Publications by authors named "Sarah Lee"

329 Publications

An Australian Neuro-Palliative perspective on Huntington's disease: a case report.

BMC Palliat Care 2021 Apr 1;20(1):53. Epub 2021 Apr 1.

Calvary Health Care Bethlehem, Melbourne, Australia.

Background: Huntington's Disease (HD) is an incurable, progressive neuro-degenerative disease. For patients with HD access to palliative care services is limited, with dedicated Neuro-Palliative Care Services rare in Australia. We discuss the experiences of and benefits to a patient with late-stage HD admitted to our Neuro-Palliative Care service.

Case Presentation: We present the case of a patient with a 16-year history of HD from time of initial genetic testing to admission to our Neuro-Palliative Care service with late-stage disease.

Conclusions: Given the prolonged, fluctuating and heterogenous HD trajectory, measures need to be implemented to improve earlier access to multi-specialty integrative palliative care services. Given the good outcomes of our case, we strongly advocate for the role of specialised Neuro-Palliative Care services to bridge the gap between clinical need and accessibility.
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http://dx.doi.org/10.1186/s12904-021-00744-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8017854PMC
April 2021

Determinants of nurse manager job satisfaction: A systematic review.

Int J Nurs Stud 2021 Feb 20;118:103906. Epub 2021 Feb 20.

Faculty of Nursing, Edmonton Clinic Health Academy, University of Alberta, 11405 87 Ave NW, Edmonton, Alberta T6G 1C9, Canada. Electronic address:

Background: Front-line nurse managers provide direct oversight of healthcare delivery to ensure organizational expectations are implemented to achieve optimal patient and staff outcomes. Ensuring the job satisfaction of front-line nurse managers is key to retaining these individuals in their roles. Understanding factors influencing job satisfaction of nurse managers can support the development and implementation of strategies to enhance job satisfaction and sustain retention.

Objectives: We aimed to systematically review the empirical literature measuring determinants of job satisfaction among nurse managers.

Design: We conducted a systematic review using 11 electronic databases.

Data Sources: Electronic databases included ABI Inform, Academic Search Premier, CINAHL, EMBASE, ERIC, Health Source Nursing, Medline, ProQuest Dissertations and Theses, PsychINFO, and LILACS.

Review Methods: We included research articles that examined the determinants of job satisfaction for front-line nurse managers. Two research team members independently reviewed and determined inclusion of each study. Each study was appraised independently for quality by two team members. Data extraction was completed for included studies. Content analysis was used to categorize factors associated with job satisfaction of nurse managers.

Results: A total of 5608 articles were screened for inclusion or exclusion. Thirty-eight studies were included. One hundred and one factors influencing nurse manager job satisfaction were reported in the included studies. Factors were grouped into three main categories: job characteristics, organizational characteristics, and personal characteristics. Most factors were examined in single studies or their relationship with job satisfaction was equivocal. However, across these categories, findings included significant positive relationships between autonomy, power, social support among team members and job satisfaction of front-line nurse managers. A significant negative relationship between job stress and nurse manager job satisfaction was indicated in the findings.

Conclusions: Promoting autonomy, power to make decisions for change, social support, team cohesion, and strategies to reduce job stress may improve job satisfaction of front-line nurse managers. Innovative solutions such as co-management and targeted administrative and electronic resources warrant further investigation. Promoting prosocial group behaviours, team building, coaching and the implementation of wellness programs may improve social support, team cohesion, and wellbeing. Examining factors of nurse managers job satisfaction beyond the acute care setting could provide further insights into the role that the practice environment plays in nurse manager job satisfaction.

Tweetable Abstract: Promoting autonomy, power to effect decisions for change, social support, team cohesion, and strategies to reduce job stress are important drivers of job satisfaction of front-line managers.
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http://dx.doi.org/10.1016/j.ijnurstu.2021.103906DOI Listing
February 2021

Mycotoxin occurrence in breast milk and exposure estimation of lactating mothers using urinary biomarkers in São Paulo, Brazil.

Environ Pollut 2021 Mar 12;279:116938. Epub 2021 Mar 12.

Department of Food Engineering, School of Animal Science and Food Engineering, University of São Paulo, Av. Duque de Caxias Norte, 225, CEP 13635-900, Pirassununga, SP, Brazil. Electronic address:

In this study, the occurrence of aflatoxins (AFs), fumonisins (FBs), ochratoxin A (OTA), deoxynivalenol (DON), zearalenone (ZEN) and some of their metabolites were assessed in breast milk and urine of lactating women (N = 74) from Pirassununga, São Paulo, Brazil. Exposure estimations through urinary mycotoxin biomarkers was also performed. Samples were collected in four sampling times (May and August 2018, February and July 2019) and analyzed by liquid chromatography coupled to tandem mass spectrometry. Aflatoxin M (AFM) was not detected in breast milk. However, two samples (3%) presented FB at 2200 and 3400 ng/L, while 4 samples (5%) had OTA at the median level of 360 ng/L. In urine, AFM and aflatoxin P (AFP) were found in 51 and 11% of samples, respectively (median levels: 0.16 and 0.07 ng/mg creatinine, respectively). Urinary DON (median level: 38.59 ng/mg creatinine), OTA (median level: 2.38 ng/mg creatinine) and ZEN (median level: 0.02 ng/mg of creatinine) were quantified in 18, 8 and 10% of the samples, respectively. Mean probable daily intake (PDI) values based on urinary biomarkers were 1.58, 1.09, 5.07, and 0.05 μg/kg body weight/day for AFM, DON, OTA, and ZEN, respectively. Although a low mycotoxin occurrence was detected in breast milk, the PDI for the genotoxic AFs was much higher than those reported previously in Brazil, while PDI values obtained for OTA and DON were higher than recommended tolerable daily intakes. These outcomes warrant concern on the exposure of lactating women to these mycotoxins in the studied area.
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http://dx.doi.org/10.1016/j.envpol.2021.116938DOI Listing
March 2021

Association of Children's Mode of School Instruction with Child and Parent Experiences and Well-Being During the COVID-19 Pandemic - COVID Experiences Survey, United States, October 8-November 13, 2020.

MMWR Morb Mortal Wkly Rep 2021 Mar 19;70(11):369-376. Epub 2021 Mar 19.

