bluuebunny/crossref_metadata_2025_split huggingface dataset:
Modeling of the Behavior of Natural Polysaccharides Hydrogels for Bio-pharma Applications
Authors: Caccavo Diego , Cascone Sara , Lamberti Gaetano , Dalmoro Annalisa , Barba Anna Angela 
Published: March 2019

Hydrogels, even if not exclusively obtained from natural sources, are widely used for pharmaceuticals and for biomedical applications. The reasons for their uses are their biocompatibility and the possibility to obtain systems and devices with different properties, due to variable characteristics of the materials. In order to effectively design and produce these systems and devices, two main ways are available: i) trial-and-error process, at least guided by experience, during which the composition of the system and the production steps are changed in order to get the desired behavior; ii) production process guided by the a-priori simulation of the systems’ behavior, thanks to proper tuned mathematical models of the reality. Of course the second approach, when applicable, allows tremendous savings in term of human and instrumental resources. In this mini-review, several modeling approaches useful to describe the behavior of natural polysaccharide-based hydrogels in bio-pharma applications are reported. In particular, reported case histories are: i) the size calculation of micro-particles obtained by ultrasound assisted atomization; ii) the release kinetics from core-shell micro-particles, iii) the solidification behavior of blends of synthetic and natural polymers for gel paving of blood vessels, iv) the drug release from hydrogel-based tablets. This material can be seen as a guide toward the use of mathematical modeling in bio-pharma applications.
Liver injury after methylprednisolone pulses: A disputable cause of hepatotoxicity. A case series and literature review
Authors: Zoubek Miguel Eugenio , Pinazo-Bandera José , Ortega-Alonso Aida , Hernández Nelia , Crespo Javier , Contreras Fernando , Medina-Cáliz Inmaculada , Sanabria-Cabrera Judith , Sanjuan-Jiménez Rocío , González-Jiménez Andrés , García-Cortés Miren , Lucena M Isabel , Andrade Raúl J , Robles-Díaz Mercedes 
Published: March 2019

Background and ObjectivesCorticosteroids are often empirically used to treat idiosyncratic hepatotoxicity with severe features. Interestingly, intravenous methylprednisolone (MP) is increasingly being recognized as being responsible for liver injury. We aimed to characterize MP‐induced liver injury by analyzing demographical, clinical, laboratory and outcome data of three MP‐induced hepatotoxicity cases and compared this information with that of previously published cases.Case seriesThree females with multiple sclerosis (MS) were treated intravenously with MP, mean daily dose 767 mg. Liver damage occurred 2 to 6 weeks after exposure. Severity was mild to moderate. Two patients suffered positive rechallenge.Literature reviewWe identified 50 published cases of MP hepatotoxicity. Most of these cases were female (86%) and main treatment indications were MS (29 cases) and Graves' ophthalmopathy (13 cases). Hepatocellular damage predominated and mean time to onset was 6 weeks. Four patients died and rechallenge occurred in 19 cases.ConclusionMP pulses can induce severe liver injury, often with an autoimmune phenotype, particularly in patients with MS and Graves' ophthalmopathy. Consequently, these patient groups should have liver tests monitored when treated with MP to provide safer patient care.
Incidence, Mechanisms, and Severity of Game-Related High School Football Injuries Across Artificial Turf Systems of Various Infill Weights
Authors: Meyers Michael C. 
Published: March 2019

