bluuebunny/crossref_metadata_2025 huggingface dataset:
And yet it flips: connecting galactic spin and the cosmic web
Authors: Kraljic Katarina , Davé Romeel , Pichon Christophe
Published: January 2020

We study the spin alignment of galaxies and haloes with respect to filaments and walls of the cosmic web, identified with DisPerSE , using the Simba simulation from z = 0 − 2. Massive haloes’ spins are oriented perpendicularly to their closest filament’s axis and walls, while low-mass haloes tend to have their spins parallel to filaments and in the plane of walls. A similar mass-dependent spin flip is found for galaxies, albeit with a weaker signal particularly at low mass and low-z, suggesting that galaxies’ spins retain memory of their larger scale environment. Low-z star-forming and rotation-dominated galaxies tend to have spins parallel to nearby filaments, while quiescent and dispersion-dominated galaxies show preferentially perpendicular orientation; the star formation trend can be fully explained by the stellar mass correlation, but the morphology trend cannot. There is a dependence on HI mass, such that high-HI galaxies tend to have parallel spins while low-HI galaxies are perpendicular, suggesting that HI content may trace anisotropic infall more faithfully than the stellar component. Finally, at fixed stellar mass, the strength of spin alignments correlates with the filament’s density, with parallel alignment for galaxies in high density environments. These findings are consistent with conditional tidal torque theory, and highlight a significant correlation between galactic spin and the larger scale tides that are important e.g., for interpreting weak lensing studies. Simba allows us to rule out numerical grid locking as the cause of previously-seen low mass alignment.
Searching for ultra-fast outflows in AGN using variability spectra
Authors: Igo Z , Parker M L , Matzeu G A , Alston W , Alvarez Crespo N , Fürst F , Buisson D J K , Lobban A , Joyce A M , Mallick L , Schartel N , Santos-Lleó M
Published: January 2020

We present a qualitative search for ultra-fast outflows (UFOs) in excess variance spectra of radio-quiet active galactic nuclei (AGNs). We analyse 42 sources from the spectroscopic UFO detection sample, and an additional 22 different sources from the variability sample. A total of 58 sources have sufficient observational data from XMM–Newton EPIC-pn and variability for an excess variance spectrum to be calculated. We examine these spectra for peaks corresponding to variable blue-shifted H- and He-like ion absorption lines from UFOs. We find good evidence for such outflows in 28 per cent of the AGN sample and weak evidence in a further 31 per cent, meaning that ∼30–60 per cent of the AGN sample hosts such UFOs. The mean and median blue-shifted velocity is found to be ∼0.14c and 0.12c, respectively. Current variability methods allow for a fast, model-independent determination of UFOs; however, further work needs to be undertaken to better characterize the statistical significance of the peaks in these spectra by more rigorous modelling. Detecting good evidence for variable UFO lines in a large number of sources also lays the groundwork for detailed analysis of the variability time-scales of the absorbers. This will allow us to probe their densities and hence distances from the central supermassive black hole.
Vortex pinning in the superfluid core of neutron stars and the rise of pulsar glitches
Authors: Sourie Aurélien , Chamel Nicolas
Published: January 2020

Timing of the Crab and Vela pulsars has recently revealed very peculiar evolutions of their spin frequency during the early stage of a glitch. We show that these differences can be interpreted from the interactions between neutron superfluid vortices and proton fluxoids in the core of these neutron stars. In particular, pinning of individual vortices to fluxoids is found to have a dramatic impact on the mutual friction between the neutron superfluid and the rest of the star. The number of fluxoids attached to vortices turns out to be a key parameter governing the global dynamics of the star. These results may have implications for the interpretation of other astrophysical phenomena such as pulsar-free precession or the r-mode instability.
Good guide, bad guide: spacer sequence-dependent cleavage efficiency of Cas12a
Authors: Creutzburg Sjoerd C A , Wu Wen Y , Mohanraju Prarthana , Swartjes Thomas , Alkan Ferhat , Gorodkin Jan , Staals Raymond H J , van der Oost John
Published: January 2020

Genome editing has recently made a revolutionary development with the introduction of the CRISPR–Cas technology. The programmable CRISPR-associated Cas9 and Cas12a nucleases generate specific dsDNA breaks in the genome, after which host DNA-repair mechanisms can be manipulated to implement the desired editing. Despite this spectacular progress, the efficiency of Cas9/Cas12a-based engineering can still be improved. Here, we address the variation in guide-dependent efficiency of Cas12a, and set out to reveal the molecular basis of this phenomenon. We established a sensitive and robust in vivo targeting assay based on loss of a target plasmid encoding the red fluorescent protein (mRFP). Our results suggest that folding of both the precursor guide (pre-crRNA) and the mature guide (crRNA) have a major influence on Cas12a activity. Especially, base pairing of the direct repeat, other than with itself, was found to be detrimental to the activity of Cas12a. Furthermore, we describe different approaches to minimize base-pairing interactions between the direct repeat and the variable part of the guide. We show that design of the 3′ end of the guide, which is not involved in target strand base pairing, may result in substantial improvement of the guide's targeting potential and hence of its genome editing efficiency.
JASS: command line and web interface for the joint analysis of GWAS results
Authors: Julienne Hanna , Lechat Pierre , Guillemot Vincent , Lasry Carla , Yao Chunzi , Araud Robinson , Laville Vincent , Vilhjalmsson Bjarni , Ménager Hervé , Aschard Hugues
Published: January 2020

