bluuebunny/crossref_metadata_2025 huggingface dataset:
Edoxaban in atrial fibrillation patients with percutaneous coronary intervention by acute or chronic coronary syndrome presentation: a pre-specified analysis of the ENTRUST-AF PCI trial
Authors: Vranckx Pascal , Valgimigli Marco , Eckardt Lars , Lewalter Thorsten , Unikas Ramunas , Marin Francisco , Schiele François , Laeis Petra , Reimitz Paul-Egbert , Smolnik Rüdiger , Zierhut Wolfgang , Tijssen Jan , Goette Andreas
Published: July 2020

Aims 

To compare the safety and efficacy of edoxaban combined with P2Y12 inhibition following percutaneous coronary intervention (PCI) in patients with atrial fibrillation (AF) presenting with an acute coronary syndrome (ACS) or chronic coronary syndrome (CCS).

Methods and results 

In this pre-specified sub-analysis of the ENTRUST-AF PCI trial, participants were randomly assigned 1:1 to edoxaban- or vitamin K antagonist (VKA)-based strategy and randomization was stratified by ACS (edoxaban n = 388, VKA n = 389) vs. CCS (edoxaban n = 363, VKA = 366). Participants received edoxaban 60 mg once-daily plus a P2Y12 inhibitor for 12 months, or VKA combined with a P2Y12 inhibitor and aspirin 100 mg (for 1–12 months). The primary bleeding endpoint at 12 months occurred in 59 (15.2%) vs. 79 (20.3%) ACS patients [hazard ratio (HR): 0.73, 95% confidence interval (CI): 0.59–1.02, P = 0.063], and in 69 (19.0%) vs. 73 (19.9%) CCS patients (HR: 0.94, 95%CI: 0.68–1.31, P = 0.708) with edoxaban- and VKA-based therapy, respectively [P for interaction (P-int) = 0.2741]. The main secondary endpoint (composite of CV death, myocardial infarction, stroke, systemic embolic events, or definite stent thrombosis) in ACS patients was 33 (8.5%) vs. 28 (7.2%) (HR: 1.16, 95%CI: 0.70–1.92), compared with 16 (4.4%) vs. 18 (4.9%) (HR: 0.91, 95%CI: 0.47–1.78) CCS patients with edoxaban and VKA-based therapy, respectively (P-int = 0.5573).

Conclusions 

In patients with AF who underwent PCI, the edoxaban-based regimen, as compared with VKA-based regimen, provides consistent safety and similar efficacy for ischaemic events in patients with AF regardless of their clinical presentation.
A statistical approach to account for azimuthal variability in single-station HVSR measurements
Authors: Cheng Tianjian , Cox Brady R , Vantassel Joseph P , Manuel Lance
Published: July 2020

The horizontal-to-vertical spectral ratio (HVSR) of ambient noise is commonly used to infer a site's resonance frequency (${f_{0,site}}$). HVSR calculations are performed most commonly using the Fourier amplitude spectrum obtained from a single merged horizontal component (e.g. the geometric mean component) from a three-component sensor. However, the use of a single merged horizontal component implicitly relies on the assumptions of azimuthally isotropic seismic noise and 1-D surface and subsurface conditions. These assumptions may not be justified at many sites, leading to azimuthal variability in HVSR measurements that cannot be accounted for using a single merged component. This paper proposes a new statistical method to account for azimuthal variability in the peak frequency of HVSR curves (${f_{0,HVSR}}$). The method uses rotated horizontal components at evenly distributed azimuthal intervals to investigate and quantify azimuthal variability. To ensure unbiased statistics for ${f_{0,HVSR}}$ are obtained, a frequency-domain window-rejection algorithm is applied at each azimuth to automatically remove contaminated time windows in which the ${f_{0,HVSR}}$ values are statistical outliers relative to those obtained from the majority of windows at that azimuth. Then, a weighting scheme is used to account for different numbers of accepted time windows at each azimuth. The new method is applied to a data set of 114 HVSR measurements with significant azimuthal variability in ${f_{0,HVSR}}$, and is shown to reliably account for this variability. The methodology is also extended to the estimation of a complete lognormal-median HVSR curve that accounts for azimuthal variability. To encourage the adoption of this statistical approach to accounting for azimuthal variability in single-station HVSR measurements, the methods presented in this paper have been incorporated into hvsrpy, an open-source Python package for HVSR processing.
Early rupture signals predict the final earthquake size
Authors: Colombelli Simona , Festa Gaetano , Zollo Aldo
Published: July 2020

When a seismic rupture starts, the process may evolve into multiple ways, generating different size earthquakes. Contrasting models have been proposed to describe the evolution of the rupture process while limited observations at the scale of real earthquake data are available, so that a unifying theory is still missing. Here we show that small and large earthquake ruptures are different before the arrest and they do not exhibit a common, size-independent, universal behaviour. For earthquakes with magnitude 4 < M < 9 occurred in Japan, we measure the initial rate of the P-wave peak amplitude and show that this quantity is correlated to the final event magnitude and not affected by distance attenuation, thus being a proxy for the initiation time of the rupture process. While opening new views on the rupture preparation process, our findings can have significant implications on the effective development of fast and reliable methods for source characterization and ground shaking prediction.
Added value of buccal cell FISH analysis in the diagnosis and management of Turner syndrome
Authors: Graff A , Donadille B , Morel H , Villy M C , Bourcigaux N , Vatier C , Borgel A , Khodawardi A , Siffroi J P , Christin-Maitre S
Published: July 2020

STUDY QUESTION

Is there an added diagnosis value of buccal cell FISH analysis compared with blood lymphocyte chromosomal investigations in patients with Turner syndrome (TS)?

