bluuebunny/crossref_metadata_2025 huggingface dataset:
Glimma: interactive graphics for gene expression analysis
Authors: Su Shian , Law Charity W , Ah-Cann Casey , Asselin-Labat Marie-Liesse , Blewitt Marnie E , Ritchie Matthew E
Published: February 2017

Motivation

Summary graphics for RNA-sequencing and microarray gene expression analyses may contain upwards of tens of thousands of points. Details about certain genes or samples of interest are easily obscured in such dense summary displays. Incorporating interactivity into summary plots would enable additional information to be displayed on demand and facilitate intuitive data exploration.

Results

The open-source Glimma package creates interactive graphics for exploring gene expression analysis with a few simple R commands. It extends popular plots found in the limma package, such as multi-dimensional scaling plots and mean-difference plots, to allow individual data points to be queried and additional annotation information to be displayed upon hovering or selecting particular points. It also offers links between plots so that more information can be revealed on demand. Glimma is widely applicable, supporting data analyses from a number of well-established Bioconductor workflows (limma, edgeR and DESeq2) and uses D3/JavaScript to produce HTML pages with interactive displays that enable more effective data exploration by end-users. Results from Glimma can be easily shared between bioinformaticians and biologists, enhancing reporting capabilities while maintaining reproducibility.

Availability and Implementation

The Glimma R package is available from http://bioconductor.org/packages/Glimma/.
BCFtools/csq: haplotype-aware variant consequences
Authors: Danecek Petr , McCarthy Shane A
Published: February 2017

Motivation

Prediction of functional variant consequences is an important part of sequencing pipelines, allowing the categorization and prioritization of genetic variants for follow up analysis. However, current predictors analyze variants as isolated events, which can lead to incorrect predictions when adjacent variants alter the same codon, or when a frame-shifting indel is followed by a frame-restoring indel. Exploiting known haplotype information when making consequence predictions can resolve these issues.

Results

BCFtools/csq is a fast program for haplotype-aware consequence calling which can take into account known phase. Consequence predictions are changed for 501 of 5019 compound variants found in the 81.7M variants in the 1000 Genomes Project data, with an average of 139 compound variants per haplotype. Predictions match existing tools when run in localized mode, but the program is an order of magnitude faster and requires an order of magnitude less memory.

Availability and Implementation

The program is freely available for commercial and non-commercial use in the BCFtools package which is available for download from http://samtools.github.io/bcftools.

Supplementary information

Supplementary data are available at Bioinformatics online.
Supervised multiblock sparse multivariable analysis with application to multimodal brain imaging genetics
Authors: Kawaguchi Atsushi , Yamashita Fumio
Published: February 2017

This article proposes a procedure for describing the relationship between high-dimensional data sets, such as multimodal brain images and genetic data. We propose a supervised technique to incorporate the clinical outcome to determine a score, which is a linear combination of variables with hieratical structures to multimodalities. This approach is expected to obtain interpretable and predictive scores. The proposed method was applied to a study of Alzheimer’s disease (AD). We propose a diagnostic method for AD that involves using whole-brain magnetic resonance imaging (MRI) and positron emission tomography (PET), and we select effective brain regions for the diagnostic probability and investigate the genome-wide association with the regions using single nucleotide polymorphisms (SNPs). The two-step dimension reduction method, which we previously introduced, was considered applicable to such a study and allows us to partially incorporate the proposed method. We show that the proposed method offers classification functions with feasibility and reasonable prediction accuracy based on the receiver operating characteristic (ROC) analysis and reasonable regions of the brain and genomes. Our simulation study based on the synthetic structured data set showed that the proposed method outperformed the original method and provided the characteristic for the supervised feature.
Management and outcomes of patients with atrial fibrillation and a history of cancer: the ORBIT-AF registry
Authors: Melloni Chiara , Shrader Peter , Carver Joseph , Piccini Jonathan P. , Thomas Laine , Fonarow Gregg C. , Ansell Jack , Gersh Bernard , Go Alan S. , Hylek Elaine , Herling Irving M. , Mahaffey Kenneth W. , Yu Anthony F. , Peterson Eric D. , Kowey Peter R. ,   on behalf of the ORBIT-AF Steering Committee
Published: February 2017

Aims

The presence of cancer can complicate treatment choices for patients with atrial fibrillation (AF) increasing both the risk of thrombotic and bleeding events.

Methods and results

Using data from Outcomes Registry for Better Informed Treatment of Atrial Fibrillation, we aimed to characterize AF patients with cancer, to describe their management and to assess the association between cancer and cardiovascular (CV) outcomes. Among 9749 patients, 23.8% had history of cancer (57% solid malignancy, 1.3% leukaemia, 3.3% lymphoma, 40% other type, and 2.2% metastatic cancer). Patients with history of cancer were older, more likely to have CV disease, CV risk factors, and prior gastrointestinal bleeding. No difference in antiarrhythmic and antithrombotic therapy was observed between those with and without cancer. Patients with history of cancer had a significantly higher risk of death (7.8 vs. 4.9 deaths per 100 patient-years follow-up, P = 0.0003) mainly driven by non-CV death (4.2 vs. 2.4 per 100 patient-years follow-up; P = 0.0004) and higher risk of major bleeding (5.1 vs. 3.5 per 100 patient-years follow-up; P = 0.02) compared with non-cancer patients; no differences were observed in risks of strokes/non-central nervous system embolism (1.96 vs. 1.48, P = 0.74) and CV death (2.89 vs. 2.07, P = 0.35) between the two groups.

