Publications by authors named "Patricia Rivera"

148 Publications

Sociodemographic disparities in the management of advanced lung cancer: a narrative review.

J Thorac Dis 2021 Jun;13(6):3772-3800

Division of Oncology, Department of Medicine, University of North Carolina, Chapel Hill, NC, USA.

Treatment of advanced non-small cell lung cancer (NSCLC) has markedly changed in the past decade with the integration of biomarker testing, targeted therapies, immunotherapy, and palliative care. These advancements have led to significant improvements in quality of life and overall survival. Despite these improvements, racial and socioeconomic disparities in lung cancer mortality persist. This narrative review aims to assess and synthesize the literature on sociodemographic disparities in the management of advanced NSCLC. A narrative overview of the literature was conducted using PubMed and Scopus and was narrowed to articles published from January 1, 2010, until July 22, 2020. Articles relevant to sociodemographic variation in (I) chemoradiation for stage III NSCLC, (II) molecular biomarker testing, (III) systemic treatment, including chemotherapy, targeted therapy, and immunotherapy, and (IV) palliative and end of life care were included in this review. Twenty-two studies were included. Sociodemographic disparities in the management of advanced NSCLC varied, but recurring findings emerged. Across most treatment domains, Black patients, the uninsured, and patients with Medicaid were less likely to receive recommended lung cancer care. However, some of the literature was limited due to incomplete data to adequately assess appropriateness of care, and several studies were out of date with current practice guidelines. Sociodemographic disparities in the management of advanced lung cancer are evident. Given the rapidly evolving treatment paradigm for advanced NSCLC, updated research is needed. Research on interventions to address disparities in advanced NSCLC is also needed.
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http://dx.doi.org/10.21037/jtd-20-3450DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8264681PMC
June 2021

Age, Sex, Smoking, and Race: Is Progress Being Made in Lung Cancer Screening Eligibility?

Chest 2021 Jul;160(1):31-33

Department of Medicine, University of North Carolina, Chapel Hill, NC.

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http://dx.doi.org/10.1016/j.chest.2021.03.043DOI Listing
July 2021

Sudden cessation of fluoxetine before alcohol drinking reinstatement alters microglial morphology and TLR4/inflammatory neuroadaptation in the rat brain.

Brain Struct Funct 2021 Jul 8. Epub 2021 Jul 8.

Instituto de Investigación Biomédica de Málaga-IBIMA, 29010, Málaga, Spain.

Preclinical studies on the effects of abrupt cessation of selective serotonin reuptake inhibitors (SSRIs), a medication often prescribed in alcohol use disorder (AUD) patients with depression, results in alcohol consumption escalation after resuming drinking. However, a potential neuroinflammatory component on this escalation remains unexplored despite the immunomodulatory role of serotonin. Here, we utilized a rat model of 14-daily administration of the SSRI fluoxetine (10 mg/kg/day) along alcohol self-administration deprivation to study the effects of fluoxetine cessation on neuroinflammation after resuming alcohol drinking. Microglial morphology and inflammatory gene expression were analyzed in prelimbic cortex, striatum, basolateral amygdala and dorsal hippocampus. Results indicated that alcohol drinking reinstatement increased microglial IBA1 immunoreactivity and altered morphometric features of activated microglia (fractal dimension, lacunarity, density, roughness, and cell area, perimeter and circularity). Despite alcohol reinstatement, fluoxetine cessation modified microglial morphology in a brain region-specific manner, resulting in hyper-ramified (spatial complexity of branching), reactive (lower heterogeneity and circularity)-like microglia. We also found that microglial cell area correlated with changes in mRNA expression of chemokines (Cx3cl1/fractalkine, Cxcl12/SDF1α, Ccl2/MCP1), cytokines (IL1β, IL6, IL10) and the innate immune toll-like receptor 4 (TLR4) in dorsal hippocampus. Specifically, TLR4 correlated with microglial spatial complexity assessed by fractal dimension in striatum, suggesting a role in process branching. These findings suggest that alcohol drinking reinstatement after fluoxetine treatment cessation disturbs microglial morphology and reactive phenotype associated with a TLR4/inflammatory response to alcohol in a brain region-specific manner, facts that might contribute to alcohol-induced damage through the promotion of escalation of alcohol drinking behavior.
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http://dx.doi.org/10.1007/s00429-021-02321-9DOI Listing
July 2021

Analysis of Both Lipid Metabolism and Endocannabinoid Signaling Reveals a New Role for Hypothalamic Astrocytes in Maternal Caloric Restriction-Induced Perinatal Programming.

Int J Mol Sci 2021 Jun 11;22(12). Epub 2021 Jun 11.

Instituto de Investigación Biomédica de Málaga-IBIMA, 29010 Málaga, Spain.

Maternal malnutrition in critical periods of development increases the risk of developing short- and long-term diseases in the offspring. The alterations induced by this nutritional programming in the hypothalamus of the offspring are of special relevance due to its role in energy homeostasis, especially in the endocannabinoid system (ECS), which is involved in metabolic functions. Since astrocytes are essential for neuronal energy efficiency and are implicated in brain endocannabinoid signaling, here we have used a rat model to investigate whether a moderate caloric restriction (R) spanning from two weeks prior to the start of gestation to its end induced changes in offspring hypothalamic (a) ECS, (b) lipid metabolism (LM) and/or (c) hypothalamic astrocytes. Monitorization was performed by analyzing both the gene and protein expression of proteins involved in LM and ECS signaling. Offspring born from caloric-restricted mothers presented hypothalamic alterations in both the main enzymes involved in LM and endocannabinoids synthesis/degradation. Furthermore, most of these changes were similar to those observed in hypothalamic offspring astrocytes in culture. In conclusion, a maternal low caloric intake altered LM and ECS in both the hypothalamus and its astrocytes, pointing to these glial cells as responsible for a large part of the alterations seen in the total hypothalamus and suggesting a high degree of involvement of astrocytes in nutritional programming.
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http://dx.doi.org/10.3390/ijms22126292DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8230792PMC
June 2021

Knowledge and Practice Patterns Among Pulmonologists for Molecular Biomarker Testing in Advanced Non-Small Cell Lung Cancer.

Chest 2021 Jun 25. Epub 2021 Jun 25.

Medical University of South Carolina, Division of Pulmonary and Critical Care Medicine; Charleston, SC. Electronic address:

Background: Targeted therapies for advanced non-small cell lung cancer (NSCLC) with oncogenic drivers have caused a paradigm shift in care. Biomarker testing is needed to assess eligibility for these therapies. Pulmonologists often perform bronchoscopy, providing tissue for both pathological diagnosis and biomarker analysis. We performed this survey to define the existing knowledge and practices regarding the pulmonologists' role in biomarker testing for advanced NSCLC.

