bluuebunny/crossref_metadata_2025 huggingface dataset:
A Common NLRC4 Gene Variant Associates With Inflammation and Pulmonary Function in Human Immunodeficiency Virus and Tuberculosis
Authors: Ravimohan Shruthi , Maenetje Pholo , Auld Sara C , Ncube Itai , Mlotshwa Mandla , Chase William , Tiemessen Caroline T , Vangu Mboyo-Di-Tamba , Wallis Robert S , Churchyard Gavin , Weissman Drew , Kornfeld Hardy , Bisson Gregory P
Published: September 2019

Background

Inflammasomes mediate inflammation in adults living with both human immunodeficiency virus (HIV) and tuberculosis (TB), but the relevance of inflammasome gene polymorphisms in TB-associated pulmonary damage is unknown. We hypothesized that functional single-nucleotide polymorphisms (SNPs) in inflammasome pathway genes modify systemic and pulmonary inflammation, contributing to respiratory impairment in adults living with HIV/pulmonary TB.

Methods

This was a prospective cohort study set in South Africa following individuals living with HIV/TB up to 48 weeks post-antiretroviral therapy (ART) initiation. Ten functional SNPs in 5 inflammasome pathway genes were related to circulating inflammatory biomarkers and lung function assessed by spirometry pre- and post-ART initiation. Analyses used 2-sided t tests, Wilcoxon rank sum tests, Spearman correlation coefficients, linear regression, and generalized estimating equation models.

Results

Among 102 patients with baseline samples, the minor allele (T) in NLRC4 rs385076 was independently associated with lower levels of interleukin (IL)-18 and IL-6 before and up to 12 weeks post-ART initiation (Benjamini-Hochberg corrected P values < .02). Patients with the CT/TT genotypes also had improved lung function vs CC patients up to 48 weeks post-ART initiation (forced vital capacity, 206 mL higher; 95% confidence interval [CI], 67–345 mL; P = .004 and forced expiratory volume in 1 second, 143 mL higher; 95% CI, 11–274 mL; P = .034).

Conclusions

A common SNP in the NLRC4 inflammasome may modify TB-associated inflammation in clinically relevant ways. This SNP may identify high-risk groups for lung damage in TB. Inhibition of NLRC4 activity may be an important approach for TB host-directed therapy.
Inpatient Fluoroquinolone Stewardship Improves the Quantity and Quality of Fluoroquinolone Prescribing at Hospital Discharge: A Retrospective Analysis Among 122 Veterans Health Administration Hospitals
Authors: Suzuki Hiroyuki , Perencevich Eli N , Alexander Bruce , Beck Brice F , Goto Michihiko , Lund Brian C , Nair Rajeshwari , Livorsi Daniel J
Published: September 2019

Background

Despite increasing awareness of harms, fluoroquinolones are still frequently prescribed to inpatients and at hospital discharge. Our goal was to describe fluoroquinolone prescribing at hospital discharge across the Veterans Health Administration (VHA) and to contrast the volume and appropriateness of fluoroquinolone prescribing across 3 antimicrobial stewardship strategy types.

Methods

We analyzed a retrospective cohort of patients hospitalized at 122 VHA acute-care hospitals during 2014–2016. Data from a mandatory VHA survey were used to identify 9 hospitals that self-reported 1 of 3 strategies for optimizing fluoroquinolone prescribing: prospective audit and feedback (PAF), restrictive policies (RP), and no strategy. Manual chart reviews to assess fluoroquinolone appropriateness at hospital discharge (ie, postdischarge) were performed across the 9 hospitals (3 hospitals and 125 cases per strategy type).

Results

There were 1.7 million patient admissions. Overall, there were 1 727 478 fluoroquinolone days of therapy (DOTs), with 674 918 (39.1%) DOTs prescribed for inpatients and 1 052 560 (60.9%) DOTs prescribed postdischarge. Among the 9 reviewed hospitals, postdischarge fluoroquinolone exposure was lower at hospitals using RP, compared to no strategy (3.8% vs 9.3%, respectively; P = .012). Postdischarge fluoroquinolones were deemed inappropriate in 154 of 375 (41.1%) patients. Fluoroquinolones were more likely to be inappropriate at hospitals without a strategy (52.8%) versus those using either RP or PAF (35.2%; P = .001).

Conclusions

In this retrospective cohort, the majority of fluoroquinolone DOTs occurred after hospital discharge. A large proportion of postdischarge fluoroquinolone prescriptions were inappropriate, especially in hospitals without a strategy to manage fluoroquinolone prescribing. Our findings suggest that stewardship efforts to minimize and improve fluoroquinolone prescribing should also focus on antimicrobial prescribing at hospital discharge.
Association Between the Respiratory Microbiome and Susceptibility to Influenza Virus Infection
Authors: Tsang Tim K , Lee Kyu Han , Foxman Betsy , Balmaseda Angel , Gresh Lionel , Sanchez Nery , Ojeda Sergio , Lopez Roger , Yang Yang , Kuan Guillermina , Gordon Aubree
Published: September 2019

Background

Previous studies suggest that the nose/throat microbiome may play an important role in shaping host immunity and modifying the risk of respiratory infection. Our aim is to quantify the association between the nose/throat microbiome and susceptibility to influenza virus infection.

Methods

In this household transmission study, index cases with confirmed influenza virus infection and their household contacts were followed for 9–12 days to identify secondary influenza infections. Respiratory swabs were collected at enrollment to identify and quantify bacterial species via high-performance sequencing. Data were analyzed by an individual hazard-based transmission model that was adjusted for age, vaccination, and household size.