SUMMARY ANSWER

Buccal cell FISH analysis, a non-invasive technique, modified the chromosomal results obtained with the blood karyotype in 17 patients (12%) of our cohort.

WHAT IS KNOWN ALREADY

Few studies have evaluated buccal cell FISH analysis and compared them with blood karyotype in patients with TS.

STUDY DESIGN, SIZE, DURATION

A prospective, monocentric cohort study was conducted in a rare diseases centre (CMERC) between July 2017 and August 2019.

PARTICIPANTS/MATERIALS, SETTING, METHODS

In total, 142 adult patients with TS, and at least 5% 45,X cells in a previous blood karyotype, were recruited. All the patients’ files were included in the CEMARA database. This national database has been declared to the French data protection agency (CNIL approval number 1187326). In compliance with French law, consent regarding non-opposition to collect and use the data was obtained from each patient. A FISH analysis on a buccal smear was performed.

MAIN RESULTS AND THE ROLE OF CHANCE

The percentage of 45,X cells was identical between the two tissues in only 32.4% of cases. The discrepancy was higher than 41% for 12% of the cohort. The percentage of 45,X cells was higher in blood in 53 (37.3%) patients, and higher in buccal cells in 43 (30.3%) of cases. In 17 (12%) cases, the blood karyotype had to be reconsidered in regard to the buccal cell analysis.

LIMITATIONS, REASONS FOR CAUTION

It would have been interesting to evaluate karyotypes in cells from other tissues such as cells from skin biopsy or from the urinary tract and even from blood vessels or gonads in case of surgery and to compare them with each patient’s phenotype. However, most of the time, these tissues are not available.

WIDER IMPLICATIONS OF THE FINDINGS

Although blood lymphocyte karyotype remains the gold standard for the diagnosis of TS, buccal cell FISH analysis is an efficient tool to evaluate the global chromosomal constitution in these patients, thus allowing them to have better care and follow-up. For instance, identifying a Y chromosome can prevent the occurrence of a gonadoblastoma, as gonadectomy should be discussed. On the other hand, finding normal XX cells in a patient with a previous diagnosis of homogenous 45,X TS, may be psychologically helpful and relevant for gynaecological care.

STUDY FUNDING/COMPETING INTEREST(S)

No specific funding was sought for the study. The authors declare no competing interests.

TRIAL REGISTRATION NUMBER

N/A
Decentering International Relations: The Continued Wisdom of Latin American Dependency
Authors: Zambrano Márquez Diego Miguel
Published: July 2020

Although many international relations (IR) theory and international political economy textbooks consistently reference dependency theory, it is commonly considered a passé, outdated, or defunct theoretical approach. This paper challenges conventional wisdom, stressing the continued relevance of dependency as an analytical approach. Overall, it argues that Dependency theory represents a successful effort at decentering IR. To do so, it first discusses decentering as an effort to challenge and engage core concepts in IR to transform the “universal” understandings of global politics. In this sense, Dependency theory decentered IR by introducing an understanding of the world in which Western and non-Western spaces are mutually constitutive, highlighting the role of non-core contexts in creating and maintaining the status quo of the universal. Second, the paper analyzes the influence of Dependency theory in modern discourses of political economy like the resource curse, globalization, Post-Colonialism, and Post-Developmentalism. These parallelisms show Dependency's effectiveness at decentering IR and transforming the way the discipline studies non-core spaces.
Results Multi-Laboratory Trial ISO/CD 22184—IDF/WD 244: Milk and Milk Products—Determination of the Sugar Contents—High-Performance Anion Exchange Chromatography Method with Pulsed Amperometric Detection
Authors: Brunt Kommer , Sanders Peter , Ernste-Nota Veronica , van Soest J.
Published: July 2020

Background

In this international Multi-Laboratory Trial (MLT) the precision data and the accuracy of the ISO/CD 22184 IDF/WD 244 analytical method for the quantification of 6 different mono- and disaccharides (galactose, glucose, fructose, sucrose, lactose, and maltose) in milk and milk products with high-performance anion exchange chromatography with pulsed amperometric detection (HPAEC-PAD) are established.

Objective

Thirteen different laboratories participated (located in New Zealand, the United States, and Europe). The study was divided into two parts. First, the learning/familiarization part in which the participants got experienced with the method. After successfully completing this part, the participants were allowed to continue with the second part of this trial: the analyses of the seven blind MLT duplicate samples.

Method

The selected seven MLT samples comprise five MUVA reference dairy samples, one NIST-certified infant formula and one industrial sample. In the Tables S-1 to S-6 the results of this MLT study have been summarized per sugar. There is a very good agreement between the MUVA and NIST-certified sugar contents in the MLT samples and in the MLT established sugar contents in those MUVA and NIST samples.

Results

This demonstrates that the accuracy of the newly developed HPAEC-PAD method is very good.