Research Question: What is the current knowledge and practice of pulmonologists regarding biomarker testing and targeted therapies in advanced NSCLC?

Study Design And Methods: This cross-sectional study was performed using an electronic survey of a random sample of 7,238 pulmonologists. Questions focused on diagnostic steps and biomarker analyses for NSCLC.

Results: A total of 453 pulmonologists responded. Respondents vary by reported lung cancer patient volume, ranging from 51% evaluating 1-4 new cases per month to 19% evaluating >10 per month. Interventional training, academic practice setting, and higher volume of EBUS-TBNA were associated with increased knowledge of practice guidelines for the number of recommended passes during EBUS-TBNA (p<0.05). Academic pulmonologists more commonly performed or referred for EBUS-TBNA compared to community pulmonologists (96% and 83% respectively, p<0.0005). Higher testing rates were associated with interventional training, academic setting, and the presence of an institutional policy, whereas lower testing rates were associated with general pulmonologists, practice in community settings, and lack of a guiding institutional policy (p<0.05).

Interpretation: Substantial differences among pulmonologists' evaluation of advanced NSCLC, variation in knowledge of available biomarkers and the importance of targeted therapies, and differences in institutional coordination likely lead to underutilization of biomarker testing. Interventional training appears to drive improved knowledge and practice for biomarker testing more than practice setting. Improvements are needed in tissue acquisition and interdisciplinary coordination to ensure universal and comprehensive testing for eligible patients.
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http://dx.doi.org/10.1016/j.chest.2021.06.027DOI Listing
June 2021

A Negative Energy Balance Is Associated with Metabolic Dysfunctions in the Hypothalamus of a Humanized Preclinical Model of Alzheimer's Disease, the 5XFAD Mouse.

Int J Mol Sci 2021 May 20;22(10). Epub 2021 May 20.

Instituto de investigación Biomédica de Málaga-IBIMA, 29010 Málaga, Spain.

Increasing evidence links metabolic disorders with neurodegenerative processes including Alzheimer's disease (AD). Late AD is associated with amyloid (Aβ) plaque accumulation, neuroinflammation, and central insulin resistance. Here, a humanized AD model, the 5xFAD mouse model, was used to further explore food intake, energy expenditure, neuroinflammation, and neuroendocrine signaling in the hypothalamus. Experiments were performed on 6-month-old male and female full transgenic (Tg), heterozygous (Tg), and non-transgenic (Non-Tg) littermates. Although histological analysis showed absence of Aβ plaques in the hypothalamus of 5xFAD mice, this brain region displayed increased protein levels of GFAP and IBA1 in both Tg and Tg mice and increased expression of IL-1β in Tg mice, suggesting neuroinflammation. This condition was accompanied by decreased body weight, food intake, and energy expenditure in both Tg and Tg mice. Negative energy balance was associated with altered circulating levels of insulin, GLP-1, GIP, ghrelin, and resistin; decreased insulin and leptin hypothalamic signaling; dysregulation in main metabolic sensors (phosphorylated IRS1, STAT5, AMPK, mTOR, ERK2); and neuropeptides controlling energy balance (NPY, AgRP, orexin, MCH). These results suggest that glial activation and metabolic dysfunctions in the hypothalamus of a mouse model of AD likely result in negative energy balance, which may contribute to AD pathogenesis development.
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http://dx.doi.org/10.3390/ijms22105365DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8161294PMC
May 2021

Increased Risk and Improved Survival: The Double-Edged Sword of Lung Cancer in Women.

Chest 2021 May;159(5):1719-1720

Division of Pulmonary Diseases and Critical Care Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC.

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http://dx.doi.org/10.1016/j.chest.2020.12.046DOI Listing
May 2021

Patterns and Factors Associated With Adherence to Lung Cancer Screening in Diverse Practice Settings.

JAMA Netw Open 2021 Apr 1;4(4):e218559. Epub 2021 Apr 1.

Lineberger Comprehensive Cancer Center, The University of North Carolina at Chapel Hill, Chapel Hill.

Importance: For lung cancer screening to confer mortality benefit, adherence to annual screening with low-dose computed tomography scans is essential. Although the National Lung Screening Trial had an adherence rate of 95%, current data are limited on screening adherence across diverse practice settings in the United States.

Objective: To evaluate patterns and factors associated with adherence to annual screening for lung cancer after negative results of a baseline examination, particularly in centralized vs decentralized screening programs.

Design, Setting, And Participants: This observational cohort study was conducted at 5 academic and community-based sites in North Carolina and California among 2283 individuals screened for lung cancer between July 1, 2014, and March 31, 2018, who met US Preventive Services Task Force eligibility criteria, had negative results of a baseline screening examination (American College of Radiology Lung Imaging Reporting and Data System category 1 or 2), and were eligible to return for a screening examination in 12 months.

Exposures: To identify factors associated with adherence, the association of adherence with selected baseline demographic and clinical characteristics, including type of screening program, was estimated using multivariable logistic regression. Screening program type was classified as centralized if individuals were referred through a lung cancer screening clinic or program and as decentralized if individuals had a direct clinician referral for the baseline low-dose computed tomography scan.

Main Outcomes And Measures: Adherence to annual lung cancer screening, defined as a second low-dose computed tomography scan within 11 to 15 months after baseline screening.

Results: Among the 2283 eligible individuals (1294 men [56.7%]; mean [SD] age, 64.9 [5.8] years; 1160 [50.8%] aged ≥65 years) who had negative screening results at baseline, overall adherence was 40.2% (n = 917), with higher adherence among those who underwent screening through centralized (46.0% [478 of 1039]) vs decentralized (35.3% [439 of 1244]) programs. The independent factor most strongly associated with adherence was type of screening program, with a 2.8-fold increased likelihood of adherence associated with centralized screening (adjusted odds ratio [aOR], 2.78; 95% CI, 1.99-3.88). Another associated factor was age (65-69 vs 55-59 years: aOR, 1.38; 95% CI, 1.07-1.77; 70-74 vs 55-59 years: aOR, 1.47; 95% CI, 1.10-1.96).

Conclusions And Relevance: After negative results of a baseline examination, adherence to annual lung cancer screening was suboptimal, although adherence was higher among individuals who were screened through a centralized program. These results support the value of centralized screening programs and the need to further implement strategies that improve adherence to annual screening for lung cancer.
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http://dx.doi.org/10.1001/jamanetworkopen.2021.8559DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8087957PMC
April 2021

Recombinant IGF-1 Induces Sex-Specific Changes in Bone Composition and Remodeling in Adult Mice with Deficiency.

