bluuebunny/crossref_metadata_2025 huggingface dataset:
Radio emission from the unbound debris of tidal disruption events
Authors: Yalinewich A , Steinberg E , Piran T , Krolik J H
Published: June 2019

When a star gets too close to a supermassive black hole, it is torn apart by the tidal forces. Roughly half of the stellar mass becomes unbound and flies away at tremendous velocities – around 104 km s−1. In this work, we explore the idea that the shock produced by the interaction of the unbound debris with the ambient medium gives rise to the synchrotron radio emission observed in several tidal disruption event (TDE). We use a moving mesh numerical simulation to study the evolution of the unbound debris and the bow shock around it. We find that as the periapse distance of the star decreases, the outflow becomes faster and wider. A TDE whose periapse distance is a factor of 7 smaller than the tidal radius can account for the radio emission observed in ASASSN-14li. This model also allows us to obtain a more accurate estimate for the gas density around the centre of the host galaxy of ASASSN-14li.
A fractal analysis application of the pre-whitening technique to δ Scuti stars time series
Authors: de Franciscis S , Pascual-Granado J , Suárez J C , García Hernández A , Garrido R , Lares-Martiz M , Rodón J R
Published: June 2019

Fractal fingerprints have been found recently in the light curves of several δ Scuti stars observed by Convection Rotation and planetary Transits(CoRoT) satellite. This sole fact might pose a problem for the detection of pulsation frequencies using classical pre-whitening techniques, but it is also a potentially rich source for information about physical mechanisms associated with stellar variability.

Assuming that a light curve is composed of a superposition of oscillation modes with a fractal background noise, in this work we applied the Coarse Graining Spectral Analysis (CGSA), a fast Fourier transform (FFT)-based algorithm, which can discriminate in a time series the stochastic fractal power spectra from the harmonic one.

We have found that the fractal background component is determining the frequency content extracted using classical pre-whitening techniques in the light curves of δ Scuti stars. This might be crucial to understand the amount of frequencies excited in these kinds of pulsating stars. Additionally, CGSA resulted to be relevant in order to extract the oscillation modes, this points to a new criterion to stop the pre-whitening cascade based on the percentage of fractal component in the residuals.
ALMA observations require slower Core Accretion runaway growth
Authors: Nayakshin S , Dipierro G , Szulágyi J
Published: June 2019

Due to recent high-resolution ALMA observations, there is an accumulating evidence for presence of giant planets with masses from ${\sim } 0.01 \, {\rm {M}}_{\rm {J}}$ to a few $\, {\rm {M}}_{\rm {J}}$ with separations up to 100 au in the annular structures observed in young protoplanetary discs. We point out that these observations set unique ‘live’ constraints on the process of gas accretion on to sub-Jovian planets that were not previously available. Accordingly, we use a population synthesis approach in a new way: we build time-resolved models and compare the properties of the synthetic planets with the ALMA data at the same age. Applying the widely used gas accretion formulae leads to a deficit of sub-Jovian planets and an overabundance of a few Jupiter mass planets compared to observations. We find that gas accretion rate on to planets needs to be suppressed by about an order of magnitude to match the observed planet mass function. This slower gas giant growth predicts that the planet mass should correlate positively with the age of the protoplanetary disc, albeit with a large scatter. This effect is not clearly present in the ALMA data but may be confirmed in the near future with more observations.
Effect of mutations on binding of ligands to guanine riboswitch probed by free energy perturbation and molecular dynamics simulations
Authors: Chen Jianzhong , Wang Xingyu , Pang Laixue , Zhang John Z H , Zhu Tong
Published: June 2019

Riboswitches can regulate gene expression by direct and specific interactions with ligands and have recently attracted interest as potential drug targets for antibacterial. In this work, molecular dynamics (MD) simulations, free energy perturbation (FEP) and molecular mechanics generalized Born surface area (MM-GBSA) methods were integrated to probe the effect of mutations on the binding of ligands to guanine riboswitch (GR). The results not only show that binding free energies predicted by FEP and MM-GBSA obtain an excellent correlation, but also indicate that mutations involved in the current study can strengthen the binding affinity of ligands GR. Residue-based free energy decomposition was applied to compute ligand-nucleotide interactions and the results suggest that mutations highly affect interactions of ligands with key nucleotides U22, U51 and C74. Dynamics analyses based on MD trajectories indicate that mutations not only regulate the structural flexibility but also change the internal motion modes of GR, especially for the structures J12, J23 and J31, which implies that the aptamer domain activity of GR is extremely plastic and thus readily tunable by nucleotide mutations. This study is expected to provide useful molecular basis and dynamics information for the understanding of the function of GR and possibility as potential drug targets for antibacterial.
A DEAD-box protein regulates ribosome assembly through control of ribosomal protein synthesis
Authors: Iost Isabelle , Jain Chaitanya
Published: June 2019

DEAD-box proteins (DBPs) comprise a large family of proteins that most commonly have been identified as regulators of ribosome assembly. The Escherichia coli DBP, SrmB, represents a model bacterial DBP whose absence impairs formation of the large ribosomal subunit (LSU). To define the basis for SrmB function, suppressors of the ribosomal defect of ΔsrmB strains were isolated. The major class of suppressors was found to map to the 5′ untranslated region (UTR) of the rplM-rpsI operon, which encodes the ribosomal proteins (r-proteins) L13 and S9. An analysis of protein abundance indicated that both r-proteins are under-produced in the ΔsrmB strain, but are increased in these suppressors, implicating r-protein underproduction as the molecular basis for the observed ribosomal defects. Reduced r-protein synthesis was determined to be caused by intrinsic transcription termination within the rplM 5′ UTR that is abrogated by SrmB. These results reveal a specific mechanism for DBP regulation of ribosomal assembly, indirectly mediated through its effects on r-protein expression.
Consumer switching in European retail markets
Authors: Harold Jason , Cullinan John , Lyons Seán
Published: June 2019