In March 2020, efforts to slow transmission of SARS-CoV-2, the virus that causes COVID-19, resulted in widespread closures of school buildings, shifts to virtual educational models, modifications to school-based services, and disruptions in the educational experiences of school-aged children. Changes in modes of instruction have presented psychosocial stressors to children and parents that can increase risks to mental health and well-being and might exacerbate educational and health disparities (1,2). CDC examined differences in child and parent experiences and indicators of well-being according to children's mode of school instruction (i.e., in-person only [in-person], virtual-only [virtual], or combined virtual and in-person [combined]) using data from the COVID Experiences nationwide survey. During October 8-November 13, 2020, parents or legal guardians (parents) of children aged 5-12 years were surveyed using the NORC at the University of Chicago AmeriSpeak panel,* a probability-based panel designed to be representative of the U.S. household population. Among 1,290 respondents with a child enrolled in public or private school, 45.7% reported that their child received virtual instruction, 30.9% in-person instruction, and 23.4% combined instruction. For 11 of 17 stress and well-being indicators concerning child mental health and physical activity and parental emotional distress, findings were worse for parents of children receiving virtual or combined instruction than were those for parents of children receiving in-person instruction. Children not receiving in-person instruction and their parents might experience increased risk for negative mental, emotional, or physical health outcomes and might need additional support to mitigate pandemic effects. Community-wide actions to reduce COVID-19 incidence and support mitigation strategies in schools are critically important to support students' return to in-person learning.
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http://dx.doi.org/10.15585/mmwr.mm7011a1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7976614PMC
March 2021

Long-term change in the parasite burden of shore crabs ( and ) on the northwestern Pacific coast of North America.

Proc Biol Sci 2021 Feb 24;288(1945):20203036. Epub 2021 Feb 24.

School of Aquatic and Fishery Sciences, University of Washington, Seattle, WA 98195, USA.

The abundances of free-living species have changed dramatically in recent decades, but little is known about change in the abundance of parasitic species. We investigated whether populations of several parasites have shifted over time in two shore crab hosts, and by comparing the prevalence and abundance of three parasite taxa in a historical dataset (1969-1970) to contemporary parasite abundance (2018-2020) for hosts collected from 11 intertidal sites located from Oregon, USA, to British Columbia, Canada. Our data suggest that the abundance of the parasitic isopod has varied around a stable mean for the past 50 years. No change over time was observed for larval acanthocephalans. However, larval microphallid trematodes increased in prevalence over time among hosts, from a mean of 8.4-61.8% between the historical and contemporary time points. The substantial increase in the prevalence of larval microphallid trematodes could be owing to increased abundances of their bird final hosts, increased production of parasite infective stages by snail intermediate hosts or both. Our study highlights the variability among parasite species in their temporal trajectories of change.
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http://dx.doi.org/10.1098/rspb.2020.3036DOI Listing
February 2021

Moving Toward a New Horizon of Pediatric Stroke Intervention.

Stroke 2021 Mar 22;52(3):789-791. Epub 2021 Feb 22.

Divisions of Child and Vascular Neurology, Department of Neurology, Johns Hopkins School of Medicine, Baltimore, MD (R.J.F.).

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http://dx.doi.org/10.1161/STROKEAHA.120.033496DOI Listing
March 2021

Presidential youth fitness program implementation: An antecedent to organizational change.

Eval Program Plann 2021 Jun 10;86:101919. Epub 2021 Feb 10.

Centers for Disease Control and Prevention, Division of Population Health, United States.

Introduction: Grounded in organizational change theory, the purpose of this study was to investigate the efficacy of the Presidential Youth Fitness Program (PYFP) and its association with healthy cultures within schools.

Methods: Using a qualitative approach, data were collected through interviews, site visits and artifacts across 374 schools. An explanatory collective case study approach was used to identify key events related to implementation.

Results: Pivotal antecedents to organizational change included prolonged, continual PD, direct support of PYFP implementation, and recognition. Further, three key themes of leveling of the playing field, strategically overcoming barriers, and recruiting teacher fitness champions were identified.

Conclusions: Creating a healthy school culture was an unexpected, but feasible outcome stemming from the implementation of the PYFP. A collective effort, led by physical education teachers and fitness champions and embraced by the administration, faculty, and community, is necessary for the school culture to unfreeze from its present status.
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http://dx.doi.org/10.1016/j.evalprogplan.2021.101919DOI Listing
June 2021

Syk/NF-κB-targeted anti-inflammatory activity of Melicope accedens (Blume) T.G. Hartley methanol extract.

J Ethnopharmacol 2021 May 1;271:113887. Epub 2021 Feb 1.

Department of Integrative Biotechnology, Sungkyunkwan University, Suwon, 16419, Republic of Korea. Electronic address:

Ethnopharmacological Relevance: Melicope accedens (Blume) Thomas G. Hartley is a plant included in the family Rutaceae and genus Melicope. It is a native plant from Vietnam that has been used for ethnopharmacology. In Indonesia and Malaysia, the leaves of M. accedens are applied externally to decrease fever.

Aim Of The Study: The molecular mechanisms of the anti-inflammatory properties of M. accedens are not yet understood. Therefore, we examined those mechanisms using a methanol extract of M. accedens (Ma-ME) and determined the target molecule in macrophages.

Materials And Methods: We evaluated the anti-inflammatory effects of Ma-ME in lipopolysaccharide (LPS)-stimulated RAW264.7 cells and in an HCl/EtOH-triggered gastritis model in mice. To investigate the anti-inflammatory activity, we performed a nitric oxide (NO) production assay and ELISA assay for prostaglandin E2 (PGE). RT-PCR, luciferase gene reporter assays, western blotting analyses, and a cellular thermal shift assay (CETSA) were conducted to identify the mechanism and target molecule of Ma-ME. The phytochemical composition of Ma-ME was analyzed by HPLC and LC-MS/MS.

Results: Ma-ME suppressed the production of NO and PGE and the mRNA expression of proinflammatory genes (iNOS, IL-1β, and COX-2) in LPS-stimulated RAW264.7 cells without cytotoxicity. Ma-ME inhibited NF-κB activation by suppressing signaling molecules such as IκBα, Akt, Src, and Syk. Moreover, the CETSA assay revealed that Ma-ME binds to Syk, the most upstream molecule in the NF-κB signal pathway. Oral administration of Ma-ME not only alleviated inflammatory lesions, but also reduced the gene expression of IL-1β and p-Syk in mice with HCl/EtOH-induced gastritis. HPLC and LC-MS/MS analyses confirmed that Ma-ME contains various anti-inflammatory flavonoids, including quercetin, daidzein, and nevadensin.