Conclusion

A history of cancer is common among AF patients with up to one in four patients having both. Antithrombotic therapy, rates of cerebrovascular accident, other thrombotic events and cardiac death were similar in AF patients with or without a history of cancer. Patients with cancer, however, were at higher risk of major bleeding and non-CV death.
Improving public health by improving clinical trial guidelines and their application
Authors: Landray Martin J. , Bax Jeroen J. , Alliot Laurence , Buyse Marc , Cohen Adam , Collins Rory , Hindricks Gerhard , James Stefan K. , Lane Sile , Maggioni Aldo P. , Meeker-O'Connell Ann , Olsson Gunnar , Pocock Stuart J. , Rawlins Michael , Sellors Jonathan , Shinagawa Kaori , Sipido Karin R. , Smeeth Liam , Stephens Richard , Stewart Murray W. , Stough Wendy Gattis , Sweeney Fergus , Van de Werf Frans , Woods Kerrie , Casadei Barbara
Published: February 2017

Evidence generated from randomized controlled trials forms the foundation of cardiovascular therapeutics and has led to the adoption of numerous drugs and devices that prolong survival and reduce morbidity, as well as the avoidance of interventions that have been shown to be ineffective or even unsafe. Many aspects of cardiovascular research have evolved considerably since the first randomized trials in cardiology were conducted. In order to be large enough to provide reliable evidence about effects on major outcomes, cardiovascular trials may now involve thousands of patients recruited from hundreds of clinical sites in many different countries. Costly infrastructure has developed to meet the increasingly complex organizational and operational requirements of these clinical trials. Concerns have been raised that this approach is unsustainable, inhibiting the reliable evaluation of new and existing treatments, to the detriment of patient care. These issues were considered by patients, regulators, funders, and trialists at a meeting of the European Society of Cardiology Cardiovascular Roundtable in October 2015. This paper summarizes the key insights and discussions from the workshop, highlights subsequent progress, and identifies next steps to produce meaningful change in the conduct of cardiovascular clinical research.
Acute coronary syndrome in women: rising hospitalizations in middle-aged French women, 2004–14
Authors: Gabet Amélie , Danchin Nicolas , Juillière Yves , Olié Valérie
Published: February 2017

Aims

We aimed to analyse trends in annual incidence of hospitalized acute coronary syndrome (ACS) in France from 2004 to 2014.

Methods and results

Primary diagnosis of ACS and subtypes on admissions were selected in national and exhaustive French Hospitalization Database from 2004 to 2014. Age-standardized rates were computed using standardization on the census of the 2010 European population and mean annual percent changes were estimated by using Poisson regression model. In 2014, 113 407 patients, 36 480 women (32.2%) and 76 927 men (67.8%) were hospitalized for ACS. Among women, the proportion aged under 65 years was 25.2% (n = 9206) and there was 34.4% of STEMI, 18.2% of NSTEMI and 47.4% of UA. From 2004 to 2014, the rates of age-standardized admissions for ACS in women less than 65 years old increased by 6.3%.This rise in ACS was driven by significant increases in STEMI (+21.7%) and NSTEMI (+53.7%). The largest increase in STEMI mean annual percent change was observed among women aged 45–54 years old (+3.6%/per year). After 65 years of age, significant decreases in all ACS types were observed.

Conclusion

This nationwide study showed substantial rising trends in STEMI annual incidence, especially among younger women. This increase could be attributed to increase in smoking and obesity. Efforts to strengthen primary prevention of CVD in younger women is needed as the main risk factors are modifiable, and as there is a growing evidence of higher short-term mortality of CHD in women.
Making space for shellfish farming along the Adriatic coast
Authors: Brigolin Daniele , Porporato Erika Maria Diletta , Prioli Giuseppe , Pastres Roberto
Published: February 2017

This work focuses on the selection of new areas for shellfish farming along the coast of the Northern Adriatic Sea (Italy). Shellfish site suitability was assessed by means of a methodology based on Spatial Multi-Criteria Evaluation (SMCE), which provided the framework to combine mathematical models and operational oceanography products. Intermediate level criteria considered in the analysis included optimal growth conditions, environmental interactions, and socio-economic evaluation (e.g. organic carbon deposition; distance to harbour). Results showed that the whole coastal area comprised within 0 and 3 nm is highly suitable for farming of mussel, while the area comprised between 3 and 12 nm is divided between a highly suitable northern part, and a less suitable southern one. Seven different scenarios of development of shellfish aquaculture industry were explored. The introduction of a new species, and the assessment of the exposure to storm events are specific aspects taken into account in development scenarios. Results show that the degree of suitability for shellfish aquaculture in this area would not change dramatically with the introduction of oyster farming. Furthermore, results highlight that: (i) the growth potential in this area is high; (ii) the space with suitability index >0.5 increases when prioritizing the optimal growth condition criteria, and (iii) the socio-economic is the most restrictive Intermediate Level Criteria. Results were discussed by deriving general lessons concerning the use of SMCE in aquaculture space allocation, from the specific application in the Northern Adriatic Sea. Challenges and opportunities related to the proposed methodological framework, with particular reference to the use of resources provided by remote sensing and operational oceanography by means of mathematical models, were also discussed. Results can support a science-based identification of allocated zones for aquaculture in order to avoid conflicts, and promote sustainable aquaculture in the Mediterranean Sea, where the space for these activities is becoming increasingly limited.
Meaningful use in the safety net: a rapid ethnography of patient portal implementation at five community health centers in California
Authors: Ackerman Sara L , Sarkar Urmimala , Tieu Lina , Handley Margaret A , Schillinger Dean , Hahn Kenneth , Hoskote Mekhala , Gourley Gato , Lyles Courtney
Published: February 2017

Objective:US health care institutions are implementing secure websites (patient portals) to achieve federal Meaningful Use (MU) certification. We sought to understand efforts to implement portals in “safety net” health care systems that provide services for low-income populations.