Genome-wide association study (GWAS) has been the driving force for identifying association between genetic variants and human phenotypes. Thousands of GWAS summary statistics covering a broad range of human traits and diseases are now publicly available. These GWAS have proven their utility for a range of secondary analyses, including in particular the joint analysis of multiple phenotypes to identify new associated genetic variants. However, although several methods have been proposed, there are very few large-scale applications published so far because of challenges in implementing these methods on real data. Here, we present JASS (Joint Analysis of Summary Statistics), a polyvalent Python package that addresses this need. Our package incorporates recently developed joint tests such as the omnibus approach and various weighted sum of Z-score tests while solving all practical and computational barriers for large-scale multivariate analysis of GWAS summary statistics. This includes data cleaning and harmonization tools, an efficient algorithm for fast derivation of joint statistics, an optimized data management process and a web interface for exploration purposes. Both benchmark analyses and real data applications demonstrated the robustness and strong potential of JASS for the detection of new associated genetic variants. Our package is freely available at https://gitlab.pasteur.fr/statistical-genetics/jass.
TP53, ATRX alterations, and low tumor mutation load feature IDH-wildtype giant cell glioblastoma despite exceptional ultra-mutated tumors
Authors: Cantero Diana , Mollejo Manuela , Sepúlveda Juan M , D’Haene Nicky , Gutiérrez-Guamán Myriam J , Rodríguez de Lope Ángel , Fiaño Concepción , Castresana Javier S , Lebrun Laetitia , Rey Juan A , Salmon Isabelle , Meléndez Bárbara , Hernández-Laín Aurelio
Published: January 2020

Background

Giant cell glioblastoma (gcGBM) is a rare morphological variant of IDH-wildtype (IDHwt) GBM that occurs in young adults and have a slightly better prognosis than “classic” IDHwt GBM.

Methods

We studied 36 GBMs, 14 with a histopathological diagnosis of gcGBM and 22 with a giant cell component. We analyzed the genetic profile of the most frequently mutated genes in gliomas and assessed the tumor mutation load (TML) by gene-targeted next-generation sequencing. We validated our findings using The Cancer Genome Atlas (TCGA) data.

Results

p53 was altered by gene mutation or protein overexpression in all cases, while driver IDH1, IDH2, BRAF, or H3F3A mutations were infrequent or absent. Compared to IDHwt GBMs, gcGBMs had a significant higher frequency of TP53, ATRX, RB1, and NF1 mutations, while lower frequency of EGFR amplification, CDKN2A deletion, and TERT promoter mutation. Almost all tumors had low TML values. The high TML observed in only 2 tumors was consistent with POLE and MSH2 mutations. In the histopathological review of TCGA IDHwt, TP53-mutant tumors identified giant cells in 37% of the cases. Considering our series and that of the TCGA, patients with TP53-mutant gcGBMs had better overall survival than those with TP53wt GBMs (log-rank test, P < .002).

Conclusions

gcGBMs have molecular features that contrast to “classic” IDHwt GBMs: unusually frequent ATRX mutations and few EGFR amplifications and CDKN2A deletions, especially in tumors with a high number of giant cells. TML is frequently low, although exceptional high TML suggests a potential for immune checkpoint therapy in some cases, which may be relevant for personalized medicine.
Respiratory health, occupation and the healthy worker effect
Authors: Senthilselvan A , Coonghe W V L , Beach J
Published: January 2020

Background

Workers are exposed to physical, chemical and other hazards in the workplace, which may impact their respiratory health.

Aims

To examine the healthy worker effect in the Canadian working population and to identify the association between occupation and respiratory health.

Methods

Data from four cycles of the Canadian Health Measures Survey were utilized. The current occupation of employed participants was classified into 10 broad categories based on National Occupation Category 2011 codes. Data relating to 15 400 subjects were analysed.

Results

A significantly lower proportion of those in current employment than those not in current employment reported respiratory symptoms or diseases or had airway obstruction. Similarly, those currently employed reported better general health and had greater mean values for percent-predicted forced vital capacity (FVC), forced expiratory volume in one second (FEV1), forced expiratory flow between 25% and 75% of FVC (FEF25–75%) and FEV1/FVC ratio. Among males, females and older age groups, significant differences were observed for almost all the respiratory outcomes for those in current employment. Those in ‘Occupations unique to primary industry’ had a significantly greater likelihood of regular cough with sputum and ever asthma and had lower mean values of percent-predicted FEV1/FVC and FEF25–75% than those in ‘Management occupations’. Those in ‘Health occupations’ had the highest proportion of current asthma.

Conclusions

Participants in current employment were healthier than those not in current employment providing further support for the healthy worker effect. Those in ‘Occupations unique to primary industry’ had an increased risk of adverse respiratory outcomes and reducing workplace exposures in these occupations has the potential to improve their respiratory health.
Pain due to Ehlers-Danlos Syndrome Is Associated with Deficit of the Endogenous Pain Inhibitory Control
Authors: Leone Caterina Maria , Celletti Claudia , Gaudiano Gianfranco , Puglisi Paola Anna , Fasolino Alessandra , Cruccu Giorgio , Camerota Filippo , Truini Andrea
Published: January 2020

Objectives

Although pain is a common complication of the hypermobile type of Ehlers–Danlos syndrome, its underlying mechanisms are still an issue of controversy. In this psychophysical study, we aimed at testing small-fiber function and the endogenous pain inhibitory control in patients with pain due to Ehlers-Danlos syndrome.