Conclusions: Ma-ME exhibited anti-inflammatory activities in vitro and in vivo by targeting Syk in the NF-κB signaling pathway. Therefore, we propose that Ma-ME could be used to treat inflammatory diseases such as gastritis.
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http://dx.doi.org/10.1016/j.jep.2021.113887DOI Listing
May 2021

Parl. Extracts Reduce Acute Inflammation by Targeting Oxidative Stress.

Evid Based Complement Alternat Med 2021 13;2021:7924645. Epub 2021 Jan 13.

College of Pharmacy, Chung-Ang University, Seoul 06974, Republic of Korea.

Parl. (PTP) has traditionally been used for edible and medicinal purposes to treat several disorders, including diabetes and neuralgia. Therefore, this study sought to evaluate the inhibitory effects of PTP leaf ethanol extracts on acute inflammation. Moreover, the reactive oxygen species (ROS) scavenging activity, superoxide dismutase (SOD) activity, lipopolysaccharide (LPS)-induced nitric oxide (NO) generation, and HO-induced lipid peroxidation capacity of PTP were assessed in RAW 264.7 macrophages. Our results suggest that PTP prevents cell damage caused by oxidative free radicals and downregulates the expression of LPS-induced inflammation-associated factors including inducible nitric oxidase synthetase (iNOS), cyclooxygenase-2 (COX-2), and prostaglandin E (PGE). PTP inhibited NO production by 53.5% ( < 0.05) and iNOS expression by 71.5% ( < 0.01) at 100 g/mL. PTP at 100 g/mL also inhibited ROS generation by 58.2% ( < 0.01) and SOD activity by 29.3%, as well as COX-2 expression by 83.3% ( < 0.01) and PGE2 expression by 98.6% ( < 0.01). The anti-inflammatory effects of PTP were confirmed using an arachidonic acid (AA)-induced ear edema mouse model. Ear thickness and myeloperoxidase (MPO) activity were evaluated as indicators of inflammation. PTP inhibited edema formation by 64.5% ( < 0.05) at 1.0 mg/ear. A total of 16 metabolites were identified in PTP extracts and categorized into subgroups, including two phenolic acids (mainly quinic acid), seven flavonoids, five lignans, one sesquiterpenoid, and one long-chain fatty acid. Therefore, our results suggest that PTP possesses anti-inflammatory properties.
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http://dx.doi.org/10.1155/2021/7924645DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7817271PMC
January 2021

The Effect of Patient Specific Factors on Occlusal Forces Generated: Best Evidence Consensus Statement.

J Prosthodont 2021 Apr;30(S1):52-60

Department of Restorative Dentistry, University of Detroit Mercy School of Dentistry, Detroit, MI.

Purpose: The purpose of this Best Evidence Consensus Statement was to search the literature to determine if there is a relationship between patient specific factors and occlusal force.

Materials And Methods: A literature review was conducted in the following databases: Evidence-Based Medicine Reviews (EBMR), Cochrane Database of Systematic Reviews, Embase, and Ovid MEDLINE(R) and Epub Ahead of Print. Articles on patient factors and occlusal force were compiled by using a combination of the key words: "bite force," "occlusal force," "partial and complete edentulism," "bruxism," and "orthognathic class." Inclusion criteria included meta-analyses, systematic reviews, randomized controlled trials, case series, and journal articles. Exclusion criteria were case reports, studies in children, animals, and bench studies.

Results: Of the 1502 articles that met the initial search criteria, 97 related to patient-specific factors affecting occlusal forces. These articles were evaluated, rated, and organized into appropriate categories addressing questions of foci.

Conclusions: The range of occlusal force is highly variable among subjects correlated to patient specific factors such as age, gender, partial and complete edentulism, the presence of a maxillofacial defect, location of edentulous area, orthognathic profile, and magnitude of occlusal vertical dimension. Tooth replacement therapies targeted at increasing occlusal contact seem to have a positive effect on increasing occlusal force. Bruxism does not necessarily demonstrate higher occlusal powering but may have greater tooth contact time. Occlusal force is not clearly affected by the type of dental restoration or restorative material used. The clinical significance of the changes in occlusal forces is yet to be determined.
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http://dx.doi.org/10.1111/jopr.13334DOI Listing
April 2021

The essentials of nursing leadership: A systematic review of factors and educational interventions influencing nursing leadership.

Int J Nurs Stud 2021 Mar 7;115:103842. Epub 2020 Dec 7.

Faculty of Nursing, Edmonton Clinic Health Academy, University of Alberta, 11405 87 Ave NW, Edmonton, AB T6G 1C9, Canada.

Background: Nursing leadership plays a vital role in shaping outcomes for healthcare organizations, personnel and patients. With much of the leadership workforce set to retire in the near future, identifying factors that positively contribute to the development of leadership in nurses is of utmost importance.

Objectives: To identify determining factors of nursing leadership, and the effectiveness of interventions to enhance leadership in nurses.

Design: We conducted a systematic review, including a total of nine electronic databases.

Data Sources: Databases included: Medline, Academic Search Premier, Embase, PsychInfo, Sociological Abstracts, ABI, CINAHL, ERIC, and Cochrane.

Review Methods: Studies were included if they quantitatively examined factors contributing to nursing leadership or educational interventions implemented with the intention of developing leadership practices in nurses. Two research team members independently reviewed each article to determine inclusion. All included studies underwent quality assessment, data extraction and content analysis.

Results: 49,502 titles/abstracts were screened resulting in 100 included manuscripts reporting on 93 studies (n=44 correlational studies and n=49 intervention studies). One hundred and five factors examined in correlational studies were categorized into 5 groups experience and education, individuals' traits and characteristics, relationship with work, role in the practice setting, and organizational context. Correlational studies revealed mixed results with some studies finding positive correlations and other non-significant relationships with leadership. Participation in leadership interventions had a positive impact on the development of a variety of leadership styles in 44 of 49 intervention studies, with relational leadership styles being the most common target of interventions.

