total hepatic sPRR contents, suggesting the liver as a major source of elevated plasma sPRR in adipose-PRR KO mice. To mimic the elevation of circulating sPRR and define the direct contribution of systemic sPRR to the regulation of the RAS and vasopressin, C57BL/6 female mice fed a standard diet were infused with recombinant sPRR. sPRR infusion increased plasma renin levels, renal and hepatic angiotensinogen expression, and vasopressin. Together, these results demonstrate that the deletion of adipose-PRR induced an elevation of SBP likely mediated by an intrarenal ANG II-dependent mechanism and that sPRR participates in RAS regulation and body fluid homeostasis via its capacity to activate the RAS and increase vasopressin levels.

NEW & NOTEWORTHY The elevation of systolic blood pressure appears to be primarily mediated by cortical ANG II in high-fat diet-fed adipose-prorenin receptor knockout female mice. In addition, our data support a role for soluble prorenin receptor in renin-angiotensin system activation and vasopressin regulation.
Transbronchial Cryobiopsies for Diagnosing Interstitial Lung Disease: Real-Life Experience from a Tertiary Referral Center for Interstitial Lung Disease
Authors: Wälscher Julia , Groß Benjamin , Eberhardt Ralf , Heussel Claus Peter , Eichinger Monika , Warth Arne , Lasitschka Felix , Herth Felix J.F. , Kreuter Michael
Published: December 2018

Background: Transbronchial cryobiopsy (cTBB) may offer an alternative to surgical lung biopsy (SLB) for histopathological diagnosis of interstitial lung diseases (ILDs). However, real-life experience is limited, although case series are increasingly reported. Objectives: We aimed to evaluate the value of cTBB performed under real-life conditions in a tertiary care center for ILDs. Methods: Data on all patients undergoing a cTBB for evaluation of suspected ILD between October 2015 and January 2017 were included in this retrospective case series. Procedure details, complication rates, histopathological results, and diagnostic consensus reached by a multidisciplinary team (MDT) discussion were collated and evaluated. Results: A total of 109 patients (mean age 64 years, range 19–85; 66% male, 38% never smokers) referred to our center with features suggestive of ILD underwent cTBB. The mean FVC% predicted was 77% (range 41–131), with a mean DLCO of 51% (range 20–86), and a 6-min walking test (6MWT) of 402 m (range 100–642). On average, 4 samples were taken from each patient (range 1–8), with a mean biopsy diameter of 5 mm (range 2–12). Complications included pneumothorax (11.9%), all treated with chest drain. Moderate bleeding occurred in 28.4% (all resolved without active measures). No acute disease exacerbations and no deaths occurred. A histopathological pattern diagnosis was possible in 80 cases (73.4%), and 26.6% of cases were considered nonspecific. An MDT consensus diagnosis was reached in 83.5% of cases. Subsequent SLB was proposed in 13 cases and performed in 8 cases. Conclusions: In the real-world setting, cTBB has a meaningful diagnostic value in the context of a MDT approach and may enable histopathological assessment even in patients with more advanced disease unsuitable for SLB.
Recent Incidence Trend of Surgically Resected Esophagogastric Junction Adenocarcinoma and Microsatellite Instability Status in Japanese Patients
Authors: Imamura Yu , Watanabe Masayuki , Toihata Tasuku , Takamatsu Manabu , Kawachi Hiroshi , Haraguchi Ikumi , Ogata Yoko , Yoshida Naoya , Saeki Hiroshi , Oki Eiji , Taguchi Kenichi , Yamamoto Manabu , Morita Masaru , Mine Shinji , Hiki Naoki , Baba Hideo , Sano Takeshi
Published: December 2018