Methods

In 22 patients with pain due to Ehlers-Danlos syndrome and 22 healthy participants, matched for age and sex, we tested small-fiber function using quantitative sensory testing and the endogenous pain inhibitory control using the conditioned pain modulation (CPM) protocol. As quantitative sensory testing methods, we included thermal pain and mechanical pain thresholds and the wind-up ratio. The CPM protocol consisted of two heat painful stimuli, that is, a test stimulus and a conditioning stimulus.

Results

All patients complained of widespread pain. Quantitative sensory testing revealed no small-fiber deficit; in the area of maximum pain, we found an increased wind-up ratio. Whereas in the healthy participants the CPM protocol showed that the test stimulus rating was significantly reduced during conditioning, in patients with pain due to hEDS, the test stimulus rating increased during conditioning.

Conclusions

Our psychophysical study showing that patients with pain due to hEDS have an increased wind-up ratio in the area of maximum pain and abnormal CPM protocol suggests that in this condition, pain is associated with central sensitization, possibly due to deficit of the endogenous pain inhibitory control. These data might be relevant to pharmacological treatment.
Macroprudential Regulation versus mopping up after the crash
Authors: Jeanne Olivier , Korinek Anton
Published: January 2020

How should macroprudential policy be designed when policymakers also have access to liquidity provision tools to manage crises? We show in a tractable model of systemic banking risk that there are three factors at play: first, ex post liquidity provision mitigates financial crises, and this reduces the need for macroprudential policy. In the extreme, if liquidity provision is untargeted and costless or if it completely forestalls crises by credible out-of-equilibrium lending-of-last-resort, there is no role left for macroprudential regulation. Second, however, macroprudential policy needs to consider the ex ante incentive effects of targeted liquidity provision. Third, if shadow banking reduces the effectiveness of macroprudential instruments, it is optimal to commit to less generous liquidity provision as a second-best substitute for macroprudential policy.
Enthesitis in psoriatic arthritis (Part 3): clinical assessment and management
Authors: Mease Philip
Published: January 2020

Enthesitis is a common clinical feature of PsA, which is characterized by inflammation at the site of insertion of tendons, ligaments and joint capsule fibres into bone. Enthesitis is relatively unique to the spondyloarthritides, setting this group of diseases apart from other rheumatological conditions. The pathophysiological underpinnings of this clinical domain, and the imaging assessment of it, are described in accompanying articles in this supplement. The focus of this article is on the assessment of enthesitis by physical examination, the impact of enthesitis on function and quality of life, the impact of concomitant FM on clinical assessment, and the evidence for therapy of enthesitis garnered in trials of biologic and targeted synthetic DMARDs. Several physical examination measures of enthesitis have been developed and have proved reliable in assessment of enthesitis. Enthesitis has a significant deleterious impact on function and quality of life. The presence of concomitant FM in ≤20% of patients may result in artefactual worsening of assessment of disease severity and hinder achievement of the goal of low disease activity or remission. Several targeted therapies, which, for example, target the TNF, IL-17, IL-23, phosphodiesterase 4 or Janus kinase pathways, have shown significant efficacy in the treatment of enthesitis, resulting in improvement of function and quality of life for patients with PsA.
What dose of aspirin should be used in the initial treatment of Kawasaki disease? A meta-analysis
Authors: Jia Xinyi , Du Xiao , Bie Shuxian , Li Xiaobing , Bao Yunguang , Jiang Mizu
Published: January 2020

Objective

The use of IVIG plus high- or low-dose aspirin for the initial treatment of Kawasaki disease remains controversial. The aim of this study was to evaluate the efficacy of IVIG plus high-dose aspirin compared with IVIG plus low-dose aspirin in the treatment of Kawasaki disease.

Methods

Studies related to aspirin therapy for Kawasaki disease were selected by searching the databases of Medline (PubMed), Embase and the Cochrane Library before March 2019. Statistical analyses were performed by using a Review Manager Software package and STATA v.15.1.

Results

Eight retrospective cohort studies, characterizing 12 176 patients, were analysed. Overall, no significant difference was found in the incidence of coronary artery abnormalities between the high- and low-dose aspirin groups [relative risk (RR) 1.15; 95% CI: 0.93, 1.43; P = 0.19; random-effects model]. The patients treated with high-dose aspirin had slightly faster resolution of fever [mean difference (MD) −0.30; 95% CI: −0.58, −0.02; P = 0.04; random-effects model]. but the rates of IVIG resistance (RR, 1.26; 95% CI: 0.55, 2.92; P = 0.59; random-effects model) and days in hospital (MD, 0.22; 95% CI: −0.93, 1.37; P = 0.71; random-effects model) were similar between the two groups.

