bluuebunny/crossref_metadata_2025 huggingface dataset:
The Cytokine Response Profile of Ebola Virus Disease in a Large Cohort of Rhesus Macaques Treated With Monoclonal Antibodies
Authors: Banadyga Logan , Siragam Vinayakumar , Zhu Wenjun , He Shihua , Cheng Keding , Qiu Xiangguo
Published: February 2019

Ebola virus (EBOV) is a highly pathogenic filovirus that causes outbreaks of a severe hemorrhagic fever known as EBOV disease (EVD). Ebola virus disease is characterized in part by a dysregulated immune response and massive production of both pro- and anti-inflammatory cytokines. To better understand the immune response elicited by EVD in the context of treatment with experimental anti-EBOV antibody cocktails, we analyzed 29 cytokines in 42 EBOV-infected rhesus macaques. In comparison to the surviving treated animals, which exhibited minimal aberrations in only a few cytokine levels, nonsurviving animals exhibited a dramatically upregulated inflammatory response that was delayed by antibody treatment.
The Contra Proferentem Rule: Contract Law’s Great Survivor
Authors: McCunn Joanna
Published: February 2019

The contra proferentem rule has been under sustained attack in recent years, as judges doubt whether it has any role to play in modern commercial contract law. This article sheds light on the function of the rule by examining its historical development. The rule has been part of English contract law for over 600 years, playing very different roles at each stage of its development. Lawyers since the medieval period have criticised the rule, but have succeeded in continually repurposing it to fit with new conceptions of contract law and to address the most pressing concerns of their day. This article shows that the contra proferentem rule can provide a fascinating case study in the development of common law doctrine, and argues that the future need not be wholly bleak for one of our longest-lived canons of construction.
Subfrontal Infrachiasmatic Approach to a Craniopharyngioma Resection: 2-Dimensional Operative Video
Authors: Aldave Guillermo , Zinn Pascal , Whitehead William E
Published: February 2019

Craniopharyngioma constitutes one of the most challenging tumors. The surgery may be the definitive treatment and multiple approaches have been described based on different anatomical considerations. The choice of the right approach is the key to optimize the resection and minimize the risks. Besides, the presentation of this tumor in the pediatric population can carry additional challenges that are not present in adults, like the absence of pneumatization of the sphenoid bone for an endoscopic endonasal approach. In this video, we present a case of a 6-yr-old girl with a large sellar-suprasellar craniopharyngioma. The fact that the sphenoid was not pneumatized and the chiasm was elevated 1.2 cm from the planum sphenoidal were some of the reasons to choose a subfrontal infrachiasmatic approach as we discuss and we show in the video. This approach has not been very well established in the literature but we demonstrate it can become a good alternative for a particular type of sellar-suprasellar tumors. Appropriate video authorization consent was obtained from the parent of the patient.
The Impact of Consumer Credit Access on Unemployment
Authors: Herkenhoff Kyle F
Published: February 2019

Unemployed households’ access to unsecured revolving credit more than tripled over the last three decades. This article analyses how both cyclical fluctuations and trend increases in credit access impact the business cycle. The main quantitative result is that credit expansions and contractions have contributed to moderately deeper and more protracted recessions over the last 40 years. As more individuals obtained credit from 1977 to 2010, cyclical credit fluctuations affected a larger share of the population and became more important determinants of employment dynamics. Even though business cycles are more volatile, newborns strictly prefer to live in the economy with growing, but fluctuating, access to credit markets.
Increased and Decreased Superficial White Matter Structural Connectivity in Schizophrenia and Bipolar Disorder
Authors: Ji Ellen , Guevara Pamela , Guevara Miguel , Grigis Antoine , Labra Nicole , Sarrazin Samuel , Hamdani Nora , Bellivier Frank , Delavest Marine , Leboyer Marion , Tamouza Ryad , Poupon Cyril , Mangin Jean-François , Houenou Josselin
Published: February 2019

Schizophrenia (SZ) and bipolar disorder (BD) are often conceptualized as “disconnection syndromes,” with substantial evidence of abnormalities in deep white matter tracts, forming the substrates of long-range connectivity, seen in both disorders. However, the study of superficial white matter (SWM) U-shaped short-range tracts remained challenging until recently, although findings from postmortem studies suggest they are likely integral components of SZ and BD neuropathology. This diffusion weighted imaging (DWI) study aimed to investigate SWM microstructure in vivo in both SZ and BD for the first time. We performed whole brain tractography in 31 people with SZ, 32 people with BD and 54 controls using BrainVISA and Connectomist 2.0. Segmentation and labeling of SWM tracts were performed using a novel, comprehensive U-fiber atlas. Analysis of covariances yielded significant generalized fractional anisotropy (gFA) differences for 17 SWM bundles in frontal, parietal, and temporal cortices. Post hoc analyses showed gFA reductions in both patient groups as compared with controls in bundles connecting regions involved in language processing, mood regulation, working memory, and motor function (pars opercularis, insula, anterior cingulate, precentral gyrus). We also found increased gFA in SZ patients in areas overlapping the default mode network (inferior parietal, middle temporal, precuneus), supporting functional hyperconnectivity of this network evidenced in SZ. We thus illustrate that short U-fibers are vulnerable to the pathological processes in major psychiatric illnesses, encouraging improved understanding of their anatomy and function.
Assessing the efficiency of national innovation systems in developing countries
Authors: Choi Hyeri , Zo Hangjung
Published: February 2019