Results

We recruited 115 index cases with influenza A(H3N2) or B infection and 436 household contacts. We estimated that a 10-fold increase in the abundance in Streptococcus spp. and Prevotella salivae was associated with 48% (95% credible interval [CrI], 9–69%) and 25% (95% CrI, 0.5–42%) lower susceptibility to influenza A(H3N2) infection, respectively. In contrast, for influenza B infection, a 10-fold increase in the abundance in Streptococcus vestibularis and Prevotella spp. was associated with 63% (95% CrI, 17–83%) lower and 83% (95% CrI, 15–210%) higher susceptibility, respectively.

Conclusions

Susceptibility to influenza infection is associated with the nose/throat microbiome at the time of exposure. The effects of oligotypes on susceptibility differ between influenza A(H3N2) and B viruses. Our results suggest that microbiome may be a useful predictor of susceptibility, with the implication that microbiome could be modulated to reduce influenza infection risk, should these associations be causal.
Pericardial Manifestations in Inflammatory Bowel Disease: A Report of Two Cases
Authors: Qazi T , Christian K E , Farraye F A , Cross R K
Published: September 2019

Pericardial involvement in the setting of inflammatory bowel disease can occur not only as an adverse event related to medical therapy but also as an extraintestinal manifestation of the disease itself. In the following case series, we describe 2 cases of pericarditis in patients diagnosed with Crohn disease. Our first case reviews the clinical presentation of acute pericarditis as an adverse event associated with anti-tumor necrosis factor therapy. In contrast, our second patient is a case of acute pericarditis as a precursor of the clinical recurrence of Crohn disease following operative resection. Pericardial disease should be considered in the differential diagnosis of acute and subacute presentations of chest discomfort and shortness of breath in patients with inflammatory bowel disease.
CRISPR/Cas9 gene-editing strategies in cardiovascular cells
Authors: Vermersch Eva , Jouve Charlène , Hulot Jean-Sébastien
Published: September 2019

Cardiovascular diseases are among the main causes of morbidity and mortality in Western countries and considered as a leading public health issue. Therefore, there is a strong need for new disease models to support the development of novel therapeutics approaches. The successive improvement of genome editing tools with zinc finger nucleases (ZFNs), transcription activator-like effector nucleases (TALENs), and more recently with clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated 9 (Cas9) has enabled the generation of genetically modified cells and organisms with much greater efficiency and precision than before. The simplicity of CRISPR/Cas9 technology made it especially suited for different studies, both in vitro and in vivo, and has been used in multiple studies evaluating gene functions, disease modelling, transcriptional regulation, and testing of novel therapeutic approaches. Notably, with the parallel development of human induced pluripotent stem cells (hiPSCs), the generation of knock-out and knock-in human cell lines significantly increased our understanding of mutation impacts and physiopathological mechanisms within the cardiovascular domain. Here, we review the recent development of CRISPR–Cas9 genome editing, the alternative tools, the available strategies to conduct genome editing in cardiovascular cells with a focus on its use for correcting mutations in vitro and in vivo both in germ and somatic cells. We will also highlight that, despite its potential, CRISPR/Cas9 technology comes with important technical and ethical limitations. The development of CRISPR/Cas9 genome editing for cardiovascular diseases indeed requires to develop a specific strategy in order to optimize the design of the genome editing tools, the manipulation of DNA repair mechanisms, the packaging and delivery of the tools to the studied organism, and the assessment of their efficiency and safety.
The optimal drug adherence to maximize the efficacy and safety of non-vitamin K antagonist oral anticoagulant in real-world atrial fibrillation patients
Authors: Kim Daehoon , Yang Pil-Sung , Jang Eunsun , Yu Hee Tae , Kim Tae-Hoon , Uhm Jae-Sun , Kim Jong-Youn , Sung Jung-Hoon , Pak Hui-Nam , Lee Moon-Hyoung , Lip Gregory Y H , Joung Boyoung
Published: September 2019

Aims

To investigate the association between adherence to non-vitamin K antagonist oral anticoagulant (NOAC) and clinical outcomes and to determine the optimal cut-off level of NOAC adherence among patients with atrial fibrillation (AF).

Methods and results

Using the Korean National Health Insurance Service database, we identified 96 197 patients with non-valvular AF who initiated NOAC or warfarin in 2013–16. We compared clinical outcomes between adherent [proportion of days covered (PDC) ≥80%] vs. non-adherent (PDC <80%) NOAC users, and further with warfarin users. We assessed the outcomes according to different levels of adherence. The proportion of adherent NOAC users was 64.0%. Compared with non-adherent NOAC users, adherent NOAC users were at lower risks of ischaemic stroke/systemic embolism (SE) [adjusted hazard ratio (aHR) 0.73, 95% confidence interval (CI) 0.69–0.79], and myocardial infarction (aHR 0.82, 95% CI 0.72–0.93), whereas there was no significant risk alteration for major bleeding (aHR 1.01, 95% CI 0.91–1.11). Compared with warfarin, non-adherent NOAC use failed to have better efficacy against ischaemic stroke/SE (aHR 0.99, 95% CI 0.93–1.05) and rather had increased risk of myocardial infarction (aHR 1.13, 95% CI 1.03–1.25). In NOAC users, the risks of adverse outcomes decreased according to gradual increase of adherence rates with the lowest risks in ≥90%, except for major bleeding in which there were no significant associations.