Conclusion

Low-dose aspirin plus IVIG might be as effective as high-dose aspirin plus IVIG for the initial treatment of Kawasaki disease. Considering that high-dose aspirin may cause more adverse reactions than low-dose aspirin, low-dose aspirin plus IVIG should be recommended as the first-line therapy in the initial treatment of Kawasaki disease.
Who Will Be Left to Care?
Authors: Kennedy Maureen Shawn
Published: January 2020

Stress and burnout among clinicians require immediate attention.
Preparing for NCLEX-RN Success: Communication, Support, Mentoring, and Tutoring for New BSN Graduates
Authors: Stuckey Lanette Christine , Wright Ariel Nicole
Published: January 2020

Nurse educators are charged with designing and delivering preparation initiatives that will enable graduates to be successful on the National Council Licensure Examination for Registered Nurses (NCLEX-RN®). Research focusing on nursing students from the time of graduation until they take the NCLEX-RN is limited. To assist with increasing NCLEX-RN pass rates, an innovative approach to mentoring BSN graduates while preparing for the NCLEX-RN was developed. The postgraduate mentorship program was implemented through communication, support, mentoring, and tutoring of BSN students after graduation. Results indicate that the mentorship program was successful at increasing pass rates and was beneficial for students.
Systemic hypereosinophilic syndromes: when autoimmunity is Th2 mediated
Authors: Matucci Andrea , Nencini Francesca , Maggi Enrico , Vultaggio Alessandra
Published: January 2020

Purpose of review

Clinical conditions associated with hypereosinophilia represent a field of particular interest, taking into account the epidemiological impact of the different primary and secondary forms. In addition to a classical Th1 response, also Th2 cells can be involved in the pathogenesis of autoimmune diseases, among them eosinophilic forms such as eosinophilic granulomatosis with polyangiitis.

Recent findings

In patients with severe asthma, recent evidence highlights the role of pathogenic autoantibodies against autologous eosinophil proteins (e.g. eosinophil peroxidase) suggest the role of autoimmune mechanisms, particularly in patients in which asthma is included in eosinophilic vasculitis with antineutrophilic autoantibody positivity. Is now evident that in addition to Th2 cells, also type 2 innate lymphoid cells and Th1/Th17 cells play a central role in the pathogenesis of hypereosinophilic syndrome.

The definition of cellular and molecular mechanisms and the critical role of specific cytokines involved in the pathogenesis of hypereosinophilic syndrome open the way to new therapeutic strategies by using biological agents targeting these specific factors.
Childhood asthma in the new omics era: challenges and perspectives
Authors: Golebski Korneliusz , Kabesch Michael , Melén Erik , Potočnik Uroš , van Drunen Cornelis M. , Reinarts Susanne , Maitland-van der Zee Anke H. , Vijverberg Susanne J.H.
Published: January 2020

Purpose of review

Childhood asthma is a heterogeneous inflammatory disease comprising different phenotypes and endotypes and, particularly in its severe forms, has a large impact on the quality-of-life of patients and caregivers. The application of advanced omics technologies provides useful insights into underlying asthma endotypes and may provide potential clinical biomarkers to guide treatment and move towards a precision medicine approach.

Recent findings

The current article addresses how novel omics approaches have shaped our current understanding of childhood asthma and highlights recent findings from (pharmaco)genomics, epigenomics, transcriptomics, and metabolomics studies on childhood asthma and their potential clinical implications to guide treatment in severe asthmatics.

Until now, omics studies have largely expanded our view on asthma heterogeneity, helped understand cellular processes underlying asthma, and brought us closer towards identifying (bio)markers that will allow the prediction of treatment responsiveness and disease progression. There is a clinical need for biomarkers that will guide treatment at the individual level, particularly in the field of biologicals. The integration of multiomics data together with clinical data could be the next promising step towards development individual risk prediction models to guide treatment. However, this requires large-scale collaboration in a multidisciplinary setting.
Alcohol Use Behaviors and Reasons to Abstain From or Limit Drinking Among Medically Vulnerable Youth
Authors: Wisk Lauren E. , Magane Kara M. , Levy Sharon , Weitzman Elissa R.
Published: January 2020

Background:

Youth with chronic medical conditions (YCMC) use alcohol at levels similar to their healthy peers but face elevated risk for adverse health consequences. As salient reasons to abstain from or limit drinking (RALD) among YCMC are unknown, we sought to identify clusters of RALD and test associations with use behaviors.

Methods:

Eligible YCMC (ages 9–18) recruited from outpatient clinics reported their use behaviors and importance of potential RALD. Cluster analysis was used to discern RALD patterns, which were examined as predictors of alcohol use using multivariate regression.

Results:

Among 398 participants, 30.9% reported past year alcohol use. Concerns about impacts on medications, school, and disease status were the most frequently endorsed RALD; prior negative experiences with alcohol and family history were the least frequently endorsed. Five RALD clusters were identified for all YCMC and 2 for recent drinkers. Compared to the cluster with high endorsement of multiple general and health-related RALD, those predominantly citing concerns about addiction and those not strongly endorsing any RALD consistently reported greater alcohol use. Among recent drinkers, the cluster characterized by low concern across multiple RALD also consistently reported greater alcohol use compared to their counterparts expressing moderate concern.

Conclusions:

For YCMC, RALD are complex but endorsement of multiple general and health-related RALD is associated with less use, and health concerns are especially prevalent. More research is needed to understand how salient RALD can inform tailored interventions that aim to delay and reduce substance use and improve health outcomes for YCMC.
Neural Selective Cryoneurolysis with Ice Slurry Injection in a Rat Model
Authors: Garibyan Lilit , Moradi Tuchayi Sara , Wang Ying , Khodorova Alla , Stemmer-Rachamimov Anat , Purschke Martin , Osseiran Sam , Evans Conor L. , Mao Jianren , Strichartz Gary , Anderson R. Rox
Published: January 2020

Background

Postoperative pain caused by trauma to nerves and tissue around the surgical site is a major problem. Perioperative steps to reduce postoperative pain include local anesthetics and opioids, the latter of which are addictive and have contributed to the opioid epidemic. Cryoneurolysis is a nonopioid and long-lasting treatment for reducing postoperative pain. However, current methods of cryoneurolysis are invasive, technically demanding, and are not tissue-selective. This project aims to determine whether ice slurry can be used as a novel, injectable, drug-free, and tissue-selective method of cryoneurolysis and resulting analgesia.

