bluuebunny/crossref_metadata_2025 huggingface dataset:
The Pseudomonas aeruginosa product pyochelin interferes with Trypanosoma cruzi infection and multiplication in vitro
Authors: Sass Gabriele , Miller Conrad Laura C , Nguyen Terrence-Thang H , Stevens David A
Published: March 2020

Background

Bacteria are sources of numerous molecules used in treatment of infectious diseases. We investigated effects of molecules produced by 26 Pseudomonas aeruginosa strains against infection of mammalian cell cultures with Trypanosoma cruzi, the aetiological agent of Chagas disease.

Methods

Vero cells were infected with T. cruzi in the presence of wild-type P. aeruginosa supernatants or supernatants of mutants with defects in the production of various virulence, quorum sensing and iron acquisition factors. Quantification of T. cruzi infection (percentage of infected cells) and multiplication (number of amastigotes per infected cell) was performed and cell viability was determined.

Results

Wild-type P. aeruginosa products negatively affected T. cruzi infection and multiplication in a dose-dependent manner, without evident toxicity for mammalian cells. PvdD/pchE mutation (loss of the P. aeruginosa siderophores pyoverdine and pyochelin) had the greatest impact on anti–T. cruzi activity. Negative effects on T. cruzi infection by pure pyochelin, but not pyoverdine, or other P. aeruginosa exoproducts studied, were quantitatively similar to the effects of benznidazole, the current standard therapy against T. cruzi.

Conclusions

The P. aeruginosa product pyochelin showed promising activity against T. cruzi and might become a new lead molecule for therapy development.
Cost Effectiveness of Latest Recommendations for Group B Streptococci Screening in the United States
Authors: Williams Marvin , Zantow Emily , Turrentine Mark
Published: March 2020

OBJECTIVE:

To evaluate whether group B streptococci (GBS) screening using the 2010 guideline (screening at 35 0/7–37 6/7 weeks of gestation) compared with the 2019 guideline (screening at 36 0/7–37 6/7 weeks of gestation with re-screening of women with GBS-negative results 5 weeks later) was more cost effective.

METHODS:

We constructed a decision-analysis model to compare the outcome of GBS early-onset disease in a hypothetical cohort of 3,614,049 women at 35 0/7 weeks of gestation or greater (the number of live births in 2017 excluding births based on population frequency from 23 to 34 weeks of gestation, women with GBS bacteriuria during the current pregnancy, and those with a history of a previous neonate with GBS disease). We took both a health care and societal perspective and all costs were expressed in 2017 U.S. dollars. Effectiveness was based on neonatal quality-adjusted life years (QALYs) gained. An incremental cost-effectiveness ratio was estimated with a willingness to pay threshold set at $100,000/QALY. All model inputs were derived from the literature. One-way probability and cost sensitivity analysis were performed to investigate model assumptions.

RESULTS:

Screening at 36 0/7–37 6/7 weeks of gestation with re-screening of women with GBS-negative results if 5 weeks passed from culture to delivery resulted in a 6% increase in neonatal QALYs gained (2,162 vs 2,037), 12% fewer cases of neonatal death (30 vs 34), and a 10% estimated reduction in total societal health care expenditures related to GBS early-onset disease ($639 million vs $707 million) when compared with the 2010 strategy of only screening at 35 0/7–37 6/7 weeks of gestation. The 2019 approach was cost effective, with an incremental cost-effectiveness ratio of $43,205 per neonatal QALY gained.

CONCLUSION:

Screening at 36 0/7–37 6/7 weeks of gestation with a 5-week re-screening for women with GBS-negative results is more cost effective than past strategies used in the United States.
The Added Value of Lactate and Lactate Clearance in Prediction of In-Hospital Mortality in Critically Ill Patients With Sepsis
Authors: Baysan Meryem , Baroni Gianluca D. , van Boekel Anna M. , Steyerberg Ewout W. , Arbous Mendi S. , van der Bom Johanna G.
Published: March 2020

Objective:

We investigated the added predictive value of lactate and lactate clearance to the Acute Physiology and Chronic Health Evaluation IV model for predicting in-hospital mortality in critically ill patients with sepsis.

Design:

Retrospective observational cohort study.

Setting:

Mixed ICU of Leiden University Medical Center, The Netherlands.

Patients:

Critically ill patients adult patients with sepsis who have been admitted to the ICU of Leiden University Medical Center, The Netherlands, from 2006 to January 2018.

Interventions:

None.

Measurements and Main Results:

We fitted a baseline model with the Acute Physiology and Chronic Health Evaluation IV predictors and added 13 prespecified combinations of lactate and lactate clearance at 0, 6 and 24 hours after admission to create a set of extended models to compare with the baseline Acute Physiology and Chronic Health Evaluation IV model. Among 603 ICU admissions, 451 patients met the inclusion criteria. A total of 160 patients died in-hospital, of which 106 died in the ICU. Their lactate and lactate clearance measurements were higher at all time points than those of survivors. The Akaike Information Criterion score improved in 10 of 13 prespecified extended models, with best performance for models that included lactate at 24 hours, alone or in combination with lactate at admission or lactate clearance at 24 hours. We compared the observed and predicted probabilities of in-hospital mortality of the baseline Acute Physiology and Chronic Health Evaluation IV model with the best model in our data, lactate at 24 hours added to the Acute Physiology and Chronic Health Evaluation IV model. This resulted in an increase in specificity of 29.9% (95% CI, 18.9–40.9%).