Conclusions

In an adherence level-dependent fashion, adherent use of NOAC showed better clinical outcomes without increasing bleeding risk. Maintaining ≥90% of adherence optimizes effectiveness of NOAC therapy without compromising its safety.
Infliximab and Adalimumab Concentrations May Vary Between the Enzyme-Linked Immunosorbent Assay and the Homogeneous Mobility Shift Assay in Patients With Inflammatory Bowel Disease: A Prospective Cross-Sectional Observational Study
Authors: Clarke William T , Papamichael Konstantinos , Vande Casteele Niels , Germansky Katharine A , Feuerstein Joseph D , Melmed Gil Y , Siegel Corey A , Irving Peter M , Cheifetz Adam S
Published: September 2019

This prospective observational study including consecutive patients with inflammatory bowel disease treated with either infliximab or adalimumab showed that although the correlation between the ELISA and the homogeneous mobility shift assay was good for both drugs, the agreement was poor.
Enteroendocrine Cells: Sensing Gut Microbiota and Regulating Inflammatory Bowel Diseases
Authors: Yu Yanbo , Yang Wenjing , Li Yanqing , Cong Yingzi
Published: September 2019

Host sensing in the gut microbiota has been crucial in the regulation of intestinal homeostasis. Although inflammatory bowel diseases (IBDs), multifactorial chronic inflammatory conditions of the gastrointestinal tract, have been associated with intestinal dysbiosis, the detailed interactions between host and gut microbiota are still not completely understood. Enteroendocrine cells (EECs) represent 1% of the intestinal epithelium. Accumulating evidence indicates that EECs are key sensors of gut microbiota and/or microbial metabolites. They can secrete cytokines and peptide hormones in response to microbiota, either in traditional endocrine regulation or by paracrine impact on proximal tissues and/or cells or via afferent nerve fibers. Enteroendocrine cells also play crucial roles in mucosal immunity, gut barrier function, visceral hyperalgesia, and gastrointestinal (GI) motility, thereby regulating several GI diseases, including IBD. In this review, we will focus on EECs in sensing microbiota, correlating enteroendocrine perturbations with IBD, and the underlying mechanisms.
Impact of follow-up time and analytical approaches to account for reverse causality on the association between physical activity and health outcomes in UK Biobank
Authors: Strain Tessa , Wijndaele Katrien , Sharp Stephen J , Dempsey Paddy C , Wareham Nick , Brage Søren
Published: September 2019

Background

The advent of very large cohort studies (n > 500 000) has given rise to prospective analyses of health outcomes being undertaken after short (<4 years) follow-up periods. However, these studies are potentially at risk of reverse causality bias. We investigated differences in the associations between self-reported physical activity and all-cause and cardiovascular disease (CVD) mortality, and incident CVD, using different follow-up time cut-offs and methods to account for reverse causality bias.

Methods

Data were from n = 452 933 UK Biobank participants, aged 38–73 years at baseline. Median available follow-up time was 7 years (for all-cause and CVD mortality) and 6.1 years (for incident CVD). We additionally analysed associations at 1-, 2- and 4-year cut-offs after baseline. We fit up to four models: (1) adjusting for prevalent CVD and cancer, (2) excluding prevalent disease, (3) and (4) Model 2 excluding incident cases in the first 12 and 24 months, respectively.

Results

The strength of associations decreased as follow-up time cut-off increased. For all-cause mortality, Model 1 hazard ratios were 0.73 (0.69–0.78) after 1 year and 0.86 (0.84–0.87) after 7 years. Associations were weaker with increasing control for possible reverse causality. After 7-years follow-up, the hazard ratios were 0.86 (0.84–0.87) and 0.88 (0.86–0.90) for Models 1 and 4, respectively. Associations with CVD outcomes followed similar trends.

Conclusions

As analyses with longer follow-up times and increased control for reverse causality showed weaker associations, there are implications for the decision about when to analyse a cohort study with ongoing data collection, the interpretation of study results and their contribution to meta-analyses.
Oral corticosteroids during pregnancy and offspring risk of congenital heart defects: a nationwide cohort study
Authors: Schmidt Amalie Bøggild , Lund Marie , Corn Giulia , Øyen Nina , Wohlfahrt Jan , Melbye Mads
Published: September 2019

Background

Pre-pregnancy diabetes is a strong risk factor for congenital heart defects (CHDs), suggesting a role for glucose in the causal pathway. Oral corticosteroids may cause hyperglycemia and maternal use could affect embryonic heart development. The objective of this study was to determine the association between maternal intake of oral corticosteroids 0–8 weeks after conception and CHDs in offspring.

Methods

A register-based nationwide prevalence study including all live singleton births in Denmark, 1996–2016, was conducted. In total, 1 194 687 individuals and their mothers were identified and linked with information on offspring CHDs and the mothers’ use of oral corticosteroids in early pregnancy. Corticosteroid use was defined as a filled prescription for maternal use of oral corticosteroid 0–8 weeks after conception. CHDs were identified through International Classification of Diseases codes. The association was estimated by prevalence (odds) ratios using logistic regression and propensity score-matched analyses.

Results

Among 1 194 687 live births, 2032 had a mother who had used oral corticosteroids 0–8 weeks from conception. Of these offspring, 32 had a heart defect. Among the offspring of never-users of oral corticosteroids, 10 534 had a heart defect. The adjusted prevalence ratio was 1.29 (95% confidence interval, 0.90–1.84) comparing offspring prevalence of heart defects in oral corticosteroid users with that in oral corticosteroid never-users. Propensity score-matched analysis yielded similar results (prevalence ratio 1.38; 95% confidence interval, 0.95–2.02).

Conclusions

This study supports that there is no association between maternal use of oral corticosteroids in the first 8 weeks after conception and CHDs.
Characterization of the developmental landscape of murine RORγt+ iNKT cells
Authors: Klibi Jihene , Li Shamin , Amable Ludivine , Joseph Claudine , Brunet Stéphane , Delord Marc , Parietti Veronique , Jaubert Jean , Marie Julien , Karray Saoussen , Eberl Gerard , Lucas Bruno , Toubert Antoine , Benlagha Kamel
Published: September 2019