Consumer switching can play a significant role in enabling competitive retail markets. This paper examines the factors influencing consumer switching across 14 different retail markets in 27 European countries (EU27) using a micro-econometric analysis of consumer switching behaviour data from the European Commission’s Consumer Market Monitoring Survey. The results provide evidence that consumer attitudes to various market components are highly significant factors in explaining consumer switching behaviour in the EU27. In addition, this paper also examines cross-market effects on consumer switching behaviour. Focusing on the case of energy retail markets, the odds of switching in these markets are found to be considerably greater for a consumer who has switched in at least one other retail market. Finally, consumers’ accessibility to the internet is also shown to have a strong positive association with switching.
Recombinant production and purification of the human protein Tau
Authors: Ferrari Luca , Rüdiger Stefan G D
Published: June 2019

Tau protein is a microtubule-stabilising protein whose aggregation is linked to Alzheimer’s Disease and other forms of dementia. Tau biology is at the heart of cytoskeletal dynamics and neurodegenerative mechanisms, making it a crucial protein to study. Tau purification, however, is challenging as Tau is disordered, which makes it difficult to produce in recombinant system and is degradation-prone. It is thus challenging to obtain pure and stable preparations of Tau. Here, we present a fast and robust protocol to purify Tau recombinantly in Escherichia coli. Our protocol allows purifying Tau either tag-less or FLAG-tagged at its N-terminus, and Tau fragments of interest. By exploiting a cleavable affinity tag and two anion exchange columns, we obtained Tau preparations of high purity, stable and suitable for in vitro studies, including aggregation experiments that resemble neurodegenerative processes.
Calculations with graded perverse-coherent sheaves
Authors: Achar Pramod N , Hardesty William D
Published: June 2019

In this paper, we carry out several computations involving graded (or ${{\mathbb {G}}_{\textrm {m}}}$-equivariant) perverse-coherent sheaves on the nilpotent cone of a reductive group in good characteristic. In the first part of the paper, we compute the weight of the ${{\mathbb {G}}_{\textrm {m}}}$-action on certain normalized (or ‘canonical’) simple objects, confirming an old prediction of Ostrik. In the second part of the paper, we explicitly describe all simple perverse-coherent sheaves for $G = PGL_3$, in every characteristic other than 2 or 3. Applications include an explicit description of the cohomology of tilting modules for the corresponding quantum group, as well as a proof that $\textsf {PCoh}^{{{\mathbb {G}}_{\textrm {m}}}}({\mathcal {N}})$ never admits a positive grading when the characteristic of the field is greater than 3.
Long-term safety of sarilumab in rheumatoid arthritis: an integrated analysis with up to 7 years’ follow-up
Authors: Fleischmann Roy , Genovese Mark C , Lin Yong , St John Gregory , van der Heijde Désirée , Wang Sheldon , Gomez-Reino Juan Jose , Maldonado-Cocco Jose Antonio , Stanislav Marina , Kivitz Alan J , Burmester Gerd R
Published: June 2019

Objective

Sarilumab is a human monoclonal antibody that blocks IL-6 from binding to membrane-bound and soluble IL-6 receptor-α. We assessed the long-term safety of sarilumab in patients from eight clinical trials and their open-label extensions.

Methods

Data were pooled from patients with rheumatoid arthritis who received at least one dose of sarilumab in combination with conventional synthetic disease-modifying antirheumatic drugs (csDMARDs; combination group) or as monotherapy (monotherapy group). Treatment-emergent adverse events (AEs) and AEs and laboratory values of special interest were assessed.

Results

2887 patients received sarilumab in combination with csDMARDs and 471 patients received sarilumab monotherapy, with mean exposure of 2.8 years and 1.7 years, maximum exposure 7.3 and 3.5 years, and cumulative AE observation period of 8188 and 812 patient-years, respectively. Incidence rates per 100 patient-years in the combination and monotherapy groups, respectively, were 9.4 and 6.7 for serious AEs, 3.7 and 1.0 for serious infections, 0.6 and 0.5 for herpes zoster (no cases were disseminated), 0.1 and 0 for gastrointestinal perforations, 0.5 and 0.2 for major adverse cardiovascular events, and 0.7 and 0.6 for malignancy. Absolute neutrophil counts <1000 cells/mm3 were recorded in 13% and 15% of patients, respectively. Neutropenia was not associated with increased risk of infection or serious infection. Analysis by 6-month interval showed no signal for increased rate of any AE over time.