Conclusions:

Lactate measurements at 24 hours after admission add predictive value to the prediction of mortality with Acute Physiology and Chronic Health Evaluation IV among ICU patients with sepsis. External validation is needed to develop extended prediction models.
Residential Proximity to Intensive Animal Agriculture and Risk of Lymphohematopoietic Cancers in the Agricultural Health Study
Authors: Fisher Jared A. , Freeman Laura E. Beane , Hofmann Jonathan N. , Blair Aaron , Parks Christine G. , Thorne Peter S. , Ward Mary H. , Jones Rena R.
Published: March 2020

Background:

Although occupational exposure to animals has been associated with lymphohematopoietic malignancies, to our knowledge no studies have evaluated adult cancer risks associated with living near intensive animal agriculture.

Methods:

We linked participants in the prospective Agricultural Health Study to permitted animal feeding operations in Iowa. We created metrics reflecting the intensity of animal exposures within 2 and 5 km of participants’ residences, enumerating both total and inverse distance-weighted animal units (AUs), standardized by animal size and manure production. We estimated risk of lymphohematopoietic malignancies and subtypes [hazard ratio (HR), 95% confidence interval (95% CI)], adjusting for demographic and farming-related factors, including occupational pesticide exposure. We stratified associations by animal type and animal-related work activities.

Results:

We observed 519 cases (1993–2015) among 32,635 pesticide applicators and 211 cases among 19,743 spouses. Among applicators, no associations were evident within 2 km, but risk of any lymphohematopoietic cancer was elevated across quintiles of weighted AUs within 5 km. Risk of non-Hodgkin lymphoma (NHL) was elevated for the second (HR = 1.5; 95% CI, 1.1, 2.1), third (HR = 1.6; 95% CI, 1.1, 2.2), and fourth (HR = 1.7; 95% CI, 1.3, 2.4) highest quintiles of weighted AUs within 5 km (P
trend = 0.52) and increased with dairy cattle AUs (P
trend = 0.04). We found positive trends for leukemia and some NHL subtypes with increasing numbers of both beef and dairy cattle. Risks did not vary by animal-related work (P
interaction = 0.61). Associations were similar using the total exposure metric and inconsistent among spouses.

Conclusion:

Residential proximity to intensive animal agriculture was positively associated with risk of NHL and leukemia, even after consideration of occupational animal and pesticide exposures.
Transduction Efficiency of Adenovirus Vectors in Endothelial Cells and Vascular Smooth Muscle Cells
Authors: Mokhashi Nikita , Choi Robert Y. , Cicalese Stephanie , Eguchi Kunie , Boyer Michael J. , Cooper Hannah A. , Kimura Yayoi , Akiyama Tomoko , Scalia Rosario , Rizzo Victor , Eguchi Satoru
Published: March 2020

Adenoviral vectors are useful tools in manipulating a gene of interest in vitro and in vivo, including in the vascular system. The transduction efficiencies of adenoviral vectors in vascular cells such as endothelial cells (ECs) and vascular smooth muscle cells (VSMCs) are known to be lower than those in epithelial cell types. The effective entry for adenoviral vectors is primarily mediated through the coxsackievirus and adenovirus receptor (CAR), which has been shown to be expressed in both cell types. Cationic liposomes have been used to enhance adenovirus transduction efficiency in nonepithelial cells. Accordingly, the aim of this study is to obtain new information regarding differences in transduction efficiencies, cationic liposome sensitivity, and CAR expression between ECs and VSMCs. Using cultured rat aortic ECs and VSMCs, here, we have compared transduction efficiency of adenoviruses with or without inclusion of liposomes and CAR expression. A significant increase in basal transduction efficiency was observed in ECs compared with VSMCs. Cationic liposome polybrene enhanced transduction efficiency in VSMCs, whereas decreased efficiency was observed in ECs. Western blotting demonstrated expression of the CAR in ECs but not in VSMCs. Proteomic analysis and mouse aorta immunostaining further suggests significant expression of the CAR in ECs but not in VSMCs. In conclusion, adenoviruses can effectively transduce the gene of interest in aortic ECs likely because of abundant expression of the CAR, whereas cationic liposomes such as polybrene enhance the transduction efficiency in VSMCs lacking CAR expression.
CT Irradiation-induced Changes of Gene Expression within Peripheral Blood Cells
Authors: Kaatsch Hanns Leonhard , Majewski Matthäus , Schrock Gerrit , Obermair Richard , Seidel Jillyen , Nestler Kai , Abend Michael , Waldeck Stephan , Port Matthias , Ullmann Reinhard , Becker Benjamin Valentin
Published: March 2020

Computed tomography (CT) is a crucial element of medical imaging diagnostics. The widespread application of this technology has made CT one of the major contributors to medical radiation burden, despite the fact that doses per individual CT scan steadily decrease due to the advancement of technology. Epidemiological risk assessment of CT exposure is hampered by the fact that moderate adverse effects triggered by low doses of CT exposure are likely masked by statistical fluctuations. In light of these limitations, there is need of further insights into the biological processes induced by CT scans to complement the existing knowledge base of risk assessment. This prompted us to investigate the early transcriptomic response of ex vivo irradiated peripheral blood of three healthy individuals. Samples were irradiated employing a modern dual-source-CT-scanner with a tube voltage of 150 kV, resulting in an estimated effective dose of 9.6 mSv. RNA was isolated 1 h and 6 h after exposure, respectively, and subsequently analyzed by RNA deep sequencing. Differential gene expression analysis revealed shared upregulation of AEN, FDXR, and DDB2 6 h after exposure in all three probands. All three genes have previously been discussed as radiation responsive genes and have already been implicated in DNA damage response and cell cycle control after DNA damage. In summary, we substantiated the usefulness of AEN, FDXR, and DDB2 as RNA markers of low dose irradiation. Moreover, the upregulation of genes associated with DNA damage reminds one of the genotoxic nature of CT diagnostics even with the low doses currently applied.
Randomized trial of intracoronary adenosine as adjunctive therapy for prevention of the no-reflow phenomenon
Authors: Naghshtabrizi Nima , Sajedi Manijeh , Naghshtabrizi Behshad , Mozayanimonfared Azadeh , Ali Seif Rabiei Mohamad , Kanonisabet Ali
Published: March 2020