Conclusions: The findings of this review make it clear that targeted educational interventions are an effective method of leadership development in nurses. However, due to equivocal results reported in many included studies and heterogeneity of leadership measurement tools, few conclusions can be drawn regarding which specific nurse characteristics and organizational factors most effectively contribute to the development of nursing leadership. Contextual and confounding factors that may mediate the relationships between nursing characteristics, development of leadership and enhancement of leadership development programs also require further examination. Targeted development of nursing leadership will help ensure that nurses of the future are well equipped to tackle the challenges of a burdened health-care system.
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http://dx.doi.org/10.1016/j.ijnurstu.2020.103842DOI Listing
March 2021

Stereodivergent Carbon-Carbon Bond Formation between Iminium and Enolate Intermediates by Synergistic Organocatalysis.

J Am Chem Soc 2021 Jan 24;143(1):73-79. Epub 2020 Dec 24.

Department of Chemistry, Yonsei University, Seoul 03722, Republic of Korea.

We report here a stereodivergent method for the Michael addition of aryl acetic acid esters to α,β-unsaturated aldehydes catalyzed by a combination of a chiral pyrrolidine and a chiral Lewis base. This reaction proceeds through a synergistic catalytic cycle which consists of one cycle leading to a chiral iminium electrophile and a second cycle generating a nucleophilic chiral enolate for the construction of a carbon-carbon bond. By varying the combinations of catalyst enantiomers, all four stereoisomers of the products with two vicinal stereocenters are accessible with high enantio- and diastereoselectivity. The products of the Michael addition, 1,5-aldehyde esters, can be readily transformed into a variety of other valuable enantioenriched structures, including those bearing three contiguous stereocenters in an acyclic system, thus providing an efficient route to an array of structural and stereochemical diversity.
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http://dx.doi.org/10.1021/jacs.0c11077DOI Listing
January 2021

The Anti-Cancer Effect of Linusorb B3 from Flaxseed Oil through the Promotion of Apoptosis, Inhibition of Actin Polymerization, and Suppression of Src Activity in Glioblastoma Cells.

Molecules 2020 Dec 12;25(24). Epub 2020 Dec 12.

Department of Integrative Biotechnology, Biomedical Institute for Convergence at SKKU (BICS), Sungkyunkwan University, Suwon 16419, Korea.

Linusorbs (LOs) are natural peptides found in flaxseed oil that exert various biological activities. Of LOs, LOB3 ([1-9-NαC]-linusorb B3) was reported to have antioxidative and anti-inflammatory activities; however, its anti-cancer activity has been poorly understood. Therefore, this study investigated the anti-cancer effect of LOB3 and its underlying mechanism in glioblastoma cells. LOB3 induced apoptosis and suppressed the proliferation of C6 cells by inhibiting the expression of anti-apoptotic genes, B cell lymphoma 2 (Bcl-2) and p53, as well as promoting the activation of pro-apoptotic caspases, caspase-3 and -9. LOB3 also retarded the migration of C6 cells, which was achieved by suppressing the formation of the actin cytoskeleton critical for the progression, invasion, and metastasis of cancer. Moreover, LOB3 inhibited the activation of the proto-oncogene, Src, and the downstream effector, signal transducer and activator of transcription 3 (STAT3), in C6 cells. Taken together, these results suggest that LOB3 plays an anti-cancer role by inducing apoptosis and inhibiting the migration of C6 cells through the regulation of apoptosis-related molecules, actin polymerization, and proto-oncogenes.
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http://dx.doi.org/10.3390/molecules25245881DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7764463PMC
December 2020

Insights on the Quest for the Structure-Function Relationship of the Mitochondrial Pyruvate Carrier.

Biology (Basel) 2020 Nov 19;9(11). Epub 2020 Nov 19.

São Carlos Institute of Physics, University of São Paulo, São Carlos 13563-120, Brazil.

The molecular identity of the mitochondrial pyruvate carrier (MPC) was presented in 2012, forty years after the active transport of cytosolic pyruvate into the mitochondrial matrix was first demonstrated. An impressive amount of and studies has since revealed an unexpected interplay between one, two, or even three protein subunits defining different functional MPC assemblies in a metabolic-specific context. These have clear implications in cell homeostasis and disease, and on the development of future therapies. Despite intensive efforts by different research groups using state-of-the-art computational tools and experimental techniques, MPCs' structure-based mechanism remains elusive. Here, we review the current state of knowledge concerning MPCs' molecular structures by examining both earlier and recent studies and presenting novel data to identify the regulatory, structural, and core transport activities to each of the known MPC subunits. We also discuss the potential application of cryogenic electron microscopy (cryo-EM) studies of MPC reconstituted into nanodiscs of synthetic copolymers for solving human MPC2.
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http://dx.doi.org/10.3390/biology9110407DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7699257PMC
November 2020

Anti-Melanogenic Effects of Ethanol Extracts of the Leaves and Roots of (Thunb.) Juss through Their Inhibition of CREB and Induction of ERK and Autophagy.

Molecules 2020 Nov 17;25(22). Epub 2020 Nov 17.

Department of Integrative Biotechnology and Biomedical, Institute for Convergence at SKKU (BICS), Sungkyunkwan University, Suwon 16419, Korea.

(Thunb.) Juss is a traditional herb commonly used in East Asia including Korea, Japan, and China. It has been administered to reduce and treat inflammation in Donguibogam, Korea. The mechanism for its anti-inflammatory effects has already been reported. In this study, we confirmed the efficacy of (Thunb.) Juss ethanol extract (Pv-EE) for inducing autophagy and investigate its anti-melanogenic properties. Melanin secretion and content were investigated using cells from the melanoma cell line B16F10. Pv-EE inhibited melanin in melanogenesis induced by α-melanocyte-stimulating hormone (α-MSH). The mechanism of inhibition of Pv-EE was confirmed by suppressing the mRNA of microphthalmia-associated transcription factor (MITF), decreasing the phosphorylation level of CREB, and increasing the phosphorylation of ERK. Finally, it was confirmed that Pv-EE induces autophagy through the autophagy markers LC3B and p62, and that the anti-melanogenic effect of Pv-EE is inhibited by the autophagy inhibitor 3-methyl adenine (3-MA). These results suggest that Pv-EE may be used as a skin protectant due to its anti-melanin properties including autophagy.
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http://dx.doi.org/10.3390/molecules25225375DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7698407PMC
November 2020

Boron Lewis Acid-Catalyzed Hydrophosphinylation of -Heteroaryl-Substituted Alkenes with Secondary Phosphine Oxides.