Conclusion

The long-term safety profile of sarilumab, either in combination with csDMARDs or as monotherapy, remained stable and consistent with the anticipated profile of a molecule that inhibits IL6 signalling.
Evaluation of Allyl Isothiocyanate as a Soil Fumigant for Tomato (Lycopersicon esculentum Mill.) Production
Authors: Yu Jialin , Vallad Gary E. , Boyd Nathan S.
Published: June 2019

Fusarium wilt (Fusarium oxysporum f. sp. lycopersici), root-knot nematodes (Meloidogyne spp.), and purple nutsedge (Cyperus rotundus L.) are among the most damaging soilborne pests for tomato (Lycopersicon esculentum Mill.) production in the southeastern United States. Allyl isothiocyanate (allyl ITC) was evaluated as a potential fumigant alternative for control of soilborne pathogens, nematodes, and weeds. Shank- or drip-injected allyl ITC at rates ranging from 221 to 367 kg ha−1 exhibited excellent performance, reducing the recovery of total F. oxysporum from treated soils. Shank- or drip-injected allyl ITC at 367 kg ha−1 provided equivalent control of C. rotundus compared with 1,3-dichloropropene + chloropicrin and metam potassium, respectively. Totally impermeable film (TIF) did not further reduce the recovery of F. oxysporum and various nematodes from soil treated with allyl ITC compared with virtually impermeable film (VIF). However, TIF mulch significantly improved C. rotundus control versus shank- or drip-injected allyl ITC treatments under VIF mulch. Overall, allyl ITC is an effective methyl bromide alternative against F. oxysporum, C. rotundus, and plant-parasitic nematodes Criconemella spp. and Hoplolaimus spp. in plasticulture tomato production.
Biologics and anaphylaxis
Authors: Sala-Cunill Anna , Luengo Olga , Cardona Victoria
Published: June 2019

Purpose of review

The use of biologicals as therapeutic agents in oncology and other inflammatory diseases has dramatically increased during the last years. Due to their biological nature and inherent immunological activity, they are able to induce important adverse events, such as cytokine release reactions (rapid release of proinflammatory cytokines), serum sickness disease, and immediate or delayed hypersensitivity reactions, including anaphylaxis. The aim of the current article is to review the state of the art of anaphylaxis because of biological agents.

Recent findings

Different phenotypes, and potential underlying endotypes, have been described in anaphylactic reactions to biologicals. There seems to be a spectrum from type 1 reactions (IgE or non-IgE-mediated) to cytokine release reactions, with some reactions falling in between both. Management should be directed according to such phenotypes.

There is ongoing research to further define immediate adverse reactions to biologicals and to find relevant biomarkers to aid in their diagnosis. Such information will serve in defining their immediate and long term management.
Role of the ocular surface microbiome in allergic disease
Authors: Cavuoto Kara M. , Stradiotto Allison C. , Galor Anat
Published: June 2019

Purpose of review

The purpose of this review is to provide an update regarding new and emerging data on the role of the ocular surface microbiome in allergic disease.

Recent findings

Recent findings support the role of the microbiome in the pathophysiology of allergic disease of the ocular surface.

Understanding the role of the ocular surface microbiome in allergic disease may provide a new target for the development of therapeutic interventions.
Positioning the Work of Health Professions Education Scholarship Units: How Canadian Directors Harness Institutional Logics Within Institutional Orders to Convey Unit Legitimacy
Authors: Kahlke Renate , Varpio Lara
Published: June 2019

Purpose

Health professions education scholarship unit (HPESU) leaders often struggle to articulate their impact within local contexts. Previous research has described what markers of success and institutional logics to consider when crafting statements of impact; there is a need to clarify how HPESU leaders convey their messages to navigate competing demands. This study examined how leaders argue the legitimacy of their HPESUs’ activities.

Method

The institutional logics perspective offered a lens for understanding how legitimacy claims are constructed through larger institutional orders. Interviews with leaders from 12 Canadian HPESUs discussed their unit’s work, the stakeholders that leaders sought to satisfy, and how they defined success. Data were generated in 2011–2012 and analyzed anew in 2017–2018. The authors inductively analyzed the data, using institutional logics and institutional orders as sensitizing concepts to identify the linguistic constructions harnessed by participants.

Results

HPESU leaders engaged with 2 dominant logics: research and service. These aligned with institutional orders: the profession and community, respectively. While a few HPESU leaders deployed only one logic throughout the course of an interview, many engaged with more than one, compartmentalizing logics specific to different audiences and activities or blending logics to create novel ways of framing their work.

Conclusions

The institutional logics available in a context vary. What constitutes a compelling legitimacy claim is different from one institutional context to the next. The authors identify strategies that leaders used to position their HPESU for success and discuss the basis on which these claims are made.
Competencies and Feedback on Internal Medicine Residents’ End-of-Rotation Assessments Over Time: Qualitative and Quantitative Analyses
Authors: Tekian Ara , Park Yoon Soo , Tilton Sarette , Prunty Patrick F. , Abasolo Eric , Zar Fred , Cook David A.
Published: June 2019

Purpose

To examine how qualitative narrative comments and quantitative ratings from end-of-rotation assessments change for a cohort of residents from entry to graduation, and explore associations between comments and ratings.

Method

The authors obtained end-of-rotation quantitative ratings and narrative comments for 1 cohort of internal medicine residents at the University of Illinois at Chicago College of Medicine from July 2013–June 2016. They inductively identified themes in comments, coded orientation (praising/critical) and relevance (specificity and actionability) of feedback, examined associations between codes and ratings, and evaluated changes in themes and ratings across years.

Results

Data comprised 1,869 assessments (828 comments) on 33 residents. Five themes aligned with ACGME competencies (interpersonal and communication skills, professionalism, medical knowledge, patient care, and systems-based practice), and 3 did not (personal attributes, summative judgment, and comparison to training level). Work ethic was the most frequent subtheme. Comments emphasized medical knowledge more in year 1 and focused more on autonomy, leadership, and teaching in later years. Most comments (714/828 [86%]) contained high praise, and 412/828 (50%) were very relevant. Average ratings correlated positively with orientation (β = 0.46, P < .001) and negatively with relevance (β = −0.09, P = .01). Ratings increased significantly with each training year (year 1, mean [standard deviation]: 5.31 [0.59]; year 2: 5.58 [0.47]; year 3: 5.86 [0.43]; P < .001).