No-reflow phenomenon as a serious complication following percutaneous coronary intervention, deteriorates clinical outcomes. Intracoronary (IC) Adenosine, seems to be a way to deal with it. One hundred four consecutive patients with ST-segment elevation myocardial infarction were randomized into two groups. Each group consisted of 52 patients who managed with two bolus doses of IC Adenosine (Adenosine group) or two bolus doses of IC normal saline (placebo group) administered before and after stenting. Thrombolysis in myocardial infarction (TIMI) grade flow, ST-segment resolution (STR) and post-procedural clinical outcomes were used as endpoints. IC adenosine led to lower rates of no-reflow based on TIMI grade flow scaling (15.4% vs. 44.3%; P-value: 0.02). STR classified as complete, partial and no resolution was similar between two groups (P-value: 0.748). Also, post-interventional clinical outcomes, including arrhythmia, left ventricular ejection fraction, hospitalization time, and 30 days mortality were similar between Adenosine and placebo groups.
Both baseline Selvester QRS score and change in QRS score predict prognosis in patients with acute ST-segment elevation myocardial infarction after percutaneous coronary intervention
Authors: Liu Qian , Zhang Yong , Zhang Pengqiang , Zhang Junbo , Cao Xiaojiao , He Shanshan , Yang Donghui
Published: March 2020

Background:

We aimed to demonstrate the prognostic value of Selvester QRS scores in patients with acute ST-segment elevation myocardial infarction (STEMI).

Methods:

In this prospective, observational study, we screened 289 patients with acute STEMI who underwent percutaneous coronary intervention (PCI) from 1 January 2014 to 1 June 2015 at the Second Hospital of Dalian Medical University. Selvester QRS scores were calculated at the time of hospital admission and within 24 h after treatment for PCI. The primary endpoint was the 2-year mortality rate, and the secondary endpoint was any nonfatal major adverse cardiovascular event (MACE).

Results:

Of the 289 patients, the QRS score increased in 115 (39.8%), and the 2-year mortality and MACE rates were significantly higher in these patients than in those in whom the QRS score decreased or remained unchanged after the treatment of PCI. Multivariable Cox regression analysis revealed that both baseline QRS scores and changes in QRS scores were independently associated with the 2-year mortality rate [hazard ratio (HR) 1.462, 95% confidence interval (95% CI) 1.279–1.671 and HR 5.122, 95% CI 2.128–12.328, respectively), MACE rate (HR 1.119, 95% CI 1.019–1.229 and HR 2.585, 95% CI 1.260–5.303, respectively) and composite endpoint (HR 1.137, 95% CI 1.047–1.236 and HR 3.152, 95% CI 1.704–5.829, respectively) after adjusting for other risk factors.

Conclusion:

In conclusion, both baseline Selvester QRS scores and changes in QRS scores independently predicted poor outcomes in patients with acute STEMI who underwent PCI.
Relationship between cardio-ankle vascular index and obstructive coronary artery disease
Authors: Birudaraju Divya , Cherukuri Lavanya , Kinninger April , Chaganti Bhanu T. , Haroun Pishoy , Pidikiti Sivakrishna , Lakshmanan Suvasini , Hamal Sajad , Flores Ferdinand , Dailing Christopher , Shaikh Kashif , Roy Sion K. , Budoff Matthew J.
Published: March 2020

Background

Cardio-ankle vascular index (CAVI) is an inexpensive, noninvasive, office-based method to evaluate arterial stiffness in the aorta and legs, which reflects the degree of coronary atherosclerosis. It has been applied clinically to assess arterial stiffness in patients who were diagnosed with coronary artery disease (CAD), stroke and those at risk. We intend to evaluate relationship between the CAVI and obstructive CAD.

Methods

We enrolled 285 individuals with mean age of 55.8 ± 13.5 years, clinically referred for Coronary Artery Calcium (CAC) scoring and coronary computed tomography angiography (CCTA) at our site. After informed consent, CAVI measurements were done using a vascular screening system, VaSera VS-1500 AU (FUKUDA Denshi) on the same day of CCTA. CAC was measured using the Agatston method. A semiquantitative scale was used by CCTA readers to grade the extent of luminal stenosis as a percentage of the vessel diameter using visual estimations. We evaluated if CAVI was associated with severe stenosis (>50%) or CAC >100, defined as obstructive CAD.

Results

The degree of CAC and severe coronary stenosis demonstrated significant correlation with CAVI (r = 0.44, P ≤ 0.0001 and r = 0.43, P ≤ 0.0001). Receiver operating characteristic curve analysis indicated that CAVI measure of 7.8 was an optimal cut-point for sensitivity and specificity in detecting obstructive CAD. Unadjusted logistic regression demonstrated CAVI >7.8, significantly associated with obstructive CAD [odds ratio (OR) = 4.60, 95% confidence interval (CI) (2.0–10.56), P = 0.0003] and CAC score >100 [OR = 6.96, 95% CI (3.68–13.17), P < 0.0001].