Invariant natural killer T (iNKT) cells expressing the retinoic acid receptor-related orphan receptor γt (RORγt) and producing IL-17 represent a minor subset of CD1d-restricted iNKT cells (iNKT17) in C57BL/6J (B6) mice. We aimed in this study to define the reasons for their low distribution and the sequence of events accompanying their normal thymic development. We found that RORγt+ iNKT cells have higher proliferation potential and a greater propensity to apoptosis than RORγt− iNKT cells. These cells do not likely reside in the thymus indicating that thymus emigration, and higher apoptosis potential, could contribute to RORγt+ iNKT cell reduced thymic distribution. Ontogeny studies suggest that mature HSAlow RORγt+ iNKT cells might develop through developmental stages defined by a differential expression of CCR6 and CD138 during which RORγt expression and IL-17 production capabilities are progressively acquired. Finally, we found that RORγt+ iNKT cells perceive a strong TCR signal that could contribute to their entry into a specific ‘Th17 like’ developmental program influencing their survival and migration. Overall, our study proposes a hypothetical thymic developmental sequence for iNKT17 cells, which could be of great use to study molecular mechanisms regulating this developmental program.
An Instrumentalist Account of How to Weigh Epistemic and Practical Reasons for Belief
Authors: Steglich-Petersen Asbjørn , Skipper Mattias
Published: September 2019

When one has both epistemic and practical reasons for or against some belief, how do these reasons combine into an all-things-considered reason for or against that belief? The question might seem to presuppose the existence of practical reasons for belief. But we can rid the question of this presupposition. Once we do, a highly general ‘Combinatorial Problem’ emerges. The problem has been thought to be intractable due to certain differences in the combinatorial properties of epistemic and practical reasons. Here we bring good news: if we accept an independently motivated version of epistemic instrumentalism—the view that epistemic reasons are a species of instrumental reasons—we can reduce The Combinatorial Problem to the relatively benign problem of how to weigh different instrumental reasons against each other. As an added benefit, the instrumentalist account can explain the apparent intractability of The Combinatorial Problem in terms of a common tendency to think and talk about epistemic reasons in an elliptical manner.
Interaction of the electromagnetic precursor from a relativistic shock with the upstream flow – II. Induced scattering of strong electromagnetic waves
Authors: Lyubarsky Yuri
Published: September 2019

This is the second in the series of papers aiming to study interaction of the electromagnetic precursor waves from relativistic shocks with the upstream flow. Here, I consider the induced scattering of strong waves. In such a wave, the electrons oscillate with relativistic velocities therefore, the scattering generally occurs in harmonics of the incident wave. I show that the induced scattering occurs predominantly in the first harmonics. I also show that even though in the weak case regime, the induced scattering rate is proportional to the intensity of the incident wave, in the strong wave case, the rate decreases as the wave amplitude grows.
Dipeptidyl peptidase-4 inhibitor treatment could decrease chronic rhinosinusitis in diabetic patients
Authors: Li S -Y , Chen H -H , Lai C -C , Lin C -L , Kao C -H
Published: September 2019

Aim

To evaluate the relationship between dipeptidyl peptidase-4 inhibitor (DPP4i) treatment and chronic rhinosinusitis (CRS) in diabetic patients.

Methods

We used the Longitudinal Health Insurance Database for this population-based and population-matched cohort design study. Chi-square and Wilcoxon rank-sum tests were used to evaluate the association between categorical and continuous variables, respectively. The Kaplan–Meier method with the log-rank test was used to estimate the risk of CRS and DPP4i users.

Results

A total of 6198 diabetic patients were included in this cohort study. DPP4i users had a lower risk of developing CRS. The risk of CRS was significantly lower in women, patients with a Diabetes Complications Severity Index score higher than 4, patients with comorbidities, and patients with higher cumulative defined daily dose in the DPP4i group.

Conclusion

The results of our study demonstrate that the use of DPP4i treatment could decrease CRS risk in diabetic patients in Taiwan.
SHARP UPPER BOUNDS FOR FRACTIONAL MOMENTS OF THE RIEMANN ZETA FUNCTION
Authors: Heap Winston , Radziwiłł Maksym , Soundararajan K
Published: September 2019

We establish sharp upper bounds for the $2k$th moment of the Riemann zeta function on the critical line, for all real $0 \leqslant k \leqslant 2$. This improves on earlier work of Ramachandra, Heath-Brown and Bettin–Chandee–Radziwiłł.
The quantitative assessment of interstitial lung disease with positron emission tomography scanning in systemic sclerosis patients
Authors: Peelen Daphne M , Zwezerijnen Ben G J C , Nossent Esther J , Meijboom Lilian J , Hoekstra Otto S , Van der Laken Conny J , Voskuyl Alexandre E
Published: September 2019

Objectives

The reversibility of interstitial lung disease (ILD) in SSc is difficult to assess by current diagnostic modalities and there is clinical need for imaging techniques that allow for treatment stratification and monitoring. 18F-Fluorodeoxyglucose (FDG) PET/CT scanning may be of interest for this purpose by detection of metabolic activity in lung tissue. This study aimed to investigate the potential role of 18F-FDG PET/CT scanning for the quantitative assessment of SSc-related active ILD.

Methods

18F-FDG PET/CT scans and high resolution CT scans of eight SSc patients, including five with ILD, were analysed. For comparison, reference groups were included: eight SLE patients and four primary Sjögren’s syndrome (pSS) patients, all without ILD. A total of 22 regions of interest were drawn in each patient at apical, medial and dorsobasal lung levels. 18F-FDG uptake was measured as mean standardized uptake value (SUVmean) in each region of interest. Subsequently, basal/apical (B/A) and medial/apical (M/A) ratios were calculated at patient level (B/A-p and M/A-p) and at tissue level (B/A-t and M/A-t).

Results

SUVmean values in dorsobasal ROIs and B/A-p ratios were increased in SSc with ILD compared with SSc without ILD (P = 0.04 and P = 0.07, respectively), SLE (P = 0.003 and P = 0.002, respectively) and pSS (P = 0.03 and P = 0.02, respectively). Increased uptake in the dorsobasal lungs and increased B/A-t ratios corresponded to both ground glass and reticulation on high resolution CT.

