bluuebunny/crossref_metadata_2025_split huggingface dataset:
Supracerebellar Infratentorial Approach for Complex Thalamic Cavernous Malformation: 2-Dimensional Operative Video
Authors: Hendricks Benjamin K , Spetzler Robert F 
Published: September 2019

Abstract
Key points for the approach include the use of a supracerebellar infratentorial craniotomy, dynamic and gravity retraction, lighted bipolar forceps and suction, and stereotactic navigation. This patient has a large cavernous malformation extending from the midbrain to the thalamus in craniocaudal extent. The cavernous malformation extends to the midbrain surface along the interface with the ambient cistern, making it appropriate for the supracerebellar infratentorial approach. By cutting the tentorium access to the superior extension becomes feasible. The cavernous malformation is excised in a piecemeal manner utilizing a CO2 laser. Because removal of the large mass allowed the partial collapse of the cavity, a small segment of the cavernous malformation obscured by the collapse is retained cranially along the foramen of Monro. This situation required a return to the operating room for complete excision. The patient tolerated both procedures well and remained at her neurological baseline postoperatively. The patient gave informed consent for surgery and video recording. Institutional review board approval was deemed unnecessary. The surgical video has been used with permission from the Barrow Neurological Institute.
Minimally Invasive Separation Surgery for Metastases in the Vertebral Column: A Technical Report
Authors: Vega Rafael A , Traylor Jeffrey I , Habib Ahmed , Rhines Laurence D , Tatsui Claudio E , Rao Ganesh 
Published: September 2019

Abstract

BACKGROUND
Epidural spinal cord compression (ESCC) is a common and severe cause of morbidity in cancer patients. Minimally invasive surgical techniques may be utilized to preserve neurological function and permit the use of radiation to maximize local control. Minimally invasive techniques are associated with lower morbidity.

OBJECTIVE
To describe a novel, minimally invasive operative technique for the management of metastatic ESCC.

METHODS
A minimally invasive approach was used to cannulate the pedicles of the thoracic vertebrae, which were then held in place by Kirschner wires (K-wires). Following open decompression of the spinal cord, cannulated screws were placed percutaneously with stereotactic guidance through the pedicles followed by cement induction. Stereotactic radiosurgery is performed in the postoperative period for residual metastatic disease in the vertebral body.

RESULTS
The minimally invasive technique used in this case reduced tissue damage and optimized subsequent recovery without compromising the quality of decompression or the extent of metastatic tumor resection. Development of more minimally invasive techniques for the management of metastatic ESCC has the potential to facilitate healing and preserve quality of life in patients with systemic malignancy.

CONCLUSION
ESCC from vertebral metastases poses a challenge to treat in the context of minimizing potential risks to preserve quality of life. Percutaneous pedicle screw fixation with cement augmentation provides a minimally invasive alternative for definitive treatment of these patients.
Lung Purinoceptor Activation Triggers Ventilator-Induced Brain Injury
Authors: González-López Adrian , López-Alonso Ines , Pickerodt Philipp A. , von Haefen Clarissa , Amado-Rodríguez Laura , Reimann Henning , Niendorf Thoralf , Kuebler Wolfgang , Albaiceta Guillermo M. , Francis Roland C.E. , Spies Claudia D. 
Published: September 2019

Objectives:
Mechanical ventilation can cause ventilator-induced brain injury via afferent vagal signaling and hippocampal neurotransmitter imbalances. The triggering mechanisms for vagal signaling during mechanical ventilation are unknown. The objective of this study was to assess whether pulmonary transient receptor potential vanilloid type-4 (TRPV4) mechanoreceptors and vagal afferent purinergic receptors (P2X) act as triggers of ventilator-induced brain injury.

Design:
Controlled, human in vitro and ex vivo studies, as well as murine in vivo laboratory studies.

Setting:
Research laboratory.

Subjects:
Wild-type, TRPV4-deficient C57BL/6J mice, 8–10 weeks old. Human postmortem lung tissue and human lung epithelial cell line BEAS-2B.