Conclusion

CAVI reflects coronary atherosclerosis and may be used as a screening tool for early identification of subclinical atherosclerosis in preventive care and optimize management.
A real-world analysis of cardiac rupture on incidence, risk factors and in-hospital outcomes in 4190 ST-elevation myocardial infarction patients from 2004 to 2015
Authors: Hao Ziyong , Ma Jun , Dai Jinjie , Shao Qin , Shen Lan , He Ben , Jiang Lisheng
Published: March 2020

Background

Cardiac rupture is a disastrous but uncommon complication of acute ST-elevation myocardial infarction (STEMI). The incidence, risk factors and in-hospital outcomes related to cardiac rupture in the current era are unknown.

Methods

This study consecutively collected all acute STEMI patients admitted to a single tertiary center in China from January 2004 to December 2015. Characteristics of each cardiac rupture were collected and analyzed.

Results

Among 4190 patients, 75 (1.8%) patients had cardiac rupture, including 33 at the ventricular septum and 42 at the left ventricle free wall (LVFW). Patients with cardiac rupture were more likely to be female, with more advanced age, lower rate of primary percutaneous coronary intervention (PPCI), and higher in-hospital mortality. Compared with survivors, the death cases were older, had a higher white blood cell count, higher rate of delayed admission (>12 h from symptom onset to door), earlier occurrence of cardiac rupture, higher percentage of LVFW rupture and lower rate of surgical repair. Logistic regression analysis showed that surgical repair served as the most valuable factor affecting survival. Moreover, elevated white blood cell count and advanced age might be related to an increased in-hospital death due to cardiac rupture.

Conclusions

In this contemporary cohort, female sex, advanced age and low rate of PPCI post-STEMI are associated with an increased risk of cardiac rupture. Advanced age and elevated white blood cell count might be related to an increased in-hospital mortality after cardiac rupture, whereas surgical repair served as the most valuable factor affecting survival.
Mediation Effects of Compassion Satisfaction and Compassion Fatigue in the Relationships Between Resilience and Anxiety or Depression Among Hospice Volunteers
Authors: Jo Minjeong , Na Hyunjoo , Jung Young-Eun
Published: March 2020

Hospice volunteers are a high-risk group for anxiety and depression owing to their frequent exposure to patients at the end of life and their subsequent deaths. Resilience is known to be a powerful factor that affects the occurrence of anxiety and depression; however, research on this subject is scarce. We investigated the relationship of resilience with anxiety or depression in hospice volunteers. A total of 145 volunteers were included in the analysis. Participants completed self-reported scales, including the Korean version of the Connor-Davidson Resilience Scale, the State-Trait Anxiety Inventory, Patient Health Questionnaire-9, and the Professional Quality of Life Scale version 5. Pearson correlation coefficients were analyzed to identify the relationship of compassion satisfaction and compassion fatigue with anxiety or depression. A PROCESS macro mediation analysis was used to investigate the mediation effects of compassion satisfaction and compassion fatigue on the relationship between resilience and anxiety or depression. There were significant associations of compassion satisfaction and compassion fatigue with anxiety and depression. The relationship between resilience and anxiety/depression was mediated by compassion fatigue, which had indirect effects on anxiety and depression. Efforts to reduce compassion fatigue and increase resilience could help prevent anxiety and depression in hospice volunteers.
Effects of Mydriatics on Rod/Cone- and Melanopsin-driven Pupil Responses
Authors: Flanagan Sarah C. , Saunders Kathryn J. , Queener Hope M. , Richardson Patrick , Ostrin Lisa A.
Published: March 2020

SIGNIFICANCE

Pupillometry protocols evaluating rod/cone- and melanopsin-driven responses often use mydriatics to ensure maximal stimulus exposure; however, retinal effects of mydriatics are not fully understood. We demonstrate that dilation with either atropine or phenylephrine results in similar enhancements of rod/cone- and melanopsin-driven pupil responses.

PURPOSE

The purposes of this study were to compare the effects of atropine, a muscarinic antagonist, and phenylephrine, an adrenergic agonist, on consensual pupil responses and to assess the repeatability of pupil metrics without mydriasis.

METHODS

Right eye pupil responses of 20 adults aged 21 to 42 years were recorded before and 45 minutes after instillation of 0.5% atropine or 2.5% phenylephrine in the left eye. Stimuli were presented to the left eye and included six alternating 1-second 651-nm “red” and 456-nm “blue” flashes. Metrics included baseline pupil diameter, maximal constriction, 6- and 30-second post-illumination pupil responses, and early (0 to 10 seconds) and late (10 to 30 seconds) areas under the curve.

RESULTS

Dilation of the stimulated eye with either mydriatic significantly increased the 6-second post-illumination pupil response and early and late areas under the curve for blue stimuli, and early area under the curve for red stimuli (P < .05 for all). Melanopsin-driven post-illumination pupil responses, achieved with either phenylephrine or atropine, did not significantly differ from each other (P > .05 for all). Without mydriasis, intersession intraclass correlation coefficients for pupil metrics were 0.63 and 0.50 (6- and 30-second post-illumination pupil responses, respectively) and 0.78 and 0.44 (early and late areas under the curve, respectively) for blue stimuli, with no significant difference between sessions (P > .05 for all).