Materials and Methods:Our rapid ethnography involved visits at 4 California safety net health systems and in-depth interviews at a fifth. Visits included interviews with clinicians and executives (n = 12), informal focus groups with front-line staff (n = 35), observations of patient portal sign-up procedures and clinic work, review of marketing materials and portal use data, and a brief survey (n = 45).

Results:Our findings demonstrate that the health systems devoted considerable effort to enlisting staff support for portal adoption and integrating portal-related work into clinic routines. Although all health systems had achieved, or were close to achieving, MU benchmarks, patients faced numerous barriers to portal use and our participants were uncertain how to achieve and sustain “meaningful use” as defined by and for their patients.

Discussion:Health systems’ efforts to achieve MU certification united clinic staff under a shared ethos of improved quality of care. However, MU’s assumptions about patients’ demand for electronic access to health information and ability to make use of it directed clinics’ attention to enrollment and message routing rather than to the relevance and usability of a tool that is minimally adaptable to the safety net context.

Conclusion:We found a mismatch between MU-based metrics of patient engagement and the priorities and needs of safety net patient populations.
Crossing the health IT chasm: considerations and policy recommendations to overcome current challenges and enable value-based care
Authors: Adler-Milstein Julia , Embi Peter J , Middleton Blackford , Sarkar Indra Neil , Smith Jeff
Published: February 2017

While great progress has been made in digitizing the US health care system, today’s health information technology (IT) infrastructure remains largely a collection of systems that are not designed to support a transition to value-based care. In addition, the pursuit of value-based care, in which we deliver better care with better outcomes at lower cost, places new demands on the health care system that our IT infrastructure needs to be able to support. Provider organizations pursuing new models of health care delivery and payment are finding that their electronic systems lack the capabilities needed to succeed. The result is a chasm between the current health IT ecosystem and the health IT ecosystem that is desperately needed.

In this paper, we identify a set of focal goals and associated near-term achievable actions that are critical to pursue in order to enable the health IT ecosystem to meet the acute needs of modern health care delivery. These ideas emerged from discussions that occurred during the 2015 American Medical Informatics Association Policy Invitational Meeting. To illustrate the chasm and motivate our recommendations, we created a vignette from the multistakeholder perspectives of a patient, his provider, and researchers/innovators. It describes an idealized scenario in which each stakeholder’s needs are supported by an integrated health IT environment. We identify the gaps preventing such a reality today and present associated policy recommendations that serve as a blueprint for critical actions that would enable us to cross the current health IT chasm by leveraging systems and information to routinely deliver high-value care.
Selling Pain to the Saturated Self
Authors: Scott Rebecca , Cayla Julien , Cova Bernard
Published: February 2017

How can we comprehend people who pay for an experience marketed as painful? On one hand, consumers spend billions of dollars every year to alleviate different kinds of pain. On the other hand, millions of individuals participate in extremely painful leisure pursuits. In trying to understand this conundrum, we ethnographically study a popular adventure challenge where participants subject themselves to electric shocks, fire, and freezing water. Through sensory intensification, pain brings the body into sharp focus, allowing individuals to rediscover their corporeality. In addition, painful extraordinary experiences operate as regenerative escapes from the self. By flooding the consciousness with gnawing unpleasantness, pain provides a temporary relief from the burdens of self-awareness. Finally, when leaving marks and wounds, pain helps consumers create the story of a fulfilled life. In a context of decreased physicality, market operators play a major role in selling pain to the saturated selves of knowledge workers, who use pain as a way to simultaneously escape reflexivity and craft their life narrative.
Acquisition of radioresistance by IL-6 treatment is caused by suppression of oxidative stress derived from mitochondria after γ-irradiation
Authors: Tamari Yuki , Kashino Genro , Mori Hiromu
Published: February 2017

Interleukin (IL)-6 is a multifunctional cytokine and is one of the radiation-induced bystander factors. This study aimed to clarify the mechanism of acquisition of radioresistance through the control of reactive oxygen species (ROS) by IL-6. We used a rat glioma cell line (C6) as tumor cells and a rat astrocyte cell line (RNB) as non-tumor cells. Our results showed that the surviving fraction of C6 cells after 6 Gy irradiation was increased by the addition of IL-6, but that this was not the case in RNB cells. In addition, the number of 53BP1 foci in C6 cells at 30 min after γ-irradiation were decreased by IL-6. Levels of ROS in whole C6 cells, and superoxide in the mitochondria of C6 cells immediately after γ-irradiation, were reduced by IL-6, but this was not observed in RNB cells. The mitochondrial membrane potential detected by JC-1 in C6 and RNB cells was inhibited by IL-6 alone. Therefore, it was concluded that IL-6 leads specifically to radioresistance in tumor cells by inhibition of increases in ROS after γ-irradiation.
Combined modality therapy in Stage IIIA non–small cell lung cancer: clarity or confusion despite the highest level of evidence?
Authors: Jeremic Branislav , Casas Francesc , Dubinsky Pavol , Gomez-Caamano Antonio , Čihorić Nikola , Videtic Gregory , Latinovic Miroslav
Published: February 2017