J Org Chem 2020 Dec 12;85(23):15476-15487. Epub 2020 Nov 12.

Department of Chemistry, Yonsei University, Seoul 03722, Republic of Korea.

We report the boron-catalyzed hydrophosphinylation of -heteroaryl-substituted alkenes with secondary phosphine oxides that furnishes various phosphorus-containing -heterocycles. This process proceeds under mild conditions and enables the introduction of a phosphorus atom into multisubstituted alkenylazaarenes. The available mechanistic data can be explained by a reaction pathway wherein the C-P bond is created by the reaction between the activated alkene (by coordination to a boron catalyst) and the phosphorus(III) nucleophile (in tautomeric equilibrium with phosphine oxide).
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http://dx.doi.org/10.1021/acs.joc.0c02246DOI Listing
December 2020

Clinical Diffusion Mismatch to Select Pediatric Patients for Embolectomy 6 to 24 Hours After Stroke: An Analysis of the Save ChildS Study.

Neurology 2021 01 3;96(3):e343-e351. Epub 2020 Nov 3.

From the Department of Neuroradiology (P.B.S., M.-N.P., A.B.), Clinic for Radiology & Nuclear Medicine, University Hospital Basel, Switzerland; Department of Diagnostic and Interventional Neuroradiology (P.B.S., U.H., G.B., J.F.), University Medical Center Hamburg-Eppendorf, Hamburg; Departments of Pediatrics (R.S.), and Neurology (J.M.), University Hospital of Muenster; Department of Neuroradiology (R.C.), Alfried-Krupp Hospital, Essen; Department of Neuroradiology (H.H., E.H.), Klinikum Stuttgart, Germany; Department of Neuroradiology (A.G.), Medical University of Innsbruck, Austria; Department for Diagnostic and Interventional Neuroradiology (F.D.), University of Munich (LMU), Campus Grosshadern; Department of Neuroradiology (O.N., M.W.), RWTH Aachen University; Diagnostic and Interventional Neuroradiology (G.B.), Eberhard Karls University Tuebingen; Department of Radiology and Neuroradiology (A.W.), University Hospital Knappschaftskrankenhaus Bochum Langendreer; Department of Neuroradiology (D.K.), University Hospital Carl Gustav Carus, Dresden7; Department of Neuroradiology (U.Y.), Saarland University Hospital, Homburg, Germany; ASST Valcamonica (A.M.), Ospedale di Esine, UOSD Neurologia, Esine, Italy; Division of Neuroradiology and Musculoskeletal Radiology (W.M.), Department of Biomedical Imaging and Image-Guided Therapy, and Department of Biomedical Imaging and Image-Guided Therapy (R.N.), Division of Cardiovascular and Interventional Radiology, Medical University of Vienna, Austria; Department of Radiology and Neuroradiology (U.J.-K.), University Hospital of Schleswig-Holstein, Kiel; Section of Neuroradiology (M.B.), University of Ulm, Guenzburg; Department for Neuroradiology (S.S.), University Hospital Leipzig; Department of Neuroradiology (O.B.), University Hospital of Magdeburg; Department of Diagnostic and Interventional Neuroradiology (F.G.), Hannover Medical School, Germany; Institute of Neuroradiology (J.T.), Kepler University Hospital, Johannes Kepler University Linz, Austria; Institute of Neuroradiology (B.T.), University Hospital Duesseldorf; Department of Neuroradiology at Heidelberg University Hospital (M.M.); Department of Radiology (C.W.), University Hospital Regensburg; Department of Neuroradiology (P.S., A. Kemmling), University Hospital of Luebeck, Germany; Department of Neurology (P.L.M.), Massachusetts General Hospital, Harvard Medical School, Boston; Division of Child Neurology (S.L.), Department of Neurology, Stanford University, CA; Department of Neuroradiology (M.S.), University Hospital of Cologne; Department of Diagnostic and Interventional Radiology and Neuroradiology (A.R.), University Hospital Essen, University of Duisburg-Essen; Institute of Epidemiology and Social Medicine (A. Karch, N.R.), University of Muenster; and Department of Radiology, University of Munich (LMU) (M.W.), Campus Grosshadern, Germany.

Objective: To determine whether thrombectomy is safe in children up to 24 hours after onset of symptoms when selected by mismatch between clinical deficit and infarct.

Methods: A secondary analysis of the Save ChildS Study (January 2000-December 2018) was performed, including all pediatric patients (<18 years) diagnosed with arterial ischemic stroke who underwent endovascular recanalization at 27 European and United States stroke centers. Patients were included if they had a relevant mismatch between clinical deficit and infarct.

Results: Twenty children with a median age of 10.5 (interquartile range [IQR] 7-14.6) years were included. Of those, 7 were male (35%), and median time from onset to thrombectomy was 9.8 (IQR 7.8-16.2) hours. Neurologic outcome improved from a median Pediatric NIH Stroke Scale score of 12.0 (IQR 8.8-20.3) at admission to 2.0 (IQR 1.2-6.8) at day 7. Median modified Rankin Scale (mRS) score was 1.0 (IQR 0-1.6) at 3 months and 0.0 (IQR 0-1.0) at 24 months. One patient developed transient peri-interventional vasospasm; no other complications were observed. A comparison of the mRS score to the mRS score in the DAWN and DEFUSE 3 trials revealed a higher proportion of good outcomes in the pediatric compared to the adult study population.

Conclusions: Thrombectomy in pediatric ischemic stroke in an extended time window of up to 24 hours after onset of symptoms seems safe and neurologic outcomes are generally good if patients are selected by a mismatch between clinical deficit and infarct.

Classification Of Evidence: This study provides Class IV evidence that for children with acute ischemic stroke with a mismatch between clinical deficit and infarct size, thrombectomy is safe.
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http://dx.doi.org/10.1212/WNL.0000000000011107DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7884981PMC
January 2021

Vision Screening among Children with Autism Spectrum Disorder.

Optom Vis Sci 2020 Nov;97(11):917-928

NOVA Southeastern University College of Optometry, Ft. Lauderdale, Florida.

