bluuebunny/crossref_metadata_2025 huggingface dataset:
Forage silica and water content control dental surface texture in guinea pigs and provide implications for dietary reconstruction
Authors: Winkler Daniela E. , Schulz-Kornas Ellen , Kaiser Thomas M. , De Cuyper Annelies , Clauss Marcus , Tütken Thomas
Published: January 2019

Significance

Ingesta leave characteristic wear features on the tooth surface, which enable us to reconstruct the diet of extant and fossil vertebrates. However, whether dental wear is caused by internal (phytoliths) or external (mineral dust) silicate abrasives is controversially debated in paleoanthropology and biology. To assess this, we fed guinea pigs plant forages of increasing silica content (lucerne < grass < bamboo) without any external abrasives, both in fresh and dried state. Abrasiveness and enamel surface wear increased with higher forage phytolith content. Additionally, water loss altered plant material properties. Dental wear of fresh grass feeding was similar to lucerne browsing, while dried grass caused more grazer-like wear. Fresh grass grazing could be confounded with browsing, being a major pitfall for paleodietary reconstructions.
Temporal variabilities of δ13C and δ15N in an ecosystem from the Central-East Gulf of California: estimating trophic relationships
Authors: Del Rio-Salas Martha , Martínez-Durazo Angel , Castro-Longoria Reina , Jara-Marini Martín E.
Published: January 2019

The foodweb of El Tóbari Lagoon (central-east Gulf of California) was studied for four seasons through the carbon and nitrogen isotopic characterization of primary producers, invertebrates, fish, birds and potential food sources. The range of δ13C measured was much wider for potential food sources than for consumers. Many organisms presented enrichments of δ13C and δ15N values. There was a clear trend toward increasing δ13C and δ15N from base organisms to top-predators in the four seasons. The isotopic and percentage of contribution data confirmed that suspended particulate organic matter and phytoplankton are the main organic source supporting the foodweb. Our results also imply the occurrence of a nutrient transfer from zooplankton to some invertebrates and juvenile fishes. Consumers were composed in four trophic levels, with trophic level 2 occupied by zooplankton and filter-feeders and trophic level 4 occupied by carnivorous fish and most bird species. Carnivorous fish exhibited dietary similarities by a considerable sharing of resources, which could be related to the abundance of possible prey, between invertebrates and juvenile fishes. Crustaceans and fish represented the main food sources of birds, although some birds showed more dietary variation (marine and offshore prey).
Phosphatase Shp2 exacerbates intestinal inflammation by disrupting macrophage responsiveness to interleukin-10
Authors: Xiao Peng , Zhang Huilun , Zhang Yu , Zheng Mingzhu , Liu Rongbei , Zhao Yuan , Zhang Xue , Cheng Hongqiang , Cao Qian , Ke Yuehai
Published: January 2019

Inflammatory cytokines produced by activated macrophages largely contribute to the pathological signs of inflammatory bowel disease (IBD). Interleukin-10 (IL-10) is the predominant anti-inflammatory cytokine in the intestine, and its therapeutic efficacy for IBD has been clinically tested. Nevertheless, how the function of IL-10 is regulated in the intestinal microenvironment remains unknown, which largely hinders the further development of IL-10–based therapeutic strategies. Here, we found that the expression of phosphatase Shp2 was increased in colonic macrophages and blood monocytes from IBD patients compared with those from healthy controls. Shp2 deficiency in macrophages protects mice from colitis and colitis-driven colon cancer. Mechanistically, Shp2 disrupts IL-10–STAT3 signaling and its dependent anti-inflammatory response in human and mouse macrophages. Furthermore, a Shp2-inducing role of TNF-α is unveiled in our study. Collectively, our work identifies Shp2 as a detrimental factor for intestinal immune homeostasis and hopefully will be helpful in the future exploitation of IL-10 immunotherapy for IBD.
Cycles of singularities appearing in the resolution problem in positive characteristic
Authors: Hauser Herwig , Perlega Stefan
Published: January 2019

We present a hypersurface singularity in positive characteristic which is defined by a purely inseparable power series, and a sequence of point blowups so that, after applying the blowups to the singularity, the same type of singularity reappears after the last blowup, with just certain exponents of the defining power series shifted upwards. The construction hence yields a cycle. Iterating this cycle leads to an infinite increase of the residual order of the defining power series. This disproves a theorem claimed by Moh about the stability of the residual order under sequences of blowups. It is not a counterexample to the resolution in positive characteristic since larger centers are also permissible and prevent the phenomenon from happening.
KASPspoon: an in vitro and in silico PCR analysis tool for high-throughput SNP genotyping
Authors: Alsamman Alsamman M , Ibrahim Shafik D , Hamwieh Aladdin
Published: January 2019

Motivation

Fine mapping becomes a routine trial following quantitative trait loci (QTL) mapping studies to shrink the size of genomic segments underlying causal variants. The availability of whole genome sequences can facilitate the development of high marker density and predict gene content in genomic segments of interest. Correlations between genetic and physical positions of these loci require handling of different experimental genetic data types, and ultimately converting them into positioning markers using a routine and efficient tool.

