bluuebunny/crossref_metadata_2025 huggingface dataset:
Pseudoaneurysm of Facial Artery After Orthognathic Surgery
Authors: Neto Tiburtino José de Lima , Maranhão Carlos Alexandre de Albuquerque , Neto Patrício José de Oliveira
Published: June 2019

Sagittal osteotomy of the mandibular branch is to be included common approach for alteration of facial tooth shapes and it is treated technically safe. This conduct can breed various complications, among other things vascular complications. A clinical case has described the development of pseudoaneurysm in the facial artery in a 33-year patient undergoing bilateral osteotomy Le Fort I sagittal osteotomy of the mandibular branch. Subsequently, there was a vascular complication treated by the vascular surgeon that generated a rejection process to the material used for treatment, generating aesthetic damage to the patient and the need for plastic surgery intervention. The leading mode of conduct of vascular injuries are analyzed, and embolization is established to be technically secure conduct.
Myocardial Edema: an Overlooked Mechanism of Septic Cardiomyopathy?
Authors: Vasques-Nóvoa Francisco , Laundos Tiago L. , Madureira António , Bettencourt Nuno , Nunes José P.L. , Carneiro Fátima , Paiva José A. , Pinto-do-Ó Perpétua , Nascimento Diana S. , Leite-Moreira Adelino F. , Roncon-Albuquerque Roberto
Published: June 2019

Septic cardiomyopathy is an increasingly relevant topic in clinical management of septic shock. However, pathophysiological mechanisms and long-term consequences of sepsis-induced myocardial injury are still poorly understood. Herein, new clinical and histological evidence is provided suggesting an association of myocardial edema formation with tissue injury and subsequent remodeling in septic shock patients. This preliminary data supports myocardial edema as a potentially relevant and largely unexplored mechanism of human septic cardiomyopathy.
Multimorbidity in older adults living with and beyond cancer
Authors: Corbett Teresa , Bridges Jackie
Published: June 2019

Purpose of review

The current review draws attention to the need for longer term management of multiple conditions in older adults with cancer.

Recent findings

Older people living with and beyond cancer are more likely than younger people to have higher prevalence of multimorbidity leading to an overall increase in illness and treatment burdens, limiting health-related quality of life (QoL), and capacity to self-manage. Older age presents a higher risk of cancer treatment side-effects and development or progression of other conditions, leading to worsening health, long-lasting functional problems, and social isolation. Although many prioritize functional independence and continuance of valued activities over survival, older people living with multimorbidity are more likely to experience poor physical functioning during and beyond cancer treatment.

Cancer treatment decisions and survivorship plans should be developed in the context of other conditions and in line with the individual's priorities for continued QoL. More research is needed to guide service development and clinical practice in this important area.
Vaginal Estrogen for the Prevention of Recurrent Urinary Tract Infection in Postmenopausal Women: A Randomized Clinical Trial
Authors: Ferrante Kimberly L. , Wasenda Erika J. , Jung Carrie E. , Adams-Piper Emily R. , Lukacz Emily S.
Published: June 2019

Objectives

We aimed to compare the efficacy of 2 commonly used contemporary vaginal estrogen administrations versus placebo for the prevention of urinary tract infection (UTI) in postmenopausal women with a clinical diagnosis of recurrent UTI (rUTI).

Methods

This was an investigator-initiated, multicenter, single-blind, randomized, placebo-controlled trial of vaginal estrogen (delivered via ring or cream) compared with placebo. Postmenopausal women with documented rUTI were randomized to receive either vaginal estrogen (via ring or cream) or placebo cream in a 1:1:1 fashion. The primary outcome was occurrence of UTI at 6 months. After 6 months, open-label use of ring or active cream was offered to all participants for an additional 6 months. Because of slower than expected recruitment, sample size calculations and block randomization schema were revised to combine estrogen groups (ring or cream) for statistical comparisons to placebo cream in a 1:1 fashion.

Results

Thirty-five women were randomized with 9 dropouts (1 ring, 2 cream, and 6 placebo) prior to the 6 months. Intention-to-treat analysis (assuming dropouts as failures) revealed fewer women treated with vaginal estrogen had a UTI within 6 months versus placebo (11/18 vs 16/17, respectively; P = 0.041). Per-protocol analysis revealed fewer subjects treated with vaginal estrogen had a UTI at 6 months (8/15 vs 10/11, respectively; P = 0.036).

Conclusions

Commonly prescribed forms of vaginal estrogen with contemporary dosing schedules prevent UTIs in postmenopausal women with an active diagnosis of rUTI.
Multi-lineage evolution in viral populations driven by host immune systems
Authors: Marchi Jacopo , Lässig Michael , Mora Thierry , Walczak Aleksandra M.
Published: June 2019

Viruses evolve in the background of host immune systems that exert selective pressure and drive viral evolutionary trajectories. This interaction leads to different evolutionary patterns in antigenic space. Examples observed in nature include the effectively one-dimensional escape characteristic of influenza A and the prolonged coexistence of lineages in influenza B. Here we use an evolutionary model for viruses in the presence of immune host systems with finite memory to delineate parameter regimes of these patterns in a in two-dimensional antigenic space. We find that for small effective mutation rates and mutation jump ranges, a single lineage is the only stable solution. Large effective mutation rates combined with large mutational jumps in antigenic space lead to multiple stably co-existing lineages over prolonged evolutionary periods. These results combined with observations from data constrain the parameter regimes for the adaptation of viruses, including influenza.
Nucleocytoplasmic Proteomic Analysis Uncovers eRF1 and Nonsense Mediated Decay as Modifiers of ALS C9orf72 Toxicity
Authors: Ortega Juan A. , Daley Elizabeth L. , Kour Sukhleen , Samani Marisa , Tellez Liana , Smith Haley S. , Hall Elizabeth A. , Taylan Esengul Y. , Tsai Yung-Hsu , Gendron Tania F. , Donnelly Christopher J. , Siddique Teepu , Savas Jeffrey N. , Pandey Udai B. , Kiskinis Evangelos
Published: June 2019