Conclusions

Narrative comments address resident attributes beyond the ACGME competencies and change as residents progress. Lower quantitative ratings are associated with more specific and actionable feedback.
Multi-Compartment Profiling of Bacterial and Host Metabolites Identifies Intestinal Dysbiosis and Its Functional Consequences in the Critically Ill Child
Authors: Wijeyesekera Anisha , Wagner Josef , De Goffau Marcus , Thurston Sarah , Rodrigues Sabino Adilson , Zaher Sara , White Deborah , Ridout Jenna , Peters Mark J. , Ramnarayan Padmanabhan , Branco Ricardo G. , Torok M. Estee , Valla Frederic , Meyer Rosan , Klein Nigel , Frost Gary , Parkhill Julian , Holmes Elaine , Pathan Nazima
Published: June 2019

Objectives:

Adverse physiology and antibiotic exposure devastate the intestinal microbiome in critical illness. Time and cost implications limit the immediate clinical potential of microbial sequencing to identify or treat intestinal dysbiosis. Here, we examined whether metabolic profiling is a feasible method of monitoring intestinal dysbiosis in critically ill children.

Design:

Prospective multicenter cohort study.

Setting:

Three U.K.-based PICUs.

Patients:

Mechanically ventilated critically ill (n = 60) and age-matched healthy children (n = 55).

Interventions:

Collection of urine and fecal samples in children admitted to the PICU. A single fecal and urine sample was collected in healthy controls.

Measurements and Main Results:

Untargeted and targeted metabolic profiling using 1H-nuclear magnetic resonance spectroscopy and liquid chromatography-mass spectrometry or urine and fecal samples. This was integrated with analysis of fecal bacterial 16S ribosomal RNA profiles and clinical disease severity indicators. We observed separation of global urinary and fecal metabolic profiles in critically ill compared with healthy children. Urinary excretion of mammalian-microbial co-metabolites hippurate, 4-cresol sulphate, and formate were reduced in critical illness compared with healthy children. Reduced fecal excretion of short-chain fatty acids (including butyrate, propionate, and acetate) were observed in the patient cohort, demonstrating that these metabolites also distinguished between critical illness and health. Dysregulation of intestinal bile metabolism was evidenced by increased primary and reduced secondary fecal bile acid excretion. Fecal butyrate correlated with days free of intensive care at 30 days (r = 0.38; p = 0.03), while urinary formate correlated inversely with vasopressor requirement (r = –0.2; p = 0.037).

Conclusions:

Disruption to the functional activity of the intestinal microbiome may result in worsening organ failure in the critically ill child. Profiling of bacterial metabolites in fecal and urine samples may support identification and treatment of intestinal dysbiosis in critical illness.
Reversible Impaired Methotrexate Clearance After Platinum-Based Chemotherapy for Osteosarcoma
Authors: Oude Munnink Thijs , van der Meer Alex , de Haan Jacco , Touw Daan , van Kruchten Michel
Published: June 2019

The authors present a case of an 18-year-old man with metastasized osteosarcoma, admitted for methotrexate (MTX) treatment combined with cisplatin and doxorubicin. During the first cycle, severe MTX toxicity was observed with increased MTX serum levels and delayed MTX clearance requiring rescue treatment with intensified leucovorin. In the following cycles, cisplatin and doxorubicin were discontinued, and MTX dose was reduced. The elimination half-life slowly improved over the following cycles suggesting a reversible cause responsible for reduced MTX clearance and toxicity during the first cycle. Cisplatin is well-known for its nephrotoxic effects and can induce reversible tubular injury. Previous treatment with cisplatin may well have been responsible for decreased MTX clearance, and combination treatment should be used with adequate monitoring of MTX levels. Other factors that may have contributed, such as urine alkalization, gene polymorphisms, and other drug–drug interactions are discussed.
Early versus late recurrence of centrally located hepatocellular carcinoma after mesohepatectomy
Authors: Zhao Jun , Li Wei , Mao Jie
Published: June 2019

The aim of this study was to investigate the features, treatment, and prognosis of early versus late recurrence of centrally located hepatocellular carcinoma (CL-HCC) after mesohepatectomy (MH).

Three hundred forty eight patients with CL-HCC undergoing MH were included. Data on clinicopathological characteristics, initial surgical details, timing and sites of tumor recurrence, management after recurrence, and long-term outcomes were analyzed.

The optimal cutoff value to differentiate early (71 patients, 64.5%) versus late (39, 35.5%) recurrence was defined as 12 months. Patients with early recurrence (ER) had higher alpha fetoprotein (AFP) level (P < .001), more advanced tumor stage (P = .024), and higher incidence of microvascular invasion (MVI, P = .001). Patients with ER had higher incidence of local tumor recurrence (P = .027) and higher average number of recurrent nodules (P = .016) than patients with LR. Patients after ER showed a better overall survival (from date of diagnosis of recurrence) than after late recurrence (LR). Patients with ER had less chances of curative treatment (14.1% vs 41.0%, P = .004) after tumor recurrence than patients with LR. Multivariable analyses revealed that liver cirrhosis (P < .001) and tumor differentiation (P < .001) were associated with an increased likelihood of LR, while multiple tumor number (P = .005), type IV classification (P = .012), and MVI (P < .001) were independent risk factors related to ER.