Methods

The authors developed an injectable and selective method of cryoneurolysis using biocompatible ice slurry, using rat sciatic nerve to investigate the effect of slurry injection on the structure and function of the nerve. Sixty-two naïve, male Sprague-Dawley rats were used in this study. Advanced Coherent anti-Stokes Raman Scattering microscopy, light, and fluorescent microscopy imaging were used at baseline and at various time points after treatment for evaluation and quantification of myelin sheath and axon structural integrity. Validated motor and sensory testing were used for evaluating the sciatic nerve function in response to ice slurry treatment.

Results

Ice slurry injection can selectively target the rat sciatic nerve. Being injectable, it can infiltrate around the nerve. The authors demonstrate that a single injection is safe and selective for reversibly disrupting the myelin sheaths and axon density, with complete structural recovery by day 112. This leads to decreased nocifensive function for up to 60 days, with complete recovery by day 112. There was up to median [interquartile range]: 68% [60 to 94%] reduction in mechanical pain response after treatment.

Conclusions

Ice slurry injection selectively targets the rat sciatic nerve, causing no damage to surrounding tissue. Injection of ice slurry around the rat sciatic nerve induced decreased nociceptive response from the baseline through neural selective cryoneurolysis.

Editor’s Perspective

What We Already Know about This Topic

What This Article Tells Us That Is New
Telehealth Interventions to Improve Obstetric and Gynecologic Health Outcomes
Authors: DeNicola Nathaniel , Grossman Daniel , Marko Kathryn , Sonalkar Sarita , Butler Tobah Yvonne S. , Ganju Nihar , Witkop Catherine T. , Henderson Jillian T. , Butler Jessica L. , Lowery Curtis
Published: January 2020

OBJECTIVE:

To systematically review the effectiveness of telehealth interventions for improving obstetric and gynecologic health outcomes.

DATA SOURCES:

We conducted a comprehensive search for primary literature in ClinicalTrials.gov, Cochrane Library, Cochrane Collaboration Registry of Controlled Trials, EMBASE, PubMed, and MEDLINE.

METHODS OF STUDY SELECTION:

Qualifying primary studies had a comparison group, were conducted in countries ranked very high on the United Nations Human Development Index, published in English, and evaluated obstetric and gynecologic health outcomes. Cochrane Collaboration's tool and ROBINS-I tool were used for assessing risk of bias. Summary of evidence tables were created using the United States Preventive Services Task Force Summary of Evidence Table for Evidence Reviews.

TABULATION, INTEGRATION, RESULTS:

Of the 3,926 published abstracts identified, 47 met criteria for inclusion and included 31,967 participants. Telehealth interventions overall improved obstetric outcomes related to smoking cessation and breastfeeding. Telehealth interventions decreased the need for high-risk obstetric monitoring office visits while maintaining maternal and fetal outcomes. One study found reductions in diagnosed preeclampsia among women with gestational hypertension. Telehealth interventions were effective for continuation of oral and injectable contraception; one text-based study found increased oral contraception rates at 6 months. Telehealth provision of medication abortion services had similar clinical outcomes compared with in-person care and improved access to early abortion. Few studies suggested utility for telehealth to improve notification of sexually transmitted infection test results and app-based intervention to improve urinary incontinence symptoms.

CONCLUSION:

Telehealth interventions were associated with improvements in obstetric outcomes, perinatal smoking cessation, breastfeeding, early access to medical abortion services, and schedule optimization for high-risk obstetrics. Further well-designed studies are needed to examine these interventions and others to generate evidence that can inform decisions about implementation of newer telehealth technologies into obstetrics and gynecology practice.
Penicillin Allergy in Pregnancy
Authors: Turrentine Mark A. , King Tekoa L. , Silverman Neil S.
Published: January 2020

The emergence of beta-lactam–resistant pathogenic organisms has resulted in limitation or even elimination of drugs such as penicillin and ampicillin from available antibiotic choices for treating common infections in obstetrics and gynecology. In clinical situations for which penicillins and cephalosporins are appropriate or recommended first-line agents, the problem of patient-reported penicillin allergies has led to routine use of alternative but potentially less effective agents. The use of broader-spectrum and potentially suboptimal alternative antibiotic regimens for intrapartum antibiotic prophylaxis against group B streptococcus or for surgical prophylaxis for cesarean delivery in women with a reported penicillin allergy may affect these women during labor and birth. Most individuals who report a penicillin allergy are neither truly allergic nor at risk of developing a hypersensitivity reaction after exposure to penicillin. The available evidence suggests that there are important roles for both targeted history-taking, to determine the nature of drug allergies and penicillin allergy testing in pregnant women, to optimize their antibiotic-related treatment both during pregnancy and for their lifetimes. Wider consideration and adoption of penicillin allergy testing in pregnant women specifically, as well as the general population of women cared for by providers of obstetrics and gynecology, is recommended.
Genes Implicated in Rare Congenital Inner Ear and Cochleovestibular Nerve Malformations
Authors: Kari Elina , Llaci Lorida , Go John L. , Naymik Marcus , Knowles James A. , Leal Suzanne M. , Rangasamy Sampath , Huentelman Matthew J. , Liang Winnie , Friedman Rick A. , Schrauwen Isabelle
Published: January 2020

Objective:

A small subset of children with congenital hearing loss have abnormal cochleovestibular nerves (i.e., absent, aplastic, or deficient cochlear nerves), with largely unknown etiology. Our objective was to investigate the underlying pathways and identify novel genetic variants responsible for cochleovestibular malformations and nerve abnormalities. It is our hypothesis that several cochleovestibular nerve abnormalities might share common causative pathways.

