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Article: Genetic and Epigenetic Discoveries in Human Retinoblastoma.

McEvoy, Justina D / Dyer, Michael A

2015 Volume 20, Issue 3-4, Page(s) 217–225

Abstract: Retinoblastoma is a rare pediatric cancer of the retina. Nearly all retinoblastomas are initiated through the biallelic inactivation of the retinoblastoma tumor susceptibility gene (RB1). Whole-genome sequencing has made it possible to identify secondary ...

Abstract	Retinoblastoma is a rare pediatric cancer of the retina. Nearly all retinoblastomas are initiated through the biallelic inactivation of the retinoblastoma tumor susceptibility gene (RB1). Whole-genome sequencing has made it possible to identify secondary genetic lesions following RB1 inactivation. One of the major discoveries from retinoblastoma sequencing studies is that some retinoblastoma tumors have stable genomes. Subsequent epigenetic studies showed that changes in the epigenome contribute to the rapid progression of retinoblastoma following RB1 gene inactivation. In addition, gene amplification and elevated expression of p53 antagonists, MDM2 and MDM4, may also play an important role in retinoblastoma tumorigenesis. The knowledge gained from these recent molecular, cellular, genomic, and epigenomic analyses are now being integrated to identify new therapeutic approaches that can help save lives and vision in children with retinoblastoma, with fewer long-term side effects.
MeSH term(s)	Animals ; Child ; Epigenomics/methods ; Epigenomics/trends ; Gene Amplification/genetics ; Genetic Therapy/methods ; Genetic Therapy/trends ; Humans ; Retinoblastoma/diagnosis ; Retinoblastoma/genetics ; Retinoblastoma/therapy ; Retinoblastoma Protein/genetics
Chemical Substances	Retinoblastoma Protein
Language	English
Publishing date	2015-08-27
Publishing country	United States
Document type	Journal Article ; Review
ZDB-ID	1036388-9
ISSN	0893-9675
ISSN	0893-9675
DOI	10.1615/critrevoncog.2015013711
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Zs.A 2587: Show issues

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Article: Constitutive turnover of cyclin E by Cul3 maintains quiescence.

McEvoy, Justina D / Kossatz, Uta / Malek, Nisar / Singer, Jeffrey D

Molecular and cellular biology

2007 Volume 27, Issue 10, Page(s) 3651–3666

Abstract: Two distinct pathways for the degradation of mammalian cyclin E have previously been described. One pathway is induced by cyclin E phosphorylation and is dependent on the Cul1/Fbw7-based E3 ligase. The other pathway is dependent on the Cul3-based E3 ... ...

Abstract	Two distinct pathways for the degradation of mammalian cyclin E have previously been described. One pathway is induced by cyclin E phosphorylation and is dependent on the Cul1/Fbw7-based E3 ligase. The other pathway is dependent on the Cul3-based E3 ligase, but the mechanistic details of this pathway have yet to be elucidated. To establish the role of Cul3 in the degradation of cyclin E in vivo, we created a conditional knockout of the Cul3 gene in mice. Interestingly, the biallelic loss of Cul3 in primary fibroblasts derived from these mice results in increased cyclin E expression and reduced cell viability, paralleling the loss of Cul3 protein expression. Cell cycle analysis of viable, Cul3 hypomorphic cells shows that decreasing the levels of Cul3 increases both cyclin E protein levels and the number of cells in S phase. In order to examine the role of Cul3 in an in vivo setting, we determined the effect of deletion of the Cul3 gene in liver. This gene deletion resulted in a dramatic increase in cyclin E levels as well as an increase in cell size and ploidy. The results we report here show that the constitutive degradation pathway for cyclin E that is regulated by the Cul3-based E3 ligase is essential to maintain quiescence in mammalian cells.
MeSH term(s)	Animals ; Cell Cycle/physiology ; Cell Cycle Proteins/genetics ; Cell Cycle Proteins/metabolism ; Cell Survival ; Cells, Cultured ; Cullin Proteins/genetics ; Cullin Proteins/metabolism ; Cyclin E/genetics ; Cyclin E/metabolism ; Fibroblasts/cytology ; Fibroblasts/physiology ; Hepatocytes/cytology ; Hepatocytes/physiology ; Mice ; Mice, Knockout ; Phenotype
Chemical Substances	Cell Cycle Proteins ; Cul3 protein, mouse ; Cullin Proteins ; Cyclin E
Language	English
Publishing date	2007-05
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	779397-2
ISSN	1098-5549 ; 0270-7306
ISSN (online)	1098-5549
ISSN	0270-7306
DOI	10.1128/MCB.00720-06
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Article ; Online: Cross-species genomic and epigenomic landscape of retinoblastoma.