Conclusion

Semi-quantitative assessment of 18F-FDG PET/CT is able to distinguish ILD from non-affected lung tissue in SSc, suggesting that it may be used as a new biomarker for SSc-ILD disease activity.
Eradicating hepatitis C virus
Authors: Pozza Renee , McCoy-Hill Catherine , Hall Katherine , Hefner Anna , Wilgers Kimberly , Tapelband Julia , Masroor Momin , Hassanein Tarek
Published: September 2019

Chronic hepatitis C virus (HCV) infection is a leading cause of liver disease. The World Health Organization has called for the global elimination of HCV by 2030. NPs can significantly expand the availability of community-based providers and bridge gaps in HCV treatment to assist in eradicating this curable virus.
One-Year Prognosis of Kidney Injury at Discharge From the ICU: A Multicenter Observational Study
Authors: Legrand Matthieu , Hollinger Alexa , Vieillard-Baron Antoine , Dépret François , Cariou Alain , Deye Nicolas , Fournier Marie-Céline , Jaber Samir , Damoisel Charles , Lu Qin , Monnet Xavier , Rennuit Isabelle , Darmon Michael , Zafrani Lara , Leone Marc , Guidet Bertrand , Friedman Diane , Sonneville Romain , Montravers Philippe , Pili-Floury Sébastien , Lefrant Jean-Yves , Duranteau Jacques , Laterre Pierre-François , Brechot Nicolas , Oueslati Haikel , Cholley Bernard , Launay Jean-Marie , Ishihara Shiro , Sato Naoki , Mebazaa Alexandre , Gayat Etienne
Published: September 2019

Objectives:

The association between outcome and kidney injury detected at discharge from the ICU using different biomarkers remains unknown. The objective was to evaluate the association between 1-year survival and kidney injury at ICU discharge.

Design:

Ancillary investigation of a prospective observational study.

Setting:

Twenty-one ICUs with 1-year follow-up.

Patients:

Critically ill patients receiving mechanical ventilation and/or hemodynamic support for at least 24 hours were included.

Interventions:

Serum creatinine, plasma Cystatin C, plasma neutrophil gelatinase-associated lipocalin, urinary neutrophil gelatinase-associated lipocalin, plasma Proenkephalin A 119-159, and estimated glomerular filtration rate (on serum creatinine and plasma Cystatin C) were measured at ICU discharge among ICU survivors.

Measurements and Main Results:

The association between kidney biomarkers at discharge and mortality was estimated using logistic model with and without adjustment for prognostic factors previously identified in this cohort. Subgroup analyses were performed in patients with discharge serum creatinine less than 1.5-fold baseline at ICU discharge. Among 1,207 ICU survivors included, 231 died during the year following ICU discharge (19.2%). Estimated glomerular filtration rate was significantly lower and kidney injury biomarkers higher at discharge in nonsurvivors. The association between biomarker levels or estimated glomerular filtration rate and mortality remained after adjustment to potential cofounding factors influencing outcome. In patients with low serum creatinine at ICU discharge, 25–47% of patients were classified as subclinical kidney injury depending on the biomarker. The association between kidney biomarkers and mortality remained and mortality was higher than patients without subclinical kidney injury. The majority of patients who developed acute kidney injury during ICU stay had elevated biomarkers of kidney injury at discharge even with apparent recovery based on serum creatinine (i.e., subclinical acute kidney disease).

Conclusions:

Elevated kidney biomarkers measured at ICU discharge are associated with poor 1-year outcome, including in patients with low serum creatinine at ICU discharge.
Reactive oxygen species-regulating proteins peroxiredoxin 2 and thioredoxin, and glyceraldehyde-3-phosphate dehydrogenase are differentially abundant in induced sputum from smokers with lung cancer or asbestos exposure
Authors: Rostila Annina M. , Anttila Sisko L. , Lalowski Maciej M. , Vuopala Katri S. , Toljamo Tuula I. , Lindström Irmeli , Baumann Marc H. , Puustinen Anne M.
Published: September 2019

Lung cancer is a deadly disease, typically caused by known risk factors, such as tobacco smoke and asbestos exposure. By triggering cellular oxidative stress and altering the antioxidant pathways eliminating reactive oxygen species (ROS), tobacco smoke and asbestos predispose to cancer. Despite easily recognizable high-risk individuals, lung cancer screening and its early detection are hampered by poor diagnostic tools including the absence of proper biomarkers. This study aimed to recognize potential lung cancer biomarkers using induced sputum noninvasively collected from the lungs of individuals in risk of contracting lung cancer. Study groups composed of current and former smokers, who either were significantly asbestos exposed, had lung cancer, or were unexposed and asymptomatic. Screening of potential biomarkers was performed with 52, and five differentially abundant proteins, peroxiredoxin 2 (PRDX2), thioredoxin (TXN), glyceraldehyde-3-phosphate dehydrogenase (GAPDH), extracellular matrix protein 1 (ECM1), and protein S100 A8 (S100A8), were chosen to undergo validation, for their previously known connection with oxidative stress or cancer. Results from the validation in 123 sputa showed that PRDX2, TXN, and GAPDH were differentially abundant in sputa from individuals with lung cancer. TXN had a negative correlation with asbestos exposure, yet a positive correlation with smoking and lung cancer. Thus, tobacco smoking, asbestos exposure, and lung carcinogenesis may disturb the cellular redox state in different ways. A strong correlation was found among PRDX2, TXN, GAPDH, and S100A8, suggesting that these proteins may present a diagnostic biomarker panel to aid recognizing individuals at high risk of contracting lung cancer.
Drug consumption and melanocytic nevi: correlation between oral contraceptives or hormone replacement therapy and a high melanocytic nevi count
Authors: Colucci Roberta , Buzzoni Carlotta , Dragoni Federica , Traniello Gradassi Alessandro , Galeone Massimiliano , Crocetti Emanuele , Moretti Silvia
Published: September 2019