Despite the growing importance of developing countries to the global economy and their increasing role in innovation, limited academic attention has been given to the national innovation systems (NIS) of these countries. Given that they commonly suffer a lack of resources, efficiency in the operation of innovation seems crucial. This study aims to assess the innovation efficiency of developing countries. Breaking down the NIS into two stages, knowledge production and application process, we additionally introduce the knowledge absorption perspective in the latter stage as the consideration for the context of developing countries. Based on the results of the efficiency assessment, clustering analysis is implemented to identify several typologies of the operation of NIS in developing countries and to provide implications for each case. This study will constitute a meaningful attempt to provide a general understanding of innovation status and operations in developing countries, thereby suggesting policy directions for several cases.
Addressing the evolving standardisation challenges of ‘smart systems’ innovation: Emerging roles for government?
Authors: Ho Jae-Yun , O’Sullivan Eoin
Published: February 2019

At a time when standardisation is increasingly recognised as an important area of innovation policy, the emergence of cyber-physical ‘smart systems’ presents significant challenges. Such complex technological systems have unprecedented levels of complexity and interoperability requirements, and pervade many critical national infrastructures, so calling for active roles for government to support their effective standardisation. Existing literature, however, offer limited insights into where, why, and how policy intervention can address the evolving variety of innovation challenges associated with standardisation. This article, thus, proposes a novel innovation systems-based framework, for structured analyses of complex dynamics between standard-related innovation problems, relevant roles of government, and appropriate policy instruments. The historical case study of photovoltaic technology (from its early R&D to integration into Smart Grid) illustrates the framework, and provides practical implications for policymakers, suggesting evolving roles of government in the transition to cyber-physical smart systems in response to growing risks of systemic problems.
The different effects of basic research in enterprises on economic growth: Income-level quantile analysis
Authors: Jung Euy-Young , Liu Xielin
Published: February 2019

In the open innovation era, enterprises should conduct more of their own basic research or not rely on contextual factors. We use quantile regression to determine that basic research in the business sector has different effects on economic performance by national income level using thirty-one Organization for Economic Co-operation and Development (OECD) and non-OECD countries including China during 1996–2014. We find that basic research expenditure has a negative relationship with economic growth in low-income countries, whereas in high-income countries, the relationship is positive. Furthermore, the greater the national income, the higher the importance of basic research for economic growth. However, increased absorptive capacity mediates the positive relationship between basic research investment and economic growth in high-income countries, and, in low-income countries, it mediates the negative relationship between the two. In this study, we provide a more detailed understanding of the relationships between basic research investment in the business sector and economic growth.
Education-Based Status in Comparative Perspective: The Legitimization of Education as a Basis for Social Stratification
Authors: van Noord Jochem , Spruyt Bram , Kuppens Toon , Spears Russell
Published: February 2019

Classical and recent accounts of education posit that education legitimately, and authoritatively, classifies individuals to positions of lower or higher status. However, despite these general theoretical claims, empirical evidence that provides an in-depth picture of the relationship between educational attainment and social status remains scarce. In this paper, based on a dataset of 31 countries (International Social Survey Programme), we investigate the extent to which education is related to subjective social status, the degree to which this is seen as legitimate, and how this relationship varies between countries. We contextualize this relationship with the influence of the centrality of education in countries (operationalized as the share of higher educated). Results showed that education is an important source of subjective social status for individuals across all countries, and is seen as relatively legitimate and uncontroversial among all educational groups. Moreover, among those who perceive education to be more important for status, subjective status differences between educational groups are larger. Additionally, in countries with larger shares of higher educated, educational differences in subjective social status correlate more strongly with whether or not people obtained a degree of higher (tertiary) education. Lastly, the relationship between education and subjective social status in these countries is more independent from other sources of status, such as income and gender. It therefore seems to be that as higher education becomes more central and widely shared in a society, rather than leveling social differences, ironically it also becomes more distinctive and diagnostic in distinguishing people along group lines.
Best Practice Tips for the Assessment of Learning of Undergraduate Nursing Students via Multiple-Choice Questions
Authors: Cox Catherine Wilson
Published: February 2019

AIM

This article explores the current literature regarding multiple-choice testing and presents best practice tips to incorporate when designing a multiple-choice test.

BACKGROUND

Multiple-choice testing is used extensively in undergraduate nursing programs as an evaluation tool, yet many nurse educators struggle with developing high quality multiple-choice tests. Flawed multiple-choice items disadvantage nursing students, conceivably resulting in failing tests they should have passed.

METHOD

This integrative review included articles published in English from 2008 to 2017; the electronic databases explored were CINAHL, Scopus, ERIC, and Education Source; and 17 search terms were applied. Twenty-eight articles were included in the final sample.

RESULTS

The integrative review of the literature revealed 29 valuable tips, via four categories, for developing and using multiple-choice tests.