Results

To convert classical QTL markers into KASP assay primers, KASPspoon simulates a PCR by running an approximate-match searching analysis on user-entered primer pairs against the provided sequences, and then comparing in vitro and in silico PCR results. KASPspoon reports amplimers close to or adjoining genes/SNPs/simple sequence repeats and those that are shared between in vitro and in silico PCR results to select the most appropriate amplimers for gene discovery. KASPspoon compares physical and genetic maps, and reports the primer set genome coverage for PCR-walking. KASPspoon could be used to design KASP assay primers to convert QTL acquired by classical molecular markers into high-throughput genotyping assays and to provide major SNP resource for the dissection of genotypic and phenotypic variation. In addition to human-readable output files, KASPspoon creates Circos configurations that illustrate different in silico and in vitro results.

Availability and implementation

Code available under GNU GPL at (http://www.ageri.sci.eg/index.php/facilities-services/ageri-softwares/kaspspoon).

Supplementary information

Supplementary data are available at Bioinformatics online.
Statistical force-field for structural modeling using chemical cross-linking/mass spectrometry distance constraints
Authors: Ferrari Allan J R , Gozzo Fabio C , Martínez Leandro
Published: January 2019

Motivation

Chemical cross-linking/mass spectrometry (XLMS) is an experimental method to obtain distance constraints between amino acid residues which can be applied to structural modeling of tertiary and quaternary biomolecular structures. These constraints provide, in principle, only upper limits to the distance between amino acid residues along the surface of the biomolecule. In practice, attempts to use of XLMS constraints for tertiary protein structure determination have not been widely successful. This indicates the need of specifically designed strategies for the representation of these constraints within modeling algorithms.

Results

A force-field designed to represent XLMS-derived constraints is proposed. The potential energy functions are obtained by computing, in the database of known protein structures, the probability of satisfaction of a topological cross-linking distance as a function of the Euclidean distance between amino acid residues. First, the strategy suggests that XL constraints should be set to shorter distances than usually assumed. Second, the complete statistical force-field improves the models obtained and can be easily incorporated into current modeling methods and software. The force-field was implemented and is distributed to be used within the Rosetta ab initio relax protocol.

Availability and implementation

Force-field parameters and usage instructions are freely available online (http://m3g.iqm.unicamp.br/topolink/xlff).

Supplementary information

Supplementary data are available at Bioinformatics online.
Late-career Physicians Prescribe Longer Courses of Antibiotics
Authors: Fernandez-Lazaro Cesar I , Brown Kevin A , Langford Bradley J , Daneman Nick , Garber Gary , Schwartz Kevin L
Published: January 2019

Background

Antibiotic duration is often longer than necessary. Understanding the reasons for variability in antibiotic duration can inform interventions to reduce prolonged antibiotic use. We aim to describe patterns of interphysician variability in prescribed antibiotic treatment durations and determine physician predictors of prolonged antibiotic duration in the community setting.

Methods

We performed a retrospective cohort analysis of family physicians in Ontario, Canada, between 1 March 2016 and 28 February 2017, using the Xponent dataset from IQVIA. The primary outcome was proportion of prolonged antibiotic course prescribed, defined as >8 days of therapy. We used multivariable logistic regression models, with generalized estimating equations to account for physician-level clustering to evaluate predictors of prolonged antibiotic courses.

Results

There were 10 616 family physicians included in the study, prescribing 5.6 million antibiotic courses. There was substantial interphysician variability in the proportion of prolonged antibiotic courses (median, 33.3%; interdecile range, 13.5%–60.3%). In the multivariable regression model, later physician career stage, rural location, and a larger pediatric practice were significantly associated with greater use of prolonged courses. Prolonged courses were more likely to be prescribed by late-career physicians (adjusted odds ratio [aOR], 1.48; 95% confidence interval, 1.38–1.58) and mid-career physicians (aOR, 1.25; 1.16–1.34) when compared to early-career physicians.

Conclusions

We observed substantial variability in prescribed antibiotic duration across family physicians, with durations particularly long among late-career physicians. These findings highlight opportunities for community antimicrobial stewardship interventions to improve antibiotic use by addressing practice differences in later-career physicians.
Co-circulation of Multidrug-resistant Shigella Among Men Who Have Sex With Men in Australia
Authors: Ingle Danielle J , Easton Marion , Valcanis Mary , Seemann Torsten , Kwong Jason C , Stephens Nicola , Carter Glen P , Gonçalves da Silva Anders , Adamopoulos James , Baines Sarah L , Holt Kathryn E , Chow Eric P F , Fairley Christopher K , Chen Marcus Y , Kirk Martyn D , Howden Benjamin P , Williamson Deborah A
Published: January 2019

Background

In urban Australia, the burden of shigellosis is either in returning travelers from shigellosis-endemic regions or in men who have sex with men (MSM). Here, we combine genomic data with comprehensive epidemiological data on sexual exposure and travel to describe the spread of multidrug-resistant Shigella lineages.

Methods

A population-level study of all cultured Shigella isolates in the state of Victoria, Australia, was undertaken from 1 January 2016 through 31 March 2018. Antimicrobial susceptibility testing, whole-genome sequencing, and bioinformatic analyses of 545 Shigella isolates were performed at the Microbiological Diagnostic Unit Public Health Laboratory. Risk factor data on travel and sexual exposure were collected through enhanced surveillance forms or by interviews.

Results

Rates of antimicrobial resistance were high, with 17.6% (95/541) and 50.6% (274/541) resistance to ciprofloxacin and azithromycin, respectively. There were strong associations between antimicrobial resistance, phylogeny, and epidemiology. Specifically, 2 major MSM-associated lineages were identified: a Shigellasonnei lineage (n = 159) and a Shigella flexneri 2a lineage (n = 105). Of concern, 147/159 (92.4%) of isolates within the S. sonnei MSM-associated lineage harbored mutations associated with reduced susceptibility to recommended oral antimicrobials: namely, azithromycin, trimethoprim-sulfamethoxazole, and ciprofloxacin. Long-read sequencing demonstrated global dissemination of multidrug-resistant plasmids across Shigella species and lineages, but predominantly associated with MSM isolates.