Conclusions

Certificates of analysis were available for both the MUVA samples and the NIST sample. There is a very good agreement between the by MUVA- and NIS-certified sugar contents in the MLT samples and the corresponding in the MLT established sugar contents. This demonstrates that the accuracy of the HPAEC-PAD method is very good. In the IDF/ISO Analytical Week in June 2019 in Prague the report on the MLT study were discussed and adopted.
Acute abdomen due to spilled gallstones: a diagnostic dilemma 10 years after laparoscopic cholecystectomy
Authors: Kafadar Mehmet Tolga , Çetinkaya İsmail , Aday Ulaş , Başol Ömer , Bilge Hüseyin
Published: July 2020

Laparoscopic cholecystectomy (LC) carries a significant risk of gallbladder perforation and resulting scattering of bile stones into the abdominal cavity. The retrieval of the spilled stones is not always possible by laparoscopic technique. Most cases do not create long-term problems, although some cases may be complicated in future and create uncertainties regarding the correct diagnosis. Diagnosis can be difficult, and in most cases the patient may require open surgery for management of these complications. Herein, we report a case of acute abdomen due to spilled stones occurring 10 years after LC. In the first stage, definitive diagnosis could not be made with computed tomography examination. Finally, the patient was diagnosed with explorative laparotomy.
Geolocated Twitter social media data to describe the geographic spread of SARS-CoV-2
Authors: Bisanzio Donal , Kraemer Moritz U G , Brewer Thomas , Brownstein John S , Reithinger Richard
Published: July 2020

Openly available, geotagged Twitter data from 2013 to 2015 was used to estimate the 2019–2020 human mobility patterns in and outside of China to predict the spatiotemporal spread of severe acute respiratory syndrome coronavirus 2. Countries with the highest number of visiting Twitter users outside of China were the USA, Japan, UK, Germany and Turkey. A high correlation was observed when comparing country-level Twitter user visits and reported cases.
The complex large-scale magnetic fields in the first Galactic quadrant as revealed by the Faraday depth profile disparity
Authors: Ma Y K , Mao S A , Ordog A , Brown J C
Published: July 2020

The Milky Way is one of the very few spiral galaxies known to host large-scale magnetic field reversals. The existence of the field reversal in the first Galactic quadrant near the Sagittarius spiral arm has been well established, yet poorly characterized due to the insufficient number of reliable Faraday depths (FDs) from extragalactic radio sources (EGSs) through this reversal region. We have therefore performed broad-band (1–$2\, {\rm GHz}$) spectropolarimetric observations with the Karl G. Jansky Very Large Array (VLA) to determine the FD values of 194 EGSs in the Galactic longitude range of 20°–52° within ±5° from the Galactic mid-plane, covering the Sagittarius arm tangent. This factor of five increase in the EGS FD density has led to the discovery of a disparity in FD values across the Galactic mid-plane in the Galactic longitude range of 40°–52°. Combined with existing pulsar FD measurements, we suggest that the Sagittarius arm can host an odd-parity disc field. We further compared our newly derived EGS FDs with the predictions of three major Galactic magnetic field models, and concluded that none of them can adequately reproduce our observational results. This has led to our development of new, improved models of the Milky Way disc magnetic field that will serve as an important step towards major future improvements in Galactic magnetic field models.
Restoring the night sky darkness at Observatorio del Teide: First application of the model Illumina version 2
Authors: Aubé Martin , Simoneau Alexandre , Muñoz-Tuñón Casiana , Díaz-Castro Javier , Serra-Ricart Miquel
Published: July 2020

The propagation of artificial light into real environments is complex. To perform its numerical modelling with accuracy, one must consider hyperspectral properties of the lighting devices and their geographic positions, the hyperspectral properties of the ground reflectance, the size and distribution of small-scale obstacles, the blocking effect of topography, the lamps angular photometry and the atmospheric transfer function (aerosols and molecules). A detailed radiative transfer model can be used to evaluate how a particular change in the lighting infrastructure may affect the sky radiance. In this paper, we use the new version (v2) of the Illumina model to evaluate a night sky restoration plan for the Teide Observatory located on the island of Tenerife, Spain. In the past decades, the sky darkness was severely degraded by growing light pollution on the Tenerife Island. In this work, we use the contribution maps giving the effect of each pixel of the territory to the artificial sky radiance. We exploit the hyperspectral capabilities of Illumina v2 and show how the contribution maps can be integrated over regions or municipalities according to the Johnson–Cousins photometric bands spectral sensitivities. The sky brightness reductions per municipality after a complete shutdown and a conversion to light-emitting diodes are calculated in the Johnson–Cousins B, V, R bands. We found that the conversion of the lighting infrastructure of Tenerife with LED (1800 and 2700 K), according to the conversion strategy in force, would result in a zenith V-band sky brightness reduction of ≈0.3 mag arcsec−2.
The last breath of the Sagittarius dSph
Authors: Vasiliev Eugene , Belokurov Vasily
Published: July 2020

We use the astrometric and photometric data from Gaia Data Release 2 and line-of-sight velocities from various other surveys to study the 3D structure and kinematics of the Sagittarius dwarf galaxy. The combination of photometric and astrometric data makes it possible to obtain a very clean separation of Sgr member stars from the Milky Way foreground; our final catalogue contains 2.6 × 105 candidate members with magnitudes G < 18, more than half of them being red clump stars. We construct and analyse maps of the mean proper motion and its dispersion over the region ∼30 × 12 deg, which show a number of interesting features. The intrinsic 3D density distribution (orientation, thickness) is strongly constrained by kinematics; we find that the remnant is a prolate structure with the major axis pointing at ∼45° from the orbital velocity and extending up to ∼5 kpc, where it transitions into the stream. We perform a large suite of N-body simulations of a disrupting Sgr galaxy as it orbits the Milky Way over the past 2.5 Gyr, which are tailored to reproduce the observed properties of the remnant (not the stream). The richness of available constraints means that only a narrow range of parameters produce a final state consistent with observations. The total mass of the remnant is $\sim \!4\times 10^8\, \mathrm{M}_\odot$, of which roughly a quarter resides in stars. The galaxy is significantly out of equilibrium, and even its central density is below the limit required to withstand tidal forces. We conclude that the Sgr galaxy will likely be disrupted over the next Gyr.
Evolutionary and functional classification of the CARF domain superfamily, key sensors in prokaryotic antivirus defense
Authors: Makarova Kira S , Timinskas Albertas , Wolf Yuri I , Gussow Ayal B , Siksnys Virginijus , Venclovas Česlovas , Koonin Eugene V
Published: July 2020