CONCLUSION

New and seasoned educators will benefit from this refreshing update, armed with best practice tips to consider the next time a multiple-choice test is designed.
Simulation-Based Interprofessional Education in a Rural Setting: The Development and Evaluation of a “Remote-In” Telehealth Scenario
Authors: Scott Ann , Dawson Robin M. , Mitchell Sheryl , Catledge Courtney
Published: February 2019

Simulation-based interprofessional education (IPE) is challenging to implement, especially on rural campuses. This article describes an innovative approach to IPE implementation using telehealth technology. Twenty-nine interdisciplinary students (nursing, pharmacy, and medical) participated in a simulation-based IPE scenario using a telehealth robot. Student experiences were evaluated using a mixed-methods approach. Surveys and video-recorded debriefing sessions revealed the majority of students felt the experience was superior to their previous IPE experiences, facilitated better understanding of disciplinary roles, and provided experience using telehealth tools. Programs considering this approach should have strong community partnerships, institutional support, and shared vision among key stakeholders.
New Clinical Nurse Faculty Orientation: A Review of the Literature
Authors: Ross Jennifer Gunberg , Silver Dunker Kimberly
Published: February 2019

AIM

The aim of this literature review was to obtain relevant information and research findings about orientation for new clinical nurse faculty.

BACKGROUND

Hiring clinical experts as clinical faculty is common practice to address the nurse faculty shortage. As clinical experts do not possess the pedagogical expertise needed for effective teaching, they require specialized orientation when entering a faculty role. There is no consensus as to best practices for new clinical faculty orientation due to a dearth of research in this area.

METHOD

A comprehensive search of the literature was conducted to obtain relevant information and research findings about orientation for new clinical nursing faculty.

RESULTS

Current orientation strategies include face-to-face, hybrid, and mentoring components. The limited empirical research is mostly descriptive or pilot studies.

DISCUSSION

More research is needed on the effectiveness of various forms of orientation for new clinical faculty to support clinical faculty competence, patient safety, and evidence-based practices in this area.
Delays in Cardiopulmonary Resuscitation, Defibrillation, and Epinephrine Administration All Decrease Survival in In-hospital Cardiac Arrest
Authors: Bircher Nicholas G. , Chan Paul S. , Xu Yan ,   for the American Heart Association’s Get With The Guidelines–Resuscitation Investigators
Published: February 2019

Editor’s Perspective

What We Already Know about This Topic

What This Article Tells Us That Is New

Background

Because the extent to which delays in initiating cardiopulmonary resuscitation (CPR) versus the time from CPR to defibrillation or epinephrine treatment affects survival remains unknown, it was hypothesized that all three independently decrease survival in in-hospital cardiac arrest.

Methods

Witnessed, index cases of cardiac arrest from the Get With The Guidelines–Resuscitation Database occurring between 2000 and 2008 in 538 hospitals were included in this analysis. Multivariable risk-adjusted logistic regression examined the association of time to initiation of CPR and time from CPR to either epinephrine treatment or defibrillation with survival to discharge.

Results

In the overall cohort of 57,312 patients, there were 9,802 survivors (17.1%). Times to initiation of CPR greater than 2 min were associated with a survival of 14.7% (91 of 618) as compared with 17.1% (9,711 of 56,694) if CPR was begun in 2 min or less (adjusted odds ratio [95% CI], 0.68 [0.54 to 0.87]; P < 0.002). Times from CPR to either defibrillation or epinephrine treatment of 2 min or less were associated with a survival of 18.0% (7,654 of 42,475), as compared with 15.0% (1,680 of 11,227) for 3 to 5 min (reference, 0 to 2 min; adjusted odds ratios [95% CI], 0.83 [0.78 to 0.88]; P < 0.001), 12.8% (382 of 2,983) for 6 to 8 min (0.67 [0.60 to 0.76], P < 0.001), and 13.7% (86 of 627) for 9 to 11 min (0.54 [0.42 to 0.69], P < 0.001).

Conclusions

Delays in the initiation of CPR and from CPR to defibrillation or epinephrine treatment were each associated with lower survival.
Feasibility and Safety of the Preemie Orthotic Device to Manage Deformational Plagiocephaly in Extremely Low Birth Weight Infants
Authors: Knorr Aimee , Giambanco Deborah , Staude Mary V. , Germain Monique , Porter Courtney , Serino Emily , Gauvreau Kimberlee , DeGrazia Michele
Published: February 2019

Background:

Premature infants are predisposed to developing deformational plagiocephaly. Deformational plagiocephaly may affect the infant's social well-being and neurobehavioral development.

Purpose:

This pilot study investigated the feasibility and safety of the preemie orthotic device (POD); a noncommercial, supportive orthotic device to manage deformational plagiocephaly.

Methods:

The setting for this prospective, descriptive, phase 1 clinical trial was 2 urban and 1 suburban neonatal intensive care units that provided care for critically ill premature and term infants. Participants included a convenience sample of 10 premature extremely low-birth-weight infants weighing less than 1 kg. All participants received the experimental treatment with the POD. Time spent on the device with and without the supportive foam insert, provider perception, adverse events, and head shape measurements were collected to assess feasibility and safety of the device.

Results:

Participants had a median gestational age of 25.4 weeks and median birth weight of 0.673 kg. The POD was used a median of 21.2 hours per day and the foam insert was used a median of 11.1 hours per day. At enrollment, 1 participant had a normal cranial index compared with 5 participants at study completion. All participants had normal cranial symmetry at study enrollment and completion. No device-related adverse events were reported.