Background: The incidence trend of esophagogastric junction (EGJ) adenocarcinoma in Japan has not been sufficiently investigated. Little is known about the microsatellite instability (MSI) status of this tumor. Summary: Previously published studies analyzing the trend of EGJ adenocarcinoma in Japan were reviewed. And a trend of surgically resected cases (Siewert type I-III) utilizing a retrospective multicenter cohort of 379 patients from 4 academic institutions in Japan investigated. Although an increasing trend in the last 2 reports was considered controversial, our cohort demonstrated a growing number of EGJ adenocarcinoma cases between 2006 and 2013. This trend was evident, especially in Siewert type I cases. In the previous 16 studies that performed MSI testing, MSI-high tumors ranged 0–8.3%, though there were no fixed microsatellite markers on EGJ adenocarcinoma. In a recent comprehensive genetic analysis by The Cancer Genome Atlas, MSI testing using the following 7 markers, BAT25, BAT26, BAT40, D2S123, D5S346, D17S250 and TGFR-II showed a favorable correlation with hypermutated tumors. We performed MSI testing using 6 of those markers, except TGFR-II, on 206 cases from one institution, and detected 15 cases (7.3%) with MSI-high. The prevalence of MSI-high was 0% in Siewert type I, 7.6% in type II, and 16.7% in type III. Key message: The number of surgically resected EGJ adenocarcinoma cases gradually increased, and MSI-high was infrequent in Siewert type I-II tumors in our Japanese cohort. Considering MSI-high as a predictive biomarker for emerging immune checkpoint inhibitors, MSI status is becoming more beneficial in EGJ adenocarcinoma.
Liquid Biopsy for the Management of Patients with Colorectal Cancer
Authors: Yamada Takeshi , Matsuda Akihisa , Koizumi Michihiro , Shinji Seiichi , Takahashi Goro , Iwai Takuma , Takeda Kohki , Ueda Kohji , Yokoyama Yasuyuki , Hara Keisuke , Hotta Masahiro , Matsumoto Satoshi , Yoshida Hiroshi
Published: December 2018

Background: Liquid biopsy is a collective term that refers to the analysis of tumor-derived biomarkers isolated from biological fluids of cancer patients. Recently, many authors reported the usefulness of liquid biopsy for the management of malignancy. Summary and Key Messages: The peripheral blood of cancer patients is a pool of cells and/or cell products derived from the primary or metastatic tumor, including circulating tumor cells (CTCs), circulating free (cf) DNA or RNA, and exosomes containing proteins, nucleic acids, and lipids. CTCs are tumor cells that can be isolated from peripheral blood. Free circulating DNA with a tumor-specific mutation is called circulating tumor DNA (ctDNA). Some patients who undergo curative surgery experience recurrent disease, which can be due to the presence of minimal residual disease (MRD). Thus, MRD indicates a high risk of relapse. Detection of ctDNA or CTC after surgery is a direct proof of MRD. Molecular volume (e.g., the number of CTCs and level of ctDNA) might reflect tumor burden, thus high molecular volume may indicate poor prognosis. The most notable application of liquid biopsy in cancer is to understand spatial and temporal heterogeneities. Heterogeneity is one of the causes of refractoriness and hampers prediction of chemotherapeutic effect. Emerging mutations that are not present in primary tumors but are found in their metastases can be detected in ctDNA. Some colorectal cancer patients with wild-type RAS do not respond to epidermal growth factor receptor blockade. In a subset of these patients, RAS mutation is detected in ctDNA, indicating heterogeneity.
Recurrence Patterns and Outcomes of Salvage Surgery in Cases of Non-Curative Endoscopic Submucosal Dissection without Additional Radical Surgery for Early Gastric Cancer
Authors: Takizawa Kohei , Hatta Waku , Gotoda Takuji , Kawata Noboru , Nakagawa Masahiro , Takahashi Akiko , Esaki Mitsuru , Mitoro Akira , Yamada Shinya , Tanaka Keiko , Matsuda Mitsuru , Takada Jun , Oka Shiro , Ito Hirotaka , Ohnita Ken , Shimoda Ryo , Hoteya Shu , Oyama Tsuneo , Shimosegawa Tooru
Published: December 2018