Background: Artificial turf surfaces are developed to duplicate playing characteristics of natural grass. With the newer generations of sand and rubber infill systems, the infill is a common component that varies between fields and is a critical factor that could influence the player-surface interaction. Because the influence of infill weight on sport trauma is unknown, this study quantified football trauma in high schools in the United States across artificial turf systems of various infill weights. Hypothesis: Athletes would not experience differences in game-related injuries across artificial turf systems of various infill weights. Study Design: Cohort study; Level of evidence, 2. Methods: Artificial turf systems were divided into 4 sand/rubber infill weight groups by pounds per square foot: ≥9.0, 6.0-8.9, 3.0-5.9, and 0.0-2.9. A total of 57 high schools in 4 states participated over the course of 5 seasons. Outcomes of interest included injury severity, as a function of infill weight, across head, knee, and shoulder traumas; injury category; primary type of injury; tissue type; specific body location of injury; cleat design; environmental factors; and turf age. Data were subject to multivariate analyses of variance (MANOVAs) and Wilks λ criteria through use of general linear model procedures. Results: Of 1837 games documented, 528 games were played on infill weights of ≥9.0 lb/ft2, 521 on 6.0-8.9 lb/ft2, 525 on 3.0-5.9 lb/ft2, and 263 on 0.0-2.9 lb/ft2, with 4655 total injuries reported. MANOVAs indicated significant infill weight effects across injury severity ( F2,4648 = 5.087; P = .0001), with significant main effects also observed by injury category, tissue injured, lower extremity joint and muscle, cleat design, environmental factors, and turf age. Post hoc analyses indicated significantly lower ( P < .05 to .0001) total and substantial traumas, concussions, shoe-surface interaction during contact trauma, surface impacts, muscle-tendon overload, cleat design influence, adverse weather trauma, lower extremity injuries, and turf age effect while athletes were competing on the 6.0 to ≥9.0 lb/ft2 infill weight systems compared with the lighter infill weight systems. Conclusion: As infill surface weight decreased, football trauma significantly increased across numerous playing conditions. Based on findings, high school football fields should minimally contain 6.0 pounds of infill per square foot.
Rehabilitation Variability After Elbow Ulnar Collateral Ligament Reconstruction
Authors: Lightsey Harry M. , Trofa David P. , Sonnenfeld Julian J. , Swindell Hasani W. , Makhni Eric C. , Ahmad Christopher S. 
Published: March 2019

Background: Investigations specifically delineating the safest and most efficacious components of physical therapy after ulnar collateral ligament (UCL) reconstruction of the elbow are lacking. As such, while a number of recommendations regarding postoperative therapy have been published, no validated rehabilitation guidelines currently exist. Purpose: To assess the variability of rehabilitation protocols utilized by orthopaedic residency programs in the United States (US) and those described in the scientific literature. Study Design: Cross-sectional study. Methods: Online UCL reconstruction rehabilitation protocols from US orthopaedic programs and from the scientific literature were reviewed. A comprehensive scoring rubric was developed to assess each protocol for the presence of various rehabilitation components as well as the timing of their introduction. Results: Overall, 22 protocols (14%) from 155 US Electronic Residency Application Service (ERAS) orthopaedic programs and 8 protocols published in the scientific literature detailing UCL reconstruction postoperative rehabilitation were identified and reviewed. After reconstruction, the majority of ERAS and review article protocols (77% and 88%, respectively) advised immediate splinting at 90° of elbow flexion. The mean time to splint discontinuation across all protocols was 2.0 weeks (range, 1-3 weeks). There was considerable variability in elbow range of motion recommendations; however, most protocols detailed goals for full extension and full flexion (>130°) at a mean 5.3 weeks (range, 4-6 weeks) and 5.5 weeks (range, 4-6 weeks), respectively. Significant diversity in the inclusion and timing of strengthening, proprioceptive, and throwing exercises was also apparent. Thirteen ERAS (59%) and 7 review article (88%) protocols specifically mentioned return to competition as an endpoint. ERAS protocols permitted return to competition significantly earlier than review article protocols (29.6 vs 39.0 weeks, respectively; P = .042). Conclusion: There is notable variability in both the composition and timing of rehabilitation components across a small number of protocols available online. While our understanding of postoperative rehabilitation for UCL reconstruction evolves, outcome-based studies focused on identifying clinically beneficial modalities and metrics are necessary to enable meaningful standardization.
Relationship-Centered Advising in a Medical School Learning Community
Authors: Frosch Emily , Goldstein Mitchell 
Published: March 2019

Background: Medical schools are required to have formal advising structures; however, there are limited data on how to optimally meet that mandate. Learning communities (LC), with their emphasis on longitudinal relationships, offer a unique scaffold for advising. Program description: The Johns Hopkins School of Medicine (JHSOM) LC focuses on curricular and extracurricular longitudinal connections between students and advisors. A core component of the LC is a relationship-centered advising (RCA) model drawing from best practices in physician–patient relationships, life coaching, and social contract theories. The key elements of the model include dyadic and small group advising, while the LC structure allows for faculty development in these domains. Relationship-centered advising approaches the collaborative advising work between students and advisors through explicit valuing of personal experiences, mutual respect, and earned trust. Framing the advising relationship in this way allows it to grow with the student along their medical school journey. Program evaluation & results: Student and faculty satisfaction with this model is high. Data from annual, anonymous student evaluations consistently indicate high degree of trust in and satisfaction from these relationships. Discussion: Relationship-centered advising aims to create a relationally anchored platform on which students can develop their personal and professional identities. This LC-based advising model is adaptable across schools regardless of structure and resources.
Soluble urokinase plasminogen activator receptor for the prediction of ventilator-associated pneumonia
Authors: van Oort Pouline M. , Bos Lieuwe D. , Póvoa Pedro , Ramirez Paula , Torres Antoni , Artigas Antonio , Schultz Marcus J. , Martin-Loeches Ignacio 
Published: March 2019