Benavente, Claudia A / McEvoy, Justina D / Finkelstein, David / Wei, Lei / Kang, Guolian / Wang, Yong-Dong / Neale, Geoffrey / Ragsdale, Susan / Valentine, Virginia / Bahrami, Armita / Temirov, Jamshid / Pounds, Stanley / Zhang, Jinghui / Dyer, Michael A

Oncotarget

2013 Volume 4, Issue 6, Page(s) 844–859

Abstract: Genetically engineered mouse models (GEMMs) of human cancer are important for advancing our understanding of tumor initiation and progression as well as for testing novel therapeutics. Retinoblastoma is a childhood cancer of the developing retina that ... ...

Abstract	Genetically engineered mouse models (GEMMs) of human cancer are important for advancing our understanding of tumor initiation and progression as well as for testing novel therapeutics. Retinoblastoma is a childhood cancer of the developing retina that initiates with biallelic inactivation of the RB1 gene. GEMMs faithfully recapitulate the histopathology, molecular, cellular, morphometric, neuroanatomical and neurochemical features of human retinoblastoma. In this study, we analyzed the genomic and epigenomic landscape of murine retinoblastoma and compared them to human retinoblastomas to gain insight into shared mechanisms of tumor progression across species. Similar to human retinoblastoma, mouse tumors have low rates of single nucleotide variations. However, mouse retinoblastomas have higher rates of aneuploidy and regional and focal copy number changes that vary depending on the genetic lesions that initiate tumorigenesis in the developing murine retina. Furthermore, the epigenetic landscape in mouse retinoblastoma was significantly different from human tumors and some pathways that are candidates for molecular targeted therapy for human retinoblastoma such as SYK or MCL1 are not deregulated in GEMMs. Taken together, these data suggest there are important differences between mouse and human retinoblastomas with respect to the mechanism of tumor progression and those differences can have significant implications for translational research to test the efficacy of novel therapies for this devastating childhood cancer.
MeSH term(s)	Animals ; Disease Models, Animal ; Epigenomics ; Gene Expression Regulation, Neoplastic ; Genetic Engineering/methods ; Genomics/methods ; Humans ; Mice ; Mice, Knockout ; Retinoblastoma/genetics ; Retinoblastoma/metabolism ; Retinoblastoma/pathology ; Retinoblastoma Protein/genetics ; Retinoblastoma Protein/metabolism ; Species Specificity
Chemical Substances	Retinoblastoma Protein
Language	English
Publishing date	2013-06-14
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	2560162-3
ISSN	1949-2553 ; 1949-2553
ISSN (online)	1949-2553
ISSN	1949-2553
DOI	10.18632/oncotarget.1051
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Article ; Online: The myogenesis program drives clonal selection and drug resistance in rhabdomyosarcoma.

Developmental cell

2022 Volume 57, Issue 10, Page(s) 1226–1240.e8

Abstract: Rhabdomyosarcoma (RMS) is a pediatric cancer with features of skeletal muscle; patients with unresectable or metastatic RMS fare poorly due to high rates of disease recurrence. Here, we use single-cell and single-nucleus RNA sequencing to show that RMS ... ...