Conclusions

Our contemporary data highlight the ongoing public health threat posed by resistant Shigella, both in Australia and globally. Urgent multidisciplinary public health measures are required to interrupt transmission and prevent infection.
The Effects of Hepatitis C Treatment Eligibility Criteria on All-cause Mortality Among People With Human Immunodeficiency Virus
Authors: Breskin Alexander , Westreich Daniel , Hurt Christopher B , Cole Stephen R , Hudgens Michael G , Seaberg Eric C , Thio Chloe L , Tien Phyllis C , Adimora Adaora A
Published: January 2019

Background

The cost of direct-acting antivirals (DAAs) for hepatitis C virus (HCV) prompted many payers to restrict treatment to patients who met non–evidence-based criteria. These restrictions have implications for survival of people with HCV, especially for people with human immunodeficiency virus (HIV)/HCV coinfection who are at high risk for liver disease progression. The goal of this work was to estimate the effects of DAA access policies on 10-year all-cause mortality among people with HIV.

Methods

The study population included 3056 adults with HIV in the Women’s Interagency HIV Study and Multicenter AIDS Cohort Study from 1 October 1994 through 30 September 2015. We used the parametric g-formula to estimate 10-year all-cause mortality under DAA access policies that included treating (i) all people with HCV; (ii) only people with suppressed HIV; (iii) only people with severe fibrosis; and (iv) only people with HIV suppression and severe fibrosis.

Results

The 10-year risk difference of treating all coinfected persons with DAAs compared with no treatment was –3.7% (95% confidence interval [CI], –9.1% to .6%). Treating only those with suppressed HIV and severe fibrosis yielded a risk difference of –1.1% (95% CI, –2.8% to .6%), with 51% (95% CI, 38%–59%) of coinfected persons receiving DAAs. Treating a random selection of 51% of coinfected persons at baseline decreased the risk by 1.9% (95% CI, –4.7% to .3%).

Conclusions

Restrictive DAA access policies may decrease survival compared to treating similar proportions of people with HIV/HCV coinfection with DAAs at random. These findings suggest that lives could be saved by thoughtfully revising access policies.
A comparison of pump-controlled retrograde trial off to arterio-venous bridging for weaning from venoarterial extracorporeal membrane oxygenation†
Authors: Pandya Nischal R , Daley Michael , Mattke Adrian , Shikata Fumiaki , Betts Kim , Haisz Emma , Black Anthony , Anderson Benjamin , Alphonso Nelson , Venugopal Prem
Published: January 2019

OBJECTIVES

The aim of the study is to compare a technique of pump-controlled retrograde trial off (PCRTO) to insertion of an arterio-venous (AV) bridge to conduct a trial from venoarterial extracorporeal membrane oxygenation (VA ECMO).

METHODS

We studied all patients who were weaned from VA ECMO using either PCRTO or AV bridging from November 2014 to April 2018. Demographic data, indications for ECMO, duration of ECMO, duration of trial period off ECMO and survival were compared between the 2 groups.

RESULTS

Seventy-nine patients were placed on VA ECMO from November 2014 to April 2018, of whom, 51 (65%) patients met the study inclusion criteria: 31 (61%) patients who had a trial period from VA ECMO using PCRTO and 20 (39%) patients who were weaned using an AV bridge. The indications for ECMO included cardiac (n = 16 and 11, respectively) and non-cardiac aetiologies (n = 15 and 9, respectively). There was 1 death in each group. The duration of the trial off VA ECMO was significantly shorter in the PCRTO group (median = 88.0 vs 196.6 min, P < 0.001). There were 2 conversions from PCRTO to AV bridging during the trial period off ECMO (2.9-kg neonate following a Norwood procedure and 2.2-kg patient following repair of ectopia cordis).

CONCLUSIONS

PCRTO is a safe, simple and reproducible approach for enabling a trial period while preserving the circuit during weaning from VA ECMO. In our study, the duration of the trial period off VA ECMO was significantly shorter in the PCRTO group. PCRTO avoids manipulation of the ECMO circuit, provides a ‘stress test’ to evaluate cardiorespiratory reserve during the trial period off ECMO, is applicable for a wide variety of cardiac and non-cardiac indications and facilitates multiple attempts at weaning from ECMO.
Risk of death without appropriate defibrillator shock in patients with advanced renal dysfunction
Authors: Goldenberg Ido , Mor Tal , Nof Eyal , Younis Arwa , Berkovitch Anat , Rosso Raphael , Barsheshet Alon , Suleiman Mahmoud , Beinart Roy
Published: January 2019

Aims

Heart failure patients with advanced chronic kidney disease (CKD) may experience an increased rate of non-arrhythmic mortality due to associated comorbidities. We aimed to evaluate the risk of mortality without appropriate implantable cardioverter-defibrillator (ICD) shocks in this high-risk population.