The most common genetic cause of amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) is a hexanucleotide repeat expansion in C9orf72 (C9-HRE). While RNA and dipeptide repeats produced by the C9-HRE disrupt nucleocytoplasmic transport, the proteins that become redistributed remain unknown. Here, we utilized subcellular fractionation coupled with tandem mass spectrometry and identified 126 proteins, enriched for protein translation and RNA metabolism pathways, which collectively drive a shift towards a more cytosolic proteome in C9-HRE cells. Amongst these was eRF1, which regulates translation termination and nonsense-mediated decay (NMD). eRF1 accumulates within elaborate nuclear envelope invaginations in patient iPSC-neurons and postmortem tissue and mediates a protective shift from protein translation to NMD-dependent mRNA degradation. Overexpression of eRF1 and the NMD-driver UPF1 ameliorate C9-HRE toxicity in vivo. Our findings provide a resource for proteome-wide nucleocytoplasmic alterations across neurodegeneration-associated repeat expansion mutations and highlight eRF1 and NMD as therapeutic targets in C9orf72-associated ALS/FTD.
The role of iron uptake systems in the pathogenesis of colistin-resistant hypervirulent K.pneumoniae infections
Authors: Dogan Ozlem , Vatansever Cansel , Atac Nazli , Albayrak Ozgur , Karahuseyinoglu Sercin , Sahin Ozgun Ekin , Kilicoglu Bilge Kaan , Demiray Atalay , Ergonul Onder , Gönen Mehmet , Can Fusun
Published: June 2019

Here we proposed the hypothesis that hypervirulent colistin resistant K.pneumoniae (ColR-Kp) exhibit high number of virulence factors and have enhanced survival capacity against neutrophil activity.

We studied virulence genes of ColR-Kp isolates and neutrophil response in 142 patients with invasive infections.

The patients infected with hypervirulent ST101 and ST395 ColR-Kp had higher 30-day mortality (58%, p=0.005 and 75%, p=0.003, respectively. The yersiniabactin biosynthesis gene (ybtS) and ferric uptake operon associated gene (kfu) were significantly higher in ST101 (99%, p=<0.001) and in ST395 (94%, p<0.012). Being in ICU (OR: 7.9; CI: 1.43-55.98; p=0.024), kfu (OR:27.0; CI:5.67-179.65; p<0.001) and ST101 (OR: 17.2; CI: 2.45-350.40; p=0.01) were found to be predictors of 30-day mortality. The uptake of kfu+-ybtS+ ColR-Kp by neutrophils was significantly higher than kfu--ybtS- ColR-Kp (78% vs 65%, p<0.001). However, kfu+-ybtS+ ColR-Kp were more resistant to the killing activity of neutrophils than negative ones (7.90 vs 4.22; p=0.001). The kfu+-ybtS+ ColR-Kp stimulated excessive NET formation while the NET’s against kfu--ybtS- ColR-Kp were weak and rare.

Iron uptake systems enhance successful survival of K.pneumoniae against neutrophil phagocytic defense, and stimulate excessive NET formation. The drugs targeted to iron uptake systems would be a promising approach for treatment of hypervirulent K.pneumoniae infections.
Tracking the origin of island diversity: insights from divergence with the continental pool in monocots
Authors: Veron Simon , Mouchet Maud , Grandcolas Philippe , Govaerts Rafaël , Haevermans Thomas , Pellens Roseli
Published: June 2019

At their early age, a large proportion of island pools were a partial sampling of mainland pools whatever islands are oceanic or fragments of the mainland. Through time, colonization, diversification, extinctions, have deeply transformed insular and continental communities and therefore the degree to which they share species. We studied the relative importance of these mechanisms by looking at the shared evolutionary history between species pools on islands and continents. Indeed, most of these mechanisms are not neutral regarding phylogeny but are linked to species evolutionary relationships. We measured the phylogenetic divergence between continental and insular monocot communities through metrics of beta Mean Pairwise Distance and beta Mean Nearest Taxon Distance. We first tested the influence of spatial and environmental distance to the continent, two main factors of divergence, but whose explanatory power in a phylogenetic context was still unclear. We showed that both dispersal and enviromental filtering were important to explain divergence, although species that could pass these filters were not phylogenetically clustered. There was however a clear distinction between oceanic and continental islands: a stable climate in the latters was key to the survival of the original biota leading to a high proportion of shared lineages between the mainland and islands. But distance to the continent was only part of the story, we investigated additionnal mechanisms of phylogenetic divergence through their relation to island features and community structure. This showed that the most divergent islands occurred in the tropics and that processes of persistence of original species, diversification in remote archipelagos, neutral colonization on easy-to-reach islands, turnover, and high speciation rates may have driven phylogenetic divergence at a world scale. This study showed how phylogenetic approaches may explain how divergence, or similarity may have arisen and provide new insights in the continental origin of plant diversity on islands.
Towards the minimal proteome of life: Proteome profiles ofBacillus subtilisvegetative cells and spores
Authors: Swarge Bhagyashree , Roseboom Winfried , de Koster Chris G. , Brul Stanley , de Koning Leo J.
Published: June 2019