Implication for Practice:

The POD was found to be feasible and safe. Staff had favorable responses to the device. Recommendations by nursing staff included enlarging the device to extend its use.

Implication for Research:

Further studies are warranted to assess the POD's effectiveness.
Relationship Between Proprioception and Pain and Disability in People With Non-Specific Low Back Pain
Authors: Lin Jianhua , Halaki Mark , Rajan Pavithra , Leaver Andrew
Published: February 2019

Study Design.

Systematic review with meta-analysis.

Objective.

To examine the association between proprioception and pain and disability in people with non-specific low back pain (NSLBP) and the impact of potential moderators on the strength of the association.

Summary of Background Data.

NSLBP is a common musculoskeletal disorder and a leading cause of disability. Proprioception deficit has been associated with low back pain and correlated with pain and disability; however, the correlation coefficients presented are conflicting.

Methods.

Systematic literature search was performed in eight databases and Google scholar. Two independent reviewers assessed the literature and extracted data. Data of interest included participant characteristics of NSLBP group, pain and disability, proprioception test protocol, and the correlation coefficient between proprioception and pain/disability. Meta-analysis of data from homogeneous studies was performed according to proprioception test methods. Subgroup of movement directions was analyzed. The methodological quality of studies was assessed.

Results.

The literature search identified 3067 records of which 14 studies were included for meta-analysis. Proprioception was measured by active joint repositioning sense (AJRS), passive joint repositioning sense (PJRS), and threshold to detect passive motion (TTDPM). Meta-analysis revealed no significant correlation coefficient between any proprioception measures and pain or disability (P > 0.05). The subgroup analysis showed little correlation between absolute error (AE) of passive lumbar flexion and pain (r = 0.225, 95% CI 0.040–0.395), and between AE of passive lumbar extension and disability (r = 0.196, 95%CI 0.010–0.369).

Conclusion.

AJRS and TTDPM are not correlated with pain and disability in people with NSLBP. The AE of passive lumbar movement is correlated to a small degree with pain and disability. However, the degree of correlation is small and should be interpreted with caution. Therefore, the differences in proprioception observed between people with pain and people without pain seem to be independent of the symptoms.

Level of Evidence: 1
Triptolide Suppressed the Microglia Activation to Improve Spinal Cord Injury Through miR-96/IKKβ/NF-κB Pathway
Authors: Huang Yang , Zhu Ning , Chen Tao , Chen Weijie , Kong Jinsong , Zheng Wenbiao , Ruan Jianwei
Published: February 2019

Study Design.

The effect of triptolide on spinal cord injury (SCI) and inflammatory response was observed by establishing SCI rat model. And in vitro experiments were conducted to determine the underlying mechanism of triptolide-mediated in murine microglial cell line BV2.

Objective.

To determine the underlying mechanism of triptolide in suppressing the microglia activation to improve SCI.

Summary of Background Data.

Triptolide, as a major active ingredient of Chinese herb Tripterygium wilfordii, can promote spinal cord repair through inhibiting microglia activation, but the underlying mechanism is not clear.

Methods.

Locomotion recovery was accessed by Basso, Beattie, and Bresnahan score, the number of footfalls, stride length, and angle of rotation analysis. Expressions of microRNA 96 (miR-96), microglia activation marker Iba-1, and IκB kinase (IKKβ)/nuclear factor (NF)-κB-related proteins were detected by qRT-PCR or western blot. Inflammatory cytokines tumor necrosis factor-α and interleukin -1β were measured by enzyme-linked immuno sorbent assay. The regulation of miR-96 on IKKβ was confirmed by dual luciferase reporter assay.

Results.

Triptolide promoted locomotion recovery of SCI rats, upregulated the expression of miR-96, decreased microglia activation marker Iba-1 and IKKβ/NF-κB-related proteins, and inhibited inflammatory cytokines tumor necrosis factor-α and interleukin-1β levels in spinal cord tissues and lipopolysaccharide -induced microglia. Triptolide suppressed the microglia activation and inflammatory cytokines secretion in BV2 cells through up-regulating miR-96. We confirmed the interaction between miR-96 and IKKβ, and IKKβ expression was negatively regulated by miR-96. Finally, we determined that triptolide suppressed the microglia activation and inflammatory cytokines secretion through miR-96/IKKβ pathway.

Conclusion.

Triptolide suppressed microglia activation after SCI through miR-96/IKKβ/NF-κB pathway.

Level of Evidence.

N/A
Pattern of Marginal Local Failure in a Phase II Trial of Neoadjuvant Chemotherapy and Stereotactic Body Radiation Therapy for Resectable and Borderline Resectable Pancreas Cancer
Authors: Kharofa Jordan , Mierzwa Michelle , Olowokure Olugbenga , Sussman Jeffrey , Latif Tahir , Gupta Anumeha , Xie Changchun , Patel Sameer , Esslinger Hope , Mcgill Brian , Wolf Eric , Ahmad Syed A.
Published: February 2019

Objectives:

The main objectives of this study were to prospectively evaluate the safety and efficacy of stereotactic body radiation therapy (SBRT) in the neoadjuvant setting for resectable or borderline resectable pancreatic cancer.

