bluuebunny/crossref_metadata_2025 huggingface dataset:
Preoperative Opioids and 1-year Patient-reported Outcomes After Spine Surgery
Authors: Hills Jeffrey M. , Pennings Jacquelyn S. , Archer Kristin R. , Wick Joseph B. , Daryoush Joshua , Butler Marjorie , Sivaganesan Ahilan , Khan Inamullah , Call Richard , Devin Clinton J.
Published: December 2018

Study Design.

Longitudinal Cohort Study.

Objective.

Determine 1-year patient-reported outcomes associated with preoperative chronic opioid therapy and high-preoperative opioid dosages in patients undergoing elective spine surgery.

Summary of Background Data.

Back pain is the most disabling condition worldwide and over half of patients presenting for spine surgery report using opioids. Preoperative dosage has been correlated with poor outcomes, but published studies have not assessed the relationship of both preoperative chronic opioids and opioid dosage with patient-reported outcomes.

Methods.

For patients undergoing elective spine surgery between 2010 and 2017, our prospective institutional spine registry data was linked to opioid prescription data collected from our state's Prescription Drug Monitoring Program to analyze outcomes associated with preoperative chronic opioid therapy and high-preoperative opioid dosage, while adjusting for confounders through multivariable regression analyses. Outcomes included 1-year meaningful improvements in pain, function, and quality of life. Additional outcomes included 1-year satisfaction, return to work, 90-day complications, and postoperative chronic opioid use.

Results.

Of 2128 patients included, preoperative chronic opioid therapy was identified in 21% and was associated with significantly higher odds (adjusted odds ratio [95% confidence interval]) of not achieving meaningful improvements at 1-year in extremity pain (aOR:1.5 [1.2–2]), axial pain (aOR:1.7 [1.4–2.2]), function (aOR:1.7 [1.4–2.2]), and quality of life (aOR:1.4 [1.2–1.9]); dissatisfaction (aOR:1.7 [1.3–2.2]); 90-day complications (aOR:2.9 [1.7–4.9]); and postoperative chronic opioid use (aOR:15 [11.4–19.7]). High-preoperative opioid dosage was only associated with postoperative chronic opioid use (aOR:4.9 [3–7.9]).

Conclusion.

Patients treated with chronic opioids prior to spine surgery are significantly less likely to achieve meaningful improvements at 1-year in pain, function, and quality of life; and less likely to be satisfied at 1-year with higher odds of 90-day complications, regardless of dosage. Both preoperative chronic opioid therapy and high-preoperative dosage are independently associated with postoperative chronic opioid use.

Level of Evidence: 2
Conditions for the Successful Implementation of Computer-Aided Drug Monitoring From Registered Nurses' Perspective—A Case Site Analysis
Authors: Johansson-Pajala Rose-Marie
Published: December 2018

This research addressed the introduction of a computerized decision support system for drug monitoring to be used by registered nurses in nursing homes. The system was introduced, and its effects were evaluated over the period of 1 year; however, at the end of 1 year, the implementation was not successful in all the participating settings. The aim of this study was to identify the conditions needed for the successful implementation of a computerized decision support system from the registered nurses' perspective. Two case sites were purposively selected based on the implementation's success in one nursing home, but not in the other. Focus group discussions were performed, one in each setting, with eight registered nurses. An inductive thematic analysis was conducted. The findings revealed six themes illustrating the registered nurses' views about the conditions needed: need to see benefits, have the time and take the time, curb administrative hassle, collaboration at all levels, stated responsibility, and requirements set from managerial positions. The most outstanding findings, when compared with the previous implementations of nursing informatics, involved collaboration and the view of drug monitoring responsibility in relation to themselves and the physicians.
Physiological Response to Opioids
Authors: TYAN PAUL , CAREY ERIN T.
Published: December 2018

The clinical setting in which women’s health physicians practice, whether as generalist, obstetricians and gynecologists, or subspecialists, dictates our frequent clinical interaction with “pain.” Opioid-containing medications are frequently prescribed within our specialty as a means of immediate pain relief. Opioid-containing medication causes a deep physiological alteration of several systems resulting in potential harm to acute and chronic opioid users. This article includes a thorough system-based review of opioid-containing medications on physiological systems. Women’s health providers should have an in-depth understanding of such reverberations on patients’ wellbeing to maintain the safest level of care. A solid grasp of physiological repercussions of opioid use would encourage physicians to seek alternative treatment options. Such practice is essential in curbing the opioid epidemic our patients are facing.
The Case for Using Hydrogen Peroxide Contact Lens Care Solutions: A Review
Authors: Nichols Jason J. , Chalmers Robin L. , Dumbleton Kathy , Jones Lyndon , Lievens Christopher W. , Merchea Mohinder M. , Szczotka-Flynn Loretta
Published: December 2018

Despite their established disinfection and safety benefits, the use of hydrogen peroxide (H2O2) lens care systems among today's wearers of reusable contact lenses remains low in comparison with multipurpose solution (MPS) use. Multipurpose solution systems, however, present several potential drawbacks that may impact patient outcomes, including the use of chemical preservatives for disinfection, biocompatibility issues, and challenges with respect to lens care compliance. Given their unique composition and mechanism of action, one-step H2O2 systems offer the opportunity to avoid many of the challenges associated with MPS use. This article reviews the evolution of H2O2 lens care systems and examines the current scientific and clinical evidence regarding the relative ease of use, lens and tissue compatibility, disinfection efficacy, and ocular surface safety of H2O2 systems. Evaluation of the available data indicates that in comparison with MPS, one-step H2O2 systems tend to promote more favorable compliance, efficacy, comfort, and ocular surface outcomes for a wide range of contact lens–wearing patients. Based on the current published evidence, the authors recommend that eye care practitioners consider making one-step H2O2 systems their first-line contact lens care recommendation for most wearers of reusable lenses.
The Physiology and Biomechanics of the Master Runner
Authors: Willy Richard W. , Paquette Max R.
Published: December 2018