Recent years have witnessed a number of clinical trials in Stage IIIA non–small cell lung cancer (NSCLC) comparing (A) induction chemotherapy (CHT) with induction CHT and radiotherapy (RT), each followed by surgery; (B) either induction CHT or induction RT-CHT, each followed by surgery, with definitive RT-CHT (no surgery). Due to the heterogeneity of patient, tumor and treatment characteristics across these trials, various meta-analyses (MAs) have been performed to define the optimal treatment approach in this setting for this clinical presentation. Six such MAs exist. In spite of the differences between MAs, it appears that RT does not add extra benefit to induction CHT administered before surgery, and that a trimodality (i.e. including surgery) regimen is not superior to definitive concurrent RT-CHT. While one can consider both induction CHT followed by surgery and exclusive concurrent RT-CHT as feasible in this setting, lack of pre-treatment predictive factors identifying patients who might preferentially benefit from a surgical approach limits its use to well-planned clinical trials.
Effects of binary stellar populations on direct collapse black hole formation
Authors: Agarwal Bhaskar , Cullen Fergus , Khochfar Sadegh , Klessen Ralf S. , Glover Simon C. O. , Johnson Jarrett
Published: February 2017

The critical Lyman–Werner (LW) flux required for direct collapse blackholes (DCBH) formation, or Jcrit, depends on the shape of the irradiating spectral energy distribution (SED). The SEDs employed thus far have been representative of realistic single stellar populations. We study the effect of binary stellar populations on the formation of DCBH, as a result of their contribution to the LW radiation field. Although binary populations with ages > 10 Myr yield a larger LW photon output, we find that the corresponding values of Jcrit can be up to 100 times higher than single stellar populations. We attribute this to the shape of the binary SEDs as they produce a sub-critical rate of H− photodetaching 0.76 eV photons as compared to single stellar populations, reaffirming the role that H− plays in DCBH formation. This further corroborates the idea that DCBH formation is better understood in terms of a critical region in the H2–H− photodestruction rate parameter space, rather than a single value of LW flux.
The Barrow Neurological Institute Scale Revisited: Predictive Capabilities for Cerebral Infarction and Clinical Outcome in Patients With Aneurysmal Subarachnoid Hemorrhage
Authors: Dengler Nora F. , Diesing Dominik , Sarrafzadeh Asita , Wolf Stefan , Vajkoczy Peter
Published: February 2017

BACKGROUND: In 2012, a new computed tomography (CT) grading scale was introduced by the Barrow Neurological Institute group (“BNI scale”) to predict angiographic and symptomatic vasospasm in aneurysmal subarachnoid hemorrhage.

OBJECTIVE: To address the question of whether BNI grading is reliable in the prediction of cerebral infarction and clinical outcome and to compare BNI scores to existing radiographic and clinical models of outcome prediction.

METHODS: Consecutive data of 260 patients with aneurysmal subarachnoid hemorrhage was retrospectively analyzed with respect to radiographic and clinical parameters.

RESULTS: Patients presenting with more severe BNI grades were older (P = .002), displayed lower Glasgow Coma Scale scores at admission (P < .001) and were more often diagnosed with intraventricular hemorrhage (P < .001). An increasing BNI grade was associated with higher rates of severe angiographic vasospasm (P = .007), the occurrence of new cerebral infarction (P < .001), and poor patient outcome (P < .001). In contrast, analysis according to the Fisher grading system did not show a significant relationship to any outcome parameter. Multivariate analysis combining radiographic and clinical parameters showed significant results for clinical scores (Hunt and Hess and World Federation of Neurosurgical Societies) with radiographic information losing its predictive capability.

CONCLUSION: The BNI scale is easily applicable and superior to the original Fisher scale regarding prediction of angiographic vasospasm, new cerebral infarction, and patient outcome. Presence of intraventricular hemorrhage and intracerebral hemorrhage are additional radiographic factors with outcome relevance that are not part of the BNI scale. Established clinical scores like World Federation of Neurosurgical Societies and Hunt and Hess grading were more relevant for outcome prediction than any radiographic information.
A New Classification for Pathologies of Spinal Meninges, Part 1: Dural Cysts, Dissections, and Ectasias
Authors: Klekamp Jörg
Published: February 2017

BACKGROUND: The clinical significance of pathologies of the spinal dura is often unclear and their management controversial.

OBJECTIVE: To classify spinal dural pathologies analogous to vascular aneurysms, present their symptoms and surgical results.

METHODS: Among 1519 patients with spinal space-occupying lesions, 66 patients demonstrated dural pathologies. Neuroradiological and surgical features were reviewed and clinical data analyzed.

RESULTS: Saccular dural diverticula (type I, n = 28) caused by defects of both dural layers, dissections between dural layers (type II, n = 29) due to defects of the inner layer, and dural ectasias (type III, n = 9) related to structural changes of the dura were distinguished. For all types, symptoms consisted of local pain followed by signs of radiculopathy or myelopathy, while one patient with dural ectasia presented a low-pressure syndrome and 10 patients with dural dissections additional spinal cord herniation. Type I and type II pathologies required occlusion of their dural defects via extradural (type I) or intradural (type II) approaches. For type III pathologies of the dural sac no surgery was recommended. Favorable results were obtained in all 14 patients with type I and 13 of 15 patients with type II pathologies undergoing surgery.