Abstract	Rhabdomyosarcoma (RMS) is a pediatric cancer with features of skeletal muscle; patients with unresectable or metastatic RMS fare poorly due to high rates of disease recurrence. Here, we use single-cell and single-nucleus RNA sequencing to show that RMS tumors recapitulate the spectrum of embryonal myogenesis. Using matched patient samples from a clinical trial and orthotopic patient-derived xenografts (O-PDXs), we show that chemotherapy eliminates the most proliferative component with features of myoblasts within embryonal RMS; after treatment, the immature population with features of paraxial mesoderm expands to reconstitute the developmental hierarchy of the original tumor. We discovered that this paraxial mesoderm population is dependent on EGFR signaling and is sensitive to EGFR inhibitors. Taken together, these data serve as a proof of concept that targeting each developmental state in embryonal RMS is an effective strategy for improving outcomes by preventing disease recurrence.
MeSH term(s)	Child ; Drug Resistance ; ErbB Receptors ; Humans ; Muscle Development/genetics ; Neoplasm Recurrence, Local ; Rhabdomyosarcoma/drug therapy ; Rhabdomyosarcoma/genetics ; Rhabdomyosarcoma/pathology ; Rhabdomyosarcoma, Embryonal/drug therapy ; Rhabdomyosarcoma, Embryonal/genetics ; Rhabdomyosarcoma, Embryonal/pathology
Chemical Substances	ErbB Receptors (EC 2.7.10.1)
Language	English
Publishing date	2022-04-27
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	2054967-2
ISSN	1878-1551 ; 1534-5807
ISSN (online)	1878-1551
ISSN	1534-5807
DOI	10.1016/j.devcel.2022.04.003
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Zs.A 5742: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular Jg. 1995 - 2021: Lesesall (2.OG) ab Jg. 2022: Lesesaal (EG)
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Article: Subcellular localization and cytoplasmic complex status of endogenous Keap1.

Watai, Yoriko / Kobayashi, Akira / Nagase, Hiroko / Mizukami, Mio / McEvoy, Justina / Singer, Jeffrey D / Itoh, Ken / Yamamoto, Masayuki

Genes to cells : devoted to molecular & cellular mechanisms

2007 Volume 12, Issue 10, Page(s) 1163–1178

Abstract: Keap1 acts as a sensor for oxidative/electrophilic stress, an adaptor for Cullin-3-based ubiquitin ligase, and a regulator of Nrf2 activity through the interaction with Nrf2 Neh2 domain. However, the mechanism(s) of Nrf2 migration into the nucleus in ... ...

Abstract	Keap1 acts as a sensor for oxidative/electrophilic stress, an adaptor for Cullin-3-based ubiquitin ligase, and a regulator of Nrf2 activity through the interaction with Nrf2 Neh2 domain. However, the mechanism(s) of Nrf2 migration into the nucleus in response to stress remains largely unknown due to the lack of a reliable antibody for the detection of endogenous Keap1 molecule. Here, we report the generation of a new monoclonal antibody for the detection of endogenous Keap1 molecules. Immunocytochemical analysis of mouse embryonic fibroblasts with the antibody revealed that under normal, unstressed condition, Keap1 is localized primarily in the cytoplasm with minimal amount in the nucleus and endoplasmic reticulum. This subcellular localization profile of Keap1 appears unchanged after treatment of cells with diethyl maleate, an electrophile, and/or Leptomycin B, a nuclear export inhibitor. Subcellular fractionation analysis of mouse liver cells showed similar results. No substantial change in the subcellular distribution profile could be observed in cells isolated from butylated hydroxyanisole-treated mice. Analyses of sucrose density gradient centrifugation of mouse liver cells indicated that Keap1 appears to form multiprotein complexes in the cytoplasm. These results demonstrate that endogenous Keap1 remains mostly in the cytoplasm, and electrophiles promote nuclear accumulation of Nrf2 without altering the subcellular localization of Keap1.
MeSH term(s)	Adaptor Proteins, Signal Transducing/metabolism ; Adaptor Proteins, Signal Transducing/physiology ; Animals ; Anisoles/pharmacology ; Cell Nucleus/metabolism ; Cytoplasm/metabolism ; Cytoskeletal Proteins/metabolism ; Cytoskeletal Proteins/physiology ; Endoplasmic Reticulum/metabolism ; Fatty Acids, Unsaturated/pharmacology ; Fibroblasts/metabolism ; Gene Expression Regulation ; Humans ; Kelch-Like ECH-Associated Protein 1 ; Liver/metabolism ; Maleates/pharmacology ; Mice ; Models, Biological ; Rats ; Subcellular Fractions/metabolism
Chemical Substances	Adaptor Proteins, Signal Transducing ; Anisoles ; Cytoskeletal Proteins ; Fatty Acids, Unsaturated ; Keap1 protein, mouse ; Kelch-Like ECH-Associated Protein 1 ; Maleates ; mequinol (6HT8U7K3AM) ; diethyl maleate (G81WQB56OL) ; leptomycin B (Y031I2N1EO)
Language	English
Publishing date	2007-10
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	1330000-3
ISSN	1365-2443 ; 1356-9597
ISSN (online)	1365-2443
ISSN	1356-9597
DOI	10.1111/j.1365-2443.2007.01118.x
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Article ; Online: Increased [18F]fluorodeoxyglucose uptake in the left pallidum in military Veterans with blast-related mild traumatic brain injury: potential as an imaging biomarker and mediation with executive dysfunction and cognitive impairment.