The Master runner (age 35 y and above) represents a unique athletic patient. Lifelong participation in endurance running slows the inevitable age-related decline in aerobic function and muscular strength. Still, the Master runner does not escape the inevitable effects of aging. Master runners experience a steady decline in running performance, that is, typical and maximal running speeds, after the age of 50 years of age. Age-related declines in running performance are driven by a host of factors, including declining cardiovascular function, reduced muscular capacity, altered biomechanics, and greater susceptibility to running-related injury. This review discusses age-related changes in physiology, biomechanics, and running injury susceptibility and practical strategies to maximize running participation in the Master runner.
Management of Juvenile Polyposis Syndrome in Children and Adolescents
Authors: Cohen Shlomi , Hyer Warren , Mas Emmanuel , Auth Marcus , Attard Thomas M. , Spalinger Johannes , Latchford Andrew , Durno Carol
Published: December 2018

The European Society for Paediatric Gastroenterology, Hepatology and Nutrition (ESPGHAN) Polyposis Working Group developed recommendations to assist clinicians and health care providers with appropriate management of patients with juvenile polyposis. This is the first juvenile polyposis Position Paper published by ESPGHAN with invited experts. Many of the published studies were descriptive and/or retrospective in nature, consequently after incorporating a modified version of the GRADE system many of the recommendations are based on expert opinion. This ESPGHAN Position Paper provides a guide for diagnosis, assessment, and management of juvenile polyposis syndrome in children and adolescents, and will be helpful in the appropriate management and timing of procedures in children and adolescents. The formation of international collaboration and consortia is proposed to monitor patients prospectively to advance our understanding of juvenile polyposis conditions.
Bilateral Optic Perineuritis as Initial Presentation of Giant Cell Arteritis
Authors: Pappolla Agustin , Silveira Facundo , Norscini Jorge , Miquelini Luis , Patrucco Liliana
Published: December 2018

Giant cell arteritis is a large vessel vasculitis with neurological manifestations that range from visual disturbances to ischemic stroke. Among the former, visual acuity and visual field defects are prevalent, with anterior ischemic optic neuropathy being their most frequent cause. We present a clinical case in which the presenting ocular feature of the disease was a peripheral monocular visual field defect secondary to optic perineuritis.
Rare Phenomenon of Limb-shaking TIA, Resolved With Intracranial Wingspan Stenting
Authors: Ranasinghe Tamra , Boo SoHyun , Adcock Amelia
Published: December 2018

Objective:

Illustrates the importance of differentiating limb-shaking transient ischemic attack (LS-TIA) from focal seizures and carefully selecting patients for intracranial stenting.

Background:

LS-TIA is associated with severe carotid stenosis or occlusion, often precipitated by cerebral hypoperfusion. A case study of 313 patients with symptomatic intracranial artery stenosis/occlusion reported 11% with LS-TIA. In our literature search, we did not find any other cases of successful treatment of LS-TIA with an intracranial Wingspan stent.

Design/Methods:

A 66-year-old woman with a history of atrial fibrillation on anticoagulation, hypertension, hyperlipidemia and left middle cerebral artery (MCA) stroke followed by a left internal carotid artery (ICA) endarterectomy presented with transient repetitive involuntary movements (TRIMs) over her right upper and lower limbs. She described episodes of numbness followed by TRIMs over the right side of her body lasting for 1 to 2 minutes. TRIMs occurred only while standing and usually resolved on sitting or lying down.

Results:

Conventional angiogram showed severe stenosis of left supraclinoid ICA and proximal MCA. Brain single photon emission computed tomography scan showed impaired vascular reserve in the left MCA territory. An ambulatory electroencephalogram captured TRIMs without epileptiform discharges. She continued to have symptoms with no improvement over a period of 3 months on maximal medical management. She underwent successful endovascular treatment with the Wingspan stent system in the left M1 segment and terminal ICA. Following the revascularization procedure, her symptoms resolved.

Conclusions:

It is vitally important to differentiate LS-TIA from focal seizures. This is the first documented case report of complete resolution of LS-TIA symptoms following an intracranial Wingspan stenting.
Does High Cerebral Microbleed Burden Increase the Risk of Intracerebral Hemorrhage After Intravenous Tissue Plasminogen Activator for Acute Ischemic Stroke?
Authors: Arca Karissa N. , Demaerschalk Bart M. , Almader-Douglas Diana , Wingerchuk Dean M. , O’Carroll Cumara B.
Published: December 2018

Background:

The risk of developing intracerebral hemorrhage (ICH) after the administration of intravenous tissue plasminogen activator for acute ischemic stroke is well established in the general population. However, the risk associated with stroke thrombolysis in patients with a history of cerebral microbleeds (CMBs) is undetermined.

