bluuebunny/crossref_metadata_2025_split huggingface dataset:
Longitudinal Liquid Biopsy and Mathematical Modeling of Clonal Evolution Forecast Time to Treatment Failure in the PROSPECT-C Phase II Colorectal Cancer Clinical Trial
Authors: Khan Khurum H. , Cunningham David , Werner Benjamin , Vlachogiannis Georgios , Spiteri Inmaculada , Heide Timon , Mateos Javier Fernandez , Vatsiou Alexandra , Lampis Andrea , Damavandi Mahnaz Darvish , Lote Hazel , Huntingford Ian Said , Hedayat Somaieh , Chau Ian , Tunariu Nina , Mentrasti Giulia , Trevisani Francesco , Rao Sheela , Anandappa Gayathri , Watkins David , Starling Naureen , Thomas Janet , Peckitt Clare , Khan Nasir , Rugge Massimo , Begum Ruwaida , Hezelova Blanka , Bryant Annette , Jones Thomas , Proszek Paula , Fassan Matteo , Hahne Jens C. , Hubank Michael , Braconi Chiara , Sottoriva Andrea , Valeri Nicola 
Published: August 2018

Abstract
Sequential profiling of plasma cell-free DNA (cfDNA) holds immense promise for early detection of patient progression. However, how to exploit the predictive power of cfDNA as a liquid biopsy in the clinic remains unclear. RAS pathway aberrations can be tracked in cfDNA to monitor resistance to anti-EGFR monoclonal antibodies in patients with metastatic colorectal cancer. In this prospective phase II clinical trial of single-agent cetuximab in RAS wild-type patients, we combine genomic profiling of serial cfDNA and matched sequential tissue biopsies with imaging and mathematical modeling of cancer evolution. We show that a significant proportion of patients defined as RAS wild-type based on diagnostic tissue analysis harbor aberrations in the RAS pathway in pretreatment cfDNA and, in fact, do not benefit from EGFR inhibition. We demonstrate that primary and acquired resistance to cetuximab are often of polyclonal nature, and these dynamics can be observed in tissue and plasma. Furthermore, evolutionary modeling combined with frequent serial sampling of cfDNA allows prediction of the expected time to treatment failure in individual patients. This study demonstrates how integrating frequently sampled longitudinal liquid biopsies with a mathematical framework of tumor evolution allows individualized quantitative forecasting of progression, providing novel opportunities for adaptive personalized therapies.
Significance: Liquid biopsies capture spatial and temporal heterogeneity underpinning resistance to anti-EGFR monoclonal antibodies in colorectal cancer. Dense serial sampling is needed to predict the time to treatment failure and generate a window of opportunity for intervention. Cancer Discov; 8(10); 1270–85. ©2018 AACR.
See related commentary by Siravegna and Corcoran, p. 1213.
This article is highlighted in the In This Issue feature, p. 1195
Healing the heart of recovery
Authors: Liggins Jackie 
Published: August 2018

Background and Aim: Medicine is traditionally considered a healing profession, yet concepts of healing are rarely applied to mental illness, recovery being the dominant discourse. This article reports one aspect of the results of a broader exploration, through a service user lens, of aspects of place that facilitate healing in mental health care, with a resulting conceptualisation of healing. Method: The research material comprised the author’s historical writings of her experience of mental illness and recovery and in-depth individual interviews with 10 mental health service users. Analysed thematically, emerging ideas were further developed through an autoethnographically informed, reflexive and iterative process. Results: Healing is necessary when there has been a disruption of integrity and wholeness, experienced as suffering. Offering opportunities for connection, integration and transformation, and acquiring wisdom along the way, healing is a journey of exploration that takes time and is hard work. Discussion: Healing is conceptualised as the intensely personal experience at the heart of recovery, reminding us of the fundamental personal processes at the heart of our journeys. As a universal human experience, healing potentially removes the sense of othering that is at the heart of mental illness stigma.
Outcome of infants born at < 32 weeks’ gestation in a single-centre level III neonatology unit – relation to feeding strategy
Authors: Kiechl-Kohlendorfer Ursula , Biermayr Marlene , Pupp Peglow Ulrike , Griesmaier Elke 
Published: August 2018