The prolonged use of drugs such as beta-blockers, acetylsalicylic acid, omeprazole, statins, oral contraceptives and hormone replacement therapy might have some role in melanocytic nevi development and be ultimately linked to melanoma risk. Aims of the study were to evaluate a possible association between the above-mentioned drugs and features such as number and atypia of melanocytic nevi in long-term users. We retrospectively looked at pharmacological, clinical and dermoscopic records of 1321 patients that attended our unit for routine mole check between January 2013 and January 2018. Patients were divided into two groups (low or high melanocytic nevi count), and multivariate analysis was performed with regards to the presence and number of melanocytic nevi and drug assumption. A positive association between the use of oral contraceptives or hormone replacement therapy (P = 0.012) and a high melanocytic nevi count was found through multivariate analysis, after adjusting for sex, age and multiple confounding factors, such as freckles, phototype and a reported history of sun exposure and sunburns. Further prospective studies are necessary to establish whether women using oral contraceptives or on hormone replacement therapy should undergo periodic monitoring of pigmented lesions.
Orbital Fractures and Associated Ocular Injuries in Operation Iraqi Freedom and Operation Enduring Freedom Referred to a Tertiary Care Military Hospital and the Effect on Final Visual Acuity
Authors: Justin Grant A. , Turnage Winston A. , Brooks Daniel I. , Davies Brett W. , Ryan Denise S. , Eiseman Andrew S. , Weichel Eric D. , Colyer Marcus H.
Published: September 2019

Orbital fractures occur commonly during combat trauma and a significant number are legally blind despite appropriate treatment.

Purpose:

To update the incidence of orbital fractures in U.S. Soldiers admitted to the former Walter Reed Army Medical Center from 2001 to 2011 after sustaining combat injuries in Operation Iraqi Freedom and Operation Enduring Freedom.

Methods:

Data were collected in the Walter Reed Ocular Trauma Database. Inclusion criteria were any U.S. Soldier or Department of Defense civilian with an orbital fracture injured in Operation Iraqi Freedom/Operation Enduring Freedom. Primary outcome measures were final visual acuity and the effect of orbital fracture, number of fractures, and anatomic location of fracture on final visual acuity.

Results:

Eight-hundred ninety eye injuries occurred in 652 patients evacuated to Walter Reed Army Medical Center between 2001 and 2011. Orbital fractures occurred in 304 eyes (34.2%). A single wall was fractured in 140 eyes (46.05%), 2 in 99 (32.6%) eyes, 3 in 31 (10.2%), 4 in 28 (9.2%), and unknown in 6 (1.9%) eyes. Roof fractures were found in 74 (24.34%), medial wall in 135 (44.41%), lateral wall in 109 (35.9%), and floor fractures in 217 (71.4%). Final visual acuity was analyzed and 140 (46.05%) eyes had greater than 20/40 vision, 17 (5.59%) were 20/50 to 20/200, 26 (8.5%) were count fingers to light perception, and 95 (31.3%) were no light perception. In logistic regression analysis, roof (p = 0.001), medial (p = 0.009), and lateral fractures (p = 0.016) were significantly associated with final visual acuity less than 20/200, while floor fractures were not (p = 0.874). Orbital fracture and all fracture subtypes were significantly associated with traumatic brain injury, retrobulbar hematoma, optic nerve injury, but not for vitreous hemorrhage, commotio, hyphema, and choroidal rupture. Fracture repair was noted in 45 (14.8%).

Conclusions:

Orbital fractures occurred in a third of Operation Iraqi Freedom/Operation Enduring Freedom eyes of ocular trauma patients referred to one tertiary care military hospital. This resulted in approximately 40% of these eyes remaining legally blind after injury.
Surgical Management of a Recurrent Orbit-Eroding Mucocele Associated With Frontal-Ethmoidal Sinus Inverted Papilloma
Authors: Desjarlais Eric B. , Jovanovic Nina , Teo Honeylen Maryl T. , Kahana Alon
Published: September 2019

The development of orbit-eroding mucocele associated with inverted papilloma has been rarely reported.
1,2
Here, the authors present a case and surgical management of a patient with orbit-eroding mucocele associated with inverted papilloma who declined craniotomy. A combined approach utilizing frontal endoscopic sinus surgery and external sub-brow anterior orbitotomy was used to explore, drain, and excise the mucocele and inverted papilloma. Gelatin sponges soaked in gentamicin were used to cover the exposed dura and to protect the orbital content from the frontal sinus cavity.

A fronto-ethmoidal sinus inverted papilloma associated with recurrent orbit-eroding mucocele was excised by combined transnasal endoscopic and external sub-brow anterior orbitotomy approach using stereotactic navigation.
Comparative outcomes of catheter-directed thrombolysis plus rivaroxaban vs rivaroxaban alone in patients with acute iliofemoral deep vein thrombosis
Authors: Tsai Chia Ju , Lee Chiu-Yang
Published: September 2019

Background:

Since novel oral anticoagulants (NOACs) have been introduced in the past decade, the first option of deep vein thrombosis (DVT) treatment is toward NOACs. However, aggressive and early thrombus removal strategy is widely used for treating acute iliofemoral DVT. Consequently, optimal treatment duration, efficacy, and safety of rivaroxaban alone or in combination with catheter-directed intrathrombus thrombolysis (CDT) in acute iliofemoral DVT patients should be investigated.

Methods:

Patients with recent acute iliofemoral DVT treated with combined CDT–rivaroxaban (CDT) or rivaroxaban alone (control) were followed for mean (standard deviation) of 25.7 (2.5) months. DVT evolution, treatment efficacy and safety, and predisposing factors for patency and postthrombotic syndrome (PTS) development were analyzed through duplex ultrasonography, plethysmography, venography, and computed tomographic venography.