Objective:

The main objective of this study was to critically assess current evidence with regard to the risk of development of ICH after the administration of intravenous tissue plasminogen activator for acute ischemic stroke in patients with CMBs.

Methods:

The objective was addressed through the development of a critically appraised topic that included a clinical scenario, structured question, literature search strategy, critical appraisal, assessment of results, evidence summary, commentary, and bottom-line conclusions. Participants included consultant and resident neurologists, a medical librarian, clinical epidemiologists, and content experts in the field of vascular and hospital neurology.

Results:

A recent individual patient data meta-analysis was selected for critical appraisal. Cohorts were analyzed with pretreatment magnetic resonance imaging to determine CMB burden and were followed-up to assess subsequent symptomatic ICH, hemorrhagic transformation, parenchymal hemorrhage (PH), and remote PH (PHr) following intravenous thrombolysis. Risk of symptomatic ICH, PH, and PHr was increased in the presence of CMBs, with PHr having the strongest association with increasing CMB burden. Only patients with >10 CMBs were found to have associations with poor outcome at 3 to 6 months, whereas there was no association with 3 to 6 months’ mortality.

Conclusions:

CMBs are associated with an increased risk of postthrombolysis ICH; however, the clinical implications have yet to be determined.
Comparison of Three Different Tonometers in Eyes with Angle Closure
Authors: Lee Tae-Eun , Yoo Chungkwon , Kim Yong Yeon
Published: December 2018

SIGNIFICANCE

Precise measurement of intraocular pressure (IOP) is essential when diagnosing and managing glaucoma. We compared the IOP readings of three different tonometers and analyzed agreement among tonometers in eyes with high IOPs.

PURPOSE

The purpose of this study was to compare the IOP readings obtained using a Goldmann applanation tonometer (GAT), a rebound tonometer (RT), and a Tono-Pen (TP) in angle-closure eyes with elevated IOP before and after medical IOP-lowering therapy.

METHODS

Twenty-five eyes of 25 patients with angle closure and IOPs of greater than 30 mmHg were enrolled. Intraocular pressure was measured using RT (iCare Pro), TP (Tono-Pen XL), and GAT before and after medical treatment. The mean IOP readings of the tonometers were compared before and after treatment. The agreement among the tonometers was assessed via Bland-Altman analysis.

RESULTS

The measurements from 22 eyes of 22 patients were suitable for statistical analyses. Before medical treatment, the mean TP-IOP was significantly lower than the mean GAT-IOP (44.0 ± 10.3 vs. 50.4 ± 8.9 mmHg, respectively; P < .001), but no significant difference was evident between the RT-IOP and the GAT-IOP (50.8 ± 10.9 vs. 50.4 ± 8.9 mmHg, respectively; P = .79). After IOP-lowering treatment, the mean GAT-IOP (14.9 ± 4.7 mmHg) did not differ from either the mean RT-IOP (15.6 ± 4.4 mmHg) or the mean TP-IOP (15.4 ± 5.0 mmHg; P = .05 and P = .18, respectively). The random measurement error among tonometers was greater for high IOP readings.

CONCLUSIONS

Compared with RT or GAT, TP underestimated IOP in angle-closure eyes with a GAT-IOP of greater than 30 mmHg. Intraocular pressure reading agreement among the three tonometers was lower in eyes with high IOP.
Outcomes After Comprehensive Vision Rehabilitation Using Vision-related Quality of Life Questionnaires: Impact of Vision Impairment and National Eye Institute Visual Functioning Questionnaire
Authors: Selivanova Alexandra , Fenwick Eva , Man Ryan , Seiple William , Jackson Mary Lou
Published: December 2018

SIGNIFICANCE

This research is significant because, although vision-related quality of life (VRQoL) is improved after vision rehabilitation (VR), patients with certain characteristics respond less positively on VRQoL measures, and this should inform future care.

PURPOSE

The purposes of this study were to evaluate how two VRQoL questionnaires compare in measuring change in patient-reported outcomes after VR and to determine if patient characteristics or occupational therapy (OT) predict higher scores after rehabilitation.

METHODS

In a prospective clinical cohort study, 109 patients with low vision completed the Impact of Vision Impairment (IVI) and the National Eye Institute Visual Functioning Questionnaire (NEI VFQ-25) before and after VR. Comprehensive VR included consultation with an ophthalmologist and OT if required. The relationships of six baseline characteristics (age, sex, visual acuity, contrast sensitivity, field loss, diagnosis) and OT were assessed with VRQoL scores using multivariable logistic regression.

RESULTS

The mean (SD) age was 68.5 (19.2) years, and 61 (56%) were female. After rehabilitation, increases in scores were observed in all IVI subscales (reading [P < .001], mobility [P = .002], well-being [P = .0003]) and all NEI VFQ-25 subscales (functional [P = .01], socioemotional [P = .003]). Those who were referred to OT but did not attend and those who had hemianopia/field loss were less likely to have higher VRQoL in IVI mobility and well-being. Those attending OT for more than 3 hours were less likely to have better scores in emotional NEI VFQ. Men were less likely to have increased scores in functional and emotional NEI VFQ, whereas those with diagnoses of nonmacular diseases had higher odds of having increased scores on the emotional NEI VFQ (all, P < .05).