Methods and results

The study population comprised 3542 patients who received an ICD, were enrolled, and prospectively followed-up in the Israeli ICD registry. Study patients were categorized into two groups: those with advanced CKD [defined by a glomerular filtration rate of <30 mL/min/1.73 m2 or being on dialysis at time of implantation (n = 197)], and those without advanced CKD (n = 3344). The primary endpoint was the risk of death without receiving appropriate ICD shock. Kaplan–Meier survival analysis showed that at 5 years of follow-up the rates of death without prior ICD shock were significantly higher in the advanced kidney disease group (46%) compared with the non-advanced CKD group (19%; log-rank P-value <0.001). Consistently, multivariate analysis showed that the risk of death without receiving appropriate ICD shock therapy at 5 years was 2.5-fold (P < 0.001) higher among advanced CKD patients. In contrast, the rate of appropriate ICD shock therapy at 5 years among advanced CKD patients was only 9%, with a very high mortality rate (63%) within 3.5 years subsequent to shock therapy.

Conclusion

Nearly one-half of ICD with advanced CKD die within 5 years without receiving an appropriate ICD shock. These findings stress the importance of appropriate patient selection for primary ICD implantation in this high-risk population.
Extensive Serological Survey of Multiple African Nonhuman Primate Species Reveals Low Prevalence of Immunoglobulin G Antibodies to 4 Ebola Virus Species
Authors: Ayouba Ahidjo , Ahuka-Mundeke Steve , Butel Christelle , Mbala Kingebeni Placide , Loul Severin , Tagg Nikki , Villabona-Arenas Christian-Julian , Lacroix Audrey , Ndimbo-Kumugo Simon-Pierre , Keita Alpha K , Toure Abdoulaye , Couacy-Hymann Emmanuel , Calvignac-Spencer Sebastien , Leendertz Fabian H , Formenty Pierre , Delaporte Eric , Muyembe-Tamfum Jean-Jacques , Mpoudi Ngole Eitel , Peeters Martine
Published: January 2019

Bats are considered a reservoir species for Ebola viruses, but nonhuman primates (NHPs) have represented a source of infection in several outbreaks in humans. Here we report serological screening of blood or fecal samples from monkeys (n = 2322) and apes (n = 2327). Thirty-six NHP species from Cameroon, Democratic Republic of the Congo, and Ivory Coast were tested with a sensitive and specific Luminex-based assay for immunoglobulin G antibodies to 4 Ebola virus species. Using the simultaneous presence of antibodies to nucleoproteins and glycoproteins to define positivity, we showed that specific Ebola virus antibodies are not widespread among NHPs. Only 1 mustached monkey (Cercopithecus cephus) from Cameroon was positive for Sudan ebolavirus. These observations support that NHPs are most likely intermediate hosts for Ebola viruses. With the increasing frequency of Ebola outbreaks, it is crucial to identify the animal reservoir and understand the ecology of Ebola viruses to inform disease control.
WALLABY Early Science – II. The NGC 7232 galaxy group
Authors: Lee-Waddell K , Koribalski B S , Westmeier T , Elagali A , For B-Q , Kleiner D , Madrid J P , Popping A , Reynolds T N , Rhee J , Serra P , Shao L , Staveley-Smith L , Wang J , Whiting M T , Wong O I , Allison J R , Bhandari S , Collier J D , Heald G , Marvil J , Ord S M
Published: January 2019

We report on neutral hydrogen (H i) observations of the NGC 7232 group with the Australian Square Kilometre Array Pathfinder (ASKAP). These observations were conducted as part of the Wide-field ASKAP L-Band Legacy All-sky Blind surveY (WALLABY) Early Science program with an array of 12 ASKAP antennas equipped with Phased Array Feeds, which were used to form 36 beams to map a field of view of 30 deg2. Analysing a subregion of the central beams, we detect 17 H i sources. Eleven of these detections are identified as galaxies and have stellar counterparts, of which five are newly resolved H i galaxy sources. The other six detections appear to be tidal debris in the form of H i clouds that are associated with the central triplet, NGC 7232/3, comprising the spiral galaxies NGC 7232, NGC 7232B, and NGC 7233. One of these H i clouds has a mass of MH i ∼ 3 × 108 M⊙ and could be the progenitor of a long-lived tidal dwarf galaxy. The remaining H i clouds are likely transient tidal knots that are possibly part of a diffuse tidal bridge between NGC 7232/3 and another group member, the lenticular galaxy IC 5181.
The morpho-kinematics of the circumstellar envelope around the AGB star EP Aqr
Authors: Hoai D T , Nhung P T , Tuan-Anh P , Darriulat P , Diep P N , Le Bertre T , Phuong N T , Thai T T , Winters J M
Published: January 2019

ALMA observations of CO(1–0) and CO(2–1) emissions of the circumstellar envelope of EP Aqr, an oxygen-rich asymptotic giant branch star, are reported. A thorough analysis of their properties is presented using an original method based on the separation of the data cube into a low-velocity component associated with an equatorial outflow and a faster component associated with a bipolar outflow. A number of important and new results are obtained concerning the distribution in space of the effective emissivity, the temperature, the density, and the flux of matter. A mass-loss rate of (1.6 ± 0.4)×10−7 solar masses per year is measured. The main parameters defining the morphology and kinematics of the envelope are evaluated and uncertainties inherent to de-projection are critically discussed. Detailed properties of the equatorial region of the envelope are presented including a measurement of the line width and a precise description of the observed inhomogeneity of both morphology and kinematics. In particular, in addition to the presence of a previously observed spiral enhancement of the morphology at very small Doppler velocities, a similarly significant but uncorrelated circular enhancement of the expansion velocity is revealed, both close to the limit of sensitivity. The results of the analysis place significant constraints on the parameters of models proposing descriptions of the mass-loss mechanism, but cannot choose among them with confidence.
Exchange Arrangements Entering the Twenty-First Century: Which Anchor will Hold?*
Authors: Ilzetzki Ethan , Reinhart Carmen M , Rogoff Kenneth S
Published: January 2019