Design:

We used a family-based exome sequencing approach to study 12 children with known rare inner ear and/or cochleovestibular nerve malformations.

Results:

Our results highlight a diverse molecular etiology and suggest that genes important in the developing otic vesicle and cranial neural crest, e.g., MASP1, GREB1L, SIX1, TAF1, are likely to underlie inner ear and/or cochleovestibular nerve malformations.

Conclusions:

We show that several cochleovestibular nerve malformations are neurocristopathies, which is consistent with the fact that cochleovestibular nerve development is based on otic placode-derived neurons in close association with neural crest-derived glia cells. In addition, we suggest potential genetic markers for more severely affected phenotypes, which may help prognosticate individual cochlear implantation outcomes. Developing better strategies for identifying which children with abnormal nerves will benefit from a cochlear implantation is crucial, as outcomes are usually far less robust and extremely variable in this population, and current neuroimaging and electrophysiologic parameters cannot accurately predict outcomes. Identification of a suitable treatment early will reduce the use of multiple interventions during the time-sensitive period for language development.
Pulling the Trigger: Recommendations for Surgical Care of the Pediatric Trigger Thumb
Authors: Dittmer Alison J. , Grothaus Olivia , Muchow Ryan , Riley Scott
Published: January 2020

Background:

Despite being a common pediatric hand condition, there are few clear guidelines regarding the optimal management of pediatric trigger thumb. Our primary aim was to help guide surgical management of this disorder by establishing a treatment algorithm on the basis of our institution’s experience.

Methods:

This is an institutional review board-approved retrospective study of all patients with idiopathic trigger thumbs from 2005 to 2015 at a single institution. Demographics and treatment course were recorded for all patients including duration of follow-up, observation, surgical intervention, and complications. All children were classified according to the Sugimoto classification.

Results:

A total of 149 patients with 193 thumbs met inclusion and exclusion criteria. 16.5% of patients had stage II thumbs, 10.3% of patients with stage III, and 73% of patients with stage IV thumbs. Of all patients with stage IV thumbs, 3.5% were locked in extension for an overall incidence of 2.6%.

In total, 46% of patients failed observation and underwent surgical treatment. Only 14% of stage IV trigger thumbs resolved when observed, compared with 53% of stage II and 25% of stage III trigger thumbs. Stage IV thumbs were 4.6 times more likely to fail conservative treatment and go on to surgery than stage II or III thumbs (odds ratio, 4.6; P=0.006).

Thirty-two percent of patients underwent surgery without an observation period. Older children with bilateral stage 3 thumbs were the most likely to go straight to the odds ratio instead of being observed (P=0.002, r
2=0.17).

Of the total amount of patients who underwent surgery (116), there were 4 complications for a rate of 3.4% with a recurrence rate of 1.7%.

Conclusions:

On the basis of the data in this study, the authors would recommend that stage IV thumbs undergo surgery without an observational period. Second, stage II and stage III thumbs can be safely observed for at least 1 year before surgery. Finally, our study concurs with the literature that surgery can be successful with low rates of complications and recurrence.

Level of Evidence:

Level IV.
Tendoscopy for Early-Stages (I and II) Posterior Tibial Tendon Dysfunction
Authors: Bernasconi Alessio , Mehdi Nazim , Laborde Julien , de Cesar Netto Cesar , Lintz François
Published: January 2020

Tendoscopy of tibialis posterior tendon has been proposed >20 years ago for the treatment of posterior tibial tendon dysfunction. A few studies have reported satisfactory results in stages I and II posterior tibial tendon dysfunction (Johnson and Strom classification). This approach allows us to assess the posterior tibial tendon and the spring ligament status, and if needed to perform a synovectomy with soft-tissue debridement. Longitudinal split tendon tears can also be repaired. In case of failure, a traditional corrective open surgery can normally be performed. In this manuscript, we summarize the history of this technique and also reported the indications, surgical approach, results, and complications.
Platelet-to-lymphocyte ratio predicts therapy outcomes of transarterial chemoembolization plus apatinib in the treatment of advanced hepatocellular carcinoma
Authors: Chen Lei , Ke Zunqian , Xiong Fu , Kan Xuefeng , Ren Yanqiao , Cao Yanyan , Sun Tao , Yan Liangliang , Zhou Guofeng , Zheng Chuansheng
Published: January 2020