Int J Mol Sci 2021 Apr 14;22(8). Epub 2021 Apr 14.

Departamento de Anatomía Humana, Medicina Legal e Historia de la Ciencia, Instituto de Investigación Biomédica de Málaga (IBIMA), Universidad de Málaga, 29071 Málaga, Spain.

Deficiency of pregnancy-associated plasma protein-A2 (PAPP-A2), an IGF-1 availability regulator, causes postnatal growth failure and dysregulation of bone size and density. The present study aimed to determine the effects of recombinant murine IGF-1 (rmIGF-1) on bone composition and remodeling in constitutive knock-out (ko/ko) mice. To address this challenge, X-ray diffraction (XRD), attenuated total reflection-fourier transform infra-red (ATR-FTIR) spectroscopy and gene expression analysis of members of the IGF-1 system and bone resorption/formation were performed. mice (both sexes) had reduced body and bone length. Male mice had specific alterations in bone composition (mineral-to-matrix ratio, carbonate substitution and mineral crystallinity), but not in bone remodeling. In contrast, decreases in collagen maturity and increases in , (resorption) and (formation) characterized the bone of females. A single rmIGF-1 administration (0.3 mg/kg) induced short-term changes in bone composition in mice (both sexes). rmIGF-1 treatment in females also increased collagen maturity, and , , and expression. In summary, acute IGF-1 treatment modifies bone composition and local IGF-1 response to bone remodeling in mice with deficiency. These effects depend on sex and provide important insights into potential IGF-1 therapy for growth failure and bone loss and repair.
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http://dx.doi.org/10.3390/ijms22084048DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8070906PMC
April 2021

Molecular Biomarker and Programmed Death-Ligand 1 Expression Testing in Patients With Advanced Stage Non-Small Cell Lung Cancer Across North Carolina Community Hospitals.

Chest 2021 Apr 19. Epub 2021 Apr 19.

Lineberger Comprehensive Cancer Center, The University of North Carolina, Chapel Hill, NC; Department of Radiology, The University of North Carolina, Chapel Hill, NC; Department of Epidemiology, The University of North Carolina, Chapel Hill, NC.

Background: Precision medicine in advanced non-small cell lung cancer (NSCLC) requires molecular biomarker testing in patients with nonsquamous and select patients with squamous histologies, and programmed death-ligand 1 (PD-L1) testing in both.

Research Question: What are rates of molecular and PD-L1 biomarker testing in patients with advanced NSCLC in community practices, and do rates vary by sociodemographic factors? What is the prevalence of molecular biomarker mutations and PD-L1 expression levels?

Study Design And Methods: From 389 stage IV NSCLC pathology reports obtained through the University of North Carolina Lineberger Comprehensive Cancer Center's Rapid Case Ascertainment Program from 38 community hospitals across North Carolina, we abstracted demographics, histology, molecular biomarker testing and results, and PD-L1 testing and expression. We geocoded patient and hospital addresses to determine travel time, distance to care, and census block level contextual variables. We compared molecular biomarker and PD-L1 testing rates, the prevalence of molecular biomarkers, and PD-L1 expression levels by race and sex, using χ tests. We determined predictors of testing, using multivariable logistic regression and report adjusted ORs and 95%CI.

Results: Among patients with nonsquamous NSCLC, 64.4% were tested for molecular biomarkers, and among all NSCLC patients 53.2% were tested for PD-L1 expression. Differences in biomarker testing rates by sociodemographic factors were not statistically significant in univariate or adjusted analyses. Adjusted analyses showed that patients living in areas with higher household internet access were more likely to undergo PD-L1 testing (adjusted OR = 1.66, 95% CI, 1.02-2.71). Sociodemographic differences in molecular biomarker prevalence and PD-L1 expression levels were not statistically significant, except for HER2 mutations, which occurred in 16.7% of males vs 0% in females, P = .05.

Interpretation: Biomarker testing remains underused in NSCLC. Future work should include larger populations and evaluate hospital-specific testing protocols to identify and address barriers to guideline-recommended testing.
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http://dx.doi.org/10.1016/j.chest.2021.04.014DOI Listing
April 2021

Management of Lung Nodules and Lung Cancer Screening During the COVID-19 Pandemic: CHEST Expert Panel Report.

Radiol Imaging Cancer 2020 05 23;2(3):e204013. Epub 2020 Apr 23.

Respiratory Institute (Dr Mazzone) and Department of Medicine (Dr Choi), Cleveland Clinic, Cleveland, OH; Department of Research and Evaluation (Dr Gould), Kaiser Permanente Research, Pasadena, CA; Division of Pulmonary and Critical Care Medicine (Dr Arenberg) and Department of Radiology (Dr Kazerooni), University of Michigan, Ann Arbor, MI; Division of Pulmonary and Critical Care Medicine (Dr Chen), Washington University School of Medicine, St. Louis, MO; Section of Thoracic Surgery (Dr Detterbeck), Department of Surgery, Yale University, New Haven, CT; Department of Surgery (Dr Farjah), University of Washington, Seattle, WA; Department of Thoracic Medicine (Dr Fong), The Prince Charles Hospital, Chermside, Australia; The Pulmonary Center (Dr Iaccarino), Boston University Medical Campus, Boston, MA; Lungs for Living Research Centre (Dr Janes), University College London, London, England; Department of Radiology (Dr Kanne), University of Wisconsin School of Medicine and Public Health, Madison, WI; Department of Radiology (Dr MacMahon), University of Chicago, Chicago, IL; Department of Radiology (Dr Naidich), New York University-Langone Medical Center, New York, NY; Division of Pulmonary, Critical Care, and Sleep Medicine (Dr Powell), Icahn School of Medicine at Mt. Sinai, New York, NY; Division of Pulmonary, Critical Care, and Sleep Medicine (Dr Raoof), Lenox Hill Hospital, New York, NY; Division of Pulmonary and Critical Care Medicine (Dr Rivera), Department of Medicine, University of North Carolina, Chapel Hill, NC; Division of Pulmonary, Critical Care, Allergy and Sleep Medicine (Dr Tanner), Medical University of South Carolina, Health Equity and Rural Outreach Innovation Center, Ralph H. Johnson Veterans Affairs Hospital, Charleston, SC; Department of Internal Medicine (Dr Tanoue), Section of Pulmonary, Critical Care and Sleep Medicine, Yale University School of Medicine, New Haven, CT; Division of Respiratory Medicine (Dr Tremblay), Cumming School of Medicine, University of Calgary, Calgary, AB, Canada; Pulmonary, Allergy, and Critical Care Division (Dr Vachani), University of Pennsylvania School of Medicine, Philadelphia, PA; Department of Radiology (Dr White), School of Medicine, University of Maryland, Baltimore, MD; The Pulmonary Center (Dr Wiener), Boston University School of Medicine, Boston, MA; Center for Healthcare Organization & Implementation Research (Dr Wiener), Edith Nourse Rogers Memorial Veterans Hospital, Bedford, MA; and the Division of Pulmonary and Critical Care Medicine (Dr Silvestri), Medical University of South Carolina, Charleston, SC.