CRISPR-associated Rossmann Fold (CARF) and SMODS-associated and fused to various effector domains (SAVED) are key components of cyclic oligonucleotide-based antiphage signaling systems (CBASS) that sense cyclic oligonucleotides and transmit the signal to an effector inducing cell dormancy or death. Most of the CARFs are components of a CBASS built into type III CRISPR–Cas systems, where the CARF domain binds cyclic oligoA (cOA) synthesized by Cas10 polymerase-cyclase and allosterically activates the effector, typically a promiscuous ribonuclease. Additionally, this signaling pathway includes a ring nuclease, often also a CARF domain (either the sensor itself or a specialized enzyme) that cleaves cOA and mitigates dormancy or death induction. We present a comprehensive census of CARF and SAVED domains in bacteria and archaea, and their sequence- and structure-based classification. There are 10 major families of CARF domains and multiple smaller groups that differ in structural features, association with distinct effectors, and presence or absence of the ring nuclease activity. By comparative genome analysis, we predict specific functions of CARF and SAVED domains and partition the CARF domains into those with both sensor and ring nuclease functions, and sensor-only ones. Several families of ring nucleases functionally associated with sensor-only CARF domains are also predicted.
Thoracic Paravertebral Blockade Reduces Chronic Postsurgical Pain in Breast Cancer Patients: A Randomized Controlled Trial
Authors: Lin Zeng-Mao , Li Mu-Han , Zhang Feng , Li Xue , Shao Chun-Li , Li Xue-Ying , Wang Dong-Xin
Published: July 2020

Objective

To evaluate the effect of multilevel single-shot thoracic paravertebral blockade (PVB) on the occurrence of chronic postsurgical pain (CPSP) in patients undergoing breast cancer surgery.

Design

A randomized controlled trial with two parallel groups.

Setting

A tertiary hospital.

Methods

Patients scheduled for breast cancer surgery were randomized to receive either ultrasound-guided multilevel single-shot PVB from T2 to T5 (the PVB group) or nothing (the control group). Surgery was then performed under general anesthesia. Patients were followed up for 12 months after surgery. The primary end point was incidence of CPSP at six months after surgery.

Results

A total of 218 patients were enrolled and randomized; of these, 208 and 204 completed six- and 12-month follow-up, respectively. The incidence of CPSP at six months was significantly lower in the PVB group (12.5% [13/104]) than in the control group (24.0% [25/104], relative risk = 0.52, 95% CI = 0.28–0.96, P = 0.031). Pain scores within 48 hours both at rest and with movement were lower in the PVB group than the control group (P = 0.006 and P < 0.001, respectively). The percentages of patients with neuropathic pain were also lower in the PVB group than the control group at both six and 12 months after surgery (P = 0.016 and 0.028, respectively). Adverse events did not differ between groups.

Conclusions

For patients undergoing breast cancer surgery, multilevel single-shot PVB reduces the incidence of CPSP at six months; it also improves early postoperative analgesia and reduces neuropathic pain at six and 12 months after surgery.
Does it Matter if Respondents Look up Answers to Political Knowledge Questions?
Authors: Style Hillary , Jerit Jennifer
Published: July 2020

Using novel instrumentation from a large national sample, this research note examines respondents who look up answers to factual knowledge questions. Consistent with past work linking outside search to a self-enhancing response style, we show that people who research the answers to knowledge questions also self-report higher levels of political engagement. Moreover, validated vote data indicate that higher self-reports of registration status and turnout are overreports of the actual behaviors. Finally, we analyze the characteristics of people who engage in outside search and explore whether simple warnings are effective at reducing this behavior.
Current algebra formulation of quantum gravity and its application to cosmology
Authors: Funai Shotaro Shiba , Sugawara Hirotaka
Published: July 2020

Gravity theory based on current algebra is formulated. The gauge principle rather than general covariance combined with the equivalence principle plays a pivotal role in the formalism, and the latter principles are derived as a consequence of the theory. In this approach, it turns out that gauging the Poincaré algebra is not appropriate but gauging the $SO(N,M)$ algebra gives a consistent theory. This makes it possible to have anti-de Sitter and de Sitter space-time by adopting a relation between the spin connection and the tetrad field. The Einstein equation is part of our basic equation for gravity, which is written in terms of the spin connection. When this formalism is applied to the $E(11)$ algebra in which the three-form antisymmetric tensor is part of a gravity multiplet, we have a current algebra gravity theory based on M-theory in the sense that the internal group or the connection space representations of our model are those appearing in 11D supergravity. Moreover, when our formalism in its classical limit is applied to cosmology, by introducing conformal-like modes that connect the tetrad field/current and the spin connection field/current, we can obtain an accelerating universe in the manner of the “inflating” universe at its early stage.
Alzheimer’s disease genetic risk and sleep phenotypes in healthy young men: association with more slow waves and daytime sleepiness
Authors: Muto Vincenzo , Koshmanova Ekaterina , Ghaemmaghami Pouya , Jaspar Mathieu , Meyer Christelle , Elansary Mahmoud , Van Egroo Maxime , Chylinski Daphne , Berthomier Christian , Brandewinder Marie , Mouraux Charlotte , Schmidt Christina , Hammad Grégory , Coppieters Wouter , Ahariz Naima , Degueldre Christian , Luxen André , Salmon Eric , Phillips Christophe , Archer Simon N , Yengo Loic , Byrne Enda , Collette Fabienne , Georges Michel , Dijk Derk-Jan , Maquet Pierre , Visscher Peter M , Vandewalle Gilles
Published: July 2020

