bluuebunny/crossref_metadata_2025 huggingface dataset:
Graph analysis of fragmented long-read bacterial genome assemblies
Authors: Marijon Pierre , Chikhi Rayan , Varré Jean-Stéphane
Published: March 2019

Motivation

Long-read genome assembly tools are expected to reconstruct bacterial genomes nearly perfectly; however, they still produce fragmented assemblies in some cases. It would be beneficial to understand whether these cases are intrinsically impossible to resolve, or if assemblers are at fault, implying that genomes could be refined or even finished with little to no additional experimental cost.

Results

We propose a set of computational techniques to assist inspection of fragmented bacterial genome assemblies, through careful analysis of assembly graphs. By finding paths of overlapping raw reads between pairs of contigs, we recover potential short-range connections between contigs that were lost during the assembly process. We show that our procedure recovers 45% of missing contig adjacencies in fragmented Canu assemblies, on samples from the NCTC bacterial sequencing project. We also observe that a simple procedure based on enumerating weighted Hamiltonian cycles can suggest likely contig orderings. In our tests, the correct contig order is ranked first in half of the cases and within the top-three predictions in nearly all evaluated cases, providing a direction for finishing fragmented long-read assemblies.

Availability and implementation

https://gitlab.inria.fr/pmarijon/knot .

Supplementary information

Supplementary data are available at Bioinformatics online.
Genome-wide identification of the essential protein-coding genes and long non-coding RNAs for human pan-cancer
Authors: Zhang Yuwei , Tao Yang , Ji Huihui , Li Wei , Guo Xingli , Ng Derry Minyao , Haleem Maria , Xi Yang , Dong Changzheng , Zhao Jinshun , Zhang Lina , Zhang Xiaohong , Xie Yangyang , Dai Xiaoyu , Liao Qi
Published: March 2019

Motivation

Genome-scale CRISPR/Cas9 system has been a democratized gene editing technique and widely used to investigate gene functions in some biological processes and diseases especially cancers. Aiming to characterize gene aberrations and assess their effects on cancer, we designed a pipeline to identify the essential genes for pan-cancer.

Methods

CRISPR screening data were used to identify the essential genes that were collected from published data and integrated by Robust Rank Aggregation algorithm. Then, hypergeometrics test and random walks with restart (RWR) were used to predict additional essential genes on broader scale. Finally, the expression status and potential roles of these genes were explored based on TCGA portal and regulatory network analysis.

Results

We collected 926 samples from 10 CRISPR-based screening studies involving 33 different types of cancer to identify cancer-essential genes, which consists of 799 protein-coding genes (PCGs) and 97 long non-coding RNAs (lncRNAs). Then, we constructed a ‘bi-colored’ network with both PCGs and lncRNAs and applied it to predict additional essential genes including 495 PCGs and 280 lncRNAs on a broader scale using hypergeometrics test and RWR. After obtaining all essential genes, we further investigated their potential roles in cancer and found that essential genes have higher and more stable expression levels, and are associated with multiple cancer-associated biological processes and survival time. The regulatory network analysis detected two intriguing modules of essential genes participating in the regulation of cell cycle and ribosome biogenesis in cancer.

Availability and implementation

 

Supplementary information

Supplementary data are available at Bioinformatics online.
epic2 efficiently finds diffuse domains in ChIP-seq data
Authors: Stovner Endre Bakken , Sætrom Pål
Published: March 2019

Data from chromatin immunoprecipitation (ChIP) followed by high-throughput sequencing (ChIP-seq) generally contain either narrow peaks or broad and diffusely enriched domains. The SICER ChIP-seq caller has proven adept at finding diffuse domains in ChIP-seq data, but it is slow, requires much memory, needs manual installation steps and is hard to use. epic2 is a complete rewrite of SICER that is focused on speed, low memory overhead and ease-of-use.

Availability and implementation

The MIT-licensed code is available at https://github.com/biocore-ntnu/epic2.

Supplementary information

Supplementary data are available at Bioinformatics online.
Too Close for Comfort: Direct Address and the Affective Pull of the Confessional Comic Woman in Chewing Gum and Fleabag
Authors: Woods Faye
Published: March 2019

The 2010s saw a boom in television comedies, created by, written, and starring women, that explored the bawdy and chaotic lives of protagonists who were experiencing some form of arrested development. These comedies sought to build intimate connections with their imagined audiences by crossing boundaries—social, bodily, and physical—to produce comedies of discomfort. Drawing in part on Rebecca Wanzo’s consideration of “precarious-girl comedy” (2016) I examine how two British television comedies intensified these intimate connections through the use of direct address, binding the audience tightly to the sexual and social misadventures of their twenty-something female protagonists. Michaela Coel’s Chewing Gum (E4, 2015–2017) follows naïve and desperately horny black working-class Londoner Tracey in her quest for sexual experience, and Phoebe-Waller Bridges’ Fleabag (BBC Three, 2016–) documents an unnamed upper-middle-class white woman’s sharply misanthropic journey through grief. In both programmes direct address serves to intensify the embrace of bodily affect and intimate access to interiority found in the “precarious-girl comedy” (Wanzo, 2016), producing moments of comic and emotional repulsion. Each program uses direct address’s blend of directness and distance to different ends, but both draw audiences at times uncomfortably close to the singular perspective of their protagonists, creating an intensely affective comic intimacy.
Eligibility for a Shorter Treatment Regimen for Multidrug-resistant Tuberculosis in the United States, 2011–2016
Authors: Tsang Clarisse A , Shah Neha , Armstrong Lori R , Marks Suzanne M
Published: March 2019

Background

In 2016, the World Health Organization (WHO) recommended a shorter (9–12 month) multidrug-resistant tuberculosis (MDR-TB) treatment regimen (as compared to the conventional 18–24 month regimen) for patients without extrapulmonary TB, pregnancy, a previous second-line TB medication exposure, or drug resistance to pyrazinamide, ethambutol, kanamycin, moxifloxacin, ethionamide, or clofazimine. The recommendation was based on successful clinical trials conducted in Asia and Africa, but studies, using mainly European data, have shown few patients in higher-resource settings would meet WHO eligibility criteria.