Objective This study aimed to determine survival, neonatal morbidity, and outcomes at 1 and 2 years in children who were born very preterm, and to analyse any relation to enteral feeding. Methods We performed a prospective, observational study on very preterm infants (range: 23–31 weeks’ gestation) born at Innsbruck Medical University Hospital, Austria, between 2007 and 2014 (n = 557). Results The overall survival rate was 94.6%. Survival rates were 77.8%, 78.6%, 90.9%, and 90.9% among those born at 24, 25, 26, and 27 weeks, and 97.3%, 95.3%, 98.3%, and 100% among those born at 28, 29, 30, and 31 weeks of gestation, respectively. The overall prevalence of chronic lung disease among survivors was 7.3%. The prevalence of necrotizing enterocolitis requiring surgery, intraventricular haemorrhage grades 3 and 4, and severe retinopathy of prematurity was 3.1%, 2.1%, and 6.2%, respectively. There was no difference in short-term morbidity or neurodevelopmental outcome at 1 or 2 years of corrected age between infants who were fed with human milk at discharge and those who were formula-fed. Conclusion In the current study, mortality and short-term morbidity rates were low. No differences regarding feeding strategy were detected.
Association between angiopoietin-like protein 2 and lectin-like oxidized low-density lipoprotein receptor 1 ligand containing apolipoprotein B in patients with type 2 diabetes
Authors: Suzuki Tatsuhiko , Takebayashi Kohzo , Hara Kenji , Tsuchiya Takafumi , Inukai Toshihiko 
Published: August 2018

Objective This study was performed to evaluate the association of the serum level of angiopoietin-like protein 2 (ANGPTL2) with circulating inflammatory markers and oxidized and modified low-density lipoprotein (LDL) cholesterol as evaluated by lectin-like oxidized LDL receptor 1 ligand containing apolipoprotein B (LAB) in patients with type 2 diabetes. Methods The study included 70 patients with type 2 diabetes hospitalized for glycemic control and 9 control subjects. Results The serum level of ANGPTL2 was significantly higher in the patients with type 2 diabetes than in the healthy controls. There was a significant positive correlation between ANGPTL2 and the high-sensitivity C-reactive protein, fibrinogen, and LAB levels and a significant negative correlation between ANGPTL2 and the estimated glomerular filtration rate (eGFR). Conclusions These results suggest that the serum ANGPTL2 level has a close positive association with inflammatory markers, especially fibrinogen and oxidized and modified LDL as evaluated by LAB. The data also suggest that the serum ANGPTL2 level is influenced by renal function as reflected by the eGFR.
Succinylcholine-Induced Rhabdomyolysis in Adults: Case Report and Review of the Literature
Authors: Barrons Robert William , Nguyen Liem T. 
Published: August 2018

Purpose: A case of succinylcholine (SCh) and sevoflurane as a probable cause of rhabdomyolysis in an adult is presented, along with a review of the relevant literature and strategies for prevention. Summary: A nondiabetic, morbidly obese 32-year-old female developed rhabdomyolysis after administration of SCh and sevoflurane for diagnostic procedures of 30 minutes’ duration. Thirty-three hours following anesthesia, the patient developed diffuse muscle tenderness and progressive weakness with a creatinine kinase (CK) of 4319 U/L. Urinalysis findings indicated contamination, a white blood cells of 12.1 × 103/μL was stress induced, while all other labs were normal. Following 26 hours of intravenous fluids, the patient’s CK decreased to 1243 U/L, with pain responsive to acetaminophen and improved mobility, resulting in discharge. With a lack of reasonable alternative causes and a temporal association of symptoms, procedural medication–induced rhabdomyolysis was suspected. Based on Naranjo scale evaluation, SCh and sevoflurane were probable causes of rhabdomyolysis. We reviewed the literature for SCh-induced rhabdomyolysis among adults and found 10 cases. The majority of patients received halogenated anesthesia (HA) and prophylaxis for SCh myopathy, with no known personal or family history of neuromuscular disorders (NMD) reported. Conclusion: Rhabdomyolysis was observed in a woman following the administration of SCh and sevoflurane for diagnostic procedures lasting 30 minutes. While avoidance is possible in adults with histories of NMDs, a high index of suspicion for occurrence of rhabdomyolysis is needed whenever combining SCh with HA in all adults.
Outcomes of minor amputations in patients with peripheral vascular disease over a 10-year period at a tertiary care institution
Authors: Chan Amy S , Montbriand Janice , Eisenberg Naomi , Roche-Nagle Graham 
Published: August 2018