CONCLUSION: The majority of dural pathologies involving root sleeves remain asymptomatic, while those of the dural sac commonly lead to pain and neurological symptoms. Type I and type II pathologies were treated with good long-term results occluding their dural defects, while ectasias of the dural sac (type III) were managed conservatively.
Preoperative Stratification of Transsphenoidal Pituitary Surgery Patients Based on Surgical Urgency
Authors: Zaidi Hasan A. , Wang Amy J. , Cote David J. , Smith Timothy R. , Prevedello Daniel , Solari Domenico , Cappabianca Paolo , Quiroga Monica , Laws Edward R.
Published: February 2017

BACKGROUND

Currently, there is no prioritization scale available to distinguish those patients with pituitary tumors who require urgent surgical intervention from those who are candidates for elective treatment.

OBJECTIVE

To develop a classification system that can help primary care physicians, endocrinologists, neurosurgeons, ancillary support staff, and hospital administrators identify high-priority surgical candidates.

METHODS

An expert international panel of clinicians consisting of endocrinologists and neurosurgeons who are involved in the diagnosis and management of sellar disease was convened. The panel retrospectively reviewed individual experiences, including a cohort of patients operated upon for pituitary related disease at the Brigham and Women's Hospital from January 2008 to November 2015. A risk stratification schema was developed to streamline patient care pathways.

RESULTS

We identified 4 groups of surgical candidates with varying levels of risk, and then assigned treatment timelines and different differential diagnoses to each. The 4 groups were as follows: group A: urgent—immediate; group B: prompt—initiate treatment within 1 to 2 weeks; group C: soon—initiate treatment within 3 months; group D: elective—as soon as indicated. Among 472 patients treated at Brigham and Women's Hospital for pituitary adenomas, each was assigned to 1 of the 4 predetermined subgroups: group A, 6.8%; group B, 30.1%; group C, 31.1%; group D, 32.0%.

CONCLUSIONS

We developed a risk stratification schema that may serve as a platform to streamline care to the patients at highest risk. The expert opinions presented provide a basis for future studies regarding the risk prioritization of patients.
Prognostic Factors in Patients With Spinal Chordoma: An Integrative Analysis of 682 Patients
Authors: Zhou Jianhua , Sun James , Bai Harrison Xiao , Huang Xiangyan , Zou Yingjie , Tan Xia , Zhang Zishu , Tang Xiangqi , Tao Yongguang , Xiao Bo , Zhang Paul J , Yang Li
Published: February 2017

BACKGROUND

The low incidence of spinal chordoma precludes a prospective study of prognostic factors with a large patient cohort.

OBJECTIVE

To perform a comprehensive integrative analysis on the prognostic factors, treatment, and outcomes of patients with spinal chordoma using data from 2 institutions and the literature.

METHODS

Appropriate studies were identified per search criteria. The local database was retrospectively searched to include a similar patient cohort.

RESULTS

Overall, 108 studies from the literature and 30 patients from our local institution were identified, resulting in a total of 682 patients. The median age was 57 years old and 35.2% were female. The median follow-up was 46 months (range: 1-408). The median progression-free survival (PFS) and overall survival (OS) were 72 months and 115 months, respectively. Significant prognostic factors for PFS on multivariate analysis included age (pediatric vs adult, hazard ratio [HR]: 2.00-14.36), tumor location (mobile spine vs sacral spine, HR: 0.31-0.87), pathology (differentiated vs classic, HR: 2.48-10.90),and chemotherapy (HR:1.11-3.85). Significant prognostic factors for OS on multivariate analysis included age (geriatric vs adult, HR: 1.52-3.45 and pediatric vs adult, HR: 1.73-9.36), bladder or bowel dysfunction (HR: 1.27-5.43), pathology (dedifferentiated vs classic, HR: 2.38-11.09), recurrence or progression (HR: 1.72-4.48), and metastases (HR: 1.11-2.47).

CONCLUSION

In patients with spinal chordoma, young age, location in sacral spine, dedifferentiated pathology, and chemotherapy were negative predictors of PFS, while young and old age, bladder or bowel dysfunction at presentation, dedifferentiated pathology, recurrence or progression, and metastases portended a worse OS.
A Reliable Grading System for Prediction of Chronic Subdural Hematoma Recurrence Requiring Reoperation After Initial Burr-Hole Surgery
Authors: Stanišić Milo , Pripp Are Hugo
Published: February 2017

BACKGROUND

There is no widely adopted grading system for the prediction of postoperative recurrence requiring reoperation (RrR) in patients with chronic subdural hematoma (CSDH).

OBJECTIVE

We developed a CSDH grading system to predict RrR based on predictive characteristics that can be objectively assessed at the time of first presentation and initial surgery.

METHODS

Prospectively collected data from 107 consecutive surgical patients with CSDH were reviewed. Predictors of RrR were identified via logistic and lasso regression analyses. A prognostic CSDH grading system was proposed, with the weighing of predictors based on strength of association. The scoring system was then applied to the same set of patients in our database for internal validation.

RESULTS

The strongest predictors of RrR were an isodense or hyperdense lesions and laminar or separated lesions, and a postoperative CSDH cavity volume greater than 200 mL. The moderate predictors of RrR were a postoperative CSDH cavity volume of 80 to 200 mL and a preoperative CSDH volume greater than 130 mL. According to the prognostic CSDH grading system, no patients with a score of 0 points had RrR. RrR was observed in 6% of patients with a score of 1 to 2 points, 30% of patients with a score of 3 to 4 points, and 63% of patients with a score of 5 points (ie, the maximum score). The rate of RrR increased steadily with increases in the prognostic CSDH grading score (P< .001).