Results:

43.2%, 64.9%, 75.7%, and 72.2% of the CDT patients showed complete patency at 3, 6, 12, and 24 months of treatment compared with the control patients having 8.5%, 36.2%, 55.3%, and 57.4% of cumulative patency at 3, 6, 12, and 24 months, respectively (p = 0.001, 0.017, 0.088, and 0.081, respectively). The p value of the log-rank test comparing patency rates of the two groups was 0.009. The median (interquartile range, IQR) Villalta scores at 24 months were 3 (2-5) and 6 (4-8) in CDT and control patients, respectively (p = 0·001). PTS and bleeding events during therapy were, respectively, found in 35.1% and 63.8% (p = 0.017) and in 27% and 17% of CDT and control patients (p = 0.4). The Kaplan–Meier curve analysis of cumulative patency at 24 months for 6 months of rivaroxaban treatment was significant (p = 0.016).

Conclusion:

Treatment therapy and treatment duration with rivaroxaban alone or in combination with CDT are potentially associated with vein patency at 24 months, and a 6-month lysis rate and obstructive vein can influence PTS development. A larger randomized trial is warranted to confirm these findings.
A Prospective Outcome Assessment After Bronchoscopic Interventions for Malignant Central Airway Obstruction
Authors: Mohan Anant , Shrestha Prajowl , Madan Karan , Hadda Vijay , Pandey Ravindra M. , Upadhyay Ashish , Khilnani Gopi C. , Guleria Randeep
Published: September 2019

Background:

A systematic assessment of comprehensive clinical outcomes after various therapeutic procedures for malignant central airway obstruction (CAO) is lacking.

Methods:

Patients with symptomatic malignant CAO undergoing various therapeutic bronchoscopy procedures were assessed for symptomatic and functional improvement using the Speiser Score, spirometry, 6-minute walk distance (6MWD), and St. George Respiratory Questionnaire (SGRQ) up to 3 months after the procedures.

Results:

A total of 83 intervention procedures were performed in 65 patients, comprising 43 (66.2%) male individuals [overall mean age, 52.4; SD, 15.4 y]. The majority of these (92.3%) was done using rigid bronchoscope under general anesthesia. Airway stenting was the most common intervention performed (56.6%), followed by mechanical debulking (26.5%), cryodebulking (6%), electrosurgical removal (4.8%), balloon dilatation (3.6%), and laser ablation (2.4%).

A total of 15 complications (18.1%) were noted. Of these, 8 (53.3%) were early complications and 7 (46.7%) were late complications. Early complications included airway bleeding, hypoxia, vocal cord injury, laryngeal injury, and pneumothorax. Late complications included significant granulation tissue formation in metallic stents and lung collapse because of mucus plug.

The survival rates at 4, 8, and 12 weeks were 83%, 70.7%, and 66.1%, respectively. Significant improvement was observed in dyspnea, cough, Speiser Score, 6MWD, forced expiratory volume in 1 s, forced vital capacity, and SGRQ scores at 48 hours, 4 weeks, and at 12 weeks after the procedures and no procedure-related mortality occurred.

Conclusion:

Various therapeutic bronchoscopic interventions, including combined modalities, provide rapid and sustained improvements in symptoms, respiratory status, exercise capacity, and quality of life in malignant CAO and have a good safety profile.
Quantifying the Effect of Plasma Viscosity on In Vivo Dialyzer Performance
Authors: Schneditz Daniel , Daugirdas John T.
Published: September 2019

Dialyzer manufacturers characterize performance of their devices based on measurements of clearance using crystalloid solutions. Typically, in vitro dialyzer mass transfer area coefficients for urea (K
0
A) are substantially higher than values measured in vivo. The reason for this reduction has not been clearly determined. We hypothesized that the known effect of viscosity on reducing solute diffusivity might partially or fully account for this reduction. In vitro dialyzer clearances of urea, glucose, and lactate were measured using crystalloid solutions as well as bovine blood with varying hematocrit and plasma viscosity under a wide range of operating conditions. Viscosities of crystalloid solutions, of blood plasma, and of whole blood were measured at 37°C at a shear rate of 100/s. Diffusivity and relative K
0
A values (K
0
A
rel) in eight dialyzers were computed for each solute under these different conditions. Plasma was 1.84 times more viscous compared with crystalloid solution (η
rel = 1.84), suggesting a correction multiplier of 1/η
rel = 0.54 for in vivo K
0
A relative to the in vitro value. Experimental K
0
A
rel at that η
rel was on average reduced to 52% of crystalloid in vitro K
0
A values. The multiplier 0.52 measured in this study is close to the multiplier 0.55 predicted for average plasma viscosities and also close to the multiplier 0.54 assumed for urea kinetic modeling to provide reasonable urea distribution volumes. The known effect of viscosity on solute diffusivity is therefore sufficient to explain the reduction in dialyzer K
0
A for urea and glucose in vivo compared with in vitro measurements.
End-Stage Liver Disease Models and Outcomes in Pediatric Patients Supported With Short-Term Continuous-Flow Ventricular Assist Devices
Authors: Malik Getanshu , Pidborochynski Tara , Buchholz Holger , Freed Darren H. , Al-Aklabi Mohammed , Bozso Sabin J. , Choudhry Swati , Anand Vijay , Holinski Paula , Conway Jennifer
Published: September 2019