IntroductionDiagnosing ventilator-associated pneumonia (VAP) remains challenging. Soluble urokinase plasminogen activator receptor (suPAR) has prognostic value in critically ill patients with systemic infection. We hypothesised that plasma suPAR levels accurately predict development of VAP.MethodsThis observational, multicentre, prospective cohort study compared patients at risk for VAP with a control group. Plasma and tracheal aspirate samples were collected. Plasma suPAR levels were measured on the day of diagnosis and 3 days before diagnosis.ResultsThe study included 24 VAP patients and 19 control patients. The suPAR concentration measured 3 days before diagnosis was significantly increased in VAP patientsversusmatched samples of control patients (area under the receiver operating characteristic curve (AUC) 0.68, 95% CI 0.52–1.00; p=0.04). Similar results were found on the day of diagnosis (AUC 0.77, 95% CI 0.6–0.93; p=0.01). Plasma suPAR was significantly higher in deceased patients (AUC 0.79, 95% CI 0.57–1.00; p<0.001). Combining suPAR with the Clinical Pulmonary Infection Score, C-reactive protein and/or procalcitonin led to a significantly increased discriminative accuracy for predicting VAP and an increased specificity.ConclusionssuPAR can be used to diagnose VAP with a fair diagnostic accuracy and has a moderate prognostic accuracy to be used in critically ill intensive care unit patients. Its performance improves when added to other clinically available biomarkers (C-reactive protein and procalcitonin) or scoring systems (Clinical Pulmonary Infection Score and Sepsis-related Organ Failure Assessment).
Personalised anti-inflammatory therapy for bronchiectasis and cystic fibrosis: selecting patients for controlled trials of neutrophil elastase inhibition
Authors: Keir Holly R. , Fong Christopher J. , Crichton Megan L. , Barth Philip , Chevalier Eric , Brady Gill , Kennedy Gwen , Zimmermann Johann , Bruijnzeel Piet L.B. , Dicker Alison J. , Chalmers James D. 
Published: March 2019

BackgroundNeutrophil elastase (NE) has been linked to lung neutrophil dysfunction in bronchiectasis and cystic fibrosis (CF), making NE inhibition a potential therapeutic target. NE inhibitor trials have given mixed result perhaps because not all patients have elevated airway NE activity.MethodsWe tested whether a single baseline sputum NE measurement or a combination of clinical parameters could enrich patient populations with elevated NE activity for “personalised medicine”. Intra- and interindividual variations of total and active NE levels in induced sputum from patients with CF or bronchiectasis were monitored over 14 days. Patients with established CF and bronchiectasis (n=5 per group) were recruited. NE was measured using three different methods: one total and two active NE assays. Subsequently, we analysed the association between clinical parameters and NE from a large bronchiectasis cohort study (n=381).ResultsAll three assays showed a high degree of day-to-day variability (0–233% over 14 days). There were strong correlations found between all assays (p<0.0001). Despite high day-to-day variability, patients could be stratified into “high” or “low” groups based on moderate cut-off levels. In the bronchiectasis cohort study, factors most associated with high sputum NE levels were:Pseudomonas aeruginosainfection (β-estimate 11.5, 95% CI −6.0–29.0), sputum colour (β-estimate 10.4, 95% CI 4.3–16.6), Medical Research Council dyspnoea score (β-estimate 6.4, 95% CI 1.4–11.4) and exacerbation history (β-estimate 3.4, 95% CI 1.4–5.3). Collectively,P. aeruginosainfection, sputum colour and exacerbation frequency provided the greatest specificity for “high” NE (98.7%, 95% CI 7.0–99.6%).ConclusionThese results show that patients with bronchiectasis and CF can be effectively divided into “high” or “low” groups, based on sputum NE assays or clinical inclusion criteria.
Efficacy of Pharmacological Therapies for the Prevention of Fractures in Postmenopausal Women: A Network Meta-Analysis
Authors: Barrionuevo Patricia , Kapoor Ekta , Asi Noor , Alahdab Fares , Mohammed Khaled , Benkhadra Khalid , Almasri Jehad , Farah Wigdan , Sarigianni Maria , Muthusamy Kalpana , Al Nofal Alaa , Haydour Qusay , Wang Zhen , Murad Mohammad Hassan 
Published: March 2019