Significance: Vision problems occur at higher rates in children with autism spectrum disorder (ASD) than in the general population. Some professional organizations recommend that children with neurodevelopmental disorders need comprehensive assessment by eye care professionals rather than vision screening.

Methods: Data from the 2011 to 2012 National Survey of Children's Health (NSCH) were accessed. Logistic regression was used to evaluate differences between vision screening rates in eye care professionals' offices and other screening locations among children with and without ASD.

Results: Overall, 82.21% (95% confidence interval [CI], 78.35 to 86.06%) of children with ASD were reported to have had a vision screening as defined by the NSCH criteria. Among children younger than 5 years with ASD, 8.87% (95% CI, 1.27 to 16.5%) had a vision screening at a pediatrician's office, 41.1% (95% CI, 20.54 to 61.70%) were screened at school, and 37.62% (95% CI, 9.80 to 55.45%) were examined by an eye care professionals. Among children with ASD older than 5 years, 24.84% (95% CI, 18.42 to 31.26%) were screened at school, 22.24% (95% CI, 17.26 to 27.21%) were screened at the pediatricians' office, and 50.15% (95% CI, 44.22 to 56.08%) were examined by eye care professionals. Based on estimates from NSCH, no children in the U.S. population younger than 5 years with ASD screened in a pediatrician's office were also seen by an eye care provider.

Conclusions: If the public health goal is to have all children with ASD assessed in an eye care professional's office, data from the NSCH indicate that we as a nation are falling far short of that target.
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http://dx.doi.org/10.1097/OPX.0000000000001593DOI Listing
November 2020

Hypermethylation and global remodelling of DNA methylation is associated with acquired cisplatin resistance in testicular germ cell tumours.

Epigenetics 2020 Oct 30:1-14. Epub 2020 Oct 30.

Department of Comparative Biosciences, The University of Illinois at Urbana-Champaign , Urbana, IL, USA.

Testicular germ cell tumours (TGCTs) respond well to cisplatin-based therapy. However, cisplatin resistance and poor outcomes do occur. It has been suggested that a shift towards DNA hypermethylation mediates cisplatin resistance in TGCT cells, although there is little direct evidence to support this claim. Here we utilized a series of isogenic cisplatin-resistant cell models and observed a strong association between cisplatin resistance in TGCT cells and a net increase in global CpG and non-CpG DNA methylation spanning regulatory, intergenic, genic and repeat elements. Hypermethylated loci were significantly enriched for repressive DNA segments, CTCF and RAD21 sites and lamina associated domains, suggesting that global nuclear reorganization of chromatin structure occurred in resistant cells. Hypomethylated CpG loci were significantly enriched for EZH2 and SUZ12 binding and H3K27me3 sites. Integrative transcriptome and methylome analyses showed a strong negative correlation between gene promoter and CpG island methylation and gene expression in resistant cells and a weaker positive correlation between gene body methylation and gene expression. A bidirectional shift between gene promoter and gene body DNA methylation occurred within multiple genes that was associated with upregulation of polycomb targets and downregulation of tumour suppressor genes. These data support the hypothesis that global remodelling of DNA methylation is a key factor in mediating cisplatin hypersensitivity and chemoresistance of TGCTs and furthers the rationale for hypomethylation therapy for refractory TGCT patients.
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http://dx.doi.org/10.1080/15592294.2020.1834926DOI Listing
October 2020

Do Better Operative Reports Equal Better Surgery? A Comparative Evaluation of Compliance With Operative Standards for Cancer Surgery.

Am Surg 2020 Oct 30;86(10):1281-1288. Epub 2020 Oct 30.

Department of Surgery, School of Medicine, Loma Linda University, Loma Linda, CA, USA.

To improve the quality of cancer operations, the American College of Surgeons published , which has been incorporated into Commission on Cancer (CoC) accreditation requirements. We sought to determine if compliance with operative standards was associated with technical surgical outcomes. Oncologic operative reports from 2017 at a CoC and non-CoC institution were examined for documentation of essential steps. Lymph node (LN) yield for lung and colon cases and re-excision rates for breast cases were recorded. Correct documentation was poor for colon, breast, and lung cases with numerous elements documented in <10% of operative reports at both centers. For lung cases, there was no significant difference in meeting ≥10 LN benchmark or average LN yield between the 2 institutions. For colon cases, average lymph node yield was lower in the non-CoC facility, but there was no significant difference in meeting ≥12 LN benchmark. For breast cases, re-excision rates were similar in both programs. Many essential steps in were poorly documented in operative reports, regardless of CoC status. Achieving benchmark technical surgical outcomes was not associated with documented compliance with these standards. Whether improved documentation leads to better surgical outcomes requires further investigation.
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http://dx.doi.org/10.1177/0003134820964225DOI Listing
October 2020

Lewis acid-catalyzed double addition of indoles to ketones: synthesis of bis(indolyl)methanes with all-carbon quaternary centers.

Org Biomol Chem 2020 Nov 30;18(44):9060-9064. Epub 2020 Oct 30.

Department of Chemistry, Yonsei University, Seoul 03722, South Korea.

We report herein a Lewis acid-catalyzed nucleophilic double-addition of indoles to ketones under mild conditions. This process occurs with various ketones ranging from dialkyl ketones to diaryl ketones, thereby providing access to an array of bis(indolyl)methanes bearing all-carbon quaternary centers, including tetra-aryl carbon centers. The products can be transformed into bis(indole)-fused polycyclics and bis(indolyl)alkenes.
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http://dx.doi.org/10.1039/d0ob01916jDOI Listing
November 2020

Assessment of Dietary Acculturation in East Asian Populations: A Scoping Review.

Adv Nutr 2020 Oct 29. Epub 2020 Oct 29.

Department of Nutrition, Dietetics, and Food, Faculty of Medicine Nursing and Health Sciences, Monash University, Be Active Sleep Eat (BASE) Facility, Notting Hill, Victoria, Australia.