ER and LR after MH for CL-HCC were associated with different risk predictors and prognosis. Data on the timing of recurrence may inform decisions about postoperative adjuvant treatment, as well as help to predict long-term survival for these patients.
Predictive role of subcomponents of the left arcuate fasciculus in prognosis of aphasia after stroke
Authors: Yu Qiwei , Wang Hong , Li Shuqing , Dai Yanhong
Published: June 2019

The relationship between the left arcuate fasciculus (AF) and stroke-related aphasia is unclear. In this retrospective study, we aimed to investigate the role of subcomponents of the left AF in predicting prognosis of aphasia after stroke. Twenty stroke patients with aphasia were recruited and received language assessment as well as diffusion tensor tractography scanning at admission. According to injury of the left AF, the participants were classified into four groups: group A (4 cases), the AF preserved intactly; group B (6 cases), the anterior segment injured; group C (4 cases), the posterior segment injured; and group D (6 cases), completely injured. After a consecutive speech therapy, language assessment was performed again. Changes of language functions among the groups were compared and the relation between these changes with segments injury of the AF was analyzed. After therapy, relatively high increase score percentage changes in terms of all the subcategories of language assessment were observed both in group A and C; by contrast, only naming in group B, and spontaneous speech in group D. Although no statistical difference was demonstrated among the four groups. In addition, there was no significant correlation between improvement of language function with segments injury of the AF. The predictive role of subcomponents of the left AF in prognosis of aphasia is obscure in our study. Nevertheless, it indicates the importance of integrity of the left AF for recovery of aphasia, namely that preservation of the left AF on diffusion tensor tractography could mean recovery potential of aphasia after stroke.
The cumulative venous thromboembolism incidence and risk factors in intensive care patients receiving the guideline-recommended thromboprophylaxis
Authors: Zhang Chuanlin , Zhang Zeju , Mi Jie , Wang Xueqin , Zou Yujun , Chen Xiaoya , Nie Zhi , Luo Xinyi , Gan Ruiying
Published: June 2019

Few prospective studies have reported the cumulative incidence of venous thromboembolism (VTE) in the intensive care unit (ICU), especially for patients receiving guideline-recommended VTE prophylaxis. We aimed to design a prospective observational study to investigate the cumulative incidence and risk factors of ICU-acquired VTE for those populations.

We prospectively studied 281 consecutively included patients in the ICU at a single center. All patients provided informed consent. Patients received ultrasound evaluation and were followed for VTE before ICU discharge or within 28 days of ICU stay. The type of VTE thromboprophylaxis was also recorded for all patients. Variables from univariate analyses that were associated with VTE were included in the binary logistic regression analysis to determine VTE predictors. The cumulative VTE incidence with 95% confidence interval (CI) was estimated using Kaplan–Meier methods.

Patients had a median age of 60 years (range, 18–89) and an acute physiology and chronic health evaluation II score of 17 (range, 4–36). Despite all patients receiving guideline-recommended thromboprophylaxis, the cumulative incidence of VTE at 7, 14, 21, and 28 days was 4.45% (95% CI 2.55–7.71), 7.14% (95% CI 4.61–10.97), 7.53% (95% CI 4.92–11.43), and 9.55% (95% CI 6.55–13.81), respectively. Central venous catheter use (P = .002, odds ratio [OR] = 4.50), Caprini score (P = .012, OR = 1.20), and ICU length of stay (P = .006, OR = 1.08) were independent risk factors related to the incidence of VTE for patients admitted to the ICU.

Our prospective observational study found that the 28-day cumulative incidence of VTE was relatively high for patients admitted to the ICU, despite the use of guideline-recommended thromboprophylaxis. Patients with femoral central venous catheter, prolonged ICU length of stay, or a high Caprini score may have an increased risk of developing VTE.
Relationship between CXC chemokine receptor 4 expression and prognostic significance in acute myeloid leukemia
Authors: Cao Tingyong , Ye Yuanxin , Liao Hongyan , Shuai Xiao , Jin Yongmei , Su Jun , Zheng Qin
Published: June 2019

CXC chemokine receptor 4 (CXCR4) expression on acute myeloid leukemia (AML) cells correlated with stromal cell derived factor-1α (SDF-1α) and retained hematopoietic progenitors and leukemia cells within the bone marrow microenvironment. Here, we examined CXCR4 expression in 134 de novo AML and 21 controls by flow cytometry, evaluated the relationship between CXCR4 expression and clinical characteristics, and elucidated the prognostic significance of CXCR4 expression in AML prospectively. We found that the CXCR4 expression was significantly higher in AML patients than controls (P = .000). One hundred thirty four cases of de novo AML patients were divided into 2 groups according to the median of CXCR4 relative fluorescence intensity (RFI). CXCR4 high group (RFI >4.23) had markedly shorter overall survival (OS) and disease-free survival (DFS) than CXCR4 low group (RFI ≤4.23) in 106 AML patients who received chemotherapy (P = .002; .026, respectively). Furthermore, in the 87 non-M3 patients who received induction therapy, there was a significant decrease for OS but not for DFS in the CXCR4 high group (P = .047 and .178, respectively). Moreover, high levels of CXCR4 expression independently increased the risk of relapse in both all AML and non-M3 patients who achieved complete remission (CR) after chemotherapy (odds ratio = 1.090, P = .010; odds ratio = 1.068, P = .048, respectively). Collectively, our data suggest that CXCR4 overexpression was an independent prognostic factor for disease relapse and poorer OS in both all AML and non-M3 patients. CXCR4 expression levels can be determined at disease presentation by the flow rapidly and easily. As such, CXCR4 could be used as a potential therapeutic target in AML patients with poor prognosis.
Traditional Chinese medicine therapy reduces the risk of total knee replacement in patients with knee osteoarthritis
Authors: Lo Pei-Chia , Lin Fong-Cheng , Tsai Yao-Chien , Lin Shun-Ku
Published: June 2019