Study Objectives

Sleep disturbances and genetic variants have been identified as risk factors for Alzheimer’s disease (AD). Our goal was to assess whether genome-wide polygenic risk scores (PRS) for AD associate with sleep phenotypes in young adults, decades before typical AD symptom onset.

Methods

We computed whole-genome PRS for AD and extensively phenotyped sleep under different sleep conditions, including baseline sleep, recovery sleep following sleep deprivation, and extended sleep opportunity, in a carefully selected homogenous sample of 363 healthy young men (22.1 years ± 2.7) devoid of sleep and cognitive disorders.

Results

AD PRS was associated with more slow-wave energy, that is, the cumulated power in the 0.5–4 Hz EEG band, a marker of sleep need, during habitual sleep and following sleep loss, and potentially with larger slow-wave sleep rebound following sleep deprivation. Furthermore, higher AD PRS was correlated with higher habitual daytime sleepiness.

Conclusions

These results imply that sleep features may be associated with AD liability in young adults, when current AD biomarkers are typically negative, and support the notion that quantifying sleep alterations may be useful in assessing the risk for developing AD.
An opisthorchiid concept of the genusLiliatrema(Trematoda: Plagiorchiida: Opisthorchioidea): an unexpected systematic position
Authors: Sokolov Sergey , Frolov Evgeniy , Novokreshchennykh Semen , Atopkin Dmitry
Published: July 2020

Liliatrema is a small genus of trematodes consisting of two species. Its systematic position has long been debated, partly because of the confusing reports about the structure of male terminal genitalia. Here we test the phylogenetic position of the genus Liliatrema using data on complete 18S rRNA and partial 28S rRNA gene sequences obtained for Liliatrema skrjabini. We also provide a detailed description of terminal genitalia in adult specimens of L. sobolevi and metacercariae of both Liliatrema species. The results of the 28S rDNA-based phylogenetic analysis indicate that Liliatrema falls within a well-supported clade, which also includes Apophallus and traditional opisthorchiids. This clade, in turn, is nested within a well-supported clade, containing Euryhelmis, Cryptocotyle and Scaphanocephalus. In the 18S+8S rDNA analysis, Liliatrema appears as a sister-taxon to the Cryptocotyle + Euryhelmis group. The Liliatrema + (Cryptocotyle + Euryhelmis) clade is a well-supported sister-group to the traditional opisthorchiids. The morphology of the terminal genitalia of the liliatrematids also corresponds to that of the opisthorchioids. Thus, the results of our morphological and phylogenetic analyses favour an unexpected conclusion that the genus Liliatrema belongs to the Opisthorchioidea. We propose that the genera Liliatrema, Apophallus, Euryhelmis, Cryptocotyle and Scaphanocephalus belong, respectively, within the subfamilies Liliatrematinae, Apophallinae, Euryhelminthinae and Cryptocotylinae of the family Opisthorchiidae.
Trauma-Informed Medical Education (TIME): Advancing Curricular Content and Educational Context
Authors: Brown Taylor , Berman Sarah , McDaniel Katherine , Radford Caitlin , Mehta Pooja , Potter Jennifer , Hirsh David A.
Published: July 2020

The majority of patients and medical students experience some form of psychological trauma or adversity across their life course. All forms of trauma can be associated with adverse health consequences and can negatively affect learning and professional development. Trauma-informed care (TIC) offers a framework to address and mitigate these consequences and promote safety and health. The Substance Abuse and Mental Health Services Administration describes 6 domains of TIC: safety; trust and transparency; peer support; collaboration and mutuality; empowerment, voice, and choice; and cultural, historic, and gender issues.

At present, TIC is not taught routinely in undergraduate medical education (UME)—a crucial educational gap given that UME grounds the development of key perspectives and practices that students use throughout their careers. Further, given the prevalence of preexisting trauma among learners and the likelihood of new traumatic exposures during training, medical schools’ processes, practices, and learning environments may risk exacerbating or even causing trauma. To address this educational need and support students and their future patients, the authors propose a trauma-informed medical education (TIME) framework.