CONCLUSION

Both the IVI and the NEI VFQ-25 detected change in patients' VRQoL after rehabilitation. Most of the patient characteristics we considered predicted a lower likelihood of increased scores in VRQoL.
Experimental Study of Refraction Effects of Nominally Plano Ophthalmic Prisms and Magnifying Lenses
Authors: Atchison David A. , Lu Jianing , Yip Cleo , Suheimat Marwan , Schmid Katrina L.
Published: December 2018

SIGNIFICANCE

Nominally plano ophthalmic prisms give autorefraction results similar to those predicted on the basis of how effective powers change with pantoscopic tilt, and magnifying lenses give autorefraction results similar to those predicted on the basis of vergence changes. Without appreciation of the optics involved, these effects might wrongly be considered artifacts.

PURPOSE

The purpose of this study was to investigate the interactions of autorefractors with lenses and prisms.

METHODS

There were 15 adult participants across three experiments, with a range of ages and refractions. In experiments 1 and 2, participants wore frames containing base-up and base-down nominally plano prisms. In experiment 3, participants wore a lens that produced either 6.3% magnification or 5.9% minification, depending on which surface faced the eye. Autorefracting instruments with different operating principles were used: Shin-Nippon SRW5000 autorefractor, Grand Seiko 5100K autorefractor, Hoya AR-530 autorefractor, a Complete Ophthalmic Analysis System–High Definition wavefront sensor, and Tomey FC-800 autorefractor. A theory on the likely effects of magnifying lenses was presented.

RESULTS

For ophthalmic prisms, refractions showed results similar to those predicted on the basis of how effective prism powers change with pantoscopic tilt. As tilt increased, base-up prism gave more positive mean refractions and more negative horizontal/vertical astigmatism and vice versa for base-down prisms. In the presence of 10° tilt, 8Δ base-up prisms and 8Δ base-down prisms had different effects by a mean of 0.36 diopters. Magnifying lenses affected refractions similar to those predicted on the basis of vergence changes, with 6% magnification and minification producing mean changes of −11 and +8%, respectively, in absolute mean refraction. There was no strong evidence that different instruments had different effects.

CONCLUSIONS

The results have implications for studies in which prisms and lenses are placed in the front eyes, such as accommodation studies using thick lenses close to the eyes to stimulate accommodation rather than by changing object distance.
Supporting Dry Eye Diagnosis with a New Method for Noninvasive Tear Film Quality Assessment
Authors: Llorens-Quintana Clara , Szczesna-Iskander Dorota , Iskander D. Robert
Published: December 2018

SIGNIFICANCE

Noninvasive high-speed videokeratoscopy equipped with specific software has shown potential for assessing the homeostasis of tear film, providing clinicians with a fast and consistent tool for supporting dry eye diagnosis and management.

PURPOSE

The purpose of this study was to evaluate the efficacy of a recently proposed method for characterizing tear film dynamics using noninvasive high-speed videokeratoscopy in assessing the loss of homeostasis of tear film.

METHODS

Thirty subjects from a retrospective study, of which 11 were classified as dry eye and 19 as healthy, were included. High-speed videokeratoscopy measurements were performed using E300 videokeratoscope (Medmont Pty., Ltd., Melbourne, Australia). Raw data were analyzed using a recently proposed method to estimate the dynamics of the tear film based on a fractal dimension approach. This method provides three time-varying indicators related to the regularity of the reflected rings: tear film surface quality indicator, breaks feature indicator, and distortions feature indicator. From each indicator, five parameters were extracted and analyzed, including noninvasive breakup time, mean value of the indicator in the stability phase, mean value of the indicator in the whole interblink interval, mean value of the indicator in the leveling phase, and the general trend of the time series. Receiver operating characteristic curves were used to determine the sensitivity and specificity of each parameter in dry eye detection.

RESULTS

The best discrimination performance between dry eye and healthy subjects was achieved with the breaks feature indicator noninvasive breakup time parameter, with an area under the curve of 0.85. For a cutoff value of 10 seconds, the sensitivity was 100% and the specificity was 84%.

CONCLUSIONS

The analyzed method improves the assessment of tear film homeostasis in comparison with previous high-speed videokeratoscopy methods showing higher potential in assisting dry eye diagnosis.
Introducing BREAST-Q Computerized Adaptive Testing: Short and Individualized Patient-Reported Outcome Assessment following Reconstructive Breast Surgery
Authors: Young-Afat Danny A. , Gibbons Christopher , Klassen Anne F. , Vickers Andrew J. , Cano Stefan J. , Pusic Andrea L.
Published: December 2018

Background:

The BREAST-Q is a widely used patient-reported outcome instrument measuring health-related quality-of-life and patient satisfaction in breast surgery. Shorter assessment potentially increases patients’ willingness to complete scales, but simply offering a shortened version leads to unacceptable loss in measurement precision. The authors aimed to develop a computerized adaptive test (CAT) to shorten the BREAST-Q’s Satisfaction with Breasts scale while maintaining reliability of measurement.

Methods:

The authors created a CAT, which repetitively administered questions from the pool of 16 questions, until prespecified levels of reliability were reached [i.e., standard errors (SE) of 0.32 to 0.55]. In a simulation study, the authors tested the CAT's feasibility for all potential satisfaction scores. In a second study using actual patient data, 5000 breast reconstruction patients who had previously completed the full scale were randomly selected from a large database. Their full-scale satisfaction scores were compared with their CAT-derived scores.