CONCLUSIONS

Dilation with phenylephrine or atropine resulted in similar enhancements of the rod/cone- and melanopsin-driven pupil responses, despite differing mechanisms. Early pupil metrics without mydriasis demonstrated moderate to good intersession repeatability.
Bacteriostatic Effect of Multidose Preservative-free Buffered Saline Used in Scleral Lens Wear
Authors: Seo Wonjae , Chiu Gloria B. , She Rosemary C.
Published: March 2020

SIGNIFICANCE

Scleral lenses have become an increasingly common treatment for ocular surface disease and irregular corneas. Multidose, preservative-free saline solutions are frequently used off-label to fill scleral lenses. Because the fluid resides over the ocular surface during lens wear, contaminated solutions may increase the risk of infectious complications.

PURPOSE

We sought to assess the viability of skin microorganisms and pathogens associated with keratitis once introduced into a multidose preservative-free saline (MDPFS) solution containing the bacteriostatic agent boric acid (PuriLens Plus; The Lifestyle Co., Inc., Freehold, NJ).

METHODS

Eleven bacterial and one yeast isolate were each inoculated to three lots of MDPFS as well as to sterile normal saline for comparison. Microorganism concentrations were enumerated at baseline and days 1, 3, 7, 14, 21, and 28. Persistence of microorganism viability was compared between MDPFS lots and between MDPFS and normal saline for each organism.

RESULTS

Duration of microorganism viability was ≥24 hours in MDPFS with no significant difference in the distribution of survival duration of microorganisms in MDPFS versus normal saline (P = .15). Candida albicans concentrations declined 14 days earlier in MDPFS, whereas concentrations of viable organisms in MDPFS remained within 1 log of baseline for the longest durations for Pseudomonas aeruginosa (7 days), Escherichia coli (14 days), and Achromobacter xylosoxidans (≥28 days). Gram-positive organism concentrations remained within 1 log of baseline for no more than 3 days. Mild lot-to-lot variation in organism concentrations was noted near the end points of viability. Bacteriostasis was demonstrated in that concentrations of all organisms remained at or below baseline levels throughout the 28-day period.

CONCLUSIONS

After microbial contamination, persistence of organism viability was similar in PuriLens and normal saline. Environmental gram-negative organisms, many of which can contribute to infectious keratitis, can persist for weeks once introduced into saline solutions.
Impact of a Multidisciplinary Sepsis Initiative on Knowledge and Behavior in a Pediatric Center
Authors: Breuer Ryan K. , Hassinger Amanda B.
Published: March 2020

Objective:

Our institution performed an educational initiative targeting previously identified barriers to pediatric sepsis recognition and treatment. We hypothesized that provider knowledge, attitude, and behavior would be improved 1 year after implementation.

Methods:

This was a prospective, observational study of a multi-faceted quality initiative introduced to providers in the Emergency Department, inpatient wards, and Pediatric Intensive Care Unit of a tertiary care children’s hospital. Educational platforms consisted of quarterly electronic sepsis “newsletters,” brightly colored posters highlighting protocol and screening strategies displayed throughout the hospital, and low-fidelity simulation sessions (drills) led by trained staff and incorporated into daily workflows. The content was driven by feedback from a baseline needs assessment of sepsis education. One year after implementation, the needs assessment was repeated.

Results:

Over 3 months, facilitators conducted 197 drills and captured a majority of nurses (89%), pediatrics residents (96%), and respiratory therapists (62%). By 6 months, 241 sessions had been completed. Approximately 55.4% of the 442 eligible staff participated in our post-intervention survey. Overall, knowledge of diagnostic criteria for pediatric sepsis and septic shock increased from pre-intervention levels (P = 0.015). Among post-implementation respondents, drill participants outperformed their colleagues (P = 0.001). A greater percentage of post-intervention respondents indicated comfort with sepsis recognition (P < 0.001), and fewer reported hesitating to bring sepsis concerns to their care team (P < 0.01).

Conclusions:

Our findings suggest that a multidisciplinary curriculum balancing active education—through brief, targeted simulation—and general awareness—through electronic resources and a poster campaign—can improve sepsis-related knowledge, attitude, and behavior among pediatric practitioners.
Factors associated with psoriasis in a French Nationwide HIV cohort: the independent role of HLA-B ∗ 57:01
Authors: Hentzien Maxime , Cuzin Lise , Raffi François , Jacomet Christine , Reynes Jacques , Rey David , Ravaux Isabelle , Cheret Antoine , Viguier Manuelle , Bani-Sadr Firouzé
Published: March 2020

Objective:

Psoriasis is a T-cell-mediated inflammatory disease with genetic factors involved in its etiopathogenesis. In non-HIV populations, HLA-B
∗
57:01 has been associated with a higher risk of psoriasis. The aim of this study was to investigate demographic and immunovirological characteristics associated with psoriasis, and to assess whether HLA-B
∗
57:01 is associated with psoriasis among people living with HIV (PLHIV) followed in a large French multicenter Dat’AIDS cohort.

Methods:

All PLHIV followed up from January 2000 to December 2018 with an available result for HLA-B
∗
57:01 were included. Logistic regression models were used to identify associations between psoriasis (outcome variable) and explanatory variables.