Materials and Methods:

Eighteen patients were enrolled from November 2014 to June 2017. Following 3 cycles of chemotherapy, SBRT was delivered to the tumor and abutting vessel and a 3 mm planning target volume (PTV) margin to 33 Gy (6.6 Gy×5) with an optional elective PTV to 25 Gy (5 Gy×5) customized to the nodal space and mesenteric vessels. The primary endpoint is ≥grade 3 acute and late gastrointestinal toxicity.

Results:

Fifteen patients had borderline resectable tumors due to arterial abutment (n=7) or superior mesenteric vein encasement (n=8); 3 patients had resectable tumors. There were no ≥grade 3 acute or late gastrointestinal events. Following SBRT, surgery was performed in 12 patients (67%) with 11 (92%) R0 resections. The median overall survival and progression-free survival was 21 months (95% CI: 18-29) and 11 months (95% CI: 8.4-16). Progression occurred in 83% (10/12) of resected patients (distant [n=4, 40%], local-only [n=4, 40%], and local and distant [n=2, 20%]). The cumulative incidence of local failure (LF) at 12 months from resection was 50% (95% CI: 20-80). All LF were outside to the PTV33.

Conclusions:

Neoadjuvant SBRT was well tolerated, however LFs were predominantly observed outside the PTV33 volume that would have been covered with conventional RT volumes. The durability of local control after SBRT in the neoadjuvant setting merits examination relative to chemoradiation before incorporation into routine practice.
Animal models of liability to post-traumatic stress disorder: going beyond fear memory
Authors: Cabib Simona , Orsini Cristina , Puglisi Allegra Stefano
Published: February 2019

In this review, we advocate a dimensional approach on the basis of candidate endophenotypes to the development of animal models of post-traumatic stress disorder (PTSD) capable of including genetic liability factors, variations in symptoms profile and underlying neurobiological mechanisms, and specific comorbidities. Results from the clinical literature pointed to two candidate endophenotypes of PTSD: low sensory gating and high waiting impulsivity. Findings of comparative studies in mice of two inbred strains characterized by different expressions of the two candidate endophenotypes showed different strain-specific neural and behavioral effects of stress experiences. Thus, mice of the standard C57BL/6J strain show stress-induced helplessness, stress-learned helplessness, and stress-extinction-resistant conditioned freezing. Instead, mice of the genetically unrelated DBA/2J strain, expressing both candidate endophenotypes, show stress-induced extinction-resistant avoidance and neural and behavioral phenotypes promoted by prolonged exposure to addictive drugs. These strain differences are in line with evidence of associations between genetic variants and specific stress-promoted pathological profiles in PTSD, support a role of genotype in determining different PTSD comorbidities, and offer the means to investigate specific pathogenic processes.
Clinical Features of Pingueculitis Revealed by Anterior Segment Optical Coherence Tomography Findings
Authors: Song Han , Rand Gabriel M. , Kwon Ji-Won
Published: February 2019

Purpose:

To investigate clinical features and treatment outcomes of pingueculitis with morphological assessments using anterior segment optical coherence tomography (AS-OCT).

Methods:

In this retrospective observational study, we examined 22 eyes of 22 patients with pingueculitis. All patients were treated with the same 2-week course of prednisolone acetate 1% drops four times per day. The clinical parameters evaluated were surface dimensions determined by slitlamp biomicroscopy, cross-sectional dimensions determined by AS-OCT, and symptom scores determined by patient surveys. Pretreatment and 1-month posttreatment values were compared with Wilcoxon signed-rank tests. Patients were followed up to 1 year after treatment.

Results:

Twenty-two eyes from 22 patients (4 men and 18 women) with an average age of 37.7±8.8 (range, 27–57) years and an average duration of symptoms of 22 (range, 5–60) days were included. The average follow-up period was 14.7±0.8 (range, 12–22) months. Mean pretreatment horizontal length, vertical length, conjunctival thickness, and cross-sectional area were 2.4±0.69 mm, 2.0±0.6 mm, 1.82±0.60 μm, and 5.14±2.05 mm2, respectively. Mean posttreatment horizontal length, vertical length, conjunctival thickness, and area were 1.93±0.5 mm, 1.52±0.6 mm, 1.03±0.46 μm, and 2.33±0.83 mm2, respectively. Mean pretreatment and posttreatment dry eye symptom scores were 3.27±0.77 and 1.13±0.38, respectively. The median pretreatment and posttreatment changes were statistically significant by Wilcoxon signed-rank tests for horizontal length (P<0.001), vertical length (P<0.001), conjunctival thickness (P=0.003), cross-sectional area (P=0.003), and dry eye symptom scores (P<0.001).

Conclusion:

Anterior segment optical coherence tomography allows the quantification of differences in the pingueculitis measurements before and after treatment. In this retrospective study, a short course of topical steroids effectively treated the inflammation in a sustained manner. Anterior segment optical coherence tomography demonstrated significant reduction in the thickness and cross-sectional area of the pinguecula and a conversion back to a homogeneous conjunctival stroma.
Central Toxic Keratopathy After Contact Lens Wear and Mechanical Debridement: Clinical Characteristics, and Visual and Corneal Tomographic Outcomes
Authors: Ting Darren Shu Jeng , Ghosh Saurabh
Published: February 2019

Objectives:

To highlight the clinical characteristics, and visual and corneal tomographic outcomes of central toxic keratopathy (CTK) after contact lens (CL) wear and mechanical debridement.