Short-term continuous-flow ventricular assist devices (STCF-VADs) are increasingly being utilized in pediatrics. End-stage liver disease (ELD) models have been associated with outcomes in adult patients on mechanical circulatory support. We sought to determine the relationship between outcomes in children on STCF-VADs and three ELD models: model for end-stage liver disease-excluding international normalized ratio (MELD-XI; all) and MELD-XI (> 1 year), PELD, and a novel score, PedMELD-XI. All patients (< 19 years) supported with STCF-VADs, between June 2009 and December 2016 were included. The MELD-XI, PELD, and PedMELD-XI scores were calculated and their association with adverse events and a composite measure of death, major bleeding, and neurologic dysfunction was analyzed. Of 32 patients, median age was 0.57 years (interquartile range [IQR], 0.10–4.43), median weight was 7.15 kg (IQR, 3.68–16.53), 53.1% had congenital heart disease, and 53.1% were male. In total, 78.1% patients experienced an adverse event (78.1% a major bleed, 25.0% neurologic dysfunction, and 15.6% death). The median MELD-XI score was 11.17 (IQR, 9.44–30.01), MELD-XI (>1 year) 9.44 (IQR, 9.44–24.33), PELD 6.00 (IQR, 4.00–13.75), and PedMELD-XI −14.91 (IQR, −18.85 to −12.25). A higher MELD-XI for all ages (13.80 vs. 9.44, p = 0.037) and less negative PedMELD-XI (−14.16 vs. −19.34, p = 0.028) scores were significantly associated with bleeding and the composite outcome. PedMELD-XI was significantly associated with death (−12.87 vs. −16.84, p = 0.041) while a trend was seen for increased MELD-XI in all ages being associated with death (31.52 vs. 10.11, p = 0.051). Last, there was no association with the models and neurologic events. MELD-XI and PedMELD-XI were significantly associated with major bleeding and the composite endpoints with PedMELD-XI also being associated with death. These results suggest that ELD models can be used to predict outcomes in this specific patient population, however, further analysis in a larger population is required.
Large body mass index and waist circumference are associated with high blood pressure and impaired fasting glucose in young Chinese men
Authors: Zhang Ying-xiu , Wang Shu-rong
Published: September 2019

Background:

Obesity is closely related to many chronic diseases and metabolic risk factors. The present study examined the relationship of obesity-related indices to blood pressure (BP) and fasting plasma glucose (FPG) among young Chinese men.

Methods:

A total of 1193 male college students aged 18–22 years participated in the study. Height, weight, waist circumference (WC), body mass index (BMI), waist-to-height ratio (WHtR), systolic blood pressure (SBP), diastolic blood pressure (DBP) and FPG were measured. High BP was defined as SBP ≥140 mmHg and/or DBP ≥90 mmHg. Impaired fasting glucose (IFG) was defined as FPG ≥5.6 mmol/L.

Results:

BMI, WC and WHtR were positively correlated with BP and FPG (rBMI-SBP = 0.455, rBMI-DBP = 0.367, rBMI-FPG = 0.113, rWC-SBP = 0.445, rWC-DBP = 0.382, rWC-FPG = 0.115, rWHtR-SBP = 0.396, rWHtR-DBP = 0.302, rWHtR-FPG = 0.106, P all < 0.01). When categorized by BMI (underweight, normal weight, overweight and obesity), the mean values of SBP, DBP, FPG and the prevalence of high BP and IFG increased with BMI, significant differences were observed among the four groups (P < 0.01). When categorized by WC and WHtR, similar differences were observed, with subjects in the large WC/WHtR group had a higher BP and FPG than their counterparts in the low WC/WHtR group (P < 0.01).

Conclusion:

Large BMI and WC/WHtR are associated with high BP and IFG. Our results suggested that prevention of obesity in youth may be an effective approach for preventing the development of diabetes and hypertension in the future.
Tc-99m-MAA lung shunt fraction before Y-90 radioembolization is low among patients with non-hepatocellular carcinoma malignancies
Authors: Elsayed Mohammad , Martin Jonathan G. , Dabrowiecki Alexander , Goldman Daryl T. , Faraj Razan , McMahon James T. , Kokabi Nima , Duszak Richard , Newsome Janice , Bercu Zachary L.
Published: September 2019

Objective

Lung shunt fraction studies using technetium-99 m macro aggregated albumin are routinely performed before yttrium-90 radioembolization regardless of underlying liver malignancy type. This study evaluates the role of lung shunt fraction studies in hepatocellular carcinoma compared to non-hepatocellular carcinoma liver tumors.

Methods

A single-institution retrospective analysis of all pre-yttrium-90 technetium-99 m macro aggregated albumin lung shunt fraction studies between November 2012 to March 2018 was performed. Patient variables including age, underlying malignancy, laboratory values, lung shunt fraction, and severity of liver disease were compared between hepatocellular carcinoma and non-hepatocellular carcinoma cases.

Results

A total of 734 technetium-99 m macro aggregated albumin studies were identified in 653 patients. Among these cases, the liver tumor was hepatocellular carcinoma in 368 (50.1%), colorectal cancer in 112 (15.3%), neuroendocrine tumor in 89 (12.1%), cholangiocarcinoma in 59 (8.0%), breast cancer in 27 (3.7%), and other metastatic malignancies in 79 (10.7%). The mean lung shunt fraction for non-hepatocellular carcinoma cases was 7.4%, which was significantly lower than the mean lung shunt fraction, 11.7%, for hepatocellular carcinoma cases (P = 0.0001). In only one non-hepatocellular carcinoma case was yttrium-90 radioembolization not pursued due to high lung shunt fraction (69.3%), wherein large scale shunting was grossly apparent on angiography in a patient with metastatic gastrointestinal stromal tumor. In comparison, the lung shunt fraction was too high to pursue radioembolization in 37 hepatocellular carcinoma cases (mean lung shunt fraction 35.1%).

Conclusion

Lung shunt fraction appears low among patients with non-hepatocellular carcinoma liver malignancies. Further analysis examining the necessity of pre-Y90 technetium-99 m macro aggregated albumin lung shunt fraction studies in patients with non-hepatocellular carcinoma malignancies is warranted, since a consolidated yttrium-90 radioembolization without prior lung shunt fraction evaluation could reduce resource consumption, improve workflows, and patient access.