Results:

Among 31 076 PLHIV, the overall prevalence of psoriasis and HLA-B
∗
57:01 were 2.25 and 4.73%, respectively and varied according to ethnicity. By multivariate analysis, male gender [OR 1.81 (95% CI 1.46–2.24), P < 10–4], positive HLA-B
∗
57:01 [OR 2.66 (95% CI 2.12–3.33), P < 10–4], nadir CD4+ cell count less than 200 cells/μl [OR 1.41 (95% CI 1.19–1.67), P < 10–4] and positive HCV serology [OR 1.45 (95% CI 1.20–1.76), P < 10–4] were significantly associated with a higher risk of psoriasis. Being born in West and Central Africa [OR 0.15 (95% CI 0.10–0.25), P < 10–4], the Caribbean islands [OR 0.14 (95% CI 0.05–0.45), P = 0.0008] or Latin America [OR 0.31 (95% CI 0.14–0.69), P = 0.004] was associated with a lower risk of psoriasis compared with patients born in mainland France.

Conclusion:

PLHIV carrying HLA-B
∗
57:01 have around a three-fold increased risk of psoriasis. This association might provide a possible explanation for the observed differences in psoriasis prevalence between ethnic groups.
Accuracy of an Artificial Intelligence Deep Learning Algorithm Implementing a Recurrent Neural Network With Long Short-term Memory for the Automated Detection of Calcified Plaques From Coronary Computed Tomography Angiography
Authors: Fischer Andreas M. , Eid Marwen , De Cecco Carlo N. , Gulsun Mehmet A. , van Assen Marly , Nance John W. , Sahbaee Pooyan , De Santis Domenico , Bauer Maximilian J. , Jacobs Brian E. , Varga-Szemes Akos , Kabakus Ismail M. , Sharma Puneet , Jackson Logan J. , Schoepf U. Joseph
Published: March 2020

Purpose:

The purpose of this study was to evaluate the accuracy of a novel fully automated deep learning (DL) algorithm implementing a recurrent neural network (RNN) with long short-term memory (LSTM) for the detection of coronary artery calcium (CAC) from coronary computed tomography angiography (CCTA) data.

Materials and Methods:

Under an IRB waiver and in HIPAA compliance, a total of 194 patients who had undergone CCTA were retrospectively included. Two observers independently evaluated the image quality and recorded the presence of CAC in the right (RCA), the combination of left main and left anterior descending (LM-LAD), and left circumflex (LCx) coronary arteries. Noncontrast CACS scans were allowed to be used in cases of uncertainty. Heart and coronary artery centerline detection and labeling were automatically performed. Presence of CAC was assessed by a RNN-LSTM. The algorithm’s overall and per-vessel sensitivity, specificity, and diagnostic accuracy were calculated.

Results:

CAC was absent in 84 and present in 110 patients. As regards CCTA, the median subjective image quality, signal-to-noise ratio, and contrast-to-noise ratio were 3.0, 13.0, and 11.4. A total of 565 vessels were evaluated. On a per-vessel basis, the algorithm achieved a sensitivity, specificity, and diagnostic accuracy of 93.1% (confidence interval [CI], 84.3%-96.7%), 82.76% (CI, 74.6%-89.4%), and 86.7% (CI, 76.8%-87.9%), respectively, for the RCA, 93.1% (CI, 86.4%-97.7%), 95.5% (CI, 88.77%-98.75%), and 94.2% (CI. 90.2%-94.6%), respectively, for the LM-LAD, and 89.9% (CI, 80.2%-95.8%), 90.0% (CI, 83.2%-94.7%), and 89.9% (CI, 85.0%-94.1%), respectively, for the LCx. The overall sensitivity, specificity, and diagnostic accuracy were 92.1% (CI, 92.1%-95.2%), 88.9% (CI. 84.9%-92.1%), and 90.3% (CI, 88.0%-90.0%), respectively. When accounting for image quality, the algorithm achieved a sensitivity, specificity, and diagnostic accuracy of 76.2%, 87.5%, and 82.2%, respectively, for poor-quality data sets and 93.3%, 89.2% and 90.9%, respectively, when data sets rated adequate or higher were combined.

Conclusion:

The proposed RNN-LSTM demonstrated high diagnostic accuracy for the detection of CAC from CCTA.
Tablet-Based Decision Support Tool Improves Performance of Neonatal Resuscitation
Authors: Roitsch Charles M. , Patricia Karen E. , Hagan Joseph L. , Arnold Jennifer L. , Sundgren Nathan C.
Published: March 2020

Introduction

Decision support tools (DST) may aid compliance of teams with the Neonatal Resuscitation Program (NRP) algorithm but have not been adequately tested in this population. Furthermore, the optimal team size for neonatal resuscitation is not known. Our aim was to determine whether use of a tablet-based DST or team size altered adherence to the NRP algorithm in teams of healthcare providers (HCPs) performing simulated neonatal resuscitation.

Method

One hundred nine HCPs were randomized into a team of 2 or 3 and into using a DST or memory alone while performing 2 simulation scenarios. The primary outcome was NRP compliance, assessed by the modified Neonatal Resuscitation Performance Evaluation (NRPE). Secondary outcomes were the subcomponents of the NRPE score, cumulative time error (the cumulative time in seconds to perform resuscitation tasks in error, early or late, from NRP guidelines), and the interaction between DST and team size.

Results

Decision support tool use improved total NRPE score when compared with memory alone (p = 0.015). There was no difference in NRPE score within teams of 2 compared with 3 HCPs. Cumulative time error was decreased with DST use compared with memory alone but was not significant (p = 0.057). Team size did not affect time error.