The method of15N metabolic labelling ofBacillus subtilisenabled mass spectrometric quantification of relative protein levels in the vegetative cells and the spores of this model organism. A total of 1501 proteins have been identified from the combined spore and vegetative cell samples. From these 1086 proteins have been relatively and reproducibly quantified between spores and vegetative cells. Of the quantified proteins, 60% are common to the vegetative cells and spores, indicating that spores host a minimal set proteins sufficient for the resumption of metabolism upon completion of germination. The shared proteins represent, the most basic ‘survival kit’ for life on earth that is known thus far.
XenoCell: classification of cellular barcodes in single cell experiments from xenograft samples
Authors: Cheloni Stefano , Hillje Roman , Luzi Lucilla , Pelicci Pier Giuseppe , Gatti Elena
Published: June 2019

Single-cell sequencing technologies provide unprecedented opportunities to deconvolve the genomic, transcriptomic or epigenomic heterogeneity of complex biological systems. Its application in samples from xenografts of patient-derived biopsies (PDX), however, is limited by the presence in the analysed samples of a mixture of cells arising from the host and the graft.

We have developed XenoCell, the first stand-alone pre-processing tool that performs fast and reliable classification of host and graft cellular barcodes. We show its application on a single cell dataset composed by human and mouse cells.

Availability and implementation

XenoCell is available for non-commercial use on GitLab: https://gitlab.com/XenoCell/XenoCell
Type I-F CRISPR-Cas resistance against virulent phage infection triggers abortive infection and provides population-level immunity
Authors: Watson Bridget N.J. , Vercoe Reuben B. , Salmond George P.C. , Westra Edze R. , Staals Raymond H.J , Fineran Peter C.
Published: June 2019

Type I CRISPR-Cas systems are the most abundant and widespread adaptive immune systems of bacteria and can greatly enhance bacterial survival in the face of temperate phage infection. However, it is less clear how these systems protect against virulent phages. Here we experimentally show that type I CRISPR immunity of Pectobacterium atrosepticum leads to rapid suppression of two unrelated virulent phages, ΦTE and ΦM1. However, unlike the case where bacteria are infected with temperate phages, this is the result of an abortive infection-like phenotype, where infected cells do not survive the infection but instead become metabolically inactive and lose their membrane integrity. Our findings challenge the view of CRISPR-Cas as a system that protects the individual cell and supports growing evidence of an Abi-like function for some types of CRISPR-Cas systems.
The probability distribution of the reconstructed phylogenetic tree with occurrence data
Authors: Gupta Ankit , Manceau Marc , Vaughan Timothy , Khammash Mustafa , Stadler Tanja
Published: June 2019

We consider a homogeneous birth-death process with incomplete sampling. Three successive sampling schemes are considered. First, individuals can be sampled through time and included in the tree. Second, they can be occurrences which are sampled through time and not included in the tree. Third, individuals reaching present day can be sampled and included in the tree. Upon sampling, individuals are removed (i.e. die).

The outcome of the process is thus composed of the reconstructed evolutionary tree spanning all individuals sampled and included in the tree, and a timeline of occurrence events which are not placed along the tree. We derive a formula allowing one to compute the joint probability density of these, which can readily be used to perform maximum likelihood or Bayesian estimation of the parameters of the model.

In the context of epidemiology, our probability density allows us to estimate transmission rates through a joint analysis of epidemiological case count data and phylogenetic trees reconstructed from pathogen sequences. Within macroevolution, our equations are the basis for taking into account fossil occurrences from paleontological databases together with extant species phylogenies for estimating speciation and extinction rates. Thus, we provide the theoretical framework for bridging not only the gap between phylogenetics and epidemiology, but also the gap between phylogenetics and paleontology.
The WD40-repeat protein WDR-48 promotes the stability of the deubiquitinating enzyme USP-46 by inhibiting its ubiquitination and degradation
Authors: Hodul Molly , Ganji Rakesh , Dahlberg Caroline L , Raman Malavika , Juo Peter
Published: June 2019

Ubiquitination is a reversible post-translational modification that has emerged as a critical regulator of synapse development and function. However, mechanisms that regulate the deubiquitinating enzymes (DUBs) that are responsible for the removal of ubiquitin from target proteins are poorly understood. We previously showed that the DUB USP-46 removes ubiquitin from the glutamate receptor GLR-1 and regulates it trafficking and degradation in C. elegans. We found that WD40-repeat proteins WDR-20 and WDR-48 bind and stimulate the catalytic activity of USP-46. Here, we identify another mechanism by which WDR-48 regulates USP-46. We found that increased expression of WDR-48, but not WDR-20, promotes USP-46 abundance in mammalian cells in culture and in C. elegans neurons in vivo. Inhibition of the proteasome promotes the abundance of USP-46, and this effect is non-additive with increased expression of WDR-48. We found that USP-46 is ubiquitinated, and expression of WDR-48 reduces the levels of ubiquitin-USP-46 conjugates and increases the half-life of USP-46. A point mutant version of WDR-48 that disrupts binding to USP-46 is unable to promote USP-46 abundance in vivo. Together, these data support a model in which WDR-48 binds and stabilizes USP-46 protein levels by preventing the ubiquitination and degradation of USP-46 in the proteasome. Given that a large number of USPs interact with WDR proteins, we propose that stabilization of DUBs by their interacting WDR proteins may be a conserved and widely used mechanism to control DUB availability and function.
Radiation‐induced tumor immunity in patients with non‐small cell lung cancer
Authors: Lockney Natalie A. , Zhang Mei , Morris Christopher G. , Nichols Romaine Charles , Okunieff Paul , Swarts Steven , Zhang Zhenhuan , Zhang Bingrong , Zhang Amy , Hoppe Bradford S.
Published: June 2019