Methods

We assessed eligibility for the shorter regimen among US MDR-TB cases that had full drug susceptibility testing (DST) results and were reported during 2011–2016 to the US National TB Surveillance System. We estimated costs by applying the eligibility criteria for the shorter regimen, and proportional inpatient/outpatient costs from a previous, population-based study, to all MDR-TB patients reported to the National TB Surveillance System.

Results

Of 586 reported MDR-TB cases, 10% (59) were eligible for the shorter regimen. Of 527 ineligible patients, 386 had full DST, of which 246 were resistant to ethambutol and 217 were resistant to pyrazinamide. Compared with conventional MDR-TB treatment, implementing the shorter regimen would have reduced the US annual societal MDR-TB cost burden by 4%, but the cost burden for eligible individuals would have been reduced by 37–46%.

Conclusions

Relying on full DST use, our analysis found a minority of US MDR-TB patients would have been eligible for the shorter regimen. Cost reductions would have been minimal for society, but large for eligible individuals.
‘WhatsApp®’ening in nephrology training
Authors: Jhaveri Kenar D , Pascarelli Briana , Hasan Alia , Kozikowski Andrzej , Fishbane Steven , Pekmezaris Renee
Published: March 2019

Background

Teaching methods in most residency and fellowship programs have not yet addressed the challenges of rapid dissemination of new scientific information. Our Northwell nephrology fellowship program used the smartphone application WhatsApp® to facilitate nephrology education. A qualitative study was conducted to explore perceptions of nephrology fellows and faculty using WhatsApp® as a teaching tool.

Methods

A WhatsApp® messenger group called ‘Northwell Renal Forum’ was created in 2018, which included all eight fellows and seven selected faculty members. Multiple choice questions on various nephrology topics were posted, about one to two per week. Fellows responded at their leisure. After 7 months, data were analyzed following two 1-h focus groups (one for faculty and one for fellows). Focus groups were moderated by two qualitative researchers, unknown to the participants, who asked open-ended questions about the WhatsApp® learning approach.

Results

Faculty feedback was generally positive. Three major themes arose: control over learning material, comfort being fostered between faculty and fellows and faculty perceptions of fellows. The fellows also reported an overall positive experience. Control and comfort were themes again identified in this focus group. Fellows reported feeling control over which faculty member was in the group and when to respond to questions. Fellows also felt comfort from learning without pressure. Variety was the third theme that arose.

Conclusion

Focus group evaluations elucidated the strengths of using WhatsApp®, and the overall positive experience of both faculty and fellows. This inexpensive and easy-to-use tool can augment the learning of nephrology during fellowship.
The effectiveness of supplemental vibrational force on enhancing orthodontic treatment. A systematic review
Authors: Lyu Chunxiao , Zhang Li , Zou Shujuan
Published: March 2019

Background and objectives

The results from the literature regarding the influence of supplemental vibrational forces (SVFs) on orthodontic treatment are controversial. Therefore, this systematic review aimed to evaluate whether SVFs have positive effects, such as in accelerating tooth movement, alleviating pain, and preventing root resorption, in orthodontic patients.

Search methods

Searches through five electronic databases (PubMed, MEDLINE, EMBASE, Web of Science, and Cochrane Central) were complemented by hand searches up to January, 2019.

Selection criteria

Randomized controlled trials and controlled clinical trials reporting on the effects of SVFs in orthodontic patients in English were included.

Data collection and analysis

Study selection, data extraction, and a risk of bias assessment were independently performed by two reviewers. Study characteristics and outcomes were reported according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. A qualitative analysis of the effects of SVFs on orthodontic tooth movement, pain experience, and root resorption was conducted.

Results

Thirteen studies, including nine clinical trials, were eligible for inclusion in the systematic review. There was no significant evidence to support the positive effects of SVFs in orthodontic patients, neither in accelerating tooth movement nor in alleviating pain experience. According to the Grading of Recommendations Assessment, Development and Evaluation (GRADE) criteria, the quality of the evidence was very low for all the outcomes in the qualitative analysis.

Limitations

The results of this systematic review are based on a limited number of studies and the methodological heterogeneity and non-comparability of original outcomes made it difficult to conduct a meta-analysis.

Conclusions

There is insufficient evidence to support the claim that SVFs have positive clinical advantages in the alignment of the anterior teeth. The potential positive effects of vibrational forces on space closure, pain experience, and root resorption in orthodontic patients are inconclusive with no sufficient information at present. High-quality clinical trials with larger sample sizes are needed to find more comprehensive evidence of the potential positive effects of vibrational forces.

Registration

The protocol for this systematic review was registered on PROSPERO (CRD42018098788).

Funding

This study has not received any contributions from private or public funding agencies.