Knee osteoarthritis is a degenerative disease occurring in elderly people worldwide. For severe knee osteoarthritis, total knee replacement is the final treatment option. Traditional Chinese medicine (TCM) is popular in Taiwan and has been shown to exert therapeutic effects on knee osteoarthritis. We investigated the long-term clinical effects of TCM for reducing the need for total knee replacement risk in patients with knee osteoarthritis.

We used the National Health Insurance Research Database to conduct a retrospective study of patients with knee osteoarthritis between 1997 and 2003 in Taiwan. Data from the date of diagnosis of knee osteoarthritis to total knee replacement were assessed using the Cox regression proportional hazards model, and the Kaplan–Meier survival curve was used to determine the association between total knee replacement risk and TCM use.

A total of 34,231 patients with knee osteoarthritis, who were diagnosed by orthopedic or rehabilitation physicians between 1997 and 2003 were included. Patients were categorized into 2 groups: 26,257 (76.7%) were TCM users and 7974 (23.3%) were TCM non-users. The mean follow-up period was 9.26 years. Multivariate regression demonstrated that using TCM may decrease the need for total knee replacement in patients with knee osteoarthritis (adjusted hazards ratio [aHR] = 0.69, 95% confidence interval [95% CI]: 0.64–0.77) compared with TCM non-users. A relationship between longer TCM use and reduced total knee replacement use was observed, especially in patients who used TCM for ≥120 days (aHR = 0.49, 95% CI: 0.42–0.56).

The results of this study suggested that TCM is associated with a reduced risk of total knee replacement in patients with knee osteoarthritis, with enhanced benefits from longer durations of TCM use.
Combining procalcitonin with the qSOFA and sepsis mortality prediction
Authors: Yu Hua , Nie Lu , Liu Aibo , Wu Kuihai , Hsein Yenh-Chen , Yen Debra W. , Lee Meng-tse G. , Lee Chien-Chang
Published: June 2019

To investigate whether procalcitonin (PCT) can improve the performance of quick sequential organ failure assessment (SOFA) score in predicting sepsis mortality, we conducted a retrospective multicenter cohort study with independent validation in a prospectively collected cohort in 3 tertiary medical centers. Patients with presumed sepsis were included. Serum PCT levels were measured at admission. Quick SOFA score and systemic inflammatory response syndrome (SIRS) criteria were calculated for each patient. PCT levels were assigned into 0, 1, and 2 points for a serum level of <0.25, 0.25 to 2, and >2 ng/mL, and added to the quick sepsis-related organ failure assessment (qSOFA) score. The incremental value of PCT to qSOFA was then evaluated by logistic regression, receiver-operating characteristic (ROC) curve, and reclassification analysis.

In all, 1318 patients with presumed severe infection were enrolled with a 30-day mortality of 13.5%. Serum level of PCT showed a high correlation with qSOFA score and 30-day inhospital mortality. The area under the ROC curve was 0.56 for SIRS criteria, 0.67 for qSOFA score, and 0.73 for qSOFA_PCT in predicting 30-day mortality. The risk prediction improvement was reflected by a net reclassification improvement of 35% (17%–52%). Incorporation of PCT into the qSOFA model could raise the sensitivity to 86.5% (95% confidence interval 80.6%–91.2%). In the validation cohort, qSOFA_PCT greatly improved the sensitivity to 90.9%.

A simple modification of qSOFA score by adding the ordinal scale of PCT value to qSOFA could greatly improve the suboptimal sensitivity problem of qSOFA and may serve as a quick screening tool for early identification of sepsis.
Diagnosis and management of linear scleroderma in children
Authors: Peña-Romero Adriana G. , García-Romero Maria T.
Published: June 2019

Purpose of review

Linear scleroderma is the most common subtype of localized scleroderma (LoS) in children. It can be associated with extracutaneous manifestations and long-term sequelae. Thus, appropriate diagnosis and management are key to improve the prognosis. In this review, we summarize the most relevant recent publications for the diagnosis, evaluation of disease activity and adequate management of patients with linear scleroderma.

Recent findings

There are specific clinical features that indicate activity in LoS; dermoscopy and Wood's lamp may be useful. Summarizing, scoring methods seem to provide the most adequate assessment of LoS; but several biomarkers that correlate with activity have been studied: E-selectin and IL-2 receptor, CD34+ dermal dendritic cells and Th/Th1 immunophenotype with decreased T helper (Th2), T regulatory (Tregs), B and natural killer (NK) cells. Recent studies propose hydroxychloroquine monotherapy and tocilizumab as potential therapeutic options.

Clinical evaluation, both physical exam and history, is the most important aspect in diagnosing and assessing activity of linear scleroderma. Clinical scoring methods may be most useful for evaluation of activity; eventually, other biomarkers could be relevant in clinical practice. For most patients with linear scleroderma, the first choice of treatment is methotrexate, but physical therapy, plastic surgery and/or orthopedic management are key to improve residual limitations and quality of life.