Background/Aims: The outcomes of salvage surgery for recurrence after non-curative endoscopic submucosal dissection (ESD) without additional radical surgery for early gastric cancer (EGC) remain unclear. We determined the recurrence patterns and outcomes of salvage surgery in such cases using data from a multicenter, retrospective study. Methods: Of 15,785 patients who underwent ESD for EGC at 19 participating institutions between January 2000 and August 2011, 1,969 failed to meet the current curative criteria after ESD. Of these, 905 patients received no additional treatment. We evaluated the pattern of recurrence, clinical course after salvage surgery, and long-term survival rate for these patients. Results: Over a median 64-month follow-up period, recurrence was detected in 27 patients. Two patients with missing data were excluded. Three, seven, and 15 (60%) patients showed intragastric relapse, regional lymph node metastasis, and distant metastasis, respectively. The first line of treatment for recurrence in 1, 7, 6, and 11 patients was endoscopic treatment, salvage surgery, chemotherapy, and best supportive care, respectively. One patient survived without recurrence for 31 months after salvage surgery, one died of acute myocardial infarction 1 month after salvage surgery, and 5 showed recurrence at 0, 2, 3, 5, and 30 months after salvage surgery and eventually succumbed to the disease. The median survival times for all patients with recurrence and the 7 patients who underwent salvage surgery were 5 months after recurrence and 7 months after salvage surgery, respectively. Conclusion: The survival rate after salvage surgery for recurrence after non-curative ESD without additional radical surgery for EGC is quite low, with distant metastasis being the most common recurrence pattern in these cases.
Gastric Cancer with Submucosal Invasion after Successful Helicobacter pylori Eradication: A Propensity Score-Matched Analysis of Patients with Annual Patient Endoscopic Survey
Authors: Hata Kosaku , Ito Masanori , Boda Tomoyuki , Kotachi Takahiro , Kiso Mariko , Masuda Kazuhiko , Kurihara Mio , Kuroki Kazutaka , Yorita Naoki , Nagasaki Naoko , Abduwali Madina , Tanaka Shinji , Chayama Kazuaki
Published: December 2018

Background and Aim: The incidence of gastric cancer occurring after successful Helicobacter pylori eradication has been increasing. We aimed to clarify the influence of eradication therapy on the ability to diagnose early gastric cancer after successful H. pylori eradication in patients who underwent annual endoscopic screening. Methods: A total of 220 patients (179 men; mean age 71.0 years) had differentiated-type early gastric cancer that was discovered through annual endoscopic screening. Patients were categorized into 2 groups: the H. pylori-eradicated group (n = 81) and the non-eradicated control group (n = 139). After matching patients by propensity scores, we retrospectively analyzed the clinicopathological characteristics of 162 patients (81 patients in each group). Furthermore, we compared the characteristics of gastric cancer with submucosal invasion between the 2 groups. Results: The prevalence of early gastric cancer with submucosal invasion was significantly higher in the eradicated group than in the control group, both before propensity score matching (16.0 vs. 7.2%, respectively; p = 0.038) and after propensity score matching of 81 pairs (16.0 vs. 4.9%, respectively; p = 0.021). In the comparative analysis of gastric cancer with submucosal invasion, there was no difference between the 2 groups with respect to factors influencing the ability to diagnose its presence endoscopically. Conclusion: H. pylori eradication therapy increased the prevalence of differentiated-type gastric cancer with submucosal invasion despite patients’ completion of annual endoscopic screening after eradication.
Metabolic Alterations in Celiac Disease Occurring after Following a Gluten-Free Diet
Authors: Ciccone Antonio , Gabrieli Dolores , Cardinale Rossella , Di Ruscio Mirko , Vernia Filippo , Stefanelli Gianpiero , Necozione Stefano , Melideo Dina , Viscido Angelo , Frieri Giuseppe , Latella Giovanni
Published: December 2018

Background and Aim: Many investigations have demonstrated that changes in body weight are frequent in patients with coeliac disease (CD) after a gluten-free diet (GFD); conversely data on the metabolic syndrome (MS) and hepatic steatosis (HS) are still rare. The aim is to evaluate the prevalence of MS and HS in patients with CD, before and after a GFD. Methods: One hundred eighty-five coeliac adult patients were enrolled in the study. Diagnosis of MS was made according to the current international criteria including waist circumference (WC), hypertension, reduction of high-density lipoprotein (HDL) cholesterol, hypertriglyceridemia, and hyperglycemia. Body mass index (BMI), hypercholesterolemia, and HS were also assessed. Results: CD patients showed an increased risk of developing both MS and HS after following a GFD. MS was reported in 3.24% of the cases at the time of CD diagnosis and in 14.59% after GFD (p < 0.0001). HS was reported in 1.7% at the time of diagnosis and in 11.1% after GFD (p < 0.0001). With regard to metabolic sub-categories, the prevalence of the increase in WC, hypertension, reduction of HDL cholesterol, hyperglycemia, hypercholesterolemia, and BMI > 25 was significantly higher after GFD compared to baseline at CD diagnosis. Conclusion: In CD patients, following a GFD maybe can contribute to the development of MS and HS. Patients should be informed about this possible risk.
Relação entre biofábrica e porosidade, coquinas da Formação Morro do Chaves (Barremiano/Aptiano), Bacia de Sergipe-Alagoas, NE-Brasil
Authors: Chinelatto Guilherme Furlan , Kuroda Michelle Chaves , Vidal Alexandre Campane
Published: December 2018