Conflict of Interest

None.
Neutral and polar lipid fatty acids in five families of demersal and pelagic fish from the deep Northwest Atlantic
Authors: Şen Özdemir Nurgül , Parrish Christopher C , Parzanini Camilla , Mercier Annie
Published: March 2019

Fatty acids in neutral and polar lipids were used to investigate trophic connections in species from five families of demersal (Rajella fyllae, Malacoraja senta, Alepocephalus bairdii, Borostomias antarcticus) and pelagic fish (Bathytroctes macrolepis, Lampanyctus spp., Chaulidos sloani, Serrivomer beanii) sampled in the deep Atlantic Ocean off Newfoundland, Canada. Lipid extracts were fractionated into neutral, acetone-mobile polar, and phospholipids to separate fatty acids in storage from those in membranes. Multivariate analysis of fatty acids showed that there were greater differences among the three lipid fractions than there were among the species when all fatty acid fractions were considered together. Neutral lipid fatty acids were characterized by monoenes, acetone-mobile polar lipids (AMPL) by C18 polyenes, and phospholipids by 16:0 and DHA. Multivariate analysis of fatty acids in phospholipids showed a strong grouping by taxonomic family (>80% similarity), while the neutral lipid fatty acids showed a weaker grouping by family (72.5% similarity) but groupings that also related to habitat and vertical migration. The neutral lipid data supported the use of 20:1ω9 as a biomarker of calanoid copepods and of 16:1ω7 as a marker of diatoms to determine food web connections in deep-sea fish, but not some other common markers. In addition, correlations with δ15N showed that series of ω6 and ω7 fatty acids were trophically transferred though neutral lipids, especially the essential fatty acid, ARA. Neutral lipids were also reservoirs for essential ω3 fatty acids in demersal species, but the major reservoir for DHA was AMPL and phospholipid in pelagic species.
Universal first-order logic is superfluous in the second level of the polynomial-time hierarchy
Authors: Borges Nerio , Pin Edwin
Published: March 2019

In this paper we prove that $\forall \textrm{FO}$, the universal fragment of first-order logic, is superfluous in $\varSigma _2^p$ and $\varPi _2^p$. As an example, we show that this yields a syntactic proof of the $\varSigma _2^p$-completeness of value-cost satisfiability. The superfluity method is interesting since it gives a way to prove completeness of problems involving numerical data such as lengths, weights and costs and it also adds to the programme started by Immerman and Medina about the syntactic approach in the study of completeness.
Delayed Colonoscopy Following a Positive Fecal Test Result and Cancer Mortality
Authors: Flugelman Anath A , Stein Nili , Segol Ori , Lavi Idit , Keinan-Boker Lital
Published: March 2019

Background

A fecal test followed by diagnostic colonoscopy for a positive result is a widely endorsed screening strategy for colorectal cancer (CRC). However, the relationship between the time delay from the positive test to the follow-up colonoscopy and CRC mortality has not been established.

Methods

From a population-based screening program, we identified CRC patients newly diagnosed from 2005 through 2015 by a positive fecal occult test followed by a colonoscopy. The primary outcome measure was CRC-specific mortality according to four categories for the time elapsed between the positive result and the subsequent colonoscopy.

Results

The 1749 patients underwent colonoscopies within 0–3 months (n = 981, 56.1%), 4–6 months (n = 307, 17.5%), 7–12 months (n = 157, 9.0%), and later than 12 months (n = 304, 17.4%). CRC-specific deaths according to exposure groups were: 13.8% (135 of 981) for 0–3 months, 10.7% (33 of 307) for 4–6 months (crude hazards ratio [HR] = 0.74, 95% confidence interval [CI] = 0.51 to 1.14), 11.5% (18 of 157) for 7–12 months (crude HR = 0.83, 95% CI = 0.51 to 1.42), and 22.7% (69 of 304) for longer than 12 months (crude HR = 1.40, 95% CI = 1.04 to 1.90). The only variable that was associated with mortality risk was the number of positive slides (P = .003). High positivity was twice the value in the 0–3 as the longer-than-12 months group: 51.9% vs 25.0% and similar for the 4–6 and 7–12 months groups (38.1% and 36.5%), respectively. The adjusted HRs for CRC mortality were 0.81 (95% CI = 0.55 to 1.19); 0.83 (95% CI = 0.50 to 1.41), and 1.53 (95% CI = 1.13 to 2.12, P = .006) for the 4–12, 7–12, and longer-than-12-months groups, respectively, compared with the shortest delay group.

Conclusions

Among screen-diagnosed CRC patients, performance of colonoscopy more than 12 months after the initial positive fecal occult blood test was associated with more advanced disease and higher mortality due to CRC.
CjPLE, a PLENA-like gene, is a potential regulator of fruit development via activating the FRUITFUL homolog in Camellia
Authors: Lyu Tao , Fan Zhengqi , Yang Wen , Yan Chao , Hu Zhikang , Li Xinlei , Li Jiyuan , Yin Hengfu
Published: March 2019