Conclusions

Teams with the DST had improved NRP adherence compared with teams relying on memory alone in 1 of 2 scenarios. Two and 3 HCP teams performed similarly. Given the positive results observed in the simulated environment, further testing the DST in the clinical environment is warranted.
Unilateral Stent Insertion With High-intensity Focused Ultrasound Ablation for Hilar Cholangiocarcinoma
Authors: Cao Qiang , Li Juan-Juan , Feng Tao , Shi Yi-Bing , Wang Gang , Xia Feng-Fei
Published: March 2020

Purpose:

To evaluate the clinical effectiveness and long-term outcomes of unilateral stent insertion with high-intensity focused ultrasound ablation (HIFUA) in patients with hilar cholangiocarcinoma (HCCA).

Materials and Methods:

From March 2016 to June 2019, consecutive patients presenting with HCCA were treated with single stent insertion or stent with HIFUA. The long-term outcomes of the 2 groups were compared.

Results:

During the study period, 37 patients were included who underwent single stent insertion and 32 patients who underwent stent insertion with HIFUA. Eight (21.6%) patients in the single stent group and 6 (18.8%) in the combined group experienced stent dysfunction (P=0.767). Median stent patency in the single stent and combined groups was 169 and 225 days, respectively (P<0.001). All patients died because of tumor progression. The median poststent overall survival for patients in the single stent and combined groups were 178 and 246 days, respectively (P<0.001).

Conclusion:

HIFUA after unilateral stent insertion can prolong stent patency and survival of patients with inoperable HCCA.
Prednisolone as Adjunctive Treatment to Risperidone in Children With Regressive Type of Autism Spectrum Disorder: A Randomized, Placebo-Controlled Trial
Authors: Malek Malekfarhad , Ashraf-Ganjouei Amir , Moradi Kamyar , Bagheri Sayna , Mohammadi Mohammad-Reza , Akhondzadeh Shahin
Published: March 2020

Objectives

This study aimed to evaluate efficacy and safety of prednisolone as an adjunctive treatment to risperidone, in children with regressive autism spectrum disorder (ASD).

Methods

The current 12-week, randomized, single-blinded, placebo-controlled trial recruited 37 patients with regressive ASD. The participants were allocated to receive either 1 mg/kg per day prednisolone or matched placebo in addition to risperidone. The Aberrant Behavior Checklist-Community Edition (ABC-C) scale and Childhood Autism Rating Scale (CARS) were used to measure behavioral outcomes at weeks 0, 4, 8, and 12 of the study course. The primary outcome was the change in ABC-irritability subscale score, whereas the secondary outcomes were the change in scores of other ABC-C subscales, in CARS score, and in the level of inflammatory biomarkers.

Results

Twenty-six patients completed the 12 weeks of study period. Repeated-measures analysis demonstrated significant effect for time-treatment interaction in the CARS (F (1, 2.23) = 13.22, P < 0.001), as well as 4 subscales of the ABC-C including: irritability (F (1, 2.12) = 3.84, P = 0.026), hyperactivity (F (1, 2.09) = 3.56, P = 0.039), lethargy (F (1, 2.18) = 31.50, P < 0.001), and stereotypy (F (1, 1.89) = 4.04, P = 0.026). However, no significant time-treatment interaction was identified for inappropriate speech subscale (F (1, 2.03) = 1.71, P = 0.191). In addition, inflammatory biomarkers were significantly decreased after 3 months of prednisolone add-on. No significant adverse event was detected during the trial.

Conclusions

Prednisolone, as an add-on to risperidone, could remarkably improve core features in children with regressive ASD.
Whole-genome DNA methylation profiling of CD14+ monocytes reveals disease status and activity differences in Crohn’s disease patients
Authors: Li Yim Andrew Y.F. , Duijvis Nicolette W. , Ghiboub Mohammed , Sharp Catriona , Ferrero Enrico , Mannens Marcel M.A.M. , D’Haens Geert R. , de Jonge Wouter J. , te Velde Anje A. , Henneman Peter
Published: March 2020

Crohn’s disease (CD) is a multifactorial incurable chronic disorder. Current medical treatment seeks to induce and maintain a state of remission. During episodes of inflammation, monocytes infiltrate inflamed mucosa whereupon they differentiate into macrophages with a pro-inflammatory phenotype. Here, we sought to characterize the circulating monocytes by profiling their DNA methylome and relate it to the level of CD activity. We gathered an all-female age-matched cohort of 16 CD patients and 7 non-CD volunteers. CD patients were further subdivided into 8 CD patients with active disease (CD-active) and 8 CD patients in remission (CD-remissive) as determined by physician global assessment. We identified 15 and 12 differentially methylated genes (DMGs) when comparing CD with non-CD and CD-active with CD-remissive, respectively. Differential methylation was predominantly found in the promoter regions of inflammatory genes. Comparing our observations with gene expression data on classical (CD14++CD16-), non-classical (CD14+CD16++) and intermediate (CD14++CD16+) monocytes indicated that while 7 DMGs were differentially expressed across the 3 subsets, the remaining DMGs could not immediately be associated with differences in known populations. We conclude that CD activity is associated with differences in DNA methylation at the promoter region of inflammation-associated genes.
The demand for inpatient and ICU beds for COVID-19 in the US: lessons from Chinese cities
Authors: Li Ruoran , Rivers Caitlin , Tan Qi , Murray Megan B , Toner Eric , Lipsitch Marc
Published: March 2020

Background

Sustained spread of SARS-CoV-2 has happened in major US cities. Capacity needs in Chinese cities could inform the planning of local healthcare resources.