This article provides a comprehensive history of anchor or reference currencies, exchange rate arrangements, and a new measure of foreign exchange restrictions for 194 countries and territories over 1946–2016. We find that the often cited post–Bretton Woods transition from fixed to flexible arrangements is overstated; regimes with limited flexibility remain in the majority. Even if central bankers’ communications jargon has evolved considerably in recent decades, it is apparent that many still place a large implicit weight on the exchange rate. The U.S. dollar scores as the world's dominant anchor currency by a very large margin. By some metrics, its use is far wider today than 70 years ago. In contrast, the global role of the euro appears to have stalled. We argue that in addition to the usual safe assets story, the record accumulation of reserves since 2002 may also have to do with many countries’ desire to stabilize exchange rates in an environment of markedly reduced exchange rate restrictions or, more broadly, capital controls: an important amendment to the conventional portrayal of the macroeconomic trilemma.
Use of population data for assessing trends in work-related asthma mortality
Authors: Mazurek Jacek M. , Henneberger Paul K.
Published: January 2019

Purpose of review

Work-related asthma has been associated with poorer asthma control and frequent unscheduled healthcare visits, and can be fatal. Case reports of work-related asthma deaths are rare, but can initiate efforts to prevent additional cases. We reviewed relevant literature and data sources to evaluate whether analyzing mortality data at the population level can help identify potential sources of exposures that contribute to work-related asthma.

Recent findings

A limited number of population-based studies have addressed work-related asthma mortality. Data on asthma mortality are derived from death certificates using the International Classification of Diseases (ICD) as a standard for coding cause. However, no discrete code for work-related asthma is available. Analysis of asthma mortality relative to industries and occupations appears to identify high-risk jobs that were not identified by analyzing asthma morbidity data.

Beyond recognized work-related asthma deaths, it is possible that occupational exposures have contributed to other asthma deaths that have gone unnoticed and could potentially be identified by the analysis of mortality data at the population level. Such analyses in the United States appear to assist in recognizing high-risk occupations and industries. Additional analyses would be possible if a work-related asthma ICD code were available.
The impact of exercise on asthma
Authors: Lang Jason E.
Published: January 2019

Purpose of review

Asthma is one of the most common chronic diseases in children and adults in developed countries around the world. Despite international treatment guidelines, poor asthma control remains a frequent problem leading to missed school and work, and emergency room visits and hospitalizations. Many patients with asthma report exercise as a trigger for their asthma, which likely leads to exercise avoidance as a means to control symptoms. Evolving research has suggested that routine exercise may actually help improve some aspects of asthma control. This review discusses the recent research addressing how routine exercise affects important asthma-related outcomes including symptoms, lung function and quality of life.

Recent findings

Several systematic reviews and meta-analyses have been conducted in recent years, which strongly support the safety of routine exercise in children and adults with asthma. Exercise appears to favor improvements in aerobic fitness, asthma symptoms and quality of life, but results so far are less consistent in demonstrating improvements to lung function and airway hyperresponsiveness.

In addition to routine management guidelines, clinicians should recommend for their patients with asthma routine exercise for its general health benefits and likely improvement in asthma symptoms and quality of life.
Long-Term Patient-Reported Functional Outcome of Polytraumatized Patients With Operatively Treated Pelvic Fractures
Authors: Bott Alasdair , Odutola Adekoyejo , Halliday Ruth , Acharya Mehool R. , Ward Anthony , Chesser Timothy J. S.
Published: January 2019

Objectives:

To report the long-term functional outcome of a cohort of patients with operatively treated unstable pelvic fractures using validated patient-reported outcome measures.

Design:

Long-term observational study using prospective and retrospective data.

Setting:

Tertiary referral pelvic trauma center, Bristol, United Kingdom.

Patients:

Seventy-four polytraumatized patients with operatively treated unstable pelvic ring injuries (50 OTA/AO type B and 24 OTA/AO type C, mean Injury Severity Score 17) treated between 1994 and 2005.

Intervention:

Sixty-four (86%) patients were treated with internal fixation. The remaining 10 patients (14%) were treated with either combined percutaneous posterior fixation and anterior external fixation or external fixation in isolation.

Main Outcome:

Patient-reported functional outcome.

Measurements:

Short Form-36, with UK norm-based comparator scores and EQ-5D-3L.

Results:

Patients were between 11 and 22 years after injury (mean 15 years). We found no significant association between fracture classification and outcome score, but compared with age- and sex-matched scores for a UK population, differences were statistically significant in 3 of the 8 domains of health: physical function (P = 0.04), bodily pain (P = 0.001), and vitality (P = 0.001). The level of disability remained constant for these patients compared with their patient-reported outcome measure scores reported 8 years previously.

Conclusion:

Patients who sustain an unstable pelvic fracture continue to have significant functional limitations compared with an uninjured population. These changes were not found to be related to age, injury pattern, genitourinary injury, or neurological injury. Functional outcome scores did not change over the 2 long-term time points.