Results:

In both studies, by applying CAT, the Satisfaction with Breasts scale could be reduced to an average of 10 questions when using the minimum level of measurement precision for individual-patient measurement (SE, 0.32), compared with four questions when using the minimum precision level for group-based research (SE, 0.55). Score estimates were highly correlated between the CAT assessment and the full scale (0.91 to 0.98 in the simulation study, and 0.89 to 0.98 in the patient data study).

Conclusions:

Applying computerized adaptive testing to the BREAST-Q’s Satisfaction with Breasts scale facilitates reliable assessment, with 38 to 75 percent fewer questions than the full version. The novel BREAST-Q CAT version may decrease response burden and help overcome barriers to implementation in routine care.
Arterial Wall Penetration Forces in Needles versus Cannulas
Authors: Pavicic Tatjana , Webb Katherine L. , Frank Konstantin , Gotkin Robert H. , Tamura Bhertha , Cotofana Sebastian
Published: December 2018

Background:

If safety is defined as the diminished ability to penetrate facial arteries, the goal of this study was to investigate whether different-sized cannulas are safer than correspondingly sized needles for the application of facial soft-tissue fillers.

Methods:

Two hundred ninety-four penetration procedures of the facial and superficial temporal arteries were performed in four fresh frozen cephalic specimens using both needles (20-, 22-, 25-, and 27-gauge) and cannulas (22-, 25-, and 27-gauge). Continuously increasing force was applied and measured until intraarterial penetration occurred.

Results:

No statistically significant differences were detected when comparing forces required to penetrate the facial arterial vasculature between different sexes, arteries, or sides of the face (all p > 0.05). Forces needed to penetrate significantly (p < 0.001) decreased with smaller diameter needles (20-gauge, 1.12 ± 0.29 N; 22-gauge, 1.08 ± 0.25 N; 25-gauge, 0.69 ± 0.24 N; and 27-gauge, 0.70 ± 0.29 N) and in cannulas (22-gauge, 1.50 ± 0.31 N; 25-gauge, 1.04 ± 0.36 N; and 27-gauge, 0.78 ± 0.35 N). Comparing 27-gauge injectors, no statistically significant difference was detected between needles and cannulas; an artery could be penetrated with a similar force independent of whether the injector was a needle or a cannula (0.70 ± 0.29 N versus 0.78 ± 0.35 N; p = 0.558).

Conclusions:

Cannulas, in all measured sizes except 27-gauge, required greater forces for intraarterial penetration compared with correspondingly sized needles, confirming the safety of 22- and 25-gauge cannulas; 27-gauge cannulas, however, required similar forces as 27-gauge needles, indicating that 27-gauge cannulas are not safer than 27-gauge needles.

CLINICAL QUESTION/LEVEL OF EVIDENCE:

Therapeutic, V.
Low-Dose Perfusion Computed Tomography for Breast Cancer to Quantify Tumor Vascularity
Authors: Park Eun Kyung , Seo Bo Kyoung , Kwon Myoungae , Cho Kyu Ran , Woo Ok Hee , Song Sung Eun , Cha Jaehyung , Lee Hye Yoon
Published: December 2018

Objectives

The aim of this study was to investigate the feasibility of using low-dose perfusion computed tomography (CT) in breast cancers for quantification of tumor vascularity and to correlate perfusion indexes with prognostic biomarkers.

Materials and Methods

This preliminary study was approved by our institutional review board. Signed informed consent was obtained from all 70 enrolled patients with invasive breast cancers. Low-dose perfusion CT was performed with the patient in the prone position using a spectral CT device set at 80 kVp and 30 mAs (1.30–1.40 mSv). Images were analyzed using commercial software applying the maximum slope algorithm. On CT perfusion maps, perfusion (mL/min per 100 mL), blood volume (mL/100 g), time-to-peak enhancement (second), and peak enhancement intensity (HU) were measured in the tumor, normal breast glandular tissues, and fat. Tumor grade, estrogen receptor (ER), human epidermal growth factor receptor 2 (HER2), and Ki67 level were evaluated using histopathology. Statistically, CT perfusion indexes of the tumor and normal glandular tissues or fat were compared using the Wilcoxon signed-rank test, and CT indexes were correlated with histological characteristics using the Mann-Whitney U or Kruskal-Wallis tests. We also correlated CT indexes with magnetic resonance imaging enhancement characteristics.

Results

In breast cancers, perfusion, blood volume, and peak enhancement intensity values were significantly higher, and time to peak was shorter than in normal glandular tissues and fat (P < 0.001). Perfusion increased significantly in high-grade, ER–, or HER2+ cancers (P < 0.05). Time to peak decreased in ER–, HER2+, and high-grade cancers or in those with high Ki67 levels (P < 0.05). Peak enhancement intensity significantly increased in high-grade cancers (P < 0.05). HER2 overexpressing cancers showed significantly higher perfusion and shorter time to peak than luminal-type cancers (P < 0.05). Perfusion increased and time to peak decreased significantly in cancers with washout enhancement patterns on magnetic resonance imaging.