Terry, Garth E / Pagulayan, Kathleen / Muzi, Mark / Mayer, Cynthia / Murray, Daniel R / Schindler, Abigail / Richards, Todd / McEvoy, Cory Burke / Crabtree, Adam / McNamara, Chris / Means, Gary / Muench, Peter / Powell, Jacob / Mihalik, Jason / Thomas, Ronald / Raskind, Murray / Peskind, Elaine / Meabon, James

Journal of neurotrauma

2024

Abstract: ... <0.0001; q=3.29 x 10-9 (Cohen's d, 1.38, 95% CI (.96, 1.79)). The degree of left pallidum [18F]FDG ... to facilitate accurate diagnosis, not just for symptom management and rehabilitation but for prognostication and ...

Abstract	Blast-related mild traumatic brain injury (blast-mTBI) can result in a spectrum of persistent symptoms leading to substantial functional impairment and reduced quality of life. Clinical evaluation and discernment from other conditions common to military service can be challenging and subject to patient recall bias and the limitations of available assessment measures. The need for objective biomarkers to facilitate accurate diagnosis, not just for symptom management and rehabilitation but for prognostication and disability compensation purposes is clear. Toward this end, we compared regional brain [18F]fluorodeoxyglucose positron emission tomography ([18F]FDG-PET) intensity-scaled uptake measurements and motor, neuropsychological, and behavioral assessments in 79 combat Veterans with retrospectively recalled blast-mTBI with 41 control participants having no lifetime history of TBI. Using an agnostic and unbiased approach, we found significantly increased left pallidum [18F]FDG-uptake in Veterans with blast-mTBI versus control participants, p<0.0001; q=3.29 x 10-9 (Cohen's d, 1.38, 95% CI (.96, 1.79)). The degree of left pallidum [18F]FDG-uptake correlated with the number of self-reported blast-mTBIs, r2=0.22; p<0.0001. Greater [18F]FDG-uptake in the left pallidum provided excellent discrimination between Veterans with blast-mTBI and controls, with a Receiver Operator Characteristic Area Under the Curve of 0.859 (p<0.0001) and likelihood ratio of 21.19 (threshold:SUVR≥0.895). Deficits in executive function assessed using the Behavior Rating Inventory of Executive Function-Adult Global Executive Composite T-score were identified in Veterans with blast-mTBI compared to controls, p<0.0001. Regression-based mediation analyses determined that in Veterans with blast-mTBI, increased [18F]FDG-uptake in the left pallidum mediated executive function impairments, adjusted causal mediation estimate p=0.021; total effect estimate, p=0.039. Measures of working and prospective memory (Auditory Consonant Trigrams test and Memory for Intentions Test, respectively) were negatively correlated with left pallidum [18F]FDG-uptake, p<0.0001, with mTBI as a covariate. Increased left pallidum [18F]FDG-uptake in Veterans with blast-mTBI compared to controls did not covary with dominant handedness or with motor activity assessed using the Unified Parkinson's Disease Rating Scale. Localized increased [18F]FDG-uptake in the left pallidum may reflect a compensatory response to functional deficits following blast-mTBI. Limited imaging resolution does not allow us to distinguish subregions of the pallidum, however the significant correlation of our data with behavioral but not motor outcomes suggests involvement of the ventral pallidum, which is known to regulate motivation, behavior, and emotions via basal ganglia-thalamo-cortical circuits. Increased [18F]FDG-uptake in the left pallidum in blast-mTBI versus control participants was consistently identified using two different PET scanners, supporting the generalizability of this finding. While confirmation of our results by single-subject-to-cohort analyses will be required prior to clinical deployment, this study provides proof-of-concept that [18F]FDG-PET bears promise as a readily available noninvasive biomarker for blast-mTBI. Further, our findings support a causative relationship between executive dysfunction and increased [18F]FDG-uptake in the left pallidum.
Language	English
Publishing date	2024-04-25
Publishing country	United States
Document type	Journal Article
ZDB-ID	645092-1
ISSN	1557-9042 ; 0897-7151
ISSN (online)	1557-9042
ISSN	0897-7151
DOI	10.1089/neu.2023.0429
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Article: Subcellular localization and cytoplasmic complex status of endogenous Keap1