As coquinas da Formação Morro do Chaves são consideradas rochas análogas aos reservatórios da fase rifte do pré-sal nas bacias de Campos e Santos, são compostas principalmente por conchas e fragmentos de bivalves revelando uma grande variedade da biofábrica e do sistema poroso que possibilita o uso da tafonomia para relacionar o ambiente deposicional dessas rochas com as características de porosidade. Os principais atributos tafonômicos abordados nesse trabalho são: orientação das valvas; empacotamento das conchas; granulometria e seleção; e grau de fragmentação, abrasão e arredondamento. A interpretação dos dados teve como objetivo agrupar as amostras com relação às diferentes características tafonômicas e a porosidade, tendo como ferramenta auxiliar o método de redes neurais artificias (Self-Organization Map — SOM). A análise dos dados resultou em três agrupamentos: A1 com altos valores de porosidade (entre 11 e 23%), cujas características tafonômicas revelam ambientes de alta energia; A2 com valores intermediários de porosidade (entre 7 e 15%), cujas características tafonômicas indicam um ambiente de transição entre alta e baixa energia; por fim, o grupo A3 com menores valores de porosidade (entre 0 e 7%), cuja tafonomia indica ambientes de baixa energia. Como resultado final, as características tafonômicas revelam a energia do ambiente deposicional e é possível associar ambientes de alta energia com as altas porosidades para as coquinas da Formação Morro do Chaves.
Early Follow-Up Optical Coherence Tomographic Findings of Significant Drug-Eluting Stent Malapposition
Authors: Lee Seung-Yul , Ahn Chul-Min , Yoon Hyuck-Jun , Hur Seung-Ho , Kim Jung-Sun , Kim Byeong-Keuk , Ko Young-Guk , Choi Donghoon , Jang Yangsoo , Hong Myeong-Ki
Published: December 2018

Background:

Using optical coherence tomography, we evaluated early follow-up findings of significant stent malapposition (SSM) in patients treated with second-generation drug-eluting stent.

Methods and Results:

From the DETECT-OCT randomized trial (Determination of the Duration of the Dual Antiplatelet Therapy by the Degree of the Coverage of the Struts on Optical Coherence Tomography From the Randomized Comparison Between Everolimus- Versus Biolimus-Eluting Stent), a total of 386 patients (390 lesions) who underwent both postintervention and 3-month follow-up optical coherence tomography examinations were included for the present analysis. SSM was defined as a stent that had a strut with a maximal wall-to-strut distance of ≥200 μm. Postintervention, SSM was detected in 175 lesions (44.9%), including 117 lesions with a maximal wall-to-strut distance of ≥200 to <400 μm and 58 lesions with a maximal wall-to-strut distance of ≥400 μm. As the implanted stent diameter-to-reference vessel diameter ratio grew, the risk of postintervention SSM dropped (odds ratio, 0.587; 95% CI, 0.367–0.941;
P
=0.0398). The optimal value that best separated SSM from non-SSM postintervention was a stent diameter-to-reference vessel diameter ratio of 1.0. At 3 months follow-up, the frequency of SSM decreased from 44.9% to 33.6% (131 lesions;
P
=0.0001), mainly driven by the decrease in lesions with a maximal wall-to-strut distance of ≥200 to <400 μm. As the maximal wall-to-strut distance on postintervention optical coherence tomography was larger, the risk of 3-month SSM increased (odds ratio, 1.607; 95% CI, 1.131–2.286;
P
=0.0284). The optimal value that best separated SSM from non-SSM at 3 months follow-up was a maximal wall-to-strut distance postintervention of 230 μm.

Conclusions:

A spontaneous decrease in SSM was observed early in this qualified study with a large number of study patients treated with second-generation drug-eluting stent.