Conclusions

Low-dose perfusion CT in the prone position is feasible to quantify tumor vascularity in breast cancers, and CT perfusion indexes are significantly correlated with prognostic biomarkers and molecular subtypes of breast cancer.
Matching and Homogenizing Convolution Kernels for Quantitative Studies in Computed Tomography
Authors: Mackin Dennis , Ger Rachel , Gay Skylar , Dodge Cristina , Zhang Lifei , Yang Jinzhong , Jones Aaron Kyle , Court Laurence
Published: December 2018

The sharpness of the kernels used for image reconstruction in computed tomography affects the values of the quantitative image features. We sought to identify the kernels that produce similar feature values to enable a more effective comparison of images produced using scanners from different manufactures. We also investigated a new image filter designed to change the kernel-related component of the frequency spectrum of a postreconstruction image from that of the initial kernel to that of a preferred kernel. A radiomics texture phantom was imaged using scanners from GE, Philips, Siemens, and Toshiba. Images were reconstructed multiple times, varying the kernel from smooth to sharp. The phantom comprised 10 cartridges of various textures. A semiautomated method was used to produce 8 × 2 × 2 cm3 regions of interest for each cartridge and for all scans. For each region of interest, 38 radiomics features from the categories intensity direct (n = 12), gray-level co-occurrence matrix (n = 21), and neighborhood gray-tone difference matrix (n = 5) were extracted. We then calculated the fractional differences of the features from those of the baseline kernel (GE Standard). To gauge the importance of the differences, we scaled them by the coefficient of variation of the same feature from a cohort of patients with non–small cell lung cancer. The noise power spectra for each kernel were estimated from the phantom's solid acrylic cartridge, and kernel-homogenization filters were developed from these estimates. The Philips C, Siemens B30f, and Toshiba FC24 kernels produced feature values most similar to GE Standard. The kernel homogenization filters reduced the median differences from baseline to less than 1 coefficient of variation in the patient population for all of the GE, Philips, and Siemens kernels except for GE Edge and Toshiba kernels. For prospective computed tomographic radiomics studies, the scanning protocol should specify kernels that have been shown to produce similar feature values. For retrospective studies, kernel homogenization filters can be designed and applied to reduce the kernel-related differences in the feature values.
Precision Oncology in Surgery
Authors: Dreyer Stephan B. , Pinese Mark , Jamieson Nigel B. , Scarlett Christopher J. , Colvin Emily K. , Pajic Marina , Johns Amber L. , Humphris Jeremy L. , Wu Jianmin , Cowley Mark J. , Chou Angela , Nagrial Adnan M. , Chantrill Lorraine , Chin Venessa T. , Jones Marc D. , Moran-Jones Kim , Carter Christopher Ross , Dickson Euan J. , Samra Jaswinder S. , Merrett Neil D. , Gill Anthony J. , Kench James G. , Duthie Fraser , Miller David K. , Cooke Susanna , Aust Daniela , Knösel Thomas , Rümmele Petra , Grützmann Robert , Pilarsky Christian , Nguyen Nam Q. , Musgrove Elizabeth A. , Bailey Peter J. , McKay Colin J. , Biankin Andrew V. , Chang David K.
Published: December 2018

Objective:

We aimed to define preoperative clinical and molecular characteristics that would allow better patient selection for operative resection.

Background:

Although we use molecular selection methods for systemic targeted therapies, these principles are not applied to surgical oncology. Improving patient selection is of vital importance for the operative treatment of pancreatic cancer (pancreatic ductal adenocarcinoma). Although surgery is the only chance of long-term survival, 80% still succumb to the disease and approximately 30% die within 1 year, often sooner than those that have unresected local disease.

Method:

In 3 independent pancreatic ductal adenocarcinoma cohorts (total participants = 1184) the relationship between aberrant expression of prometastatic proteins S100A2 and S100A4 and survival was assessed. A preoperative nomogram based on clinical variables available before surgery and expression of these proteins was constructed and compared to traditional measures, and a postoperative nomogram.

Results:

High expression of either S100A2 or S100A4 was independent poor prognostic factors in a training cohort of 518 participants. These results were validated in 2 independent patient cohorts (Glasgow, n = 198; Germany, n = 468). Aberrant biomarker expression stratified the cohorts into 3 distinct prognostic groups. A preoperative nomogram incorporating S100A2 and S100A4 expression predicted survival and nomograms derived using postoperative clinicopathological variables.

Conclusions:

Of those patients with a poor preoperative nomogram score, approximately 50% of patients died within a year of resection. Nomograms have the potential to improve selection for surgery and neoadjuvant therapy, avoiding surgery in aggressive disease, and justifying more extensive resections in biologically favorable disease.
Metastatic Potential and Survival of Duodenal and Pancreatic Tumors in Multiple Endocrine Neoplasia Type 1
Authors: Vinault Sandrine , Mariet Anne-Sophie , Le Bras Maëlle , Mirallié Eric , Cardot-Bauters Catherine , Pattou François , Ruszniewski Philippe , Sauvanet Alain , Chanson Philippe , Baudin Eric , Elias Dominique , Menegaux Fabrice , Gaujoux Sébastien , Borson-Chazot Françoise , Lifante Jean-Christophe , Caron Philippe , Carrère Nicolas , Tabarin Antoine , Laurent Christophe , Klein Marc , Brunaud Laurent , Niccoli Patricia , Sebag Frédéric , Cadiot Guillaume , Kianmanesh Reza , Luu Maxime , Binquet Christine , Goudet Pierre
Published: December 2018

Objective:

To assess the distant metastatic potential of duodeno-pancreatic neuroendocrine tumors (DP-NETs) in patients with MEN1, according to functional status and size.

Summary Background Data:

DP-NETs, with their numerous lesions and endocrine secretion-related symptoms, continue to be a medical challenge; unfortunately they can become aggressive tumors associated with distant metastasis, shortening survival. The survival of patients with large nonfunctional DP-NETs is known to be poor, but the overall contribution of DP-NETs to metastatic spread is poorly known.