Intervention:
Mice subjected to mechanical ventilation were studied using functional MRI to assess hippocampal activity. The effects of lidocaine (a nonselective ion-channel inhibitor), P2X-purinoceptor antagonist (iso-PPADS), or genetic TRPV4 deficiency on hippocampal dopamine-dependent pro-apoptotic signaling were studied in mechanically ventilated mice. Human lung epithelial cells (BEAS-2B) were used to study the effects of mechanical stretch on TRPV4 and P2X expression and activation. TRPV4 levels were measured in postmortem lung tissue from ventilated and nonventilated patients.

Measurements and Main Results:
Hippocampus functional MRI analysis revealed considerable changes in response to the increase in tidal volume during mechanical ventilation. Intratracheal lidocaine, iso-PPADS, and TRPV4 genetic deficiency protected mice against ventilationinduced hippocampal pro-apoptotic signaling. Mechanical stretch in both, BEAS-2B cells and ventilated wild-type mice, resulted in TRPV4 activation and reduced Trpv4 and P2x expression. Intratracheal replenishment of adenosine triphosphate in Trpv4–/–
mice abrogated the protective effect of TRPV4 deficiency. Autopsy lung tissue from ventilated patients showed decreased lung TRPV4 levels compared with nonventilated

Conclusions:
TRPV4 mechanosensors and purinergic receptors are involved in the mechanisms of ventilator-induced brain injury. Inhibition of this neural signaling, either using nonspecific or specific inhibitors targeting the TRPV4/adenosine triphosphate/P2X signaling axis, may represent a novel strategy to prevent or treat ventilator-induced brain injury.
Which Multicenter Randomized Controlled Trials in Critical Care Medicine Have Shown Reduced Mortality? A Systematic Review
Authors: Santacruz Carlos A. , Pereira Adriano J. , Celis Edgar , Vincent Jean-Louis 
Published: September 2019

Objectives:
To determine which multicenter randomized controlled trials in critically ill patients have shown that the study intervention was associated with a statistically significant reduction in mortality. Our analysis provides an update to a report published 10 years ago.

Data Sources:
MEDLINE database and PubMed interface from inception until April 30, 2019.

Study Selection:
All adult multicenter randomized controlled trials that evaluated the effects of any intervention or monitoring system in critically ill patients and reported mortality as a primary or secondary outcome were included.

Data Extraction:
Numbers of centers and patients, type of intervention, reported mortality outcome, and rate and level of significance were extracted into predefined tables. Included randomized controlled trials were classified as reporting reduced, increased, or no effect of the intervention on mortality. Methodologic quality of trials was evaluated using the updated Consolidated Standards of Reporting Trials statement.

Data Synthesis:
A total of 212 trials met the inclusion criteria: 27 (13%) reported a significant reduction in mortality, 16 (7%) an increase in mortality, and 170 (80%) no difference in mortality (one study was reported in 2 groups). Of the 27 trials reporting reduced mortality, six had assessed interventions likely to decrease ventilator-induced lung injury, including low tidal volume, prone position, and neuromuscular blockers, demonstrating the negative effects of mechanical ventilation strategies or improved process of care rather than positive effects of new therapies. Seven of the 27 trials reported beneficial effects of noninvasive ventilation. Results from some positive randomized controlled trials, for example, studies of recombinant activated protein C, talactoferrin, interleukin-1 receptor antagonist in sepsis, and muscle relaxants in severe acute respiratory distress syndrome were not replicated in subsequent randomized controlled trials. Other interventions, for example, gastric tonometry, have been abandoned.