Fruit patterning involves the cooperation of multiple processes, including metabolic change, cell differentiation, and cell expansion. The FRUITFUL (FUL) and SHATTERPROOF1/2 (SHPs) MADS-box genes are master regulators directing fruit patterning in several eudicots. However, the regulatory mechanisms of the FUL–SHP network in different fruit types remain unclear. Here, we characterized the functions of an ortholog (CjPLE) of SHPs from Camellia japonica. We showed that CjPLE was predominantly expressed in stamen and carpel tissues during the early stage of floral development and that transcripts were abundant in the pericarp tissues during fruit development. The ectopic expression of CjPLE in Arabidopsis caused enhanced development of the carpels, whereas no defects in floral identity were observed. To investigate the downstream targets of CjPLE, overexpression transformants were analysed through a callus transformation system in Camellia azalea. We examined the expression levels of potential downstream target genes and found that two previously identified APETALA1-like genes (CjAPL1/2) were significantly up-regulated. We showed that CjPLE directly bound to the CArG motifs in the promoter region of CjAPL1 (the FUL ortholog). Taken together, our results reveal a possible positive regulation of FUL by SHP in the control of fruit development in Camellia.
Orphan genes are involved in drought adaptations and ecoclimatic-oriented selections in domesticated cowpea
Authors: Li Guojing , Wu Xinyi , Hu Yaowen , Muñoz-Amatriaín Maria , Luo Jie , Zhou Wen , Wang Baogen , Wang Ying , Wu Xiaohua , Huang Lijuan , Lu Zhongfu , Xu Pei
Published: March 2019

Orphan genes (OGs) are genes that are restricted to a single species or a particular taxonomic group. To date, little is known about the functions of OGs in domesticated crops. Here, we report our findings on the relationships between OGs and environmental adaptation in cowpea (Vigna unguiculata). We identified 578 expressed OGs, of which 73.2% were predicted to be non-coding. Transcriptomic analyses revealed a high rate of OGs that were drought inducible in roots when compared with conserved genes. Co-expression analysis further revealed the possible involvement of OGs in stress response pathways. Overexpression of UP12_8740, a drought-inducible OG, conferred enhanced tolerance to osmotic stresses and soil drought. By combining Capture-Seq and fluorescence-based Kompetitive allele-specific PCR (KASP), we efficiently genotyped single nucleotide polymorphisms (SNPs) on OGs across a 223 accession cowpea germplasm collection. Population genomic parameters, including polymorphism information content (PIC), expected heterozygosity (He), nucleotide diversity (π), and Tajima’s D statistics, that were calculated based on these SNPs, showed distinct signatures between the grain- and vegetable-type subpopulations of cowpea. This study reinforces the idea that OGs are a valuable resource for identifying new genes related to species-specific environmental adaptations and fosters new insights that artificial selection on OGs might have contributed to balancing the adaptive and agronomic traits in domesticated crops in various ecoclimatic conditions.
CHARACTERISATION OF TLDS-200 AND OSLDS AT LOW X-RAY ENERGIES AND DETERMINATION OF EYE LENS DOSE, THYROID DOSE AND MEAN GLANDULAR DOSE DURING STANDARD MAMMOGRAPHY AND TOMOSYNTHESIS
Authors: Pirchio R , Stefanic A , Rojas R R
Published: March 2019

The objective of this study was to characterise thermoluminescent (TLDs) and optically stimulated luminescent dosimeters (OSLDs) at low X-ray energies and estimate the eye lens (DL), thyroid (DT) and mean glandular (DG) doses received during Full-Field Digital Mammography (FFDM) and Digital Breast Tomosynthesis (DBT). The dosimeters were characterised in mammography energies. DL, DT and DG were estimated in FFDM and DBT mode taping dosimeters on the skin of the thyroid gland and on the left eye lens of an Alderson phantom. Dosimeters were also placed on the top of a NORMI PAS phantom simulating a compressed breast. The accuracy, precision and lower limit of detection (LLD) for TLDs and OSLDs were 5 and 8%, 6 and 3%, and 38 and 11 μSv, respectively. The linearity of the kerma response had an R2 > 0.99 and energy dependence was lower than 40%. DT ranged from 0.40 to 2.87 μGy for FFDM and 1.27 to 5.99 μGy for DBT. DG was between 0.50 and 1.27 mGy for FFDM and 1.07 and 1.60 mGy for DBT. DL was below the LLD. Dosimeters showed good performance. DG values were lower than those found in the literature, whereas DT value agreed with references. Differences between DG and DT determined with OSLDs and TLDs were lower than 10% and 200%.
An updated meta-analysis of the association between Toxoplasma gondii infection and risk of epilepsy
Authors: Sadeghi Maryam , Riahi Seyed Mohammad , Mohammadi Mona , Saber Vafa , Aghamolaie Somayeh , Moghaddam Solmaz Alizadeh , Aghaei Shima , Javanian Mostafa , Gamble H Ray , Rostami Ali
Published: March 2019

Toxoplasma gondii is a neurotropic pathogen with worldwide distribution. To evaluate the association between Toxoplasma infection and the risk of epilepsy by meta-analysis, observational peer-reviewed studies were retrieved from PubMed, Embase, Web of Science, Scopus and Google Scholar (up to 10 October 2018) and by reference review. Pooled risk estimates were calculated using a random effects model. Heterogeneity was assessed using Cochrane’s Q-test and I2. In total, 16 eligible studies involving 19 data sets were included for the final analysis. A total 7897 participants (3771 epileptic patients, 4026 healthy controls) were included. The pooled odds ratio (OR) for Toxoplasma infection was increased to 1.72 (95% confidence interval [CI] 1.37 to 2.16) among patients with epilepsy. There was moderate heterogeneity among the studies (χ2=39.8, I2=62.3%, p=0.001). The ORs from subgroup analyses showed that both cryptogenic epilepsy (OR 2.65 [95% CI 1.91 to 3.68]) and active convulsive epilepsy (OR 1.37 [95% CI 1.09 to 1.72]) were significantly associated with Toxoplasma infection. Another subgroup analyses according to age showed a significant positive association in children (OR 1.33), adults (OR 1.57) and in all ages (OR 1.89). Our findings support the association between Toxoplasma infection and epilepsy. More prospective studies with larger sample sizes and more experimental studies are recommended to elucidate a causative relationship.
Transient Neurological Events After Surgery for Pediatric Moyamoya Disease: A Retrospective Study of Postoperative Sedation Practices
Authors: Matsuura Hideki , Yoshitani Kenji , Nakamori Yuki , Tsukinaga Akito , Takahashi Jun C. , Nakai Michikazu , Ohnishi Yoshihiko
Published: March 2019