CONCLUSION

The prognostic CSDH grading system is an applicable tool for RrR risk stratification in patients with CSDH.
The use of cannabis in supportive care and treatment of brain tumor
Authors: Likar Rudolf , Nahler Gerhard
Published: February 2017

Cannabinoids are multitarget substances. Currently available are dronabinol (synthetic delta-9-tetrahydrocannabinol, THC), synthetic cannabidiol (CBD) the respective substances isolated and purified from cannabis, a refined extract, nabiximols (THC:CBD = 1.08:1.00); and nabilone, which is also synthetic and has properties that are very similar to those of THC. Cannabinoids have a role in the treatment of cancer as palliative interventions against nausea, vomiting, pain, anxiety, and sleep disturbances. THC and nabilone are also used for anorexia and weight loss, whereas CBD has no orexigenic effect. The psychotropic effects of THC and nabilone, although often undesirable, can improve mood when administered in low doses. CBD has no psychotropic effects; it is anxiolytic and antidepressive. Of particular interest are glioma studies in animals where relatively high doses of CBD and THC demonstrated significant regression of tumor volumes (approximately 50% to 95% and even complete eradication in rare cases). Concomitant treatment with X-rays or temozolomide enhanced activity further. Similarly, a combination of THC with CBD showed synergistic effects. Although many questions, such as on optimized treatment schedules, are still unresolved, today’s scientific results suggest that cannabinoids could play an important role in palliative care of brain tumor patients.
Efficacy and Safety of Oritavancin Relative to Vancomycin for Patients with Acute Bacterial Skin and Skin Structure Infections (ABSSSI) in the Outpatient Setting: Results From the SOLO Clinical Trials
Authors: Lodise Thomas P. , Redell Mark , Armstrong Shannon O. , Sulham Katherine A. , Corey G. Ralph
Published: February 2017

Background

The objective of this analysis was to evaluate the efficacy and safety of oritavancin compared with vancomycin for patients with acute bacterial skin and skin structure infections (ABSSSIs) who received treatment in the outpatient setting in the Phase 3 SOLO clinical trials.

Methods

SOLO I and SOLO II were 2 identically designed comparative, multicenter, double-blind, randomized studies to evaluate the efficacy and safety of a single 1200-mg dose of intravenous (IV) oritavancin versus 7–10 days of twice-daily IV vancomycin for the treatment of ABSSSI. Protocols were amended to allow enrolled patients to complete their entire course of antimicrobial therapy in an outpatient setting. The primary efficacy outcome was a composite endpoint (cessation of spread or reduction in size of the baseline lesion, absence of fever, and no rescue antibiotic at early clinical evaluation [ECE]) (48 to 72 hours). Key secondary endpoints included investigator-assessed clinical cure 7 to 14 days after end of treatment (posttherapy evaluation [PTE]) and 20% or greater reduction in lesion area at ECE. Safety was assessed until day 60.

Results

Seven hundred ninety-two patients (oritavancin, 392; vancomycin, 400) received entire course of treatment in the outpatient setting. Efficacy response rates at ECE and PTE were similar (primary composite endpoint at ECE: 80.4% vs 77.5% for oritavancin and vancomycin, respectively) as was incidence of adverse events. Five patients (1.3%) who received oritavancin and 9 (2.3%) vancomycin patients were subsequently admitted to a hospital.

Conclusions

Oritavancin provides a single-dose alternative to multidose vancomycin for treatment of ABSSSI in the outpatient setting.
A Randomized Placebo Controlled Trial of Aspirin Effects on Immune Activation in Chronically Human Immunodeficiency Virus-Infected Adults on Virologically Suppressive Antiretroviral Therapy
Authors: O’Brien Meagan P. , Hunt Peter W. , Kitch Douglas W. , Klingman Karin , Stein James H. , Funderburg Nicholas T. , Berger Jeffrey S. , Tebas Pablo , Clagett Brian , Moisi Daniela , Utay Netanya S. , Aweeka Fran , Aberg Judith A.
Published: February 2017

Background

Immune activation persists despite suppressive antiretroviral therapy (ART) in human immunodeficiency virus (HIV) infection and predicts non-Acquired Immune Deficiency Syndrome (AIDS) comorbidities including cardiovascular disease. Activated platelets play a key role in atherothrombosis and inflammation, and platelets are hyperactivated in chronic HIV infection. Aspirin is a potent inhibitor of platelet activation through the cyclooxygenase-1 (COX-1) pathway. We hypothesized that platelet activation contributes to immune activation and that aspirin would reduce immune activation and improve endothelial function in ART-suppressed HIV-infected individuals.

Methods

In this prospective, double-blind, randomized, placebo-controlled 3-arm trial of 121 HIV-infected participants on suppressive ART for >48 weeks, we evaluated the effects of 12 weeks of daily aspirin 100 mg, aspirin 300 mg, or placebo on soluble and cellular immune activation markers, flow-mediated dilation (FMD) of the brachial artery, and serum thromboxane B2, a direct readout of platelet COX-1 inhibition.

Results

The 300-mg and 100-mg aspirin arms did not differ from placebo in effects on soluble CD14, interleukin (IL)-6, soluble CD163, D-dimer, T-cell or monocyte activation, or the other immunologic endpoints measured. Endothelial function, as measured by FMD, also was not significantly changed when comparing the 300-mg and 100-mg aspirin arms to placebo.