Conclusions:
A systematic literature search provided no conclusive evidence of any pharmacologic intervention that has consistently reduced mortality in critically ill patients. Strategies associated with improved or noninvasive mechanical ventilation were associated with reduced mortality.
Cancer Chemotherapy: The Case for Therapeutic Drug Monitoring
Authors: Knezevic Claire E. , Clarke William 
Published: September 2019

Abstract:The selection of an appropriate therapy and dosing regimen is a significant challenge in the treatment of cancer. Although there are recommended standardized chemotherapy protocols for some types of cancer, protocol changes that usually only occur after large clinical trials demonstrate improvements and individual patients often require dose modifications (amount or interval) or delays in dose administration as toxicities arise. In other areas of medicine, therapeutic drug monitoring is commonly and successfully used to ensure appropriate drug exposure and to limit dose-related toxicities. Currently, the wide pharmacokinetic variability of cytotoxic chemotherapies is addressed clinically by the use of body surface area to determine drug doses; however, this is outdated and demonstrably ineffective for this purpose. This review discusses the challenges of dosing cytotoxic chemotherapies, dose determination strategies for cytotoxic, targeted, and antibody-based biological anticancer drugs, and provides an overview of the recent literature regarding the use of therapeutic drug monitoring in cancer.
Development of a comprehensive health-risk prediction tool for postmenopausal women
Authors: Hedlin Haley , Weitlauf Julie , Crandall Carolyn J. , Nassir Rami , Cauley Jane A. , Garcia Lorena , Brunner Robert , Robinson Jennifer , Stefanick Marica L. , Robbins John 
Published: September 2019

Abstract

Objective:
The aim of the study was to develop a web-based calculator that predicts the likelihood of experiencing multiple, competing outcomes prospectively over 5, 10, and 15 years.

Methods:
Baseline demographic and medical data from a healthy and racially and ethnically diverse cohort of 161,808 postmenopausal women, aged 50 to 79 at study baseline, who participated in the Women's Health Initiative (WHI), were used to develop and evaluate a risk-prediction calculator designed to predict individual risk for morbidity and mortality outcomes. Women were enrolled from 40 sites arranged in four regions of the United States. The calculator predicts all-cause mortality, adjudicated outcomes of health events (ie, myocardial infarction [MI], stroke, and hip fracture), and disease (lung, breast, and colorectal cancer). A proportional subdistribution hazards regression model was used to develop the calculator in a training dataset using data from three regions. The calculator was evaluated using the C-statistic in a test dataset with data from the fourth region.

Results:
The predictive validity of our calculator measured by the C-statistic in the test dataset for a first event at 5 and 15 years was as follows: MI 0.77, 0.61, stroke 0.77, 0.72, lung cancer 0.82, 0.79, breast cancer 0.60, 0.59, colorectal cancer 0.67, 0.60, hip fracture 0.79, 0.76, and death 0.74, 0.72.

Conclusion:
This study represents the first large-scale study to develop a risk prediction calculator that yields health risk prediction for several outcomes simultaneously. Development of this tool is a first step toward enabling women to prioritize interventions that may decrease these risks.

Video Summary:
http://links.lww.com/MENO/A463.
Psychometric properties of Short Form-36 Health Survey, EuroQol 5-dimensions, and Hospital Anxiety and Depression Scale in patients with chronic pain
Authors: LoMartire Riccardo , Äng Björn Olov , Gerdle Björn , Vixner Linda 
Published: September 2019

Abstract
Recent research has highlighted a need for the psychometric evaluation of instruments targeting core domains of the pain experience in chronic pain populations. In this study, the measurement properties of Short Form-36 Health Survey (SF-36),EuroQol 5-dimensions (EQ-5D) and Hospital Anxiety and Depression Scale (HADS) were analyzed within the item response-theory framework based on data from 35,908 patients. To assess the structural validity of these instruments, the empirical representations of several conceptually substantiated latent structures were compared in a cross-validation procedure. The most structurally sound representations were selected from each questionnaire and their internal consistency reliability computed as a summary of their precision. Finally, questionnaire scores were correlated with each other to evaluate their convergent and discriminant validity. Our results supported that SF-36 is an acceptable measure of 2 independent constructs of physical and mental health. By contrast, although the approach to summarize the health-related quality of life construct of EQ-5D as a unidimensional score was valid, its low reliability rendered practical model implementation of doubtful utility. Finally, rather than being separated into 2 subscales of anxiety and depression, HADS was a valid and reliable measure of overall emotional distress. In support of convergent and discriminant validity, correlations between questionnaires showed that theoretically similar traits were highly associated, whereas unrelated traits were not. Our models can be applied to score SF-36 and HADS in chronic pain patients, but we recommend against using the EQ-5D model due to its low reliability. These results are useful for researchers and clinicians involved in chronic pain populations because questionnaires' properties determine their discriminating ability in patient status assessment.
Toll-like Receptor 4 Signaling and Downstream Neutrophilic Inflammation Mediate Endotoxemia-Enhanced Blood–Labyrinth Barrier Trafficking
Authors: Urdang Zachary D. , Bills Jessica L. , Cahana David Y. , Muldoon Leslie L. , Neuwelt Edward A. 
Published: September 2019