Watai, Yoriko / Kobayashi, Akira / Nagase, Hiroko / Mizukami, Mio / McEvoy, Justina / Singer, Jeffrey D / Itoh, Ken / Yamamoto, Masayuki

Genes to cells. 2007 Oct., v. 12, no. 10

2007

Abstract	Keap1 acts as a sensor for oxidative/electrophilic stress, an adaptor for Cullin-3-based ubiquitin ligase, and a regulator of Nrf2 activity through the interaction with Nrf2 Neh2 domain. However, the mechanism(s) of Nrf2 migration into the nucleus in response to stress remains largely unknown due to the lack of a reliable antibody for the detection of endogenous Keap1 molecule. Here, we report the generation of a new monoclonal antibody for the detection of endogenous Keap1 molecules. Immunocytochemical analysis of mouse embryonic fibroblasts with the antibody revealed that under normal, unstressed condition, Keap1 is localized primarily in the cytoplasm with minimal amount in the nucleus and endoplasmic reticulum. This subcellular localization profile of Keap1 appears unchanged after treatment of cells with diethyl maleate, an electrophile, and/or Leptomycin B, a nuclear export inhibitor. Subcellular fractionation analysis of mouse liver cells showed similar results. No substantial change in the subcellular distribution profile could be observed in cells isolated from butylated hydroxyanisole-treated mice. Analyses of sucrose density gradient centrifugation of mouse liver cells indicated that Keap1 appears to form multiprotein complexes in the cytoplasm. These results demonstrate that endogenous Keap1 remains mostly in the cytoplasm, and electrophiles promote nuclear accumulation of Nrf2 without altering the subcellular localization of Keap1.
Language	English
Dates of publication	2007-10
Size	p. 1163-1178.
Publisher	Blackwell Publishing Inc
Publishing place	Malden, USA
Document type	Article
ZDB-ID	1330000-3
ISSN	1356-9597
ISSN	1356-9597
DOI	10.1111/j.1365-2443.2007.01118.x
Database	NAL-Catalogue (AGRICOLA)

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Article ; Online: Prevalence and Correlates of Elevated NT-proBNP in Pregnant Women in the General U.S. Population.

Minhas, Anum S / Rooney, Mary R / Fang, Michael / Zhang, Sui / Ndumele, Chiadi E / Tang, Olive / Schulman, Steven P / Michos, Erin D / McEvoy, J William / Echouffo-Tcheugui, Justin / Christenson, Robert / Selvin, Elizabeth

JACC. Advances

2023 Volume 2, Issue 2

Abstract: Background: Physiologic changes in N-terminal pro-B-type natriuretic peptide (NT-proBNP) across trimesters of pregnancy have not been well studied.: Objectives: The authors aimed to measure NT-proBNP in adult women, by pregnancy status and trimester, ...