Background:

Moyamoya disease is a cerebrovascular disease characterized by bilateral stenosis of the intracranial internal carotid arteries and an abnormal collateral vascular network at the base of the brain. Transient neurological events (TNEs), which are episodes of neurological dysfunction lasting <24 hours, are associated with stroke in pediatric patients with Moyamoya disease. Perioperative agitation often occurs in pediatric patients. We hypothesized that anesthetic technique and postoperative sedation would modify the association between TNE and superficial temporal artery-middle cerebral artery (STA-MCA) bypass in pediatric patients with Moyamoya disease.

Methods:

We retrospectively reviewed the medical records of patients with Moyamoya disease aged 15 years and below who underwent STA-MCA bypass under general anesthesia at a single cerebrovascular center in Japan between January 1999 and March 2016. The primary outcome was TNE. Mixed-effects logistic regression was used to evaluate whether postoperative sedation and anesthetic agents were associated with TNE.

Results:

Among 277 hemispheres in 154 pediatric patients who underwent STA-MCA bypass, 107 patients (39%) experienced TNE within 1 week after surgery. Crying (adjusted odds ratio, 3.11; 95% confidence interval, 1.01-9.59; P=0.048) was an independent risk factor for TNE. Postoperative sedation was associated with a lower incidence of TNE (adjusted odds ratio, 0.514; 95% confidence interval, 0.264-0.997; P=0.049), but premedication and anesthetic agents were not associated with TNE.

Conclusion:

In pediatric patients with Moyamoya disease, crying was associated with increased TNE and postoperative sedation is associated with decreased TNE.
Neonatal and Maternal Morbidity Among Low-Risk Nulliparous Women at 39–41 Weeks of Gestation
Authors: Chen Han-Yang , Grobman William A. , Blackwell Sean C. , Chauhan Suneet P.
Published: March 2019

OBJECTIVE:

To use a large national database to compare composite maternal or neonatal morbidity among low-risk, full-term women.

METHODS:

This cohort study, using the U.S. vital statistics datasets (2011–2015), evaluated low-risk nulliparous women with nonanomalous singleton gestations who labored at 39, 40, or 41 weeks of gestation (as reported in completed weeks of gestation; eg, 39 weeks include 39 0/7 to 39 6/7 weeks). The primary outcome, composite neonatal morbidity, included any of the following: Apgar score below 5 at 5 minutes, assisted ventilation longer than 6 hours, seizure, or mortality. The secondary outcome, composite maternal morbidity, included any of the following: intensive care unit admission, blood transfusion, uterine rupture, or unplanned hysterectomy. Multivariable Poisson regression was used to estimate the association between gestational age and morbidity (using adjusted relative risk [aRR] and 95% CI).

RESULTS:

Of 19.8 million live births during the study interval, 3.3 million met inclusion criteria: 43.5% were delivered at 39 weeks of gestation, 41.4% at 40 weeks, and 15.1% at 41 weeks. The overall rates of composite neonatal and maternal morbidity were 8.8 and 2.8 per 1,000 live births, respectively. Composite neonatal morbidity was higher for those delivered at 40 (aRR 1.22; 95% CI 1.19–1.25) and 41 (aRR 1.53; 95% CI 1.49–1.58) weeks of gestation when compared with 39 weeks. Composite maternal morbidity was also significantly higher with delivery at 40 (aRR 1.19; 95% CI 1.14–1.25) and 41 weeks of gestation (aRR 1.56; 95% CI 1.47–1.65).

CONCLUSION:

Among low-risk nulliparous women, the rate of composite neonatal and maternal morbidity increases, albeit modestly, from 39 through 41 weeks of gestation.
Safety Assessment of a Large-Scale Improvement Collaborative to Reduce Nulliparous Cesarean Delivery Rates
Authors: Main Elliott K. , Chang Shen-Chih , Cape Valerie , Sakowski Christa , Smith Holly , Vasher Julie
Published: March 2019

OBJECTIVE:

To evaluate maternal and neonatal safety measures in a large-scale quality improvement program associated with reductions in nulliparous, term, singleton, vertex cesarean delivery rates.

METHODS:

This is a cross-sectional study of the 2015–2017 California Maternal Quality Care Collaborative (CMQCC) statewide collaborative to support vaginal birth and reduce primary cesarean delivery. Hospitals with nulliparous, term, singleton, vertex cesarean delivery rates greater than 23.9% were solicited to join. Fifty-six hospitals with more than 119,000 annual births participated; 87.5% were community facilities. Safety measures were derived using data collected as part of routine care and submitted monthly to CMQCC: birth certificates, maternal and neonatal discharge diagnosis and procedure files, and selected clinical data elements submitted as supplemental data files. Maternal measures included chorioamnionitis, blood transfusions, third- or fourth-degree lacerations, and operative vaginal delivery. Neonatal measures included the severe unexpected newborn complications metric and 5-minute Apgar scores less than 5. Mixed-effect multivariable logistic regression model was used to calculate odds ratios (Ors) and 95% CIs.