Video abstract

http://links.lww.com/MOP/A35.
The past, present, and future of costimulation blockade in organ transplantation
Authors: Schroder Paul M. , Fitch Zachary W. , Schmitz Robin , Choi Ashley Y. , Kwun Jean , Knechtle Stuart J.
Published: June 2019

Purpose of review

Manipulating costimulatory signals has been shown to alter T cell responses and prolong graft survival in solid organ transplantation. Our understanding of and ability to target various costimulation pathways continues to evolve.

Recent findings

Since the approval of belatacept in kidney transplantation, many additional biologics have been developed targeting clinically relevant costimulation signaling axes including CD40-CD40L, inducible costimulator-inducible costimulator ligand (ICOS-ICOSL), and OX40-OX40L. Currently, the effects of costimulation blockade on posttransplant humoral responses, tolerance induction, and xenotransplantation are under active investigation. Here, we will discuss these pathways as well as preclinical and clinical outcomes of biologics targeting these pathways in organ transplantation.

Targeting costimultion is a promising approach for not only controlling T cell but also B cell responses. Consequently, costimulation blockade shows considerable potential for improving outcomes in antibody-mediated rejection and xenotransplantation.
Outcomes of Children With Chronic Intestinal Failure
Authors: Jo Sz‐Ying C. , McCallum Zoe , Shalley Helen , Peterkin Megan , Rogers Elizabeth , Paxton Georgia , Wong Theodoric , Bines Julie E.
Published: June 2019

Background and Aims:

The aim of the study was to aid decisions on prognosis and transplantation; this study describes the outcome of children with intestinal failure managed by the multidisciplinary intestinal rehabilitation program at the Royal Children's Hospital, Melbourne.

Methods:

Retrospective review of children requiring parenteral nutrition (PN) for >3 months who were assessed for home PN between 1991 and 2011.

Results:

A total of 51 children were included. Forty‐two (82%) had short bowel syndrome (SBS), 5 (10%) had chronic intestinal pseudo‐obstruction syndrome, and 4 (8%) had congenital enteropathies. Median small bowel length for patients with SBS was 45 cm (interquartile range 30–80) or 23.9% of the expected length for age (interquartile range 17.0%–40.6%). Overall survival rate was 84% (43/51). Mortality in children (n = 7) occurred after a median of 13.2 months (range 6.2–29.2) with intestinal failure–associated liver disease (IFALD) being the only predictor (P = 0.001). Out of 50 children 21 (42%) had IFALD. Children who were premature (P = 0.013), had SBS (P = 0.038), and/or frequent sepsis (P = 0.014) were more likely to develop IFALD. PN weaning occurred in 27 of 35 (77%) SBS survivors, after a median of 10.8 months (up to 8.2 years), with longer residual small bowel (P = 0.025), preservation of the ileocecal valve (P = 0.013) and colon (P = 0.011) being predictors. None of 5 (0%) patients with chronic intestinal pseudo‐obstruction syndrome and 2 of 4 (50%) patients with congenital enteropathies weaned off PN. Overall sepsis rate was 7.3 episodes/1000 line days. Frequency of sepsis and longevity of central lines improved with time as patients grew older (both P < 0.001).

Conclusions:

Long‐term PN with intestinal rehabilitation was effective in treating most children with intestinal failure. Children with severe refractory IFALD may have benefited from intestinal transplantation.
The Use of Tranexamic Acid (TXA) for the Management of Hemorrhage in Trauma Patients in the Prehospital Environment: Literature Review and Descriptive Analysis of Principal Themes
Authors: Stansfield Rachel , Morris Danielle , Jesulola Emmanuel
Published: June 2019

Tranexamic acid (TXA) is an antifibrinolytic agent used to prevent traumatic exsanguination. It was first introduced to clinical practice for the management of patients with bleeding disorders, especially adapted to reduce bleeding in hemophiliacs undergoing oral surgical interventions. TXA exerts its action on the coagulation process by competitively inhibiting plasminogen activation, thereby reducing conversion of plasminogen into plasmin. This ultimately prevents fibrinolysis and reduces hemorrhage. Thus, TXA may be well suited for the management of traumatic hemorrhage in the prehospital setting.

Despite multiplicity of studies on the use of TXA in clinical practice, there is no consensus regarding the use of TXA for the management of hemorrhage in trauma patients in the prehospital environment. Thus, a review on this topic was warranted. An extensive literature search yielded 14 full journal articles which met the inclusion criteria. These articles were thoroughly analyzed and the following themes were identified: “dose of TXA administration,” “route of TXA administration,” “optimal window of TXA administration,” “safety of TXA use,” “clinical effectiveness of TXA application,” and the “feasibility of TXA use in the prehospital setting.”

Overall, to achieve the best possible outcomes, the literature supports the use of a loading dose of 1 g of TXA, followed by 1 g infusion over 8 h, given by intravenous administration within a 3-h window period of traumatic injury. TXA is very effective and safe to use in the prehospital setting, and its use is clinically and economically feasible.
Temporal Trends and Clinical Outcomes Associated with Vasopressor and Inotrope Use in The Cardiac Intensive Care Unit
Authors: Jentzer Jacob C. , Wiley Brandon , Bennett Courtney , Murphree Dennis H. , Keegan Mark T. , Kashani Kianoush B. , Bell Malcolm R. , Barsness Gregory W.
Published: June 2019

Background:

The use of norepinephrine may be associated with better outcomes in some patients with shock. We sought to determine whether norepinephrine was associated with lower mortality in unselected cardiac intensive care unit (CICU) patients compared with other vasopressors, and whether patterns of vasopressor and inotrope usage in the CICU have changed over time.