Background: The risks from potential exposure to coronavirus disease 2019 (COVID-19), and resource reallocation that has occurred to combat the pandemic, have altered the balance of benefits and harms that informed current (pre-COVID-19) guideline recommendations for lung cancer screening and lung nodule evaluation. Consensus statements were developed to guide clinicians managing lung cancer screening programs and patients with lung nodules during the COVID-19 pandemic.

Materials And Methods: An expert panel of 24 members, including pulmonologists (n = 17), thoracic radiologists (n = 5), and thoracic surgeons (n = 2), was formed. The panel was provided with an overview of current evidence, summarized by recent guidelines related to lung cancer screening and lung nodule evaluation. The panel was convened by video teleconference to discuss and then vote on statements related to 12 common clinical scenarios. A predefined threshold of 70% of panel members voting agree or strongly agree was used to determine if there was a consensus for each statement. Items that may influence decisions were listed as notes to be considered for each scenario.

Results: Twelve statements related to baseline and annual lung cancer screening (n = 2), surveillance of a previously detected lung nodule (n = 5), evaluation of intermediate and high-risk lung nodules (n = 4), and management of clinical stage I non-small cell lung cancer (n = 1) were developed and modified. All 12 statements were confirmed as consensus statements according to the voting results. The consensus statements provide guidance about situations in which it was believed to be appropriate to delay screening, defer surveillance imaging of lung nodules, and minimize nonurgent interventions during the evaluation of lung nodules and stage I non-small cell lung cancer.

Conclusion: There was consensus that during the COVID-19 pandemic, it is appropriate to defer enrollment in lung cancer screening and modify the evaluation of lung nodules due to the added risks from potential exposure and the need for resource reallocation. There are multiple local, regional, and patient-related factors that should be considered when applying these statements to individual patient care.© 2020 RSNA; The American College of Chest Physicians, published by Elsevier Inc; and The American College of Radiology, published by Elsevier Inc.
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http://dx.doi.org/10.1148/rycan.2020204013DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7233408PMC
May 2020

The impact of pathologic staging of the hilar/mediastinal nodes on outcomes in patients with early-stage NSCLC receiving stereotactic body radiotherapy.

J Thorac Dis 2021 Feb;13(2):1045-1054

Department of Radiation Oncology, University of North Carolina Hospitals, Chapel Hill, NC, USA.

Background: The importance of invasive mediastinal nodal staging in early-stage non-small cell lung cancer (NSCLC) in the PET/CT era is dependent on tumor factors that increase risk of nodal metastasis. At our institution, patients undergo biopsy via either CT-guidance (without nodal staging) or navigational bronchoscopy with endobronchial ultrasound transbronchial needle aspiration for nodal staging. This study aims to compare outcomes after stereotactic body radiotherapy (SBRT) stratified by receipt of invasive mediastinal nodal staging.

Methods: In this retrospective study, records of all consecutive patients undergoing SBRT for early-stage NSCLC between 2010 and 2017 were analyzed. The association between time-to event outcomes (recurrence and survival) were evaluated with covariates of interest including tumor size, location, histology, smoking history, prior lung cancer history, radiation dose and receipt of nodal staging. Both univariable and multivariable analyses were used to examine these comparisons.

Results: Overall, 158 patients were treated with SBRT. One hundred forty-nine out of one hundred fifty-eight patients (94%) underwent PET/CT staging, and all patients underwent tumor-directed biopsy. Seventy-nine patients underwent navigational bronchoscopy with nodal staging and 79 patients underwent CT-guided biopsy without nodal staging. Receipt of nodal staging was not associated with tumor size (P=0.35), yet was associated with central tumor location (P<0.001). There was no statistically significant association between receipt of nodal staging and time-to-event recurrence or survival outcomes; for example 3-year overall survival (OS) was 65% 67% (P=0.65) and 3-year freedom from nodal failure was 84% 69% (P=0.1) for those with and without nodal staging, respectively.

Conclusions: Similar recurrence and survival outcomes were observed after SBRT regardless of receipt of invasive mediastinal nodal staging. Further prospective evaluation can help identify which patients might derive greatest benefit from invasive staging of the mediastinum in the PET/CT era.
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http://dx.doi.org/10.21037/jtd-20-2808DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7947488PMC
February 2021

Broadened Eligibility for Lung Cancer Screening: Challenges and Uncertainty for Implementation and Equity.

JAMA 2021 03;325(10):939-941

Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill.

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http://dx.doi.org/10.1001/jama.2020.26422DOI Listing
March 2021

Cardiovascular Risk in the Lung Cancer Screening Population: A Multicenter Study Evaluating the Association Between Coronary Artery Calcification and Preventive Statin Prescription.

J Am Coll Radiol 2021 Feb 26. Epub 2021 Feb 26.

Director Epidemiology Research Team, Director Carolina Mammography Registry; Co-Lead, Cancer Epidemiology Program at Lineberger Comprehensive Cancer Center; Department of Radiology, University of North Carolina School of Medicine., Chapel Hill, North Carolina.

Objective: Coronary artery calcification (CAC) is a marker of atherosclerotic cardiovascular disease (ASCVD), the leading cause of death in individuals receiving lung cancer screening (LCS) with low-dose CT. Our purpose was to determine the proportion of the LCS population eligible for primary ASCVD preventive statin therapy by American College of Cardiology/American Heart Association guidelines, assess statin prescription rates among statin-eligible individuals, and determine associations of CAC on downstream statin prescribing within 90 days of LCS.

Methods: Individuals receiving LCS between January 1, 2016, and December 31, 2018, across three centers were retrospectively enrolled. Statin eligibility in individuals without pre-existing ASCVD was determined by 2013 American College of Cardiology/American Heart Association guidelines: (1) low-density lipoprotein ≥190 mg/dL, (2) diabetes, or (3) ASCVD risk score ≥7.5%. CAC presence and severity (mild, moderate, heavy) were extracted from LCS reports. Variation in statin prescription rates and associations between CAC and statin prescription were determined using mixed-effects logistic regression.