RESULTS:

Among collaborative hospitals, the nulliparous, term, singleton, vertex cesarean delivery rate fell from 29.3% in 2015 to 25.0% in 2017 (2017 vs 2015 adjusted OR [aOR] 0.76, 95% CI 0.73–0.78). None of the six safety measures showed any difference comparing 2017 to 2015. As a sensitivity analysis, we examined the tercile of hospitals with the greatest decline (31.2%–20.6%, 2017 vs 2015 aOR 0.54, 95% CI 0.50–0.58) to evaluate whether they had greater risk of poor maternal and neonatal outcomes. Again, no measure was statistically worse, and the severe unexpected newborn complications composite actually declined (3.2%–2.2%, aOR 0.71, 95% CI 0.55–0.92).

CONCLUSION:

Mothers and neonates participating in a large-scale Supporting Vaginal Birth collaborative had no evidence of worsened birth outcomes, even in hospitals with large cesarean delivery rate reductions, supporting the safety of efforts to reduce primary cesarean delivery using American College of Obstetricians and Gynecologists and Society for Maternal-Fetal Medicine guidelines and enhanced labor support.
Multimodal Stepwise Approach to Reducing In-Hospital Opioid Use After Cesarean Delivery
Authors: Smith Alisha M. , Young Paul , Blosser Colleen C. , Poole Aaron T.
Published: March 2019

OBJECTIVE:

To evaluate the association of a standardized, structured approach to in-hospital postcesarean delivery pain management with maternal opioid use after cesarean delivery.

METHODS:

We conducted a retrospective cohort study of women who underwent cesarean delivery before and after a quality improvement intervention at a single tertiary care center. A multidisciplinary task force revised electronic order sets for all patients who underwent cesarean delivery with neuraxial anesthesia. The revised order set separated acetaminophen from opioids, scheduled acetaminophen and nonsteroidal antiinflammatory drug administration, and limited opioid use to breakthrough pain. Data were collected by electronic chart review. The primary outcome was median morphine milligram equivalents per hospital stay. Secondary outcomes included median morphine milligram equivalents per day, median pain scores, time to discharge, and opioid–nonopioid pain medication use. Descriptive and bivariable analyses were performed.

RESULTS:

There were no significant differences in baseline characteristics in the preintervention (n=283) and postintervention (n=286) groups. There was a 75% reduction in median morphine milligram equivalents per stay from 120 (90–176 interquartile range) preintervention to 30 (5–68) postintervention (P<.001) and a 77% reduction in median morphine milligram equivalents per day (51 [41–60] vs 12 [2–25], P<.001). There was no difference between groups in time to discharge or median pain scores. There was no difference in ketorolac use (80% preintervention vs 75% postintervention, P=.14) or in median ibuprofen mg per day (1,391 preintervention vs 1,347 postintervention, P=.22). There was an increase in median acetaminophen mg per day (753 preintervention vs 2,340 postintervention, P<.001). There was a significant increase in patients who used no opioids during their hospital stay (6% preintervention vs 19% postintervention, P<.001).

CONCLUSION:

A multimodal stepwise approach to postcesarean delivery pain control was associated with markedly reduced opioid consumption without increasing hospital stay or median pain scores. By separating acetaminophen from opioids and limiting opioids to breakthrough pain, we were able to operationalize a tier-based approach to pain management.
An Integrated, Trauma-Informed Care Model for Female Survivors of Sexual Violence
Authors: Ades Veronica , Wu Stephanie X. , Rabinowitz Emily , Chemouni Bach Sonya , Goddard Brian , Pearson Ayala Savannah , Greene Judy
Published: March 2019

This article describes the Engage, Motivate, Protect, Organize, self-Worth, Educate, Respect (EMPOWER) Clinic for Survivors of Sex Trafficking and Sexual Violence located at Gouverneur Health in New York, New York, as a model for integrated gynecologic and psychiatric care of survivors of sexual and gender-based violence. Although patients with a history of sexual trauma often have critical health needs that persist long after the traumatic event, most existing services for survivors of sexual violence focus solely on the provision of acute care immediately after the violence has occurred. There are very few clinics in the United States dedicated to managing the significant long-term medical consequences and sequelae of sexual violence in a trauma-informed setting. We report on best practices for the provision of trauma-sensitive medical care to this patient population based on those employed at the EMPOWER Clinic. In particular, we outline some of the unique considerations for treating survivors relating to taking a patient history, conducting the physical and gynecologic examinations, ensuring confidentiality, and managing legal issues. Finally, we reflect on the challenges faced in sustaining the EMPOWER Clinic and the importance of the existence of a clinic dedicated to this specific population.
Radiographic Healing of Far Cortical Locking Constructs in Distal Femur Fractures: A Comparative Study With Standard Locking Plates
Authors: Plumarom Yanin , Wilkinson Brandon G. , Marsh J. Lawrence , Willey Michael C. , An Qiang , Gao Yubo , Karam Matthew D.
Published: March 2019

Objectives:

To investigate the radiographic healing of far cortical locking (FCL) construct fixation in distal femur fractures compared with traditional locking plate (LP) constructs.

Design:

A retrospective cohort of 143 consecutive patients with 146 distal femur fractures.

Setting:

Level I trauma center.

Patients/Participants:

After excluding patients with OTA/AO type B fractures, referred nonunion cases, patients younger than 16 years, and patients with less than 24 weeks of follow-up, 69 patients with 70 total fractures were included for analysis.

Intervention:

AP and lateral knee radiographs were blinded to type of screws and individually reviewed by 3 orthopaedic trauma surgeons.