Methods

We described the intensive care unit (ICU) and inpatient bed needs for confirmed COVID-19 patients in two Chinese cities (Wuhan and Guangzhou) from January 10 to February 29, 2020, and compared the timing of disease control measures in relation to the timing of SARS-CoV-2 community spread. We estimated the peak ICU bed needs in US cities if a Wuhan-like outbreak occurs.

Results

In Wuhan, strict disease control measures were implemented six weeks after sustained local transmission of SARS-CoV-2. Between January 10 and February 29, COVID-19 patients accounted for an average of 637 ICU patients and 3,454 serious inpatients on each day. During the epidemic peak, 19,425 patients (24.5 per 10,000 adults) were hospitalized, 9,689 (12.2 per 10,000 adults) were considered to be in serious condition, and 2,087 patients (2.6 per 10,000 adults) needed critical care per day. In Guangzhou, strict disease control measures were implemented within one week of case importation. Between January 24 and February 29, COVID-19 accounted for an average of 9 ICU patients and 20 inpatients on each day. During the epidemic peak, 15 patients were in critical condition, and 38 were classified as serious. If a Wuhan-like outbreak were to happen in a US city, the need for healthcare resources may be higher in cities with a higher prevalence of vulnerable populations.

Conclusion

Even after the lockdown of Wuhan on January 23, the number of seriously ill COVID-19 patients continued to rise, exceeding local hospitalization and ICU capacities for at least a month. Plans are urgently needed to mitigate the effect of COVID-19 outbreaks on the local healthcare system in US cities.
Novel Coronavirus (COVID-19) Knowledge and Perceptions: A Survey of Healthcare Workers
Authors: Bhagavathula Akshaya Srikanth , Aldhaleei Wafa Ali , Rahmani Jamal , Mahabadi Mohammadjavad Ashrafi , Bandari Deepak Kumar
Published: March 2020

Background

During the first week of March, the surge of coronavirus disease 2019 (COVID-19) cases reached over 100 countries with more than 100,000 cases. Healthcare authorities have already initiated awareness and preparedness activities beyond borders. A poor understanding of the disease among healthcare workers (HCWs) may result in delayed treatment and the rapid spread of infection. This study aimed to investigate the knowledge and perceptions of HCWs about COVID-19.

Methods

A cross-sectional, web-based study was conducted among HCWs about COVID-19 during the first week of March 2020. A 23-item survey instrument was developed and distributed randomly to HCWs using social media; it required 5 minutes to complete. A chi-square test was used to investigate the level of association among variables at the significance level of p<0.05.

Results

Of 529 participants, a total of 453 HCWs completed the survey (response rate: 85.6%); 51.6% were males, 32.1% were aged 25-34 years, and most were doctors (30.2%) and medical students (29.6%). Regarding COVID-19, most of the participants used social media to obtain information (61%), and a significant proportion of HCWs had poor knowledge of its transmission (61%) and symptom onset (63.6%) and showed positive perceptions of COVID-19 prevention and control. Factors such as age and profession were associated with inadequate knowledge and poor perception of COVID-19.

Conclusion

As the global threat of COVID-19 continues to emerge, it is critical to improve the knowledge and perceptions of HCWs. Educational interventions are urgently needed to reach HCWs beyond borders, and further studies are warranted.
Protocol for a randomized controlled trial testing inhaled nitric oxide therapy in spontaneously breathing patients with COVID-19
Authors: Lei Chong , Su Binxiao , Dong Hailong , Fakhr Bijan Safaee , Grassi Luigi Giuseppe , Di Fenza Raffaele , Gianni Stefano , Pinciroli Riccardo , Vassena Emanuele , Morais Caio Cesar Araujo , Bellavia Andrea , Spina Stefano , Kacmarek Robert , Berra Lorenzo
Published: March 2020

Introduction

the current worldwide outbreak of Coronavirus disease 2019 (COVID-19) due to a novel coronavirus (SARS-CoV-2) is seriously threatening the public health. The number of infected patients is continuously increasing and the need for Intensive Care Unit admission ranges from 5 to 26%. The mortality is reported to be around 3.4% with higher values for the elderly and in patients with comorbidities. Moreover, this condition is challenging the healthcare system where the outbreak reached its highest value. To date there is still no available treatment for SARS-CoV-2. Clinical and preclinical evidence suggests that nitric oxide (NO) has a beneficial effect on the coronavirus-mediated acute respiratory syndrome, and this can be related to its viricidal effect. The time from the symptoms’ onset to the development of severe respiratory distress is relatively long. We hypothesize that high concentrations of inhaled NO administered during early phases of COVID-19 infection can prevent the progression of the disease.

Methods and analysis

This is a multicenter randomized controlled trial. Spontaneous breathing patients admitted to the hospital for symptomatic COVID-19 infection will be eligible to enter the study. Patients in the treatment group will receive inhaled NO at high doses (140-180 parts per million) for 30 minutes, 2 sessions every day for 14 days in addition to the hospital care. Patient in the control group will receive only hospital care. The primary outcome is the percentage of patients requiring endotracheal intubation due to the progression of the disease in the first 28 days from enrollment in the study. Secondary outcomes include mortality at 28 days, proportion of negative test for SARS-CoV-2 at 7 days and time to clinical recovery.

Ethics and dissemination

The trial protocol has been approved at the Investigation Review Boards of Xijing Hospital (Xi’an, China) and The Partners Human Research Committee of Massachusetts General Hospital (Boston, USA) is pending. Recruitment is expected to start in March 2020. Results of this study will be published in scientific journals, presented at scientific meetings, and on related website or media in fighting this widespread contagious disease.

Trial registration

Clinicaltrials.gov. NCT submitted