Results: Of 5,495 individuals receiving LCS, 31.4% (1,724 of 5,495) had pre-existing ASCVD. Of the remaining 3,771 individuals, 73.6% were statin eligible (2,777 of 3,771). However, most lacked statin prescription (60.5%, 1,681 of 2,777). CAC was associated with downstream statin prescribing (adjusted odds ratio = 2.60, 95% confidence interval: 1.12-6.02), with a higher likelihood of statin prescribing with increasing CAC severity (adjusted odds ratio = 2.21, 95% confidence interval: 1.35-3.60).

Conclusion: Although most of the LCS population is eligible for guideline-directed statin therapy, statins are underprescribed in this group. Radiologist reporting of CAC at LCS reflects a potential opportunity to raise awareness of ASCVD risk and improve preventive statin prescribing.
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http://dx.doi.org/10.1016/j.jacr.2021.01.015DOI Listing
February 2021

Immune Checkpoint Inhibitor-Related Pneumonitis in Lung Cancer: Real-World Incidence, Risk Factors, and Management Practices Across Six Health-Care Centers in North Carolina.

Chest 2021 Feb 20. Epub 2021 Feb 20.

Division of Pulmonary Diseases and Critical Care Medicine, Department of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC.

Background: Immune checkpoint inhibitors (ICIs) are standard treatments for advanced non-small cell lung cancer and have expanded use in small cell lung cancer. Although generally better tolerated than traditional chemotherapy, immune-related adverse events, such as immune checkpoint inhibitor-related pneumonitis (ICI-P), remain poorly understood toxicities that limit ICI treatment and can result in considerable morbidity. In this retrospective case-control study, we assessed a lung cancer cohort to identify ICI-P risk factors.

Research Question: What are the risk factors, clinical presentations, radiographic findings, and outcomes for ICI-P in a real-world lung cancer cohort? Do chronic pulmonary diseases confer increased risk for ICI-P?

Study Design And Methods: Medical records from lung cancer patients receiving nivolumab, pembrolizumab, or combination ipilimumab and nivolumab at six centers in North Carolina were reviewed (January 2004-July 2017). Patients with ICI-P and control participants were characterized, and logistic regression was used to assess for ICI-P risk factors.

Results: Three hundred fifteen lung cancer patients who predominantly received nivolumab (76.5%) or pembrolizumab (22%) were included. The incidence of ICI-P was 9.5%, with a median time to diagnosis of 52.5 days. Most patients with ICI-P had cases of high severity, and eight patients (27%) died with ongoing ICI-P treatment. Development of ICI-P was associated independently with the presence of baseline fibrosis on chest CT scan (adjusted OR [aOR], 6.61; 95% CI, 2.48-17.7), a composite measure of obstructive lung disease (aOR, 2.79; 95% CI, 1.07-7.29), and treatment with pembrolizumab (aOR, 2.57; 95% CI, 1.08-6.11).

Interpretation: In this cohort, ICI-P was more common and severe than previously reported and carried an unexpectedly high mortality rate. Risk for ICI-P seems to be associated independently with several chronic pulmonary diseases, which may account for the higher incidence of ICI-P in patients with lung cancer.
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http://dx.doi.org/10.1016/j.chest.2021.02.032DOI Listing
February 2021

Lung Cancer Screening With Low Dose Computed Tomography in Patients With and Without Prior History of Cancer in the National Lung Screening Trial.

J Thorac Oncol 2021 06 10;16(6):980-989. Epub 2021 Feb 10.

Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, North Carolina; Division of Pulmonary and Critical Care Medicine, Department of Medicine, University of North Carolina, Chapel Hill, North Carolina.

Introduction: Patients with a prior history of cancer (PHC) are at increased risk of second primary malignancy, of which lung cancer is the most common. We compared the performance metrics of positive screening rates and cancer detection rates (CDRs) among those with versus without PHC.

Methods: We conducted a secondary analysis of 26,366 National Lung Screening Trial participants screened with low dose computed tomography between August 2002 and September 2007. We evaluated absolute rates and age-adjusted relative risks (RRs) of positive screening rates on the basis of retrospective Lung CT Screening Reporting & Data System (Lung-RADS) application, invasive diagnostic procedure rate, complication rate, and CDR in those with versus without PHC using a binary logistic regression model using Firth's penalized likelihood. We also compared cancer type, stage, and treatment in those with versus without PHC.

Results: A total of 4.1% (n = 1071) of patients had PHC. Age-adjusted rates of positive findings were similar in those with versus without PHC (Baseline: PHC = 13.7% versus no PHC = 13.3%, RR [95% confidence interval (CI)]: 1.04 [0.88-1.24]; Subsequent: PHC = 5.6% versus no PHC = 5.5%, RR [95% CI]: 1.02 [0.84-1.23]). Age-adjusted CDRs were higher in those with versus without PHC on baseline (PHC=1.9% versus no PHC = 0.8%, RR [95% CI]: 2.51 [1.67-3.81]) but not on subsequent screenings (PHC = 0.6% versus no PHC = 0.4%, RR [95% CI]: 1.37 [0.99-1.93]). There were no differences in cancer stage, type, or treatment by PHC status.

Conclusions: Patients with PHC may benefit from lung cancer screening, and with their providers, should be made aware of the possibility of higher cancer detection, invasive procedures, and complication rates on baseline lung cancer screening, but not on subsequent low dose computed tomography screening examinations.
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http://dx.doi.org/10.1016/j.jtho.2021.02.003DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8159850PMC
June 2021

Response.

Chest 2021 01;159(1):438-439

University of Pennsylvania, Philadelphia, PA.

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http://dx.doi.org/10.1016/j.chest.2020.08.2087DOI Listing
January 2021

Impact of the COVID-19 Pandemic on Volumes and Disparities in Lung Cancer Screening.

Chest 2021 07 5;160(1):379-382. Epub 2021 Jan 5.

Lineberger Comprehensive Cancer Center, Division of Pulmonary Disease and Critical Care Medicine, University of North Carolina, Chapel Hill, NC; Division of Cardiothoracic Surgery, and the Department of Medicine, Division of Pulmonary Disease and Critical Care Medicine, University of North Carolina, Chapel Hill, NC.

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http://dx.doi.org/10.1016/j.chest.2020.12.033DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7784535PMC
July 2021

Using Prediction-Models to Reduce Persistent Racial/Ethnic Disparities in Draft 2020 USPSTF Lung-Cancer Screening Guidelines.