Level of Evidence:

Therapeutic Level IV. See Instructions for Authors for a complete description of levels of evidence.
Unstable Pelvic Ring Injuries: How Soon Can Patients Safely Bear Weight?
Authors: Marchand Lucas S. , Working Zachary M. , Rane Ajinkya A. , Elliott Iain S. , Howenstein Abby , Haller Justin M. , Rothberg David L. , Higgins Thomas F.
Published: January 2019

Objective:

To determine if time to weight bearing (WB) is associated with complications in operatively treated pelvic ring injuries.

Design:

Retrospective cohort study.

Setting:

Academic Level I trauma hospital.

Patients:

Two hundred eighty-six patients with pelvic ring injuries treated operatively over a 10-year period [OTA/AO 61-B1-3, 61-C1-3; Young-Burgess lateral compression (LC) 1–3, anterior–posterior compression (APC) 1–3, and vertical shear] were included.

Intervention:

Patients were stratified into early (≤8 weeks) and late (>8 weeks) time to full WB groups.

Main Outcome Measure:

Composite outcome of implant failure [broken screw(s)/plate(s), screw(s) loosening], revision surgery, and malunion.

Results:

We identified 286 patients with a mean age of 39.9 years (range: 18–81 years) and an average follow-up of 1.2 years (1.0–9 years). There were 132 and 154 patients in the early and late WB groups, respectively. A total of 142 Young-Burgess LC-1, 48 LC-2, 23 LC-3, 10 APC-1, 45 APC-2, 8 APC-3, and 8 vertical shear injuries were noted. Complications were noted in 47 patients (16%). Complications included 18 implant failures, 16 malunions, and 13 patients who required revision operations for loss of reduction. Time to WB was not associated with composite complication rates (P = 0.24). APC-2, LC-3, and injuries with bilateral rami fractures were noted to have a higher complication rates independent of time to WB (P = 0.005, 0.03, and 0.03, respectively).

Conclusions:

No difference in implant failure, malunion, or early loss of reduction between operatively treated pelvic ring injuries allowed to WB as tolerated before 8 weeks compared with those who remained on protected WB protocol for any time greater than 8 weeks was noted. These data may provide information to support early WB protocols.

Level of Evidence:

Therapeutic Level III. See Instructions for Authors for a complete description of levels of evidence.
Opiate Prescribing Practices After Common Isolated Lower Extremity Injuries
Authors: Rodriguez-Buitrago Andres , Attum Basem , Enata Nichelle , Evans Adam , Okwumabua Ebubechi , Gajari Vamshi , Obremskey William T. , Jahangir Alex
Published: January 2019

Objective:

This retrospective study aimed at identifying opiate prescribing practices, the number of morphine milligram equivalents (MMEs) prescribed by orthopaedic and nonorthopaedic providers in patients with operatively treated isolated lower extremity fractures, and provide opiate prescribing recommendations.

Methods:

Patients older than 18 years with isolated lower extremity (unicondylar, bicondylar, tibial shaft, pilon, and ankle) fractures between 2005 and 2016 were identified. Prescribing information was obtained from the State Controlled Substance Monitoring Database. Descriptive statistics were calculated for each injury and plotted for MME use. Mann–Whitney and Wilcoxon tests were used for data analysis. To aid in clinical relevance, MMEs were converted to number of pills of oxycodone 10 mg (OC 10 mg).

Results:

Three hundred forty-one patients met our inclusion criteria. Mean age was 45 years; 56% (192/341) were men. Forty-seven percent (159/341) were prescribed opiates before their injury. Orthopaedic providers prescribed more opiates to patients with pilon fractures compared with unicondylar (P = 0.010), tibial shaft (P < 0.001), and ankle (P < 0.001) fractures. Bicondylar plateau fracture patients also received more opiates when compared with unicondylar (P = 0.001), tibial shaft (P < 0.001), and ankle (P < 0.001) fractures. Nonorthopaedic providers prescribed more opiates to patients with pilon fractures when compared with unicondylar (P = 0.006), bicondylar (P < 0.001), tibial shaft (P < 0.001), and ankle fractures (P = 0.006). Differences between orthopaedic and nonorthopaedic MMEs prescribed are significantly different for each injury type (<0.05).

Conclusions:

Patients with pilon or bicondylar tibial plateau fractures are currently being prescribed more opiates when compared with other isolated fractures. We have developed an opiate prescription guideline based on what is being prescribed by orthopaedic providers.
Ultrasound-Guided Nerve Blocks as Analgesia for Nonoperative Management of Distal Radius Fractures–Two Consecutive Randomized Controlled Trials
Authors: Siebelt Michiel , Hartholt Klaas A. , van Winden Daniëlle F. M. , Boot Femke , Papathanasiou Dafni , Verdouw Bas C. , de Vries Mark R. , Mathijssen Nina M. , Kraan Gerald A.
Published: January 2019

Objectives:

To investigate whether a conventional fracture hematoma block (FHB) or an ultrasound-guided peripheral nerve block has more superior analgesic effect during nonoperative management of distal radius fractures in an emergency department setting. Two peripheral nerve block types were investigated, one at the level of the elbow, or cubital nerve block (CNB), and another an axillary nerve block (ANB).

Design:

Two prospective randomized controlled studies were performed to compare the difference in pain intensity during closed reduction of a distal radius fracture between FHB-, CNB-, and, ANB-treated patients.

Setting:

Level 2 trauma center.

Patients:

One hundred ten patients with radiographic displaced distal radius fractures were randomized. Fifty patients were randomized between FHB and CNB, and 60 patients were randomized between CNB and ANB.