Background

Radiation‐induced tumor immunity (RITI) influences primary tumor growth and development of metastases in preclinical cancer models with conventional radiotherapy. Antigen‐specific immune responses have also been shown for prostate cancer treated with radiotherapy. We examined whether RITI can be induced in patients with non‐small cell lung cancer (NSCLC) following proton radiotherapy.

Methods

Pre‐ and post‐radiotherapy plasma samples from 26 patients with nonmetastatic NSCLC who received radiotherapy between 2010 and 2012 were evaluated by western blotting for IgG and IgM bands to assess RITI response to tumor antigens from lung cancer cell lines. Statistical analysis was used to evaluate any correlation among IgG or IgM and clinical outcomes.

Results

Twenty‐one patients received proton therapy at 2 GyRBE/fraction (n = 17) or 6–12 Gy/fraction (n = 4); five received photon therapy at 2–2.5 GyRBE/fraction. Compared with the pretreatment baseline, new IgG or IgM binding was detected in 27% and 50% of patients, respectively. New IgG bands were detected in the 25–37 kD, 50–75 kD, and 75–100 kD ranges. New IgM bands were detected in the 20–25 kD, 25–37 kD, 37–50 kD, 50–75 kD, and 75–100 kD ranges. There was no difference in IgG and/or IgM RITI response in patients treated with photons versus protons, or in patients who received SBRT compared to standard fractionation (P > 0.05). There was no difference in overall survival, metastasis‐free survival, or local control based on IgG and/or IgM RITI response (P > 0.05).

Conclusion

RITI can be induced in patients with NSCLC through upregulated IgG and/or IgM. RITI response was not associated with proton versus photon therapy or with clinical outcomes in this small cohort and should be examined in a larger cohort in future studies.
Dilution and microfiltration of particulate corticosteroids for spinal epidural injections: impact on drug concentration and agglomerate formation
Authors: Alcántara Guardado A. , Cooper G. , Weightman A. , Spiess R. , Baker A.D.L.
Published: June 2019

Particulate corticosteroids have been described to lead to greater pain improvement compared with their non‐particulate counterparts when used in epidural injections. It is hypothesised that filtering may significantly impact their concentration and long‐term efficacy. We investigated if passing particulate suspensions through different commonly‐used filters affects drug dosage. Two particulate corticosteroid formulations, triamcinolone acetonide and methylprednisolone acetate, were mixed at different concentrations with either bupivacaine hydrochloride or 0.9% sodium chloride. Solutions were passed through a 5‐μm and a 0.2‐μm filter. Mass spectroscopy results indicated a complete loss of corticosteroid from the solutions using both filters, and light microscopy imaging demonstrated agglomerate formation, suggesting that filtering interferes with drug dosage. The choice of diluents must also be considered to reduce large agglomerate formation. Clinicians should be aware of the consequences of filtering particulate suspensions and carefully consider the selection of diluent when considering treatment plans.
Atrophy of the central neuroretina in patients treated for diabetic macular edema
Authors: Karst Sonja G. , Schuster Magdalena , Mitsch Christoph , Meyer Elias L. , Kundi Michael , Scholda Christoph , Schmidt‐Erfurth Ursula M.
Published: June 2019

Purpose

To examine the prevalence of central retinal atrophy in patients treated for diabetic macular edema (DME) in a clinical setting.

Methods

Retrospective data analysis of patients with DME, focusing on those who developed central retinal thinning after DME treatment at the Department of Ophthalmology, Medical University Vienna. Patient characteristics and clinical data including best‐corrected visual acuity (BCVA), spectral domain optical coherence tomography and fluorescence angiography images were reviewed and DME treatment strategies analysed using descriptive statistics. The correlation between visual acuity and ocular, systemic or DME treatment factors was calculated using linear regression models and ancovas.

Results

A total of 6684 outpatient visits by 1437 patients with diabetes were analysed. Out of 149 patients, who had had a central subfield thickness (CST) below 200 μm, 32 (36 eyes) had previously been diagnosed with a centre involving DME with an average CST of 473 ± 103 μm and average visual acuity of 0.62 ± 0.44 logMAR at first presentation. At the time of central atrophy, 29 (81%) out of 36 eyes had a history of laser treatment, 11 (31%) a vitrectomy, 32 (88%) repeated intravitreal injections of anti‐vascular endothelial growth factor (VEGF; mean 5.3 ± 3.8) and 22 (61%) intravitreal corticosteroid injections (mean 2.5 ± 2.7). Visual function (0.67 ± 0.43 logMAR) at the time of atrophy was not significantly correlated to central retinal thickness (191 ± 7 μm) or any other ocular, systemic or treatment factors.