Hypothesis:
Both toll-like receptor 4 (TLR4) and downstream neutrophil activity are required for endotoxemia-enhanced blood–labyrinth barrier (BLB) trafficking.

Background:
Aminoglycoside and cisplatin are valuable clinical therapies; however, these drugs often cause life-long hearing loss. Endotoxemia enhances the ototoxicity of aminoglycosides and cisplatin in a TLR4 dependent mechanism for which downstream proinflammatory signaling orchestrates effector immune cells including neutrophils. Neutrophil-mediated vascular injury (NMVI) can enhance molecular trafficking across endothelial barriers and may contribute to endotoxemia-enhanced drug-induced ototoxicity.

Methods:
Lipopolysaccharide (LPS) hypo-responsive TLR4-KO mice and congenitally neutropenic granulocyte colony-stimulating factor (GCSF) GCSF-KO mice were studied to investigate the relative contributions of TLR4 signaling and downstream neutrophil activity to endotoxemia-enhanced BLB trafficking. C57Bl/6 wild-type mice were used as a positive control. Mice were treated with LPS and 24 hours later cochleae were analyzed for gene transcription of innate inflammatory cytokine/chemokine signaling molecules, neutrophil recruitment, and vascular trafficking of the paracellular tracer biocytin-TMR.

Results:
Cochlear transcription of innate proinflammatory cytokines/chemokines was increased in endotoxemic C57Bl/6 and GCSF-KO, but not in TLR4-KO mice. More neutrophils were recruited to endotoxemic C57Bl/6 cochleae compared with both TLR4 and GCSF-KO cochleae. Endotoxemia enhanced BLB trafficking of biocytin-TMR in endotoxemic C57Bl/6 cochleae and this was attenuated in both TLR4 and GCSF-KO mice.

Conclusion:
Together these results suggest that TLR4-mediated innate immunity cytokine/chemokine signaling alone is not sufficient for endotoxemia-enhanced trafficking of biocytin-TMR and that downstream neutrophil activity is required to enhance BLB trafficking. Clinically, targeting neutrophilic inflammation could protect hearing during aminoglycoside, cisplatin, or other ototoxic drug therapies.
Efficacy of Osteoporosis Prevention Smartphone App
Authors: Ryan Polly , Brown Roger L. , Csuka Mary Ellen , Papanek Paula 
Published: September 2019

Background
The Striving to be Strong study tested the efficacy of a multifaceted, theory-based, complex osteoporosis prevention smartphone application (app). We hypothesized use of the app would improve bone mineral density and trabecular bone scores.

Methods
The study was a three-group, prospective, repeated-measure, longitudinal randomized trial. Baseline sample consisted of 290 healthy women between 40 and 60 years of age. Participants were randomly assigned to one of three groups: “Striving,” a dynamically tailored, person-centered app; “Boning Up,” a standardized osteoporosis-education e-book; and “Wait List,” a participant’s choice of intervention in the final 3 months of the 12-month study. Participants had or were provided a smart phone. Bone mineral density and trabecular bone scores were measured using dual-energy X-ray absorptiometry at baseline and 12 months. To assess engagement in health behavior change processes, ecological momentary assessments were administered via text messaging during the 12 months participants actively used the app.

Results
The final sample reflects an 89.6% retention rate. There were decreases in bone mineral density over time but not among the three groups. The percentage of bone density lost over 12 months was lower than expected. Trabecular bone scores were not different over time or by group but improved across all three groups.