Methods:

A retrospective observational case series with literature review.

Results:

Four patients (4 eyes) were included in this study; 3 (75%) females, mean age 29.3±8.1 years. The mean follow-up was 13.5±7.5 months. Early central or paracentral stromal opacification, assuming an inverse dome-shaped pattern observed under anterior-segment optical coherence tomography, with corneal flattening (Kmean 40.4±1.3 D) and thinning (mean thinnest pachymetry=404.8±29.4 microns) were observed in all cases. All patients had a recent use of CL wear, with three after mechanical debridement for recurrent corneal erosion syndrome. None of them had any previous laser refractive surgery (LRS). The mean corrected distance visual acuity improved from 20/40 (ranged 20/25–20/50) initially to 20/30 (ranged 20/20–20/40) at final follow-up, and the outcome was not influenced by the use of topical steroids. A mean improvement of corneal flattening (+Kmean 1.2±1.2 D), thinning (+123.5±23.8 microns), and astigmatism (−3.0±2.7 D), via epithelial and stromal remodeling, was observed up to 15 months after CTK. Persisting reduced corneal sensation was noted in all patients at the final follow-up.

Conclusions:

Central toxic keratopathy is not an exclusive complication of LRS, and it may occur after CL wear and mechanical debridement. Our findings are similar to those of LRS-related CTK and toxic peripheral keratopathy. Awareness of the clinical associations and understanding of the clinical course and tomographic characteristics of CTK helps obviate unnecessary investigation and overtreatment. Further studies are required to elucidate the underlying pathogenesis of this rare clinical entity.
Absorption and Extraction of Inflammatory Mediators From Contact Lens Materials
Authors: Chao Cecilia , Richdale Kathryn , Willcox Mark
Published: February 2019

Objectives:

This report aimed to explore whether certain inflammatory mediators were absorbed, extracted, or bound by various contact lens materials.

Methods:

Comfilcon A, balafilcon A, omafilcon A, and etafilcon A were soaked in 500 and 100 pg/mL of interleukin-8 (IL-8), matrix metalloproteinase-9 (MMP-9), or interleukin-1 receptor antagonist (IL-1Ra), and also in combined solutions of inflammatory mediators (500 pg/mL or 100 pg/mL) separately. Lenses were then extracted in 1:1 2% trifluoroacetic acid:acetonitrile. The extracted and residual concentrations of inflammatory mediators were determined using enzyme-linked immunosorbent assays. Absorbed (control-residual) and firmly bound (absorbed–extracted) concentrations were calculated for analysis.

Results:

More MMP-9 was absorbed by omafilcon A (466±9 pg/mL) than balafilcon A (P=0.006; 437±11 pg/mL) or etafilcon A (P=0.001; 428±13 pg/mL) when soaked in 500 pg/mL, but no differences in 100 pg/mL. More MMP-9 remained firmly bound to omafilcon A (P=0.03; 174±3 pg/mL), comfilcon A (P=0.049; 168±34 pg/mL), and balafilcon A (P=0.01; 186±14 pg/mL) than etafilcon A (128±22 pg/mL). There were no differences in IL-8 absorption between lenses; however, more IL-8 remained firmly bound to omafilcon A (P=0.01; 336±25 pg/mL) than etafilcon A (106±133 pg/mL) when soaked in 500 pg/mL. No differences were found in concentrations of absorbed or firmly bound IL-1Ra between materials. When the mediators were combined, IL-8 was absorbed more in etafilcon A (P=0.03) than in other lens materials, but the absorbed IL-8 did not remain firmly bound.

Conclusions:

The uptake and extraction of inflammatory mediators from contact lenses was affected by competitive binding between the mediators.
Efficacy and Safety of Conjunctival Cystectomy Using High-Frequency Radiowave Electrosurgery: A Preliminary Report
Authors: Ji Min Jung , Lee Seung-Jun , Han Sang Beom , Hyon Joon Young
Published: February 2019

Purpose:

To evaluate the efficacy and safety of conjunctival cystectomy using high-frequency radiowave electrosurgery.

Methods:

This retrospective study included 11 patients who underwent conjunctival cystectomy using high-frequency radiowave electrosurgery and had a follow-up of at least 6 months. Briefly, conjunctival opening with a diameter of 1 mm was made with using high-frequency radiowave electrosurgery (Ellman Surgitron; Ellman International, Inc., Hewlett, NY) in cut mode. The cyst was then extracted using a nontoothed forceps through the opening without rupture. Medical record of the patients was reviewed.

Results:

In all the 11 patients, conjunctival wound healed in 1 week without any complication. No recurrence was detected in any patients over the 6-month follow-up.

Conclusions:

Conjunctival cystectomy with the adjunctive use of high-frequency radiowave electrosurgery was shown to be effective and safe.
Systematic Review on Therapeutic Strategies to Minimize Corneal Stromal Scarring After Injury
Authors: Kwok Sum S. , Shih Kendrick C. , Bu Yashan , Lo Amy C.-Y. , Chan Tommy C.-Y. , Lai Jimmy S.-M. , Jhanji Vishal , Tong Louis
Published: February 2019

Objectives:

To evaluate recent studies on available and experimental therapies in preventing or minimizing corneal stromal scarring after injury.