Conclusions

Only 4% of patients treated for DME developed central retinal thinning in our observation period. On average, our atrophy patients had higher CST and lower BCVA when they first presented with DME compared to the overall DME cohort, and they received a combination of intravitreal injections and laser for DME treatment. Central retinal atrophy might not be attributed to excessive use of intravitreally applied anti‐VEGF or any other DME therapy alone.
Distinct brain representations of processed and unprocessed foods
Authors: Coricelli Carol , Toepel Ulrike , Notter Marie‐Laure , Murray Micah M. , Rumiati Raffaella I.
Published: June 2019

Among all of the stimuli surrounding us, food is arguably the most rewarding for the essential role it plays in our survival. In previous visual recognition research, it has already been demonstrated that the brain not only differentiates edible stimuli from non‐edible stimuli but also is endowed with the ability to detect foods’ idiosyncratic properties such as energy content. Given the contribution of the cooked diet to human evolution, in the present study we investigated whether the brain is sensitive to the level of processing food underwent, based solely on its visual appearance. We thus recorded visual evoked potentials (VEPs) from normal‐weight healthy volunteers who viewed color images of unprocessed and processed foods equated in caloric content. Results showed that VEPs and underlying neural sources differed as early as 130 ms post‐image onset when participants viewed unprocessed versus processed foods, suggesting a within‐category early discrimination of food stimuli. Responses to unprocessed foods engaged the inferior frontal and temporal regions and the premotor cortices. In contrast, viewing processed foods led to the recruitment of occipito‐temporal cortices bilaterally, consistently with other motivationally relevant stimuli. This is the first evidence of diverging brain responses to food as a function of the transformation undergone during its preparation that provides insights on the spatiotemporal dynamics of food recognition.
Simulation of Flow in a Complex Aquifer System Subjected to Long‐Term Well Network Growth
Authors: Liao Hua‐Sheng , Curtis Zachary K , Sampath Prasanna Venkatesh , Li Shu‐Guang
Published: June 2019

In west‐central Lower Peninsula of Michigan, population growth and expanded agricultural activities over recent decades have resulted in significant increases in distributed groundwater withdrawals. The growth of the extensive well network and anecdotes of water shortages (dry wells) have raised concerns over the region's groundwater sustainability. We developed an unsteady, three‐dimensional (3D) groundwater flow model to describe system dynamics over the last 50 years and evaluate long‐term impacts of groundwater use. Simulating this large aquifer system was challenging; the site is characterized by strong, spatially distributed, and statistically nonstationary heterogeneity, making it difficult to avoid over‐parameterization using traditional approaches for conceptualizing and calibrating a flow model. Moreover, traditional pumping and water level data were lacking and prohibitively expensive to collect given the large‐scale and long‐term nature of this study. An integrated, stochastic‐deterministic approach was developed to characterize the system and calibrate the flow model through innovative use of high‐density water well datasets. This approached allowed (1) implementation of a “zone‐based,” nonstationary stochastic approach to conceptualize complex spatial variability using a small set of geologic material types; (2) modeling the spatiotemporal evolution of many water well withdrawals across several decades using sector‐based parameterization; and (3) critical analysis of long‐term water level changes at different locations in the aquifer system for characterizing the system dynamics and calibrating the model. Results show the approach is reasonably successful in calibrating a complex model for a highly complex site in a way that honors complex distributed heterogeneity and stress configurations.
Safety and effectiveness of lusutrombopag in Japanese chronic liver disease patients with thrombocytopenia undergoing invasive procedures: Interim results of a postmarketing surveillance
Authors: Sasaki Ritsue , Shiino Chikako , Imawari Michio , Bentley Roy , Cai Bin , Yoshida Manami , Afdhal Nezam
Published: June 2019

Aim

Lusutrombopag is approved for the treatment of thrombocytopenia in chronic liver disease patients undergoing invasive procedures. This real‐world surveillance assesses the safety and effectiveness of lusutrombopag in Japan.

Methods

This ongoing, multicenter, prospective, real‐world surveillance is collecting data from case report forms between October 2016 and May 2021. Interim data up to September 2018 were used to evaluate safety (adverse events and adverse drug reactions [ADRs]) and effectiveness (proportion of patients avoiding preoperative platelet transfusion and change in platelet count from baseline).

Results

The safety analysis set included 331 patients. The mean baseline platelet count was 46.2 ± 13.7 × 109/L. Of 377 invasive procedures, radiofrequency ablation (110 procedures, 29.2%) was the most frequent. The mean time from starting lusutrombopag treatment to invasive procedure was 12.3 days. Incidences of serious adverse events and ADRs were 8.76% and 3.32%, respectively. Six cases (1.81%) of portal vein thrombosis were considered serious adverse events; of these, four cases (1.21%) were classified as serious ADRs. Of 300 patients who underwent an invasive procedure (excluding those with platelet transfusion refractoriness), 282 (94.0%) avoided preoperative platelet transfusion. In patients with platelet measurements before and after lusutrombopag administration who did not undergo platelet transfusion, the mean maximum change in platelet count from baseline was 41.7 ± 31.4 × 109/L (range, −6 to 276; n = 286). All patients receiving second (n = 20) and third (n = 1) treatments avoided preoperative platelet transfusion without developing any ADRs.