East Asian immigrants face multiple challenges upon arrival in their destination country, including an increased risk of future diabetes and cardiovascular disease development. The adoption of food and eating patterns of their host country (i.e., dietary acculturation) may contribute to this increased disease risk. To effectively examine the dietary acculturation-disease risk relationship in East Asian immigrants, sensitive tools are necessary; however, there has been no systematic review of the methods used to assess dietary acculturation in this population. A systematic scoping review of the literature was undertaken to address this gap. A systematic search was conducted in December 2019 and returned a total of 6140 papers. Manuscripts were screened independently by 2 reviewers, resulting in the final inclusion of 30 papers reporting on 27 studies. Robust measures of dietary acculturation were lacking, with only 6 studies using validated tools. Most studies used self-reported cross-sectional surveys to determine how the individual's diet had changed since immigrating, with responses provided on Likert scales. Only 3 quantitative longitudinal studies used prospective measures of diet change, through serial food-frequency questionnaires. Qualitative studies explored dietary acculturation and factors influencing change in diet through semi-structured interviews and focus groups.  This review found there is no consensus in the literature on how to most effectively measure the magnitude and process of dietary acculturation in East Asian populations. There is a need for robust, longitudinal, and mixed-method study designs to address the lack of evidence and develop more comprehensive tools measuring dietary acculturation. Improving the assessment methods used to measure dietary acculturation is critical in helping to monitor the impact of interventions or policies aimed at reducing diet-related disease risk in East Asian immigrant populations.
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http://dx.doi.org/10.1093/advances/nmaa127DOI Listing
October 2020

Impact of Robotic Surgery on Residency Training for Herniorrhaphy and Cholecystectomy.

Am Surg 2020 Oct 25;86(10):1318-1323. Epub 2020 Oct 25.

Department of Surgery, School of Medicine, University of California, Riverside, Riverside, CA, USA.

Robotic surgery has increased for common general surgery procedures. This study evaluates how robotic use affects the case distributions of herniorrhaphy and cholecystectomy for general surgery residents according to postgraduate year (PGY). We reviewed Accreditation Council for Graduate Medical Education (ACGME) biliary or hernia cases logged by surgical residents in the academic year 2017-2018. Operative reports were reviewed to compare approaches (robotic, laparoscopic, and open) by resident role and PGY level. Open cholecystectomies were excluded. Overall, 470 hernia and 657 cholecystectomy cases were logged. Hernia repairs were performed robotically in 15.9%, laparoscopically in 9.5%, and open in 74.7%. Cholecystectomies were performed robotically in 16.4% and laparoscopically in 83.6%. Residents were teaching assistants in 1.8% of hernia repairs and 1.5% of cholecystectomies. Distribution of cases by technique and PGY level was significantly different for both procedures, with chief residents performing the majority of robotic cholecystectomies (52.6%, < .0001) and hernia repairs (59.7%, < .0001). Migration of robotic cases to senior resident level and low percentage of teaching assistant roles held by residents suggest exposure to common operations may be delayed during general surgery residency training. Introduction of new technology in surgical training should be carefully reviewed and may benefit from a structured curriculum.
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http://dx.doi.org/10.1177/0003134820964430DOI Listing
October 2020

Cancer and Tumor-Associated Childhood Stroke: Results From the International Pediatric Stroke Study.

Pediatr Neurol 2020 10 10;111:59-65. Epub 2020 Jun 10.

Division of Neurology, Children's Hospital of Philadelphia, Philadelphia, Pennsylvania; Department of Neurology, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania; Department of Pediatrics, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania.

Background: The prevalence of cancer among children with stroke is unknown. This study sought to evaluate cancer- and tumor-associated childhood ischemic stroke in a multinational pediatric stroke registry.

Methods: Children aged 29 days to less than 19 years with arterial ischemic stroke or cerebral sinovenous thrombosis enrolled in the International Pediatric Stroke Study between January 2003 and June 2019 were included. Data including stroke treatment and recurrence were compared between subjects with and without cancer using Wilcoxon rank sum and chi-square tests.

Results: Cancer or tumor was present in 99 of 2968 children (3.3%) with arterial ischemic stroke and 64 of 596 children (10.7%) with cerebral sinovenous thrombosis. Among children in whom cancer type was identified, 42 of 88 arterial ischemic stroke cases (48%) had brain tumors and 35 (40%) had hematologic malignancies; 45 of 58 cerebral sinovenous thrombosis cases (78%) had hematologic malignancies and eight (14%) had brain tumors. Of 54 cancer-associated arterial ischemic stroke cases with a known cause, 34 (63%) were due to arteriopathy and nine (17%) were due to cardioembolism. Of 46 cancer-associated cerebral sinovenous thrombosis cases with a known cause, 41 (89%) were related to chemotherapy-induced or other prothrombotic states. Children with cancer were less likely than children without cancer to receive antithrombotic therapy for arterial ischemic stroke (58% vs 80%, P = 0.007) and anticoagulation for cerebral sinovenous thrombosis (71% vs 87%, P = 0.046). Recurrent arterial ischemic stroke (5% vs 2%, P = 0.04) and cerebral sinovenous thrombosis (5% vs 1%, P = 0.006) were more common among children with cancer.

Conclusions: Cancer is an important risk factor for incident and recurrent childhood stroke. Stroke prevention strategies for children with cancer are needed.
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http://dx.doi.org/10.1016/j.pediatrneurol.2020.06.002DOI Listing
October 2020

Effect of Lactobacillus rhamnosus on growth of Listeria monocytogenes and Staphylococcus aureus in a probiotic Minas Frescal cheese.

Food Microbiol 2020 Dec 7;92:103557. Epub 2020 Jun 7.

University of São Paulo, School of Animal Science and Food Engineering, Department of Food Engineering, Av. Duque de Caxias Norte, 225, CEP 13635-900, Pirassununga, SP, Brazil. Electronic address:

This study aimed to evaluate the effect of Lactobacillus rhamnosus GG on growth of Staphylococcus aureus and Listeria monocytogenes, inoculated alone or in combination on surface of Minas Frescal cheeses, during storage for 21 days at 7 °C. Survival percentages of each individual bacterial species after exposure to in vitro simulated gastrointestinal conditions (SGC) were also determined. The addition of L. rhamnosus did not affect (P > 0.05) pH, moisture, fat, protein and texture profile of Minas Frescal cheeses. L. rhamnosus was able to survive in suitable counts (>6 Log CFU/g) in cheeses from the 7th day of storage, with high survival (>74.6-86.4%) after SGC. An inhibitory effect of L. rhamnosus on L. monocytogenes was observed in cheeses (decrease of 1.1-1.6 Log CFU/g) and after SGC (20% reduction in the survival). No inhibitory effect of L. rhamnosus was observed on S. aureus counts (P > 0.05), and this microorganism did not survive the exposure to SGC. In conclusion, the addition of L. rhamnosus in Minas Frescal cheese has a potential for L. monocytogenes inhibition. Further studies are necessary to elucidate the mechanisms involved in the inhibition process and determine the survival ability of the bacterial species evaluated in in vivo experiments.
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http://dx.doi.org/10.1016/j.fm.2020.103557DOI Listing
December 2020

Consensus Recommendations on the Use of F-FDG PET/CT in Lung Disease.