TIME informs medical schools’ curricular content and educational context. In UME, curricular content should address trauma epidemiology, physiology, and effects; trauma-informed clinical skills including sensitive communication and physical exam techniques; and trauma-informed self-care techniques including education on organizational resources, how to elicit supports, and personal self-care practices. A trauma-informed educational context encompasses curricular development, including student–faculty coproduction of educational content; curricular delivery, including faculty development on TIC principles; and learning environment, including trauma-informed educational practices, medical student advising, institutional policies, and recruitment. TIME offers practical strategies to support teaching, learning, educational administration, and professional development and aims to inspire new strategies for effective learner and faculty engagement. TIME aims to foster students’ development of competency in TIC and promote student engagement, learning, health, and well-being.
Body Habitus and Dynamic Surgical Conditions Independently Impair Pulmonary Mechanics during Robotic-assisted Laparoscopic Surgery
Authors: Tharp William G. , Murphy Serena , Breidenstein Max W. , Love Collin , Booms Alisha , Rafferty Melissa N. , Friend Alexander F. , Perrapato Scott , Ahern Thomas P. , Dixon Anne E. , Bates Jason H. T. , Bender S. Patrick
Published: July 2020

Background

Body habitus, pneumoperitoneum, and Trendelenburg positioning may each independently impair lung mechanics during robotic laparoscopic surgery. This study hypothesized that increasing body mass index is associated with more mechanical strain and alveolar collapse, and these impairments are exacerbated by pneumoperitoneum and Trendelenburg positioning.

Methods

This cross-sectional study measured respiratory flow, airway pressures, and esophageal pressures in 91 subjects with body mass index ranging from 18.3 to 60.6 kg/m2. Pulmonary mechanics were quantified at four stages: (1) supine and level after intubation, (2) with pneumoperitoneum, (3) in Trendelenburg docked with the surgical robot, and (4) level without pneumoperitoneum. Subjects were stratified into five body mass index categories (less than 25, 25 to 29.9, 30 to 34.9, 35 to 39.9, and 40 or higher), and respiratory mechanics were compared over surgical stages using generalized estimating equations. The optimal positive end-expiratory pressure settings needed to achieve positive end-expiratory transpulmonary pressures were calculated.

Results

At baseline, transpulmonary driving pressures increased in each body mass index category (1.9 ± 0.5 cm H2O; mean difference ± SD; P < 0.006), and subjects with a body mass index of 40 or higher had decreased mean end-expiratory transpulmonary pressures compared with those with body mass index of less than 25 (–7.5 ± 6.3 vs. –1.3 ± 3.4 cm H2O; P < 0.001). Pneumoperitoneum and Trendelenburg each further elevated transpulmonary driving pressures (2.8 ± 0.7 and 4.7 ± 1.0 cm H2O, respectively; P < 0.001) and depressed end-expiratory transpulmonary pressures (–3.4 ± 1.3 and –4.5 ± 1.5 cm H2O, respectively; P < 0.001) compared with baseline. Optimal positive end-expiratory pressure was greater than set positive end-expiratory pressure in 79% of subjects at baseline, 88% with pneumoperitoneum, 95% in Trendelenburg, and ranged from 0 to 36.6 cm H2O depending on body mass index and surgical stage.

Conclusions

Increasing body mass index induces significant alterations in lung mechanics during robotic laparoscopic surgery, but there is a wide range in the degree of impairment. Positive end-expiratory pressure settings may need individualization based on body mass index and surgical conditions.

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What This Article Tells Us That Is New
Role for antimalarials in the management of COVID-19
Authors: Schrezenmeier Eva V. , Burmester Gerd R. , Eckardt Kai-Uwe , Dörner Thomas
Published: July 2020

Purpose of review

The current review highlights recent insights into direct antiviral effects by antimalarials against severe acute respiratory syndrome (SARS)-CoV-2 and other viruses and their potential indirect effects on the host by avoiding exaggerated immune responses (reduced cytokine release, Toll-like receptor response, antigen presentation related to lysosomal processing).

Recent findings

Currently, there is a large debate on the use of antimalarials for prophylaxis and treatment of SARS-CoV-2-induced disease based on preclinical in-vitro data, small case series and extrapolation from earlier studies of their effect on intracellular pathogens, including many viruses. Hydroxychloroquine (HCQ) or chloroquine have not demonstrated robust efficacy in prior randomized controlled studies against several other viruses. In-vitro data indicate a reduced viral replication of SARS-CoV-2. Especially immunomodulatory effects of antimalarials might also contribute to a clinical efficacy. For SARS-CoV-2 various large studies will provide answers as to whether antimalarials have a place in prophylaxis or treatment of the acute virus infection with SARS-CoV-2 but compelling data are missing so far.

In-vitro data provide a theoretical framework for an efficacy of antimalarials in SARS-CoV-2-induced disease but clinical proof is currently missing.
Usefulness of PCR Screening in the Initial Triage of Trauma Patients During COVID-19 Pandemic
Authors: Porcel-Vazquez Juan A. , Andres-Peiro Jose V. , Garcia-Sanchez Yaiza , Guerra-Farfan Ernesto , Mestre-Torres Jaume , Minguell-Monyart Joan , Molero-Garcia Vicente , Selga Marsa Jordi , Tomas-Hernandez Jordi , Villar-Casares Maria del Mar , Bhandari Mohit , Teixidor-Serra Jordi
Published: July 2020

Background:

Hospitals worldwide have postponed all nonessential surgery during the COVID-19 pandemic, but non-COVID-19 patients are still in urgent need of care. Uncertainty about a patient's COVID-19 status risks infecting health care workers and non-COVID-19 inpatients. We evaluated the use of quantitative reverse transcription polymerase chain reaction (RT-qPCR) screening for COVID-19 on admission for all patients with fractures.