Conclusions

This real‐world surveillance further supports the safety and effectiveness of lusutrombopag in patients with chronic liver disease undergoing invasive procedures.
Co‐producing knowledge of lesbian, gay, bisexual, trans and intersex (LGBTI) health‐care inequalities via rapid reviews of grey literature in 27 EU Member States
Authors: Sherriff Nigel , Zeeman Laetitia , McGlynn Nick , Pinto Nuno , Hugendubel Katrin , Mirandola Massimo , Gios Lorenzo , Davis Ruth , Donisi Valeria , Farinella Francesco , Amaddeo Francesco , Costongs Caroline , Browne Kath ,   the Health4LGBTI Network
Published: June 2019

Background

The health inequalities experienced by lesbian, gay, bisexual, trans and intersex (LGBTI) people are well documented with several reviews of global research summarizing key inequalities. These reviews also show how the health‐care needs of LGBTI people are often poorly understood whilst suggesting that targeted initiatives to reduce inequalities should involve LGBTI people.

Objectives

To determine what is known about the health‐care inequalities faced by LGBTI people? What are the barriers faced by LGBTI people whilst accessing health care, and health professionals when providing care? What examples of promising practice exist?

Design

Rapid reviews of grey literature were co‐produced with LGBTI people in 27 countries followed by a thematic analysis and synthesis across all data sets. The review included grey literature from each country that might not otherwise be accessible due to language barriers.

Main results

Rapid reviews showed that LGBTI people faced various inequalities and barriers whilst accessing health care. Where heterosexuality, binary gender and assumed male/female sex characteristics were upheld as the norm, and where LGBTI people differed from these norms, discrimination could result. In consultations where LGBTI people feared discrimination and did not disclose their LGBTI status, health professionals lacked the information required for appropriate assessments.

Conclusion

With greater understanding of sexual orientation (LGB people), gender identity (trans people) and sex characteristics (intersex people), combined with access to contemporary knowledge and training, health professionals can work in collaboration with researchers, policymakers and LGBTI people to develop systems that are better attuned to the needs of all service users.
A systematic review of physical activity and cardiorespiratory fitness on P3b
Authors: Kao Shih‐Chun , Cadenas‐Sanchez Cristina , Shigeta Tatsuya T. , Walk Anne M. , Chang Yu‐Kai , Pontifex Matthew B. , Hillman Charles H.
Published: June 2019

Given accumulating evidence indicating that acute and chronic physical activity and cardiorespiratory fitness are related to modulation of the P3b‐ERP component, this systematic review provides an overview of the field across the last 30+ years and discusses future directions as the field continues to develop. A systematic review was conducted on studies of physical activity and cardiorespiratory fitness on P3b. PubMed, Web of Science, and Scopus were searched from database inception to March 28, 2018. Search results were limited to peer‐reviewed and English‐written studies investigating typically developed individuals. Seventy‐two studies were selected, with 39 studies examining cross‐sectional relationships between chronic physical activity (n = 19) and cardiorespiratory fitness (n = 20) with P3b, with 16 and 17 studies reporting associations of P3b with physical activity and cardiorespiratory fitness, respectively. Eight studies investigated the effects of chronic physical activity interventions, and all found effects on P3b. Eight studies investigating P3b during acute bouts of physical activity showed inconsistent results. Nineteen of 23 studies demonstrated acute modulation of P3b following exercise cessation. Conclusions drawn from this systematic review suggest that physical activity and cardiorespiratory fitness are associated with P3b modulation during cognitive control and attention tasks. Acute and chronic physical activity interventions modulate the P3b component, suggesting short‐ and long‐term functional adaptations occurring in the brain to support cognitive processes. These summary findings suggest physical activity and cardiorespiratory fitness are beneficial to brain function and that P3b may serve as a biomarker of covert attentional processes to better understand the relationship of physical activity and cognition.
Classification and influencing factors analysis of facial skin color in Chinese population
Authors: Wang Lixia , Wan Xiaoxia , Xiao Gensheng
Published: June 2019

Background

Subjective evaluation and quantitative analysis of skin color are very important both in dermatology and in cosmetology, but results of existing objective classifications tend to be incompatible to visual perception of skin color among females and males in China.

Methods

Skin color at four facial skin sites was measured in 409 volunteers with 219 males and 190 females aged 20‐79 years. Ten observers with normal color vision assessed facial skin color of 205 subjects. The relationship between visual scores and Chardon's individual typology angle (ITA°) values was investigated. Then, the variations of color in different sub‐groups were comprehensively discussed by skin color data of 409 volunteers.

Results

In order to better characterize Chinese skin color, the redness parameter must be added into the ITA formula. By comparing skin color of Chinese living in different environments or with different lifestyles, some factors not conducive to brightening skin have been identified.

Conclusion

This study indicated the different influence of skin color components on perceived brightness between Caucasian and Chinese. And skin color was significantly affected by related variables such as gender, age, working environment, and lifestyles. Therefore, this study suggests how to brighten skin color in daily life.
Reference interval estimation of small sample sizes: A methodologic comparison using a computer‐simulation study
Authors: Le Boedec Kevin
Published: June 2019

Background

According to the ASVCP and other guidelines, samples should comprise at least 120 individuals for reference interval (RI) estimation. Unfortunately, this minimum sample size is difficult to achieve in veterinary medicine. Several statistical methods are described to determine RIs from small sample sizes, but it is unclear which method provides the best accuracy.

Objectives

This study aimed to compare statistical strategies for estimating RIs and determine which strategy best enhances accuracy when the sample size is between 20 and 120.