Abstract

Background
Osteoporosis and osteopenia are associated with increased fracture incidence in postmenopausal women. We aimed to determine the comparative effectiveness of various available pharmacological therapies.

Methods
We searched MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials, ISI Web of Science, and Scopus for randomized controlled trials that enrolled postmenopausal women with primary osteoporosis and evaluated the risk of hip, vertebral, or nonvertebral fractures. A network meta-analysis was conducted using the multivariate random effects method.

Results
We included 107 trials (193,987 postmenopausal women; mean age, 66 years; 55% white; median follow-up, 28 months). A significant reduction in hip fractures was observed with romosozumab, alendronate, zoledronate, risedronate, denosumab, estrogen with progesterone, and calcium in combination with vitamin D. A significant reduction in nonvertebral fractures was observed with abaloparatide, romosozumab, denosumab, teriparatide, alendronate, risedronate, zoledronate, lasofoxifene, tibolone, estrogen with progesterone, and vitamin D. A significant reduction in vertebral fractures was observed with abaloparatide, teriparatide, parathyroid hormone 1-84, romosozumab, strontium ranelate, denosumab, zoledronate, risedronate, alendronate, ibandronate, raloxifene, bazedoxifene, lasofoxifene, estrogen with progesterone, tibolone, and calcitonin. Teriparatide, abaloparatide, denosumab, and romosozumab were associated with the highest relative risk reductions, whereas ibandronate and selective estrogen receptor modulators had lower efficacy. The evidence for the treatment of fractures with vitamin D and calcium remains limited despite numerous large trials.

Conclusions
This network meta-analysis provides comparative effective estimates for the various available treatments to reduce the risk of fragility fractures in postmenopausal women.
Comparison of Collapsibility of the Human Upper Airway During Anesthesia and During Sleep
Authors: Maddison Kathleen J. , Walsh Jennifer H. , Shepherd Kelly L. , Bharat Chrianna , Lawther Bradley K. , Platt Peter R. , Eastwood Peter R. , Hillman David R. 
Published: March 2019

BACKGROUND:
The propensities for the upper airway to collapse during anesthesia and sleep are related, although much of our understanding of this relationship has been inferred from clinical observation and indirect measures such as the apnea–hypopnea index. The aim of this study was to use an identical, rigorous, direct measure of upper airway collapsibility (critical closing pressure of the upper airway) under both conditions to allow the magnitude of upper airway collapsibility in each state to be precisely compared.

METHODS:
Ten subjects (8 men and 2 women; mean ± SD: age, 40.4 ± 12.1 years; body mass index, 28.5 ± 4.0 kg/m2) were studied. Critical closing pressure of the upper airway was measured in each subject on separate days during (1) propofol anesthesia and (2) sleep.

RESULTS:
Critical closing pressure of the upper airway measurements were obtained in all 10 subjects during nonrapid eye movement sleep and, in 4 of these 10 subjects, also during rapid eye movement sleep. Critical closing pressure of the upper airway during anesthesia was linearly related to critical closing pressure of the upper airway during nonrapid eye movement sleep (r = 0.64 [95% CI, 0.02–0.91]; n = 10; P = .046) with a similar tendency in rapid eye movement sleep (r = 0.80 [95% CI, −0.70 to 0.99]; n = 4; P = .200). However, critical closing pressure of the upper airway during anesthesia was systematically greater (indicating increased collapsibility) than during nonrapid eye movement sleep (2.1 ± 2.2 vs −2.0 ± 3.2 cm H2O, respectively, n = 10; within-subject mean difference, 4.1 cm H2O [95% CI, 2.32–5.87]; P < .001) with a similar tendency during rapid eye movement sleep (1.6 ± 2.4 vs −1.9 ± 4.3 cm H2O, respectively, n = 4; unadjusted difference, 3.5 cm H2O [95% CI, −0.95 to 7.96]; P = .087).