Abstract	Background: Physiologic changes in N-terminal pro-B-type natriuretic peptide (NT-proBNP) across trimesters of pregnancy have not been well studied. Objectives: The authors aimed to measure NT-proBNP in adult women, by pregnancy status and trimester, in a nationally representative sample from the National Health and Nutrition Examination Survey 1999 to 2004. Methods: We conducted a cross-sectional analysis of 2,134 women (546 pregnant) aged 20 to 40 years without a history of cardiovascular disease. Results: Among pregnant women in the first trimester, the prevalence of elevated NT-proBNP (>125 pg/mL) was 20.0% (SE, 6.6%) compared to 2.4% (SE, 0.8%) among women in the third trimester and 8.0% among nonpregnant women. After adjustment for demographics and cardiovascular risk factors, NT-proBNP was 44% higher (absolute difference 26.4 [95% CI: 11.2-41.6] pg/mL) in the first trimester of pregnancy compared to nonpregnant women. Among pregnant women only, adjusted NT-proBNP was 46% lower (absolute difference -22.2 [95% CI: -36.9 to -7.5] pg/mL) in women in the third trimester compared to women in the first trimester. NT-proBNP was inversely associated with body mass index and with systolic blood pressure. Conclusions: Women in the first trimester of pregnancy had significantly higher NT-proBNP than those in the third trimester and compared to similarly aged nonpregnant women. The dynamic nature of NT-proBNP should be taken into consideration when ordering NT-proBNP lab tests in pregnant women.
Language	English
Publishing date	2023-03-08
Publishing country	United States
Document type	Journal Article
ISSN	2772-963X
ISSN (online)	2772-963X
DOI	10.1016/j.jacadv.2023.100265
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Article ; Online: The effect of preoperative behaviour change interventions on pre- and post-surgery health behaviours, health outcomes, and health inequalities in adults: A systematic review and meta-analyses.

Fong, Mackenzie / Kaner, Eileen / Rowland, Maisie / Graham, Henrietta E / McEvoy, Louise / Hallsworth, Kate / Cucato, Gabriel / Gibney, Carla / Nedkova, Martina / Prentis, James / Madigan, Claire D

PloS one

2023 Volume 18, Issue 7, Page(s) e0286757

Abstract: ... outcomes just before surgery. That improvements in smoking outcomes were sustained at 12-months post ...