J Nucl Med 2020 12 18;61(12):1701-1707. Epub 2020 Sep 18.

Department of Anesthesia, Critical Care, and Pain Medicine, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts.

PET with F-FDG has been increasingly applied, predominantly in the research setting, to study drug effects and pulmonary biology and to monitor disease progression and treatment outcomes in lung diseases that interfere with gas exchange through alterations of the pulmonary parenchyma, airways, or vasculature. To date, however, there are no widely accepted standard acquisition protocols or imaging data analysis methods for pulmonary F-FDG PET/CT in these diseases, resulting in disparate approaches. Hence, comparison of data across the literature is challenging. To help harmonize the acquisition and analysis and promote reproducibility, we collated details of acquisition protocols and analysis methods from 7 PET centers. From this information and our discussions, we reached the consensus recommendations given here on patient preparation, choice of dynamic versus static imaging, image reconstruction, and image analysis reporting.
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http://dx.doi.org/10.2967/jnumed.120.244780DOI Listing
December 2020

Serous carcinoma of a prolapsed fallopian tube: A rare cause of a vaginal apex mass.

Gynecol Oncol Rep 2020 Aug 3;33:100618. Epub 2020 Aug 3.

Department of Obstetrics and Gynecology, NYU Langone Health, 550 1st Avenue, New York, NY 10016, USA.

Background: The differential diagnosis for women who present with a vaginal mass after undergoing a hysterectomy is dependent on the indication, type and timing of the hysterectomy. The differential diagnosis includes cervical dysplasia, malignancy, nabothian cysts, prolapsed endocervical polyp/fibroid, abscess, hematoma, granulation tissue, or dehiscence with organ evisceration.

Case: We introduce a case of a woman who presented with a vaginal apex mass and had a remote history of a total hysterectomy for an unknown indication. She was ultimately diagnosed with high grade serous carcinoma of a prolapsed fallopian tube.

Conclusion: This is the first reported case of serous carcinoma of a prolapsed fallopian tube and highlights the importance of maintaining a wide differential diagnosis for women who present with vaginal apex masses.
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http://dx.doi.org/10.1016/j.gore.2020.100618DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7452560PMC
August 2020

Metataxonomics contributes to unravel the microbiota of a Brazilian dairy.

J Dairy Res 2020 Aug 4;87(3):360-363. Epub 2020 Sep 4.

Faculdade de Ciências Farmacêuticas de Ribeirão Preto, Universidade de São Paulo, Ribeirão Preto, São Paulo, Brazil.

For this research communication, 90 samples of a Brazilian dairy were combined into four groups (raw material, final product, food-contact and non-food contact surfaces) and analyzed by metataxonomics based on 16S rRNA gene sequencing. The results showed high alpha-diversity indexes for final product and non-food contact surfaces but, overall, beta-diversity indexes were low. The samples were separated in two main clusters, and the core microbiota was composed by Macrococcus, Alkaliphilus, Vagococcus, Lactobacillus, Marinilactibacillus, Streptococcus, Lysinibacillus, Staphylococcus, Clostridium, Halomonas, Lactococcus, Enterococcus, Bacillus and Psychrobacter. These results highlight that rare taxa occur in dairies, and this may aid the development of strategies for food protection.
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http://dx.doi.org/10.1017/S0022029920000837DOI Listing
August 2020

Risk factors for and prediction of post-intubation hypotension in critically ill adults: A multicenter prospective cohort study.

PLoS One 2020 31;15(8):e0233852. Epub 2020 Aug 31.

Department of Critical Care Medicine, Corpus Christi Medical Center, Corpus Christi, Texas, United States of America.

Objective: Hypotension following endotracheal intubation in the ICU is associated with poor outcomes. There is no formal prediction tool to help estimate the onset of this hemodynamic compromise. Our objective was to derive and validate a prediction model for immediate hypotension following endotracheal intubation.

Methods: A multicenter, prospective, cohort study enrolling 934 adults who underwent endotracheal intubation across 16 medical/surgical ICUs in the United States from July 2015-January 2017 was conducted to derive and validate a prediction model for immediate hypotension following endotracheal intubation. We defined hypotension as: 1) mean arterial pressure <65 mmHg; 2) systolic blood pressure <80 mmHg and/or decrease in systolic blood pressure of 40% from baseline; 3) or the initiation or increase in any vasopressor in the 30 minutes following endotracheal intubation.

Results: Post-intubation hypotension developed in 344 (36.8%) patients. In the full cohort, 11 variables were independently associated with hypotension: increasing illness severity; increasing age; sepsis diagnosis; endotracheal intubation in the setting of cardiac arrest, mean arterial pressure <65 mmHg, and acute respiratory failure; diuretic use 24 hours preceding endotracheal intubation; decreasing systolic blood pressure from 130 mmHg; catecholamine and phenylephrine use immediately prior to endotracheal intubation; and use of etomidate during endotracheal intubation. A model excluding unstable patients' pre-intubation (those receiving catecholamine vasopressors and/or who were intubated in the setting of cardiac arrest) was also developed and included the above variables with the exception of sepsis and etomidate. In the full cohort, the 11 variable model had a C-statistic of 0.75 (95% CI 0.72, 0.78). In the stable cohort, the 7 variable model C-statistic was 0.71 (95% CI 0.67, 0.75). In both cohorts, a clinical risk score was developed stratifying patients' risk of hypotension.

Conclusions: A novel multivariable risk score predicted post-intubation hypotension with accuracy in both unstable and stable critically ill patients.

Study Registration: Clinicaltrials.gov identifier: NCT02508948 and Registered Report Identifier: RR2-10.2196/11101.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0233852PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7458292PMC
October 2020