Methods:

We conducted a retrospective cohort study of patients older than 18 years admitted with low-energy fractures who were tested by RT-qPCR for SARS-CoV-2 at any time during hospitalization. Two periods based on the applied testing protocol were defined. During the first period, patients were only tested because of epidemiological criteria or clinical suspicion based on fever, respiratory symptoms, or radiological findings. In the second period, all patients admitted for fracture treatment were screened by RT-qPCR.

Results:

We identified 15 patients in the first period and 42 in the second. In total, 9 (15.8%) patients without clinical or radiological findings tested positive at any moment. Five (33.3%) patients tested positive postoperatively in the first period and 3 (7.1%) in the second period (P = 0.02). For clinically unsuspected patients, postoperative positive detection went from 3 of 15 (20%) during the first period to 2 of 42 (4.8%) in the second (P = 0.11). Clinical symptoms demonstrated high specificity (92.1%) but poor sensitivity (52.6%) for infection detection.

Conclusions:

Symptom-based screening for COVID-19 has shown to be specific but not sensitive. Negative clinical symptoms do not rule out infection. Protocols and separated areas are necessary to treat infected patients. RT-qPCR testing on admission helps minimize the risk of nosocomial and occupational infection.

Level of Evidence:

Diagnostic Level IV. See Instructions for Authors for a complete description of levels of evidence.
Acquired Human Papilloma Virus Type 6–Associated Epidermodysplasia Verruciformis in a Patient With Systemic Lupus Erythematosus
Authors: Ferronika Paranita , Sijmons Rolf H. , Febiyanto Novian , Radiono Sunardi , Widodo Irianiwati
Published: July 2020

Although historically known as a genetic disorder, epidermodysplasia verruciformis (EV) might be acquired in patients with a noninherited defective cell-mediated immunity. This article reports a case of EV in a patient with systemic lupus erythematosus and a history of 3 years immunosuppressive methylprednisolone treatment. The microscopic features of the skin biopsy showed morphologic changes of the keratinocytes characteristic of human papilloma virus (HPV) infections and immunoreactivity to p16. HPV genotyping demonstrated the presence of HPV 6 which belongs to a low-risk mucosal HPV group and has not been reported in EV previously. The clinical recognition of EV in immunocompromised patients and subsequent HPV typing is important because some patients will develop squamous cell carcinoma.
Joseph von Gerlach—A Reminder of One of the Pioneers of Histochemistry on the Occasion of His 200th Birthday
Authors: Weyers Wolfgang
Published: July 2020

Joseph von Gerlach was an eminent German anatomist and pioneer of histology. He devised various techniques to assess the fine structure of tissues, most notably a procedure of staining histologic sections that marked the beginning of routine staining in histology. Gerlach was also one of the pioneers of microphotography.
Late Sodium Current in Atrial Cardiomyocytes Contributes to the Induced and Spontaneous Atrial Fibrillation in Rabbit Hearts
Authors: Chu Yanpeng , Yang Qiaomei , Ren Lu , Yu Shandong , Liu Zhipei , Chen Ying , Wei Xiaohong , Huang Sihui , Song Lv , Zhang Peihua , Ma Jihua , Wu Lin
Published: July 2020

Increased late sodium current (INa) induces long QT syndrome 3 with increased risk of atrial fibrillation (AF). The role of atrial late INa in the induction of AF and in the treatment of AF was determined in this study. AF parameters were measured in isolated rabbit hearts exposed to late INa enhancer and inhibitors. Late INa from isolated atrial and ventricular myocytes were measured using whole-cell patch-clamp techniques. We found that induced-AF by programmed S1S2 stimulation and spontaneous episodes of AF were recorded in hearts exposed to either low (0.1–3 nM) or high (3–10 nM) concentrations of ATX-II (n = 10). Prolongations in atrial monophasic action potential duration at 90% completion of repolarization and effective refractory period by ATX-II (0.1–15 nM) were greater in hearts paced at slow than at fast rates (n = 5–10, P < 0.05). Both endogenous and ATX-II-enhanced late INa density were greater in atrial than that in ventricular myocytes (n = 9 and 8, P < 0.05). Eleclazine and ranolazine reduced AF window and AF burden in association with the inhibition of both endogenous and enhanced atrial late INa with half maximal inhibitory concentrations (IC50) of 1.14 and 9.78, and 0.94 and 8.31 μM, respectively. The IC50s for eleclazine and ranolazine to inhibit peak INa were 20.67 and 101.79 μM, respectively, in atrial myocytes. In conclusion, enhanced late INa in atrial myocytes increases the susceptibility for AF. Inhibition of either endogenous or enhanced late INa, with increased atrial potency of drugs is feasible for the treatment of AF.
A Case Series of Intramuscular Orbital Choristomatous Cysts
Authors: O’Rourke Micheal , McKelvie Penny , McNab Alan
Published: July 2020

Intramuscular choristomatous cystic lesions within the orbit are rare but may require removal due to their volume effects. The authors describe 2 such cases of intramuscular cysts in adult patients. Both patients presented with symptoms due to local mass effects with swelling, proptosis and diplopia. Imaging confirmed cystic intramuscular masses. Surgical removal involved intraoperative decompression of the cyst to aid dissection with excision of some muscle fibers. Histology confirmed a keratinized stratified squamous lined dermoid cyst within lateral rectus for case 1 and stratified squamous non-keratinized conjunctival epithelium (simple primary conjunctival cyst) within inferior oblique for case 2.
Markers of gastric intestinal metaplasia under digital chromoendoscopy: systematic review and meta-analysis
Authors: Wei Ning , Mulmi Shrestha Sachin , Shi Rui Hua
Published: July 2020