Abstract	Background: Prehabilitation interventions are being delivered across surgical specialities to improve health risk behaviours leading to better surgical outcomes and potentially reduce length of hospital stay. Most previous research has focused on specific surgery specialities and has not considered the impact of interventions on health inequalities, nor whether prehabilitation improves health behaviour risk profiles beyond surgery. The aim of this review was to examine behavioural Prehabilitation interventions across surgeries to inform policy makers and commissioners of the best available evidence. Methods and findings: A systematic review and meta-analysis of randomised controlled trials (RCTs) was conducted to determine the effect of behavioural prehabilitation interventions targeting at least one of: smoking behaviour, alcohol use, physical activity, dietary intake (including weight loss interventions) on pre- and post-surgery health behaviours, health outcomes, and health inequalities. The comparator was usual care or no treatment. MEDLINE, PubMed, PsychINFO, CINAHL, Web of Science, Google Scholar, Clinical trials and Embase databases were searched from inception to May 2021, and the MEDLINE search was updated twice, most recently in March 2023. Two reviewers independently identified eligible studies, extracted data, and assessed risk of bias using the Cochrane risk of bias tool. Outcomes were length of stay, six-minute walk test, behaviours (smoking, diet, physical activity, weight change, and alcohol), and quality of life. Sixty-seven trials were included; 49 interventions targeted a single behaviour and 18 targeted multiple behaviours. No trials examined effects by equality measures. Length of stay in the intervention group was 1.5 days shorter than the comparator (n = 9 trials, 95% CI -2.6 to -0.4, p = 0.01, I2 83%), although in sensitivity analysis prehabilitation had the most impact in lung cancer patients (-3.5 days). Pre-surgery, there was a mean difference of 31.8 m in the six-minute walk test favouring the prehabilitation group (n = 19 trials, 95% CI 21.2 to 42.4m, I2 55%, P <0.001) and this was sustained to 4-weeks post-surgery (n = 9 trials, mean difference = 34.4m (95%CI 12.8 to 56.0, I2 72%, P = 0.002)). Smoking cessation was greater in the prehabilitation group before surgery (RR 2.9, 95% CI 1.7 to 4.8, I2 84%), and this was sustained at 12 months post-surgery (RR 1.74 (95% CI 1.20 to 2.55, I2 43%, Tau2 0.09, p = 0.004)There was no difference in pre-surgery quality of life (n = 12 trials) or BMI (n = 4 trials). Conclusions: Behavioural prehabilitation interventions reduced length of stay by 1.5 days, although in sensitivity analysis the difference was only found for Prehabilitation interventions for lung cancer. Prehabilitation can improve functional capacity and smoking outcomes just before surgery. That improvements in smoking outcomes were sustained at 12-months post-surgery suggests that the surgical encounter holds promise as a teachable moment for longer-term behavioural change. Given the paucity of data on the effects on other behavioural risk factors, more research grounded in behavioural science and with longer-term follow-up is needed to further investigate this potential.
MeSH term(s)	Adult ; Humans ; Exercise ; Diet ; Risk Factors ; Smoking Cessation ; Lung Neoplasms
Language	English
Publishing date	2023-07-05
Publishing country	United States
Document type	Meta-Analysis ; Systematic Review ; Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2267670-3
ISSN	1932-6203 ; 1932-6203
ISSN (online)	1932-6203
ISSN	1932-6203
DOI	10.1371/journal.pone.0286757
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Article ; Online: An improved predictive model for postoperative pulmonary complications after free flap reconstructions in the head and neck.

Smith, Derek K / Freundlich, Robert E / Shinn, Justin R / Wood, C Burton / Rohde, Sarah L / McEvoy, Matthew D

Head & neck

2021 Volume 43, Issue 7, Page(s) 2178–2184

Abstract: Background: Commonly used predictive models for postoperative pulmonary complications (PPCs) do not perform when applied to head and neck cases. A head and neck-specific risk prediction tool is needed.: Methods: Data on 794 free flap head and neck ... ...

Abstract	Background: Commonly used predictive models for postoperative pulmonary complications (PPCs) do not perform when applied to head and neck cases. A head and neck-specific risk prediction tool is needed. Methods: Data on 794 free flap head and neck surgery cases at a single center were abstracted from the electronic medical record. Each case was reviewed for the development of PPCs. A predictive model was developed and was then compared to existing predictive models for PPCs. Results: The least absolute shrinkage and selection operator procedure identified age, alcohol use, history of congestive heart failure, preoperative packed cell volume, preoperative oxygen saturation, and preoperative metabolic equivalents as predictors of PPCs in the head and neck population. The model demonstrated an area under the receiving operating characteristic curve of 0.75 (0.69-0.80) with moderately good calibration. Comparisons to the performance of existing models demonstrate superior performance. Conclusions: The model for the development of PPCs developed in this article displays superior performance to existing models.
MeSH term(s)	Free Tissue Flaps ; Head and Neck Neoplasms/surgery ; Humans ; Lung ; Postoperative Complications/epidemiology ; Postoperative Complications/etiology ; Reconstructive Surgical Procedures ; Retrospective Studies ; Risk Factors
Language	English
Publishing date	2021-03-30
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural
ZDB-ID	645165-2
ISSN	1097-0347 ; 0148-6403 ; 1043-3074
ISSN (online)	1097-0347
ISSN	0148-6403 ; 1043-3074
DOI	10.1002/hed.26689
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