Objectives Choosing an optimal amputation level requires balance between maximizing limb salvage while minimizing chances of non-healing wounds and re-amputation. Our aim was to assess the long-term outcome for minor amputations in patients with peripheral vascular disease. Methods A retrospective study of minor amputations between January 1, 2005 and December 31, 2015 was performed. Electronic medical records of eligible patients were examined to extract demographics, co morbidities and clinical data. Results Within the study period, 220 patients underwent 296 primary minor amputations in 244 lower extremities. Wound healing was achieved in 18.2% (54 of 296 amputations) and 43.6% (129 of 296 amputations) at 90 days and 365 days, respectively. Rates of progression to major amputation were 16.4% (40 or 244 limbs) and 21.7% (53 of 244 limbs) at 90 days and 365 days, respectively. In the final multivariate model, lower ipsilateral posterior tibial waveforms predicted poor 90-day healing (OR = 2.22, p = 0.01) as well as limb loss (OR = 3.02, p = 0.02) in a dose-response manner. In the final logistic regression model, emergency department admission (OR = 0.20, p < 0.01), ipsilateral posterior tibial waveform (OR = 2.63, p < 0.01), and post-operative infection (OR = 0.30, p < 0.01) were predictors of poor healing status at study endpoint. Conclusion This study shows that a majority of foot amputees require ongoing care for non-healing wounds and a proportion necessitate conversion to major amputation. Adequate vascularization is essential to promote and maintain healing.
Practice Patterns of Systemic Corticosteroid Use in Complicated Acute Rhinosinusitis Among Rhinologists and Pediatric Otolaryngologist
Authors: Wu Derek , Wasserman Jason , Boruk Marina 
Published: August 2018

Background The use of systemic corticosteroids remains controversial in the treatment of orbital complications of sinusitis. Objective To compare and contrast the current practice patterns of the use of systemic corticosteroid in the management of orbital complications of acute bacterial rhinosinusitis (ABRS) among fellowship-trained members of American Society of Pediatric Otolaryngology (ASPO) and American Rhinologic Society (ARS). Study Design Cross-sectional survey. Methods A web-based survey was electronically distributed to 497 members of ASPO and 845 members of ARS focusing on the practice habits and opinions regarding the use of systemic corticosteroids in the treatment of ABRS with orbital complications in children and adults. Results Survey completion rate was 19.1% among ASPO membership and 10.3% from ARS; 45% of respondents utilized steroids almost always or frequently in children and 36% of the time in adults. Most commonly reported indication for the use of steroid was vision change. Fellowship-trained pediatric otolaryngologists are 2.88 times more likely to prescribe corticosteroids for children than rhinologists ( P < .02). The perceived level of evidence in the literature was split between expert opinions and cohort studies. Conclusion In orbital complications of ABRS, practice patterns of the use of steroid differ significantly between fellowship-trained ASPO and ARS members with respect to its use in children. Overall, corticosteroids are administered with significant frequency, although there is little actual or perceived evidence to support their safety or efficacy. In alignment of practicing evidence-based medicine, further studies are needed to guide the use of steroids in complicated ABRS with respect to timing, dosing, route, duration, and indication.
Associations of leisure-time physical activity with cardiovascular mortality: A systematic review and meta-analysis of 44 prospective cohort studies
Authors: Cheng Wenke , Zhang Zhen , Cheng Wensi , Yang Chong , Diao Linlin , Liu Weijun 
Published: August 2018

Background Many cohort studies within the past few decades have shown the protective effect of leisure-time physical activity on cardiovascular mortality. To summarise the evidence from prospective cohort studies on the relationship between the amount of leisure-time physical activity and the risk of cardiovascular mortality, a dose–response meta-analysis was conducted in this study. Methods and results Electronic databases, including PubMed and Embase databases, Scopus and Cochrane Library, were systemically retrieved by two investigators from inception to 14 June 2018 for related studies. The maximum adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) were extracted, and a dose–response analysis was conducted using the restricted cubic splines. Finally, a total of 44 studies comprising 1,584,181 participants was enrolled into this meta-analysis. The HRs of cardiovascular mortality for moderate and high leisure-time physical activity were 0.77 (95% CI 0.74–0.81) and 0.73 (95% CI 0.69–0.77), respectively. Among these 44 studies, 19 were eligible for the dose–response meta-analysis, which suggested a linear negative correlation of leisure-time physical activity with cardiovascular mortality, regardless of age, gender and the presence of underlying cardiovascular disease or not. Conclusions Leisure-time physical activity shows a linear negative correlation with the risk of cardiovascular mortality regardless of age, gender and the presence of cardiovascular disease or not. However, the cardiovascular benefits of leisure-time physical activity is decreased for those aged over 65 years or those with a history of cardiovascular disease. Moreover, leisure-time physical activity displays more cardiovascular benefits to people followed up for over 10 years than to those followed up for less than 10 years. Besides, high-intensity leisure-time physical activity has more obvious cardiovascular benefits than those of moderate-intensity leisure-time physical activity.
Subaortic Stenosis Resection in Children: Emphasis on Recurrence and the Fate of the Aortic Valve
Authors: Mukadam Shireen , Gordon Brent M. , Olson Jeffrey T. , Newcombe Jennifer B. , Hasaniya Nahidh W. , Razzouk Anees J. , Bailey Leonard L. 
Published: August 2018