To evaluate the predictive value of preoperative biochemical marker [platelet-to-lymphocyte ratio (PLR)] in patients with advanced hepatocellular cancer receiving transarterial chemoembolization (TACE) plus targeted molecular therapy (apatinib) treatment. Clinical records of 134 patients receiving the treatment of TACE + apatinib (TACE-A) and the treatment of TACE alone were compared in a single-center study. Time to progression (TTP) and overall survival (OS) were compared between TACE-A and TACE alone groups in patients with PLR > 150 and PLR ≤ 150, respectively. The area under the receiver operating characteristic (ROC) curve was used to determine the prediction power of PLR. The median TTP and OS in the TACE-A group were significantly longer than those in the TACE alone group (P < 0.001). The median TTP and OS in the TACE-A (PLR ≤ 150) group were longer than those in the TACE-A (PLR > 150) group (P < 0.05). There was no significant difference between TACE-A (PLR > 150) and TACE alone (P = 0.232) groups in OS, but the median TTP in the TACE-A (PLR > 150) group was longer than that in the TACE alone group (P = 0.001). ROC analysis showed that the area under the curve was 0.643 and 0.623 for 6- and 12-month survival, respectively. PLR might predict the results of patients with advanced hepatocellular carcinoma received TACE-A treatment.
Multimodal Therapeutic Approach of Cytokine Release Syndrome Developing in a Child Given Chimeric Antigen Receptor-Modified T Cell Infusion
Authors: Bottari Gabriella , Merli Pietro , Guzzo Isabella , Stoppa Francesca , Ruggeri Annalisa , Di Nardo Matteo , Del Bufalo Francesca , Galaverna Federica , Corrado Cecchetti , Locatelli Franco
Published: January 2020

Objectives:

To describe a pediatric case of cytokine release syndrome secondary to chimeric antigen receptor-modified T cells associated with acute respiratory distress syndrome.

Design:

Case report.

Setting:

PICU.

Patients:

A 14-year-old boy with refractory B cell precursor acute lymphoblastic leukemia given chimeric antigen receptor cells developed severe cytokine release syndrome 7 days after the drug product infusion with progressive respiratory failure. He was admitted to PICU with a clinical picture of acute respiratory distress syndrome, requiring mechanical ventilation, and secondary hemophagocytic lymphohistiocytosis.

Interventions:

Hemoadsorption with cartridge column (Cytosorb) in combination with continuous renal replacement therapy was associated to the anti-cytokine therapy (tocilizumab, a monoclonal antibody targeting interleukin-6 receptor).

Measurements and Main Results:

Decrease of the inflammatory biomarkers (ferritin, interleukin-6, interleukin-10) in the first 96 hours associated with a progressive improvement of acute respiratory distress syndrome (Pao
2/Fio
2 ratio) 7 day after the start of the multimodal treatment.

Conclusions:

This case suggests that hemoadsorption with cartridge column in combination with continuous renal replacement therapy and tocilizumab is safe and potentially effective in pediatric patients with severe cytokine release syndrome.
The Effect of Outcome Selection on the Performance of Prediction Models in Patients at Risk for Sepsis
Authors: Taylor Stephanie P. , Chou Shih-Hsiung , McWilliams Andrew D. , Russo Mark , Heffner Alan C. , Murphy Stephanie , Evans Susan L. , Rossman Whitney , Kowalkowski Marc ,   on behalf of Acute Care Outcomes Research Network (ACORN) Investigators
Published: January 2020

Importance:

Risk prediction models for patients with suspected sepsis have been derived on and applied to various outcomes, including readily available outcomes such as hospital mortality and ICU admission as well as longer-term mortality outcomes that may be more important to patients. It is unknown how selecting different outcomes influences model performance in patients at risk for sepsis.

Objectives:

Evaluate the impact of outcome selection on risk model performance and weighting of individual predictor variables.

Design, Setting, and Participants:

We retrospectively analyzed adults hospitalized with suspected infection from January 2014 to September 2017 at 12 hospitals.

Main Outcomes and Measures:

We used routinely collected clinical data to derive logistic regression models for four outcomes: hospital mortality, composite ICU length of stay greater than 72 hours or hospital mortality, 30-day mortality, and 90-day mortality. We compared the performance of the models using area under the receiver operating characteristic curve and calibration plots.

Results:

Among 52,184 admissions, 2,030 (4%) experienced hospital mortality, 6,659 (13%) experienced the composite of hospital mortality or ICU length of stay greater than 72 hours, 3,417 (7%) experienced 30-day mortality, and 5,655 (11%) experienced 90-day mortality. Area under the receiver operating characteristic curves decreased when hospital-based models were applied to predict 30-day (hospital mortality = 0.88–0.85; –0.03, composite ICU length of stay greater than 72 hours or hospital mortality = 0.90–0.81; –0.09) and 90-day mortality (hospital mortality = 0.88–0.81; –0.07, composite ICU length of stay greater than 72 hours or hospital mortality = 0.90–0.76; –0.14; all p < 0.01). Models were well calibrated for derived (root-mean-square error = 5–15) but not alternate outcomes (root-mean-square error = 8–35).

Conclusions and Relevance:

Risk models trained to predict readily available hospital-based outcomes in suspected sepsis show poorer discrimination and calibration when applied to 30- and 90-day mortality. Interpretation and application of risk models for patients at risk of sepsis should consider these findings.
A Case Series of Vaping-Associated Lung Injury Requiring Mechanical Ventilation
Authors: Choe June , Chen Peter , Falk Jeremy A. , Nguyen Luan , Ng David , Parimon Tanyalak , Ghandehari Sara
Published: January 2020

Objectives:

Vaping-associated lung injury has rapidly become a nationwide epidemic and a threat to public health. In this case series, we describe unique clinical features of severe vaping-associated lung injury, defined as respiratory failure due to vaping that requires mechanical ventilation.