J Natl Cancer Inst 2021 Jan 5. Epub 2021 Jan 5.

Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Department of Health and Human Services, Bethesda, Maryland, USA.

We examined whether draft 2020 United States Preventive Services Task Force (USPSTF) lung-cancer screening recommendations "partially ameliorate racial disparities in screening eligibility" compared to 2013 guidelines, as claimed. Using data from the 2015 National Health Interview Survey, USPSTF-2020 increased eligibility by similar proportions for minorities (97.1%) and Whites (78.3%). Contrary to the intent of USPSTF-2020, the relative disparity (differences in percentages of model-estimated gainable life-years from National Lung Screening Trial-like screening by eligible Whites vs minorities) actually increased from USPSTF-2013 to USPSTF-2020 (African Americans: 48.3%-33.4%=15.0% to 64.5%-48.5%=16.0%; Asian Americans: 48.3%-35.6%=12.7% to 64.5%-45.2%=19.3%; Hispanic Americans: 48.3%-24.8%=23.5% to 64.5%-37.0%=27.5%). However, augmenting USPSTF-2020 with high-benefit individuals selected by the Life-Years From Screening with Computed Tomography (LYFS-CT) model nearly eliminated disparities for African Americans (76.8%-75.5%=1.2%), and improved screening efficiency for Asian/Hispanic Americans, although disparities were reduced only slightly (Hispanic Americans) or unchanged (Asian Americans). Draft USPSTF-2020 guidelines increased the number of eligible minorities versus USPSTF-2013 but may inadvertently increase racial/ethnic disparities. LYFS-CT could reduce disparities in screening eligibility by identifying ineligible people with high predicted benefit, regardless of race/ethnicity.
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http://dx.doi.org/10.1093/jnci/djaa211DOI Listing
January 2021

Augmented transcripts of kidney injury markers and renin angiotensin system in urine samples of overweight young adults.

Sci Rep 2020 12 3;10(1):21154. Epub 2020 Dec 3.

Institute of Chemistry, Pontificia Universidad Católica de Valparaíso, Valparaíso, Chile.

Obesity has been firmly established as a major risk factor for common disease states including hypertension, type 2 diabetes mellitus, and chronic kidney disease. Increased body mass index (BMI) contributes to the activation of both the systemic and intra-tubular renin angiotensin systems (RAS), which are in turn associated with increased blood pressure (BP) and kidney damage. In this cross-sectional study, 43 subjects of normal or increased body weight were examined in order to determine the correlation of BMI or body fat mass (BFM) with blood pressure, fasting blood glucose (FBG), and urinary kidney injury markers such as interleukin-18 (IL-18), connective tissue growth factor (CTGF), neutrophil gelatinase-associated lipocalin, and kidney injury molecule-1 (KIM-1). Our results showed that: (1) subjects with increased body weight showed significantly higher BP, BFM, total body water and metabolic age; (2) BMI was positively correlated to both systolic (R = 0.1384, P = 0.01) and diastolic BP (R = 0.2437, P = 0.0008); (3) BFM was positively correlated to DBP (R = 0.1232, P = 0.02) and partially correlated to urine protein (R = 0.047, P = 0.12) and FBG (R = 0.07, P = 0.06); (4) overweight young adults had higher urinary mRNA levels of renin, angiotensinogen, IL-18 and CTGF. These suggest that BMI directly affects BP, kidney injury markers, and the activation of the intra-tubular RAS even in normotensive young adults. Given that BMI measurements and urine analyses are non-invasive, our findings may pave the way to developing a new and simple method of screening for the risk of chronic kidney disease in adults.
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http://dx.doi.org/10.1038/s41598-020-78382-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7713175PMC
December 2020

Imbalance of Endocannabinoid/Lysophosphatidylinositol Receptors Marks the Severity of Alzheimer's Disease in a Preclinical Model: A Therapeutic Opportunity.

Biology (Basel) 2020 Nov 5;9(11). Epub 2020 Nov 5.

Instituto de Investigación Biomédica de Málaga-IBIMA, Unidad de Gestión Clínica de Salud Mental, Hospital Regional Universitario de Málaga, 29010 Málaga, Spain.

Alzheimer's disease (AD) is the most common form of neurodegeneration and dementia. The endocannabinoid (ECB) system has been proposed as a novel therapeutic target to treat AD. The present study explores the expression of the ECB system, the ECB-related receptor GPR55, and cognitive functions (novel object recognition; NOR) in the 5xFAD (FAD: family Alzheimer's disease) transgenic mouse model of AD. Experiments were performed on heterozygous (HTZ) and homozygous (HZ) 11 month old mice. Protein expression of ECB system components, neuroinflammation markers, and β-amyloid (Aβ) plaques were analyzed in the hippocampus. According to the NOR test, anxiety-like behavior and memory were altered in both HTZ and HZ 5xFAD mice. Furthermore, both animal groups displayed a reduction of cannabinoid (CB1) receptor expression in the hippocampus, which is related to memory dysfunction. This finding was associated with indirect markers of enhanced ECB production, resulting from the combination of impaired monoacylglycerol lipase (MAGL) degradation and increased diacylglycerol lipase (DAGL) levels, an effect observed in the HZ group. Regarding neuroinflammation, we observed increased levels of CB2 receptors in the HZ group that positively correlate with Aβ's accumulation. Moreover, HZ 5xFAD mice also exhibited increased expression of the GPR55 receptor. These results highlight the importance of the ECB signaling for the AD pathogenesis development beyond Aβ deposition.
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http://dx.doi.org/10.3390/biology9110377DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7694492PMC
November 2020

Improving Inequities in Lung Cancer Screening: Risk Prediction Models and the Potential to Achieve a Great Equalizer Effect.

J Thorac Oncol 2020 11 23;15(11):1711-1713. Epub 2020 Oct 23.

University of North Carolina, Chapel Hill, North Carolina.

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http://dx.doi.org/10.1016/j.jtho.2020.09.010DOI Listing
November 2020

Sex-specific behavioral and neurogenic responses to cocaine in mice lacking and blocking dopamine D1 or dopamine D2 receptors.

J Comp Neurol 2021 Jun 22;529(8):1724-1742. Epub 2020 Oct 22.

UGC Salud Mental, Instituto de Investigación Biomédica de Málaga (IBIMA), Hospital Universitario Regional de Málaga, Universidad de Málaga, Málaga, Spain.