Conclusions

Aspirin treatment for 12 weeks does not have a major impact on soluble CD14, IL-6, soluble CD163, D-dimer, T-cell or monocyte activation, or FMD, suggesting that inhibition of COX-1-mediated platelet activation does not significantly improve HIV-related immune activation and endothelial dysfunction. Although future studies are needed to further identify the causes and consequences of platelet activation in ART-treated HIV infection, interventions other than COX-1 inhibition will need to be explored to directly reduce immune activation in treated HIV infection.
Fatal Eastern Equine Encephalitis in a Patient on Maintenance Rituximab: A Case Report
Authors: Solomon Isaac H. , Ciarlini Pedro D. S. C. , Santagata Sandro , Ahmed Asim A. , De Girolami Umberto , Prasad Sashank , Mukerji Shibani S.
Published: February 2017

A 63-year-old woman on rituximab maintenance for follicular lymphoma presented with headaches, vomiting, and fever, and was diagnosed with eastern equine encephalomyelitis by cerebrospinal fluid polymerase chain reaction. Eastern equine encephalomyelitis immunoglobulin (Ig)G/IgM remained negative due to rituximab treatment, and magnetic resonance imaging showed minimal abnormalities, making this a diagnostically challenging case. Despite therapy with intravenous Ig, the patient rapidly declined and died on hospital day 12. Autopsy revealed perivascular and parenchymal chronic inflammation, with an absence of B lymphocytes, and virally infected neurons throughout the central nervous system.
High Prevalence of Humoral and Cellular Immunity to Influenza Viruses in Preschool Children Living in Addis Ababa, Ethiopia
Authors: Dembinski Jennifer L. , Mihret Adane , Yimer Solomon A. , Tessema Bamlak , Trieu Mai-Chi , Tarekegn Azeb , Getachew Nahom , Cox Rebecca J. , Oftung Fredrik , Haneberg Bjørn , Aseffa Abraham , Mjaaland Siri
Published: February 2017

Background

Influenza in children who reside in tropical and subtropical regions has until recently been regarded as insignificant. However, new evidence suggests that it significantly impacts hospitalization and promotes secondary bacterial coinfections. Ethiopia is situated in a subtropical area where influenza viruses are likely to circulate year round.

Methods

Clinical data were recorded in a cohort of 103 healthy preschool children recruited in Addis Ababa, Ethiopia. Humoral and cellular immune responses to influenza virus were determined by hemagglutination inhibition (HI) and interferon-γ enzyme-linked immunospot assays.

Results

Ninety-six percent of the children (2–5 years old) had pre-existing HI antibody responses to 1 or more of the circulating influenza A subtypes, H1N1 (51%), H3N2 (86%), or influenza B (51%) strains. At the age of 4, all children had been infected with at least 1 strain, and 75% had been infected with 2–4 different viral strains. CD4+ and CD8+ T-cell responses against conserved viral antigens increased with repeated exposures, indicating boosting of cross-reactive cellular immunity. Malnutrition did not seem to affect these immune responses to influenza.

Conclusions

Influenza is highly prevalent among children in this area of Ethiopia. Due to the risk of secondary bacterial pneumonia, increased influenza awareness might benefit child health.
Hepatitis B Virus Reactivation in Patients Receiving Interferon-Free Direct-Acting Antiviral Agents for Chronic Hepatitis C Virus Infection
Authors: Liu Chen-Hua , Liu Chun-Jen , Su Tung-Hung , Fang Yu-Jen , Yang Hung-Chih , Chen Pei-Jer , Chen Ding-Shinn , Kao Jia-Horng
Published: February 2017

Background

Little is known about the risk of hepatitis B virus (HBV) reactivation in patients receiving interferon (IFN)-free direct-acting antiviral agents (DAAs) for hepatitis C virus (HCV).

Methods

Patients who were seropositive for HBV core antibody and who received IFN-free DAAs for HCV were enrolled. Hepatitis B virus reactivation was defined as reappearance of serum HBV deoxyribonucleic acid (DNA) ≥100 IU/mL in patients with baseline undetectable viral load, or ≥2 log10 IU/mL increase of HBV DNA in patients with baseline detectable viral load. Hepatitis B virus-related alanine aminotransferase (ALT) flare was defined as ALT ≥5 times upper limit of normal or ≥2 times of the baseline level. Hepatitis B virus-related hepatic decompensation was defined as presence of jaundice, coagulopathy, hepatic encephalopathy, or ascites.

Results

Compared with no HBV reactivation in 81 HBV surface antigen (HBsAg)-negative patients, 2 of 12 HBsAg-positive patients had HBV reactivation (0% [confidence interval {95% CI}, 0%–4.5%] vs 16.7% [95% CI, 4.7%–44.8%], P = .015). No patients had ALT flare or hepatic decompensation. Baseline HBsAg level at a cutoff value of 500 IU/mL was associated with HBV reactivation in HBsAg-positive patients. There was no HBsAg seroreversion in HBsAg-negative patients.