Diagnosis of gastric intestinal metaplasia (GIM) under digital chromoendoscopy presents various markers. The diagnostic yield of each marker has shown variable results. A systematic review and meta-analysis were performed to evaluate the following markers: light blue crest (LBC), marginal turbid band (MTB), groove type (GT), white opaque substance (WOS). Discussion of their joint diagnosis, reliability, assessment of local GIM severity and influencing factors was also provided. PubMed, EMBASE, Cochrane Library and Web of science were searched. The Meta-DiSc and Stata software were used to analyze the data. Fourteen studies were included with a total of 3081 lesions. There were 12 studies for LBC, six for GT, four for MTB and one for WOS, respectively. The pooled results showed that the diagnostic sensitivity and specificity of LBC were 0.79 [95% confidence interval (CI) 0.76–0.81] and 0.95 (95% CI 0.94–0.96). The sensitivity of GT and MTB were 0.49 (95% CI 0.43–0.54) and 0.47 (95% CI 0.40–0.53), and the specificity were 0.92 (95% CI 0.89–0.94) and 0.92 (95% CI 0.89–0.95). The area under the summary receiver operating characteristic curve was 0.9532, 0.7791 and 0.9553 for LBC, GT and MTB, respectively. LBC resulted the most classic marker. Proper combined diagnosis can improve the diagnostic efficiency. Reliability of these markers was acceptable. These markers can help endoscopic to assess the severity of local GIM. Besides intestinal metaplasia, many factors can potentially interfere with the diagnosis.
Obstructive colon cancers at endoscopy are associated with advanced tumor stage and poor patient outcome. A retrospective study on 398 patients
Authors: Abu Baker Fadi , Taher Randa , Ganayem Mohanad , Mari Amir , Oren Gal , Kopelman Yael
Published: July 2020

Background

The detection of obstructive colorectal cancer (CRC) masses during endoscopic examination hindering the passage of endoscope and precluding complete examination is not uncommon. The significance and implications of this finding on patients’ prognosis and outcomes were not fully investigated and will be addressed in this study.

Methods

In this retrospective cohort study, we reviewed endoscopy, surgery, pathology and oncology reports of patients diagnosed with CRC over a 10-year period (2007–2016). We compared surgical stages, histologic grades and overall survival between patients with subclinical obstructive tumors at endoscopy to those with nonobstructive tumors. We performed multivariate analysis to identify independent risk factors associated with advanced CRC stage at diagnosis.

Results

A total of 144 patients had obstructive colonic tumors while 254 had nonobstructive tumors and constituted the control group. Obstructive CRC group was significantly associated with advanced tumor stage at diagnosis (69 vs. 42%, OR = 3.018, 95% CI, 1.951–4.670; P < 0.01) and had prominently higher rates of moderate to poorly differentiated tumors (64.5 vs. 38.4%; P < 0.001) when compared to non-obstructive controls. Patients with obstructive tumors were significantly associated with decreased five years overall survival (53.4 vs. 67.3% vs.; P < 0.01). Increased overall mortality was observed in survival curves of patients with obstructive tumors along all follow-up periods.

Conclusion

Even in the absence of clinical sequela, obstructive CRC at endoscopic level may be associated with higher stage at diagnosis and reduced overall survival. Further prospective studies are warranted to confirm these findings and address their implication on patients’ management.
Evaluation of hepatitis B vaccine efficacy and factors affecting vaccine nonresponse in patients receiving anti-tumor necrosis factor agents
Authors: Okay Gülay , Biberci Keskin Elmas , Akkoyunlu Yasemin , Bolukcu Sibel , Betül Uslu Ayse , Meric Koc Meliha
Published: July 2020

Objectives

The response rate of patients to hepatitis B virus (HBV) vaccination receiving anti-tumor necrosis factor (TNF) agents is quite low. We aimed to assess the efficiency of HBV vaccination in patients with chronic inflammatory diseases (CIDs) receiving anti-TNF agents as well as in healthy controls. We also evaluated the impact of different factors on the efficacy of HBV vaccination.

Methods

Patients with CIDs receiving anti-TNF agents and healthy controls vaccinated for HBV were included in the study during 2018–2019. An adequate immune response and an effective immune response to HBV were defined as >10 IU/L and > 100 IU/L, respectively.

Results

Among 274 participants, 187 were patients with CID and 87 were healthy controls. The mean age of the patients with CID (43.9 ± 11.7 years) was significantly higher than that of the healthy controls (31.4 ± 7 years) (P = 0.000). Adequate immune response was 60.8 and 94.3% in patients with CID and healthy controls (P = 0.000), respectively, whereas effective immune response was 37.9 and 75.9% (P = 0.000), respectively. In logistic regression analysis, male sex [odds ratio (OR), 0.408; 95% confidence interval (CI), 0.201–0.830; P = 0.013), use of infliximab (OR, 2.694; 95% CI, 1.203–6.035; P = 0.016) and sertoluzimab (OR, 3.307; 95% CI, 1.287–8.498; P = 0.013), vaccination after anti-TNF treatment (OR, 0.224; 95% CI, 0.083–0.602; P = 0.003) were identified as risk factors of nonresponse to HBV vaccine.

Conclusions

Infliximab and sertoluzimab usage, male sex, and vaccination after anti-TNF treatment were risk factors of nonresponse. HBV vaccination should be given to patients with CID before initiation of anti-TNF treatment and awareness should be spread on this subject.