Methods

Different sample size groups (n = 120, 100, 80, 60, 40, and 20) were randomly selected 50 times from simulated Gaussian, log‐normal, and left‐skewed populations of 5000 total values. RIs were calculated using seven different statistical strategies comprising robust, parametric, nonparametric, and bootstrap methods, alone or in combination. RI accuracy was compared among these strategies at each sample size. The strategy that was significantly more accurate than others in the largest number of comparisons was considered as the one that best‐enhanced RI accuracy.

Results

The strategies that best‐enhanced RI accuracy included using the parametric method when the Shapiro‐Wilk P > 0.2 and, otherwise, using the nonparametric method to determine the upper and lower RI limits when there were between 60 and 100 reference individuals, and finding the lower RI limit when there were 40 reference individuals. The Box‐Cox transformation parametric method best‐enhanced RI accuracy of the upper RI limit when there were 40 reference individuals, and the nonparametric method best‐enhanced RI accuracy of both RI limits when there were 20 reference individuals.

Conclusions

Using the parametric method when the Shapiro‐Wilk P > 0.2, and the nonparametric method in other instances, will likely enhance RI accuracy when there are between 40 and 100 reference individuals. For smaller samples, the nonparametric method might be preferred.
Hydroxyethyl starches in equine medicine
Authors: van Galen Gaby , Hallowell Gayle
Published: June 2019

Objective

To review and discuss the use of hydroxyethyl starches (HES) in equine veterinary medicine, and to provide recommendations for its use.

Data sources

Veterinary and human peer‐reviewed medical literature including scientific reviews, meta‐analyses, and original research articles.

Human data synthesis

Increasing evidences on adverse effects after HES use and decreasing support for beneficial effects with regards to volume expansion and colloid osmotic pressure (COP) support in critically ill subjects have led to a recent guideline to limit the use of HES in critically ill people.

Equine veterinary data synthesis

The rationale for HES use in horses is mainly extrapolated from human medicine, and very limited studies in horses are available. There is limited evidence suggesting a superiority of volume expansion effects of HES over crystalloids. The potential for HES to increase and maintain COP is well supported, but there is no evidence that maintaining or increasing plasma COP influences outcome, tissue edema formation, or rates of complications that potentially relate to edema formation. HES induce dose–dependent changes in coagulopathic parameters, but there is no evidence that HES causes clinical coagulopathies. Insufficient data are available on other adverse effects such as acute kidney injury, or mortality in horses. The use of HES should be restricted in septic patients, but may still have some use in cases of hemorrhagic shock resuscitation, hypoalbuminemia, or perioperative fluid replacement.

Conclusion

The evidence supporting the use of HES in horses is weak due to lack of species‐specific investigations. Acknowledging species differences, the use of HES should be judicious, yet with some recognition of its benefits in particular cases. More research is necessary to improve knowledge on use of HES in horses and to establish better future recommendations.
Experiences of adult patients with chronic non-communicable disease using electronic personal health records for self-management: a qualitative systematic review protocol
Authors: Eastway Julia , Lizarondo Lucylynn
Published: June 2019

Objective:

The objective of the systematic review is to explore adult patients’ experiences using electronic personal health records (e-PHRs) for chronic non-communicable disease self-management.

Introduction:

Self-management is a key component of chronic disease management. One of the strategies to support self-management in patients with chronic disease is the use of e-PHRs. Electronic personal health records offer patients the opportunity to actively engage with their own health information, promote continuity of care and collaboration through disease tracking, and provide patients and providers with an ongoing connection. To adopt e-PHRs and maximize any benefits for chronic disease management, they should align with patients’ values and preferences.

Inclusion criteria:

The review will include qualitative studies that explore the experiences of adult patients (aged 18 years and over) with a chronic non-communicable disease who have used e-PHR for the self-management of their condition. This review will consider studies conducted in any setting or country.

Methods:

The systematic review will be conducted in accordance with the JBI methodology for systematic reviews of qualitative evidence, with meta-aggregation as the method of synthesis. Published studies will be searched in CINAHL, PubMed, PsycINFO, Embase and Scopus. Gray literature will also be considered. Critical appraisal and data extraction will be conducted using the appropriate JBI tools. Extracted data will be aggregated and analyzed to produce a set of synthesized findings that can be used to develop evidence-informed recommendations for the use of e-PHRs in chronic disease self-management.

Systematic review registration number:

PROSPERO CRD42019133301
Achieved oxygen saturations and retinopathy of prematurity in extreme preterms
Authors: Gantz Marie G , Carlo Waldemar A , Finer Neil N , Rich Wade , Faix Roger G , Yoder Bradley A , Walsh Michele C , Newman Nancy S , Laptook Abbott , Schibler Kurt , Das Abhik , Higgins Rosemary D
Published: June 2019

Objective

To identify achieved oxygen saturations (SpO2) associated with increased risk of severe retinopathy of prematurity (ROP).

Design

This is a secondary analysis of the Surfactant Positive Airway Pressure and Pulse Oximetry Trial (SUPPORT)randomised controlled trial. SpO2was recorded up to 36 weeks’ postmenstrual age. Saturations through 9 postnatal weeks were explored graphically, and logistic regression models were created to predict severe ROP.

Setting

20 centres of theEunice Kennedy ShriverNational Institute of Child Health and Human Development Neonatal Research Network.

Patients

984 surviving infants of 24–27 weeks’ gestational age born in 2005–2009.