Methods:

We performed an Entrez PubMed literature search using keywords “cornea,” “scarring,” “haze,” “opacity,” “ulcer,” “treatments,” “therapies,” “treatment complications,” and “pathophysiology” resulting in 390 articles of which 12 were analyzed after filtering, based on English language and publication within 8 years, and curation for relevance by the authors.

Results:

The 12 articles selected included four randomized control trials (RCTs) (two were double-blinded placebo-controlled RCTs, one was a prospective partially masked RCT, and one was an open-label RCT), two retrospective observational studies, and six laboratory-based studies including two studies having in vivo and in vitro experiments, one was in vivo study, one was ex vivo study, and the last two were in vitro studies. The current mainstay for preventing or minimizing corneal scarring involves the use of topical corticosteroids and local application of mitomycin C. However, supportive evidence for their use in clinical practice from well-designed RCTs is lacking. Laboratory studies on topical rosiglitazone therapy, vitamin C prophylaxis, gene therapy, and stem cell therapy have shown promising results but have yet to be translated to clinical research.

Conclusion:

There is a need for more robust randomized controlled trials to support treatments using topical corticosteroids and mitomycin C. Furthermore, their clinical efficacy and safety profile should be compared with new treatments that have shown promising results in the laboratory setting. Ultimately, the goal should be to personalize cornea scarring treatment according to the most effective treatment for the specific underlying pathology.
Evaluation of Long-Term Corneal Morphology After Photorefractive Keratectomy by In Vivo Confocal Microscopy and Specular Microscopy; 20-Year Follow-Up
Authors: Bilgihan Kamil , Yesilirmak Nilufer , Altay Yesim , Tefon Atike B. , Ozdemir Huseyin B. , Ozdogan Sibel , Kocamaz Mehmet F. , Gurelik Gokhan
Published: February 2019

Purpose:

To evaluate long-term corneal morphological changes after photorefractive keratectomy (PRK) using in vivo confocal microscopy (IVCM) and specular microscopy.

Methods:

This comparative case–control study included 16 eyes of 8 patients who underwent PRK for mild to moderate myopia 20 years ago and 30 eyes of 15 sex- and age-matched healthy controls. Corneal epithelial cells, sub-basal nerves, keratocytes (anterior, midstromal, and posterior), and endothelial cells were evaluated in both groups 10 and 20 years after surgery. Long-term visual outcomes were also recorded.

Results:

In vivo confocal microscopy examination revealed similar epithelial morphology, sub-basal nerve fiber morphology/density, mid/posterior stromal keratocyte density, and endothelial cell density between PRK patients and controls at their 10th and 20th year follow-up. Anterior stromal keratocyte density was lower at 10th year; however, it reached to control group value at 20th year follow-up. Extracellular matrix reflectivity was slightly higher, and there was a trace subepithelial corneal haze in PRK group (milder in 20th year than 10th year) compared with controls. At the 20th year, uncorrected distance visual acuity was 20/20 or more in 6 eyes (37.5%), 20/40 or more in 16 eyes (100%), and all eyes had corrected distance visual acuity of 20/20 or better (spherical equivalent −0.31±0.37 D).

Conclusions:

Photorefractive keratectomy in low to moderate myopia seems to be safe and effective method in the long term with preserving corneal morphology (including anterior stromal keratocyte and sub-basal nerve fiber density) and refractive outcomes as shown in this study. In appropriate patients, this method can be considered confidently.
Improved Clinical Outcome After Treatment of Mycobacterium abscessus Complex Pulmonary Disease in Children With Cystic Fibrosis
Authors: Chacko Archana , Wen Sophie C. H. , Hartel Gunter , Kapur Nitin , Wainwright Claire E. , Clark Julia E.
Published: February 2019

Background:

Mycobacterium abscessus complex pulmonary disease (M. abscessus PD) in cystic fibrosis (CF) is challenging to treat. Current guideline therapeutic regimens involving an intensive phase of intravenous (IV) antibiotics followed by a consolidation phase of inhaled and oral antibiotics are not evidence-based. The objectives of this study were to characterize the clinical outcomes and clearance of Mycobacterium abscessus complex (M. abscessus) from respiratory cultures in children with CF M. abscessus PD.

Methods:

This retrospective longitudinal cohort analysis evaluated the first course of treatment for M. abscessus PD in 33 children in Queensland, Australia between 2001 and 2015. Spirometry and nutritional outcomes 2 years pretreatment and 1 year posttreatment were compared with clearance or relapse/persistence of Mycobacterium abscessus complex from respiratory cultures.

Results:

Nine of 18 children who completed therapy, cleared infection. Three of 7 children who completed only intensive therapy cleared sputum compared with 0/8 children who did not. The trajectory of the percent predicted forced expiratory volume in 1 s and age standardized body mass index significantly improved posttreatment in those that cleared sputum (P < 0.0001).