Intervention:

FHB, CNB, or ANB. These were performed by 3 physicians new to ultrasound-guided peripheral nerve blocks and trained before onset of this study.

Main Outcome Measurement:

Pain was sequentially measured using an NRS during closed distal radius fracture reduction.

Results:

CNB patients experienced less pain during block procedure (P = 0.002), finger trap traction (P = 0.007), fracture reduction (P = 0.00001), after plaster cast application (P = 0.01), and after control radiography (P = 0.01). In our second study, ANB-treated patients reported less pain during block procedure (P = 0.04), during finger trap traction (P < 0.0001), fracture reduction (P < 0.0001), after plaster cast application (P = 0.0001), and after control radiography (P = 0.0005).

Conclusions:

Although participating clinicians had minimal expertise using ultrasound-guided peripheral nerve blocks, nonoperative management of distal radius fracture using an ANB was less painful. These block types are expected to completely eradicate sensation the best. Future studies should address technical factors including adequate placement and time to let the block set up, as well as issues such as resource utilization including time and clinician availability to better determine the relative advantages and disadvantages to other analgesia techniques such as the FHB.

Level of Evidence:

Therapeutic Level II. See Instructions for Authors for a complete description of levels of evidence.
A Practical Analgesia Approach to Fragility Hip Fracture: A Single-Center, Retrospective, Cohort Study on Femoral Nerve Block
Authors: Li Jinlei , Dai Feng , Chang Daniel , Harmon Emily , Ibe Izuchukwu , Sukumar Nitin , Halaszynski Thomas M. , Rubin Lee E. , O'Connor Mary I.
Published: January 2019

Objective:

To determine whether an effective opioid-sparing pain control modality is desirable for an aging population.

Design:

Retrospective observational study

Setting:

Academic medical center

Patients:

192 patients with various types of fragility hip fractures

Intervention:

A single-injection femoral nerve block (FNB)

Main outcome measurements:

Pain score, opioid consumption

Results:

We observed statistically significant effects of FNB on visual analogue scale pain score and the rate of opioid consumption diminution in all commonly encountered types of fragility hip fractures. The pain score reduction by FNB in subcapital femoral neck fracture, transcervical femoral neck facture, and intertrochanteric fracture are all statistically significant (P < 0.0001). There was a statistically more significant pain score reduction in intracapsular fractures than in extracapsular fractures (P = 0.006). On average, the hip fracture patients required 0.9 and 0.1 mg morphine equivalent/hour before and after FNB block placement. This decrease in opioid consumption when calculated per unit time was statistically significant in subcapital femoral neck fracture, transcervical femoral neck facture, and intertrochanteric fracture (P < 0.0001). There were no complications related to FNB placement.

Conclusions:

FNB is a sustainable, safe, and useful analgesic modality for commonly encountered fragility hip fractures.

Level of Evidence:

Therapeutic Level IV. See Instructions for Authors for a complete description of levels of evidence.
Fassier-Duval Rods are Associated With Superior Probability of Survival Compared With Static Implants in a Cohort of Children With Osteogenesis Imperfecta Deformities
Authors: Spahn Kimberly M. , Mickel Timothy , Carry Patrick M. , Brazell Christopher J. , Whalen Karen , Georgopoulos Gaia , Miller Nancy H.
Published: January 2019

Background:

The survival of Fassier-Duval (FD) telescoping rods as compared with static implants in children affected by osteogenesis imperfecta is not well characterized. The purpose of this study was to compare risk of lower extremity implant failure in FD rods versus static implants.

Methods:

Data were retrospectively collected from patients with osteogenesis imperfecta who underwent surgical treatment using either FD rods or static implants (Rush rods, flexible nails, or Steinmann pins) between 1995 and 2015. The timing of implant failure was the primary outcome variable of interest. Comparisons were limited to limbs with no previous history of implants. Cox-proportional hazards regression analyses were used to compare the hazard of implant failure across implants. Negative binomial regression analyses were used to compare the incidence of surgical procedures in the 2 implant groups.

Results:

The final cohort consisted of 64 limbs (n=21 patients). The static implant group (n=38) consisted of 24 Rush rods (63%), 14 flexible nails (37%), and 2 Steinmann pins (5%). The hazard of implant failure in the static implant group was 13.2 times [95% confidence interval (CI), 2.5-69.6; P=0.0024] the hazard of implant failure in the FD rod group. The hazard of implant failure among females was 4.8 (95% CI, 1.4-16.7; P=0.0125) times the hazard of implant failure among males. The total surgery rate in the static implant group was 7.8 (95% CI, 1.8-33.0; P=0.0056) times the total surgery rate in the FD group.

Conclusions:

Among surgically naive limbs, FD rods were associated with significantly improved probability of survival compared with static implants.

Level of Evidence:

Level II—retrospective study.
Effects of Baseline Thrombocytopenia and Platelet Decrease Following Renal Replacement Therapy Initiation in Patients With Severe Acute Kidney Injury*
Authors: Griffin Benjamin R. , Jovanovich Anna , You Zhiying , Palevsky Paul , Faubel Sarah , Jalal Diana
Published: January 2019

Objectives:

Thrombocytopenia is common in critically ill patients with severe acute kidney injury and may be worsened by the use of renal replacement therapy. In this study, we evaluate the effects of renal replacement therapy on subsequent platelet values, the prognostic significance of a decrease in platelets, and potential risk factors for platelet decreases.

Design:

Post hoc analysis of the Acute Renal Failure Trial Network Study.