Clinical Trial Registration:

URL:
https://www.clinicaltrials.gov
. Unique identifier: NCT01752894.
Contemporary Reasons and Clinical Outcomes for Patients With Severe, Symptomatic Aortic Stenosis Not Undergoing Aortic Valve Replacement
Authors: Tang Liang , Gössl Mario , Ahmed Aisha , Garberich Ross , Bradley Steven M. , Niikura Hiroki , Witt Dawn , Pedersen Wesley R. , Bae Richard , Lesser John R. , Harris Kevin M. , Sun Benjamin , Mudy Karol , Sorajja Paul
Published: December 2018

Background:

Although aortic valve replacement (AVR) can be lifesaving, many patients with symptomatic aortic stenosis do not undergo appropriate therapy. This study sought to examine the characteristics, outcomes, and reasons for not pursuing AVR in a contemporary cohort.

Methods and Results:

We examined 548 patients with severe, symptomatic aortic stenosis not treated with AVR through March 2017. Patients were grouped according to AVR appropriateness based on the presence of medical futility. Demographics, rationale for no AVR therapy, and outcomes were assessed. There were 359 (65.5%) potentially appropriate candidates for AVR and 189 (34.5%) others patients with futility. Among potentially appropriate patients, 62.1% had severe symptoms, 74.4% had not been referred for AVR, and 40.1% were low risk. Patient refusal was common (54.6%), with incorrect symptom assignment or aortic stenosis severity classification accounting for nearly all other explanations. Compared with patients with futility, potentially appropriate AVR patients had lower rates of both referral to cardiology or surgery (85.2% versus 92.6%;
P
=0.01) and complete heart team evaluations (10.6% versus 17.5%;
P
=0.02). Palliative consultation occurred in only 124 patients (22.6%) overall and in only 10.0% of those without futility. Overall, the 1-year mortality was 54.7%, with heart failure hospitalization occurring in 19.3%.

Conclusions:

In this contemporary study, two-thirds of patients with symptomatic aortic stenosis treated medically were potentially appropriate AVR candidates and had poor outcomes. Most had incomplete heart team evaluations, commonly had severe symptoms or lesion severity misinterpreted, and were not evaluated by palliative care. Given the potential for beneficial outcomes among those untreated, further efforts to address these shortcomings are needed.
Ascending Aorta Size at Birth Predicts White Matter Microstructure in Adolescents Who Underwent Fontan Palliation
Authors: Zaidi Abbas H. , Newburger Jane W. , Wypij David , Stopp Christian , Watson Christopher G. , Friedman Kevin G. , Rivkin Michael J. , Rollins Caitlin K.
Published: December 2018

Background

In neonates with single ventricle, smaller ascending aorta diameter is associated with cerebral white matter (
WM
) microstructural abnormalities. We sought to determine whether this association persists into adolescence.

Methods and Results

Ascending aorta
Z
scores were obtained from first postnatal echocardiogram. Brain magnetic resonance imaging with diffusion tensor imaging was acquired in adolescence and used to obtain fractional anisotropy, axial diffusivity, radial diffusivity, and mean diffusivity in 33
WM
tract regions of interest. Partial Pearson correlation coefficients were evaluated for associations between ascending aorta
Z
scores and
WM
microstructure measures, adjusting for sex, age at magnetic resonance imaging, scanner field strength, and Norwood status. Among 42 single ventricle patients aged 10 to 19 years, 31 had undergone the Norwood procedure as neonates. Lower ascending aorta
Z
scores were associated with lower fractional anisotropy in bilateral pontine crossing tracts (
P
=0.02), inferior fronto‐occipital fasciculus (
P
=0.02), and inferior longitudinal fasciculus (
P
=0.01); left cingulum–cingulate bundle (
P
=0.01), superior longitudinal fasciculus (
P
=0.04), and superior longitudinal fasciculus–temporal component (
P
=0.01); and right cingulum–hippocampal bundle
(P
=0.009) and inferior cerebellar peduncle (
P
=0.01). Lower ascending aorta
Z
scores were associated with higher radial diffusivity and mean diffusivity in a similar regional pattern but not with axial diffusivity.

Conclusions

In adolescents with single ventricle, smaller aorta diameter at birth is associated with abnormalities of
WM
microstructure in a subset of
WM
tracts, mostly those located in deeper brain regions. Our findings suggest that despite multiple intervening medical or surgical procedures, prenatal cerebral blood flow may have a lasting influence on
WM
microstructure in single‐ventricle patients.