Background: Recurrence after surgical resection of discrete subvalvar aortic stenosis in children often requires repeat operation. Risk factors for recurrence are poorly understood. We sought to determine potential risk factors for recurrence and postoperative comorbidities in the long term. Methods: Retrospective chart review was performed on all pediatric patients who underwent surgical resection of discrete subaortic stenosis at our institution. Demographics, perioperative findings, and clinical data were analyzed for predisposing factors. Results: From 1991 to 2015, a total of 104 patients underwent primary surgical resection of discrete subaortic stenosis. There were no postoperative deaths. Three (2.9%) patients required pacemaker implantation. Nine (8.4%) patients required repeat resection for recurrence of subaortic membrane over a median follow-up of 8.5 years (interquartile range: 5.9-13.5 years). Actuarial freedom from repeat resection was 100%, 94%, and 82% at one, five, and ten years, respectively. Repeat resection occurred more frequently in patients with genetic disease (37.5% vs 10.7%; P = .033) and preoperative mitral regurgitation (MR; 25% vs 1.2%; P < .001). Postoperative aortic insufficiency (AI) that was moderate or worse was associated with older age at the time of first resection (relative risk [RR]: 1.54, P < .05), moderate or severe preoperative AI (RR: 1.84, P = .002), and repeat resection of subaortic stenosis (RR: 1.90, P < .001). Conclusion: The majority of children who undergo surgical resection of subaortic stenosis will not experience recurrence in childhood and those who do require repeat resection may have a higher incidence of genetic disease and preoperative MR. Postoperative AI is associated with repeat resection, older age at the time of surgery, and degree of preoperative AI.
Bovine Jugular Vein Conduit: A Mid- to Long-Term Institutional Review
Authors: Patel Parth M. , Tan Corinne , Srivastava Nayan , Herrmann Jeremy L. , Rodefeld Mark D. , Turrentine Mark W. , Brown John W. 
Published: August 2018

Background: Since 1999, we have used the bovine jugular vein conduit for right ventricular outflow tract reconstruction in infants and children. Herein, we review their mid- to long-term outcomes. Methods: Between 1999 and 2016, 315 bovine jugular vein conduits were implanted in 276 patients. Patients were grouped by age at bovine jugular vein conduit implant: group 1: 0 to 1 years (N = 65), group 2: one to ten years (N = 132), and group 3: older than ten years (N = 118). For survival and hemodynamic analysis, additional group stratification was done based on conduit size. Group small: 12 and 14 mm (N = 75), group medium: 16 and 18 mm (N = 84), and group large: 20 and 22 mm (N = 156). Results: Mean follow-up for groups 1, 2, and 3 was 4.0, 4.9, and 5.9 years, respectively. Early mortality was 9%, 0%, and 1% for groups 1, 2, and 3, respectively ( P < .001). Late mortality was 5%, 2%, and 2% for groups 1, 2, and 3, respectively ( P = .337). Group 1 had the lowest ten-year freedom from conduit failure at 13%, versus 53% and 69% for groups 2 and 3, respectively ( P < .001). A total of 21 (6.6%) patients developed endocarditis, 11 (3.5%) patients required reoperation, and 10 (3.2%) patients required antibiotic therapy alone. Conclusions: The bovine jugular vein conduit is a useful option for right ventricular outflow tract reconstruction given its easy implantability and acceptable midterm durability.
Risk Factors for Survival After Heart Transplantation in Children and Young Adults: A 22-Year Study of 179 Transplants
Authors: Shah Shawn , Asante-Korang Alfred , Ghazarian Sharon R. , Stapleton Gary , Herbert Carrie , Decker Jamie , Almodovar Melvin C. , Karl Tom R. , Do Nhue L. , Quintessenza James A. , Mavroudis Constantine , Vricella Luca A. , van Gelder Hugh M. , Kartha Vyas , Alexander Plato , Carapellucci Jennifer , Krasnopero Diane , Hanson Jade , Amankwah Ernest , Roth Joeli , Jacobs Jeffrey P. 
Published: August 2018