Discussion
Small but positive results were observed across all groups, suggesting one or more aspects of participation might have affected outcomes, including dissemination of the intervention across groups, retention without participation, ecological momentary assessments functioning as both an intervention and measure, and selective engagement in research-based recommendations.
Recent and Upcoming Technological Developments in Computed Tomography
Authors: Lell Michael M. , Kachelrieß Marc 
Published: September 2019

Abstract
The advent of computed tomography (CT) has revolutionized radiology, and this revolution is still going on. Starting as a pure head scanner, modern CT systems are now able to perform whole-body examinations within a couple of seconds in isotropic resolution, single-rotation whole-organ perfusion, and temporal resolution to fulfill the needs of cardiac CT. Because of the increasing number of CT examinations in all age groups and overall medical-driven radiation exposure, dose reduction remains a hot topic. Although fast gantry rotation, broad detector arrays, and different dual-energy solutions were main topics in the past years, new techniques such as photon counting detectors, powerful x-ray tubes for low-kV scanning, automated image preprocessing, and machine learning algorithms have moved into focus today.
The aim of this article is to give an overview of the technical specifications of up-to-date available CT systems and recent hardware and software innovations for CT systems in the near future.
Evaluation of the causal effects of blood lipid levels on gout with summary level GWAS data: two-sample Mendelian randomization and mediation analysis
Authors: Yu Xinghao , Chen Haimiao , Huang Shuiping , Zeng Ping 
Published: September 2019

AbstractObjectiveMany observational studies have identified that gout patients are often comorbid with dyslipidemia, which is typically characterized by a decrease in high-density lipoprotein cholesterol (HDL) and an increase in triglycerides (TG). However, the relationship between dyslipidemia and gout is still unclear.MethodsWe first performed a two-sample Mendelian randomization (MR) to evaluate the causal effect of four lipid traits on gout and serum urate based on summary association statistics available from large scale genome-wide association studies (up to ∼100,000 for lipid, 69,374 for gout and 110,347 for serum urate). We adopted multivariable Mendelian randomization to estimate the causal effect independently. We also assessed the mediated effect by serum urate between lipids and gout with a mediation analysis. The MR results were validated with extensive sensitive analyses.ResultsGenetically lower HDL was positively associated with the risk of gout and serum urate concentration. Each standard deviation (SD) (∼12.26 mg/dL) increase was genetically associated with an odds ratio of gout of 0.75 (95% CI 0.62 ∼ 0.91,p= 3.31E-3) and with a 0.09 mg/dL (95% CI: -0.12 ∼ -0.05,p= 7.00E-04) decrease in serum urate concentration. Genetically higher TG was positively associated with the serum urate concentration. Each SD (∼112.33 mg/dL) increase was genetically associated with a 0.10 mg/dL (95% CI: 0.06 ∼ 0.14,p= 9.87E-05) increase in serum urate concentration. Those results were robust against various sensitive analyses. In addition, the multivariable Mendelian randomization confirmed the independent effect of HDL and TG on the gout/serum urate after adjustment for the other lipids. Finally, the mediation analysis showed that both HDL and TG could indirectly affect gout morbidity via the pathway of serum urate. The mediation effect accounted for about 13.0% or 28.0% of the total effect of HDL and TG, respectively.ConclusionOur study confirmed the causal associations between HDL/TG and gout/serum urate. Furthermore, the effect of HDL or TG on gout could also be mediated by serum urate.Key MessagesEpidemiological studies have identified an accompanying association between lipid and gout. However, whether the association is causal is unclear.Mendelian randomization with genetic variants as instrumental variables is a useful tool facilitate the validation of a causal relationship for modifiable risk factors.The direct and indirect effects of lipids on gout, controlling for the serum urate concentration, can be estimated by a mediation analysis with serum urate serving as a mediator.We confirmed that elevated HDL levels can directly and indirectly lead to the decreased risk of gout, whereas elevation of TG levels can directly and indirectly elevate the risk of gout.