Setting:

The Acute Renal Failure Trial Network study was a multicenter, prospective, randomized, parallel-group trial of two strategies for renal replacement therapy in critically ill patients with acute kidney injury conducted between November 2003 and July 2007 at 27 Veterans Affairs and university-affiliated medical centers.

Subjects:

The Acute Renal Failure Trial Network study evaluated 1,124 patients with severe acute kidney injury requiring renal replacement therapy.

Interventions:

Predictor variables were thrombocytopenia at initiation of renal replacement therapy and platelet decrease following renal replacement therapy initiation.

Measurements and Main Results:

Outcomes were mortality at 28 days, 60 days, and 1 year, renal recovery, renal replacement therapy free days, ICU-free days, and hospital-free days. Baseline thrombocytopenia in patients requiring renal replacement therapy was associated with increased mortality and was also associated with lower rates of renal recovery. A decrease in platelet values following renal replacement therapy initiation was associated with increased mortality. Continuous renal replacement therapy was not an independent predictor of worsening thrombocytopenia compared with those treated with intermittent hemodialysis.

Conclusions:

Baseline thrombocytopenia and platelet decrease following renal replacement therapy initiation were associated with increased mortality, and baseline thrombocytopenia was associated with decreased rates of renal recovery. Continuous renal replacement therapy did not decrease platelets compared with hemodialysis.
Meta-analysis of overall incidence and risk of ALK inhibitors-induced liver toxicities in advanced non-small-cell lung cancer
Authors: Li Jingjie , Yuan Zhi , Wang Qun , Fan Weijie , Zhang Guoping
Published: January 2019

Aim:

Activation of the anaplastic lymphoma kinase (ALK) gene has been found in several human cancers, including non-small-cell lung cancer (NSCLC). Currently, novel drugs targeting ALK gene have been extensively investigated in NSCLC. However, concerns about ALK inhibitors-induced liver toxicities have been increasing.

Materials and Methods:

Eligible prospective clinical studies have been searched in several databases. Primary outcomes of interest were incidence rates of liver toxicities, relative risks (RRs), and 95% confidence intervals (CIs).

Results:

Data from 2418 patients (1873 in the experimental arm; 545 in the control arm) were included. The incidences of all-grade alanine transaminase (ALT) and aspartate aminotransferase (AST) elevation were 26.0% (95% CI: 17.4%–37%), and 23.2% (95% CI, 16.7%–31.4%), respectively. The incidences of high-grade ALT and AST elevation were 8.4% (95% CI, 5.1%–13.4% and 7.0% (95% CI: 5.4%–9.0%), respectively. Sub-group analysis according to the ALK inhibitors found that pooled incidence of liver toxicities associated with ceritinib was higher than that of crizotinib and alectinib. In comparison with chemotherapy, ALK inhibitors significantly increased the all-grade and high-grade ALT elevation (RR 2.37, 95% CI, 1.97–2.86; P < .001; RR 7.34, 95% CI, 3.95–13.63; P < .001) and AST elevation (RR 3.27, 95% CI, 2.47–4.34; P < .001; RR 11.54, 95% CI, 4.33–30.7; P < .001), respectively. No publication bias was detected for RR of ALT and AST.

Conclusions:

The findings of the present study offer substantial evidence that ALK inhibitors treatment in advanced NSCLC significantly increases the risk of developing all-grade and high-grade liver toxicities in comparison with controls. Clinicians should recognize liver toxicities promptly as early interventions may alleviate future complications.
The effectiveness and safety of 3-dimensional printed composite guide plate for atlantoaxial pedicle screw
Authors: Wang Fei , Li Chang-Hong , Liu Zhi-Bin , Hua Zhang-Jian , He Yong-Jin , Liu Jun , Liu Yan-Xiong , Dang Xiao-Qian
Published: January 2019

This study aims to evaluate the effectiveness and safety of the application of a 3-dimensional (3D)-printed composite guide plate for atlantoaxial pedicle screw.

This was a retrospective study. A total of 43 atlantoaxial dislocation patients admitted in our hospital between January 2014 and October 2016 were retrospectively analyzed. According to the different methods of operation, patients were divided into 2 groups: 3D-printed plate group (n = 19) and traditional fixation group (n = 24). Placement time, operation duration, fluoroscopy number, intraoperative bleeding volume, and the neck and shoulder pain visual analog scale and Japanese Orthopaedic Association cervical nerve function scores were compared between pre- and postoperation.

Differences in general data between these 2 groups were not statistically significant (P > .05). For patients in the 3D-printed plate group, a total of 68 assisting screws were placed at the pedicle, the accuracy rate of screw placement was 94.1%, placement time was 2.2 ± 0.4 minutes, fluoroscopy number was 4.6 ± 1.1 times, operation duration was 197 ± 41 minutes, and intraoperative bleeding volume was 395 ± 64 mL. In the traditional fixation group, a total of 76 screws were placed at the pedicle of patients, the accuracy rate of screw placement was 76.3%, placement time was 3.4 ± 0.7 minutes, fluoroscopy number was 9.4 ± 2.7 times, operation duration was 245 ± 67 minutes, and intraoperative bleeding volume was 552 ± 79 mL. Differences in accuracy rate, placement time, fluoroscopy number, operation duration, and intraoperative bleeding volume between these 2 groups were statistically significant (P < .05).

The effectiveness and safety of 3D-printed composite guide plate for atlantoaxial pedicle screw were better than traditional method.