Outcome Measurements:

The modified RUST (mRUST) score was our primary outcome measure. mRUST scores were assigned at 6, 12, and 24 weeks and final follow-up based on AP and lateral radiographs and compared between FCL and LP groups as a tool for evaluating fracture healing. Secondary outcomes compared between FCL and LP included union rate and postoperative complications.

Results:

Statistically significant differences in mRUST scores were noted between FCL and LP groups at 6 weeks (P = 0.040), 12 weeks (P = 0.034), 24 weeks (0.044), and final follow-up (P = 0.048). There was no significant difference in union or specific complication rates between the 2 groups. The union rate was 90.5% and 82.1% for the FCL and LP groups, respectively, at final follow-up.

Conclusions:

To our knowledge, this is the first comparative study between FCL and LP constructs. The FCL group was noted to have significantly higher mRUST scores at all periods indicating increased callus formation, but the differences seen were small and there were no differences in healing rates or complications between the 2 groups, thus bringing the clinical benefit of FCL into question. Further prospective study designs are needed to compare FCL with LP constructs and to investigate the role of interfragmentary motion on callus formation in distal femur fractures.

Level of Evidence:

Therapeutic Level III. See Instructions for Authors for a complete description of levels of evidence.
Long-Term Follow-Up of Anterior Spinal Fusion for Thoracolumbar/Lumbar Curves in Adolescent Idiopathic Scoliosis
Authors: Direito-Santos Bruno , Queirós Carlos Mesquita , Serrano Pedro , Encarnação Ângelo , Campos Armando , Oliveira António
Published: March 2019

Study Design.

Retrospective patient series analysis with update of long-term data.

Objective.

To define the long-term prognosis of the thoracolumbar/lumbar correction after selective anterior spinal fusion (ASF) in adolescent idiopathic scoliosis (AIS).

Summary of Background Data.

The ASF is a well-described procedure for the treatment of AIS. The correction reliability over time, the consequences in adjacent spinal levels and patient's quality of life are fundamental for the characterization of AIS treatment.

Methods.

One hundred seven patients were submitted to single-rod ASF for thoracolumbar/lumbar (ThL/L) AIS between 1993 and 2016 in a single-surgeon experience. Seventy five were available for final follow-up evaluation 9 years ±4 (2–23) after surgery. A clinical and sequential radiographic evaluations were performed.

Results.

The mean age at surgery was 16 years ± 2.33 (14–20) and 94 (87%) were females. The mean final follow-up of the 75 patients available was 9 years ± 4 (2–23). Sixty-five patients had a Lenke type 5C curve and 10 had a type 6C curve. The mean values of the Scoliosis Research Society 22 (SRS-22) questionnaire in Lenke 5C was 92 ± 9 (71–109) and in Lenke 6C 90.3 ± 9 (75–107). In Lenke 5C group, the mean preoperative ThL Cobb angle was 38.4° ± 9.3 (21–60) and the postoperative was 5.9° ± 4.5 (0–18; P < 0.001) being similar at the final follow-up (P > 0.05). In Lenke 6C group, the mean preoperative ThL Cobb angle was 58.6° ± 13.9 (40–90) and the postoperative ThL Cobb was 22.6° ± 14.5 (5–48, P < 0.001) being similar at the final follow-up (P > 0.05). The mean preoperative Thoracic (Th) Cobb angle was 39° ± 7.6 (30–50), the postoperative was 30.6° ± 10.1 (14–49, P < 0.008) and in the final follow-up was 29.3° ± 10.7 (11–48, P < 0.011).

Conclusion.

ASF is a safe procedure in the treatment of ThL/L with good long-term results and high rates of satisfaction among patients with AIS Lenke type 5C. The partial correction was frequent in Lenke type 6C despite the absence of progression in the non-instrumented curves.

Level of Evidence: 4
Transport of Vancomycin and Cefepime Into Human Intervertebral Discs
Authors: Zhu Qiaoqiao , Gao Xin , Brown Mark D. , Eismont Frank , Gu Weiyong
Published: March 2019

Study Design.

Simulation of antibiotics transport into human intervertebral disc with intravenous infusion.

Objective.

The objective of this study was to quantitatively investigate antibiotic concentrations in the disc.

Summary of Background Data.

Intravenous infusion of antibiotics is typically used to treat intervertebral disc infection in clinics. However, it is difficult to evaluate the drug concentrations within discs in vivo.

Methods.

A computational model was used in this study. The variation of drug charge with pH was considered in the model. Thirty-minute infusions of two commonly used antibiotics in clinic—vancomycin and cefepime—were numerically investigated. Spatial and temporal concentration distributions of these drugs in both nondegenerated and moderately degenerated discs were calculated.

Results.

For intravenous infusion of 1 g vancomycin and 2 g cefepime in 30 minutes repeated every 12 hours, it was predicted that vancomycin concentration in the disc fluctuated between 17.0 and 31.0 times of its minimum inhibitory concentration (1 ug/mL) and cefepime concentration fluctuated between 1.1 and 4.2 times of its minimum inhibitory concentration (i.e., 8 ug/mL) in about 2 days. It was also found that vancomycin concentration in moderately degenerated disc was lower than that in the nondegenerated disc.

Conclusion.

This study provides quantitative guidance on selecting proper dosage for treating disc infection. The method used in this study could be used to provide quantitative information on transport of other antibiotics and drugs in discs as well.

Level of Evidence: N/A
Neurologic Injury in Complex Adult Spinal Deformity Surgery
Authors: Lui Darren F. , Butler Joseph S. , Yu Hai Ming , Malhotra Karan , Selvadurai Susanne , Benton Adam , Agu Obiekezie , Molloy Sean
Published: March 2019

Study Design.