CONCLUSIONS:
These results demonstrate that the magnitude of upper airway collapsibility during anesthesia and sleep is directly related. However, the upper airway is systematically more collapsible during anesthesia than sleep, suggesting greater vulnerability to upper airway obstruction in the anesthetized state.
Prospective Investigation of the Operating Room Time-Out Process
Authors: Freundlich Robert E. , Bulka Catherine M. , Wanderer Jonathan P. , Rothman Brian S. , Sandberg Warren S. , Ehrenfeld Jesse M. 
Published: March 2019

BACKGROUND:
Although the surgical pause or time-out is a required part of most hospitals’ standard operating procedures, little is known about the quality of execution of the time-out in routine clinical practice. An interactive electronic time-out was implemented to increase surgical team compliance with the time-out procedure and to improve communication among team members in the operating room. We sought to identify nonroutine events that occur during the time-out procedure in the operating room, including distractions and interruptions, deviations from protocol, and the problem-solving strategies used by operating room team members to mitigate them.

METHODS:
Direct observations of surgical time-outs were performed on 166 nonemergent surgeries in 2016. For each time-out, the observers recorded compliance with each step, any nonroutine events that may have occurred, and whether any operating room team members were distracted.

RESULTS:
The time-out procedure was performed before the first incision in 100% of cases. An announcement was made to indicate the start of the time-out procedure in 163 of 166 observed surgeries. Most observed time-outs were completed in <1 minute. Most time-outs were completed without interruption (92.8%). The most common reason for an interruption was to verify patient information. Ten time-out procedures were stopped due to a safety concern. At least 1 member of the operating room team was actively distracted in 10.2% of the time-out procedures observed.

CONCLUSIONS:
Compliance with preincision time-outs is high at our institution, and nonroutine events are a rare occurrence. It is common for ≥1 member of the operating room team to be actively distracted during time-out procedures, even though most time-outs are completed in under 1 minute. Despite distractions, there were no wrong-site or wrong-person surgeries reported at our hospital during the study period. We conclude that the simple act of performing a preprocedure checklist may be completed quickly, but that distractions are common.
Remote Ischemic Preconditioning Prevents Postoperative Acute Kidney Injury After Open Total Aortic Arch Replacement: A Double-Blind, Randomized, Sham-Controlled Trial
Authors: Zhou Hui , Yang Lijing , Wang Guyan , Zhang Congya , Fang Zhongrong , Lei Guiyu , Shi Sheng , Li Jun 
Published: March 2019

BACKGROUND:
Acute kidney injury is a common complication after open total aortic arch replacement but lacks effective preventive strategies. Remote ischemic preconditioning has controversial results of its benefit to the kidney and may perform better in high-risk patients of acute kidney injury. We investigated whether remote ischemic preconditioning would prevent postoperative acute kidney injury after open total aortic arch replacement.

METHODS:
We enrolled 130 patients scheduled for open total aortic arch replacement and randomized them to receive either remote ischemic preconditioning (4 cycles of 5-minute right upper limb ischemia and 5-minute reperfusion) or sham preconditioning (4 cycles of 5-minute right upper limb pseudo ischemia and 5-minute reperfusion), both via blood pressure cuff inflation and deflation. The primary end point was the incidence of acute kidney injury within 7 days after the surgery defined by the Kidney Disease: Improving Global Outcomes criteria. Secondary end point included short-term clinical outcomes.

RESULTS:
Significantly fewer patients developed postoperative acute kidney injury with remote ischemic preconditioning compared with sham (55.4% vs 73.8%; absolute risk reduction, 18.5%; 95% CI, 2.3%–34.6%; P = .028). Remote ischemic preconditioning significantly reduced acute kidney injury stage II–III (10.8% vs 35.4%; P = .001). Remote ischemic preconditioning shortened the mechanical ventilation duration (18 hours [interquartile range, 14–33] versus 25 hours [interquartile range, 17–48]; P = .01), whereas no significant differences were observed between groups in other secondary outcomes.

CONCLUSIONS:
Remote ischemic preconditioning prevented acute kidney injury after open total aortic arch replacement, especially severe acute kidney injury and shortened mechanical ventilation duration. The observed renoprotective effects of remote ischemic preconditioning require further investigation in both clinical research and the underlying mechanism.