Background: This article reviews all patients who underwent heart transplantation (HTx) within a single institution (172 patients underwent 179 HTx [167 first-time HTxs, 10 second HTxs, 2 third HTxs]) to describe diagnostic characteristics, management protocols, and risk factors for mortality. Methods: Descriptive analysis was performed for the entire cohort using mean, standard deviation, median, interquartile range, and overall range, as appropriate. Univariable and multivariable Cox proportional hazards models were performed to identify prognostic factors for outcomes over time. The primary outcome of interest was mortality, which was modeled by Kaplan-Meier analysis. Results: Median age at HTx was 263 days (range, 5 days to 24 years; mean = 4.63 ± 5.95 years; 18 neonates, 79 infants). Median weight at HTx was 7.5 kg (range, 2.2-113 kg; mean = 19.36 ± 23.54). Diagnostic categories were cardiomyopathy (n = 62), primary transplantation for hypoplastic left heart syndrome (HLHS) or HLHS-related malformation (n = 33), transplantation after cardiac surgery for HLHS or HLHS-related malformation (n = 17), non-HLHS congenital heart disease (n = 55), and retransplant (n = 12). Operative mortality was 10.1% (18 patients). Cumulative total follow-up is 1,355 years. Late mortality was 18.4% (33 patients). Overall Kaplan-Meier five-year survival was 76.2%. One hundred twenty-one patients are alive with a mean follow-up of 7.61 ± 6.46 years. No survival differences were seen among the five diagnostic subgroups ( P = .064) or between immunosensitized patients (n = 31) and nonimmunosensitized patients (n = 141; P = .422). Conclusions: Excellent results are expected for children undergoing HTx with comparable results among diagnostic groups. Pretransplant mechanical circulatory support and posttransplant mechanical circulatory support are risk factors for decreased survival. Survival after transplantation for HLHS or HLHS-related malformation is better with primary HTx in comparison to HTx after prior cardiac surgery.
AMACE: agent based multi-criterions adaptation in cloud environment
Authors: Kemchi Sofiane , Zitouni Abdelhafid , Djoudi Mahieddine 
Published: August 2018

Abstract
Efficient resource management in dynamic cloud computing is receiving more and more attentions. Many works are still ongoing, since federated cloud computing is an open environment. We present in this paper a flexible model, new cloud operators can join the federation or leave it. The model integrates interactions between broker agents organization, permitting a multi-criterion migration of a submitted customer request. To implement the presented flexible model, we propose AMACE (agent based multi-criterions adaptation in cloud environment) a run-time self-adaptive approach, oriented agent in dynamic cloud federation environment. The proposed approach is multi-criterion, where a various and no limited number of parameters can be considered during the self-adaptation strategy (i.e. computing the load balance of the mediator agent and geographical distance “network delay” between the customer and provider…). In addition, AMACE cares about maintaining run-time coherence in optimization evolution in order to guarantee a coherent system at all moment during system execution.
Discharge pathways and relapse following treatment from early intervention in psychosis services
Authors: Puntis Stephen , Oke Jason , Lennox Belinda 
Published: August 2018

BackgroundEarly intervention in psychosis (EIP) services are the dominant service model in the treatment of first-episode psychosis. They are a time-limited intervention and little is known about discharge destinations and outcomes once EIP treatment has concluded.AimsTo understand discharge pathways and predictors of relapse in an EIP service.MethodWe collected data on all patients with an electronic health record treated by EIP services in Oxford Health NHS Foundation Trust in the UK between 12 January 2006 and 7 March 2017 (n = 701). Our primary outcomes were discharge destination at end of treatment and relapse.ResultsMost patients (83.5%) were discharged to primary care. Transfer to secondary care was associated with previous in-patient admissions (odds ratio (OR) = 1.92, 95% CI 1.54–2.39) and longer EIP treatment (OR = 1.04, 95% CI 1.03–1.06). Relapse rate was highest shortly after leaving EIP services. Relapse was associated with transfer to secondary care (hazard ratio (HR) = 2.75, 95% CI 1.75–4.31), higher deprivation (HR = 1.03, 95% CI, 1.01–1.05), a substance misuse disorder (HR = 1.81, 95% CI 1.01–3.26) and a comorbid diagnosis of a personality disorder (HR = 2.96, 95% CI 1.39–6.29).ConclusionsMost patients treated by the EIP service in Oxfordshire did not receive ongoing mental healthcare from secondary mental health services. We identified high deprivation and those with substance misuse problems or personality disorders as EIP populations with a high risk of relapse.Declaration of interestNone.