Adult neurogenesis in rodents is modulated by dopaminergic signaling and inhibited by cocaine. However, the sex-specific role of dopamine D1 and D2 receptors (D1R, D2R) in the deleterious effect of cocaine on adult neurogenesis has not been described yet. Here, we explored sex differences in (a) cell proliferation (5'-bromo-2'-deoxyuridine [BrdU]), (b) neural precursor (nestin), (c) neuronal phenotype (BrdU/β3-tubulin), and (d) neuronal maturity (NeuN) in the subventricular zone (SVZ) of the lateral ventricles and striatum of mice with genetic deletion (D1 , D2 ) or pharmacological blockage (SCH23390: 0.1 mg/kg/day/5 days; Raclopride: 0.3 mg/kg/day/5 days) of D1R and D2R, and treated (10 mg/kg/day/5 days) and then challenged (5 mg/kg, 48 hr later) with cocaine. Results indicated that hyperactivity responses to cocaine were absent in D1 mice and reduced in SCH23390-treated mice. Activity responses to cocaine were reduced in D2 males, but absent in D2 females and increased in Raclopride-treated females. D1R deletion blocked the deleterious effect of cocaine on SVZ cell proliferation in males. Cocaine-exposed D1 males also had reduced neuronal phenotype of SVZ newborn cells and increased striatal neuronal maturity. D2 mice had lower proliferative and neural precursor responses. Cocaine in D2 females or coadministered with Raclopride in wild-type females improved SVZ cell proliferation, an effect that positively correlated with plasma brain-derived neurotrophic factor (BDNF) concentrations. In conclusion, the sex-specific D1R and D2R signaling on SVZ cell proliferation, neural progenitor and neuronal maturity is differentially perturbed by cocaine, and BDNF may be required to link D2R to neuroplasticity in cocaine addiction in females.
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http://dx.doi.org/10.1002/cne.25052DOI Listing
June 2021

Addressing Disparities in Lung Cancer Screening Eligibility and Healthcare Access. An Official American Thoracic Society Statement.

Am J Respir Crit Care Med 2020 10;202(7):e95-e112

There are well-documented disparities in lung cancer outcomes across populations. Lung cancer screening (LCS) has the potential to reduce lung cancer mortality, but for this benefit to be realized by all high-risk groups, there must be careful attention to ensuring equitable access to this lifesaving preventive health measure. To outline current knowledge on disparities in eligibility criteria for, access to, and implementation of LCS, and to develop an official American Thoracic Society statement to propose strategies to optimize current screening guidelines and resource allocation for equitable LCS implementation and dissemination. A multidisciplinary panel with expertise in LCS, implementation science, primary care, pulmonology, health behavior, smoking cessation, epidemiology, and disparities research was convened. Participants reviewed available literature on historical disparities in cancer screening and emerging evidence of disparities in LCS. Existing LCS guidelines do not consider racial, ethnic, socioeconomic, and sex-based differences in smoking behaviors or lung cancer risk. Multiple barriers, including access to screening and cost, further contribute to the inequities in implementation and dissemination of LCS. This statement identifies the impact of LCS eligibility criteria on vulnerable populations who are at increased risk of lung cancer but do not meet eligibility criteria for screening, as well as multiple barriers that contribute to disparities in LCS implementation. Strategies to improve the selection and dissemination of LCS in vulnerable groups are described.
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http://dx.doi.org/10.1164/rccm.202008-3053STDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7528802PMC
October 2020

Maternal hypercaloric diet affects factors involved in lipid metabolism and the endogenous cannabinoid systems in the hypothalamus of adult offspring: sex-specific response of astrocytes to palmitic acid and anandamide.

Nutr Neurosci 2020 Sep 21:1-14. Epub 2020 Sep 21.

Department of Endocrinology, Fundación Investigación Biomédica del Hospital Infantil Universitario Niño Jesús, Instituto de Investigación Biomédica la Princesa, Madrid, Spain.

We aimed to investigate whether maternal malnutrition during gestation/lactation induces long-lasting changes on inflammation, lipid metabolism and endocannabinoid signaling in the adult offspring hypothalamus and the role of hypothalamic astrocytes in these changes. We analyzed the effects of a free-choice hypercaloric palatable diet (P) during (pre)gestation, lactation and/or post-weaning on inflammation, lipid metabolism and endogenous cannabinoid signaling in the adult offspring hypothalamus. We also evaluated the response of primary hypothalamic astrocytes to palmitic acid and anandamide. Postnatal exposure to a P diet induced factors involved in hypothalamic inflammation ( and ) and gliosis ( and ) in adult offspring, being more significant in females. In contrast, maternal P diet reduced factors involved in astrogliosis (), fatty acid oxidation () and monounsaturated fatty acid synthesis (). These changes were accompanied by an increase in the expression of the genes for the cannabinoid receptor () and an enzyme involved in endocannabinoid synthesis, in females and a decrease in the endocannabinoid degradation enzyme in males. These changes suggest that the maternal P diet results in sex-specific alterations in hypothalamic endocannabinoid signaling and lipid metabolism. This hypothesis was tested in hypothalamic astrocyte cultures, where palmitic acid (PA) and the polyunsaturated fatty acid N-arachidonoylethanolamine (anandamide or AEA) were found to induce similar changes in the endocannabinoid system (ECS) and lipid metabolism. These results stress the importance of both maternal diet and sex in long term metabolic programming and suggest a possible role of hypothalamic astrocytes in this process.
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http://dx.doi.org/10.1080/1028415X.2020.1821519DOI Listing
September 2020

Rates of positive lung cancer screening examinations in academic versus community practice.

Transl Lung Cancer Res 2020 Aug;9(4):1528-1532

The University of North Carolina Lineberger Comprehensive Cancer Center, Chapel Hill, NC, USA.

The benefits and harms of lung cancer screening reported in the National Lung Screening Trial (NLST) likely differ from those observed in academic and community settings. High rates of positive screening findings in the NLST led to the development of the Lung CT Screening Reporting and Data System (Lung-RADS) to standardize interpretation and reporting. We conducted a prospective observational study of lung cancer screening data from four lung cancer screening sites in North Carolina to compare prospective use of Lung-RADS in a real-world screened population versus Lung-RADS retrospectively applied to the NLST, and to determine if Lung-RADS assessment use differs in academic versus community settings. We included 4,037 screening examinations from 11/2014 to 12/2018 in academic and community sites and 75,126 NLST LDCT screening exams. On baseline screening exams, the proportion of positive LDCT exams was higher in community versus academic sites or the NLST (17.7% 11.4% and 13.6%, P value <0.01). On subsequent screens, the proportion of positive exams was lowest in the NLST and higher in community and academic sites (5.9% 12.7% and 11.6%, P value <0.01). After adjusting for age, race, sex, and smoking status, patients screened at academic versus community sites were 34% less likely to have a positive screen at baseline [adjusted odds ratio (aOR) =0.66; 95% confidence interval (95% CI): 0.51-0.86] but on subsequent examinations, there was no difference in academic versus community sites (aOR =0.91; 95% CI: 0.58-1.43). Our findings may be due to differences in radiologists' training or experiences or the availability of prior images for comparison.
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http://dx.doi.org/10.21037/tlcr-19-673DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7481616PMC
August 2020

Palmitic acid reduces the autophagic flux in hypothalamic neurons by impairing autophagosome-lysosome fusion and endolysosomal dynamics.