Methods:

The study population included patients with DP-NETs diagnosed after 1990 and followed in the MEN1 cohort of the Groupe d’étude des Tumeurs Endocrines (GTE). A multistate Markov piecewise constant intensities model was applied to separate the effects of prognostic factors on 1) metastasis, and 2) metastasis-free death or 3) death after appearance of metastases.

Results:

Among the 603 patients included, 39 had metastasis at diagnosis of DP-NET, 50 developed metastases during follow-up, and 69 died. The Markov model showed that Zollinger-Ellison-related tumors (regardless of tumor size and thymic tumor pejorative impact), large tumors over 2 cm, and age over 40 years were independently associated with an increased risk of metastases. Men, patients over 40 years old and patients with tumors larger than 2 cm, also had an increased risk of death once metastasis appeared.

Conclusions:

DP-NETs of 2 cm in size or more, regardless of the associated secretion, should be removed to prevent metastasis and increase survival. Surgery for gastrinoma remains debatable.
Resistance to targeted therapies as a multifactorial, gradual adaptation to inhibitor specific selective pressures
Authors: Velde Robert Vander , Yoon Nara , Marusyk Viktoriya , Durmaz Arda , Dhawan Andrew , Myroshnychenko Daria , Lozano-Peral Diego , Desai Bina , Balynska Olena , Poleszhuk Jan , Kenian Liu , Abazeed Mohamed , Mian Omar , Tan Aik Choon , Haura Eric , Scott Jacob , Marusyk Andriy
Published: December 2018

Despite high initial efficacy, therapies that target oncogenic kinases eventually fail in advanced, metastatic cancers. This failure in initially responsive tumors is the direct result of the evolution of drug resistance under therapy-imposed selective pressures. In contrast to the massive body of experimental research on the molecular mechanisms of resistance, understanding of its evolutionary origins and dynamics remains fragmented. Using a combination of experimental studies and mathematical modeling, we sought to dissect the evolution of resistance to different clinical ALK inhibitors in an experimental model of ALK positive NSCLC. We found that resistance can originate from heterogeneous, weakly resistant, sub-populations with variable sensitivity to different ALK inhibitors. Instead of the commonly assumed stochastic single hit (epi) mutational transition, or drug-induced reprogramming, we found evidence of a hybrid scenario, of gradual, multifactorial development through acquisition of multiple cooperating genetic and epigenetic adaptive changes, amplified by selection. Additionally, we found that intermediate resistance phenotypes might present unique, temporally restricted collateral sensitivities, absent in therapy naïve or fully resistant cells, suggesting new opportunities for therapeutic interference.
Low dimensional dynamics for working memory and time encoding
Authors: Cueva Christopher J. , Saez Alex , Marcos Encarni , Genovesio Aldo , Jazayeri Mehrdad , Romo Ranulfo , Salzman C. Daniel , Shadlen Michael N. , Fusi Stefano
Published: December 2018

Our decisions often depend on multiple sensory experiences separated by time delays. The brain can remember these experiences and, simultaneously, estimate the timing between events. To understand the mechanisms underlying working memory and time encoding we analyze neural activity recorded during delays in four experiments on non-human primates. To disambiguate potential mechanisms, we propose two analyses, namely, decoding the passage of time from neural data, and computing the cumulative dimensionality of the neural trajectory over time. Time can be decoded with high precision in tasks where timing information is relevant and with lower precision when irrelevant for performing the task. Neural trajectories are always observed to be low dimensional. These constraints rule out working memory models that rely on constant, sustained activity, and neural networks with high dimensional trajectories, like reservoir networks. Instead, recurrent networks trained with backpropagation capture the time encoding properties and the dimensionality observed in the data.
An Analysis of the full song of five free-living urban European Blackbirds (Turdus merula); a network approach.
Authors: Kortmulder Koenraad
Published: December 2018

Is the song repertoire of male blackbirds safe-guarded against loss of variability during the breeding season? In order to answer this question the repertoires of five males were analysed from the viewpoint of network theory. In four of the five males a strong coherence of the repertoire was found to exist in anastomoses between strophe types, same elements being reached from different beginnings. The succession of strophe types in song sessions betrayed a mixture of relatively predictable cycles and chaotic connections. The former should facilitate repeated retrieval of a considerable part of the repertoire, while the chaotic component keeps the whole repertoire readily accessible from any point in a singing session. The same mixture may be considered optimal for binding the attention of conspecific listeners. It is concluded that the existing structure of blackbird song repertoires is favourable for the conservation of its richness, but it is as yet uncertain whether this is due to evolutionary (i.c. sexual) adaptation.
Multiplexed detection of RNA using MERFISH and branched DNA amplification
Authors: Xia Chenglong , Babcock Hazen P , Moffitt Jeffrey R , Zhuang Xiaowei
Published: December 2018