Methods:

We retrospectively evaluated consecutive adult patients admitted to a tertiary care hospital CICU from January 1, 2007 to December 31, 2015. Vasoactive drug doses were quantified using the peak Vasoactive-Inotropic Score (VIS). Temporal trends were assessed using the Cochran–Armitage trends test and multivariable logistic regression was used to determine predictors of hospital mortality.

Results:

We included 10,004 patients with a mean age of 67 ± 15 years; vasoactive drugs were used in 2,468 (24.7%) patients. Use of norepinephrine increased over time, whereas dopamine utilization decreased (P < 0.001 for trends). After adjustment for illness severity and other variables, the peak VIS was a predictor of hospital mortality across the entire population (unit odds ratio [OR] 1.013, 95% confidence interval [CI], 1.009–1.017,P < 0.001) and among patients receiving vasoactive drugs (OR 1.018, 95% CI, 1.013–1.022,P < 0.001). Among patients receiving vasoactive drugs, norepinephrine was associated with a lower risk of hospital mortality (OR 0.66, 95% CI, 0.49–0.90,P = 0.008) after adjustment for illness severity and peak VIS.

Conclusions:

Vasoactive drug use in CICU patients has a dose-dependent association with short-term mortality. Use of norepinephrine in CICU patients is associated with decreased odds of death when compared with other vasoactive drugs.
Learner Satisfaction and Experience With a High-definition Telescopic Camera During Vaginal Procedures: A Randomized Controlled Trial
Authors: Hobson Deslyn T. G. , Meriwether Kate V. , Gaskins Jeremy T. , Uddin M. Nazir , Stewart J. Ryan , Gupta Ankita S. , Francis Sean L.
Published: June 2019

Objective

The aim of this study was to compare learner satisfaction and experience with a table-mounted, projecting, high-definition telescopic camera system (VITOM) versus traditional learner observation during vaginal surgery.

Methods

Medical student and resident learners were randomized to vaginal surgery observation with or without the use of VITOM. We collected data on learner characteristics and their experience with vaginal surgery. After the surgery, learners completed the faculty/preceptor and working environment domains of the Veterans Affairs Learner’s Perceptions Survey (VA LPS). The primary outcome was learners who were “very satisfied” on the VA LPS faculty/preceptor domain. We queried their ability to observe the surgery and satisfaction with learning in the operating room using a 100-mm visual analog scale.

Results

Ninety-two learners completed the study (n = 44 VITOM, n = 48 no VITOM). There was no significant difference between groups in the proportion of learners “very satisfied” on the VA LPS faculty/preceptor domain (93.2% VITOM vs 91.5% no VITOM; odds ratio, 1.27; 95% confidence interval, 0.20–9.19; P = 0.99). Learners in the VITOM group were more likely to report ability to see what the main surgeon was doing (93.2% VITOM vs 62.5% no VITOM; odds ratio, 8.02; 95% confidence interval, 2.07–46.32; P < 0.01). Using the visual analog scale, learners in the VITOM group reported higher satisfaction with learning in the operating room (median, 96 [interquartile range, 89–100] VITOM vs median, 80 [interquartile range, 57–98] no VITOM; P < 0.01).

Conclusion

The use of a table-mounted, projecting, telescopic camera system during vaginal surgery showed no difference in learner satisfaction on validated questionnaires but resulted in improved experience and visualization.
Not all Pseudomonas aeruginosa are equal: strains from industrial sources possess uniquely large multireplicon genomes
Authors: Weiser Rebecca , Green Angharad E. , Bull Matthew J. , Cunningham-Oakes Edward , Jolley Keith A. , Maiden Martin C. J. , Hall Amanda J. , Winstanley Craig , Weightman Andrew J. , Donoghue Denise , Amezquita Alejandro , Connor Thomas R. , Mahenthiralingam Eshwar
Published: June 2019

Pseudomonas aeruginosa

is a highly versatile, antibiotic-resistant Gram-negative bacterium known for causing opportunistic infections and contamination of industrial products. Despite extensive genomic analysis of clinical

P. aeruginosa

strains, no genomes exist for preservative-tolerant industrial strains. A unique collection of 69 industrial isolates was assembled and compared to clinical and environmental strains; 16 genetically distinct industrial strains were subjected to array tube genotyping, multilocus sequence typing and whole-genome sequencing. The industrial strains possessed high preservative tolerance and were dispersed widely across

P. aeruginosa

as a species, but recurrence of strains from the same lineage within specific industrial products and locations was identified. The industrial

P. aeruginosa

genomes (mean=7.0 Mb) were significantly larger than those of previously sequenced environmental (mean=6.5 Mb; n=19) and clinical (mean=6.6 Mb; n=66) strains. Complete sequencing of the

P. aeruginosa

industrial strain RW109, which encoded the largest genome (7.75 Mb), revealed a multireplicon structure including a megaplasmid (555 265 bp) and large plasmid (151 612 bp). The RW109 megaplasmid represented an emerging plasmid family conserved in seven industrial and two clinical

P. aeruginosa

strains, and associated with extremely stress-resilient phenotypes, including antimicrobial resistance and solvent tolerance. Here, by defining the detailed phylogenomics of

P. aeruginosa

industrial strains, we show that they uniquely possess multireplicon, megaplasmid-bearing genomes, and significantly greater genomic content worthy of further study.