Interventions

SUPPORT targeted SpO2to a lower (85%–89%) or higher (91%–95%) range through 36 weeks’ postmenstrual age or off respiratory support.

Main outcome measures

Severe ROP defined as threshold ROP, ophthalmological surgery or bevacizumab treatment.

Results

There were statistically significant interactions between duration of oxygen supplementation and percentage of time in certain achieved saturation ranges. Specifically, for infants who spent at least 2 weeks on oxygen in postnatal weeks 1–5, a higher percentage of time at 91%–96% SpO2was associated with increased odds of severe ROP. For infants who spent at least 3 weeks on oxygen in postnatal weeks 6–9, a higher percentage of time at 97%–100% SpO2was associated with increased odds of severe ROP. Other significant risk factors were lower gestational age and birth weight, non-Hispanic white versus black race, prospectively defined severe illness, late-onset sepsis or meningitis, and clinical centre.

Conclusions

Among extremely preterm survivors to discharge, the association between SpO2and severe ROP depended on the timing and duration of oxygen supplementation.
Congenital duodenal obstruction in the UK: a population-based study
Authors: Bethell George Stephen , Long Anna-May , Knight Marian , Hall Nigel J
Published: June 2019

Objective

Congenital duodenal obstruction (CDO) comprising duodenal atresia or stenosis is a rare congenital anomaly requiring surgical correction in early life. Identification of variation in surgical and postoperative practice in previous studies has been limited by small sample sizes. This study aimed to prospectively estimate the incidence of CDO in the UK, and report current management strategies and short-term outcomes.

Design

Prospective population-based, observational study for 12 months from March 2016.

Setting

Specialist neonatal surgical units in the UK.

Main outcome measures

Incidence of CDO, associated anomalies and short-term outcomes.

Results

In total, 110 cases were identified and data forms were returned for 103 infants giving an estimated incidence of 1.22 cases per 10 000 (95% CI 1.01 to 1.49) live births. Overall, 59% of cases were suspected antenatally and associated anomalies were seen in 69%. Operative repair was carried out mostly by duodenoduodenostomy (76%) followed by duodenojejunostomy (15%). Postoperative feeding practice varied with 42% having a trans-anastomotic tube placed and 88% receiving parenteral nutrition. Re-operation rate related to the initial procedure was 3% within 28 days. Two infants died within 28 days of operation from unrelated causes.

Conclusion

This population-based study of CDO has shown that the majority of infants have associated anomalies. There is variation in postoperative feeding strategies which represent opportunities to explore the effects of these on outcome and potentially standardise approach. Short-term outcomes are generally good.
Experience with endoscopic resection of oesophageal verrucous carcinoma and literature review
Authors: Soota Kaartik , Tirumanisetty Pratyusha , Lee Ye Jin , Holm Adrian
Published: June 2019

A 65-year-old male patient with chronic dysphagia was found to have a 2 cm mass at gastro-oesophageal junction on endoscopy. Biopsy showed squamous hyperplasia without malignancy. Controlled radial expansion balloon dilatation and partial resection were performed but the symptoms recurred. He finally underwent endoscopic mucosa resection and histology showed well-differentiated verruciform squamous proliferation limited to the mucosa. Small amounts of tumour remnants were treated during subsequent follow-up endoscopies and the patient has been tumour free since then. Diagnosis of oesophageal verrucous carcinoma can be challenging and could be managed with endoscopic resection. In this report, we review the literature and present our experience with a patient with oesophageal verrucous carcinoma.
Retrospective review of tertiary and neurosyphilis cases in Alberta, 1973–2017
Authors: Landry Takaaki , Smyczek Petra , Cooper Ryan , Gratrix Jennifer , Bertholet Lindsay , Read Ron , Romanowski Barbara , Singh Ameeta E
Published: June 2019

Objectives

To review the notification rate and characteristics of tertiary and neurosyphilis cases in Alberta, Canada in the postantibiotic era.

Methods

A retrospective review of all neurosyphilis and tertiary syphilis cases reported in Alberta from 1973 to March 2017 was undertaken and cases classified into early neurosyphilis, late neurosyphilis and cardiovascular (CV) syphilis. Variables collected included demographics, sexual partners, HIV status, clinical parameters, symptoms and treatment and distributions were compared between early versus late neurosyphilis and asymptomatic versus symptomatic cases (stratified by early versus late stage). Data were analysed using IBM SPSS Statistics V.19.0.

Results

254 cases were identified; 251 were neurosyphilis and 3 were CV. No cases of gummatous syphilis were reported. Early neurosyphilis accounted for 52.4% (n=133) and 46.1% (n=117) were late neurosyphilis cases; one (0.4%) case with unknown duration. Three outbreaks of infectious syphilis were identified during the study period and a concurrent rise in both early and late neurosyphilis was observed during the outbreak periods. The most common manifestation of symptomatic neurosyphilis was ocular involvement which was more likely in early neurosyphilis. Relative to late neurosyphilis cases, early neurosyphilis cases were more likely to be younger, Caucasian, born in Canada, HIV positive and reporting same sex partners.

Conclusions

Our review of tertiary and neurosyphilis cases found that early and late neurosyphilis cases continue to occur in the context of cycling syphilis outbreaks. CV syphilis cases were extremely rare. Ongoing identification of new cases of syphilis and clinical evaluation of cases for complications continues to be important in the context of global resurgence of syphilis.