A retrospective review of prospectively collected data.

Objective.

The aim of this study was to determine the safety of MOLIF versus PSO.

Summary of Background Data.

Complex adult spinal deformity (CASD) represents a challenging cohort of patients. The Scoli-RISK-1 study has shown a 22.18% perioperative risk of neurological injury. Restoration of sagittal parameters is associated with good outcome in ASD. Pedicle subtraction osteotomies (PSO) is an important technique for sagittal balance in ASD but is associated with significant morbidity. The multilevel oblique lumbar interbody fusion (MOLIF) is an extensile approach from L1 to S1.

Methods.

Single surgeon series from 2007 to 2015. Prospectively collected data. Scoli-RISK-1 criteria were refined to only include stiff or fused spines otherwise requiring a PSO. Roentograms were examined preoperatively and 2 year postoperatively. Primary outcome measure was the motor decline in American Spinal Injury Association (ASIA) at hospital discharge, 6 weeks, 6 months, and 2 years. Demographics, blood loss, operative time, spinopelvic parameters, and spinal cord monitoring (SCM) events.

Results.

Sixty-eight consecutive patients were included in this study, with 34 patients in each Group. Group 1 (MOLIF) had a mean age 62.9 (45–81) and Group 2 (PSO) had a mean age of 66.76 years (47–79); 64.7% female versus PSO 76.5%; Body Mass Index (BMI) Group 1 (MOLIF) 28.05 and Group 2 (PSO) 27.17. Group 1 (MOLIF) perioperative neurological injury was 2.94% at discharge but resolved by 6 weeks. Group 2 (PSO) had five neurological deficits (14.7%) with no recovery by 2 years. There were four SCM events (SCM). In Group 1 (MOLIF), there was one event (2.94%) versus three events (8.88%) in Group 2 (PSO).

Conclusion.

Staged MOLIF avoids passing neurological structures or retraction of psoas and lumbar plexus. It is safer than PSO in CASD with stiff or fused spines with a lower perioperative neurological injury profile. MOLIF have less SCM events, blood loss, and number of levels fused.

Level of Evidence: 3
New Flexible Fixation for Subtle Lisfranc Injury
Authors: Nery Caio , Baumfeld Daniel
Published: March 2019

Lisfranc ligament injuries are not so common and often overlooked. If missed, they can cause long-term disability and pain. The treatment of these injuries are still controversial and very little is known about which types of injury can be treated without surgery. Successful surgical management of these injuries is predicated on anatomic reduction and stable fixation. Open reduction and internal fixation remains the standard treatment, although ligament reconstruction has emerged as a viable option for certain types of tarsometatarsal joint injuries. This paper describes the authors’ approach to treat Lisfranc’s pure ligament injury. It presents a particular view of the problems resulting from the diagnosis and a specific type of ligament reconstruction.

Level of Evidence: Level V.
Intra-Articular Osteotomy for Symptomatic Bennett Fracture Malunion
Authors: Van Royen Kjell , Vanmierlo Bert , Bonte Francis , Goorens Chul K. , Berghs Bart , Goubau Jean
Published: March 2019

Bennett’s fractures are the most common fractures around the trapeziometacarpal joint but require specialized radiographs to be correctly diagnosed. If a fracture is missed at initial presentation, it may heal with an intra-articular gap, leading to joint incongruency and a painful trapeziometacarpal joint. We present a new technique to correct the intra-articular gap and restore joint congruency in the event of a symptomatic Bennett malunion with a gap of at least 2 mm. The joint is exposed through an anterolateral approach, and the malunion is marked with K-wires under fluoroscopic control. A closing wedge osteotomy with excision of the malunion site is then performed to restore joint congruency. The osteotomy is fixed with 3 interfragmentary screws, and the joint is immobilized for 2 weeks before passive mobilization is initiated. Hardware can be removed between 3 and 6 months postoperatively after consolidation of the osteotomy. We recommend this technique in active patients without trapeziometacarpal osteoarthritis who present with a painful Bennett malunion. Restoration of the joint congruency reduces pain and may prevent the development of posttraumatic osteoarthritis.
The Evidence for Sacroiliac Joint Surgery
Authors: Whelan Ros , Duhon Bradley
Published: March 2019

Sacroiliac joint (SIJ) dysfunction is a condition that has a significant impact on patient’s quality of life. In the past, accurate diagnosis of this condition has proven difficult and even when diagnosed, effective treatments with acceptable morbidity have been lacking. Recently, the use of composites of various physical examination tests in conjunction with joint injections has proven capable of diagnosing the condition with acceptable degrees of sensitivity and specificity. In addition, the advent of minimally invasive techniques for the fusion of the SIJ now offer patients an effective treatment option with morbidity far less than traditional open approaches. This paper is intended as a review of the evidence with regard to SIJ dysfunction and the various treatment options available for this condition. We first discuss the approach to diagnosing the condition and the evidence for the use of composites of physical examination tests and joint injections in reaching the diagnosis. This is followed by a detailed discussion of the various treatment options, broadly speaking these include conservative management, open surgical fusion, and minimally invasive fusion. We discuss the evidence examining the effectiveness of these treatment strategies including the various studies that directly compare the different modalities. On the basis of this evidence we recommend patients with SIJ dysfunction should first undergo a 6-month trial of conservative management before being considered for surgical intervention. If surgery is being considered, we recommend that due to the lower morbidity, minimally invasive techniques are the preferred approach.