Conclusions

Hepatitis B virus reactivation is limited to HBsAg-positive patients receiving IFN-free DAAs for HCV. Higher baseline HBsAg levels are associated with HBV reactivation. The risk of ALT flares or hepatic decompensation is low in these patients.
Relationship of Human Immunodeficiency Virus Viral Load in Cerebrospinal Fluid and Plasma in Patients Co-infected With Cryptococcal Meningitis
Authors: Chang Christina C. , Kangethe Richard , Omarjee Saleha , Hiramen Keshni , Gosnell Bernadett , Sojane Katlego , Moosa Mohamed-Yunus S. , Lewin Sharon R. , French Martyn A. , Ndung’u Thumbi
Published: February 2017

We measured human immunodeficiency virus (HIV) ribonucleic acid (RNA) in paired cerebrospinal fluid (CSF) and plasma samples in a prospective study of 91 HIV-infected, antiretroviral therapy-naive patients with cryptococcal meningitis. Cerebrospinal fluid HIV RNA was lower than in plasma (median 4.7 vs 5.2 log10 copies/mL, P < .0001) and positively correlated with plasma HIV RNA, peripheral CD4+ T-cell percentage, and CSF CXCL10. Plasma/CSF ratio of HIV RNA ranged widely from 0.2 to 265.5 with a median of 2.6. Cerebrospinal fluid quantitative cryptococcal culture positively correlated with CSF CCL2 and CCL3. CSF-plasma viral discordance was not associated with cryptococcal-associated immune reconstitution inflammatory syndrome.
Multi-color photometric investigation of the totally eclipsing binary NO Camelopardalis
Authors: Zhou Xiao , Qian Shengbang , Zhang Bin
Published: February 2017

Multi-color photometric light curves of NO Camelopardalis in V, RC, and IC bands are obtained and analyzed simultaneously using the Wilson–Devinney program. The solutions suggest that NO Cam is an A-subtype overcontact binary with a mass ratio of q = 0.439 and a contact degree of f = 55.5%. The small temperature difference (ΔT = 44 K) between its two components indicates that the system is under thermal contact. The high orbital inclination (i = 84${^{\circ}_{.}}$5) strengthens our confidence in the parameters determined from the light curves. All available times of minimum light are collected and period variations are analyzed for the first time. The O − C curve reveals that its period is increasing continuously at a rate of dP/dt = +1.46 × 10−9, which can be explained by mass transfer from the less massive component to the more massive one. After the upward parabolic variation is subtracted, the residuals suggest that there may be a cyclic variation with a period of 2.23 yr and an amplitude of A3 = 0.00153 d, which may due to the light-travel-time effect arising from the gravitational influence of a close-in tertiary component. The close-in companion reveals that early dynamic interaction among a triple system may have played a very important role in the formation of the W UMa-type binaries.
Falling Down on the Job: Evaluation and Treatment of Fall Risk Among Older Adults With Upper Extremity Fragility Fractures
Authors: McDonough Christine M. , Colla Carrie H. , Carmichael Donald , Tosteson Anna N. A. , Tosteson Tor D. , Bell John-Erik , Cantu Robert V. , Lurie Jonathan D. , Bynum Julie P. W.
Published: February 2017

Background:

Clinical practice guidelines recommend fall risk assessment and intervention for older adults who sustain a fall-related injury to prevent future injury and mobility decline.

Objective:

The aim of this study was to describe how often Medicare beneficiaries with upper extremity fracture receive evaluation and treatment for fall risk.

Design:

Observational cohort.

Methods:

Participants were fee-for-service beneficiaries age 66 to 99 treated as outpatients for proximal humerus or distal radius/ulna (“wrist”) fragility fractures. -Participants were studied using Carrier and Outpatient Hospital files. The proportion of patients evaluated or treated for fall risk up to 6 months after proximal humerus or wrist fracture from 2007–2009 was examined based on evaluation, treatment, and diagnosis codes. Time to evaluation and number of treatment sessions were calculated. Logistic regression was used to analyze patient characteristics that predicted receiving evaluation or treatment. Narrow (gait training) and broad (gait training or therapeutic exercise) definitions of service were used.

Results:

There were 309,947 beneficiaries who sustained proximal humerus (32%) or wrist fracture (68%); 10.7% received evaluation or treatment for fall risk or gait issues (humerus: 14.2%; wrist: 9.0%). Using the broader definition, the percentage increased to 18.5% (humerus: 23.4%; wrist: 16.3%). Factors associated with higher likelihood of services after fracture were: evaluation or treatment for falls or gait prior to fracture, more comorbidities, prior nursing home stay, older age, humerus fracture (vs wrist), female sex, and white race.

Limitations:

Claims analysis may underestimate physician and physical therapist fall assessments, but it is not likely to qualitatively change the results.

Conclusions:

A small proportion of older adults with upper extremity fracture received fall risk assessment and treatment. Providers and health systems must advance efforts to provide timely evidence-based management of fall risk in this population.
Use of Maternal Early Warning Trigger Tool Reduces Maternal Morbidity
Authors: Shields Laurence E. , Wiesner Suzanne , Klein Catherine , Pelletreau Barbara , Hedriana Herman L.
Published: February 2017

(Am J Obstet Gynecol. 2016;214:527.e1–527.e6)

Over the past 20 years, maternal mortality has increased unabated in the United States along with a simultaneous increase in severe maternal morbidity. Many national and state organizations have provided recommendations regarding the use of maternal early warning tools to solve this problem. However, there are limited data that support the use of these types of clinical assessment tools to reduce maternal morbidity. The objective of this study were to determine whether maternal morbidity could be reduced with the implementation of a clinical pathway-specific Maternal Early Warning Trigger (MEWT) tool. This tool was developed internally and prospectively implemented as a pilot project in 6 of 29 hospitals within a large hospital system.