Multiplexed error-robust fluorescence in situ hybridization (MERFISH) allows simultaneous imaging of numerous RNA species in their native cellular environment and hence spatially resolved single-cell transcriptomic measurements. However, the relatively modest brightness of signals from single RNA molecules can become limiting in a number of important applications, such as increasing the imaging throughput, imaging shorter RNAs, and imaging samples with high degrees of background, such as some tissue samples. Here, we introduce a branched DNA (bDNA) amplification approach for MERFISH measurements. This approach produces a drastic signal increase in RNA FISH samples without increasing the fluorescent spot size for individual RNAs or increasing the variation in brightness from spot to spot. Using this approach in combination with MERFISH, we demonstrated RNA imaging and profiling with a near 100% detection efficiency. We further demonstrated that signal amplification improves MERFISH performance when fewer FISH probes are used for each RNA species, which should allow shorter RNAs to be imaged. We anticipate that the combination of bDNA amplification with MERFISH should facilitate many other applications and extend the range of biological questions that can be addressed by this technique in both cell culture and tissues.
NK cells acquire epigenetic memory of LPS-induced systemic inflammation
Authors: Rasid Orhan , Chevalier Christine , Camarasa Tiphaine , Fitting Catherine , Cavaillon Jean-Marc , Hamon Melanie Anne
Published: December 2018

Natural killer cells are unique mediators of innate immunity, and as such, an attractive target for immunotherapy. Following viral infection, NK cells display immune memory properties, defined by heightened responses to re-stimulation, an expansion of specific NK cell sup-populations and a protective role against re-infection. However, similar memory to bacterial infection or systemic inflammation, and the molecular mechanisms behind NK cell memory remain elusive. Here we show that following LPS-induced endotoxemia in mice, NK cells acquire cell-intrinsic memory properties as displayed by an amplified production of IFNγ upon secondary stimulation. NK cell memory is acquired even under the post-endotoxemic suppressive environment and is detectable for at least 9 weeks. Furthermore, we define an epigenetic mechanism essential for NK cell memory, where an H3K4me1-marked latent enhancer is uncovered at the ifng locus. Chemical inhibition of histone methyltransferase activity erased the enhancer and prevented NK cells from acquiring memory. Thus, NK cells develop memory to LPS during endotoxemia, in a histone methylation-dependent manner, which ensures a heightened response to secondary stimulation and confers protection against bacterial infection.
The mutational features of aristolochic acid-induced mouse and human liver cancers
Authors: Lu Zhao-Ning , Luo Qing , Zhao Li-Nan , Shi Yi , Su Xian-Bin , Han Ze-Guang
Published: December 2018

Aristolochic acid (AA) derived from traditional Chinese herbal remedies has recently been statistically associated with human liver cancer; however, the causal relationships between AA and liver cancer and the underlying evolutionary process of AA-mediated mutagenesis during tumorigenesis are obscure. Here, we subjected mice, including Pten-deficient ones, to aristolochic acid I (AAI) alone or a combination of AAI and carbon tetrachloride (CCl4), which may induce liver injury. Significantly, AAI promoted the development of liver cancer, including hepatocellular carcinoma and intrahepatic cholangiocarcinoma, in a dose-dependent manner, and it increased the incidence of liver cancer, together with CCl4 or Pten deficiency. AAI could lead to DNA damage and AAI-DNA adducts that initiate liver cancer via characteristic A>T transversions, as indicated by the comprehensive genomic analysis, which revealed recurrent mutations in Hras and some genes encoding components of the Ras/Raf, PI3K, Notch, Hippo, Wnt, DNA polymerase family and the SWI/SNF complex, some of which are also often found in human liver cancer. Mutational signature analysis across human cancer types revealed that the AA-related dominant signature was especially implicated in liver cancer in China, based on very stringent criteria derived from the animal cancer form, in which mutations of TP53 and JAK1 are prone to be significantly enriched. Interestingly, AAI-mediated characteristic A>T mutations were the earliest genetic event driving malignant subclonal evolution in mouse and human liver cancer. In general, this study provides documented evidence for AA-induced liver cancer with featured mutational processes during malignant clonal evolution, laying a solid foundation for the prevention and diagnosis of AA-associated human cancers, especially liver cancer.
Sex differences in cocaine self-administration behaviour under Long Access versus Intermittent Access conditions
Authors: Algallal Hajer , Allain Florence , Ndiaye Ndeye Aissatou , Samaha Anne-Noel
Published: December 2018

A widely accepted rodent model to study cocaine addiction involves allowing animals continuous access to drug during long self-administration sessions (Long-access or LgA). This produces continuously high brain concentrations of drug during each session. This might not model the pharmacokinetics of cocaine use in experienced human users, which are thought to involve intermittently spiking brain cocaine concentrations within and between bouts of use. Intermittent-access (IntA) cocaine self-administration models this spiking pattern in rats. IntA is also particularly effective in increasing incentive motivation for drug. Most IntA studies have been conducted in male rats. Both humans and non-human animals can show sex differences in all phases of the addiction process. We compared cocaine use in female and male rats that self-administered the drug (0.25 mg/kg/injection, i.v.) during 10 daily, 6-h LgA or IntA sessions. Cocaine intake was greatest under LgA, and female LgA rats escalated their intake. However, only IntA rats (both sexes) developed locomotor sensitization to self-administered cocaine and sensitization was greatest in the females. Five and 25 days after the last self-administration session, we quantified incentive motivation for cocaine by measuring breakpoints for the drug (0.083-0.75 mg/kg/injection) under progressive ratio. Breakpoints were similar in IntA and LgA rats. There were no sex differences in breakpoints under LgA. However, under IntA, females reached higher breakpoints for cocaine than males. Thus, LgA might be best suited to study sex differences in cocaine intake, while IntA might be best suited to study sex differences in incentive motivational processes in cocaine addiction.