Mol Cell Oncol 2020 25;7(5):1789418. Epub 2020 Jul 25.

Laboratory of Autophagy and Metabolism, Department of Physiology, Faculty of Biological Sciences, Pontificia Universidad Católica De Chile, Santiago, Chile.

High-fat diet (HFD)-induced obesity is associated with increased cancer risk. Long-term feeding with HFD increases the concentration of the saturated fatty acid palmitic acid (PA) in the hypothalamus. We previously showed that, in hypothalamic neuronal cells, exposure to PA inhibits the autophagic flux, which is the whole autophagic process from the synthesis of the autophagosomes, up to their lysosomal fusion and degradation. However, the mechanism by which PA impairs autophagy in hypothalamic neurons remains unknown. Here, we show that PA-mediated reduction of the autophagic flux is not caused by lysosomal dysfunction, as PA treatment does not impair lysosomal pH or the activity of cathepsin B.Instead, PA dysregulates autophagy by reducing autophagosome-lysosome fusion, which correlates with the swelling of endolysosomal compartments that show areduction in their dynamics. Finally, because lysosomes undergo constant dynamic regulation by the small Rab7 GTPase, we investigated the effect of PA treatment on its activity. Interestingly, we found PA treatment altered the activity of Rab7. Altogether, these results unveil the cellular process by which PA exposure impairs the autophagic flux. As impaired autophagy in hypothalamic neurons promotes obesity, and balanced autophagy is required to inhibit malignant transformation, this could affect tumor initiation, progression, and/or response to therapy of obesity-related cancers.
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http://dx.doi.org/10.1080/23723556.2020.1789418DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7469685PMC
July 2020

A combination of circulating chemokines as biomarkers of obesity-induced insulin resistance at puberty.

Pediatr Obes 2021 02 27;16(2):e12711. Epub 2020 Aug 27.

Department of Pediatrics & Pediatric Endocrinology, Hospital Infantil Universitario Niño Jesús, Universidad Autónoma de Madrid, Madrid, Spain.

Background: In obesity adipose tissue undergoes structural re-modelling leading to a chronic low-grade inflammatory state linked to insulin resistance (IR).

Objective: We aimed to develop a clinically relevant biomarker model for stratifying IR in adolescents with obesity.

Methods: Cytokines [tumour cell derived factor 1α, monocyte chemoattract protein (MCP) 1, eotaxin and fractalkine], growth factors [brain-derived neurotrophic factor, pro-fibrotic platelet-derived growth factor (PDGF-BB) and insulin-like growth factor 1] and biochemical/metabolic factors were analysed in serum of 143 pubertal patients with obesity (50% IR; 50% non-IR) and 33 controls. Factor analysis, correlation, binary logistic regression and receiver operating characteristic analysis were used to evaluate combinations of these biomarkers as possible diagnostic tools for IR.

Results: Two biomarker IR models combining levels of triglycerides (TG)/HDL, eotaxin, MCP-1 and PDGF-BB in pubertal patients with obesity of both sexes were defined. Altered levels of MCP-1, eotaxin, and PDGF-BB constitute a main component that determines 27.7% of the variance explaining IR. Growth and inflammatory factors comprise two other components linked to the first, together accounting for 59.2% of the variance determining IR.

Conclusions: PDGF-BB, MCP-1, eotaxin, TG and cholesterol concentrations constitute a solid panel of biomarkers associated with IR in pubertal children with obesity that could be useful in their stratification in a clinical setting for stratification.
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http://dx.doi.org/10.1111/ijpo.12711DOI Listing
February 2021

How Health-Care Organizations Implement Shared Decision-making When It Is Required for Reimbursement: The Case of Lung Cancer Screening.

Chest 2021 01 13;159(1):413-425. Epub 2020 Aug 13.

Eshelman School of Pharmacy, Chapel Hill, NC; UNC Lineberger Comprehensive Cancer Center, Chapel Hill, NC; Henry Ford Health System, Detroit, MI. Electronic address:

Background: The Centers for Medicare and Medicaid Services stipulate shared decision-making (SDM) counseling as a prerequisite to lung cancer screening (LCS) reimbursement, despite well-known challenges implementing SDM in practice.

Research Question: How have health-care organizations implemented SDM for LCS?

Study Design And Methods: For this qualitative study, we used data from in-depth, semistructured interviews with key informants directly involved in implementing SDM for LCS, managing SDM for LCS, or both. We identified respondents using a snowball sampling technique and used template analysis to identify and analyze responses thematically.

Results: We interviewed 30 informants representing 23 health-care organizations located in 12 states and 4 Census regions. Respondents described two types of SDM for LCS programs: centralized models (n = 7), in which front-end practitioners (eg, primary care providers) referred patients to an LCS clinic where trained staff (eg, advanced practice nurses) delivered SDM at the time of screening, or decentralized models (n = 10), in which front-end practitioners delivered SDM before referring patients for screening. Some organizations used both models simultaneously (n = 6). Respondents discussed tradeoffs between SDM quality and access. They perceived centralized models as enhancing SDM quality, but limiting patient access to care, and vice versa. Respondents reported ongoing challenges with limited resources and budgetary constraints, ambiguity regarding what constitutes SDM, and an absence of benchmarks for evaluating SDM for LCS quality.

Interpretation: Those responsible for developing and managing SDM for LCS programs voiced concerns regarding both patient access and SDM quality, regardless of organizational context, or the SDM for LCS model implemented. The challenge facing these organizations, and those wanting to help patients and clinicians balance the tradeoffs inherent with LCS, is how to move beyond a check-box documentation requirement to a process that enables LCS to be offered to all high-risk patients, but used only by those who are informed and for whom screening represents a value-concordant service.
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http://dx.doi.org/10.1016/j.chest.2020.07.078DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7893305PMC
January 2021
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