Data Sources:

Clinical observation of four patients.

Study Selection:

Case series.

Data Extraction:

Data and images were extract from medical records after approval was obtained from the institutional review board.

Data Synthesis:

Four patients were admitted to the ICU with severe manifestation of vaping-associated lung injury. Although every case required mechanical ventilatory support (venovenous extracorporeal membrane oxygenation in one patient), all patients survived and were discharged without supplemental oxygen. Systemic corticosteroids were administered in three patients and N-acetyl cysteine in one. A postdischarge pulmonary function test in one patient was normal except for mildly decreased diffusing capacity.

Conclusions:

Based on our experience, prognosis of severe vaping-associated lung injury appears favorable with aggressive supportive care, although there is evidence from existing literature that mortality rate might rise with increasing disease severity. Underlying mechanism of lung injury might be similar between vaping-associated lung injury and amiodarone pneumonitis. Foamy or lipid-laden macrophages, seen in both conditions, might be a marker of cytotoxicity from substances contained in e-cigarettes, such as vitamin E acetate. Systemic corticosteroids, and possibly N-acetyl cysteine, could be considered as therapeutic adjuncts in vaping-associated lung injury. Serial pulmonary function tests should be obtained in these patients to monitor for potential long-term complications. The primary limitations of this case series are its small sample and lack of longitudinal follow-up data.
A Practical Approach to Hybrid Coronary Revascularization
Authors: Singh Twinkle , Ayinapudi Karnika , Motwani Ayush , Hendel Robert , Le Jemtel Thierry H.
Published: January 2020

Combined surgical and percutaneous coronary revascularization, ie, hybrid coronary revascularization (HCR) consists of surgical left internal mammary artery (LIMA) bypass to the left anterior descending artery (LAD) and percutaneous revascularization of other diseased coronary arteries. Developed as a 1-stage procedure, HCR has not been widely adopted by the cardiovascular community. The recommended minimally invasive approach through a small left thoracotomy incision is technically demanding, and same-day percutaneous revascularization requires a hybrid operating room that is not available in most hospitals. In this review, we consider present HCR protocols, barriers to widespread adoption of HCR, and we give special attention to the surgical approach for the LIMA graft to the LAD and the timing of percutaneous revascularization. We conclude that grafting the LIMA to the LAD through a median sternotomy approach and delaying the percutaneous revascularization may facilitate the widespread use of HCR in patients with multivessel coronary artery disease and a low to intermediate Synergy between Percutaneous Coronary Intervention with Taxus and Cardiac Surgery score.
Apocrine Hidradenoma and Adenomyoepithelioma: Entities on a Biological Continuum of Adnexal Neoplasia
Authors: MacKinnon William F. , Moss Phillip , Pasternak Sylvia , Matheson Kara , Walsh Noreen M.
Published: January 2020

Apocrine hidradenomas (AH) once believed to harbor myoepithelial cells are now considered pure epithelial neoplasms. They are categorized separately from adenomyoepitheliomas which consist of apocrine epithelial and myoepithelial components. Reports of myoepithelial tumors arising in AH have suggested a link between the 2. Our goal was to explore whether cases diagnosed on routine microscopy as AH harbored occult myoepithelial elements, which would be disclosed by an immunohistochemical evaluation. Twenty-nine such cases, derived from a teaching collection of one of the authors, formed the basis of the study. Clinical and demographic data were documented, and morphological details of the cases were recorded. A panel of immunohistochemistry (AE1AE3, CK8/18, epithelial membrane antigen, p63, S100 protein, glial fibrillary acid protein, calponin, alpha actin, and others), designed to identify myoepithelial cells, was used. The population consisted of 14 women and 15 men (mean age 55.8; range 26–82 years). The tumors, located on the head/neck (14), limbs (10), and trunk (5), were solid (2) and solid/cystic (27). They exhibited varied (often combined) cytological elements (clear, squamoid, polygonal, and mucinous cells). On immunohistochemistry, aggregates of myoepithelial cells were identified in 5 (17%) cases. Four were calponin+ and AE1AE3+; they occupied ≤30% of tumor volumes and exhibited fusiform cytomorphology. One was S100 protein+ and AE1AE3+; it occupied 70% of tumor volume and exhibited polygonal cytomorphology. The gradation in the volume of myoepithelial elements disclosed by immunohistochemistry in a subset of our cases suggests that AH and adenomyoepitheliomas exist on a biological continuum of adnexal neoplasia. The diagnostic categorization of lesions with dual elements requires further study, but we propose that the term adenomyoepithelioma be restricted to those in which myoepithelial cells constitute ≥25% of tumor volume.
A Rare Perineurioma/Granular Cell Tumor Hybrid Peripheral Nerve Sheath Tumor
Authors: Haghayeghi Koorosh , Telang Gladys , Chen Sonja , Bevivino Jack , Mangray Shamlal , Hui Yiang , Robinson-Bostom Leslie
Published: January 2020

Hybrid peripheral nerve sheath tumors (PNSTs) are rare benign composite neoplasms demonstrating features of multiple endogenous nerve sheath cell types. Hybrid PNSTs with granular cell components are exceedingly rare. Only a handful number of hybrid PNSTs composed of granular cell tumor and perineurioma have been described to date. We present a rare hybrid of perineurioma and granular cell tumor and review the literature.