Conclusions:

These results suggest that current treatment recommendations for M. abscessus PD are associated with some success in clearing infection in children with CF and improvement in lung function and body mass index. Clinical trials are required to determine the best treatment approaches.
Paenibacillus alvei Multifocal Cavitary Lung Abscesses in an Immunocompetent Man
Authors: Ferguson John , Gailey Michael , Volk Stacy
Published: February 2019

Paenibacillus alvei (formerly Bacillus alvei) is infrequently recognized as a pathogenic bacterium in humans. P. alvei has historically been considered a nonvirulent organism found in soil and water sources and most well-described in European foulbrood, a disease of honeybees. Few case reports have been described in humans, none of which include cavitary lung abscess formation. We describe a case of multifocal lung abscesses secondary to P. alvei in an immunocompetent man and review the literature of other case reports in humans. Identification of P. alvei remains challenging, and the biochemical tests to make the diagnosis are reviewed. Treatment is generally guided by in vitro susceptibility patterns, and we will review the clinical case reports that have resulted in successful treatment of this bacterium.
Association Between Body Mass Index and Mortality in Patients With Gram-Negative Bloodstream Infections
Authors: Lines Jacob , Yang Zhengguan , Bookstaver Paul Brandon , Catchings Erin , Justo Julie Ann , Kohn Joseph , Albrecht Helmut , Al-Hasan Majdi N.
Published: February 2019

Background

Obesity is an established risk factor for many infections. Emerging data demonstrate that increased body mass index (BMI) may paradoxically protect against mortality in several disease processes. The interaction between BMI and mortality in gram-negative bloodstream infections (GN-BSIs) remains unclear.

Aim

This retrospective cohort study examines the impact of BMI on mortality in patients with GN-BSI.

Materials and Methods

Hospitalized adults with first episodes of GN-BSI from 2010 to 2015 were identified. Patients were grouped by BMI in kilograms per meter squared as normal weight (18.5–24.9; reference), overweight (25.0–29.9), obese (30.0–39.9), and morbidly obese (≥40). Multivariate Cox proportional hazards regression was used to examine risk factors for 28-day mortality after GN-BSI.

Results

Among 1069 unique patients with GN-BSI, 352 (33%) were normal weight, 319 (30%) were overweight, 303 (28%) were obese, and 95 (9%) were morbidly obese. Overall, mean age was 63 years, and 54% were women. Crude 28-day mortality was higher in the normal-weight group (21.5%) than in the overweight (11.7%), obese (11.8%), and morbidly obese groups (8.7%; P = 0.003). After adjustments for age, chronic comorbidities, acute severity of illness, and antimicrobial therapy in a multivariate model, overweight BMI remained independently associated with reduced mortality (adjusted hazards ratio [aHR], 0.53; 95% confidence intervals [CI], 0.31–0.88; P = 0.01). There was no significant reduction in mortality in obese (aHR, 0.72; 95% CI, 0.43–1.15; P = 0.17) and morbidly obese patients (aHR, 0.71; 95% CI, 0.27–1.56; P = 0.41).

Conclusions

Compared with normal BMI, overweight patients had improved survival after GN-BSI. However, this potential protective effect was lost in obese and morbidly obese patients.
Contrasting the Clinical Presentation and Prevalence of Septic, Reactive, and Crystal Arthritis in Patients With Hematologic and Solid Malignancies
Authors: Coba George A. , Velez Ana P. , Joyce David M. , Greene John N.
Published: February 2019

Background

The development of septic arthritis requires rapid identification and treatment to prevent serious and irreversible complications in cancer patients. This is further emphasized by the fact that many cancer patients are immunocompromised either through the nature of their disease or through their treatment. Septic arthritis, crystal-induced arthritis (CIA), and reactive arthritis (RA) all present in a similar fashion with erythematous, edematous, painful joints.

Methods

A retrospective review was performed using data compiled from patient charts at the Moffitt Cancer Center between the dates of January 1, 2010, and February 22, 2018. Of the original 56 patients who had joint aspirations, 45 met the inclusion criteria of also having either a solid or hematologic malignancy.

Results

Analysis of the study population suggests that septic arthritis or CIA is significantly less common compared with RA in cancer patients. In addition, the development of septic arthritis is strongly associated with both prosthetic joints and nearby malignancies. Calcium pyrophosphate crystal-induced and monosodium urate CIA presents similar to septic arthritis. Lastly, synovial fluid analysis distinguishes the etiologies of arthritis more accurately compared with serum analysis.

Conclusions

The data collected in the study support the conclusion that oncology patients presenting with an inflamed joint are more likely to have RA and unlikely to have septic arthritis unless associated with a prosthesis or nearby malignancy. Reactive arthritis is most common and readily resolves with chemotherapy and anti-inflammatory therapy with no joint destruction and rarely recurs. Lastly, synovial fluid analysis is necessary to diagnose and/or rule out specific arthritis causes.
Access to Affordable, High-Quality Health Insurance for Rural Residents and Its Impact on Their Health and on Rural Hospitals
Authors: Goldfield Norbert I. , Fuller Richard L.
Published: February 2019

Access to rural health care is an ongoing challenge for those living in America's countryside. Hospital closures, a fragmented and dislocated care delivery system, disproportionate levels of chronic illness, and poverty combine to present significant obstacles to health reform. This article highlights the major challenges in rural health care and specifies financial and delivery policy options that can strengthen rural health care. In particular, this article suggests a return to a prepaid approach within the umbrella organizational framework of what we term “rural convening entities.” These entities would serve as the control of telehealth hubs for the communities they serve.